Ijmrhs Vol 3 Issue 1

DOI: 10.5958/j.2319-5886.3.1.
001
International Journal of Medical Research

&
Health Sciences
www.ijmrhs.com
Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS
nd
Received: 2 Sep 2013
Revised: 8th Oct 2013
Research article
Copyright @2013
ISSN: 2319-5886
Accepted: 3rd Nov 2013
A STUDY OF LUMBARISATION OF FIRST SACRAL VERTEBRA AMONG THE SOUTH INDIANS

* Deepa TK1, Martin K John2
1,2
Assistant Professor, Department of Anatomy, MES medical college, Perinthalmanna, Kerala
*Corresponding author e-mail: amee2amee@yahoo.co.in

ABSTRACT
Background: In the lumbosacral region, anatomical variations occur with changes in the number of sacral vertebra
by deletion of first sacral vertebra or by the union of fifth lumbar or first coccyx with sacrum. The fifth lumbar
vertebra may be fused with the sacrum in the case of sacralisation, or the first sacral vertebra may be fused with fifth
lumbar vertebra in the case of lumbarisation. This may cause serious problems during spinal surgery if we may fail
to recognise the lumbosacral transitional vertebra. Materials and methods: We studied 117 dry human sacra of
South Indian population of known sex. Out of 117 sacra, 70 male and 47 female. The sacra with four vertebral
segments were selected and studied its morphology. Its features were carefully examined and noted. Result: A
typical sacrum consisting of five segments was observed in 103 (88.03%) specimen, while presence of
lumbarisation was noted in 2 (1.70%) cases and sacralisation was noted in 12 (10.25%) cases. Sacrum with 3 pairs
of sacral foramina is 1.70%. Among the 2 specimen, we got 1 male and 1 female respectively Conclusion: Present
study shows that the lumbarisation of first sacral vertebra leads to the formation of three pairs of sacral foramina,
which is 1.70% in South Indian population. This awareness of lumbosacral transitional vertebra (LSTV) will help to
understand its importance during surgical procedures and also in reporting the radiographs such as X-rays, CT and
MRI.
Keywords: Anatomic variations, congenital anomaly, lumbarisation, sacral foramina
INTRODUCTION
The sacrum lies below the fifth lumbar vertebra and is
formed by the fusion of five sacral vertebras. It is
wedged between the two hip bones and takes part in
forming the pelvis. It is triangular in shape. Its upper
end or base which articulates with the fifth lumbar
vertebra: a lower end or apex which articulate with the
coccyx. It has four pairs of sacral foramina that
communicate with sacral canal.
At the cranial end of sacrum, when the fifth lumbar
vertebra fuses with first sacral vertebra, known as the
sacralisation of lumbar vertebra and when the first
sacral vertebra fuses with the fifth lumbar vertebra,
known as lumbarisation of first sacral vertebra.1
Normally, the sacrum is formed by the fusion of five
rudimentary vertebrae. But anatomical variations of
the sacrum have been reported like sacralisation of

fifth lumbar vertebra and lumbarisation of first sacral
vertebra. Sacralisation of fifth lumbar vertebra is the
most common, whereas the lumbarisation of first
sacral vertebra is less common.2
In the present study, the sacrum had four sacral
vertebrae instead of five sacral vertebrae as in normal
sacrum. There were three sacral foramina along the
dorsal and pelvic sacral surface. This is due to non
fusion of 1st and 2nd segments of the sacrum ie, the
lumbarisation of the first sacral vertebra. S5 vertebra
was normal and S2 vertebra was well developed as
like S1. S1being completely separated from it, which
may be due to developmental defect.
1
Deepa et al.,
Int J Med Res Health Sci. 2014;3(1):1-4
Bertolotti observed for the first time that,

lumbarisation and sacralisation which comes under
lumbosacral transitional vertebra are congenital
anomalies of lumbosacral region.3 Defect in the
segmentation of the lumbosacral spine during
development is the main cause for this condition.3,4
Genetic factors and ossification defects are also the
potential cause of variation for the lumbosacral
transitional vertebra. In both case the morphology is
the same. So it is difficult to differentiate between the
two defects.5,6
In this study, we focused on the prevalence of sacrum
with 3 pairs of sacral foramina among the South Indian
population, that in turns help to find out the variations
in patients during radiological investigations
complaining low back pain. Knowledge of this
variation is important to diagnose lower back pain;
disc prolapsed and is helpful in procedures like lumbar
puncture and spinal anaesthesia.
male and the other one is female. Incidence of sacrum

with 3 pairs of sacral foramina is 1.70%.
Table 1: Frequency distribution of lumbarisation of
1st sacral vertebra & sacralisation of 5th lumbar
vertebra
Male Female Total
Total number of sacra
70
47
117
Normal
61
42
103
Lumbarisation
1
1
2
Sacralisation
8
4
12
DSF-1
DSF-2
DSF-3
MATERIALS AND METHODS

The present study includes 117 human sacra of known
sex, were studied. All the sacra were of adult, but
precise age was not known. Any change in the number
of sacral vertebrae were selected and studied. The
sacrum with four segments and three sacral foramina
was noted.
The specimen with lumbarisation were examined and
recorded. Two fold subdivision of lumbarisation was
used. (1) Unilateral complete lumbarisation (11)
bilateral complete lumbarisation of first sacral
vertebra.
In this study, 2 sacrum with four sacral vertebrae and 3
pairs of sacral foramina showing bilateral complete
lumbarisation of 1st sacral vertebra was selected.
Incidence of sacrum with 3 pairs of sacral foramina is
1.70%. Among the 2 specimen, one is male and the
other one is female respectively.
RESULTS
In the current study of 117 dry human sacra, 70
(60.5%) were male and 47 (39.5%) were female sacra.
14 cases (12.3%) of lumbosacral transitional vertebra
and 103 (87.7%) normal vertebra are found.
Among the 14 cases of lumbosacral transitional
vertebras, we got 2sacra with four sacral vertebrae
and three pairs of sacral foramina showing bilateral
complete lumbarisation of 1st sacral vertebra. One is
Fig 1. Dorsal surface of sacrum

(DSF-1: First pair of dorsal sacral foramina, DSF-2:
Second pair of dorsal sacral foramina, DSF-3:Third
pair of dorsal sacral foramina)
We came across the sacrum with only bilateral
complete lumbarisation and not any unilateral
complete lumbarisation in any specimen. Parameters
in sacrum with bilateral complete lumbarisation were
smaller than normal dimension.
PSF-1
PSF-2
PSF-3
Fig 2: Pelvic surface of sacrum.

(PSF1-first pair of pelvic sacral foramina, PSF2second pair of pelvic sacral foramina, PSF3- third pair
of pelvic sacral foramina)
2
Deepa et al.,
DISCUSSION
Variations in vertebrae are affected by gender,
developmental factors and race. An increased number
of vertebrae occur more often in males and a reduced
number occurs more frequently in females.
Normally sacrum is formed by the fusion of five sacral
vertebrae and it contains four pairs of sacral foramina.
In the current study, we got sacrum with three pairs of
sacral foramina showing bilateral complete
lumbarisation of first sacral vertebra. In our study, the
prevalence of sacrum with three pairs of sacral
foramina is 1.70%.
In the lumbosacral region, anatomical variations occur
frequently, making the sacrum the most variable
portion of spine. The variation may be attributed to the
dependency of the final sacral morphology to the load
related fusion of the bone structure.7 Failure to
complete the ascending fusion may create a sixth
lumbar vertebra, leaving a four piece or lumbarised
sacrum.
The occurrence of lumbosacral transitional vertebrae is
linked to its embryological development and
osteological defects. Vertebras are derived from the
sclerotomes of the somites. Each sclerotome divides
into three parts: cranial, middle and caudal.
Embryologically, the vertebra receives contribution
from caudal half of one sclerotome and from the
cranial half of succeeding sclerotome. Thus
lumbosacral transitional vertebras are caused by the
border shifts. Sacralisation of fifth lumbar vertebra is
due to cranial shift and the lumbarisation of first sacral
segment is due to caudal shift.8
The vast majority of people are affected by this spinal
abnormality are born with it ie, it is congenital. Less
common reasons could be traumatic injury, extreme
arthritic changes and purposeful spinal fusion surgery.
Mutations in the HOX 10 and HOX 11 paralogous
genes results in the normal pattering of lumbar and
sacral vertebra as well as the changes in the axial
pattern, such as lumbosacral transition vertebrae.6,9,10
A sacrum with three pairs of sacral foramina has
clinical and medicolegal implications. In order to
avoid surgery at an incorrect level, it is important to
identify the lumbarisation of first sacral vertebra and
the sacralisation of fifth lumbar vertebra. The
condition of lumbarisation of 1st sacral vertebra
deserves attention of clinical anatomist, radiologists,
morphologists and forensic experts. Hence we are
presenting such a variation which emphasize on its

clinical relevance.11-13
Variation in segmental structure of vertebral column
results in lumbarisation that demands more attention
during anaesthetic and surgical intervention11.
Knowledge of this variation is important to diagnose
lower back pain, sciatica; disc prolapse and is helpful
in procedures like spinal anesthesia and lumbar
puncture.14
CONCLUSION
The present study shows lumbarisation of first sacral
vertebra with three pairs of sacral foramina instead of
four pairs of sacral foramina.
Sacrum is clinically important for caudal epidural
block. So incorrect numbering can theorectically lead
to problems with the administration of intradural or
epidural anaesthetics.14 Surgical treatment of sacral
lesions requires understanding of the underlying
anatomy, a task made easier by understanding the
developmental aspects and morphological changes that
occur with growth.
The knowledge of this kind of anomaly is important
while reporting the CT, MRI films and Xrays for
correct clinical and radiological assessment. Thus
clinically the lumbarisation of 1st sacral vertebra is of
paramount importance to surgeons, clinical anatomists,
forensic experts and morphologists.
REFERENCES
1. Bajami Singh. Sacrum with five pairs of sacral
foramina. IJAV 2011;4:139-40
2. Frymoyer JW, Hadler NM, Kostuik JP, Weinsttein
JN, Whitecloud TS. The adult spine: Principles
and practice. New York: Raven press.
1991;2:2099
3. Delport EG, Cucuzzella TR, Marley J, Pruitt C,
Delport AG. Lumbosacral transitional vertebrae;
incidence in a consecutive patient series. Pain
physician.2006;9(1); 53-56
4. Kim NH, Suk KS. The role of transitional
vertebrae in spondylolysis and spondylolytic
spondylolisthesis Bull, hosp. Jt.Dis.1997;56(3):
161-66
5. Tini PG, Wieser C, Zinn WM. The transitional
vertebrae of lumbosacral spine: its radiological
classification, incidence, prevalence and clinical
significance. Rheumatology & rehabilitation.
1977;16(3) 180-85.
3
Deepa et al.,
6. Wellik DM, Capecchi MR. Hox 10 and Hox 11

genes are required to globally pattern the
mammalian skeleton. Science 2003; 301: 363-67.
7. Joseph S Cheng MD, John K Song MD. Anatomy
of the Sacrum. Neurosurg Focus 2003; 15(2):
8. Sharma VA, Sharma DK, Shukla CK, Osteogenic
study of lumbosacral transitional vertebra in
central india region J.Anat Soc India.2011; 60(2)
212-17
9. Sadler TW. Langmans medical embryology.
Lippincott Williams & Wilkins, Philadelphia
2010: 11th edition :142
10. Carapuco M, Novoa A, Bobola N, Mallo M. Hox
genes specify vertebral types in the presomatic
mesoderm. Genes Dev 2003; 19; 2116-21
11. Bron LJ, Van Royan BJ and Wuisman P. The
Clinical significance of lumbosacral transitional
anomalies. Acta orthopaedica Belgica 2007;73(6)
687-95
12. Dharati MK, Shailesh kumar K , Chintan Lakhani,
Srushti S Ruparelia, Shilpa patel, Padma Varlekar.
A study of sacrum with three pairs of sacral
foramina in Western India. IJMSPH 2012;1:12731.
13. Frazer JE. Anatomy of the human skeleton., edited
by Breathnach ASJ and A. Churchill Livingstone
London .1958; 5th ed: 33-38
14. Panjakash Samreen, Londhe shashikala and Kori
Rohini. Lumbarisation of first sacral vertebra a
case report. IJBAMS 2012;2;154-57.
4
Deepa et al.,
DOI: 10.5958/j.2319-5886.3.1.002

&
Health Sciences
www.ijmrhs.com
Received: 2nd Sep 2013
Research article
Copyright @2013
ISSN: 2319-5886
THE USE OF PERITONEAL DIALYSIS IN THE MANAGEMENT OF PATIENTS WITH RENAL

FAILURE AT INSTITUTE OF KIDNEY DISEASES, PESHAWAR
*Akhtar Sultan Z1, Saleem Nasir2, Hajira Bibi3
1
Professor and Head, Department of Nephrology, Institute of Kidney Diseases, Hayatabad Medical Complex,
Peshawar
2
Training Medical Officer, Medical B Unit, Hayatabad Medical Complex, Peshawar.
3
Clinical Nutritionist, Institute of Kidney Diseases, Hayatabad Medical Complex, Peshawar.
*Corresponding author email: nasirsaleems@hotmail.com
ABSTRACT
Peritoneal dialysis (PD) using an ordinary stylet cannula was studied in 253 patients (67% male and 33% female
with age ranging from 3-67 years) suffering from renal failure. The study was conducted between January 2007
and December 2012. The procedure was well tolerated by the patients. The desired aims of dialysis including
improvement in chemistry were achieved in all surviving (94.5%) cases. Mortality during PD was 5.5% and was
related to the underlying causes of renal failure. Peritonitis seen in 30% cases was the commonest complication.
Other complications in order of frequency were, hypokalemia (8%), severe hyperglycemia in diabetic patients
(6%), and sever hypovolemia (5%), pericatheter leak (5%) and catheter blockage (2%). Perforation of the bowel, a
serious complication occurring during insertion of the PD cannula was not seen in any of the cases. It is
concluded from the study that PD is a simple and cost effective alternative to hemodialysis and have special
advantages in the current set-up of the institute. The objective of our work was to study the results and
complications of peritoneal dialysis in light of its efficacy as an alternative form of renal replacement therapy
(RRT) to hemodialysis.
Keywords: Peritoneal dialysis, peritonitis, hyperglycemia, hypovolemia
INTRODUCTION
Renal replacement therapy (RRT) in the form of
dialysis (hemodialysis/ peritoneal dialysis) or
transplantation remains the sole treatment for patients
who sustain renal failure. The gold standard for renal
failure (End stage renal disease-ESRD) is
transplantation but unfortunately it is restricted by
financial limitations in developing countries like
Pakistan.1 Similarly the hemodialysis (HD) facilities
are scarce due to the lack of necessary funds. At
present there are only 175 dialysis centers throughout
the country2 and few of them are available in remote
areas. The dialysis treatment is in-fact expensive and
at the same time lifesaving but due to meager
facilities and poverty, the PD is a cheaper option in

CKD patients with good residual renal function.
Renal failure is becoming a public health problem
with increasing incidence and prevalence, high cost
and unfortunately poor outcome.3The total burden of
ESRD continues to rise including patients with many
advanced comorbidities.4The growing burden of this
special population requires the use of alternative renal
replacement therapy. Peritoneal dialysis (PD) is an
alternative renal supportive therapy (RST) to HD
which if use wisely can share some of the load. The
utilization of peritoneal dialysis is low despite of
equal patient survival on HD and PD, and fluctuates
5
Akhtar et al.,
Int J Med Res Health Sci. 2014:3(1):5-11
only at around 15% of the ESRD population.5,6 Both

PD and HD have their specific advantages and
disadvantages and different factors influence the
choice of RRT. PD is generally preferred to HD in
very small children and those with severe
cardiovascular instability.7,8
The better preservation of residual renal function,
lower risk of infections with hepatitis B and C, better
outcome after transplantation, preservation of
vascular access and lower cost are arguments to
promote PD as a good initial treatment. Hospital
based PD may be the only option for elderly with
significant morbidities making them unable to
undergo HD. Despite a valuable and effective option
with acceptable survival rates the use of PD is still
low for special group of ESRD.6,9
There have been very few publications on the clinical
experience of PD in our country; this study was
therefore conducted with the aim to describe our
experience and results of PD at our institute.
MATERIAL AND METHODS
Sample size and study location: This study was
conducted at the department of Nephrology, Institute
of Kidney Diseases, HMC, Peshawar between Jan
2007 and December 2012 after taking approval from
the ethics committee of our institution. A total of 253
patients who presented with end stage renal disease
(ESRD) / Acute Renal Failure (ARF) were recruited
from January 2007 to December 2012 (6 years).
Study subjects
Inclusion criteria: Subjects from all age groups,
including paediatric population (less than 8 years
old), patients with poor cardiovascular status (blood
pressure less than 100 systolic, evidence of previous
myocardial infarction or cerebrovascular accident)
and those with hepatitis B surface antigen were given
PD instead of HD. Patents from far flung areas were
given palliative PD if it was felt that their prospects
of long term dialysis or transplant were extremely
poor. Lack of HD slot or unavailability of
consumables in the HD unit as well as refusal for HD
by the patients or their relative were another reason
for choosing PD. Verbal and written informed
consent was obtained from the participants of the
study.
Exclusion
criteria:
Patients,
who
were
hemodynamically stable, had prospects for long term
maintenance hemodialysis and had prospects for renal
transplantation. Those patients who had access and

affordability for dialysis were excluded from the PD
group. Age group more than 10 years with
hemodynamic stability was also not included in the
PD group.
Peritoneal Dialysis Procedure: Following urinary
catheterization, PD cannula insertion was performed
as a bedside procedure in the ward using aseptic
techniques and local anesthesia. In order to avoid
perforation of the bowl and facilitate optimum
positioning of the PD catheter, intraperitoneal
infusion of about two liter dialysate using an ordinary
intravenous cannula was usually carried out prior to
insertion of the PD cannula. The cannula was secured
and the entry point was closed by applying a pursestring suture. Hourly exchanges with 500 ml to 2000
ml standard PD solution (Braun or Otsuka) were
carried out. Two hundred units of heparin were added
to each liter of dialysate. Proper record of exchange
with emphasis on accurate fluid balance was kept.
Clinical and Biochemical assessment: Patients were
assessed clinically and pre- and post-dialysis
chemistry was measured to look at the efficacy of the
dialysis.
Statistical analysis: All the results were expressed as
percentages and frequencies by using Microsoft Excel
(version 2010).
RESULTS
Gender based distribution of patients with renal
failure
The data in table 1 show gender based distribution of
patients with renal failure. It is clear from the table
that among 253 patients 170 were male and 83 were
female. The mean age of patients was 23 years ranged
between 3 to 67 years.
Table 1: Gender based distribution of patients
with renal failure
Gender
Number
Percentage
Male
170
67
Female
83
33
Causes of chronic renal failure (CRF)
The data in table 2 shows the various causes of
chronic renal failure. Out of 253 cases 152 (60%)
were suffering from chronic renal failure. Most of
these patients had small echogenic kidneys (n=93)
suggesting
the
underlying
causes
of
glomerulonephritis in the majority followed by
6
Akhtar et al.,
diabetic nephropathy (n=18). The adult polycystic

kidney disease was found in 16 cases followed by
obstructive uropathy (n=14). Renal amyloidosis and
cirrhosis was found in 6 and 5 cases, respectively.
Table 2: Causes of chronic renal failure (CRF)
(n=152)
Causes of CRF
Number %
Small echogenic kidneys 93
61.18
(chronic glomerulonephritis)
Diabetic nephropathy
18
11.84
Adult polycystic kidney 16
10.53
disease
Obstructive uropathy
14
9.21
Renal amyloidosis
6
3.95
Cirrhosis
5
3.29
Causes of acute renal failure (ARF)
40% (101) of the patients had ARF. Table 3 shows
the causes of ARF from various causes.. The
commonest cause of ARF was post-diarrheal volume
depletion (n=24) followed by hemolytic uremic
syndrome (n=15), obstetrics (n=13) and septicemia
(n=12). Other factors responsible included
obstruction
from
calculi
(n=11),
acute
glomerulonephritis (n=7), acute tublo-interstitial
nephritis (n=5), acute pyelonephritis (n=5), hemolysis
(n=3), post-operative (post-CABG) (n=3), and
poisoning (n=3), respectively.
Table 3: Causes of acute renal failure
(n=101)
Causes of ARF
Number
Post-diarrheal volume depletion 24
Hemolytic uremic syndrome
15
Obstetric
13
Septicemia
12
Obstruction from calculi
11
Acute glomerulonephritis
7
Acute tublo-interstitial nephritis 5
Acute Pyelonephritis
5
Hemolysis
3
Post-operative (post-CABG)
3
Poisoning
3
(ARF)
%
23.76
14.85
12.87
11.88
10.89
6.93
4.95
4.95
2.97
2.97
2.97
Reasons for choosing peritoneal dialysis

Reasons for choosing PD dialysis as an alternative to
HD included; very small children (22.13%), HbsAg
positive (11.86%), lack of HD slot (33.99%),
palliative PD for CRF (33.99%) and cardiovascular
instability (20.95%).
Table 4: Reasons for choosing peritoneal dialysis

Reasons for choosing PD Number Percentage
Small children
56
22.13
HbsAg +ve
30
11.86
Lack of HD slot
86
33.99
Palliative care for CRF
86
33.99
Cardiovascular instability
53
20.95
Hepatitis B surface antigen status of the patients
given peritoneal dialysis
Thirteen patients in the ARF group and twenty
patients in the CRF group had hepatitis B surface
antigen positive (Table 5). Infection with hepatitis B
may be associated with a variety of renal diseases i.e.
membranous
glomerulonephritis,
membrane
proliferative glomerulonephritis, IgA nephropathy,
mesangial glomerulonephritis and amyloidosis
etc.23,24
Table 5: Hepatitis B surface antigen of the patients
given peritoneal dialysis
HbsAg(+ve) HbsAg(-ve) Total
13
88
101
ARF
23
129
152
CRF
36
216
253
Total
(ARF: Acute renal failure, CRF: Chronic renal failure)
Effect of peritoneal dialysis on the blood chemistry

of the patients
There was an overall improvement in the blood
chemistry of the patients. The peritoneal clearance of
blood urea and serum creatinine before and after
dialysis in both ARF and CRF patients is presented in
table 6.
Table.6 Effect of peritoneal dialysis
chemistry of the patients
Blood urea
(mg/dl)
170-400
Pre-dialysis in ARF
(mean 190)
50-110
Post-dialysis in ARF
(mean 64)
280-324
Pre-dialysis in CRF
(mean 300)
100-150
Post-dialysis in CRF
(mean 120)
on the blood
S. Creatinine
(mg/dl)
8-18
(mean 12)
1.2-3.5
(mean 1.4)
13-25
(mean 15)
4-6
(mean 5.0)
(ARF: Acute renal failure, CRF: Chronic renal failure)
7
Akhtar et al.,
Complications during peritoneal dialysis

Various complications during peritoneal dialysis were
also experienced (Table 7). The most common
complication was peritonitis which occurred in 76
(30%) cases, which responded to antibiotic therapy
and removal of the PD cannula. Traumatic
complications from insertion of the PD cannula were
infrequent and were mainly minor intra-peritoneal
bleed (n=15). None of the patient had perforation of
the bowl. Other catheter related complications
included pericatheter leak (n=13). Scrotal edema
(n=10), pain on running fluid (n=8) and blockage of
catheter (n=5), the later responding to repositioning
of the catheter. Metabolic complications encountered
were hypokalemia in 20 cases, severe hyperglycemia
in 15 diabetic patients and severe hypovolemia
requiring intravenous fluids in 13 cases.
Table.7 Complications during peritoneal dialysis
Complications
Number %
PD peritonitis
76
30.04
Blood stained effluent
15
5.93
Pericatheter leak
13
5.14
Scrotal edema
10
3.95
Pain on running fluid
8
3.16
Blockage of catheter 5
1.98
(catheter repositioned)
Hypokalemia
20
7.91
Hyperglycemia
15
5.93
(in diabetes)
Hypovolemia
13
5.14
Signs and symptoms of peritonitis
Signs and symptoms of peritonitis in order of
frequency were abdominal pain (98%), fever (77%),
rigors (33%), diarrhea (17%), nausea and vomiting
(13%) and constipation (10%).
Table 8: Signs and symptoms of peritonitis (n=76)
Symptoms and signs
Number %
Abdominal pain
75
98
Fever
59
77
Rigors
25
33
Diarrhea
13
17
Nausea and vomiting
10
13
Constipation
8
10
Abdominal tenderness
64
84
Leukocytosis
56
74
Cloudy fluid
76
100
Most patients with peritonitis had pyrexia (77%),

abdominal tenderness (84%) and leukocytosis (74%).
All (100%) patients suffering from peritonitis had
cloudy fluid on return. Multiple other studies have
also observed that more than 90% of the patients have
cloudy fluid (100% of ours) and many have
abdominal pain (98% of our patients).27,28
Frequency of organisms isolated from patients
peritonitis
Table 9 shows the incidence of different organisms
responsible for peritonitis. Gram positive organisms
were responsible for 44 cases of peritonitis and were
either due to Staph aureus (28 cases) or Staph
epidermis (16 cases). Peritonitis caused by Gram
negative organisms was seen in 32 cases. These
comprised Pseudomonas (19 cases), Enterobacter (10
cases) and E.coli (3 cases). Culture from 13 cases of
peritonitis did not reveal any growth. Findings from
other studies also revealed that gram-positive
organisms are more responsible for causing most
episodes of peritonitis (64.6%) than gram-negative
organisms (20.5%).29
Table 9: Frequency of organisms isolated from
patients peritonitis (n=76)
Organisms
Number %
Staphylococcus aureus
28
36.84
Pseudomonas
19
25.00
Staphylococcus Epidemidis
16
21.05
Enterobacter
10
13.16
E.coli
3
3.95
DISUCUSSION
The effectiveness of PD was evaluated in 253
subjects at the institute of Kidney Diseases,
Peshawar. Kidney failure was more prevalent among
male than in female. This was in agreement with the
finding of Neugarten et al., (2000) that man
experiences a more rapid decline in renal function
and worse outcome than in female. The underlying
mechanisms for this gender disparity are potentially
related to differences between the sexes in glomerular
structure, glomerular hemodynamics, diet, variations
in the production and activity of local cytokines and
hormones, and/or the direct effect of sex hormones on
kidney cells.10,11 Further it is stated that men with
chronic kidney disease (CKD) are 50% more likely to
progress to renal failure.12
8
Akhtar et al.,
The causes of CRF findings suggested that a broader

spectrum of CKD risk factors including both
infectious and environmental factors as well as
genetics predisposes to earlier onset and more rapid
progression of CKD. Therefore a basic understanding
of the vulnerabilities will help the treatment and
prevention of CKD in this population. 13 On the other
hand there is variably among the causes of ARF and
differ from country to country and vary from center
to center in a country. However, there has been an
overall increase in the incidence of ARF with the
changing etiology of ARF in the recent years. The
incidence of obstetrical, surgical and diarrhea related
ARF have decreased significantly, whereas those of
ARF associated with malaria, sepsis, nephrotoxic
drugs and liver diseases have increased. 14
The reason for using PD in our unit has gradually
increased not only in ARF but also in CRF. 60% of
our patients who had received PD had CRF. The
usual form of PD given to CRF patients is CAPD
using tencknoff catheter.15,16 Unfortunately, both the
tenckoff catheter and the CAPD solution are imported
items making the treatment costly and practically
unaffordable for most of our patients. Hence we carry
out IPD using stylet cannula and ordinary PD
solution.
In addition to financial restraints there are other
reasons for our increasing use of PD. The majority of
patients with CRF are usually illiterate with poor
insight and hence generally non-compliant. Suffering
from denial syndrome they often consult Hakims
and visit shrines with the hope that their illness will
be cured. Some of the patients belong to the far flung
areas and are unable to attend frequently for
maintenance HD. Commencing such patients on HD
without ensuring HD its maintenance is of little
benefit and may, in fact hazardous. For example, HD
often causes loss of residual renal function and
aggravates oliguria.17 Oliguria has been implicated as
a poor prognostic factor in ARF and often lead to life
threatening pulmonary edema in CRF.18,19 A few days
of palliative PD rather than commencing on HD, in
our experience stabilizes such patients and provides
time for counseling and further planning such as
establishing a permanent vascular access.
Our patients with CRF often face delays in getting a
successful arterio-venous fistula. Dialysis in the
meantime is often provided via a temporary vascular
catheter usually inserted into the subclavian vein,
which often gets infected. This can lead to lifethreatening septicemia.20 It also causes stenosis or
occlusion of the vein and may lead to failure of
arteio-venous fistula on that side subsequently.21,22 By
giving PD initially, we can prevent these
complications.
Provided certain precautions are taken, insertion of
the style peritoneal cannula is usually a safe
procedure. Perforation of the bowl is, however, a
known complication which usually responds to
conservative treatment.25,26 None of patients had
either perforation of the bowel or severe hemorrhage.
This was mainly due to our policy of introducing 2 to
3 liters of fluid into the peritoneal cavity before
cannulation which minimizes the trauma. Minor
bleeding occurred in five patients.
Peritonitis curing in 76 patients was the commonest
complication and was mainly due to lack of proper
aseptic condition on part of patients relative. Dialysis
was concluded when either the required aims were
achieved or when peritonitis occurred. With removal
of catheter and antibiotic therapy, peritonitis usually
quickly settled. Pericatheter leak occurred in only five
patients and responded to reduction in volume
exchanges. Due to tremendous ultra-filtration,
significant hypovolemia requiring the replacement
fluid occurred in thirteen patients. Hypokalemia
occurring in twenty of our cases was treated by the
addition of potassium in the dialysate.
Most our patients accepted PD well. The immediate
aims of dialysis such as amelioration of uremic
symptoms, correction of acidosis and improvement in
azotemia were achieved in all patients. Fluid overload
was also successfully treated with PD. Fluid removal
facilitated the use of nutritional fluid. Some of the
patients initially treated with PD due to lack of space
in HD unit were later shifted to HD when space
became available and further dialysis required.
CONCLUSION
From our experience, we conclude that PD is an
excellent form of dialysis for the treatment of ARF,
especially
in
children
and
elderly
with
cardiovascular-instability. In addition, it can be used
as an initial treatment in those cases of CRF where
the prospects of regular follow-up for long-term
dialysis are extremely poor or when there is
likelihood of delay in getting a permanent vascular
access established.
9
Akhtar et al.,
ACKNOWLEDGMENT
The authors sincerely thank the record keepers of our
institution for maintaining and helping in retrieval of
the relevant record.
RECOMMENDATION
There is a need for further studies including a larger
sample size and long term follow up.
REFRENCES
1. Siddiqa M, Azad M, Pervaiz MK, Ghias M, Shah
GH and Hafeez U. Survival analysis of dialysis
patients under parametric and non-parametric
approaches.
Electron. J. app. stat. anal.
2012;5(2); 271-88.
2. Pakistan Kidney Foundation (2008). Dialysis
registry. http://www.kidneyfoundation.net.pk.
3. National Kidney Foundation. K/DOQI. Clinical
practice guidelines for chronic kidney disease:
evaluation, classification, and stratification. Am.
J. Kidney Dis. 2002;39(2):S1-S66.
4. Guest S, Akonur A, Ghaffari A, Sloand J, and
Leypoldt JK. Intermittent Peritoneal Dialysis:
Urea Kinetic Modeling and Implications of
Residual Kidney Function. Perit Dial Int.
2012;32(2): 142-48.
5. Gokal R, Mallick N. Peritoneal dialysis. Lancet.
1999;353(9155):82328
6. Van Biesen W, Vanholder R and Lameire N. The
role of peritoneal dialysis as the first-line renal
replacement modality. Perit Dial Int. 2000;20
(4) 375-83.
7. Donalson MDC, Spargeon P, Haycock GB,
Chantler C. Peritoneal dialysis in infants. Br
MED J. 1983;286:759-60.
8. Pur G, Korzets A, Hochhauzer E, Eschar Y,
Blum M, Avirum A. Cardiac arrhythmia during
continuous ambulatory peritoneal dialysis.
Nephron.1987; 45(3): 192-95.
9. Fourtounas C, Hardalias A, Dousdampanis P,
Savidaki E and Vlachojannis JG. Intermittent
peritoneal dialysis (IPD): an old but still effective
modality for severely disabled ESRD patients.
Nephrol. Dial. Transplant. 2009;24 (10): 321518.
10. Silbiger SR, Neugarten J. The role of gender in
the progression of renal disease. Adv. Ren.
Replace Ther. 2003;10(1):3-14.
11. Neugarten J, Acharya A, Silbiger SR. Effect of

gender on the progression of nondiabetic renal
disease: a meta-analysis. J. Am. Soc. Nephrol.
2000;11:31929.
12. National Chronic Kidney Disease Fact Sheet
2010.
http://www.cdc.gov/diabetes/pubs/
factsheets/ kidney.htm
13. Martins D, Agodoa L, and Norris K.Chronic
Kidney Disease in Disadvantaged Populations.
Int. J Nephrol.2012; http://dx.doi.org/10.1155/
2012/469265
14. Prakash J, Singh TB, Ghosh B, Malhotra V,
Rathore
SS, Vohra
R, etal.
Changing
epidemiology of community-acquired acute
kidney injury in developing countries: analysis of
2405 cases in 26 years from eastern India. Clin
Kidney J. 2013;6(2): 150-55.
15. Nolph KD, Cutler SJ, Steinberg SM and Novak
JW. Continuous ambulatory peritoneal dialysis in
the United States: a three year study. Kidney Int.
1985;28:198-205.
16. Gokal R. Continuous ambulatory peritoneal
dialysis- Ten years on. Q J Med. 1987;63(242):
465-72.
17. Ahmed M Alkhunaizi and Ribert. Management of
Acute Renal Failure: New Prospectives. W
Schrier. Am J Kidney Dis. 1996;28(3); 315-28.
18. Bullock ML, Umen AJ, Finkelstein M and Kean
WF. The assessment of risk factots in 426
patients with ARF. Am J Kidney Dis. 1985;5 (2):
97-103
19. Anderson RJ, Linas SL, Bens AS, Henrich WL,
Miller TR, Gabow PA etal., Nonoliguric acute
renal failure. N Engl J med.1977;296 (20): 113438.
20. Derrick LR, Vance GF, Daniel JS, Ralph GC,
Peter JC. Bacterial endocarditis in hemodialysis
patients. Am J Kidney Dis. 1997;30 (4):521-24.
21. Shaheen FA, Sheikh IA, Badawi L, Al-Aqeil N,
Reyati JM. Complication of subclavian vein
cannulation in hemodialysis patietns. Saudi
Kidney
Diseases
and
transplantation
Bulletin.1990
22. Schillinger F, Schillinger D, Montagnac R, Miller
T. Postcatheterization vein stenosis on
hemodialysis: comperative angiographic study of
50 subclaian and 50 internal jugular access.
Nephrol Dial Transplant. 1991; 6 (10):722-24.
10
Akhtar et al.,
23. Johnson RJ, Couser WG. Hepatitis B infection

and renal disease: clinical, immunopathogenetic
and therapeutic considerations. Kidney Int. 1990.
;37 (2):663-76.
24. Lai KN, Lai FM. Clinical features and the natural
course
of
hepatitis
B
virus-related
glomerulopathy in adults. Kidney Int Suppl.
1991;40(35);S24-S33.
25. Simkin EP, Wright FK. Perforating injuries of the
bowl
complicating
peritoneal
dialysis
catheter.insertion. Lancet. 1968;291 (7533):6466.
26. Rubin J, Oreopoulos DG, Lio TT, Mathews r,
Veber GA. Management of peritonitis and bowl
perforation during chronic peritoneal dialysis.
Nephron. 1976;16(3):220-25.
27. Tranaus A, Heimburger O, Lindholm B.
Peritonitis on continuous ambulatory dialysis
(CAPD); diagnostic findings, therapeutic
outcomes and complications. Perit. Dial. Int.
1989;9: 179-190.
28. Fanigan MJ, Freeman RM, Lim VS. Cellular
response to peritonitis among peritoneal dialysis
patients. Am J Kidney Dis.1985;6 (4); 420-4.
29. Lartundo JAQ, Palomar R, Domingues-D A,
Salas C, Ruiz-carado J, Rodrigo E, De-Francisco
ALM and Aris M.. Microbial profile of peritoneal
dialysis
peritonitis
and
predictors
of
hospitalization. Adv. Perit. Dial. 2011;27 (1): 3842.
11
Akhtar et al.,
DOI: 10.5958/j.2319-5886.3.1.003

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Coden: IJMRHS
Copyright @2013
th
Revised: 9 Oct 2013
ISSN: 2319-5886
Accepted: 4th Nov 2013
Research article
A STUDY ON CHANGES IN SERUM GGT AND MAGNESIUM LEVEL IN ALCOHOLIC LIVER
DISEASE
*Gandhi Paulin A1, Sendhav Sandip S2, Sanghani Hiren I2, Patel Arpita P3
1
Tutor, Departments of Biochemistry, G.C.S. Medical College, Ahmedabad, Gujarat, India

Senior Resident, Departments of Biochemistry, B. J. Medical College & Civil Hospital, Ahmedabad, Gujarat
3
Junior Lecturer, Departments of Biochemistry, N.H.L. Medical College, Ahmedabad, Gujarat, India
2
*Corresponding author email: pautalk@gmail.com

ABSRACT
Aims: A study on changes in Serum GGT and Magnesium level in Alcoholic Liver Disease. Material and
Methods: Serum GGT and Serum Mg++ were estimated with the help of commercially available kit in patients of
Alcoholic Liver Disease (n=50) and Normal Individuals (n=50) on fully automated biochemistry analyzer Erba
XL-640. Results: Serum GGT level was found significantly higher (P< 0.01) in Alcoholic patients as compared to
healthy non-alcoholics. Moreover Serum Mg++ was found significantly lower (P< 0.01) in Alcoholic Liver
Disease as compare to normal Individuals. In addition to that there is significant inverse correlation (r= - 0.553)
between serum GGT and Mg++ in study group. Conclusions: None of the individual tests of conventional liver
function tests are of much importance in diagnosis of liver disease; however when many of the liver function tests
are abnormal at the same time, liver disease is the most probable diagnosis. Data of the present study clearly
conclude that serum GGT activity along with serum Mg++ status can be useful marker for alcoholic liver disease.
Keywords: Gamma Glutamyl Transferase, Magnesium, Alcoholic Liver Disease
INTRODUCTION
Excessive alcohol consumption and consequent
medical disorders are considerable problems in our
countries which causes a wide variety of medical and
social problems1. It is estimated that only 20-50 % of
patients with alcoholism are actually identified in
health care and thus more reliable and accurate
methods are urgently needed. There is no exact
clinical finding or symptom clinical setting that
can detect alcohol abuse in its early phase. So
there are some biochemical substances in the body
that can indicate the presence or progress of a
condition or any genetic predisposition toward it, are
called Biomarkers 2 which may detect excessive
drinking and evaluate the extent of the resultant tissue
damage.
Gamma-glutamyl transferase (GGT) is a membranebound glycoprotein enzyme which catalyzes the
transfer of the gamma-glutamyl moiety of glutathione

to various peptide acceptors. Chronic ethanol
consumption induces a rise in serum GGT, and it has
therefore been widely used as an index of excessive
ethanol intake 3-4. Its sensitivity varied from 15 to
85% in previous studies8-10. Recent work by
comparing alcoholic group with normal control group
which emphasis on important factor serum GGT
activities which can increase in case of alcoholics 5-6.
Magnesium (Mg++) a ubiquitous element, involve in
membrane stabilization, ion transport, and Ca++
channel activity, cofactor for more than 300 enzymes
7
, may get depleted by several mechanisms associated
with alcoholism like magnesium deficiency,
including urinary Mg++ wastage, malnutrition,
gastrointestinal losses, phosphate deficiency,
acidosis/alkalosis, vitamin D deficiency etc.
12
Gandhi et al.,
This work was aimed at investigating the diagnostic

value of serum GGT level and Serum Mg++ level and
correlation of serum GGT and Mg in the evaluation
of chronic alcoholic liver disease.
In the present cross-sectional study, 50 cases of
Alcoholic liver disease and 50 normal individuals
were selected from OPD and various clinical wards of
B.J. Medical College and Civil Hospital, Ahmadabad,
Gujarat during the period of April 2010 to December
2012. The study was approved by the BJ Medical
college, Ahmadabad and inform consent form was
obtained form the all participants. All patients were
primarily evaluated by clinical examination and then
confirmed by investigations for liver involvement due
to alcoholism. In study group (n=50), we have
included male patients between age of 20 60 years,
BMI 30 kg/m 2, alcohol consumption for at least last
5 years with clinical evidence of alcoholic liver
dysfunction. In control group (n=50), we have
included normal healthy individuals having same age
and sex. Exclusion criteria: Age < 20 or >60 years,

Athletes, Clinical Evidence of current illness, Clinical
evidence of any chronic infection, Smoking had not
been allowed 1 hour prior to sampling, Protein energy
malnutrition, Post operative patient, Patient taking
anticonvulsant
therapy
(Benzodiazepines,
2
Phenobarbitone), BMI > 30 kg/m , Serum Bilirubin
level > 20 mg/dL.
Venous blood was collected in clot activator serum
vacutte from all the participants. Serum was separated
and analyzed for GGT, Mg on fully Auto Analyzer
Erba XL-640 at Biochemistry Section. Serum GGT
was analyzed by carboxy substrate8 method and
serum Mg was analyzed by calmagite method9 with
commercially available ready to use reagent kits.
Numerical variables are reported in terms of mean
and standard deviation. Comparison between two
groups is made with the Mann-Whitney test 10.
Correlations were calculated with pearson product
moment correlation coefficient by using graphpad
prism version 3.03 statistical software.
RESULTS
Table 1: Comparison of Serum GGT and Magnesium in Alcoholic Liver Disease and Normal Individual
GGT
Magnesium
Group-2
(Control
Biological
Group)
Reference Interval
n=50
Mean SD
Mean SD
10-50 U/L
101.04 52.2
42.02 12.82
1.6 3.0 mg/dL
1.50 0.49
2.03 0.36
*P< 0.01: highly significant difference between two groups
In this study we measured Serum activity of Gamma

Glutamyl Transferase and Magnesium in both groups.
There is highly significant difference observed in
between study group and control group. Correlation
between serum GGT and Magnesium level in
alcoholic liver disease and normal individual during
observation significant inverse correlation (r= - 0.533,
P<0.01) was found in alcoholic patients whereas it
was not significant in normal individual (r= 0.031,
P>0.05).
3.5
Significance
P value
P<0.01*
P<0.01*
Graph 1: Study Group
3
Magnesium(mg/dL)
Parameter
Group-1(ALD
Patients)
n=50
2.5
2
1.5
1
0.5
0
0
100
200
300
GGT (U/L)
Fig 1; Correlation of serum GGT with magnesium in
Study group
13
Gandhi et al.,
Graph 2: Control Group

Magnesium (mg/dL)
3.5
3
2.5
2
1.5
1
0.5
0
0
20
40
60
80
100
GGT ( U/L)
Fig 2: Correlation of serum GGT with magnesium in
control group
DISCUSSION
Liver serves many important biological functions to
sustain life, so early diagnosis of liver involvement is
of utmost priority to prevent life threatening
complications. Over past decade a large number of
new laboratory markers have emerged for alcohol
abuse. One of these is Gamma Glutamyl Transferase.
In order to assess its usefulness, I have studied Serum
GGT level and Serum Magnesium in 50 patients of
alcoholic liver disease and 50 normal individual. I
have tried to match control with the disease
population as far as possible.
Glutamyl transpeptidase (GT) is an enzyme
produced in the bile duct. It is induced by alcohol and
its serum activity may be increased in heavy drinkers
even in the absence of liver damage or inflammation.
In this study the serum GT levels were markedly
increased in alcoholic patients (P<0.01). The GGT
activity in serum increases after induction of the
enzyme, and the possibility of parenchymal damage
should always be considered. The elevation of GT
alone with no other liver function test abnormalities
often results from induction by alcohol 11.
The
results of present study are correlate well with earlier
studies by B. Usharani et al 2012 12, Turecky L et al.
2006 7, Subir kumar Das et al 2005 13 etc.
Chronic alcohol abuse also causes primary
malnutrition by insufficient dietary magnesium
intake. Moreover, as the cause of secondary
malnutrition chronic ethanol intake leads to
functional and structural disorders in the
gastrointestinal tract that result from its direct action
on the gastrointestinal tract and damage to the liver

and pancreas. In also affects the magnesium transport
mechanisms in the plasma membrane, either directly
(alcohol-related modification of the phospholipid
environment or acetaldehyde-protein interaction) or
indirectly (via the decrease in cellular ATP
content).One of the major reasons for ethanolinduced hypomagnesaemia in alcohol abusers is
increased urinary magnesium excretion due to
damage to the renal proximal tubules and the Henle
loop directly induced by ethanol 15-17. These study is
also supported by data of previous studies Elisaf M.
et al 1995 18 and Virginija Stasiukynien et al 2002 19.
It is concluded from the present study that the
estimation of serum GGT can be useful and more
cost-effective in diagnosing alcoholic liver diseases
as it significantly rises in alcoholic liver disease.
Moreover, serum Mg can also be used as a marker of
chronic alcoholic liver disease along with serum GGT
as they have significant correlation in alcoholic liver
disease.
CONCLUSION
It is concluded from the present study that the

estimation of serum GGT can be useful and more
cost-effective in diagnosing alcoholic liver
diseases as it significantly rises in alcoholic liver
disease. Moreover, serum Mg can also be used as
a marker of chronic alcoholic liver disease along
with serum GGT as they have significant
correlation in alcoholic liver disease.
REFERENCES
1. Room R, Babor T, Rehm, J. Alcohol and public
health. Lancet 2005; 365: 51930.
2. Peterson K. Biomarkers for alcohol use and
abuse: A summary. Alcohol Res Health 20042005; 28(1):30-37.
3. Zein M, Discombe G. Serum gamma-glutamyl
transpeptidase as a diagnostic aid. The Lancet
1970; 296: 74850.
4. Gogoi JB, Tyagi PK, Amit Singh. Study of serum
gamma glutamyl transferase as a diagnostic
marker in alcoholic hepatitis. IOSR Journal of
Pharmacy (IOSRPHR) 2012; 2; 69-71.
5. Peters TJ, Cook CC. Obesity as a cause of
falsepositive alcohol misuse laboratory
14
Gandhi et al.,
investigations. Addiction Biology 2002; 7:443

46.
6. Katri Puukka. Gamma-glutamyl Transferase As a
Marker of Alcohol Abuse: Effects of Moderate
Drinking, Obesity & Increasing Age on
Reference Intervals, University of Tampere,
Medical School Seinajoki Central Hospital,
Department of Laboratory Medicine and Medical
Research Unit, Finland, 2007: pp 15.
7. Turecky L, Kupcova V, Szantova M. Serum
magnesium levels in patients with alcoholic and
non-alcoholic fatty liver. Bratisl Lek Listy. 2006;
107(3):58-61.
chronic alcoholic patients during

withdrawal. Medicina 2002; 38:892-95.
alcohol
8. Bergmeyer H-U, Horder M, Rej R. IFCC

methods for the measurement of catalytic
concentrations of enzymes, J. Clin. Chem.
Clin Biochem. 1986; 24: 497-510.
9. Gindler E. Colorimetric Determination With
Bound "Calmagite" of. Magnesium in Human
Blood Serum. Clin. Chem.1971; 17: 662.
10. Rosie Shier. Statistics:2.3 The Mann-Whitney U
Test. Mathematics learning support center
2004:1-5.
11. Keeffe EB, Sunderland MC, Gabourel JD. Serum
gamma-glutamyl transpeptidase activity in
patients receiving chronic phenytoin therapy.Dig
Dis Sci. 1986; 31(10): 1056-61.
12. Usharani B, Vennila R, Nalini N. Biochemical
changes in Alcoholics: A case control study.
International
Journal
of
Research
in
Pharmaceutical and Biomedical Sciences 2012; 3:
201-05.
13. Subir Kumar Das, Prasunpriya Nayak,
Vasudevan DM. Biochemical markers for alcohol
consumption. IJCB 2005, 20(1): 35-42
14. Kocur J. Concentration of bioelements in alcohol
dependent patients. Biul.Magnezol. 1997; 2: 239.
15. Elisaf M, Merkooropoulos M. Pathogenetic
mechanisms of hypomagnesaemia in alcoholic
patients. J. Trace Elem. Med. Biol. 1996; 9: 210.
16. Vormann J. Magnesium: nutrition and
metabolism. Mol. Aspects Med.2003; 24: 27.
17. Elisaf M, Merkouropoulos M, Tsianos EV.
Pathogenetic mechanisms of hypomagnesemia
in alcoholic patients. J Trace Elem Med Biol
1995; 9: 210-14.
18. Virginija
Stasiukynien.
Blood
plasma
potassium, sodium and magnesium levels in
15
Gandhi et al.,
DOI: 10.5958/j.2319-5886.3.1.004

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Research article
Copyright @2013
ISSN: 2319-5886
EFFECT OF GONADAL HORMONES ON HYPOPHAGIC PROPERTY OF OPIOID ANTAGONIST

NALOXONE
Gargate Ashwini R1, Kulkarni Dushant V2
1
Associate Professor, 2M. Sc (Med Physiology) Student, Department of Physiology, Krishna Institute of Medical
Sciences Deemed University, Karad, Maharashtra, India.
*Corresponding author email: ashwinigargate@yahoo.in
ABSTRACT
Background: Studies have shown that hormonal fluctuations that occur over the estrous cycle in rats affect food
intake. It is possible that estrogen affects food intake via Opioid system and other brain areas which are involved in
regulation of food intake. Therefore it may affect the sensitivity of female rats to hypophagic effect of Opioid
antagonist Naloxone. Testosterone in male rats also changes food intake. However, little is known about hoe these
Gonadal hormones interact with Opioid receptors to modulate food intake. Objective: The aim of the study was to
find out how Gonadal hormones affect hypophagic property of Naloxone. Methods: Basal food intake of 40
healthy adult females and 20 healthy adult male rats was recorded. Then they were injected intraperitoneally with
Naloxone after fasting for 24 hrs. In female rats food intake was measured during different phases of the estrous
cycle. All the rats were then subjected to gonadectomy. The food intake was measured after gonadectomy. The
effect of Naloxone was also measured in deprivation paradigm after gonadectomy. Results: Female rats showed
decreased food intake during proestrous and estrous phases. In female rats there was no hypophagia after Naloxone
injection during these phases. Male rats showed hypophagia on Naloxone injection. Male rats showed increased
food intake after gonadectomy. In female rats the increase in food intake was not significant when gonadectomy
was done during metestrous and diestrous. However, Naloxone could induce hypophagia in all female rats after
gonadectomy. Conclusion: Estrogen decreases food intake, it decreases sensitivity of female rats to hypophasic
effects of Naloxone. Testosterone decreases food intake. Testosterone does not interfere with hypophagic effect of
Naloxone.
Keywords: Food intake, Gonadal hormones, Naloxone, Hypophagia.
INTRODUCTION
Appetite, energy balance and body weight gain are
modulated
by
diverse
neurochemical
and
neuroendocrine signals from different organs in the
body and diverse regions in the brain. Alterations in
the regulation of food intake and energy expenditure
underlie the development, progression and recurrence
of obesity.1,2 This has been the cause of obesity
related complications like diabetes and hypertension
etc.
This energy balance and fuel utilization are

significantly affected by gonadal hormones, estrogen
in females and testosterone in males. Estrous cycle
related effects on food intake have been linked to the
effects of estrogen on central nervous system and
peripheral tissues.3,4,5 Rodents typically cycle over 4-5
days and phases of estrous cycle are commonly
classified by histological changes in vaginal cytology
which is roughly divided into estrous, metestrous,
16
Gargate AR et al.,
diestrous and proestrous.6 Food intake is generally

increased during diestrous and decreased during
estrous.7 So we confirmed these findings in our
laboratory by conducting the present study.
Previous studies suggest that estradiol acts on muopioid receptors to modulate the antinociception in
rats.8 So estradiol may also modulate food intake by its
action on mu-opioid receptors. Therefore it may affect
the anorectic property of Opioid antagonist naloxone
during different phases of estrous cycle in female rats.
There are studies which show that in male rats
testosterone reduces food intake. Other studies also
show that opioid antagonist naloxone facilitates sexual
behaviour9 and there is no satisfactory explanation to
this. However, possible explanation could be the
interaction between testosterone and Naloxone which
can affect food intake as well.
So the present study was undertaken to evaluate if
Gonadal hormones alter food intake by acting on
opioid receptors in the central nervous system in
addition to their action on other parts of the CNS.
The present study was approved Institutional Animal
Ethics Committee of KIMS, Karad. 40 healthy adult
female and 40 healthy adult male Wistar rats were
used for the study. The average age was 3-4months
old. Animals were weighed, marked and housed in
separate polyvinyl cages in animal room having
controlled room temp (2520c). They were maintained
on 12 hrs dark and 12 hrs light cycle with standard
laboratory diet and water ad lib.
First 8 days baseline food intake in all animals were
recorded. In female rats food intake was recorded
during different phases of estrous cycle.
In deprivation paradigm, the animals were kept fasting
for 24 hrs. Then saline 2ml was injected
intraperitoneally at 9 am on the day of test. 30 mins
after injection the food was weighed and introduced
into the cage. Then the food intake was measured at an
interval of hr, 1hr, 2hrs and 24hrs. These values
were considered as control. Same animals were used
as control on 1st 24 hrs deprivation with saline
injection and on 2nd 24 hrs deprivation they were
injected with naloxone
The animals were kept fasting for 24 hrs again on the
next day. Then 2.5 mg/kg naloxone was injected
intraperitoneally at 9 am on the day of test. 30 mins
after injection the food was weighed and introduced
Gargate AR et al.,
into the cage. Then the food intake was measured at an

interval of hr, 1hr, 2hrs and 24hrs.
Every time the intake was measured by weighing food
prior to and after each condition and adjusting for
spillage that was collected in paper towel under wire
mesh.
Food intake in deprivation paradigm after saline and
after naloxone injection in male and female rats was
recorded. In addition to this the female rats food
intake was recorded during different phases of estrous
cycle after naloxone injection in deprivation paradigm.
Vaginal cytology for stage of estrous cycle: Daily
vaginal smears were obtained at 8.30am to assess the
stage of estrous cycle. Smears were examined under
light microscope. Stage of the cycle was assigned
using the following criteria as previously described6
1) Proestrous when predominantly nucleated epithelial
cells in the absence of leukocytes were present.
2) Estrous when sheets of nonnucleated squamus
cornified cells in absence of leucocytes were present.
3) Metestrous (D1) when there was an equal
distribution of leucocytes and cornified and nucleated
epithelial cells.
4) Diestrous (D2) when a mixture of epithelial cells
and leucocytes with predominance of leucocytes was
present.
Then both male and female rats were gonadectomised.
Procedure for ovariectomy: The female rats were
weighed and then injected with atropine sulphate in a
dose of 0.25mg subcutaneously to minimise the
respiratory discomfort. Intraperitoneal Sodium
pentobarbitone in the dose of 35mg/kg body weight
was injected for anaesthesia, whereas Ether inhalation
was used to maintain a steady level of anaesthesia
while doing gonadectomy.
Anaesthetised rat was placed on a rat operating table
with ventral surface facing towards operator. Animal
was secured properly to the operation table.
Midline incision was taken on lower abdomen
extending for 2cms lengthwise. A snip was made
through the fascia of abdominal rectus muscle. The
points of forceps were forced through the snip and
hole was extended opening the forceps. The ovary was
found embedded in the fat lying just below the dorsal
muscle mass. It was identified by fimbrial end. The
ovary was drawn through the incision, uterus clamped
in a haemostat and a ligature placed around the uterus
just below fallopian tube and was tied tightly. The
ovary was removed. Similarly other ovary was also
removed. The muscle incision was closed with catgut
17
and skin incision with thread. Powder Nebasulf was

sprinkled over the sutures and Benzathin Penicillin, 3
lakh units was injected intramuscularly to prevent
infection. Animal was allowed to recover from
anaesthesia and then was transferred to respective
cage.
A period of 10 days was allowed for recovery from
operative injury following which vaginal smears were
examined for 1 week. Continuous diestrous was taken
as an indication for successful gonadectomy.
Procedure for Orchidectomy: The male rats were
weighed and then injected with atropine sulphate in
dose of 0.25mg subcutaneously to minimise the
respiratory discomfort. Then they were anaesthetised
as in female rats. Anaesthetised rat was kept on the rat
operating table. Part to be operated was shaved
properly. Under aseptic precautions ventral midline
incision was made through the skin of the scrotum.
The slight pressure was given on abdomen as rats are
able to retract testes in abdominal cavity. They were
freely movable within the scrotum. One testis was
drawn through a skin incision. A slit was made
through tunica and the testis was freed. The spermatic

cord which was attached to the testis was doubly
ligated and cord was cut between the ties. Other testis
was removed similarly. Skin incision was closed with
thread sutures. Powder Nebasulph was sprinkled on
sutured skin and rat was injected with 3 lakh units of
Benzathin Penicillin intramuscularly to prevent
infection. 10 days were allowed for recovery from
operative injury.
After measuring 8 days basal food intake, all
gonadectomised rats were injected with 2.5mg/kg
intraperitoneally naloxone after keeping them fasting
for 24 hrs. The food intake was measured as was done
before gonadectomy. Food intake was measured in
grams.
Statistical analysis: For data analysis all the values
were expressed in terms of mean standard error of
mean. Differences between means were compared by
applying pairedt test. The effect was considered
statistically significant if the probability of chance was
less than 0.05 (p<0.005).
RESULT
Table 1: Food intake in female rats during different phases of estrous cycle
Phase of estrous cycle Food intake (in gms.) at different time of the day
1hr
1.5hr
2.5hr
Proestrous
0.6 0.44*
1.10.30*
2.0 0.71*
Estrous
1.35 0.43
1.860.53
3.30.71
Metestrous
2.870.55*
4.160.98*
6.29 0.92*
Diestrous
2.5 0.15*
3.9 0.24*
5.30.23*
*P< 0.05, data presented as Mean SEM
24hr
7.1 0.24*
9.5 0.98
13.16 0.71*
13.82 0.39
Table 2: Effect of different phases of estrous cycle on Naloxone induced hypophagia in deprivation paradigm
in female rats.
Phase of estrous cycle
Food intake (in gms.)
Proestrous
1hr
1.5hr
2.5hr
24hr.
After saline injection
1.7 0.11
2.75 0
4.2 0.37
10.25 0.33
After Naloxone injection
1.2 0.32
2.5 0.16
3.9 0.24
19.0 0.39
Estrous
1.33 + 0.40
1.98 0.46
3.45 0.42
8.23 0.77
0.93 0.09
1.75 0.27
3.00 0.42
10.11 0.29
Metestrous
3.9 0.55
5.0 0.93
7.1 0.92
15.20.71
1.2 0.31*
1.98 0.23*
3.56 0.53*
14.7 0.29
Diestrous
3.1 0.22
4.5 0.62
6.8 1.1
14.30.35
1.5 0.44*
2.25 0.33*
4.25 0.53*
15.2 0.75
Table 2 shows the effect of food deprivation on food
intake in different phases of estrous cycle. After 24 hrs
fasting in female rats during estrous phases there was

no significant increase in food intake.
18
Gargate AR et al.,
However, in metestrous, diestrous and proestrous

phases the food intake was significantly increased after
24 hrs fasting.
This table also shows effect of naloxone on food
intake in different phases of estrous cycle. It was seen
that Naloxone induced significant hypophagia in rats

after 24hrs fasting in metestrous and diestrous. In
proestrous and estrous phases naloxone could not
induce hypophagia in deprivation paradigm.
Table 3: Effect of gonadectomy on food intake and naloxone induced

deprivation paradigm.
Phase of estrous cycle
Food intake (in gms)
Proestrous
1hr
1.5hr
saline injection before gonadectomy
1.7 0.11
2.75 0
saline injection after gonadectomy
4.8 1.1*
5.89 0.76*
Naloxone injection after gonadectomy
2.9 0.32*
4.2 0.16*
Estrous
1.33 0.40
1.98 0.46
3.16 0.42*
3.6 0.53*
1.58 0.29*
2.5 0.15*
Metestrous
3.9 0.55
5.0 0.93
4.4 0.55
5.2 0.44
2.12 0.31*
3.75 0.23*
Diestrous
3.1 0.22
4.5 0.62
4.9 0.33*
5.5 0.9*
2.15 0.65*
3.96 1.07*
Table 4: Food intake after orchidectomy and naloxone injection
Before Gonadectomy
Food intake (in gms.)
1hr
1.5hrs
Basal food intake
2.2 0.27
3.2 0.46
After 24 hrs fasting
After Saline injection
3.0 0.36* 4.3 0.55*
After Naloxone injection 0.6 0.24*
1.7 0.28*
After Gonadectomy
Basal food intake
4.2 0.48*
5.5 0.45*
After 24hrs fasting
1hr
1.5hrs
After Saline injection
4.9 0.57*
6.2 0.42*
After Naloxone injection 1.0 0.19*
1.6 0.42*
Table 3 shows the effect of ovariectomy on food
intake and hypophagia induced by Naloxone in female
rats. It is seen that the food intake was significantly
increased after ovariectomy in all female rats.
However, the increase was not significant when
ovariectomy was done during metestrous phase.
hypophagia in female rats in
2.5hr
4.2 0.37
6.7 0.83*
5.3 0.24*
24hr.
10.25 0.33
14.6 0.45*
13.9 0.39
3.45 0.42
5.06 0.71*
3.75 0.53*
8.23 0.77
13.660.98*
12.95 1.46
6.1 0.92
6.7 0.13
4.25 0.53*
15.2 0.71
15.6 0.89
15.7 0.29
6.8 1.1
7.7 0.24*
5.43 0.47*
14.3 0.35
15.4 0.56*
15.9 0.98
2.5hrs
4.6 0.80
24hrs
15.1 0.82
5.7 0.82*
3.0 0.59*
15.6 0.82
11.8 1.1
6.5 0.60*
2.5hrs
7.2 0.76*
3.0 0.59*
17.0 0.71*
24hrs
17.2 1.88
11.2 1.37
This increase was more pronounced in the female rats

in which ovariectomy was done in estrous and
proestrous phases. Naloxone induced significant
hypophagia in all rats after ovariectomy in initial
period after 24hrs food deprivation.
Table 4 shows food intake in male rats. Food intake is
significantly increased after orchidectomy. In
19
Gargate AR et al.,
deprivation paradigm naloxone induced hypophagia in

initial period of the day before and after orchidectomy.
DISCUSSION
The present study was designed to examine whether
the gonadal hormones affect the hypophagic properties
of naloxone upon food deprivation induced
hyperphagia. It appears that naloxone induces
hypophagia in food deprived male and female rats as
compared to controls (saline). These concur with the
earlier studies.10
It is known that after puberty male rats weigh and eat
more than do female rats of same age. This sex
difference is more pronounced with age. We also
studied the role of sex hormones in regulation of food
intake. We found that during the estrous phase the
food intake of female rats was less and least in
proestrous phase. The food intake was increased
during diestrous but it was highest during metestrous.
These findings are consistent with other workers.11-13
This could be because of wide variations in estrogen
levels during the phases of estrous cycle. The sequence
of phases in the cycle is proestrous, estrous,
metestrous and diestrous. The estrogen levels start
rising in diestrous reaching its peak in proestrous and
start declining during estrous decreasing to lowest
level during metestrous.14,15 Estrogen is known to
affect food intake thorough central and peripheral
mechanisms. Several lines of evidence indicate that the
effects of estradiol on food intake are mediated by its
actions on estrogen receptors within the brain. In the
early 1970's, Wade and Zucker were the first to report
that direct stimulation of the ventromedial
hypothalamus (VMH) by estradiol influenced feeding
behavior in female rats. They found that central
implants of undiluted estradiol benzoate (EB) in the
VMH decreased food intake in ovariectomized rats. 16
In this study we found that after gonadectomy in
female rats there was a significant increase in food
intake. This increase was more pronounced in female
rats where gonadectomy was done during proestrous
and estrous. Perhaps this explains the effect of
withdrawal of high estrogen after gonadectomy.
In our study we found that Naloxone which is an
opioid receptor antagonist blocking mu- receptors,
induces hypophagia in food deprived male and female
rats (p<0.05) as compared to controls (saline). It
appears that naloxone induces hypophagia in food
deprived male and female rats as compared to controls
(saline injection). These concur with the earlier

studies.17,18 One of the main functions proposed for
opioid peptides in the CNS is involvement in
mediation of hunger component in the control of food
intake. Changes in the beta endorphin content of
pituitary or hypothalamus have been demonstrated
under condition designed to reflect changes in the state
of hunger or satiety in rats. In normal rats fasted for 23 days beta endorphin content of the whole
hypothalamus is decreased.19 Several investigators
have also reported that administration of beta
endorphins in CNS increased food intake.20 Intake of
palatable food containing sugar or high fat is
selectively increased by mu-opioid agonist when
injected into ventromedial striatum including nucleus
accumbens.10 Other studies also show that agonists of
mu, delta, kappa and ORL Opioid receptors increase
food intake while Opioid receptor blockade decreases
food intake.21
In female rats we studied the effect of estrous cycle
phases on the hypophagic effect of Naloxone. It was
observed that during proestrous and estrous phases the
Naloxone failed to induce hypophagia in these rats.
Our findings are consistent with earlier studies.22 It is
seen from the previous studies that gonadal steroids
modulate opioid peptides and receptors in the central
nervous system.23- 25 Ovariectomy in rats results in an
increased sensitivity to suppressive effects of
Naloxone on food intake compared with estradioltreated ovariectomised rats.26-29 The probable
explanation for this may be that estrogen acts on muopioid receptors in the brain to modulate the functions
of Opioid peptides.8 When Naloxone is injected it fails
to block the Opioid receptors which are already
blocked competitively by estrogen. So Naloxone fails
to induce hypophagia in the presence of high estrogen.
In this study we found that after gonadectomy in all
the female rats naloxone induced significant
hypophagia when estrogen was no more there for
competitive blockade of the receptors.
In male rats also Naloxone induced hypophagia in
deprivation paradigm. After gonadectomy the basal
food intake of male rats was increased. After
gonadectomy in these male rats food intake was
significantly increased. In all these rats Naloxone
induced significant hypophagia before and after
gonadectomy. These findings suggest that testosterone
in males interferes with the mechanisms on energy
intake however unlike estrogen it does not interact
20
Gargate AR et al.,
with opioid receptors to alter the hypophagic effect of

Naloxone. Our findings concur with the other studies.
Gonadectomised male rats treated with testosterone
propionate showed decrease in food intake.21
7.
CONCLUSION
Amongst the Gonadal hormones estrogen in females
and testosterone in males modulates food intake.
However, estrogen interferes with the hypophagic
effects of naloxone perhaps by competitive blockade
while there is no such alteration caused by
testosterone. How do these Gonadal hormones and
Opioid receptors interact to modulate food intake
needs to be further investigated.
ACKNOWLEDGEMENT
The authors are thankful to the vice chancellor and
principle KIMS deemed university, Karad for
providing us all the laboratory facilities for doing this
work. We are also thankful to our laboratory
technicians for assisting us during operative
procedures.
8.
9.
10.
11.
12.
Conflict of interest-None declared.

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DOI: 10.5958/j.2319-5886.3.1.005

&
Health Sciences
www.ijmrhs.com
rd
Research article
Copyright @2013
ISSN: 2319-5886
HEMOGLOBIN A1C INDUCED DOWN-REGULATION OF CD36 OF PLASMODIUM FALCIPARUM

PARASITIZED RED CELL
Hassan Hijazi1, Atif Alagib2, *Hisham Waggiallah3
1
AL-Ghad International Colleges for Applied Health Science, Qassim, Saudia Arabia
Tropical Medicine Research Institute, National Centre for research, Ministry of Science and Technology, P. O.
1304, Sudan.
3
Department of Medical Laboratory, Faculty of Medical Applied Science, Taibah University. P.O Box 3001,
Almadinah Almonawarah, Saudia Arabia.
2
*Corresponding author email: hishamwagg30@hotmail.com

ABSTRACT
Objective: High values of glycosylated hemoglobin have been found to correlate with decreased deformability of
erythrocyte. CD36 (Cluster of Differentiation 36) is an integral membrane protein found on the surface of many cell
types of class B scavenger receptor family. Plasmodium falciparum and diabetes mellitus is associated many
complications. Aim of this study to investigate the down-regulation of HbA1c to CD36 on P. falciparum parasitized
red blood cells Diabetes mellitus patients. Methods: This is cross section study conducted among diabetic patients
attending in Jabir Abo Eleiz diabetic center in Khartoum state. Venous blood samples were collected in heparin
containers for Plasmodium falciparum culture, and random blood sugar. For HbA1c in 0.04 mg EDTA
anticoagulant, 2-5 ml of blood was collected. Sample size was 45 samples and was collected from known diabetic
patients with HbA1c more than 8%. All data were analyzed by using Statistical Package for Social Science (SPSS).
Results: show the mean difference between CD36 negative control and CD36 positive control was found to be
statistically significant increasing of CD36 presence at P. value =0.001 (P 0.001). The mean difference between
CD36 positive control and diabetic patients with HbA1C more 8% was found to be statistically significant reduction
of CD36 expression at p=0.001. Conclusion: Hyperglycemia (HbA1c) leads to decrease of CD36 expression and
interfere with innate and active immunity. In this study HbA1c participates in increasing of P. falciparum malaria
complications.
Keywords: HbA1c, CD36, Plasmodium falciparum, Diabetes mellitus.
INTRODUCTION
Glycation of proteins is a frequent occurrence, but in
the case of hemoglobin, a non-enzymatic reaction
occurs between glucose and the N-end of the beta
chain. Abnormal glycation, which can adversely affect
hemoglobin and membrane proteins in erythrocytes,
has been shown to correlate with reduced membrane
fluidity1 separately, high values of glycosylated
hemoglobin have been found to correlate with
decreased deformability of erythrocyte.2
Hassan et al.,
CD36 is a multi-functional molecule. It has

independent binding sites for different classes of
ligands
Such
as
modified
phospholipids,
thrombospondins, and free fatty acids. This enables
CD36 responsible for several different cellular
processes depending on the nature of the ligand and
the type and location of the cell on which it is
expressed. On phagocytes CD36 functions as a
scavenger receptor helping in recognition and
Int J Med Res Health Sci.2014;3(1):23-27
23
internalization of apoptotic cells3, falciparum malaria

infected erythrocytes.4,5
CD36 also functions as an adhesion molecule, it has
been identified CD36 as the receptor that helps in
cytoadherence of Plasmodium Falciparum parasitized
erythrocytes6, It has been reported that CD36 on
platelet mediates clumping of P. falciparum infected
erythrocytes is strongly associated with severe
malaria.7 In contrast, CD36 on monocytes or
macrophages can help phagocytosis of falciparum
Infected erythrocytes. Thus the location of CD36
receptor can regulate the severity of malarial disease.
Several studies have suggested an important role of
CD36 in phagocytic clearance of apoptotic and
Senescent cells.8 Malaria culture is the method to grow
malaria parasite outside the body i.e. in an in vitro
environment. P. falciparum is currently the only
human malaria parasite that has been successfully
cultured continuously in vitro. Although attempts for
propagation of the parasites outside of humans or
animal models.9
METHODOLOGY
Ethical approval: Ethical clearance obtained from the
Ethical Committee Board of the Tropical Medicine
Research Institute. The consent was taken from
patients and taken the permission from medical
management of Jaber Abu Ezz Diabetes Center and
selected individual after being informed with all
objectives of the study and its health impact in the
future.
This is cross section study was conducted in Khartoum
state among diabetic patients attending in Jabir Abo
Eleiz diabetic Centre. In an aseptic conditions ml
venous blood samples were collected in heparin
containers for culture, Ox LDL, and Random Blood
Sugar (RBS). For HbA1c in 0.04 mg EDTA
anticoagulant, 2-5 ml of blood was collected. The
samples were mixed well and tested within 6 hour.
Samples were classified into three groups:
Group I: 15 samples were collected from apparently
health People free from any disease as negative
control.
Group II: 15 samples were cultured with Plasmodium

falciparum as CD36 positive control. Culture
technique as following: Erythrocytes were washed 3
times in Roswell Park Memorial Institute medium
(RPMI) 1640 to remove citrate phosphate dextrose
(CPD), serum, and leukocytes if present. Dilute to 5%
hematocrit with cMCM in small flasks of 25cm2 (0.2
mL of packed cells to 4 mL of malaria culture media
(MCM) or in 75-cm2 flasks (1.0 mL to 20 mL).
Parasites were added to an appropriate parasitemia.
Flask was put in a candle jar and loosens the screw
cap. Produce low oxygen by burnt out candle and
place the jar at 37 C. MCM was replace every day
(not necessary the day after sub cultivation).
Subculture was cultured 2 times / week.
Group III: 15 samples from known diabetic patients
(HbA1c more than 8%) and were tested for CD36.
CD36 was measured by Flow cytometer uses the
principles of light scattering, light excitation, and
emission of fluorochrome molecules to generate
specific multi-parameter data from particles and cells
in the size range of 0.5um to 40um diameter. Cells are
hydro-dynamically focused in a sheath of phosphate
buffer saline (PBS) before intercepting an optimally
focused light source; Lasers are most often used as a
light source in flow cytometer properties of single
particles (e.g. cells, nuclei, chromosomes) during their
passage within a narrow, precisely defined liquid
stream.
The hemolysate, where the labile fraction is eliminated
hemoglobins are retained by a cationic exchange
resin. Hemoglobin A1C (HbA1c) is specifically eluted
after washing away the hemoglobin A1a+b fraction1
(HbA1a+b), and is quantified by direct photometric
reading at 415 nm.
Quality control: All reagents and test equipment
were controlled according to the instructions in the
procedures manual, manufacturing control and control
sample were used in each test.
Data analysis: Data were analyzed by using Statistical
Package for Social Science (SPSS) version 21 and
Microsoft Excel 2013. Results were obtained by using
student T .test.
RESULTS
Table 1: Shows the mean difference of CD36 amount in negative control and positive control:
Group
N
Mean
SD
DF
T
P Value
CD36 negative control 15 0.3600
0.12923
28
10.513
0.001**
CD36 positive control
15 26.1000
9.48194
P * 0.05, P ** 0.01
Hassan et al.,
24
Table 2: Shows the mean difference of CD36 amount in negative control and diabetic patients with HbA1C 8%
Group
CD36 negative control
CD36 in diabetic patient with HbA1C 8%
N
15
15
Mean SD
0.3600 0.12923
5.9460 1.66648
DF
28
T
12.943
P Value
0.001**
Table 3: Shows the mean difference of CD36 amount in positive control and diabetic patient with HbA1C 8%
Group
N
Mean SD
DF
T
Sign
15
26.1000 9.48194 28
8.108
0.001**
CD36 in diabetic patient with HbA1C 8%
15
5.9460 1.66648
Table 4: Shows mean difference of RBCs percentage containing (CD36); between CD36 negative control and
positive control:
Group
N
Mean SD
DF T-value
P-value
CD36 negative control
15 1.7600 0.64454
28 3.29
0.003**
15 11.1800 11.05740
Table 5: Shows mean difference of RBCs percentage containing (CD36) between CD36 positive control and
diabetic patients with HbA1 C 8%
Group
N
Mean SD
DF
T-value P-value
15
11.1800 11.05740 28
2.64
0.013*
CD36 in diabetics patients with HbA1 C8% 15
3.6067 1.11257
Forty five (45) individuals participated in the present study.
In table: 1 the mean difference between CD36
negative control and CD36 positive control was found
to be statistically significant at P. value =0.001 (P
0.001).
The mean difference between CD36 negative control
and CD36 in diabetic patients with HbA1C 8% was
highly significant at P. value = 0.001 as shows in
table 2.
The mean difference between CD36 positive control
and diabetic patient with HbA1C more 8% was found
to be statistically significant at p=0.001 as shows in
table 3.
The mean difference percentage of RBCs containing
(CD36) between CD36 negative control and CD36
positive control was found to be statistically
significant at p = 0.003 as shown in table 4.
The mean difference of percentage of RBCs
containing (CD36) between CD36 Positive control and
CD36 in diabetics patients with HbA1 C>8% was found
to be statistically significant at p = 0.013 as shown in
table 5.
DISCUSSION
HbA1c occurs when hemoglobin joins with glucose in
the blood. Hemoglobin molecules make up the red
Hassan et al.,
blood cells in the blood stream. When glucose sticks to

these molecules it forms a glycosylated hemoglobin
molecule, also known as A1c and HbA1c. The more
glucose found in the blood the more glycated
hemoglobin (HbA1c) will be present.10
CD36 is a broadly expressed membrane glycoprotein
that acts as a facilitator of fatty acid uptake, a receptor
for low density lipoprotein, and malaria infected
erythrocytes. Despite an impressive increase in
knowledge of CD36 functions, in depth understanding
of the mechanistic aspects of this protein remains
elusive. This study focuses on the impact of
hemoglobin A1c on CD36 of Plasmodium falciparum
infection in diabetic patients.
In present study when data of red blood cells infected
with P. falciparum (P.F) was compared with normal
healthy RBCs there was significant (P < 0.001)
expression of CD36 in the red blood cell in addition,
comparison between the same groups also found
significant (P < 0.003) increasing of RBCs percentage
containing CD36 that means plasmodium falciparum
could increases the expression of CD36 on the surface
of the parasitized red cells. This agreed with Ho, M.
and White, N.J. 1999,11 who were proposed CD36 a
major receptor for P. falciparum-infected red blood
25
cells (IRBCs). Moreover, comparison of the group

that contains parasitized red blood cell (P. falciparum)
with high concentration of glycosylated hemoglobin
(HbA1c) more than 8% with normal healthy RBCs
(negative control) there was significant (P < 0.001)
expression of CD36, and the CD36 expression was
expressed in the presence of HbA1c in small amount
which indicates the P.F plays a role in IRBCs cell
membrane leads to CD36 expression, this is has no
conflict with previous study that represented .These
abnormal circulatory properties of erythrocytes
involve parasite-induced alterations in their
biomechanical and adhesive properties and are
important for survival and pathogenicity of P
falciparum.12 Cytoadhesion is mediated by the
antigenically variant P. falciparum erythrocyte
membrane protein-1 (PfEMP1), which can bind to host
receptors including CD36 and chondroitin sulfate A
CSA13 PfEMP1 is concentrated on electron-dense
elevations of the membrane referred to as knobs.14,15
providing a platform for adherence under physiologic
flow conditions.16 Increased erythrocyte rigidity and
adhesiveness result in dramatically augmented
hemodynamic resistance observed in microvasculature
perfused with P falciparuminfected erythrocytes.17
However, the group that contains CD36 with high
concentration of glycosylated hemoglobin (HbA1c)
more than 8% has been compared with the group
which contains CD36 in patient with P. falciparum
malaria only (positive control) there was significant
reduction of CD36 expression (P < 0.001), also this
study agreed with Van Nieuwenhoven et al, 199818
was proposed that hyperglycemia might play an
important role in the regulation of CD36 expression
.The result in this study shows the significant effect of
HbA1c on CD36 expression reduction. Thus, these
results was agreed with the previous study shown that
hyperglycemia is also associated with increased levels
of reactive oxygen species in diabetic red blood cell
and rise in the levels of the reactive carbonyl
compounds that worsen their compromised functions,
leading to diminished lifespan, accelerated nonenzymatic modification of proteins, and loss of protein
function.19,20 A result of increased protein
glycosylation could participate in the mechanism,
whereby diabetic erythrocytes may acquire membrane
abnormalities.21 Spectrin is a very important protein of
erythrocyte membrane and a target for glycosylation
and further oxidation, which might be responsible for
increased number of poorly deformable erythrocytes
Hassan et al.,
found among diabetic erythrocytes.22 Abnormal

glycation, which can adversely affect hemoglobin and
membrane proteins in erythrocytes, has been shown to
correlate with reduced membrane fluidity1 separately,
high values of glycosylated hemoglobin have been
found to correlate with decreased deformability of
erythrocyte.2 The reduction of CD36 expression may
have remarkable in the development of severity P.
falciparum malaria in diabetic patients.
CONCLUSION
We conclude that Plasmodium falciparum might
increase the density and amount of CD36 in
parasitized red blood cells. Hyperglycemia (HbA1c)
leads to down-regulate of CD36 expression and
interfere with innate and active immunity. In this study
HbA1c participates in increasing of P. falciparum
malaria complications.
ACKNOWLEDGEMENT
My sincere thanks extended to Hussain Higazi, and
Sayed Alshamy for their strong helping and support. I
am really indebted to the laboratories staff of Jaber
Abu Ezz Diabetic center for their help and assistance.
Conflict of Interest Statement: The authors of this
paper have no conflicts of interest, including specific
financial interests, relationships, and/ or affiliations
relevant to the subject matter or materials included.
REFERENCES
1. Watala C, Zawodniak M, Bryszewska M, Nowak
S. Nonenzymatic protein glycosylation. I.
Lowered erythrocyte membrane fluidity in
juvenile diabetes. Ann Clin Res. 1985; 17(6):327
30.
2. Bauersachs RM, Shaw SJ, Zeidler A, Meiselmann
HJ. Red blood cell aggregation and blood
Viscoelasticity in poorly controlled type 2 diabetes
mellitus. Clin Hemorheol. 1989; 9: 93552.
3. Albert ML, Pearce SF, Francisco LM, Sauter B,
Roy P, Silverstein RL etal., Immature dendritic
cells phagocytose apoptotic cells via alphavbeta5
and CD36, and cross-present antigens to cytotoxic
T lymphocytes. J Exp Med. 1998; 188:1359-68.
4. Greenberg ME, Sun M, Zhang R, Febbraio M,
Silverstein
R.,
Hazen
SL.
Oxidized
phosphatidylserine-CD36 interactions play an
essential
role
in
macrophage-dependent
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6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
phagocytosis of apoptotic cells. J Exp Med. 1998;

203: 2613-2625.
Fadok, VA, Bratton DL, Frasch SC, Warner ML,
Henson, P. M. The role of phosphatidylserine in
recognition of apoptotic cells by phagocytes. Cell
Death Differ. 1998; 5: 551-562.
Oquendo P, Hundt E, Lawler J, Seed B. CD36
directly mediates cytoadherence of Plasmodium
falciparum parasitized erythrocytes. Cell. 1989;
58: 95-101.
McGilvray ID, Serghides L, Kapus A, Rotstein
OD,
Kain
KC.
Nonopsonic
monocyte/macrophage
phagocytosis
of
Plasmodium falciparum-parasitized erythrocytes:
a role for CD36 in malarial clearance. Blood.
2000; 96:3231-40.
Podrez, E. A., Febbraio, M., Sheibani, N., Schmitt,
D., Silverstein, R. L., Hajjar, D. P., Cohen, P. A.,
Frazier, W. A., Hoff, H. F., and Hazen, S. L.
Macrophage scavenger receptor CD36 is the major
receptor for LDL modified by Monocytegenerated reactive nitrogen species. J Clin Invest.
2000; 105:1095-108.
Trager W, Jensen JB. "Continuous culture of
Plasmodium falciparum: its impact on malaria
research". Int J Parasitol. 1997; 27 (9): 9891006.
Pani LN, Korenda L, Meigs JB, Driver C,
Chamany S, Fox CS etal., Relationship Between
A1C and Glucose Levels in the General Dutch
Population Diabetes Care. 2008; 10:1991-6.
Ho M. and White NJ. Molecular mechanisms of
cytoadherence in malaria. Am. J. Physiol. 1999;
276: C1231C42.
Cooke BM, Mohandas N, Coppel RL. Malaria and
the red blood cell membrane. Semin Hematol.
2004; 41:173-188.
Baruch DI, Rogerson SJ, Cooke BM. asexual
blood stages of malaria antigens: cytoadherence.
Chem Immunol. 2002; 80:144-162.
Su XZ, Heatwole VM, Wertheimer SP. The large
diverse gene family var encodes proteins involved
in cytoadherence and antigenic variation of
Plasmodium falciparum-infected erythrocytes.
Cell. 1995; 82:89-100.
Smith JD, Trogan E, Ginsberg M, Grigaux C, Tian
J, Miyata M. Decreased atherosclerosis in mice
deficient in both macrophage colony-stimulating
factor (op) and apolipoprotein E. Proc. Natl.
Acad. Sci. U.S.A. 1995; 92: 8264-68.
Hassan et al.,
16. Crabb BS, Cooke BM, Reeder JC, Waller JC,

Caruana SR., Davern KM, et al., Targeted gene
disruption shows that knobs enable malariainfected red cells to cytoadhere under
physiological shear strees. Cell. 1997; 89:287-96.
17. Raventos SC, Kaul DK, Macaluso F, Nagel RL.
Membrane knobs are required for the
microcirculatory
obstruction
induced
by
Plasmodium falciparum- infected erythrocytes.
Proc Natl Acad Sci U S A. 1985; 82:3829-3833.
18. Van Nieuwenhoven FA, Luiken JJ, De Jong YF,
Grimaldi PA, Van der Vusse GJ, Glatz JF Stable
transfection of fatty acid translocase (CD36) in a
rat heart muscle cell line (H9c2). J Lipid Res.
1998; 39:203947.
19. Constantin A, Constantinescu E, Dumitrescu M,
Calin A, & Popov D. Effects of ageing on
carbonyl stress and antioxidant defense in RBCs
of obese Type 2 diabetic patients. Journal of
Cellular and Molecular Medicine. 2005; 9: 683
91
20. Schwartz RS, Madsen JW, Rybicki AC, Nagel RL.
Oxidation of spectrin and deformability defects in
diabetic erythrocytes. Diabetes. 1991; 40(6):70108.
21. Lux SE. Spectrin-actin membrane skeleton of
normal and abnormal red blood cells. Seminars in
Hematology. 1979; 16(1):21-51.
22. McMillan DE, Brooks SM. Erythrocyte spectrin
glucosylation in diabetes. Diabetes. 1982;
31(3):64-69.
27
DOI: 10.5958/j.2319-5886.3.1.006

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Health Sciences
www.ijmrhs.com
rd
Research article
Copyright @2013
ISSN: 2319-5886
DERMATOGLYPHICS: A PREDICTOR TOOL TO ANALYZE THE OCCURRENCE OF BREAST

CANCER
Abilasha S1, *Harisudha R2, Janaki CS3
1
Tutor, Department of Anatomy, KSR Institute of Dental Science & Research, Tiruchengode, Namakkal, Tamil
Nadu, India
2
Tutor, Department of Anatomy, Melmaruvathur Adhiparasakthi Institute of Medical Science and Research,
Melmaruvathur, Kanchipuram, Tamil Nadu, India
3
Assistant Professor Department of Anatomy , Meenakshi Medical College and Research Institute, Enathur,
Kanchipuram, Tamil Nadu, India
*Corresponding author email: ramvijii86@gmail.com
ABSTRACT
Background: Dermatoglyphics is the branch of science that deals with the study of ridge patterns on finger tips,
palm, sole and toes and when once formed, they remain unchanged throughout the except after severe injuries.
These patterns can serve as a non-invasive, cost-effective tool which can be used for the prediction of cancer. This
can also serve as a baseline guide to identify women with breast cancer. Objective: To study the digital
dermatoglyphic patterns among women with breast cancer in comparison with normal individuals. Materials and
methods: 50 female patients with breast cancer of age group between 30-70 years were compared with 50 control
group of individuals with no history of cancer. The breast cancer patients and the control group were of the same
age and sex. Digital dermatoglyphic patterns were taken among these individuals with the aid of a dermatoglyphic
kit. Procedure involved was modified purvis smith method. Results: digital dermatoglyphic patterns were analyzed
between the patients and control group of individuals which showed statistical difference. Conclusion: we conclude
that there is a genetic influence on the dermatoglyphic patterns. With the aid of this, the occurrence of breast cancer
can be predicted and this dermatoglyphics can serve as a non-invasive, anatomical marker and a predictor tool to
determine the individuals with breast cancer.
Keywords: Breast cancer, Dermatoglyphics, Ridge patterns, Genetic marker
INTRODUCTION
Dermatoglyphics is a branch of science that deals with
the study of ridge patterns on finger tips, palm, sole
and toes. Dermatoglyphics traits are epidermal ridges
formed under genetic control early in development but
may be affected by environmental factors during the
first trimester of pregnancy. They however do not
change significantly thereafter, thus maintaining
stability not greatly affected by age. These epidermal
ridges are closely related to volar pads and these ridge
patterns form at the site of these pads. Harold and

Cummins1coined the term dermatoglyphics in 1926,
which they first used in a paper, the American journal
of physical anthropology. A detailed description on
ridge patterns was described in 17th century2.
Widespread medical interest towards epidermal ridges
developed only in the last few decades when it became
an apparent factor that many patients with
chromosomal aberrations had unusual ridge patterns.
28
Abilasha et al.,
Inspection of these ridges therefore seems to provide a

simple and cost effective means of information to
determine whether the patients could have any
underlying changes in genotype. 3
individuals and whorl was maximum in breast cancer

patients which showed statistical significance.(p>0.05)

The material for this present study consisted of
fingerprints of patients selected from those attending
outpatient and inpatient clinics in the department of
Meenakshi Hospital, Kanchipuram and Jeevodhaya
Cancer Hospital Retteri, Chennai.
Sample size:
The study consisted of 100 subjects categorized into
two groups including 50 patients with breast cancer
and 50 control groups of individuals.
Inclusion criteria: 1. 50 histopathologically
conformed female breast cancer patients age between
30-65 years.
2. Age matched 50 female control group individuals
with no history of cancer or any other genetic
disorders.
3. Treated, untreated and operated patients were used
for this study.
Exclusion criteria: 1. Individuals who had
deformities in their hands like burns or injury were
excluded.
2. Genetic disorders other than breast cancer were also
excluded. 3. Females under 30 years of age.
Fig 1: Comparison of dermatoglyphics pattern

between control and breast cancer (left hand)
(A=Arch, UL= Ulnar Loop,RL= Radial Loop, W=
Whorl, Tl-R= Twinned Loop Radial, Lp-U= Lateral
Pocket Ulnar, Lp-R= Lateral Pocket Radial, Cp=
Central Pocket Loop, Al= Accidental Loop.)
In left hand ring finger, arch and ulnar loop were
maximum in control group of individuals and whorls
were maximum in breast cancer patients when
compared to normal group.
In left hand little finger ulnar loop was maximum in
control group and arch, whorl was maximum in breast
cancer patients which showed statistical significance.
MATERIAL & METHODS

Data collection: After obtaining permission from the
Institutional Ethics Committee also inform consent
form was taken from the patient. Total 100 patients
(50 histopathologically conformed breast cancer and
50 normal age match control) were informed about the
procedure in detail and data comprising of age, sex
and address were taken.
Method : In our study with the help of the modified
Purvis smith method4 we have studied the fingerprint
patterns of controls and breast cancer individuals by
the arrangements of loop-ulnar loop, radial loop,
whorl- plain whorl, central pocket loop whorl, archesplain arch, tented arch, radial twinned loop, ulnar
twinned loop, accidental loop. The prints were
analyzed with the help of the finger print analyst.
RESULTS
In left hand thumb, ulnar loop, twinned loop ulnar and
twinned radial loop was maximum in control group of
Fig 2: Comparison of dermatoglyphics pattern

between control and breast cancer (right hand)
(A=Arch, UL= Ulnar Loop,RL= Radial Loop, W=
Whorl, Tl-R= Twinned Loop Radial, Lp-U= Lateral
Pocket Ulnar, Lp-R= Lateral Pocket Radial, Cp=
Central Pocket Loop, Al= Accidental Loop.)
In right hand ring finger arch and whorl were
maximum in breast cancer patients and arch was
maximum in control group of individuals which
showed statistical significance. (p>0.05)
29
Abilasha et al.,
DISCUSSION
Chintamani5, Bierman6, RJ Meier7, has identified a
pattern of 6 or more digital whorls has been used to
identify women with breast cancer and whorls were
commonly observed in right ring finger and right little
finger in breast cancer patients. Hence, the
determination of dermatoglyphic pattern of the finger
and palm is genetic, so it could serve as a suitable
parameter for differentiating individuals. Our study
also goes in accordance with the previous study that
we identified a pattern of whorls in 6 out of 10 digits
in 62% of the breast cancer patients whereas in a
control group of individuals it was the ulnar loop
pattern present in 6 out of digits. So this was a major
difference observed in our study, and in our study too
whorls were commonly seen in right ring finger and
little finger among the breast cancer patients. Oladipo8
has observed a significant association with ulnar loop
in 8 out of 10 digits in Nigerians and he has also
concluded that these dermatoglyphic findings will
serve as a baseline in the identification of women who
are at increased risk of developing breast cancer and
perhaps aid early treatment of the disease. He has also
observed that ulnar loop had highest mean percentage
frequency of the digital dermatoglyphic pattern
followed by whorl, arch and radial loop i.e., ulnar loop
and whorl was higher in right hand and radial loop and
arch in left hand of breast cancer -patients. In our
study, we identified a significant association with
whorls and we have also observed that ulnar loop had
highest mean percentage frequency followed by whorl,
arch and radial loop. According to Natekar PE9, out of
1000 fingerprints, cancer patients had 33% whorls,
66.6% loops, 0.4% arches whereas the control group
had 63.8% whorls, 35.5% loops and 0.7% arches.
There was the presence of more than 6 loops in breast
cancer patients. In our study, out of 2000 fingerprints,
breast cancer patients had 47% loops, 44% whorls, 4%
arches, 2% ulnar twinned loop, 0.8% radial twinned
loop whereas the control group had 56% loops, 25%
whorls, 8% arches, 7% ulnar twinned loop, 3% radial
twinned loop. We have also observed there was the
presence of 0.4% tented arch and 0.4% accidental loop
among the breast cancer patients which was absent in a
control group of individuals. There was presence of
whorls in 6 out of 10 digits in 62% of the breast cancer
patients. Sakineh Abbasi 10, with an ever increasing
population it is important that methods be developed
to identify individuals who are either at risk or already
having illness in the most cost efficient manner

without sacrificing quality of care. The use of
dermatoglyphics is a unique approach and cost
effective for identification in such individuals. In his
study of dermatoglyphic patterns, he has observed the
significant difference in right hand middle finger, ring
finger, left hand index finger, middle finger, ring
finger, little finger where there was an increase in loop
in all these digits and also observed whorls in 6 out of
10 digits in 48.7% of the breast cancer cases. In our
study, we have observed the significant difference in
the left hand thumb, ring finger, little finger, right
hand ring finger. We have also observed that the
whorls in <6 out of 10 digits in 62% of the breast
cancer patients.
CONCLUSION
The present study concludes that as there is a genetic
influence on the digital ridge patterns, these do not
change throughout the life. Hence with the aid of this
digital and dermatoglyphic pattern we can predict the
occurrence of breast cancer and this dermatoglyphics
can serve as a non-invasive, anatomical marker and a
predictor tool to determine the individuals with breast
cancer. We also conclude that with the help of this
ability to predict the earliest changes associated with
breast cancer it may allow to the introduction of more
effective preventive strategies.
ACKNOWLEDGEMENT
I would like to thank Dr. Deenadayalan for his
immense support to this work.
REFERENCES
1. Cummins HH. Epidermal Ridge Configurations in
Developmental
Defects,
with
Particular
References to the Ontogenetic Factors Which
Condition Ridge Direction. American Journal of
Anatomy.1926;38(1), 89-151.
2. Huang CM, Mi MP. Digital dermal patterns in
breast cancer. Proc Natl Sci Counc Repub China
B. 1987;11(2): 133-6
3. Book JA. A fingerprint method for genetical
studies. Hereditas 1948;34:368
4. Purvis-Smith SG. Finger and palm printing
technique for the children. Med J Austria 1969;
2:189.
5. Chintamani, Rohan khandelwal, Aliza mittal,
Saijanani, Amita tuteja, Anju bansal etal.,
30
Abilasha et al.,
6.
7.
8.
9.
10.
Qualitative and quantitative dermatoglyphic traits

in patients with breast cancer. New Delhi, India.
BMC Cancer 2007, 7:44
Bierman HR, Faith MR, Stewart ME. Digital
dermatoglyphics in mammary cancer. Cancer
Invest., 1988; 6(1): 15-27.
Schaumann BA, Meier RJ. Trends in
dermatoglyphic research. International Journal of
Anthropology1989;4(4):247- 54
Oladipo GS, Paul CW, Bob-Manuel IF,
Fawehinmi HB, Edibamode EI. Study of digital
and palmar dermatoglyphic patterns of Nigerian
women with malignant mammary neoplasm. J.
Appl. Biosci.2009; 15: 829-34.
Natekar PE, Desouza S, Motghare DD, Pandey
AK. Digital dermal patterns in Carcinoma Breast.
J. Anthropologist. 2006; 8: 251254.
Sakineh Abbasi, Nahid Einollahi, Nasrin Dashti,
Vaez-zadeh F. Study of dermatoglyphic patterns of
hands in women with breast cancer. Pak J Med
Sci.2006,22(1): 18-22
31
Abilasha et al.,
DOI: 10.5958/j.2319-5886.3.1.007

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Health Sciences
www.ijmrhs.com
Received: 1st Oct 2013
Research article

Copyright @2013
ISSN: 2319-5886
A PROFILE OF CARDIOVASCULAR DISEASES IN A TEACHING HOSPITAL IN KERALA

*Celine TM1, Jimmy Antony2
1
Assistant Professor of Statistics, 2Assistant Professor of Health Education, Department of Community Medicine,
MOSC Medical College, Kolenchery, Kerala, India
*Corresponding author email: celin09@rediffmail.com
ABSTRACT
Background and objective: cardiovascular diseases are increased in each year in India. Cardiovascular diseases
more are occurred in the economically productive age group. This will affect their family and also the nation. Aim
of the study is to find out the different types of heart diseases and the case fatality rate of cardiovascular disease
from 1st April 2005 to 31st March 2010 in a teaching hospital. Materials and Methods: The retrospective study
conducted on hospitalized patients admitted with cardiovascular diseases from 1st April 2005 to 31st March 2010.
Medical records department follows the guide lines of International Classification of Diseases (ICD)-10 coding for
entering the data, from that data were collected. Results: Of 10427 cases, 6324 (60.65%) were males and
4103(39.35%) females. Cardiovascular disease was more among males than females. It was more occurred in 60
years. Most of them were occurred due to cerebrovascular disease (33.7%). Ischemic heart disease was more among
males than females. Total number of deaths due to cardiovascular disease was 797. Of them 525(65.87%) were
males and 272(34.13%) females. Case fatality due to cardiovascular diseases was 7.64%. Case fatality among males
(8.3%) were more than females (6.63%) (P=0.00). Conclusion: This study mentioned that most of the cases and
deaths were occurred in 60 and above years. Second leading age group is 25-59 years. Accident in economically
productive people was high. It will affect their family and also the nation. Hence it can be reduced by conducting
health awareness programme.
Key words: Case fatality, cardiovascular diseases, ischemic heart disease.
INTRODUCTION
Heart and blood vessel disease is called cardiovascular
disease (CVD) or heart disease. It is the number one
killer of women in worldwide, accounting for onethird of all deaths. Atherosclerosis is a term which
describes any hardening of large arteries; it happened
due to plaque. It causes the arteries narrow and this
leads to the flow of blood through the arteries is
difficult. Blood clots in anywhere in the narrow
arteries then blood cannot flow it will lead to heart
attack or stroke. An ischemic stroke occurred due to
obstruction within the blood vessel supplying blood to
brain. When the blood supply of that part of the brain
Celine etal.,
is cutoff; it will cause the brain cell die. It will affect

the smooth functioning of the body. A hemorrhagic
stroke mostly happened due to the unrestrained
hypertension; it leads to explosion of blood vessel in
the brain. Heart failure, it occurs when the heart cannot
supply sufficient blood for the functioning of the body.
If it is not treated in time it becomes most terrible.
A cross sectional study reported that the prevalence of
coronary heart disease (CHD) in rural and urban areas
of India was 3-4% and 8-10% respectively.1 The main
objective of the study is to find out the different types
of heart diseases and the case fatality rate of
32
Int J Med Res Health Sci. 2014;3(1): 32-36
cardiovascular disease during the period from 1st April

2005 to 31st March 2010 in a teaching hospital.
METHOD
Study design: The study was a retrospective study
conducted on patients admitted with cardiovascular
diseases in M.O.S.C Medical College, Kolenchery,
Ernakulam, Kerala, India from 1st April 2005 to 31st
March 2010.
Selection of Description of patients:
The study population consists of all patients admitted
in the hospital due to cardiovascular diseases during
the period from 1st April 2005 to 31st March 2010. The
data were collected with the permission of Institutional
Ethical Committee from the Medical Records
department, follows the guide lines of International
Classification of Diseases (ICD)-10 coding. 2
Statistics: Z test is applied for the comparison
between proportions. Z test is used for comparing the
sex wise difference between proportions of age, type
of diseases. Critical ratio (Z) = sex wise difference
between proportions age / standard error of difference
between sex wise proportions. Formula for calculating
Standard error of difference between sex wise
proportions is (p1q1 / n1) + (p2q2 / n2). P value is taken
from the unit normal distribution table with the
corresponding value of Z (critical ratio), its cut off
value is 0.05. If it is less than or equal to 0.05 then
there is significant difference between proportions
otherwise there is no significant difference between
proportions. Analyzing the data by using Microsoft
excel.
RESULT
Table 1: Demographic distribution
Age
Male (%)
Female
Total (%) P Value
(Yr)
(%)
0-4
143(2.3)
97 (2.4)
240(2.3) 0.74
5-24 352 (5.6)
242(5.9) 594(5.7) 0.52
25-49 1096 (17.3) 534(13)
1630(15.6) 0.00
50-59 1309 (20.7) 610 (14.9) 1919(18.4) 0.00
60 & 3424(54.1) 2620(63.9) 6044(58.0) 0.00
above
Total 6324
4103
10427
Out of 10427 cardiovascular cases 6324 (60.65%)
were males and 4103(39.35%) were females.
Cardiovascular disease was more in the age group of
60 and above years. In this age group, it was more in
females than males. But it was more among males than

females in the age group of 25-59, Shown in Table
No.1.
Table 2: Sex wise cardiovascular diseases of
patients admitted with cardiovascular diseases
P
Diagnosis
M
F
Total
Value
18
14
32
Acute Rheumatic
1
fever(I00)
0.3%
0.3%
0.3%
65
99
164
Chronic rheumatic
0.00
heart diseases(I05-I09) 1.0%
2.4%
1.6%
1072
936
2008
Hypertension(I10-I15)
0.00
17.0% 22.8% 19.3%
2070
862
2932
Ischemic heart
0.00
disease(I20-I25)
32.7% 21.0% 28.1%
Pulmonary heart
63
40
103
disease and diseases
1
of pulmonary
1.0%
1.0%
1.0%
circulation(I26-I28)
691
1531
Other forms of heart 840
0.00
disease(I30-I52)
13.3% 16.8% 14.7%
2093
1417
3510
Cerebrovascular
0.14
diseases (I60-I69)
33.1% 34.5% 33.7%
Diseases of arteries, 103
44
147
arterioles and
0.63
1.6%
1.1%
1.4%
capilliaries(I70-I79)
6324
4103
10427
Total
100.0% 100.0% 100%
Of the cardiovascular cases, most of them due to
cerebrovascular disease and it occurred in both sex
was same.
Chronic rheumatic heart disease,
hypertension and other forms of heart disease were
more among females than males. But ischemic heart
disease was more among males than females, shown in
Table No.2.
Of the ischemic heart disease, most of them were due
to Chronic ischemic heart disease 1859(63.4%), 273
(9.3%) were due to Acute Myocardial infarction,
410(14.0%) were due to subsequent myocardial
infarction and 390(13.3%) were due to other reasons.
Of the cerebrovascular diseases, most of them were
due to cerebral infarction1394(39.72%), 924(26.32%)
were due to stroke, not specified as hemorrhage or
infarction, 414(11.79%)were due to intracerebral
hemorrhage, 193(5.5%) were due to subarachnoid
hemorrhage and 585(16.67%) were due other reasons.
33
Celine etal.,
Fig 1: Sex wise Trend of Cardiovascular cases

reported in a Teaching Hospital from 1st April 2005
to 31st March 2010
Highest number of cases reported during the year 1st
April 2009 to 31st March 2010. Cardiovascular disease
was more among males than females in each year,
shown in Figure 1.
Of the 10427 cases, 797 deaths were reported during
the period from 1st April 2005 to 31st March 2010.Case
fatality due to cardiovascular diseases was 7.64%. Of
797 deaths, 525(65.87%) were males and 272(34.13%)
were females. Case fatality among male was 8.30%
and among females 6.63%. Case fatality among males
was more than females. (P=0.00)
Table 3: Age wise case fatality of patients admitted
with cardiovascular diseases from 1st April 2005 to
31st March 2010
Age
No. of
deaths
Total
P value
cases
0-4
14 (5.8)
240
0.52
5-24
23(3.9)
594
0.4
25-49
78(4.8)
1630
Reference group
50-59
133(6.9)
1919
0.00
60 & above 549(9.1)
6044
0.00
Total
797(7.6) 10427
Within the column 2, represent the number of deaths
and case fatality of each age group. Case fatality was
more in the age group of 50 and above years compared
to the age group 25-49 years. Case fatality was more in
the age group of 60 and above years compared to the
age group 50-59 years (P=0.00), shown in Table No. 3.
Deaths due to cardiovascular diseases were more
during 1st April 2007 to 31st March 2008. Male deaths
were more than females in each year, shown in Fig 2.
Fig 2: Sex wise trend of deaths due to

cardiovascular diseases from 1st April 2005 to 31st
March 2010
DISCUSSION
In the developing countries most of the people have
stimulated from their agrarian diets with physical
activities to fast food with inactive habits. These types
of changes lead to increase the possibility of
developing cardiovascular diseases among people. It is
a burden of disease over several decades in the
developed countries. It is the leading cause of death in
India.2
Several studies in India mentioned that prevalence of
coronary heart disease in urban and rural areas was
between 7-13 % and 2-7 % respectively.3,4 Dinesh C
Sharma reported that the proportion of deaths due to
heart disease is more in south India ,it was 25% and
least in central region, it was 12 %. 5 A study reported
that 25% of total mortality was due to cardiovascular
diseases.6 Another study reported that cardiovascular
disease in South India showed 10-15% increase
occurred among young women. 7 A study mentioned
that 50% of all deaths occurred in Kerala was due to
cardiovascular diseases. (8) In the present study
cardiovascular diseases was more among males
(60.65%) than females (39.35%). It was more occurred
in the age group of 60 and above years. It was more
among females than males in the age group of 60 and
above years. But it was more among males than
females in the age group of 25-59.
Hypertension was an important factor in the beginning
of both cerebrovascular and ischemic heart disease.
Thus 22 per cent of the cases of ischemic heart disease
and 31.7 per cent of cases of myocardial infarction
were hypertensive; 42.0 per cent of the cases of
cerebral thrombosis were also hypertensive. The
overall ratio of ischemic heart disease to
cerebrovascular disease was 1.4:1; this ratio was same
34
Celine etal.,
for both sexes. A study mentioned that 8.72 million

individuals go through hypertension and 3.48 million
individuals go through diabetics in Kerala..8
Hypertension was the most powerful cause of vascular
diseases among females than males. In the present
study 19.3.3% hypertensive cases were reported.
Hypertension was more among females than males.
A study reported that the prevalence of Coronary
Artery Diseases in the urban and rural areas of India
was 12% and 7.5% respectively. 1 Raghavans study 9
mentioned that out of 4,335 autopsies, 13.1 per cent
was due to cardiovascular diseases. Of the
cardiovascular disease, 9.8% was due coronary artery
disease. According to Wigs study, the incidence of
coronary artery disease was more in Amritsar and
Calcutta.10, 11 Padmavatis study report mentioned that
0.2 % of the medical admissions above 40 years of age
was due to coronary artery diseases.12 In the present
study mentioned that 1.4% of cardiovascular diseases
were due to diseases of arteries, arterioles and
capilliaries.
According to Schroeder 13 the incidence of
cerebrovascular and ischemic heart disease is different
in different parts of the world. The prevalence of
coronary artery disease in India is found to be less than
other countries. Cerebrovascular disease was more
occurred than ischemic heart disease in males. Among
females cerebrovascular disease was occurred twice as
that of ischemic heart disease. Chamberss study
pointed out that in India the consumption of less
amount vitamin B-6 and folate content food and the
increase fatty food consumption without physical
exercise may increase the risk of ischemic heart
disease.14 A study mentioned that mortality due
ischemic heart disease among Indians living abroad
was 40% more than that of Europeans. 15 According to
Dhars study, 0.3% of all admission and 0.7% of all
medical admission was due to ischemic heart disease.
Myocardial infarction was 6.5 times more in males
than females.16 In the present study ischemic heart
disease was 28.1% of all cases. Ischemic heart disease
was more among males than females. In the present
study, of the ischemic heart disease, most of them
were occurred due to Chronic ischemic heart disease
1859(63.4%), 273 (9.3%) were due to Acute
Myocardial infarction, 410(14.0%) were due to
subsequent myocardial infarction and 390(13.3%)
were due to other reasons.
Celine etal.,
Result of Dhars study mentioned that 0.44% of all

admission and 1.1% of medical admission was due to
cerebrovascular
diseases.
The
incidence
of
crebrovascular disease is 0.44 per cent and 1.1 per cent
of total and medical admissions, respectively.16
Muirs study17 reported that incidence of
cerebrovascular diseases was high in Indians and less
among Chinese in Singapore. Another study also
found the same result. 18 In the present study 33.7% of
cardiovascular diseases was due to cerebrovascular
disease. Of the cardiovascular cases most of the
patients were admitted with Cerebrovascular disease.
Proportion of Cerebrovascular disease in both sexes
was same. In the present study, of the cerebrovascular
cases, most of them were due to cerebral infarction
1394 (39.72%), 924(26.32%) were due to stroke, not
specified as hemorrhage or infarction, 414(11.79%)
were due to intracerebral hemorrhage, 193(5.5%) were
due to subarachnoid hemorrhage and 585(16.67%)
were due other reasons.
Report of a study mentioned that about 25% of
mortality occurred in the age group of 25- 69 years
was due to heart diseases. Mortality occurred due to
heart disease in the urban and rural areas was 32.8%
and 22.9% respectively 5 In the present study case
fatality was more in the age group of 60 and above
years (9.1%) compared to the age group 50-59
years(6.9%).Case fatality occurred in the age group of
25-59 years was 5.9%.
Padmavatis study mentioned that 7.7% of total
medical causes of death and 3% of total deaths was
due to heart disease.12 A study report mentioned that in
the western countries 50% of total deaths were due to
heart disease.19,20 Another study mentioned that 19%
of total deaths was due to heart disease and also
mentioned that it is a leading cause of in both sexes.5
In the present study case fatality due to cardiovascular
diseases was 7.64%. Case fatality among males (8.3%)
was more than females (6.63%).
CONCLUSION
Cardiovascular disease was more among males than
females. It was a no.1 killer disease. It will affect the
smooth running of the affected peoples family.
Prevention is better than cure. For reducing this with
the help of implementing simple but effective
prevention strategies, strengthening the health system
and conduct quality improvement programmes. And
also identify the reason for the onset of cardiovascular
35
disease in the younger age group and conduct

awareness programmes.
REFERENCES
1. Cardiological Society of India, Kerala Chapter.
ACS
Registry.
http://www.csikerala.org/
acsregistry.php
2. Dorairaj Prabhakaran and Salim Yusuf, Guest
Editors. Cardiovascular disease in India: Lessons
learnt & challenges ahead. Indian Journal of
Medical Research 2010;132(5): 529530.
3. Xavier D, Pais P, Devereaux PJ, Xie C,
Prabhakaran D, Reddy KS et al. Treatment and
outcomes of acute coronary syndromes in India
(CREATE): a prospective analysis of registry data.
Lancet 2008; 371 : 1435-42
4. Prabhakaran D, Yusuf S, Mehta S, Pogue J,
Avezum A, Budai A, et al. Two-year outcomes in
patients admitted with non-ST elevation acute
coronary syndrome: results of the OASIS registry
1 and 2. Indian Heart J 2005; 57 : 217-25
5. Dinesh C. Sharma India's no.1 killer: Heart
disease. India Today. 2010;April12
6. Mukherjee AK. Indias health: today and
tomorrow. J Indian Med Assoc1995;93: 31215.
7. The Times of India. Heart diseases rising among
women. Hyderabad.2013; June 29.
8. Shyam PV. In Kerala, 110 die of heart disease
daily Times of India. 2011;Sep 24
9. Raghavan, P. Etiological incidence of heart
disease in Bombay. Analysis of 4335 autopsies. J.
Indian M. A. 1941;10: 365,
10. Wig KL, Malhotra RP, Pathania NS. A study of
clinical data of 500 cases of congestive heart
failure. Indian Heart J.1953;5: 45
11. Gupta JC. A plea for concerted attack on
atherosclerosis. Indian Heart J. 1957;9: 59
12. Padmavati S. The cardiac patient in
underdeveloped countries. Am. Heart J. 1959;8:
418
13. Schroeder HA. Degenerative cardiovascular
disease in the Orient. I. Atherosclerosis. Chron.
Dis. 1958;8: 287
14. Chambers JC, Obeid OA, Refsum H. Plasma
homocysteine concentrations and risk of coronary
heart disease in UK Indian Asians and European
men. Lancet 2000; 355: 52327
15. Balarajan R. Ethnicity and variations in mortality

from
coronary
heart
disease.
Health
Trends1996;28:4551
16. Dhar P. Thesis for M.D. (Medicine). Unpublished.
17. Muir CS. Coronary heart disease in seven racial
groups in Singapore. Brit. Heart J.1960; 22:45
18. Danraj TJ, Acker MS, Danraj W, Ong WH, Yan
TV. Ethnic group differences in coronary heart
disease in Singapore. An analysis of necropsy
records. Am. Heart J. 1959;58: 518
19. Wood PH. Diseases of the Heart and Circulation.
Ed. 2. London, Eyre and Stottiswoode.1956.
20. White PD. Heart Disease. New York, The
Macmillan Company, 1951,4th ed.
36
Celine etal.,
DOI: 10.5958/j.2319-5886.3.1.008

&
Health Sciences
www.ijmrhs.com
nd
Received: 2 Oct 2013
Revised: 20th Nov 2013
Research article
Copyright @2013
ISSN: 2319-5886
USE OF PROTON PUMP INHIBITORS IN GENERAL PRACTICE: IS IT RATIONALE?

*Nousheen1, Tadvi NA2, Shareef SM3
1
IInd year MBBS student, Kamineni Institute of Medical Sciences, Narketpally, Andhra Pradesh, India
2
Department of Pharmacology, College of Medicine, Majmaah University, Kingdom of Saudia Arabia
3
Assistant Professor, Department of Pharmacology, Kamineni Institute of Medical Sciences, Narketpally
*Corresponding author email:nasertadvi@yahoo.co.uk
ABSTRACT
Background: The incidence of improper use of PPIs varies from 40-70% in various studies. Initiation and the
continuous use of these drugs without correct indications will result in significant cost to the patient. The present
study was planned with the aim of finding out the rational use of PPIs in the in patients of a rural tertiary care
hospital. Objectives: To assess indications of use of PPIs along with their dose, frequency, rationality of treatment,
safety and efficacy. Methods: Prospective observational drug-utilization study of PPIs was conducted for two
months in the inpatients of General Medicine and General Surgery wards. The sample size of study was (n=100).
The case sheets of the patients were reviewed for PPIs prescription and relevant data was taken. A five point Likert
scale with validated Reflux Disease Diagnostic Questionnaire (RDQ) having 12 items was used for evaluating
symptoms score for assessing efficacy of PPIs. Results: A total of 46.72% inpatients were on proton pump
inhibitors, in surgery(47.52% ) and medicine wards (46.01%). The indications for PPIs therapy were acute gastritis
(4%) , Gastro Esophageal reflux disease (5%) , Duodenal ulcer(1%) , co-administration with Non Steroidal AntiInflammatory Drugs(32%). PPIs were prescribed irrationally in 58 % of patients without any valid indication. The
incidence of polypharmacy was high, average number of drugs per prescription was 4.93. Antimicrobials were the
most common drugs used in (71%). CONCLUSION: Proton pump inhibitors should be used more judiciously and
awareness should be created among the clinicians in the hospital so that appropriate prescription of PPIs will
improve the patient care at low cost.
Keyword: Proton pump inhibitors, General practice, Rationale
INTRODUCTION
Proton pump inhibitors (PPIs) are a group of drugs that
cause pronounced and long-lasting reduction of gastric
acid production. They are most potent gastric acid
suppressing drugs currently in clinical use.1 PPIs
irreversibly inhibit the gastric H+-K+ ATPase pump
also known as proton pump and reduce both basal and
stimulated gastric output. Currently the PPIs available
in India are omeprazole, esomeprazole, pantoprazole,
rabeprazole and lansoprazole. PPIs are used
therapeutically in active ulcers, Zollinger-Ellison
syndrome,
Gastro
oesophageal
Reflux
Disease(GERD), GI bleeding, dyspepsia from

NSAIDs and along with antibiotics for helicobacter
pylori.2 PPIs are also given prophylactically along
with NSAIDs or Steroids in patients with history of
peptic ulcer / previous GI bleed / elderly patients.3
Proton pump inhibitors have been demonstrated to be
safe and well tolerated drugs but short term adverse
effects like headache, dizziness, diarrhoea, fatigue,
rashes and abdominal pain have been reported in 5%
of the patients taking proton pump inhibitors.4,5
Chronic therapy of PPIs carries an increased risk of
bacterial enteritis due to decreased gastric acidity
37
Nousheen etal.,
allowing colonization of ingested pathogens and also

infection with clostridium difficile .6,7 long term use of
PPIs have also been associated with increased risk of
hip fractures, and community acquired pneumonia.8,9
In setting with low rate of such infections benefit of
PPI therapy outweighs the risk developing it.10
Polypharmacy can also make the elderly patients
more likely to confuse their use of medication
schedule.11 Such risks are worth taking for life saving
drugs that are clearly indicated, but prescribing PPIs
that may not be clinically necessary can put patients at
risk of complications.
Inspite of the above mentioned concerns with PPIs,
they have become one of the most commonly
prescribed medicines worldwide. Some reports suggest
that upto 60% of patients suffering from dyspepsia are
on drugs like PPIs without proper indication. 12,13 .
PPIs take longer time to provide symptom relief than
H2 blockers or antacids. For sporadic dyspepsia, and
immediate symptoms relief agents other than PPIs will
provide greater patient satisfaction and better clinical
outcomes.14
The prescriptions for the PPIs have increased
consistently over the past years. Many drug utilization
studies have reported widespread use of PPIs and that
are outside the current prescribing guidelines.15,16 The
incidence of improper use of PPIs varies from 40-70%
in various studies. 17-19
Initiation and the continuous use of these drugs
without correct indications will result in significant
cost to the patient. The significance of rational use of
drugs can be described by WHO definition which
states that rational use of drugs require that, patients
receive medications appropriate to their clinical needs
in doses that meet their own individual requirement for
an adequate period of time at lowest cost to them and
their community. 17
Hence in this present scenario, where the use of PPIs is
overwhelming, the present study is planned to know
the rational use of PPIs in the in patients of General
Surgery and General Medicine wards of a rural tertiary
care hospital.
Objectives
To assess the indications of PPIs usage
To find out percentage of irrational prescriptions
with PPIs (Improper prescriptions without justified
indication)
To assess the frequency of usage of PPIs along with
their dosage.
To assess the safety, efficacy and cost effectiveness

of PPIs.
METHODOLOGY
The study was conducted in the inpatient wards of
General medicine and General surgery in Kamineni
Institute of Medical Sciences (KIMS), Hospital in
collaboration with the Department of pharmacology
after taking permission from Institutional Ethics
Committee. It was a prospective observational study
conducted during the period of June 2013 to August
2013. Patients of either sex, admitted into the inpatient
wards of General Medicine and General Surgery in
KIMS hospital, Narketpally, between the age group of
20-70 yrs were included in the study. Informed
consent was taken from all the patients. Patients not
willing to give consent were excluded from the study.
The sample size for the study was (n=100).
The demographic data and the detailed history of
patient regarding past, present, family, personal and
drug history was taken. The other details like the
present diagnosis, reason for the present admission,
any investigations done to confirm the diagnosis, like
endoscopy etc were also noted. The number of drugs,
dosage form, frequency and duration of medications
the patient is kept on were also taken. Patient were
inquired regarding improvement in the symptoms or
any adverse drug reactions during the present stay. A
five point Likert scale with validated Reflux Disease
Diagnostic Questionnaire (RDQ) 20having 12 items
was used for evaluating symptoms score for assessing
efficacy of PPIs. This questionnaire was filled by
personal interview of the patient on inclusion in the
study and on discharge of the patient from hospital.
The questionnaire had maximum scoring of 40 and
minimum of 12 depending on severity of symptoms
like epigastric pain, bloating, vomiting, nausea, heart
21
burn, belching, anorexia etc. Inquiry regarding the
adverse or untoward events occurring during the
therapy with PPIs was also made from patients
included in the study. The cost analysis of the PPIs
was done by taking into consideration the available
PPIs in the hospital and used in the study. Rationality
of the prescription was assessed according to criteria
mentioned in previous studies. 16,18,22-27
RESULTS
Total 214 case sheets were reviewed, 101 from surgery
department and 113 from medicine department over a
38
Nousheen etal.,
period of two months. Out of these 214 cases 100

(46.72%) were on proton pump inhibitors. 47.52%
inpatients of surgery wards and 46.01% of inpatients
in medicine wards were on proton pump inhibitor
therapy as shown in Table 1.
Table1: Department wise distribution of patients on
Proton pump inhibitors
No. of No. of case patients
Department patients sheets
on PPIs
on PPIs reviewed
(%)
48
101
47.52
Surgery
52
113
46.01
Medicine
100
214
46.72
Total
Z=0.442, Hence no significant difference in the
prescription of PPIs between the Departments (test for
difference between two proportions). Out of 100
patients on proton pump inhibitors majority of them
41% were middle aged between 41-60 years age
group, and 61% were males and 39 % females shown
in Table 2 and Table 3.
Table 2: Age wise distribution of patients on proton
pump inhibitors
Age
% of Patients
20-40
44
41-60
41
60 and above
15
Table 3: Gender Distribution of patients on proton
pump inhibitors
Gender
% of patients
Male
61
Female
39
Z= 4.5081, Hence significant difference in the
prescription of PPIs between males and females
Table 4: Indications for prescribing PPIs
S.No Indication
% of patients
1.
Acute Gastritis
4
2.
Duodenal ulcer
1
3.
With NSAIDS
32
4.
GERD
05
5.
Others
58
4% of patients with acute gastritis , 5 % of patients for
Gastro Esophageal Reflux Disease (GERD) , 1%
Duodenal ulcer , 32 % of patients along with Non
Steroidal Anti-Inflammatory Drug and 58 % of
patients were prescribed PPIs for other reasons and
were neither on NSAIDS nor were having any
symptom related to GERD or acid peptic disease as

shown in Table 4. Oral therapy with PPIs was
prescribed in 70 % of patients and intravenous PPIs in
30% of patients. The intravenous PPI used in all these
patients was Pantoprazole 40 mg given once daily
early in the morning.
Majority of the patients were prescribed PPIs once
daily 97% only in 3% of the patients Twice daily
therapy was administered. As shown in Table 5and
Table 6.
Table 5: Route of administration of PPI
Route
% of patients
Oral
70
Intravenous
30
Table 6: frequency of administration of PPIs
% of patients
Frequency
Once daily
97
Twice daily
03
Concomitant drugs
The incidence of polypharmacy was high all the
patients in the study were prescribed multiple drugs.
Average number of drugs per prescription was 4.93.
Antimicrobials were the most common drugs used in
(71%) patients followed by non steroidal antiinflammatory drugs and multivitamin preparations in
32% patients as shown in Table 7.
Table 7: Concomitant drugs used along with Proton
pump inhibitors
S.No
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
Drugs used
Antimicrobials
NSAIDs
Multivitamin preparations
Calcium and vitamin D
Antihypertensives
Vitamin C
Antidiabetics
Antiemetics
Antiplatelets
Purgatives /laxatives
Corticosteroids
Diuretics
Antiepileptics
Antacids
Antimalarial
Oral Iron therapy
Hypolipidemics
Tramadol
patients %
71
32
32
07
09
10
03
13
03
02
01
03
01
03
04
05
03
22
39
Nousheen etal.,
Majority of the patients 88% were having a low Likert

score of < 20, prior to start of therapy only 12 % of the
patients were having significant symptoms (Likert
score above 21) related to Acid peptic disease or
GERD as shown in Table 9.
Table 8: Categorization based on likert scale
Likert
scale
score
12
13-20
21-30
Above 30
% of patients at % of patients at
onset of therapy
discharge
47
41
07
05
73
22
05
00
DISCUSSION
Table 9: Likert Score of patients at start of therapy

with PPIs and at discharge (Mean SD)
Likert score
(Mean SD)
At start of therapy
15.15 5.28
At discharge
12.98 1.90
Z Value= 3.86, Hence significant difference in the
Likert score demonstrating efficacy of PPIs.
Pantoprazole was most commonly prescribed PPI in
82% of patients followed by omeprazole in 11% and
esomepraole in 7 % as shown in Table 10.
Table 10: Proton pump inhibitors used in the study
PPI
Pantoprazole
Omeprazole
Esomeprazole
% of patients
82
11
07
Table 11: Cost analysis of Proton pump inhibitors

used in the study
Drug
Formu
lation
Dose
Pantoprazole
Oral
40 mg
Pantoprazole
IV
40 mg
Omeprazole
Oral
20 mg
Esomeprazole Oral
20 mg
OD= Once daily, Rs=Rupees
Table 12: Common adverse effects during therapy

with PPIs
%
of
S.No Adverse effect
patients
1.
At least one adverse effect
14
2.
Headache
5
3.
Rash
3
4.
Abdominal pain
3
5.
Nausea
2
6.
Constipation
2
7.
Diarrhoea
1
8.
Rhinitis
1
Freq
uency
Cost per
day
OD
OD
OD
OD
6.5 Rs
60 RS
3 RS
3 RS
Omeprazole and esomeprazole were cheaper in

comparison to pantoprazole
The prescriptions of proton pump inhibitors are

increasing rapidly in India as well as worldwide and
PPIs have become one of the most commonly
prescribed drugs. The present study shows that total of
46.72 % of hospitalized patients were on proton pump
inhibitors during the study period. This is in
accordance with the previous study by Ramirez E et
al28, who reported that the use of PPIs range from
28.65 % to 82.65% and Sandozi T17who reported use
in 45 % of hospitalized patients. There was no
significant difference in the prescription of proton
pump inhibitor between the surgery and medicine
departments (Z=0.442). The use of PPIs was
significantly more in males in comparison to females
Z= 4.5081. This is in accordance with the previous
study by Mayet AY16. Only 42 % of the patients were
prescribed PPIs according to the criteria of rationality.
58 % of the prescriptions of PPI were unjustifiable.
This is in accordance to the study by Sandozi T17 (55
%) but more than the study by Mayet AY16 (43%).
Study by Brandhagen DJ et al29 has reported 77.5% of
unjustified prescriptions. Naunton M et al15 (39.6%).
The frequency of administration of PPIs was once
daily in 97% of cases, the doses of PPIs are
recommended as once daily but can be given twice
daily also for rapid action as steady state is achieved
rapidly. The most common concomitant medications
used with PPIs were Antimicrobials, this is a serious
issue as 58% of the prescriptions of PPI were
unjustified and it is well known fact that patients on
proton pump inhibitors are also susceptible to
colonization of pathogens which can lead to bacterial
gastroenteritis and also their is higher risk of
development of infection by Clostridium difficle
(antibiotic associated diarrhoea). 32% of cases PPIs
40
Nousheen etal.,
were given along with NSAIDS. This is in accordance

with the studies by Kumar A et al30and Raghavendra B
et al31 who have found high incidence of coprescription of PPIs with NSAIDs. The use of NSAIDs
is an important predisposing factor for peptic ulcer
disease in the community thus one of the important
indications of PPIs is co-administration with NSAIDS
to reduce the risk of gastrointestinal bleeding and
peptic ulcers. In our study we used questionnaire based
five point Likert assessment scale to evaluate the
presence of GERD symptoms, dyspepsia and to assess
the symptom severity and response to treatment.20
Though a number of symptom scales and Quality of
life instruments have been used in clinical trials , not
all have been fully validated. We used the Reflux
Disease Diagnostic Questionnaire (RDQ) as it is
specific for GERD and dyspepsia. The validity,
reliability and responsiveness of this test have been
well demonstrated. In our study 47 % of patients had
RDQ score of 12 indicating that majority of the
patients had no symptoms of GERD as this was the
minimum possible score and only 12% patients had
significant symptoms as demonstrated by RDQ score
of more than 20. There was significant improvement in
the RDQ score of the patients demonstrating the
efficacy of PPIs (Z= 3.86). We cannot comment much
on the efficacy as our study was non interventional and
the duration of therapy with PPIs varied in the
patients. The study design was not appropriate to
evaluate our objective of efficacy with PPIs.
Randomized prospective clinical trials are better in this
regards. The most common proton pump inhibitor
used was Pantoprazole in 82% of patients, followed by
Omeprazole(11%) and Esomeprazole (7%). Atleast
one adverse effect was seen in 14 % of the patients.
Most common adverse effect was headache seen in 5
% of the patients. No serious or life threatening
adverse effect was observed in patients receiving
proton pump inhibitors. Cost analysis revealed that
pantoprazole was twice more costly than omeprazole
and esomeprazole formulations available in the
hospital pharmacy.
CONCLUSION
Fifty eight percent of the patients in our study received
Proton pump inhibitors improperly for unjustified
indications. Increased awareness should be created
among the clinicians in the hospital so that appropriate
prescription of PPIs will improve the patient care at
low cost. Although we found PPIs to be efficacious in

our study, the study design was not suitable for
evaluating efficacy. More drug utilization and
pharmacoeconomic studies should be conducted in
future to compare the rationality of use of proton pump
inhibitors and other anti secretory drugs like H2
blockers to know the exact scenario and plan the
remedial measures.
ACKNOWLEDGEMENT
We thank Indian Council of Medical Research (ICMR)
for funding this project through Short Term
Studentship Programme. We also thank the
Management and Principal, Kamineni Institute of
Medical Sciences, Narketpally for cooperation during
the conduct of study.
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Pharmacokinetic drug interaction profiles of
proton pump inhibitors. Drug Safety. 2006;29(9):
769-84.
2. Hetzel D. Acid pump inhibitors. The treatment of
gastroesophageal reflux. Australian Family
Physician.1998;27(6):487-91.
3. Hawkins C, Hank GW. The gastroduodenal
toxicity of nonsteroidal anti-inflammatory drugs:A
review of the literature. J Pain Symptom Manage
2000;20(2):140-51.
4. Katelaris PH. Proton pump inhibitors. Medical
Journal of Australia.1998; 169(4):208-11.
5. Reilly JP. Safety profile of the proton-pump
inhibitors. American Journal of Health-System
Pharmacy.1999;56(23 Suppl 4):S11-7.
6. Lewis SJ, Franco S, Young G, O Keefe SJ.
Altered bowel function and duodenal bacterial
overgrowth in patients treated with omeprazole.
Alimentary Pharmacology and Therapeutics.
1996;10(4):557-61.
7. Waldum HL, Brenna E, Kleveland PM, Sandvik
AK, Syversen U. Review article: the use of gastric
acid-inhibitory
drugs,
physiological
and
pathophysiological considerations. Alimentary
Pharmacology and Therapeutics.1993;7(6):589-96.
8. Yang YX, Lewis JD, Epstein S, Metz DC. Longterm proton pump inhibitor therapy and risk of hip
fracture. JAMA. 2006;296(24):294753.
9. Eurich DT, Sadowski CA, Simpson SH, Marrie
TJ, Majumdar SR. Recurrent community-acquired
41
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pneumonia in patients starting acid-suppressing

drugs. Am J Med. 2010;123(1):47-53.
Dalton BR, Lye-Maccannell T, Henderson EA,
Maccannell DR. Proton pump inhibitors increase
significantly the risk of Clostridium difficile
infection in a low-endemicity, non-outbreak
hospital setting. Alimentary Pharmacology and
Therapeutics.2009; 29(6): 62634
Colley CA. Polypharmacy: The cure becomes the
disease.
Journal
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General
Internal
Medicine.1993;8(5):278-83.
Sachs G. Proton pump inhibitors and acid-related
diseases. Pharmacotherapy. 1997;17(1):22-37.
Bashford JN, Norwood J, Chapman SR. Why
patients are prescribed proton pump inhibitors?
Retrospective analysis of link between morbidity
and prescribing in the General Practice Research
Database.BMJ 1998;317(7156):452-6.
Zacny J, Zamakhshary M, Sketris I, Veldhuyzen
van Zanten S. Systematic review: the efficacy of
intermittent and on-demand therapy with
histamine H2-receptor antagonists or proton pump
inhibitors for gastro-oesophageal reflux disease
patients.
Alimentary
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Naunton M, Peterson GM, Bleasel MD. Overuse
of proton pump inhibitors. J Clin Pharm Ther
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Mayet AY. Improper use of antisecretory drugs in
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Sandozi T. A Comparative Study of Cost
Analysis of H2 Antagonists and Proton Pump
Inhibitors in a Tertiary Care Hospital. Research
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Mat Saad AZ, Collins N, Lobo MM, O Connor
HJ. Proton pump inhibitors: a survey of
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Walker NM, McDonald J. An evaluation of the
use of proton pump inhibitors. Pharm World Sci
2001;23(3):116-7.
Shaw MJ, Talley NJ, Beebe TJ,Rockwood T,
Carlsson R,Adlis S, et al. Initial validation of a
diagnostic questionnaire for gastroesophageal
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96(1):527.
21. Forgacs I, Loganayagam . Overprescribing proton

pump inhibitors. BMJ. 2008; 336(7634): 23.
22. Hawkins C, Hank GW. The gastroduodenal
toxicity of nonsteroidal anti-inflammatory drugs.
A review of the literature. J Pain Symptom
Manage 2000;20(2):140-51.
23. Tannenbuam H, Bombardier C, Davis P, Russell
AS; Third Canadian Consensus Conference
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24. Allen ME, Kopp BJ, Erstad BL. Stress ulcer
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25. Atkins AM, Chandra Sekar M. Proton pump
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26. Carvagal A, Arias HM, Vega E, Sanchez AG,
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27. Heidelbaugh JJ, Inadomi JM. Magnitude and
economic impact of inappropriate use of stress
ulcer prophylaxis in non-ICU hospitalized
patients. Am J Gastroenterol.2006;101(10):2200-5
28. Ramirez E, Lei S, Borobia A, Pinana E, Fudio S,
Munoz R, et al. Overuse of PPIs in patients at
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29. Brandhagen DJ, Phaley AM, Onstad GR, Freeman
ML, Lurie N. Omeprazole use at an urban county
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1995;10(9):513-5.
30. Kumar A, Dalai CK, Ghosh AK, Ray M. Drug
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31. Raghavendra B , Narendranath S, Ullal SD,
Kamath R, Pai MR, Kamath S, et al. Trends in
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42
Nousheen etal.,
DOI: 10.5958/j.2319-5886.3.1.009

&
Health Sciences
www.ijmrhs.com
Received: 5th Oct 2013
Research article

Copyright @2013
ISSN: 2319-5886
A STUDY ON SEXUAL DIMORPHISM OF THE HUMERUS IN TAMILNADU REGION

*Anil Kumar Reddy Y1, Sheela Grace Jeevamani1, Indira Vijay Ingole2, Raghavendra1
1
Department of Anatomy, KFMS&R, Coimbatore, Tamilnadu, India

Department of Anatomy, Dr. PDMMC, Amravati, Maharashtra, India
*Corresponding author email: kumarlucky48@gmail.com

ABSTRACT
Sex determination from bones is of vital importance in anthropological studies and medico-legal cases. The present
study focused on measurements of the Humerus and to evaluate the differences in sex present in the morphology
through statistical analysis. Method: In our study, 120 dry adult humeri (56 right side & 64 left side) were studied
of known sex. Damaged bones were excluded from the study. Each Humerus was measured for 11 parameters;
measurements were taken by using a sliding caliper as described in the textbook of anthropology and previous
studies. The osteometric data of the Humerus of present study is statistically analyzed and compared with other
similar studies. Results: Statistical tests were applied to the metrical data obtained to assess whether the differences
between the means of each parameter are statistically significant or not. Length of Humerus, the weight of the
Humerus, Mid-shaft circumference, Transverse and Vertical diameter of superior articular surface, Bi-epicondylar
width of the Humerus have been found to be more discriminatory parameters for the identification of sex from
Humerus.
Keywords: Sex determination, Humerus, Anthropology, Tamil Nadu
INTRODUCTION
Sex determination from bones is of vital importance in
anthropological studies and medico-legal cases. The
role of the skeleton is invaluable in estimating
attributes such as age, sex, race, stature and presence
of disease. If the whole skeleton is available, there
should be no difficulty in arriving at an accurate
diagnosis of sex, but when only a part of the skeleton
is available, it poses increasing difficulty in
assessment. Origin: L humerus, umerus, the shoulder,
upper arm < IE *om(e)sos, the shoulder > Sans sa-,
Gr mos
The humerus is the longest and largest bone of the
upper extremity; it is divisible into a body and two
extremities.1 Many workers have studied the
morphometric data for the humerus in both sexes and
statistical assessment of the value of this metrical
study for sex determination of humerus. Present study
Anil et al.,
focused on measurements of the humerus and to

evaluate the differences in sex present in the
morphology through statistical analysis. This study
gives information regarding the role of human
humerus in the determination of sex and to compare
the present data with that of other workers. Many
workers have studied the morphometric data for the
humerus in both sexes and statistical assessment of the
value of this metrical study for sexing humerus.
Almost all bones of the human skeleton show some
degree of sexual dimorphism. The accuracy of sex
determination depends on the type and condition of the
bone, age of the subject, the degree of fragmentation
of the bones and biological variability. Obvious sex
differences do not become apparent until after puberty,
though specialized measurements on the pelvis can
indicate sex even in fetal material. It is recognized that
43
long bone cross-sectional area is greater in males as

compared to females which reflects more rapid
periosteal bone growth in boys.2
9. Transverse diameter of the lower end or

Biepicondylar width
10. Maximum length of the humerus
11. Weight of the humerus
120 dried adult humeri (56right side & 64 left side)

were collected from the Anatomy Department of
Karpagam Faculty of Medical Sciences & Research,
Coimbatore. Damaged bones were excluded from the
study. Measurements were taken by using a caliper as
described in textbook of anthropology3 and previous
studies.
Metrical data of each humerus was collected using 11
Anthropometric parameters as described below.
1. Vertical diameter of the superior articular surface
2. Transverse diameter of superior articular surface
3. Circumference of the superior articular surface of
humerus
4. Maximum width of the upper end or transverse
diameter of the upper end
5. Circumference of the surgical neck
6. Mid-shaft circumference
7. Least shaft circumference
8. Transverse diameter of the lower articular surface
Table 1: Measurements of Right Humerus (n=56)
Mean
Vertical diameter of the superior articular
surface (cms)
Transverse diameter of superior articular
surface (cms)
Circumference of the superior articular
surface of humerus (cms)
Maximum width of the upper end or
transverse diameter of the upper end cms)
Circumference of the surgical neck (cms)
Mid-shaft circumference (cms)
Least shaft circumference (cms)
Transverse diameter of the lower articular
surface (cms)
Transverse diameter of the lower end or
Biepicondylar width (cms)
Maximum length of the humerus (cms)
Weight of the humerus (cms)
Fig 1: Measuring the maximum width of the upper end
RESULT
120 dried adult humerus (56right side & 64 left sides)
were studied in present study. Each humerus was
measured for 11 parameters were already described as
above. The measurements were tabulated and
statistically analyzed. For each parameter we
calculated Mean, Median, Mode, Standard deviation,
T value and P Value.
Range
Standard
Deviation
M*
4.2
3.3-4.5
0.38
F*
3.8
3.2-4.1
0.55
M
3.96
3.5-4.1
0.26
F
3.7
3.2-4.3
0.38
M
12.8 11.5-14.3
0.88
F
12.1 10.8-14.5
1.10
M
4.63
4.2-5.2
0.28
F
4.4
3.9-5.2
0.36
M
8.6
6.7-10
1.11
F
7.2
5.6-9.4
1.13
M
6
5.1-5.2
0.67
F
5.5
5.2-6.6
0.56
M
5.6
5.2-6.4
0.58
F
5.4
5-6.4
0.52
M
5.1
3.5-6.2
0.99
F
4.6
4.5-5.9
0.74
M
5.2
4.2-6.4
0.89
F
4.5
3.3-6
1.2
M
31
26-32.7
6.64
F
26
28.5-33.6
9.68
M
99.3
60-126
24.9
F
84.8
60-120
19.2
P<0.05 considered as Significance;
T
value
Degree of
Freedom
P
value
2.37
54
<0.02
2.2
54
<0.02
2.9
54
<0.001
2.2
54
<0.02
2.7
54
<0.001
2.49
54
<0.01
1.24
54
>0.1
1.6
54
>0.1
2.5
54
<0.01
2.2
54
<0.02
2.1
54
<0.05
M-Male; F- Female
44
Anil et al.,
Table 2: Measurements of Left Humerus (n=64)
Vertical diameter of the superior

articular surface (cms)
Transverse diameter of superior
Circumference of the superior articular
surface of humerus (cms)
Maximum width of the upper end or
transverse diameter of the upper end
(cms)
Circumference of the surgical neck
(cms)
Mid-shaft circumference (cms)
M*
F*
M
F
M
F
M
F
M
F
M
F
Least shaft circumference (cms)
M
F
Transverse diameter of the lower M
F
Transverse diameter of the lower end or M
Biepicondylar width (cms)
F
Maximum length of the humerus (cms) M
F
Weight of the humerus (cms)
M
F
Mean
Range
3.87
3.9
3.91
3.7
12.2
11.5
4.4
3.2-4.4
3.4-4
3.6-4.2
3.1-4.4
10.8-13.5
10.2-13.4
3.9-4.8
Standard
Deviation
0.38
0.45
0.24
0.36
0.83
1.14
0.29
4.22
3.7-5.2
0.41
T
value
Degree of
Freedom
P
value
2.79
62
<0.01
2.4
62
<0.01
2.73
62
<0.01
1.8
62
<0.05
6.85
6.6-9.3
1.47
2.06
62
<0.05
6.25
5.8-9.7
1.05
5.8
5.2-6.8
0.47
3.7
62
<0.001
5.69
5.2-6.4
0.53
5.54
5-6.6
0.48
1.6
62
>0.1
5.22
3.5-5.9
0.82
4.52
4.3-6.1
0.92
0.5
62
>0.3
4.39
4.2-6.1
0.88
4.9
3.8-6.4
0.97
2.5
62
<0.01
4.35
3.4-6.2
0.86
30.2
26.3-32.4
1.99
2.5
62
<0.01
29
27.8-32.5
1.77
97.2
70-140
22.84
2.3
62
<0.02
81.2
60-120
28.97
P<0.05 considered as Significance; *M- Male; F-Female
DISCUSSION
In the present study, there has been found a difference
in the Vertical diameter, Transverse diameter and
Circumference of the superior articular surface of right
and left sides in the male and female humerus.
These findings of our study are in conformity with the
studies of Girish Patil (2011)4 study on south Indians
and Derya Atamturk,
M. Akif Akcal, Nucket mas
5
(2010) , but it is lower than the studies of Iscan MY et
al (1998).6 The Maximum width of the upper end
shown high differences between right and left sides in
male and female humerus. Similar findings are
reported by Derya Atamturk (2010).5
Significant range of differences observed in the
measurements of Mid-shaft circumference and least
shaft circumference. These findings of our study are in
conformity with the studies of Singh S (1972)7,
Kshirasagar et al (2001)8, Salles AD et al (2009)9,
Derya Atamturk, (2010)5 and Iscan M.Y et al (1998)6,
and Girish patil (2011)4, a study on south Indians.

in the Bi-epicondylar width of right (table-17) and left
sides (table-18) in male and female humerus and it is
statistically highly significant. Results of our study are
tallying with the results of studies by Singh S (1972)7,
Singh et al (1974), Derya Atamturk, (2010)5, Girish
patil (2011)4 study on south Indians, but not tallying
with the findings of Iscan MY et al (1998).6
In the present study, the Maximum length of humerus
is highly significant parameter there is a considerable
amount value difference is found between males and
females. Our findings are in conformity with the
findings reported
by Singh S (1972)7, Derya
5
Atamturk, (2010) and Iscan M.Y et al (1998)6, and
Girish patil (2011)4 study on south Indians, show
statistically significant sex differences between mean
of Maximum length of right and left in males and
females.
45
Anil et al.,

in the Weight of the humerus of right and left sides in
male and female humerus. Reports of similar study
(same parameter) are not available for comparison.
CONCLUSION
To know the significant findings for identification of
sex of humerus 120 (56right side & 64 left side) adult,
fully ossified, dried humeri were studied. The
measurements obtained from the humerus were
compared to the values reported by previous workers.
From the results it is cleared that based on no single
parameter, sex of humeri cannot be decided. All the
parameters have to be considered together for this
purpose.
Length of the humerus, Weight of the humerus, Midshaft circumference, Transverse and Vertical diameter
of the superior articular surface, Bi-epicondylar width
of
humerus have been found to be more
discriminating parameters for the identification of sex
from humerus. However, the sex overlap is observed
in all the parameters and indices. This may be due to
genetic, nutritional and socio-economical difference in
the individuals or may be due to hypo masculinity in
female humerus and hyper masculinity in male
humerus.
7. Singh S, Singh SP. Identification of sex from the

humerus. Indian Journal of Medicine and
Research. 1972, 60:1061-66.
8. Salles AD. Reconstruction of humeral length from
measurements of its proximal and distal
fragments. Braz. J. Morphol. Sci. 2009;26 (2): 5561
9. Kshirasagar SV, Chavan SK, Makhani CS,
Kamkhedkar SG. Sexual Dimorphism of
Humerus: A Study in Marathwada Region. Indian
journal of Forensic Medicine and Pathology. 2001,
2(4): 10-45
10. A Tagaya, inter to pelation variation of sex
disseresnces, an analesis of the extremity long
bone measurements of Japonese, J.Anshroses, soe,
Nippon 1987; 95: 45 76
11. Robinson MS, Bldmos MA. The Skull and
humerus in the determination of sex: reliability of
discriminant function equations. Forensic Sci Int.
2009, 186(1-3): 86e1-5
12. Beck TJ, Ruff CB, Shaffer RA, Betsinger K,
Trone DW, Brodine SK (2000) Stress fracture in
military recruits: gender differences in muscle and
bone susceptibility factors. 2000, 27(3):437-44
REFERENCES
1. Arnold F. Handbook of Functional Anatomy.
Ester babnd Freiburg Im Breisgau. 1844. 1st
Edition, p. 243.
2. Williams and Warwick Editors. Grays Anatomy
Churchill Livingstone (1995), 38th Edition, p.626.
3. Krogman WM. The human skeleton in Forensic
Medicine charise and Thomax springeld Illinosin,
U.S.A. 1st Edition. 1962)
4. Girish patil, Sanjeev Kolagi, Umesh Ramadurg.
Sexual dimorphism in the Humerus: South
Indians. Journal of clinical and Diagnostic
Research. 2011;5(3): 538-41.
5. Derya Atamturk, M. Akif Akcal, Izzet Duyar and
Nuket Mas. Sex estimation from the radiographic
measurements of the humerus. Eurasian J.
Anthropol. 2010;1(2): 99-108.
6. Iscan MY. Forensic Anthropology around the
world. For. Scl. Inter. 1998;74: 1-3.
46
Anil et al.,
DOI: 10.5958/j.2319-5886.3.1.010

&
Health Sciences
www.ijmrhs.com
Received: 8th Oct 2013
Research article

Copyright @2013
ISSN: 2319-5886
PROGNOSTIC INDICATORS AND PATTERNS OF RENAL RECOVERY IN PATIENTS REQUIRING

HEMODIALYSIS FOR ACUTE KIDNEY INJURY
*
Vaddadi Suresh1, Usha Bhargavi E2, N.S.R.C Guptha3, Vinod L4, Vijay Kumar P 5, Ravinder P6.
Associate professor, 3Assistant professor, 4Post Graduate, 5Professor; Dept of Medicine, GSL General Hospital,
Rajahmundry, Andhra Pradesh, India.
2
Assistant professor, Dept of Pathology, GSL General Hospital, Rajahmundry, Andhra Pradesh, India
6
Consultant Nephrologist, Apollo hospitals, Kakinada, Andhra Pradesh, India
*Corresponding author email: sureshvaddadi@yahoo.co.in
ABSTRACT
Background: The outcome of patients with acute kidney injury (AKI) is highly variable. Patients who receive
renal replacement therapy (RRT) for similar diseases may recover differently. The factors that operate in each
patient may alter the prognosis and outcome. Aims: Our study aims at identification of prognostic factors
influencing recovery in patients who required hemodialysis for AKI. Material and Methods: Patients admitted in
different ICUs with AKI who underwent hemodialysis in a tertiary care hospital over a three year period were
included in the study. Time from day one of disease to first dialysis, hematological and biochemical parameters
were noted. Patients were grouped based on the time taken for recovery of renal function following hemodialysis
into group A (<2 weeks) and group B (>2 weeks). Studied parameters have been statistically analyzed to find any
significant association with recovery time. Results: Out of 63 patients, 9 progressed to chronic kidney disease.
In the remaining 54, Group A comprised 31 and group B 23. Out of all the factors studied, serum creatinine
(7.01.3 vs 8.43.8; P=0.018), S. bicarbonate (21.72.8 vs 19.73.8; P=0.03), pH at admission (7.250.13 vs
7.10.19; P=0.048); number of hemodialysis sessions (3.5 1.5 vs 52.4; P=0.016) and time lag from day one of
disease to first hemodialysis (8.6 3.6 vs 11.55.9; P=0.007) showed significant association with recovery time.
Conclusion: Recovery following AKI is influenced by factors liked delayed presentation, late initiation of
hemodialysis, low pH and low bicarbonate which can predict delayed renal recovery following hemodialysis.
Keywords: Acute Kidney Injury, Hemodialysis, Seurm creatinine.
INTRODUCTION
Acute kidney injury (AKI) is defined as a sudden loss
of kidney function that results in the retention of urea
and other nitrogenous waste products along with
dysregulation of extracellular volume, electrolytes
and acid base balance.1 It constitutes up to 20% of
critically ill patients and is easily identified by a rise
in the serum creatinine.2
The quantitative definition of AKI has long been a
debate due to gross variations in various methods
employed in measuring the glomerular filtration rate
(GFR). In view of the need for a simple and uniform

definition, RIFLE criteria was proposed and was later
modified and presented as AKIN criteria.3,4 This,
along with the recent change in the name of ARF to
AKI will represent the entire spectrum of kidney
disease and help in early detection of cases. These
criteria rely on the baseline serum creatinine and the
relative rise is used in the categorization into risk or
injury or failure group. Even though serum creatinine
is not an ideal marker of renal failure, it is
47
Suresh et al.,
inexpensive and is readily available making it an

invaluable investigation. Novel biomarkers of AKI
like cystatin-C, Neutrophil gelatinase-associated
lipocalin (NGAL), Kidney injury molecule 1(KIM 1)
and many others are available, but their clinical utility
is still under validation.5
The etiologies of AKI vary, most common being
sepsis as reported from many studies globally.
Infectious causes dominate the charts all over the
world and severe malaria is an important addition to
the list of AKI in India. It is known that patients with
persistently high serum creatinine are at increased
risk of developing chronic kidney disease due to
tubular damage and interstitial scarring. The rates of
renal recovery in different studies varied from 3699%, but these studies defined recovery by dialysis
independence.6-8
Renal replacement therapy is life saving, especially in
AKI and the decision to initiate, type and timing of
RRT is the choice of the treating physician as per
certain indications like anuria, uremic symptoms,
refractory hyperkalemia, volume overload and
metabolic acidosis. It is prudent to initiate timely
rather than early hemodialysis as too early dialysis
is as bad as delayed dialysis as it can result in
increase in mortality.9 Intermittent hemodialysis is
the most common method of RRT employed in India
with varied outcomes. Renal transplantation is rarely
if at all, needed for AKI patients. Following RRT, the
decision to wean to conservative management is done
based on the recovery of clinical, biochemical and
metabolic parameters. These patients who are weaned
from RRT generally recover; some early, some late
and some may progress to ESRD, the factors
operating are unclear.10 In India, non availability of
RRT in many centers, financial constraints and
patient unawareness regarding disease are major
barriers for measuring the burden of renal disease in
the community. The factors that determine the
prognosis in these patients are believed to be multiple
and our study aims at their identification.
MATERIAL & METHOD
This study was done in a tertiary hospital over a three
year period from 2010 March to February 2013.
Informed consent was taken from all the patients and
Ethical clearance was obtained from Institutional
Ethics Committee of the hospital.
Inclusion criteria: 1) Patients both male and female

aged between 20 to 70 years. 2) Patients admitted for
various diseases in different intensive care units
(ICU) including medical, surgical, cardiac, obstetric,
Cardiothoracic and burns unit who developed AKI or
admitted with AKI. 3) Patients who required
hemodialysis in our hospital for severe renal disease.
A total number of 63 patients formed the study
population.
Exclusion criteria: Patients with renal disease who
did not receive hemodialysis, Patients with previous
history of renal disease, obstructive uropathy or acute
on chronic kidney disease and patients who already
received hemodialysis outside before admission were
excluded from the study.
Their age, sex, place of living and occupation were
noted. Physical examination was done and history
regarding possible risk factors was taken. All patients
have undergone hematological tests including Hb%,
total and differential counts, and platelet counts.
Their Serum creatinine, urea, random blood sugar,
electrolytes and arterial blood gas analysis at
admission were noted. Along with the treatment for
primary
condition,
all
patients
underwent
hemodialysis for different indications like uremic
encephalopathy,
Anuria/oliguria,
refractory
hyperkalemia, metabolic acidosis, volume overload
etc. Standard bicarbonate hemodialysis protocol was
given to all the patients which included two hours of
dialysis at initiation and then increased to four hours
during subsequent sessions. The number of sessions
of dialysis required for the recovery of each patient
was noted. The decision to wean from dialysis was
made after the correction of primary metabolic
abnormality or achievement of significant clinical
improvement or adequate urine output. These patients
were followed up thereafter starting from day one
after weaning from dialysis. Serial measurements of
S. Creatinine and urea were done after the 1st week,
2nd week, 3rd week and after 3 months. Falling
patterns of Serum creatinine in patients who
successfully completed the follow up was noted.
Patients were classified based on the time taken for
normalization of Serum creatinine (recovery) into two
groups: Those who recovered within 2 weeks were
placed in group A (N=31 ) and those who recovered
after 2 weeks were kept under Group-B (N=23 ).
Various parameters mentioned above were studied
between the two groups to identify any significant
48
Suresh et al.,
differences which are likely to influence the

prognosis and outcome.
RESULTS
Out of 64 patients admitted for hemodialysis,
41(65%) were males and 22 (35%) were females.
Most of the patients were agricultural laborers (65%).
Out of 63 patients who completed three months of
follow up, 9 (14.3%) met the definition of CKD at

third month and hence these patients were not
considered to have recovered. The remaining 54
Patients who recovered following hemodialysis, were
grouped into group-A (n=31) and group-B. (n=23).
The most common age group involved was between
41-50 years.
Table 1: Patients age groups

Age in years
Group A (%)
Group B (%)
20 or below 20
1
0
21-30
2
2
31-40
6
5
41-50
9
10
51-60
8
4
Above 60
5
2
Total
31 ( 57 %)
23 ( 43 %)
Various hematological and biochemical parameters, risk factors, number of dialysis sessions were compared
between the two groups to find any association with recovery time, as shown in Table-2
Table 2: showing comparison of various parameters between the two groups.
Group-A (n=31)
Group-B (n=23)
Mean SD
Mean SD
P value
Age in years
48.4 12.9
45.510.6
0.38
Hb%
9.62.5
9.52.2
0.87
TLC (cells/mm3)
128905602
136265974
0.64
RBS (mg/dl)
14668.6
156.7123.7
0.68
S.Creatinine (mg/dl)
6.41.1
8.63.7
0.01*
B.Urea (mg/dl)
183.358.9
210.876.1
0.14
Serum.Na+ (mEq/L)
1427.94
1379.8
0.06
+
Serum.K (mEq/L)
4.981.12
5.391.34
0.22
H
P
7.250.13
7.160.19
0.048*
S.Bicarbonate (meq/L)
21.72.86
19.73.86
0.03*
HDS
3.541.52
5.042.40
0.01*
T.D (days)
8.63.6
11.55.9
0.04*
Recovery duration(weeks)
1.830.37
3.571.2
----HDS- number of hemodialysis sessions required, T.D- time delay between first symptom to
hemodialysis. *Significance.
Table 3: showing Gender, Habits and Other risk factors between two groups
Group-A (n=31)
Group-B (n=23)
RISK FACTOR
P value
Sex
Male
18
16
0.28
Female
13
7
0.27
Diabetes
5
10
0.028*
Hypertenson
8
3
0.21
Smoking
11
9
0.5
Alcoholism
4
3
0.56
NSAID abuse
7
2
0.16
. Group A Patients who recovered within two weeks; Group B Patients who recovered after
two weeks; (* represents statically significant )
49
Suresh et al.,
Table 4: showing different causes of AKI
S.Creatinine in mg/dL
Etiology of AKI
Severe Malaria
Sepsis
Post Gastroenteritis
Leptospirosis
Acute glomerulonephritis
Unknown
Post cardiac or abdominal surgery
Acute pyelonephritis
Dengue Hemorrhagic fever
Road traffic accident with Rhabdomyolysis
Snakebite
Contrast Nephropathy
Acute Pancreatitis
Total
N=54 (%)
17 (27.2%)
9 (14.3%)
7 (11.1%)
6 (9.6%)
5 (8%).
7(11%)
5 (8%)
2 (3.2%)
1 (1.61%)
1 (1.61%)
1 (1.61%)
1 (1.61%)
1 (1.61%)
54 (100%)
Followup creatinine between two groups

5
4
3
gr A
gr B
1
0
1 WEEK
2 WEEK
3WEEK
3MTH
Fig 1: Shows fall of serum creatinine from day-1 after last session of hemodialysis
(Note: The curves belonging to both the groups are steep during the first week)
Statistics: All the statistical work was performed by
using SPSS trail version 16 and Microsoft Excel
2007. Descriptive statistics were presented in the
form of Mean Standard Deviation and Percentages.
The independent samples T test is used to compare
means and a p value < 0.05 is taken as statically
significant.
DISCUSSION
Hemodialysis forms an important therapeutic option
for severe AKI, but treatment of the primary
condition is as important. In our study, all the patients
fell into failure stage of RIFLE due to very high
serum creatinine at presentation and stage 3 of AKIN
criteria as all of them underwent hemodialysis. Males
are commonly affected as they mostly work outside,
getting exposed to infections, toxins and sustain
dehydration.11 Patients over 40 years of age

comprised 75% of the cases. This could be explained
by gradually falling renal reserve with age. Our study
highlighted the importance of recognizing severe
malaria as important cause of AKI in India as it was
the most common cause. Overall, infections
comprised 75% of all causes of AKI. Nine patients
(14.3%) met the definition of CKD after three months
but their disease progression was not followed
thereafter. Maximum recovery following weaning
from hemodialysis was noticed in the immediate first
week. There was a gradual fall of serum creatinine
during subsequent three months.
Comparison between patients with early (group-A)
and late recovery (group-B) was done after the follow
up period of three months. Age and hematological
parameters showed no difference between the two
50
Suresh et al.,
groups. Mean random blood sugar, blood urea, serum

potassium are higher in group-B but showed no
statical significance. Mean serum creatinine (6.41.1
vs 8.63.7; p <0.05), S. Bicarbonate (21.72.8 vs
19.73.8; p <0.05) and pH at admission ( 7.250.13
vs 7.10.19; p < 0.05), total number of hemodialysis
sessions (3.51.5 vs 52.4; p <0.05 ), time delay
between disease and treatment ( 8.63.6 vs 11.55.9;
p <0.05), has shown statically significant association
with the recovery time. Patients with high serum
creatinine at admission (implying higher renal
functional loss) took much longer to recover. Studies
have shown that higher stages of AKI can result in
prolonged hospital stay due to delayed renal
recovery.12 patients with severe metabolic acidosis
characterized by low bicarbonate and low pH took
much longer time to recover. Metabolic acidosis
results due to multiple factors apart from inability of
the kidney to excrete metabolic acids. Hepatic
involvement, which is commonly seen in Malaria,
Leptospirosis, Dengue infections, Sepsis and as a
component of multi organ dysfunction syndrome
(MODS) along with starvation in these patients can
contribute to significant metabolic acidosis.
AKI patients who required more number of
hemodialysis sessions had delayed recovery. This is
because patients who had severe disease required
more number of sessions and the recovery after
weaning is also delayed owing to the severity. A very
important outcome of this study is that delay in the
initiation of hemodialysis in indicated patients
resulted in delayed recovery following weaning. This
is evidenced by the significantly higher time gap (
days ) between first symptoms and first hemodialysis
in group B patients ( A vs B = 8.6 3.6 vs 11.5 5.9;
p=0.04). The exact timing of dialysis, duration and
withdrawal of dialysis sessions is Physicians
discretion, and is subjected to variations.13 Adding to
delayed hospitalization, conservative approach is
implemented by some, even when there is clear
indication for RRT, which can actually worsen the
metabolic complications and there by mitigating the
chances of recovery even after subsequent RRT. The
term door to dialysis time is suggested by some
authors to emphasize the importance of timely
hemodialysis. 14
In our study, patients with diabetes had delayed
recovery. This could be because of underlying
preexisting diabetic nephropathy in these patients.
Contrast nephropathy is one condition where

unequivocal evidence exists regarding renal damage
and poor recovery following RRT in diabetes.15
whether or not, this can be extrapolated to other
causes of AKI is not known. In our study, factors like
gender, hypertension, smoking, alcoholism and even
NSAID intake have not shown any association with
recovery time. This is in contrast to earlier studies
documenting NSAID use as a potential cause of renal
damage as well as delayed renal recovery.16 However,
we did not collect the data regarding the type,
quantity and duration of use of NSAIDS in any
patient included in the groups due to unreliability of
patient history.
The limitations of our study include small sample
size, lack of application of Glomerular filtration rate,
lack of long term follow up in recovered patients as
some of them could have landed in worsening of
renal function following apparent recovery, thus
missing the true burden of AKI progressing into
CKD.
CONCLUSION
AKI can have varied etiologies, and infections form
the bulk of these cases. Along with the correction of
primary cause, timely RRT can have significant
impact on the recovery of patients. Patients
presenting late, patients with high serum creatinine,
low Ph and low serum bicarbonate at admission,
patients who required more number of hemodialysis
sessions and known diabetics irrespective of diabetes
control, are prone for delayed recovery following
weaning from hemodialysis.
ACKNOWLEDGEMENTS
We are thankful G.K Anand Kumar, dialysis
technician and Ganapathi Swamy, statistician for
their immense help in this project.
REFERENCES
1. Fauci AS, Braunwald E, Kaspar DL, Hauser SL,
Longo DL, Jameson JL. Acute renal failure.
Harrisons Principles of Internal Medicine.17th
Ed.,McGrawHill; 2008:175261
2. Lameire N, Van Biesen W, Vanholder R. The
changing epidemiology of Acute renal failure.
Nat Clin Pract Nephrol 2006;2:364-77.
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3. Bellomo R, Ronco C, Kellum JA Mehta RL,

Palevsky
P.
Acute
renal
failure
definition,outcome measures, animal models,
fluid therapy and information technology needs:
the Second International Consensus Conference
of the Acute Dialysis Quality Initiative (ADQI)
Group. Crit Care 2004; 8:20412.
4. Mehta RL, Kellum JA, Shah SV, Molitoris
BA, Ronco C, Warnock DG, et al. Acute kidney
injury network: report of an initiative to improve
outcomes in acute kidney injury. Crit Care
2007;11: R31.
5. Waring WS, Stephen AF. Earlier recognition of
nephrotoxicity using novel biomarkers of acute
kidney injury. Clinical Toxicology.2011;49: 720
28.
6. Ishani A, Xue JL, Himmelfarb J, Eggers PW.
Acute kidney injury increases risk of ESRD
among elderly. J Am Soc Nephrol.2009; 20: 223
228.
7. Coca SG, Yusuf B, Shlipak MG, Garg AX,
Parikh CR. Long-term risk of mortality and other
adverse outcomes after acute kidney injury: a
systematic review and meta-analysis. Am J
Kidney Dis.2009; 53: 96173.
8. Wald R, Quinn RR, Luo J, Li P, Scales
DC, Mamdani MM, et al. Chronic dialysis and
death among survivors of acute kidney injury
requiring dialysis. JAMA .2009;302:11791185
9. Shiao CC, Ko WJ, Wu VC, Huang TM, Lai CF,
Lin YF, et al. U-curve association between timing
of renal replacement therapy initiation and inhospital mortality in postoperative acute kidney
injury. PLoS One 2012;7:e42952
10. Steven GC, Swathi Singanamala. Chronic Kidney
Disease after Acute Kidney Injury: A Systematic
Review
and
Meta-analysis.kidney
Intestinal.2012; 81(5): 442-48.
11. Kute VB, Shah PR. Outcome and prognostic
factors of malaria-associated acute kidney injury
requiring hemodialysis: A single center
experience. Indian J nephrol. 2012; 22(1): 33-38.
12. Mehta P, Sinha A,Sami Hari P, Kalaivani
M, Gulati A. Incidence of acute kidney injury in
hospitalized children. Indian Pediatr.2012;49:
53742
13. Gibney N, Hoste E, Burdmann EA, Bunchman T,
Kher V, Viswanathan R et.al Timing of Initiation
and Discontinuation of Renal Replacement

Therapy in AKI: Unanswered Key Questions.
Clin J Am Soc Nephrol. 2008;3(3):876-80
14. Andrade L, Cleto S, Seguro AC. Door-to-dialysis
time and daily hemodialysis in patients with
leptospirosis: Impact on mortality. Clin J Am Soc
Nephrol. 2007; 2: 739 44
15. Weisberg, Lawrence S., Peter B. Kurnik, and
Brenda RC Kurnik. Risk of radiocontrast
nephropathy in patients with and without diabetes
mellitus. Kidney international. 1994;45(1): 25965.
16. Abraham PA, Keane WF. Glomerular and
interstitial disease induced by nonsteroidal antiinflammatory drugs. American Journal of
Nephrology. 1984;4(1): 1-6
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DOI: 10.5958/j.2319-5886.3.1.011

&
Health Sciences
www.ijmrhs.com
th
Research article
Copyright @2013 ISSN: 2319-5886

PSYCHOSOCIAL DETERMINANTS OF CONTRACEPTIVE

REPRODUCTIVE AGE IN A RURAL AREA OF MAHARASHTRA
USE
AMONG
WOMEN
OF
*Minhas S1, Sekhon H2

1
Reader, Department of Community Medicine, Armed Forces Medical College, Pune, Maharashtra, India.
Psychiatrist & Chief Medical Officer, Composite Hospital, Central Reserve Police Force, Bantalab, Jammu, Jammu
& Kashmir, India.
2
*Corresponding author email: sukhmeetminhas@yahoo.com

ABSTRACT
The World Health Organisation reports that an estimated 94 per cent of the population of the world lives in
countries with policies that favour family planning. Despite this, five of every six couples of reproductive age do not
use adequate measures of fertility regulation. Gender inequalities in patriarchal societies ensure that men play a
critical role in the decisions on family matters. The present study was undertaken to study the nature of acceptance
of contraceptive practices and the psychosocial determinants. Methods: This was a community based cross
sectional descriptive study. The anticipated prevalence of contraceptive practices among the 206 women in the age
group of 15-49 years was 50%. Considering a margin of error of 10%, with finite correction and 10% of nonresponse and 95% CI, the sample size was calculated. 90 married women in the reproductive age group of 15-49
years residing at the village were studied after drawing the sample with simple random sampling method. Results:
There were 55 (61.11%) women who practised contraception. In case of 03 (3.33%) couples, husbands used
condoms, while in case of remaining 52 (57.78%), wife had undergone tubectomy. Conclusion: From the present
study, it was concluded that the most common method of contraception practiced in the study population was
tubectomy and a range of psychosocial factors played an important role in decision making.
Keywords: Women, Rural, Contraception, Psychosocial, Tubectomy.
INTRODUCTION
An expert Committee of the World Health
Organisation (WHO) has defined family planning as
a way of thinking and living that is adopted
voluntarily, upon the basis of knowledge, attitudes and
responsible decisions by individuals and couples to
attain certain objectives.1 Even though the technology
was available, only nine per cent of women in the
developing countries had access to contraceptive
services in 1965. The use increased to 50 per cent by
1990. Nonetheless, wide geographical variations still
persisted.2 The world conference of the International
Womens Year 1975 declared the right of the women
to decide freely and responsibly on the number and
spacing of their children and to have access to
information and means to enable them to exercise that

right. The United Nations International Womens
Decade (1976-1985) helped to increase awareness
about many issues concerning womens health
including excessive pregnancies, inappropriate timing
and spacing of pregnancies and poor educational
levels2. During the International Conference on
Population Development programme of action, it was
recognized that demographic goal-driven family
planning programmes, may by their very nature violate
basic human rights (ICPD 1994).3 The WHO reports
that an estimated 94 per cent of population of the
world lives in countries with policies that favour
family planning. Despite these policies five of every
53
Minhas et al.,
six couples of reproductive age do not use adequate

measures of fertility regulation.4 Currently, over 97
percent of sterilisations are tubectomies.5 It has been
deduced by research that family planning is the first
and most important step for rural development.6
Family planning means better health for the mothers
and their children and more opportunities for the
family as a whole.7 A majority of women in most
developing countries are aware of the health risks
posed by frequent pregnancies, and thus the
importance of birth spacing, but this awareness has not
satisfactorily translated into action.2A study conducted
on eligible rural women revealed that most of them
were concerned about child survival and also that they
viewed children as an important source of their
support in old age. The size of family was usually
decided by in-laws and partner support played a
predominant role in the decision. Pressure from the inlaws to have more number of children was found to be
significantly higher in families where the women were
less educated or illiterate.8 Despite the decline in total
fertility rate worldwide, there are still millions of
women with unmet contraceptive needs in developing
countries. There are more married women with an
unmet contraceptive need (about 31 million) in India
than any other country.9 The National Family Health
Survey III (NFHS III), carried out in 29 states during
2005-06, shows that nearly 45 per cent of women in
India were married off before they turned 18. It also
shows that over 71 per cent of women who got
married under 18 years had received no education.
Early marriage impacts a woman's health and
education. It shows that women who are getting
married early are giving birth also at an early age.
While 52.5 per cent of the under 18 marriages were in
rural areas, it was 28.1 per cent in urban areas.10 But
the Total Fertility Rate (TFR) has shown a decline
over the years. In the state of Maharashtra itself, the
TFR has shown a decline, from 2.9 (NFHS-I), to 2.5
(NFHS -II) and 2.1 (NFHS -III).11 Many studies have
been conducted till now on this issue but still there are
gaps in the information on the sporadic nature of
acceptance of contraceptive practices, especially in
this rural area of the state.12 In view of the same, this
study was undertaken in a rural area of Maharashtra,
India.
Aim: This study aimed at conducting an
epidemiological survey among the married women in
the age group of 15-49 years, residing a rural area of
Maharashtra, India to find out the current

contraceptive practices.
Objectives: 1. To determine the current contraceptive
practices among married women in a village in Pune
district of Mahrashtra. 2. To suggest promotional
strategies for better utilisation of family planning
services
It was a community based cross sectional descriptive
study. The reference population was women who were
married and in the reproductive age group (aged 15-49
years) residing in the rural areas of Maharashtra. The
exclusion criteria were all women who were divorced,
separated, widowed, infertile, who had attained
menopause, who had undergone hysterectomy and
women who had migrated to the village but were not
permanently residing there. The actual study
population included all married women in the
reproductive age group of 15 49 years residing in the
village. Simple random sampling was done. The
anticipated prevalence of contraceptive practices
among the 206 married women, considering a margin
of error of 10%, with finite correction and 10% of nonresponse and 95% CI, the sample size was calculated
to be 90. For selection of subjects, a serial list of all
the married women in the reproductive age group of
15 49 years was made. Using random number table
generated random numbers and the women
corresponding to these numbers from this population
were included in the sample. House to house visits
were carried out and the eligible women were
interviewed using a pre-tested standardized
questionnaire. Verbal consent of the respondents was
taken before the questionnaire was administered. A
pilot study was undertaken on 20 subjects (who were
later excluded from the actual study) which helped to
further standardize the questionnaire and make certain
amendments in it. A brief introduction about the study
was given by the principal worker to the subjects. The
services of a medico-social worker were sought for
interpretation and better communication with the
subjects. Confidentiality of the identity of the
respondent and the information provided was assured.
RESULTS
Out of the sample of 90, there were 55 (61.11%) who
practiced contraception (table-1).
54
Minhas et al.,
Table 1: Distribution of Respondents Based on

Contraception Usage
Contraceptive users (%)
Non-users Total
Tubectomy Condom (%)
52 (57.78)
03 (3.33) 35 (38.89) 90
In case of three (3.33%) couples, the husbands used
condoms, while in the case of remaining 52 (57.78%),
the wives had undergone tubectomy. No other mode of
contraception was found in the subjects who were
studied as a sample. For analysis purposes, the three
(3.33%) couples using condoms were excluded.
Subsequent analysis was done against tubectomy users
and non-users of any contraceptive method. On
studying the distribution of tubectomy status by age of
respondent (table-2), a significant association was
found between defined age groups and tubectomy
status (p<0.01).
Table 2: Distribution of Tubectomy Status by Age
of Respondent
Tubectomy (%)
Age
Total (%)
User
Non-User
(Years)
<25
06 (11.54) 19 (54.29)
25 (28.73)
25-34
24 (46.15) 12 (34.29)
36 (41.38)
35
22 (42.31) 04 (11.43)
26 (29.89)
Total
52 (100.00) 35 (100.00) 87 (100.00)
Chi square Statistic: 20.689
df = 2 p<0.01
Mean (SD): Users: 33.23 (6.94) Non-users: 25.31
(6.03), t statistic=5.49, df=85, p<0.01
There was a significant difference in age of husbands
between users and non-users (p<0.01) (table 3).
of Husband
Age
Tubectomy (%)
(Years) User
Total (%)
Non-User
<30
04 (07.69) 19 (54.29)
23 (26.44)
30-40
31 (59.62) 14 (40.00)
45 (51.72)
>40
17 (32.69) 02 (05.71)
19 (21.84)
Total
52 (100.00) 35 (100.00) 87 (100.00)
Chi square Statistic: 25.706
df = 2 p<0.01
Mean (SD): Users: 37.83 (6.75) Non-users: 29.23
(6.64), t statistic=5.86, df=85, p<0.01
Two-third of users i.e. 39 (75.00%) users got married
before the age of 18 years and only 13 (25.00%) users
did so at or after attaining the age of 18 years (table 4).

of Respondent at Marriage
Age
Tubectomy (%)
(Years) User
Total (%)
Non-User
<18
39 (75.00) 14 (40.00)
53 (60.92)
18
13 (25.00) 21 (60.00)
34 (39.08)
Total
52 (100.00) 35 (100.00) 87 (100.00)
Chi square Statistic (Yates corrected): 9.344, p value:
<0.01
Median age at marriage: Users:16, Non-users: 18
It was found that significantly higher percentage of
users had age at marriage less than 18 years as
compared to non-users (p<0.01). There were more
users with three or more children than non-users
(table-5).
Table 5: Distribution of Tubectomy Status by Total
Number of Children
Number of
Tubectomy(%)
Children
User
Non-user Total (%)
1-2
18 (34.62) 24 (88.89) 42 (53.16)
3
34 (65.38) 03 (11.11) 37 (46.84)
Total
52 (100.00)
27 (100.00)
79 (100.00)
Note: Eight couples who do not have any children

were excluded.
Chi square Statistic (Yates corrected): 18.90, p
value<0.01
The highest level of education was found to be
graduation while the lowest was illiterate in the case of
husbands, while it was high school and illiterate in the
case of the respondents (table -6,7).
Table 6: Distribution of Tubectomy Status by
Educational Qualification of Husband
Educational Tubectomy (%)
Qualification User
Total (%)
Non-User
<Middle
14 (26.92) 12 (34.29)
26 (29.89)
Middle
38 (73.08) 23 (65.71)
61 (70.11)
Total
52 100.00) 35 (100.00) 87 (100.0)
Chi square Statistic (Yates corrected): 0.246, p value =
0.6
Table 7: Distribution of Tubectomy Status by
Educational Qualification of Respondent
Educational Tubectomy (%)
Qualification User
Total (%)
Non-User
<Middle
22 (42.31)
17 (48.57)
39 (44.83)
Middle
30 (57.69)
18 (51.43)
48 (55.17)
Total
52
35
87
55
Minhas et al.,
Chi square Statistic (Yates corrected): 0.126, p value =

0.7
Level of education of the husband did not have a
significant association with tubectomy (p>0.05). It was
also observed that greater is the income, the more is
the acceptance for tubectomy (table 8).
Table 8: Distribution of Tubectomy Status by Total
Monthly Income
Income
Tubectomy (%)
Total (%)
User
Non-User
<2000
01 (01.92)
07 (20.00)
08 (09.19)
2000-2999 10 (19.23)
13 (37.14)
23 (26.44)
3000-3999 25 (48.08)
09 (25.71)
34 (27.59)
4000
16 (30.77)
06 (17.14)
22 (25.29)
Total
52 (100.00) 35 (100.00) 87 (100.0)
Chi square Statistic (Yates corrected): 10.30,
p
value <0.01
Logistic Regression
A model for Logistic Regression Analysis was
prepared, taking those predictor variables which had
shown a significance of p0.1 in the univariate
analysis. The multivariate analysis was done to assess
the effect or association or impact of age of
respondents, age of husband, age of respondent at
marriage, age of respondent at birth of first child, total
number of children, occupation of respondents,
combined income of respondents and husband, on
tubectomy status. Women with no child were excluded
from this analysis, since they will not have information
regarding age at birth of the first child and a number of
children will be zero. In this analysis, only the
combined income was found to have a significant
association with tubectomy status, with p value less
than the conventional i.e. p<0.05, Odds Ratio = 15.29
with 95% Confidence Interval: 2.44 95.69. It was
observed that the odds of acceptance of tubectomy
among those couples who had a combined income of
3000 rupees per month were 15.29 times more than
the couples who had a combined monthly income less
than this figure.
DISCUSSION
In the present study, the figures for contraceptive
prevalence as well as female sterilization, both are
above the corresponding national figures. The current
level of contraceptive use i.e. contraceptive prevalence
rate defined as percentage of currently married women
aged 15-49 years who are currently using a method or
whose husbands are using a contraceptive method, is

one of the principal determinants of fertility. It is also
an indicator of the success of family planning
programmes.11 As per NFHS III, contraceptive
prevalence rate for currently married women in India
is 56 percent (four percent more than NFHS II).
Female sterilization with a prevalence of 37 percent,
accounts for 66 percent of all contraceptive use (NFHS
II: 34.2 percent; NFHS I: 27.3 percent). In the state of
Maharashtra, the prevalence of female sterilization is
44.2 percent.11 Sterilisation has been a widely used
method of contraception in India.
It has been found that unmet need decreases with age,
from 27 percent for women aged 15-19 years, to two
percent for women aged 45-49 years. The unmet need
for family planning among currently married women is
13 percent, down from 16 percent in NFHS II.11 In the
present study, it was revealed that the age of users was
significantly higher than non-users, which is similar to
findings of previous studies.13-15 A significant
association was also found between tubectomy and the
age of the respondent at marriage (p<0.01). The
median age at marriage is 16 years and 18 years
among users and non-users respectively. One in six
women begins childbearing in the age group 15-19
years. The age at which women start bearing children
is an important demographic determinant of fertility.11
Similar results were observed in the present study i.e.,
46 (58.22%) of the respondents had given birth to their
first child before they turned 20 years of age. Delayed
childbearing may reduce maternal and infant health
risks but in addition, also provide increased
opportunities for women to acquire education, skills
and great aspiration for herself and her family.15 The
permanent method of contraception has been found to
be accepted by 70.7% of the women with three or
more children and only 29.3% accepted this method
with one or two living children.16 In the present study,
a significant association was observed between
tubectomy and the total number of children (p<0.01).
The mean number of children for currently married
women was found to be 2.96 and 1.37 in case of users
and non-users respectively. There were six
respondents who had only female children and all of
them were non-users. It appears that the family is
considered complete only if male children are there,
whether they are in addition to the female children or
not; only then is tubectomy resorted to. It shows that
the gender of the children is a determining factor for
56
Minhas et al.,
undergoing tubectomy. The extent to which the status

of women is related to awareness, knowledge, and
practice of family planning in India shows a definite
statistical relationship between women's status and
women's ability to control fertility. It was found that a
higher percentage of couples who have two or more
surviving children, particularly if they are boys,
practiced family planning.17, 18
Education as such has not been found to have any
significant association with tubectomy although better
is the educational qualification, more likely is the
decision to resort to it.16,17,19-21 In NFHS III, overall,
just over half i.e. 55 percent of women were found to
be literate while 78 percent males were found to be so.
In case of rural areas, 49.7 percent of women and 23.0
percent of men were found to be illiterate. In fact,
besides income, the greatest difference in fertility was
found to be due to education. The use of female
sterilization is higher for females with less education.11
In a study conducted in a developed country, it was
hypothesised that the current contraceptive use among
the sexually active, fertile women was related to their
attitude towards the different types of contraceptive
methods available, social influences, the perceptions
of ability to use a method correctly and also
consistently, and communication with their respective
partner. In the present study too, education has been
observed to play an important role in partner support
and the decision making process.22
Wealth has been found to have a positive effect on
womens contraceptive use. In NFHS III,
contraceptive use was found to be 42 percent among
the lowest quintile, while it increased to 68 percent in
the highest quintile. It was observed in the present
study that in the case of those couples who had both
members earning, acceptance of tubectomy was more.
Income has been found to influence the acceptance of
family planning methods and an increasing trend of
acceptance has been observed with the increase in
income.16
From the present study it is evident that sterilization is
fairly well accepted, however more knowledge is
needed on reversible methods. Since the findings of
the current study are comparable to other similar
studies and the NFHS III data, it highlights that the
results of the current study can be used as a
background to conduct more such studies so as to add
on to the information that already exists. It would help
to generate community specific data in order to benefit

for research, development and planning purposes.
CONCLUSION
This study brings out that knowledge about
contraceptive is nearly universal and that education
enhances the ability of individuals to achieve desired
demographic goals.11 It reiterates the fact that
education plays a major role in creating better
awareness amongst people. The choice of
contraceptive appears to be determined a lot more by a
general like or dislike towards medical methods, rather
than weighing merits of the individual available
methods.22 Effective contraceptive practices have the
potential, not only to improve the lives of the women,
men and children involved, but also to benefit couples,
families and communities.23
RECOMMENDATIONS
Based on this study, it is recommended that what is
required is the need to strengthen social marketing
programmes for non-clinical family planning products
and services in such areas. Greater effort needs to be
made to involve men in the process of family planning
and male sterilization requires to be given impetus.
Awareness about methods other than female
sterilization must be improved by village level
campaigns. To help encourage adoption of family
planning and reduce fertility, the government should
emphasize education for women, enforce the legal
minimum age at marriage, promote employment
opportunities for women, improve women's role in
decision making, and encourage inter-spousal
communication in family affairs.
Conflicts of interest; None identified.
REFERENCES
1. Park K. Parks Textbook of Preventive and Social
Medicine. 22nd Edition. Banarsidas Bhanot,
Jabalpur, India, 2007; 389, 392.
2. Sein T, Rafei UM. The history and development
of public health in developing countries. In: Detels
Roger, McEwen James, Beaglehole Robert and
Tanaka Heizo editors. Oxford Textbook of Public
Health. 4th Edition. Oxford Medical Publications,
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3. Gruskin S, Tarantola D. Health and human rights.
In: Detels Roger, McEwen James, Beaglehole
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Textbook of Public Health. 4th Edition. Oxford

Textbook of Public Health. Oxford Medical
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Tyler CW, Peterson BH. Family planning
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National Population Policy 2000. Operational
Strategies: Meeting the unmet needs. Available at
https://www.
india.unfpa.org/drive/National
Population-Policy2000.pdf. Accessed on 06-122013.
Mokarapong T. Family planning is the first and
most important step for rural development. J Thai
Assoc Volunt Steriliz. 1983; 75-85.
Gandhi I. India: the human factor in overcoming
population problems. Asian Pac Popul Programme
News. 1984;13 (1):15-6
Kartikeyan S, Chaturvedi RM. Family planning:
views of female non-acceptors in rural India. J
Postgrad Med. 1995 Apr-Jun; 41(2):37-9.
Wang S, An L, Cochran SD. Women. In: Detels
Roger, McEwen James, Beaglehole Robert and
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Health.. Oxford Medical Publications, 2005; 4th
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Daily News and Analysis: NFHS III. February 23,
2007. www.dnaindia.com.
International Institute for Population Sciences
(IIPS) and Macro International. National Family
Health Survey (NFHS-3), 200506: India:
2007;Volume I.
Department of International Economic and Social
Affairs. Population Division UN: Recent trends
and conditions of fertility. United Nations. Popul
Bull UN. 1983; (15):1-14.
Sengupta R, Lhungdim H .Factors associated with
Contraceptive Practices and Unmet Need among
Young Currently Married Women in the Rural
Areas of Empowered Action Group (EAG) States
of India. IIPS Seminar Jul 2011. Available at:
iipsindia.org/pdf/Vol.%2052%20No.%203%20&
%204%20July-2011.pdf. Accessed on 06-12-2013.
Susuman SA. Son Preference and Contraceptive
Practice among Tribal Groups in Rural South
India. Stud. Tribes Tribals, 2006;4(1): 31-40.
15. Khokhar A, Mehra M. Contraceptive Use in

Women From a Resettlement Area in Delhi.
Indian Journal of Community Medicine, 2005;30
Available at:http://www.indmedica.com/journals.
php?journalid=7&issueid=28&articleid=302
&action=article. Accessed on 06-12-2013.
16. Mohanan P, Kamath A, Sajjan BS. Fertility pattern
and family planning practices in a rural area in
Dakshina Kannada. Indian Journal of Community
Medicine, 2003;28 (1): 15-18
17. Vaidyanathan KE. Status of women and family
planning: the Indian case. Asia Pac Popul J. 1989;
4 (2):3-18
18. (No authors cited) India: sterilization is common;
women know little about other methods. Prog
Hum Reprod Res. 1991;18:2-3.
19. Kaur G, Singh TR. Acceptance of family planning
practice among rural women clientele. Indian J
Public Health. 1982; 26 (3):194-9
20. Takkar N, Goel P, Saha PK, Dua D. Contraceptive
practices
and
awareness
of
emergency
contraception in educated working women. Indian
J Med Sci 2005;59:143-9
21. Gupta VM, Jain R, Sen P. Study of interspouse
communication and adoption of family planning
and immunization services in a rural block of
Varanasi District. Indian J Public Health. 2001;45
(4):110-5.
22. Oddens BJ. Determinants of contraceptive use
among women of reproductive age in Great
Britain and Germany. II: Psychological factors. J
Biosoc Sci. 1997;29(4):437-70
23. TMM Maja. Factors impacting on contraceptive
practices. Health Sa Gesondheid. 2007;12(1):3038.
58
Minhas et al.,
DOI: 10.5958/j.2319-5886.3.1.012

&
Health Sciences
www.ijmrhs.com
th
Revised: 3rd Dec 2013
Research article
Copyright @2013
ISSN: 2319-5886
Accepted: 12th Dec 2013
CLINICO-PATHOLOGICAL PROFILE IN THE INFANTS AND CHILDREN IN DENGUE 2012

EPIDEMIC, KOLKATA
*Saha K Ashis1, Ghosh Shibendu2.
1
Assistant Professor, General Medicine, K P C Medical College & Hospital, Jadavpur, Kolkata, West Bengal
Professor, General Medicine, Ramkrisna Mission Seba Pratisthan, Kolkata, West Bengal, India
*Corresponding author email: asissaha2008@gmail.com

ABSTRACT
Background: Dengue fever (DF) is responsible for cyclical and frequent epidemic in different parts of India in its
varieties of presentations. In 1992 large number of children died of Dengue hemorrhagic fever (DHF). Aims and
objective: In this study, we evaluated the demography and clinico-pathological profile in dengue affected infants
and children in 2012 Kolkata epidemic. Materials and methods: Total 233 patients (between 1-18 years, with
either Non structural protein 1 antigen or dengue Immunoglobulin positive) admitted in our hospital. After taking
proper history and physical examination, blood were sent for different hematological and biochemical examinations
on the day of admission and after 24-48 hours of admission. We differentiated the dengue patients into DF and DHF
based on platelet count. Results: Male female ratio and DF to DHF ratio were 1: 0.86 and 1: 3.5 respectively. Mean
age of DF and DHF were 10.315.41 years and 12.64.51 years respectively. Mean duration of fever in DF and
DHF cases were 5.331.13 and 6.081.79 days respectively. Headache, backache, nausea/vomiting, rash, anorexia,
loose motions were statistically significant in DF. In spite of significant positive tourniquet test in DHF patients
(76.92%), only 13 patients showed evidence of bleeding. Hematocrit (Hct) values between 30-40 and below 30
were significant in DHF and DF patients respectively. Leucopenia and increased liver enzymes (SGOT and SGPT)
were commonly observed in both DF and DHF patients. Hepatomegaly was observed in 13.72% of DF patients,
whereas, isolated hepatomegaly, ascites, combined hepatomegaly with ascites and evidence of pleural effusion were
observed in 4.94%, 1.64%, 3.29% and 7.14% of DHF patients respectively. Conclusion: In seropositive DHF
patients, fever, headache, backache, loose motions were the predominant symptoms associated with hepatomegaly,
elevated liver enzymes and evidence of plasma leakage.
Keywords: Clinico-pathology, Dengue epidemic, Infants, Children, Kolkata
INTRODUCTION
Over several decades, Dengue, an Arbo virus
infection, is responsible for cyclical and more frequent
epidemic in rural as well as urban areas of India,
showing a wide variety of presentations from
subclinical or mild self limiting disease to severe form
of disease, like, dengue hemorrhagic fever (DHF) and
dengue shock syndrome (DSS).1 DHF first crept into
Kolkata in 1963-65, this was followed by the recurrent

occurrence of outbreaks.2 In the 1992 epidemic, large
number of affected children died of DHF/DSS.
Dengue may be manifested by its typical clinical
features, but its presentation may be variable making
the doctor puzzled. Our present study was to evaluate
the demography and clinic-pathological profile of
59
Saha et al.,
dengue fever in infants and children during the 2012

dengue epidemic in Kolkata.
PATIENTS & METHODOLOGY
Inclusion criteria: In 2012 epidemic, total 233 infants
and children between the ages of 1 to 18 years, were
admitted in our hospital on and from the month of 1st
August to 31st October with either Non structural
protein 1 antigen (NS1, antigen) positive or dengue
Immunoglobulin M (IgM) positive.
Exclusion criteria: Patient suffering from any
infection, viral hepatitis during this period.
Ethical clearance: This study was started after getting
approval from Ethical Committee and informed
consent form obtained from the patients parties.
Methodology: Thorough history-taking and physical
examination was performed in all these patients. Just
after admission, 5 ml. of blood was collected
aseptically from each patient. 1 ml of clotted blood
was used for non structural protein 1 (NS1) antigen
and immunoglobulin M (IgM) antibody by Mac
ELISA manufactured by Panibo Diagnostics,
remaining 4ml of Blood sample was used for
examination of hematological and biochemical profile
immediately.
Between the interval of 24 and 48 hours after
admission, 4 ml of blood sample was collected. 2 ml
of blood was kept in EDTA vial and was sent for
platelet count both by manual methods (light
microscopy and Neubauer chamber) and Coulter
counter method and hematocrit. Rest 2 ml of clotted
blood was used for biochemical tests (SGPT, SGOT).
Daily platelet count was advised for those patients
having platelet count less than 100000/cc.
Imaging studies like, Ultrasonography and chest x-ray
were performed to detect Ascites and pleural effusion
respectively. We differentiated the dengue patients
into Dengue fever (DF) and DHF based on platelet
count. (Since there was no DSS detected among in this
group). These patients were treated with intravenous
fluid, Paracetamol according to WHO protocol.3 No
Table 1: Demographic distribution
Features
Mean age yrs
Male sex
Female sex
*significant
patient was treated with NSAID. When vital statistics

of these patients came to normal; they were discharged
from hospital.
Statistics: Then, we compared the demographic data,
symptoms, laboratory investigations between DF and
DHF by Open stat and Statcalc statistical Calculators.
P value of <0.05 was considered as statistical
significance.
RESULTS
In our study, all our patients were either NS1 (79%) or
IgM (21%) positive. Male female ratio was 1: 0.86,
whereas ratio of DF to DHF ratio was 1: 3.5. Male to
female ratio in DF was 1: 1 and in DHF, 1:1.16. Mean
age of DF and DHF were 10.315.41 years and
12.64.51 years respectively [table 1]. All the patients
were admitted with fever. Mean duration of fever in
DF and DHF cases were 5.331.13 and 6.081.79
days respectively.
Common symptoms were
Headache (62.74%, 30.76%), backache (58.82%,
30.76%), nausea/vomiting (62.74%, 47.25%), rash
(29.41%, 15.93%), anorexia (60.78%, 13.73%), loose
motion (35.29%, 18.68%) in both DF and DHF
respectively. In spite of significant positive tourniquet
test in DHF patients (76.92%), severe bleeding was
seen in only 13 patients. [Table 2]. Most of the
patients were anemic. Hematocrit (Hct) between 30-40
was significant in DHF patients, whereas, Hct was
observed below 30 in significant number of DF
patients. Leucopenia and raised liver enzymes (SGOT
and SGPT) were commonly observed in both DF and
DHF patients without any statistical difference. But,
the International normalized ratio (INR) was only
elevated more than 1.5 in DHF patients [Table 3].
Sonographically, Isolated hepatomagaly observed in
13.72% and 4.94% DF and DHF patients respectively,
whereas, ascites and ascites associated with
hepatomagaly were observed in 1.64% and 3.29% of
DHF patients respectively. Again, chest x-ray showed
evidence of pleural effusion in DHF patients only
[Table 4].
DF (51)
10.31 5.41
26
25
DHF (182)
12.6 4.51
98
84
P value
0.04*
0.35
0.35
60
Saha et al.,
Table 2: Common symptoms

Symptoms
DF (51)
DHF (182)
Fever (days)
5.331.13
6.081.79
Headache
32 (62.74 %)
56(30.76%)
Backache
30 (58.82%)
56 (30.76%)
Nausea/vomiting
32 (62.74%)
86 (47.25%)
Rash
15 (29.41%)
29 (15.93%)
Anorexia
31 (60.78%)
52 (13.73%)
Loose motion
18 (35.29%)
34 (18.68%)
Retro orbital pain
4 (7.8%)
6 (3.29%)
Types of bleeding
Positive tourniquet test 0
140 (76.92%)
Epistaxis
0
3 (1.64%)
Skin
0
4 (2.19%)
Gum
0
3 (1.64%)
Hematemesis/melena
0
3 (1.64%)
*-- Significant, **-- Very significant, *** -- Extremely significant
Table 3: Hematological, biochemical distribution:
Parameter
DF (51)
DHF (182)
Hematocrit (L/L)
40 (37)
2 (3.92%)
4 (2.19%)
(30-40)
20 (39.21%)
120 (65.93%)
(<30)
29 (56.86%)
58 (31.86%)
Hemoglobin (gm/dl)
10.51.4
10.31.1
Total leukocyte count
<1000-3000/cc
20 (39.21%)
60 (32.96%)
>3000-4000/cc
19 ( 37.25%)
80 (43.95%)
>4000/cc
12 (23.52%)
42 (23.07 %)
Platelet count
20000/cc (8)
0
8 ( 4.39%)
>20000 40000/cc
0
28 (15.38%)
SGOT >3 times normal
15 (29.41%)
66 (36.26%)
SGPT >100 200 IU/L
10 (19.60%)
31 (17.03%)
SGPT >200 350 IU/L
5 (9.80%)
18 (9.89%)
SGPT >350 IU/L
2 (3.92%)
14 (7.69%)
INR >1.5 (21)
0
21 (11.53%)
% Amongst total (233)

88 (37.76%)
86(36.90%)
136(58.36%)
44 (18.88%)
83(35.62%)
52 (22.31%)
10 (4.29%)
P value
0.0001**
0.00001***
0.0001**
0.02*
0.01*
0.00001***
0.005**
0.07
140 (60.08%)
3(1.28%)
4(1.71%)
3(1.28%)
3 (1.28%)
% amongst total (233)
P value
6 (2.57%)
140 (60.08%)
37.33
-
2.46
0.0003**
0.0006**
80 (34.33%)
99(42.48%)
54(23.17%)
0.20
0.19
0.47
8(3.43%)
28(12.01%)
81(34.76%)
41(17.59%)
23 (9.87%)
16 (6.86%)
21 (9.01%)
0.18
0.33
0.49
0.17
-
** Very significant, SGOT: Serum aspartate aminotransferase, SGPT: Serum alanine aminotransferase; INR:
International normalized ratio
Table 4: Radiological distribution:

Items
Ascites
Hepatomegaly
USG
Ascites & Hepatomegaly
Hepatosplenomegaly
Chest x-ray
DF (51)
0
7 (13.72%)
0
0
0
DHF (182)
3 (1.64%)
9 (4.94%)
6 (3.29%)
0
13 (7.14%)
% Amongst total patients (233)

1.28
6.86
2.57
0
5.57
61
Saha et al.,
DISCUSSION
Age group affected by dengue fever as shown by
Narayanan et al4 was 7 to 8 years of age, which was
similar to the study done by Kabra SK et al5 and Banik
GB et al.6 Though dengue fever is a well-known
disease of child-age group, but since 1980s there is
slight inclination towards higher age group in case of
DHF, as shown in various studies in Latin America
and South-East Asia. Similarly, in our study, the mean
age was 10.31 and 12.6 years in DF and DHF
respectively. Though according to previous belief,
DHF/DSS is due to either previous infection or passive
transfer of antibody from the mother7, but in our study,
DHF occurred at higher age group so it may be due
to antibodies, acquired by the patients at earlier ages.
According to some author, it may be due to virulent
virus rather than pre-infection antibody status.8
Few available hospital studies demoed male-female
distribution in dengue fever. Kabra SK et al5 showed
girl preponderance as also seen in the study done by
Mittal H et al.9 Three independent studies in India and
Singapore showed that males were twice more
common than females.10 , 11 Hospital based study in
Delhi showed male to female ratio 2.5:1.12 Similarly,
in our study, there was slight edging of boys over girls.
In study done by Mittal et al showed that fever
(100%), headache (63%), abdominal pain (71%) and
petechiae (35.5%) were more common.9 Fever,
vomiting were most frequent symptoms as shown by
Narayanan M et al.4 Similar pictures were observed in
our study, but in addition, headache, anorexia was also
frequently found.
In our study, 76.92% DHF patients showed positive
tourniquet test, which was much higher than that was
observed in the study of Kabra et al.5 It may be due to
thrombocytopenia and capillary fragility, either or
both. Low proportion of positivity in tourniquet test in
Indian population may be due to darker skin color or
dengue strain difference in Indian subcontinent.13, 14.
The tourniquet test will never correlate with overt
bleeding manifestation as shown by Wali et al.15 It
may be due to difference in pathogenesis, like,
vascular permeability and/or capillary fragility.
Since in our study, only 13 patients showed evidence
of bleeding, amongst them, evidence of epistaxis, gum
bleeding and hematemesis were observed in 1.64% of
DHF patients, which was very low as compared to
other studies 5. According to WHOs protocol for

management of DHF, 1-2 hourly documentation of
Hematocrit (Hct) value is very essential for monitoring
intravenous fluid therapy. But, if pretreatment Hct
value is not known, it is very difficult to demonstrate
the percentage of hemoconcentration in DHF.
Hemoconcentration is very important factor that
correlates platelet count with bleeding manifestations.
This was shown in different studies.16, 17. In our study,
Hct >40 was observed in 3.92% of DF and 2.19% of
DHF patients, whereas, Hct >30-40 was observed in
65.93% of DHF patients. So according to our study, it
may not be a good indicator of monitoring fluid
therapy in infants and children in presence of moderate
anemia which was near 10 gm% in our study
population.
In our study, leucopenia (<5000/cc) was observed in
76.81% of patients, whereas, Ratageri et al18 showed
21% of patients suffered from leucopenia and
Benerjee19 et al demonstrated no evidence of
leucopenia in their studies. So, leucopenia may be an
indicator of virulent dengue strain in our epidemic.
Our study showed 182 (78.11%) children suffered
from thrombocytopenia, amongst them, 36 (19.77%)
had platelet count <40000/cc. Similarly, 82% and
96%rombocytopenic patients were described in the
studies of Ratageri et al18 and Banerjee et al19
respectively. This thrombocytopenia may be due to
decreased production in bone marrow, temporary bone
marrow suppression20, virus-antibody complex
mediated immune destruction21 of platelet or increased
consumption of platelet induced by secondary
infection associated with release of high level of
platelet activating factors or increased adhesiveness of
platelet to the vascular endothelial cells.22
In DHF, there may be evidence of plasma leakage as
evidenced by ascites and pleural effusion. In our study,
13 (7.14%) patients showed evidence of pleural
effusion in the chest x-ray, 3 (1.64%) patients suffered
from isolated ascites and 6 patients (3.29%) suffered
from ascites associated with hepatomegaly. On the
contrary, 70% and 54% of children demonstrated
pleural effusion and ascites respectively in the study of
Ratageri et al.18 According to some observations,
massive T-cell activation producing cytokines
(interferon , interleukin 2 and TNF ) and infected
cell lysis by CD 4+ and CD8+ dengue specific
lymphocytes are mainly responsible for plasma
62
Saha et al.,
leakage. Interaction between infected cells and

immune cells induces release of cytokines directly by
macrophages and monocytes.
One important laboratory finding is elevation of liver
enzymes, which was reported in various studies.23-.25.
Similarly, in our study, the rise in SGPT >100 U/L
was observed in 34.32% of patients.
Evidence of vomiting, hepatomegaly and elevated
liver enzymes may be a clue to the diagnosis of
dengue in the background of the epidemic.
CONCLUSION
Dengue fever is more prevalent in Kolkata. Mean age
of DF and DHF patients were 10.31 and 12.6 years
respectively. Male to female ratio was 1.13:1. In
seropositive DHF patients, fever, headache, backache,
loose motions were the predominant symptoms
associated with hepatomegaly, elevated liver enzymes
and evidence of plasma leakage. Leucopenia may be
due to a virulent strain of dengue virus.
Key-massage: Evidence of fever, vomiting, backache
with or without bleeding associated with
hepatomegaly,
elevated
liver
enzymes
and
thrombocytopenia may be a clue to the diagnosis of
dengue hemorrhagic fever. Due to the high prevalence
of anemia, rise in Hematocrit is not at all helpful to the
diagnosis of DHF.
Funding: Nil.
Competing interests: Nil.
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7. Halstead SB. Antibody, macrophage, dengue
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8. Sumaro W, Jahja E, Gubler DJ, Suharyono W,
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9. Mittal H, Faridi MM, Arora SK, Patil R.
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11. Goh KT, Ng SK, Chan YC, Lim SJ, Chua EC:
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DOI: 10.5958/j.2319-5886.3.1.013

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EVALUATION OF MODIFIED HODGE TEST AS AN INDICATOR OF KLEBSIELLA PNEUMONIAE

CARBAPENEMASE (KPC) PRODUCTION BY USING bla KPC GENE PCR
*Priyadarshini Shanmugam, Nirupa Soundararajan, Jeya Meenakshisundaram
Department of Microbiology, Chettinad Hospital and Research Institute, Tamilnadu, India
*Corresponding author email: priyadarshini0018@gmail.com
ABSTRACT
Introduction: Carbapenems belong to the Beta Lactam group of antimicrobial agents. They are often used as lastline agents or antibiotics of last resort in critically ill patients. Carbapenem resistance in Enterobacteriaceae may
be due to various reasons but Klebsiella pneumoniae Carbapenemase (KPC) enzyme production is the commonest.
Phenotypic as well as genotypic methods can be used to detect Carbapenemases. Among the phenotypic tests,
Modified Hodge Test (MHT) is relatively easy to perform. Aims and Objectives: This study aimed to determine
the prevalence of carbapenem resistance among Enterobacteriaceae isolates and calculate the sensitivity of MHT as
an indicator of KPC production. Materials and Methods: All Enterobacteriaceae isolates from clinical samples
were included in this study and were screened for Carbapenem resistance. 45 randomly chosen Carbapenem
Resistant Enterobacteriaceae isolates were subjected to MHT and blaKPC gene detection by PCR. Results: 2035
Enterobacteriaceae isolates were tested and 5.2% were found to be resistant to Imipenem, 22.9 % were resistant to
Meropenem and 4.42 % were resistant to both Imipenem and Meropenem. The sensitivity of MHT was calculated to
be 90% and specificity was calculated to be 60%
Keywords: Carbapenemase, Modified Hodge Test, Enterobacteriaceae, bla KPC gene
INTRODUCTION
Bacteria belonging to the Enterobacteriaceae family
are normally present as harmless human gut flora.
These bacteria are the leading cause of a wide range of
opportunistic infections.1 Carbapenems belongs to the
Beta Lactam group of antimicrobial agents, which kill
bacteria by inhibiting the bacterial cell wall synthesis.2
They possess the broadest spectrum of activity and
greatest potency against Gram-positive and Gramnegative bacteria. 3 As a result, they are often used as
last-line agents or antibiotics of last resort when
patients with infections become gravely ill or are
suspected of harboring resistant bacteria.3 Carbapenem
resistance among Enterobacteriaceae members is of
great concern as these bacteria are easily transmissible
among patients, leading to hospital acquired infections
Priyadarshini et al.,
(HAI), but can also spread into the community,

resulting in community acquired cases.1
Carbapenem resistance in Enterobacteriaceae may be
due to various reasons that include hyper production of
the Amp C beta lactamase, loss of porins, production
of metallo beta lactamases (MBL) and production of K
pneumonia carbapenemases.1
Carbapenemases increasingly have been reported
worldwide in Enterobacteriaceae in the past 10
years.4, 5 A large variety of carbapenemases has been
identified in Enterobacteriaceae belonging to 3 classes
of -lactamases: the Ambler class A, B, and D lactamases. 3 In addition, rare chromosome encoded
cephalosporinases (Ambler class C) produced by
Enterobacteriaceae may possess slight extended
65
activity toward carbapenems.4 Their identification is of

primary importance since carbapenemase producers
are resistant not only to most Beta-lactams but also to
other main classes of antibiotics. 5
Carbapenemases can be detected by phenotypic as
well as genotypic methods.6 Modified Hodge Test
(MHT) is a phenotypic method which is relatively
simple and easy to perform in a laboratory. 6 This
cloverleaf technique, or Modified Hodge test, has been
extensively used as a phenotypic technique for
detecting carbapenemase activity. 5
Limitations of the MHT in terms of clinical
performance are its lack of specificity and the delay in
obtaining the results upto 24 or 48 hours after isolation
of a bacterial colony.5 The molecular detection of
blaKPC is the gold standard for diagnosis, but the
majority of laboratories in our country does not have
the resources necessary to perform this test. 7
The aim of this study was to determine the prevalence
of Carbapenem resistance among Enterobacteriaceae
and detect the bla KPC gene prevalence among
randomly
chosen
Carbapenem
resistant
Enterobacteriaceae clinical isolates in our 750 bed
hospital. The study also aimed to evaluate the
performance of the Modified Hodge test and calculate
the sensitivity of MHT as an indicator of Klebsiella
Pneumoniae Carbapenemase (KPC) production.
The isolates in this study were collected in a period of
one year from July 2012 to June 2013. The study was
conducted at Chettinad Hospital and Research
Institute, Chennai. The institutional ethical committee
approval was obtained prior to commencement of this
study. All Enterobacteriaceae isolates from clinical
samples like pus, wound swab, sputum, endotracheal
aspirate, blood and urine were included in this study.
The samples were collected after obtaining informed
consent from the patients. For evaluation of Modified
Hodge Test by PCR, 45 isolates which were resistant
to both or either Imipenem or Meropenem were
randomly selected. MHT and bla KPC PCR were
performed on these 45 isolates
These isolates were screened for Carbapenem
resistance in addition to the routine antibiotic
susceptibility testing, which was performed by the
Kirby Bauer method, as per the CLSI guidelines 2012.
8
Antimicrobial discs used were Ampicillin (10g),
Gentamicin (10g), Amikacin (30g), Cefazolin (30
g), Cefuroxime (30g) Ceftazidime (30g),

Cefotaxime (30g), Ceftriaxone (30g), Cefepime
(30g),
Ciprofloxacin
(5g),
Cotrimoxazole
(23.75/1.25g), Piperacillin/ tazobactam (100/10g),
Imipenem (10g), Meropenem (10 g), Polymyxin B
(300 units) and Colistin (10g).
Modified Hodge Test
Phenotypic detection of Carbapenemase production
was done by using the Modified Hodge test. This test
was performed as per the CLSI guidelines 2012. 8 A
0.5 Mac Farlands suspension of ATCC Escherichia
coli 25922 was diluted 1:10 in sterile saline. This was
inoculated on a Mueller Hinton agar plate, as for the
routine disc diffusion testing. The plate was dried for 5
minutes and a disc of Imipenem 10 g was placed in
the centre of the agar plate. 3-5 colonies of the test
organism were picked and inoculated in a straight line,
from the edge of the disc, up to a distance of at least
20mm. The plates were incubated at 370C overnight
and they were examined next day. They were checked
for an enhanced growth around the test organism, at
the intersection of the streak and for a zone of inhibition. The presence of an enhanced growth indicated
Carbapenemase production, and the absence of an
enhanced growth meant that the test isolate did not
produce carbapenemase. 8
bla KPC gene detection
The isolates which gave positive results for the
modified Hodge test were submitted to molecular
detection of the bla KPC gene by PCR. The PCR Kits
were procured from Helini Biomolecules, Chennai.
Isolates with negative test results were also randomly
chosen for PCR. The Polymerase Chain Reaction was
set up in a PCR vial, after adding the master mix, the
forward and reverse primers and the extracted DNA
from the isolates. The primers used for PCR
amplification and the reaction conditions were
Forward Primer: 5-GCT CAG GCG CAA CTG TAA
G-3 Reverse Primer: 5-AGC ACA GCG GCA GCA
AGA AAG-3. The PCR vial was placed in PCR
machine (Corpect Research 96 wells, Australia) and it
was subjected to initial denaturation at 94C for 3 min,
followed by 30 cycles of denaturation at 94C for 1
minute, annealing at 60C for 1minute and extension at
72C for 1minute. A final extension procedure was
carried out at 72 C for 5 min. Next the PCR products
were subjected to electrophoresis on 2% agarose gel
stained with ethidium bromide and visualized with UV
66
light The antibiogram for the Carbapenem Resistant

Enterobacteriaceae was analyzed
RESULTS
2035 non repetitive isolates of Enterobacteriaceae
were obtained from clinical samples such as pus, urine,
blood, sputum and endotracheal aspirates, over a
period of 1 year. Of these, 1178 (57.88%) were
Escherichia coli, 444 (21.81) were Klebsiella species,
178 (8.7%) Proteus species, 154 (7.56%) Citrobacter
species and 81 (3.9%) were Enterobacter isolates
Fig 1: Total number of Enterobacteriaceae isolates
(Figure1). Figure 2 shows the number of carbapenem

resistant isolates among the individual genera. The
antibiogram of the Enterobacteriaceae isolates is
tabulated in Table 1 and the antibiotic resistance
pattern of the CRE are tabulated in Table 2.
Of the total of 2035 isolates, 106 (5.2%) were resistant
to Imipenem and 468 (22.9 %) were resistant to
Meropenem and 90 (4.42 %) were resistant to both
Imipenem and Meropenem.
Fig 2: Carbapenem Resistance pattern of the Isolates
Table 1: Antibiotic Resistance pattern of the Enterobacteriaceae (% of Resistance)

ANTIBIOTIC
Amikacin
Ampicillin
Cefazolin
Cefuroxime
Cefotaxime
Cefepime
Ciprofloxacin
Cotirmox
Colistin
Genta
Imipenem
Meropenem
Nitrofurantoin
Norfloxacin
Piperacillin Tazobactam
Polymyxin B
Tobramycin
Ecoli
9.67 %
85.7 %
71.3%
64.9 %
61.1 %
53.2 %
63.1 %
55.2 %
0%
36.76 %
3.23 %
21.3 %
11.7 %
59.54 %
19.9 %
0%
39.47 %
Klebsiella
16.64 %
100 %
66.67 %
59.46 %
53.38 %
42.79 %
47.07 %
50.9 %
0%
34.0 %1
9.68 %
20.95 %
31.15 %
31.15 %
21.78 %
0%
16.17 %
Proteus
31.46 %
71.51%
82.58 %
66.83 %
49.43 %
39.32 %
58.99 %
68.02 %
100 %
46.07 %
6.82 %
50.15 %
87.87 %
49.2 %
15.47 %
100 %
48.14 %
Citrobacter
16.88 %
88.42 %
72.73 %
58.44 %
51.3 %
37.66 %
40.26 %
46.75 %
2.6 %
34.42 %
5.84 %
16.23 %
33.78 %
36.49 %
21.52 %
0%
29.49 %
Enterobacter
11.11 %
69.14 %
82.72 %
65.43 %
46.91 %
38.27 %
41.98 %
45.68 %
0%
32.1 %
4.94 %
13.58 %
43.48 %
30.43 %
13.58 %
1.23 %
34.78 %
67
Table 2: Antibiotic resistance pattern of the 45 Multi Drug Resistant Enterobacteriaceae

Percentage of Resistance
Klebsiella(n =22) Ecoli (n =20) Citrobacter (n =2
Proteus (n = 1)
Amikacin
59 %
33%
100 %
100 %
Ampicillin
100 %
100 %
100 %
100 %
Cefazolin
100 %
100 %
100 %
100 %
Cefuroxime
100 %
100 %
100 %
100 %
Cefotaxime
100 %
100 %
100 %
100 %
Cefipime
96%
100 %
100 %
100 %
Ciprofloxacin
91 %
91%
100 %
100 %
Cotrimoxazole
100 %
100 %
100 %
100 %
Colistin
0%
5%
0%
100 %
Gentamicin
73 %
67%
100 %
100 %
Imipenem
77 %
67%
100 %
100 %
Meropenem
96 %
95%
50 %
100 %
Nitrofurantoin (urine)
100%
20%
100 %
100 %
Piperacillin Tazobactam
100 %
100 %
100 %
100 %
Polymyxin B
0%
0%
0%
100 %
Tobramycin
94 %
73%
100 %
100 %
For evaluation of Modified Hodge Test by bla KPC
detection using PCR, 45 isolates which were resistant
to both or either Imipenem or Meropenem had been
selected. Of these, 22 were Klebsiella pneumoniae, 20
were Escherichia coli, 2 were Citrobacter species and
1 was Proteus mirabilis). Of the 45 isolates, 43 (95.5
%) were resistant to Meropenem, 34 (75.5%) were
resistant to Imipenem and 29 (64.4%) were resistant to
both Imipenem and Meropenem. Modified Hodge Test
was positive in 37 (82.2%) out of 45 isolates and bla
KPC gene was detected in 30 (66.7 %) isolates (Table
3). Of the 30 blaKPC gene positive isolates, MHT was
positive in 27 and negative in 3 isolates. Of the 15
blaKPC gene negative isolates, MHT was positive in 10
(66.6%) and negative in 5 (33.3%) isolates.
Considering PCR for bla KPC gene as the gold standard
for the detection of Klebsiella pneumoniae
Carbapenemase, the sensitivity and specificity of MHT
was calculated using the formula: Sensitivity = a/a+b
and Specificity = d/ c+d. [Where a is True Positive
(27), 'b' is False Negative (3), 'c' is False Positive (10)
andd is True Negative (15) ]. In the present study, the
sensitivity of MHT was calculated to be 90 % and the
specificity was 60%. The positive predictive value was
72.97% and the Negative predictive value was
83.33%. Figure 3 shows isolates with positive MHT,
displaying the characteristic clover leaf like
indentation and Figure 4 shows the visualization of the
PCR products by gel electrophoresis.
Fig 3: Positive Modified Hodge Test
Fig4: bla KPC gene PCR : Gel Electrophoresis

showing positive and negative isolates
Table 3: Results of MHT and blaKPC gene PCR
MHT &
Total
MHT Bla KPC bla KPC
Isolates (+ve) gene(+ve) gene (+ve)
22
19
13
11
Klebsiella
E coli
20
16
15
14
Citrobacter 2
1
1
1
Proteus
1
1
1
1
Total
45
37
30
27
68
DISCUSSION
In our study, 5.2% of the isolates were resistant to
Imipenem, 22.9 % were resistant to Meropenem and
4.42 % were resistant to both Imipenem and
Meropenem. The highest percentage of resistance to
Carbapenems was seen in Klebsiella species, 9.68% to
Imipenem and 20.9% to Meropenem, followed by
Escherichia coli, Proteus, Citrobacter and Enterobacter
(Table 1). A study by Ramana et al 1 showed that,
among the different Enterobacteriaceae members
tested, Klebsiella spp. showed the highest percentage
of carbapenem resistance at 30%, whereas Proteus
spp. and Citrobacter spp revealed comparatively low
carbapenem resistance of 17% and 12%, respectively.
The prevalence of carbapenem resistance in our study
was less than that of Ramana et al. Another study by
Parveen et al 9 showed that 45 (43.6%) of K.
pneumoniae from clinical specimens, were resistant to
meropenem by the disk diffusion test. Among isolates
reported to the National Healthcare Safety Network in
20062007 carbapenem resistance was reported in up
to 4.0% of Escherichia coli and 10.8% of K.
pneumoniae isolates that were associated with certain
device-related infections. 10
In the present study, the sensitivity of Modified Hodge
test was calculated to be 90%. A similar study by
Anderson et al 11 which had also evaluated the
modified Hodge test for detection of KPC-mediated
resistance inferred that the test demonstrated 100%
sensitivity and specificity for detection of KPC
activity. Diana Doyle et al 12 in her study showed that
MHT had a sensitivity of 98% for detecting KPC
producers and 93% for OXA-48-like enzyme
producers but was less than optimal for detecting
MBLs. The sensitivity of MHT as inferred by our
study was less than that of the sensitivity of the other 2
studies. This could necessitate changes in the MHT to
make it more sensitive. A study was carried out by
Pasteren et al 13 using an optimized MHT known as
Pseudomonas aeruginosa MHT (PAE MHT) which
demonstrated 100% sensitivity and 98% specificity for
detection of KPC activity without any indeterminate
result. Another study in Greece, showed that Modified
Hodge test detected 98% KPC producers, keeping
PCR as the gold standard [6] In contrast, another study
by D. Girlich et al 5 showed that the overall sensitivity
and specificity of the MHT was low (77.4% and
38.9%, respectively). In our study too, the specificity
of MHT was low- only 60%. Hatipoglu et al 14 also
state that the MHT has a low specificity. This could be

because Modified Hodge Test detects other
carbapenemase enzymes in addition to KPC.
Of the 3 MHT negative isolates, one was positive for
bla KPC gene. Adriane BC et al 15 have also reported
such isolates carrying silent genes. 8 (17.7%) isolates
were resistant to carbapenems, but were MHT
negative. They may have developed a different
resistance mechanism other than carbapenemase
production.
Prevalence of bla KPC gene was found to be 66.67%
among the carbapenem resistant isolates. blaKPC gene
was not detected in 10 MHT positive isolates. This
could indicate the presence of a carbapenemase other
than KP Carbapenemase. Resistance to both imipenem
and meropenem is a strong indicator of carbapenemase
production rather resistance to either one of the
carbapenems, as this may imply a different resistance
mechanism
CONCLUSION
Modified Hodge Test is a sensitive test for Klebsiella
pneumoniae Carbapenemase production. It is
recommended that all isolates showing intermediate
sensitivity or resistance pattern to carbapenems be
screened for the production of carbapenemases by
Modified Hodge test, which will provide a costeffective and rapid approach for the detection of
carbapenemases in Enterobacteriaceae.
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70
DOI: 10.5958/j.2319-5886.3.1.014

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Received: 4 Nov 2013
Research article
STUDY OF NEURAL
INDIVIDUALS
PLASTICITY
IN
BRAILLE
Copyright @2013
ISSN: 2319-5886
READING
VISUALLY
CHALLENGED
*Nikhat Yasmeen1, Mohammed Muslaiuddin Khalid2, Abdul Raoof Omer siddique1, Madhuri Taranikanti1,
Sanghamitra Panda1, D.Usha Rani3
1
Department of Physiology, Shadan Institute of Medical Sciences, Hyderabad, Andhrapradesh, India

Department of Emergency Medicine, Care Hospital, Hyderabad, Andhra Pradesh, India
3
Department of Physiology, Apollo Institute of Medical Sciences & Research, Hyderabad,Andhra Pradesh, India
2
*Corresponding author mail: yasmeen78692@yahoo.com

ABSTRACT
Background: Neural plasticity includes a wide range of adaptive changes due to loss or absence of a particular
sense. Cortical mapping or reorganization is evolutionary conserved mechanism which involves either an
unmasking of previously silent connections and/or sprouting of new neural elements. Aims & Objectives -To
compare the Somatosensory evoked potentials (SSEPs) wave form in normal and visually challenged individuals.
Materials & Methods: 20 visually challenged males in the age group of 21 -31 yrs were included in the study along
with 20 age & sex matched individuals. Subjects were screened for general physical health to rule out any medical
disorder, tactile sensibility i.e., sensation of light touch, pressure, tactile localization & discrimination to rule out
any delay in the peripheral conduction disorder. Somatosensory evoked potentials were recorded on Nicolet Viking
select neuro diagnostic system version 10.0.The placement of electrodes & recording of potentials were done based
on methodology in chiappa. Data was subjected to various statistical analyses using SPSS version 17.0 software.
N20 & P25 latencies were shorter and amplitudes were larger in visually challenged individuals compared to age &
sex matched individuals. Conclusions: In visually challenged individuals, decrease in latencies indicate greatly
improved of information in the nervous system & increase in amplitudes indicate the extent and synchronization of
neural network involved in processing of vision.
Keywords: Neural plasticity, Somatosensory evoked potentials, Cortical mapping, Visually challenged
INTRODUCTION
In humans as well as in many animals, cortical area
has enormous capacity for reorganization i.e plastic
changes.1 The present study was undertaken to study
the cross modal interactions of sensory modalities in
visually challenged individuals for the exploration of
neural plasticity using somatosensory evoked
potentials. In our central nervous system perception is
modulated due to the redundant informational inputs
from more than one sensory organ. In blind individuals
Occipital cortex that is deprived of its normal inputs is
Nikhat et al.,
invaded by inputs from other modalities supporting the

concept of cross-modal plasticity.2-5
Specific electrophysiological recordings & functional
imaging studies of visually challenged individuals
have depicted that touch modality is not only
sharpened in these individuals but also plays a major
role in their perception.Various animal models have
been used to study the changes occur both at the
cellular & synaptic level i.e activity based competition
between the differential sensory inputs.6
71
The molecular mechanism underlying neural plasticity

is probably due to unmasking of connections or the upregulation of synaptic efficacy.7 As we all know that
the thalamus is considered as the gateway for the
sensory information reaching the cortex, the
reorganization can occur at this level or at the level of
polymodal association areas.8
Specific somatosensory & auditory evoked potentials
have demonstrated that cross-modal plasticity
develops in visually challenged individuals due to their
dependence on tactile & auditory information.9- 12 In
blind Braille readers there was structural & functional
cortical reorganization along with relevant changes in
the behavior & perceptual capacities as demonstrated
by imaging studies.
METHODS
20 visually challenged individuals were recruited from
Govt. hostel for blind boys, Dilsukhnagar area,
Hyderabad & study was conducted at the
Electrophysiology lab, Upgraded Department of
Physiology, Osmania Medical College, Koti, Hyd.,
during Dec.2009 to Dec.2011. 20 Age & Sex matched
controls were also included in the study. Subjects with
history of nervous system disorders, usage of
antidepressants, narcotic drugs, CNS stimulants were
not included in the study. Subjects with late onset of
blindness due to other medical reasons were excluded
from the study. Subjects were screened for general
physical health to rule out any medical disorder, tactile
sensibility i.e sensation of light touch, pressure, tactile
localization & discrimination to rule out any delay in
the peripheral conduction disorder. Prior to study,
ethical guidelines were followed; consent was taken,
after the subjects were told about the aims &
objectives of the study.
Procedure : This study was conducted on patients
using 3-channel with normal averaging technique.13
The procedure was explained to the patient and
consent taken.Patient was asked to sit comfortably on
a chair and instructed to gently close his/her eyes
while relaxing all the head and neck muscles during
the recording. Patient is asked to count the number of
stimuli so as to get proper recordings. Electrodes of
the 3 channels were placed on the patient at
appropriate sites after its proper abrasion. Placement
of electrodes & recording of potentials were done in
accordance with the methodology in Chiappa.13
Surface EEG electrodes are used. Frontol electrode

[Fz] is used as the reference in most montages.
Active recording electrodes are placed as follows:
1. 1st channel: Over the contralateral C3/C4 scalp
region (2cm posterior to C3 or C4)
2. 2nd channel: Over the C5/C2 cervical spinous
process (referred to as C5S or C2S and located
relative to the prominent C7 spinous process with
the neck flexed.
3. 3rd channel: At Erbs point (2-3 cm above clavicle
in the angle between it and posterior border of the
clavicular head of the Sternocleidomastoid muscle
ipsilaterally.
4. Inactive recording electrodes of the 3 channels
were placed on Fz position on the scalp.
5. Ground electrode: is placed between the
stimulating and the recording electrodes relatively
close to the former. We have used a band around
the forearm.
6. Stimulation electrode: using surface disk
electrodes placed between the tendons of palmaris
longus and flexor carpi radialis, i.e., at the
supinated wrist, median nerve was stimulated.
Stimuli of 0.2-0.3 msec duration are given at 4-7
Hz. The intensity of the current was adjusted till a
visible twitch was produced.
Data-sheet was made using Microsoft word & excel
sheets.Statistical analysis was done using PASW
18.0 (SPSS Inc.Chicago,USA)
RESULTS
This Comparative study consisted of 20 congenitally
blind males (Group A) and 20 normal sighted
individuals(Group B)
The mean pattern of latency of SEP-N20 after wrist
stimulation was found to be significant I.e P value =
0.000 (<0.0001) for right side & P-value = 0.001
(<0.005) for left wrist.The mean pattern of latency of
SEP-P25 after wrist stimulation was found to be
significant i.e. P value =0.000(<0.0001) &
p=0.022(<0.05).The mean pattern of latencies of N9&
N13, inter-peak latencies of SEPs did not show
significant difference (P > 0.05) between the two
groups.(TABLE I)
72
Nikhat et al.,
Table 1: Statistical analysis of mean pattern of latencies on wrist stimulation

MEAN PATTERN OF LATENCIES
N9
N13
N20
P25
N9-N13
N9-N20
N13-N20
WRIST
RIGHT
LEFT
RIGHT
LEFT
RIGHT
LEFT
RIGHT
LEFT
RIGHT
LEFT
RIGHT
LEFT
RIGHT
LEFT
GROUP A
9.250.62
9.170.69
12.540.39
12.540.43
17.50.58
17.80.53
20.630.53
21.031.08
3.410.62
3.580.84
8.070.22
8.690.81
5.310.52
5.190.25
GROUP B
9.480.68
8.890.64
12.680.78
12.490.53
18.490.7
18.540.79
21.691.08
21.811.0
3.471.06
3.220.77
8.200.19
8.880.72
5.330.39
5.280.34
Table 2: Statistical analysis of mean pattern of Amplitude on wrist stimulation

MEAN
PATTERN
OF WRIST
GROUP A
GROUP B
AMPLITUDE
N9
RIGHT
2.122.44
1.91.73
LEFT
1.901.57
1.671.77
N13
RIGHT
0.870.55
0.910.66
LEFT
0.790.73
0.410.68
N20
RIGHT
4.821.36
2.740.95
LEFT
4.22.5
2.760.83
P25
RIGHT
1.240.68
0.770.52
LEFT
1.280.56
1.140.62
The mean pattern of amplitude of SEP-N20 after wrist
stimulation was found to be significant i.e
P- value = 0.000 (<0.0001) for right side & P-value =
0.004 (<0.005) for left wrist. The mean pattern of
amplitude of SEP-P25 after wrist stimulation was
found to be significant i.e. P value =0.021(<0.05) for
right side .The mean pattern of amplitudes of N9&
N13 SEPs did not show significant difference (P >
0.05) between the two groups.(TABLE-II)
DISCUSSION
This study compares the latencies and amplitudes of
SEPs in normal and congenitally blind individuals
thereby giving an insight into the sharpening of other
sensory modalities in the absence of vision.
The present study throws light on the efficiency and
rapidity of neural processing of information in
congenitally blind subjects.
P-VALUE
0.274
0.270
0.463
0.725
0.000
0.001
0.000
0.022
0.83
0.168
0.105
0.438
0.894
0.406
P-VALUE
0.778
0.667
0.834
0.092
0.000
0.004
0.021
0.452
Following SEP parameters were recorded - N20, P25,

N13, N9 latencies and amplitude; N9-N13, N9-N20,
N13-N20 inter-peak latencies and N20-P25 amplitude
in blind and was compared with that of age-matched
normal controls using the independent samplet test.
The congenitally blind individuals use more than one
finger for Braille reading;index middle & ring finger.
Hence the median nerve was stimulated in the wrist to
get a cumulative record of the reading fingers.
Somatosensory evoked potentials like other evoked
potentials are path-specific electrical signals are
produced in the areas of signal processing which
correspond to the synaptic junctions of various
neurons and they give good temporal resolution in
milliseconds domain.N20 & P25 Latencies were
decreased and N20 & p25 amplitudes increased in the
congenitally blind when compared to same group in
the congenitally blind individuals,there were highly
73
Nikhat et al.,
significant differences in N20 & P25 Latencies &

amplitudes stimulation on right side than the left side.
According to previous studies done by Alvaro et al &
Dayanand G et al;there was increase in amplitude of
N20 Potential & the increase was more on the
right/dominant side14
In another comparative study SEPs were recorded in
10 blind & 15 control subjects & data revealed that
there were significant increase in N20 & P22 SEPS
on right-sided stimulation suggesting activity
dependant alteration in spatio-temporal components of
signal processing15
In a PET study to decipher the cross-modal plasticity
in the visually challenged individuals by electro-tactile
stimulation of tongue,results have shown that the
occipital area is part of a neural network for
discriminating touch sensations along with posterior
parietal cortex as there was increase in regional blod
flow(rRBF) in the occipital cortex & that the increase
was related to the performance of particular task16
In another functional magnetic resonance imaging
study 12 congenitally and early-onset blind
subjects were studied with fMRI reading & results
reveal that there was activation of the primary sensory
area along with polymodal association areas17
Studies in congenitally blind Braille readers have
shown that there was reorganization of tactile &
auditory tracts to the central retinal targets both at the
sub-cortical & cortical levels.18-20
Another brain -imaging study demonstrated that there
is difference in pattern of activation of visual cortex in
late and congenitally blind subjects. Early blind
subjects when compared to late blind have better
tactile & auditory sensibility as demonstrated by event
related potentials recorded over the posterior cortical
areas.21-22
CONCLUSIONS
In congenitally blind individuals, decrease in N20 &
P25 latencies indicate greatly improved processing of
information in the nervous system; increase in N20 &
P25
amplitudes
indicate
the
extent
and
synchronization of neural network involved in
processing of information for a wider Neural network
could be due to changes in the local connectivity as
several local mechanisms have been proposed,
including sprouting, unmasking of silent synapses
and/or changes in the modulatory effects of lateral

connections.
In accordance with the principles of lateral inhibition;
the tactile & auditory modalities also exert the
modulatory effects on perception of visual modality
both at the sub-cortical & cortical level.
Thus it can be formulated that in the spatio-temporal
framework the demarcation between uni-modal &
polymodal association areas can undergo reorganization i.e plastic changes both at gross & at
molecular level.
ACKNOWLEDGEMENT
I would like to express my heartfelt gratitude to Prof.&
Hod Dr. B.Ram Reddy & all those who have helped
me in completing my work
REFERENCES
1. Norihiro S, Tomohisa O, Manabu H, Yoshiharu Y.
Critical Period for Cross-Modal Plasticity in Blind
Humans: A Functional MRI Study NeuroImage.
2002;16:389400
2. Kato N. Plasticity in an aberrant geniculocortical
pathway in neonatally lesioned cats. Neuroreport.
1993;4:915-18.
3. Florence SL, Taub HB, Kaas JH. Large-scale
sprouting of cortical connections after peripheral
injury in adult macaque monkeys.Science. 1998;
282:1062
4. Frost DO, Metin C. Introduction of functional
retinal projections to the somatosensory system
Nature. 1985;317:16264.
5. Sterr A, Muller MM, Elbert T, Rockstroh B,
Pantev C, Taub E. Perceptual correlates of
changes in cortical representation of fingers in
blind multifinger Braille readers. J Neurosci;
1998; 18: 441723
6. Bavelier D, Neville HJ . Cross-modal plasticity:
where and how? Nat Rev Neurosci.2002;3:44352
7. Pascual-Leone A. Modulation of human cortical
motor outputs during the acquisition of new fine
motor skills. J. Neurophysiol.1995;74:103745
8. Buchel C, Price C, Frackowiak RS, Friston K.
Different activation patterns in the visual cortex of
late and congenitally blind subjects. Brain.
1998;121;40919
9. Hamilton RH, Pascual-Leone A, Rodriguez D,
Schlaug G. Increased prevalence of absolute pitch
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10.
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20.
in blind musicians; Abstr Soc Neurosci; 2000; 26:

73913.
Lessard N, Pare M, Lepore F, Lassonde M.
Earlyblind human subjects localize sound sources
better than sighted subjects. Nature 1998;
395:27880.
Thomas Elbert, Annette Sterr, BrigitteRockstroh,
Christo Pantev, Matthias M, Muller et al;
Expansion of the tonotopic area in the auditory
cortex of blind; J Neurosci.2002;15(22): 994144.
Yabe, Takao CA, Kaga, Kimitaka. Sound
lateralization test in adolescent blind individuals.
Neuroreport. 2005;16(9): 93942.
Chiappa KH. Evoked Potentials in Clinical
Medicine. Raven Press, New York 1990, 2nd
ed.371-473
Dayanand G, Roopkala MS, Srinivas R, Ranjeev
Sharma. A Comparative study of median nevre
somatosensory evoked potentials in the totally
blind and normal subjects. Indian journal of
physiology and pharmacology.2008 ; 52(2 ) 183188
Alvaro Pascual-Leone, Fernando Torres. Plasticity
of the sensorimotor cortex representation of the
reading
finger
in
Braille
readers
Brain.1992;116:39-52
Ptito M, Moesgaard S, Gjedde A and Kupers R.
Cross modal plasticity revealed by electro tactile
stimulation in the congenitally blind. Brain.
12824.
Norihiro Sadato, Tomohisa Okada, Manabu
Honda, Yoshiharu Yonekura. Critical Period for
Cross-Modal Plasticity in Blind Humans: A
Functional MRI
Ron Kupers, Arnaud Fumal, Alain Maertens, De
Noordhout, Albert Gjedde, Jean Schoenen, etal.,
Maurice Ptito; Transcranial magnetic stimulation
of the visual cortex induces somatotopically
organized qualia in blind subjects. Proc Natl Acad
Sci USA;2006;103(35):1325
rost DO. Boire, D, Gingras, G, Ptito M. Surgically
created neural pathways mediate visual pattern
discrimination. Proc. Natl. Acad. Sci. USA;2000;
97, 1106873
Sur M. Garraghty PE. Roe AW. Experimentally
induced projections into auditory thalamus and
cortex. Science. 1988; 242, 143741
21. Neimeyer W, Starlinger I. Do the blind hear

better? Investigations on auditory processing in
congenital or early acquired blindness. II. Central
functions. Audiology;1981; 20;510-15
22. Roder B, Teder-Salejarvi W, Sterr A, Rosier
F,Hillyard SA, Neville HJ. Improved auditory
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DOI: 10.5958/j.2319-5886.3.1.015

&
Health Sciences
www.ijmrhs.com
th
Revised: 8th Dec 2013
Research article
Copyright @2013
ISSN: 2319-5886
NUTRITIONAL STATUS OF TRIBAL CHILDREN IN ANDHRA PRADESH

*Gangam Sukhdas1, Sairam Challa1, Prakash Bhatia2, A.R. Rao3, Koteswara Rao.P4
1
Associate Professor, 2Principal and Professor, 3Assistant Professor, Department of Community Medicine, Apollo
Institute of Medical Sciences and Research, Hyderabad, India
4
Health Officer, Urban Health Center (AIMSR), Shaikpet Nala, Hyderabad, India.
* Corresponding author email:sukhdas.gangam@gmail.com
ABSTRACT
Context: Tribes constitute separate socio-cultural groups, having distinct customs, traditions, marriage, kinship, and
property inheritance systems. They live largely in agricultural and pre-agricultural level of technology. Their
dependency on nature and impoverished economy bear effect on the nutritional status different compared to the
general population. Aims: To study the prevalence of malnutrition in the under-five years age group tribal children
in the three regions of Andhra Pradesh and compare the same with national statistics. Methods and Material: A
cross sectional survey was carried out to assess the nutritional status of under-five age group children in three
Integrated Tribal Development Agency (ITDA) blocks of Andhra Pradesh. Results & Conclusions: Based on the
WHO Child Growth Standards, the prevalence of malnutrition was lower in the AP tribal blocks than the national
averages among tribal populations, but higher than the overall national and state averages.
Keywords: Nutrition, Scheduled Tribes, Wasting, Stunting, Underweight.
INTRODUCTION
The Tribal Population in India is 8.6 percent according
to 2011 census.1 Tribes constituted separate sociocultural groups having distinct customs, traditions,
marriage, kinship, property inheritance system and
living largely in agricultural and pre-agricultural level
of technology. Their dependency on nature and
impoverished economy may affect the nutritional
status as compared to their counterparts in the general
population. Young children in India suffer from some
of the highest levels of stunting, underweight, and
wasting observed in any country in the world, and 7
out of every 10 young children are anaemic.2 The
percentage of children under age five years who are
underweight is almost 20 times as high in India as
would be expected in a healthy, well-nourished
population and is almost twice as high as the average
percentage of underweight children in sub-Saharan
African countries. Near about fifty percent of the

children under the age of five years in India are
moderately or severely malnourished. The prevalence
of under nutrition is more in vulnerable groups like
Tribal population. While Andhra Pradesh harbors
nearly 9 percent of the Indian Tribal population, there
are limited studies on the nutritional status of Tribal
Children in Andhra Pradesh. Hence a study was
contemplated to assess the nutritional status of Tribal
children in Andhra Pradesh.
Objectives
1. To study the prevalence of malnutrition in the
Under-Five years age group tribal children in the
three regions of Andhra Pradesh.
2. To compare the nutritional status of tribal children
in Andhra Pradesh with that of national statistics.
76
Sukhdas et al.,
METHODS AND MATERIAL

Study Design: A large community based, cross
sectional study was conducted in 2007 to assess
various health indicators in tribal blocks of Andhra
Pradesh. The current article is an extract from this
study. The study was planned to cover three Integrated
Tribal Development Agency (ITDA) blocks one each
in Rayalseema, Telangana and Coastal area to cover
all the three regions of the state of Andhra Pradesh.
Three ITDA blocks were selected including, Srisailam
ITDA project (21 villages; Rayalaseema region),
Bhadrachalam ITDA project (25 villages; Telangana
region), and Rampachodavaram ITDA (19 villages;
Coastal region).
In each of the selected ITDA blocks 1000 households
were covered thereby a total of 3000 households were
covered with 5% as attrition rate to accommodate the
locked houses and also migrated population. The
target was to cover over 10,000 populations. The
villages were listed out in cumulative order as was
provided by the tribal welfare department and among
them villages were randomly selected to cover the
1000 households.
Clearance from Institutional Ethics Committee was
obtained. All children less than five completed years
of age were included in the study with the informed
consent of the mother. A pretested questionnaire was
used to interview the mothers and record the Childs
anthropometric data. The questionnaire included
variables of demography, gestational history, birth
history, immunization status, feeding history and
clinical findings apart from Height/Length, Weight
and Mid Arm circumference. Standard procedures
were followed to measure Weight and Height/Length
of the child. WHO Child Growth Standards3,4 were
used for assessment of nutritional status of the
children.
A stunted child4 has a height-for-age z-score that is at
least 2 standard deviations (SD) below the median for
the WHO Child Growth Standards. Chronic
malnutrition is an indicator of linear growth
retardation that results from failure to receive adequate
nutrition over a long period and may be exacerbated
by recurrent and chronic illness. A wasted child4 has a
weight-for-height z-score that is at least 2 SD below
the median for the WHO Child Growth Standards.

Wasting represents a recent failure to receive adequate
nutrition and may be affected by recent episodes of
diarrhea and other acute illnesses. An underweight
child4 has a weight-for-age z-score that is at least 2 SD
below the median for the WHO Child Growth
Standards. This condition can result from either
chronic or acute malnutrition, or both.
RESULTS AND DISCUSSION
A total of 1,013 Tribal children under five years of age
were surveyed. Of these 544 were boys and 469 girls.
Among the 1,013 tribal children who were assessed for
malnutrition, 489 (48.27 %) were stunted, 239 (23.59
%) wasted and 490 (48.37%) underweight as per
WHO Growth Standards.4 The Prevalence of stunting
was 49.50 percent in Bhadrachalam, 51.21 percent in
Srisailam and 48.66 percent in Rampachodavaram.
The prevalence of wasting was 23.08 percent in
Bhadrachalam, 24.06 percent in Srisailam and 23.37
percent in Rampachodavaram. The prevalence of
underweight was 48.16 percent in Bhadrachalam,
49.23 percent in Srisailam and 47.13 percent in
Rampachodavaram (Table 1).
The prevalence of stunting (height-for-age) in the
tribal children of Andhra Pradesh (48.27 percent) as
assessed by the current study is similar to that of the
national average of 48 percent. But it is much lower
than the national average of stunting among the
scheduled tribes of 54 percent as found in National
Family Health Survey (NFHS -3). 2 Whereas it is
higher than the overall prevalence in Andhra Pradesh
of 43 percent as found in NFHS-35 (Fig 1).
The prevalence of wasting (weight-for-height) is 23.59
percent in the current study which is more than overall
percent of India (20 percent) or Andhra Pradesh (12
percent). But lesser percent are wasted as compared to
a national average of wasting among the scheduled
tribes of 28 percent as found in NFHS-3.
The prevalence of underweight (weight-for-age) in the
current study was 48.37 percent which is higher than
the overall average of the country (43 percent) and AP
state (33 percent). But it is lower than the prevalence
of underweight among the tribal children of India (55
percent).
77
Sukhdas et al.,
Table 1 : Prevalence of Under Nutrition Among Under Five Age Group Children in Three ITDA Blocks Of
Andhra Pradesh
POPULATION Sample
Stunted
%
N
AP (TRIBAL)
Boys
544
Girls
469
Pooled
1013
Bhadrachalam
Boys
163
Girls
136
Pooled
299
Srisailam
Boys
252
Girls
201
Pooled
453
Rampachodavaram
Boys
129
Girls
132
Pooled
261
Wasted
%
260
229
489
47.79
48.83
48.27
129
110
239
23.71
23.45
23.59
263
227
490
48.35
48.40
48.37
80
68
148
49.08
50.00
49.50
38
31
69
23.31
22.79
23.08
78
66
144
47.85
48.53
48.16
130
102
232
51.59
50.75
51.21
61
48
109
24.21
23.88
24.06
124
99
223
49.21
49.25
49.23
62
65
127
48.06
49.24
48.66
30
31
61
23.26
23.48
23.37
61
62
123
47.29
46.97
47.13
60
50
55
54
48.27
48.37
48
43
43
40
30
Underweight
N
%
33
28
23.59
20
20
12
10
0
AP ITDA
Stunted
AP
Wasted
INDIA
INDIA TRIBAL
Underweight
(All values in percentages)

Fig1: Status of Under-Five Child Nutrition: Current Study & NFHS-3
CONCLUSION
Malnutrition continues to be a persistent public health
problem in India and more so among the Scheduled
Tribes of the country. While the indicators of
malnutrition among the under five tribal children in
the current study done in Andhra Pradesh are better
than the country figures, they are much higher than the
national averages of tribal populations. With a wide

cultural diversity among tribes, like in AP, efforts to
identify food taboos and fads and addressing the same
through ICDS support may help in the long run to
bridge the gaps.
78
Sukhdas et al.,
ACKNOWLEDGMENTS
We are thankful to the Director, Tribal Cultural
Research and Training Institute, Tribal welfare
Department, Hyderabad, and also thankful to Project
Officers of ITDA Bhadrachalam, Srisailam and
Rampachodavaram for their support while conducting
the study.
REFERENCES
1. Primary Census Abstract for Total population,
Scheduled Castes and Scheduled Tribes, 2011
Office of the Registrar General & Census
Commissioner,India.http://www.censusindia.gov.i
n/2011-Documents/SCST%20Presentation%202810-2013.ppt
2. Fred
Arnold,
Sulabha
Parasuraman,
P.
Arokiasamy, and Monica Kothari. Nutrition in
India. National Family Health Survey (NFHS-3),
India, 2005-06. Mumbai: International Institute for
Population Sciences; Calverton, Maryland, USA:
ICF Macro. 2009
3. WHO Multicentre Growth Reference Study
Group. WHO Child Growth Standards based on
length/height, weight and age. Acta Paediatr Suppl
2006;450:76 -85.
4. World Health Organization. Training Course on
Child Growth Assessment. Geneva, WHO, 2008.
5. International Institute for Population Sciences
(IIPS) and Macro International. 2008. National
Family Health Survey (NFHS-3), India, 2005-06:
Andhra Pradesh. Mumbai: IIPS.
79
Sukhdas et al.,
DOI: 10.5958/j.2319-5886.3.1.016

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Research article
Copyright @2013
ISSN: 2319-5886
INCIDENCE AND LOCATION OF ZYGOMATICOFACIAL FORAMEN IN ADULT HUMAN SKULLS

Senthil Kumar. S*, Kesavi D
Department of Anatomy; Sri Ramachandra Medical College and Research Institute, Chennai 600 116
*Corresponding author email: ssksrmc@gmail.com
ABSTRACT
This study was to investigate the morphology, topographic anatomy and variations of Zygomaticofacial foramen
(ZFF). Frequency variations and Location/distance of ZFF from surrounding standard landmarks were evaluated in
100 adult human dry skulls. The frequency of ZFF was varied from being single to as many as four foramina and
absence of ZFF, which was classified into Type I V for single, double, triple, four foramina and absence of ZFF
respectively. The frequency (%) of these types was Type I: 46 & 51, Type II: 31 & 26, Type III: 4 & 6, Type IV: 1
& 1 and Type V: 18 & 16 respectively on right & left sides of the skulls. The mean distance of Zygomaticofacial
foramen from Zygomaticomaxillary suture, nearest part of Orbital margin, Frontozygomatic suture,
Zygomaticotemporal suture and Zygomatic angle was 13.8 & 12.2mm, 6.8 & 6.9mm, 24.8 & 26.7mm, 20.8 &
21.5mm and 12.4 & 13.5mm respectively on right & left sides of skulls. Knowledge on these variables will be
helpful for surgeons for various surgical procedures like Orbitozygomatic craniotomy, for nerve block and Malar
reduction surgeries.
Keywords: Zygomaticofacial foramen, Orbital margin, Zygomaticbone, Zygomaticofacial nerve
INTRODUCTION
Zygomaticofacial foramen (ZFF) usually situated on
the Zygoma nearer to infraorbital margin.1
Zygomaticofacial nerves and vessels emerge out
through this foremen.1, 2 It is more predominant on
right side in male and left side in female population.3
The location and frequency of ZFF vary significantly
among individuals and races due to the difference of
anthropometry of human from region to region.
Current understanding on ZFF is very limited in the
Indian population. ZFF with its structures serves as an
important landmark for locating inferior orbital fissure
during Orbitozygomatic craniotomy,4 for nerve block,
Malar reduction surgeries5, in management of
infraorbital tumors, Plastic and Reconstructive
surgeries. Hence this study has been aimed to evaluate
the location and frequency variations of ZFF in adult
human dry skulls.

Study has been conducted in the Department of
Anatomy, Sri Ramachandra Medical College and
Research Institute, Chennai. A total of 100 adult dry
skulls were collected from the dissection hall and
observed for frequency variations of ZFF. Distance of
Zygomaticofacial foramen from Zyomaticomaxillary
suture,
nearest
part
of
Orbital
margin,
Frontozygomatic suture, Zygomaticotemporal suture
and Zygomatic angle (fig: 1) has been measured with
digital vernier caliper on both sides (Right and Left) of
the skull and compared.
Specimens with very small decalcified pits were
excluded.
80
Senthil Kumar. S et al.,
Fig 1: Showing the distance from ZFF (encircled) to

Zygomaticomaxillary suture (a), nearest part of Orbital
margin (b), Zygomaticofrontal suture (c), Zygomatic
angle (d), Zygomaticotemporal suture (e)
Observations:
A total of 100 dry skulls were examined.
The frequency of ZFF were varied from being absent
to as many as four foramina. Based on it all the skulls
were classified in to following types.
Type I: Single Foramen (fig: 2)
Type II: Double Foramina (fig: 3)
Type III: Triple Foramina (fig: 4)
Type IV: Four Foramina (fig: 5)
Type V: Absence of ZFF (fig: 6)
Fig 4: Type III: Triple Foramina
Fig 5: Type IV: Four Foramina
Fig 6: Type V: Absence of ZFF

Fig 2: Type I: Single Foramen
Table 1: Frequencies of
Zygomaticofacial foramina
SIDE
Type I
(%)
Type II
(%)
different
Type III
(%)
types of
Type IV
(%)
Type V
(%)
RIGHT 46
31
4
2
18
LEFT
51
26
6
1
16
The mean distance of ZFF from Zyomaticomaxillary
suture,
nearest
part
of
Orbital
margin,
Frontozygomatic suture, Zygomaticotemporal suture
and Zygomatic angle was 13.8 & 12.2mm, 6.8 &
6.9mm, 24.8 & 26.7mm, 20.8 & 21.5mm and 12.4 &
13.5mm respectively on right & left sides of skulls.
Fig 3: Type II: Double Foramina
81
DISCUSSION
In the present study absence of ZFF (Type V) has been
found in 18 & 16% of right & left sides of skulls. Aksu
F et al6 stated absence of ZFF at 15.6% of cases which
includes both right and left side skulls. Whereas
Marios Loukas et al7 quoted absence of ZFF at 1%
among 200 specimens. Cajeron DM et8 al found ZFF
in 38 and 13% of right and left of the skulls which is
lower than our study (right: 82 and left: 84%).
In line with most of the studies frequency of ZFF was
ranging from absent to as many as four but Aksu F et
al6 found five foramina in 1.3% of skulls (5 of
160sides, i.e. 80 skulls). Based on the frequency of
ZFF we classified them into Type I V as mentioned
earlier.
Type I to IV were occurred in 46 & 51%, 31 & 26%, 4
& 6% and 1 & 1% of right & left sides of the 100
skulls. In the similar study with 100 sample conducted
by Ongeti et al9 only three types i.e. from Type I, II
and III of our study were reported in 42 & 45%, 35 &
31% and 23 & 17% of right and left side of skulls
respectively. Among these types only Type I and II are
similar to present study and Type III was with higher
frequency than the present findings.
Likewise, the current study is showing the wide
variations from the existing studies in the frequency of
ZFF (table 2).
The mean distance of ZFF from Zygomaticomaxillary
suture was 13.8mm (right) and 12.2mm (left) among
100 skulls whereas it was 18.8mm in the study by
Aksu F et al6.
The mean distance of ZFF from nearest part of Orbital
margin was 6.8 & 6.9 mm (right & left) respectively in
our study which is higher than Aksu F et al6 (5.94mm)
and Hwang SH et al5 (7.61mm).
ZFF situated in 24.8mm (right) & 26.7mm (left)

distance from Frontozygomatic suture which is almost
similar to the Martins C et al (25mm)4 and Aksu F et
al6 (26.2mm).
Likewise the mean distance of ZFF from
Zygomaticotemporal suture was 20.8mm (right) &
21.5mm (left) and Zygomatic angle was 12.4mm
(right) & 13.5mm (left) in the present study.
The etiology behind the absence of ZFF and the path
by which the neurovascular bundle emerges out in
such cases has not reported in the existing literature
and the same could not be evaluated in the present
study because of the fact that present study has been
conducted in the dry skulls, which holds the limitation
of the study. Since the cone-beam computed
tomography (CBCT) has an excellent accuracy in
evaluating the ZFF10, further studies can be conducted
using CBCT to evaluate the fate of neurovascular
bundle in absence of ZFF along with the medical
history of subjects.
The present study is not similar to the most of the
existing studies. The comparisons made in the
discussion were with non Indian studies as there was
very less/nil number of studies we encountered in
literature search. The variant anthropometric
measurements were probably due to difference of skull
anthropometry in different regions of the World.
Similar studies are suggested to be conducted in the
India in order to standardize the foresaid findings
which will be helpful for different surgical procedures
like Orbitozygomatic craniotomy, for nerve block,
Malar reduction surgeries and in management of
infraorbital tumors.
Table 2: Comparison of Present study findings with different existing studies

AUTHOR
Present study
Ongeti et al9
Aksu
Cajeron DM et Marios
6
TYPE
etal
al8
Loukas et al7
Right
Left
Right
Left
Righ Left
(%)
(%)
(%)
(%)
(%)
t (%) (%)
(%)
TYPE I
46
51
42
52
44
46
12
40
TYPE II
31
26
35
31
45
20
75
15
TYPE III
4
6
23
17
6.3
13
13
5
TYPE IV
1
1
--4.4
0.5
0.5
1
TYPE V
Absent
1.3
Absent
Hwang
et al5
(%)
SH
50.9
30
9
0.9
82
CONCLUSION
Frequency of ZFF and its distance from surrounding
standard landmarks were varying from existing studies
and knowledge on them is helpful for surgeons for
various surgical procedures.
reliability in cone-beam computed tomography.

Acta Odontol Scand. 2013; Posted online on 1 Jul
2013. (doi:10.3109/00016357.2013.814804)
ACKNOWLEDGEMENT
I would like to thank Sri Ramachandra University for
giving the opportunity.
REFERENCES
1. Susan Standring. Face and Scalp In Grays
Anatomy An Anatomical Basis of Clinical
Practice. 5th ed. Elsevier. China. 467-497.
2. Dutta AK. The Skull In Essentials of Human
Anatomy
Current
Books
International.Kolkata.2012: 2(5th ed);3-65.
3. Kaur J, Choudhry R, Raheja S, Dhissa NC. Non
metric traits of the skull and their role in
anthropological studies. J. Morphol. Sci,
2012;29(4):189-94
4. Martins C, Li X, Rhoton Al Jr. role of the
Zygomaticofacial foramen in the orbitozygomatic
craniotomy: Anatomic report. Neurosurgery 2003
Jul; 53(1): 168 -73
5. Hwang SH, Jin S, Hwang K. Location of the
Zygomaticofacial foramen related to malar
reduction. J Craniofac Surg 2007; 18(4):872 74
6. Aksu F, Ceri NG, Arman C, Zeybek FG, Tetik S.
Location and Incidence of the zygomaticofacial
foramen: An anatomic study. Clin Anat. 2009;
22(5):559 62
7. Marios Loukas, Deyzi Gueorguieva Owens, Shane
Tubbs,
Georgi.
Zygomaticofacial,
Zygomaticoorbital
and
Zygomaticotemporal
foramina: anatomical study. Anatomical Science
International 2008; 83(2):77 - 82
8. Cajeron DM, Osses AO, Faig-leite H.
Zygomaticofacialforamens anatomical stusy and
its importance in the ondontology.2007. available
from:
http://ojs.fosjc.unesp.br/index.php/cob/
article/download/329/259
9. K. Ongeti, J. Hassanali, J. Ogengo, H. Saidi.
Biometric features of facial foramina in adult
Kenyan skulls. Eur J Anat 2008; 12(1):89-95
10. Del Neri NB, Araujo-Pires AC, Andreo JC,
Rubira-Bullen
IR,
Ferreira
Junior
O.
Zygomaticofacial foramen location accuracy and
83
DOI: 10.5958/j.2319-5886.3.1.017

&
Health Sciences
www.ijmrhs.com Volume 3 Issue 1 (Jan- Mar) Coden: IJMRHS
Received: 15th Nov 2013
Research article
Copyright @2013
ISSN: 2319-5886
ROLE OF MRI IN EVALUATION OF PAINFUL KNEE

*Rajpal Yadav1, Sushil G Kachewar2
1
Chief Resident, 2Professor, Department of Radio-diagnosis, Rural Medical College, PIMS (DU), Loni,
Maharashtra, India
*Corresponding author email: raajpaalyadaav@rediffmail.com
ABSTRACT
Introduction: Requests for knee Magnetic Resonance Imaging (MRI) are most often made when the patient
presents with a painful knee. This pain might be due to trauma or infection or inflammation. Complete clinical
examination is not possible in such situations as the patients cannot co-operate due to severe pain. There comes the
role of noninvasive multiplanar imaging. Hence this study was undertaken to evaluate how MRI can evaluate
painful knee. Methods: 50 consecutive patients who were referred for MRI evaluation of painful knee were
included in this study. Specific findings that explained the cause of pain were compiled. Results: In this present
study of 50 patients, and 17 were females (34%) and 33 were males (66%).The mean age was 36.70 13.14 years.
Traumatic causes outnumbered non traumatic etiologies of painful knee. Injury to the anterior cruciate ligament
(ACL) was the commonest soft tissue abnormality encountered. Partial tears were more common than complete
tears. Tibial attachment was commonly affected than femoral attachment. Injured posterior horn of the medial
meniscus and medial collateral ligament, were the commonest associated findings. Conclusion: MRI evaluation in
patients with painful knee is of vital importance, as MRI can demonstrate the exact nature and extent of bony as
well as soft tissue abnormality. Multiplanar imaging capacity and noninvasive nature of MRI enable a satisfactory
diagnosis in such patients in whom a complete clinical examination is almost impossible due to pain.
Keywords: Painful Knee; MRI; Ligaments, Imaging.
INTRODUCTION
Painful knees can bring tears to our eyes. It may either
be of traumatic origin or non traumatic origin like
infection or inflammation. Examination by a surgeon
or orthopedician is usually not conclusive to pinpoint
the exact lesion causing pain.1, 2 Hence optimum
treatment is hampered. Therefore non invasive
imaging which can demonstrate the underlying
pathology without any significant discomfort to the
patient is needed.3 This study was therefore undertaken
to analyze the utility of magnetic resonance imaging
(MRI) in pinpointing the cause of painful knee. The
aim was to find common imaging findings in our
setup.

Inclusion criteria: Patients of either sex from
>20years, having acute or chronic painful knee were
included in this study, history of painful knee was
noted but as such patients cannot be accurately
evaluated clinically due to their pain. Exclusion
criteria: Patients who could not co-cooperate for MRI
examination, patients have undergone prior surgical
procedures and who had metallic implants or metallic
clips in situ were also excluded as these are
contraindications for MRI evaluation. Methodology:
Philips Achieva 1.5Tesla High Gradient MRI Scanner
was used for evaluating 50 consecutive patients having
84
Rajpal et al.,
Int J Med Res Health Sci. 2014;3(1):84- 87
painful knee as the presenting complaint. The present

study was approved by the Institutional Ethical and
Research Cell and informed consent from all the
patients was obtained for this study.
RESULTS
Analysis of demographic characteristics shows that in
this present study of 50 patients, 17 were females
(34%) and 33 were males (66%). This is because
males are generally more active than females and
travel a lot. Hence their knees are exposed to more
wear and tear. Also they are at more risk of injury.
The following table shows the distribution of patients
as per different age groups. The mean age of patients
in this study was 36.70 13.14. The maximum
numbers of patients were seen in 40-50 years age
group.
Table 1: Distribution of patients according to age
AGE (Years) No. of Patients
%
<20
08
16%
20-30
10
20%
30-40
10
20%
40-50
14
28%
50-60
07
14%
>60
01
02%
TOTAL
50
100%
MEAN SD
36.7013.14
MRI could satisfactorily identify the exact nature of
injury in all cases. Anterior cruciate ligament (ACL)
was the most commonly injured ligament. Right sided
injuries were more common than the left side. Partial
thickness tears were more common. Tibial attachment
was more involved than the femoral attachment.
Table 2: Distribution of MRI findings of ACL
involvement
Number of
Findings
%
Patients
Side
Left
18
36%
Right
32
64%
ACL tear
Compete
17
34%
Partial
27
54%
Location of ACL tear
Midsubstance
14
28%
Femoral attachment
8
16%
Tibial attachment
27
54%
Involvement of medial as well as lateral meniscus was

also seen satisfactorily on MRI. The distribution of
findings of meniscal involvement is summarized in
Table 3. Overall medial meniscus was more
commonly involved rather than the lateral meniscus.
Posterior horn was more involved in either of the cases
than the anterior horn.
Table 3: Distribution of findings of meniscal
involvement on MRI
Findings
Medial
Meniscus
Lateral
Meniscus
No. of patients (%) No. of patients (%)
8(16%)
Anterior Horn 7(14%)
21(42%)
Posterior Horn 35(70%)
Involvement of posterior cruciate ligament (PCL) was
also satisfactorily demonstrated by MRI. The
distribution of findings of PCL involvement is
summarized in Table 4.
Table 4: Distribution of findings of meniscal
involvement on MRI
Findings
Complete Tear
Partial Tear
BUCKLING
No. of patients
04
02
21
(%)
08%
04%
42%
DISCUSSION
A plethora of pathologies can present as painful knee.
Imaging is useful to identify and confirm the clinically
suspected pathologies and also to assessing its extent
and gravity.3-6
Clinical examination in such cases usually suggests
internal derangement. So correct diagnosis is needed
to perform or to avoid invasive procedures like
Arthroscopy.
A host of imaging modalities is available for
evaluation of the knee joint. Plain radiographs
demonstrate bone pathologies clearly. Soft tissue and
cystic lesions may be missed. Only a focal bulge on
overlying soft tissues may be noticed. Computerized
tomography (CT scan) may show the lesions, but the
exact tissue characterization may be limited. In
experienced hands, musculoskeletal ultrasound can
very well depict the soft tissue pathology. The biggest
advantage of MRI is that it shows the entire lesion in
multiple planes so that correct diagnosis and
management strategy can be planned. The MRI
85
Rajpal et al.,
appearance of various soft tissue lesions has been

studied and mentioned in literature. 4-16
On MRI ACL and PCL are seen as hypo intense bands
on T1W, T2W as well as STIR (Short Tau Inversion
Recovery) images. Any injury to them manifests as a
hyperintense appearance on T2W and STIR images.
This injury may result in partial or full thickness tear
of these structures.
Fig 1: STIR sagittal images showing pathologies of

ACL and PCL
Similarly, the meniscus of knee too is seen as a hypo

intense structure on T1W, T2W as well as STIR
images. Any injury to them manifests as a
hyperintense appearance on T2W and STIR images.
This injury may result in partial or full thickness tear
of these structures.
MRI is used to obtain the sections of these regions of
interest in different planes. Standard planes are the
axial, coronal and sagittal planes. Sometimes oblique
images too may be required. The representative MRI
appearance of soft tissue injury presenting as painful
knee is shown in following image.
It has been found that the disruption of a knee
ligament is commonest pathology in patients having
post traumatic knee pain. It is important to develop a
mechanistic approach to associate the imaging
findings with their anatomic relevance.17
Substantial pain and disability caused in Osteoarthritis
of the knee shows a poor correlation with plain
radiographs. Pain receptors have been found in joint
capsule, ligaments, synovium as well as in the
subchondral bone. It has now been understood that no
definitive treatment modality can relieve the pain and
knee surgery does not necessarily guarantee
improvement. Hence a proper clinical assessment of
knee and appropriate MRI examination can permit
proper treatment.18
Not only adults, but children and adolescents too,

commonly present with knee pain. Again the
commonet performed a pediatric cross-sectional
imaging study is the MRI of the knee. Differences
between adult and pediatric knee imaging exist and in
younger age group one has to remember normal
developmental variants, injury and disease patterns
unique to children and adolescents.19
MRI has revolutionized diagnostic imaging of the knee
as this innovative technology allows superior soft
tissue details with multiplanar imaging capability that
provide accurate evaluation of the intra and extra
articular structure of the knee which are demonstrated
with other imaging modalities.MRI is accurate, non
invasive technique for evaluating the structures of the
knee, marrow space, synovium and periarticular soft
tissue concerning the knee.20, 21 It has great capacity in
diagnosing meniscal tear and classifying them into
grade and type which would avoid unnecessary
arthroscopic examination. It is a very good modality to
diagnose a complete tear of the ACL.
New discoveries in the field of computer science and
telecommunications have reduced the cost of MRI
knee studies. This too has increased the acceptance of
MRI imaging by the orthopedic community with quote
results almost same and satisfactory as a non invasive
replacement for arthrography and non therapeutic
Arthroscopy. 22
CONCLUSION
Plethora of causes can cause painful knee. It is a
common symptom in all age groups. Correct treatment
necessitates accurate noninvasive diagnosis. Imaging
of the knee joint by MRI can satisfactorily provide the
correct diagnosis. This has led to the increase use as
well as the increased acceptance of MRI in the
imaging evaluation of painful knee.
REFERENCES
1. Terry GC, Tagert BE, Young MJ. Reliability of
the clinical assessment in predicting the cause of
internal derangement of the knee. Arthroscopy.
1995;11(5):568-76
2. Yoon YS, Rah JH, Park HJ: A prospective study
of the accuracy of clinical examination evaluated
by arthroscopy of the knee. Int Orthop.
1997;21(4):223-27
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Rajpal et al.,
3. McCarthy CL, McNally EG. The MRI appearance

of cystic lesions around the knee. Skeletal Radiol.
2004;33:187209
4. Trieshmann HW Jr, Mosure JC: The impact of
magnetic resonance imaging of the knee on
surgical
decision
making.
Arthroscopy.
1996;12(5):550-55
5. Dorsey ML, Liu PT, Leslie KO, Beauchamp CP.
Painful suprapatellar swelling: Diagnosis and
discussion. Skeletal Radiol. 2008;37:93738
6. Christian SR, Anderson MB, Workman R,
Conway WF, Pope TL. Imaging of anterior knee
pain. Clin Sports Med. 2006; 25(4):681-702
7. Janzen DL, Peterfy CG, Forbes JR, Tirman PF,
Genant HK. Cystic lesions around the knee joint:
MR imaging findings. AJR Am J Roentgenol.
1994;163:15561.
8. Hirji Z, Hanjun JS, Choudur HN. Imaging of
Bursae. J Clin Imaging Sci. 2011;1:22.
9. Burk DL, Dalinka MK, Kanal E. Meniscal and
ganglion cysts of the knee: MR evaluation AJR
Am J Roentgenol 1988; 150:331-336
10. Pouders C, De Maeseneer M, Van Roy P,
Gielen J, Goossens A, Shahabpour M. Prevalence
and MRI-anatomic correlation of bone cysts in
osteoarthritic knees. Am J Roentgenol. 2008;
190:1721.
11. Recht MP, Applegate G, Kaplan P. The MR
appearance of cruciate ganglion cysts: A report of
16 cases. Skeletal Radiol. 1994;23:597-600
12. Fielding JR, Franklin PD, Kustan J . Popliteal
cysts: a reassessment using magnetic resonance
imaging. Skeletal Radiol. 1991;20:433-35
13. Miller TT, Staron RB, Koenigsberg T. MR
imaging of Bakers cyst: association with internal
derangement,
effusion
and
degenerative
arthropathy. Radiology. 1996;201:247-50
14. Fritschy D, Fasel J, Imbert JC, Bianchi S, Verdonk
R, Wirth CJ. The popliteal cyst. Knee Surg Sports
Traumatol Arthrosc. 2006; 14:62328
15. Dorsey ML, Liu PT, Leslie KO, Beauchamp CP.
Painful suprapatellar swelling: Diagnosis and
discussion. Skeletal Radiol. 2008; 37:93738
16. Recht MP, Applegate G, Kaplan P. The MR
appearance of cruciate ganglion cysts: A report of
16 cases. Skeletal Radiol. 1994; 23:597-600
17. Miller LS, Yu JS. Radiographic indicators of acute
ligament injuries of the knee: a mechanistic
approach. Emerg Radiol. 2010;17(6):435-44
18. Haviv B, Bronak S, Thein R. The complexity of

pain around the knee in patients with
osteoarthritis. Isr Med Assoc J. 2013;15(4):178-81
19. Orth RC. The pediatric knee. Pediatr Radiol.
2013;43:90-98
20. Kachewar SG, Kulkarni DS. Distant perijoint
calcifications: sequel of non traumatic brain
injury-a review and case report. Journal of Clinical
and Diagnostic Research. 2013;7:2606-2609.
21. Kachewar SG, Singh H. Perigenicular Heterotopic
Ossification: A rare sequelae of non traumatic
brain injury. Nepal Journal of Neurosciences.
2010;1:21-23
22. Nikken JJ, Oei EHG, Ginai AZ. Acute peripheral
joint injury: cost and effectiveness of low-fieldstrength MR imaging results of randomized
controlled trail. Radiology. 2005;236: 95867
87
Rajpal et al.,
DOI: 10.5958/j.2319-5886.3.1.018

&
Health Sciences
Research article

Accepted: 21st Dec 2013
A RETROSPECTIVE STUDY OF PRESCRIPTION PATTERN OF ANTIMICROBIALS IN AN URBAN

HEALTH CENTRE RUN BY A MEDICAL COLLEGE
*Bala Sharmin S, Chincholkar Aparna S, Wagh Ranjit J, Mutalik Madhav M.
Department of Pharmacology, MIMER Medical College, Talegaon Dabhade, India
* Corresponding author email: sharminbala@gmail.com
ABSTRACT
Background: Antimicrobials are widely prescribed agents in clinical practice. Overuse of antimicrobials has led to
emergence of drug resistance. Aims: The present study was aimed at knowing the choice of antimicrobial
prescribing and to understand the rationality of antimicrobial usage. Materials and Methods: A retrospective
prescription audit was done of all 655 prescriptions issued between 01/01/2012 and 31/12/2012 at the outpatient
department of Urban Health Centre attached to a medical college. Demographic information, diagnosis, and
medication details (dose, duration, frequency) were recorded and analyzed, and data was expressed as percentages.
Results: Of the total number of prescriptions, 46% prescriptions were containing at least one or more than one
antimicrobial agent. Average number of antimicrobials prescribed per prescription was 1.35. Cotrimoxazole was the
most common antimicrobial agent prescribed. Of the total 307 items of prescribed antimicrobials, 57% were
prescribed by proprietary name and 43% by nonproprietary name. Out of the antimicrobial items prescribed, 44%
were available at the pharmacy of the Urban Health Centre. Fifty eight percent of antimicrobials prescribed were
from WHO Essential Drug List. Conclusion: Among the various antimicrobials prescribed at the Urban Health
Centre, cotrimoxazole was found to be the most commonly prescribed antimicrobial agent in the year 2012. More
than half of the antimicrobials were prescribed by proprietary name. Less than half of the antimicrobials prescribed
were available at the Urban Health Centre. Majority of the antimicrobials prescribed were from the WHO Essential
Drug List.
Keywords: Prescription pattern, Antimicrobials, retrospective study, Cotrimoxazole
INTRODUCTION
Antimicrobial agents are widely prescribed in health
care set-ups for treatment of common ailments like
coryza, cough, fever or pain in abdomen.1 Irrational
and unnecessary use of antimicrobials remains
common in developing countries.1,2 The overuse or
inadvertent use of antimicrobials is known to lead to
the emergence of drug resistance.3,4 Drug resistance is
one of the major obstacles in medical management of
diseases.1 Many physicians augment the drug therapy
with a high dose of antimicrobials and prescribe
various antimicrobial combinations. A study showed
that polypharmacy is now-a-days a common practice.5

Also, many medications are available as over the
counter drugs. Many antimicrobials thus may be
taken without knowing the appropriate dosage and
frequency. Many times the antimicrobials are
discontinued before completing the antimicrobial
course of the specified days. This results in inadequate
treatment, and also increases the possibility of
emergence of drug resistance. Considering all these
issues, the present study was undertaken. The
objectives of the present study were: 1) To know the
88
Bala Sharmin et al.,
prevalence of conditions associated with infections

and to know what antimicrobial agents were
prescribed, 2) To determine whether the drug
prescribing was rationally in accordance with WHO
guidelines for prescribing drugs, 3) To identify
common errors in prescriptions, and propose
interventions for improvement.
This was a retrospective prescription audit. The study
was approved by the Institutional Ethics Committee.
All the prescriptions issued in the outpatient
department of the Urban Health Centre of Bhausaheb
Sardesai Rural Hospital attached to MIMER Medical
College, Talegaon-Dabhade (located in Pune district of
Maharashtra) were studied. The prescriptions issued
from 01/01/2012 to 31/12/2012 were included in the
study, and the total number of prescriptions were 655.
It was not necessary to exclude any prescriptions on
account of incompleteness or illegibility. Demographic
information of the patients, diagnosis of the illnesses,
the medication details (dose, duration, frequency,
formulation, and whether prescribed from WHO
Essential Drug List6 or not), and the follow-up details
of the patients were recorded. All prescriptions were
critically evaluated using guidelines of WHO as
described in How to investigate drug use in health
facilities.10 The common antimicrobial agents
prescribed, the different types of antimicrobials
prescribed, the number of antimicrobials prescribed
per prescription, and the availability of antimicrobial
agents at the Urban Health Centre were recorded.
Further, whether the physicians prescribed the
medications with proprietary or nonproprietary names
was also noted.
Indicators used for prescription pattern study:
A. Prescribing Indicators: 1, 8
1. Average number of drugs per encounter was
calculated by dividing the total number of drugs
prescribed by the total number of prescriptions.
2. Average number of antimicrobials per prescription
was calculated by dividing total number of
antimicrobials prescribed by the total number of
prescriptions.
3. Percentage of drugs prescribed from WHO Essential
Drug List was determined by dividing the number of
products prescribed from the WHO Essential Drug
List by the total number of drugs prescribed,
multiplied by 100.
B) Facility indicators: 1, 8
a) Availability of copy of Essential Drug List by
stating Yes or No.
b) Availability of drugs was calculated by dividing the
number of specified products actually in stock by the
total number of drugs on the checklist of essential
drugs multiplied by 100.
Selection of Cases: All the prescriptions issued at the
Urban Health Centre from 01/01/2012 to 31/12/2012
were included in the study.
Statistical Analysis: It is a descriptive study and
purposive sampling was done. Data was analyzed and
expressed as a percentage.
RESULTS
Of the total 655 prescriptions, 46% prescriptions were
containing at least one or more antimicrobial agents.
Average number of antimicrobials prescribed per
prescription was 1.35. Of the total 226 patients taking
antimicrobials, 82 were males and 142 were females.
There were 84 children. Upper respiratory tract
infection was the most common diagnosis in all adults
and children followed by diarrhea (Figure 1) (Table 1).
There were 26 different antimicrobials prescribed, of
which 4 were prescribed most commonly.
Cotrimoxazole was the most common drug prescribed
to both adults and children (36.2%) followed by
metronidazole, norfloxacin, and amoxicillin (Figure
2). A single antimicrobial was prescribed in 81% of all
prescriptions, whereas 17% prescriptions contained
two antimicrobial agents. The prescriptions containing
cephalosporins were 2%. Percentage of antimicrobial
items prescribed by brand name (proprietary name)
was 57% and those prescribed by non-proprietary
name was 43%. The doses of the antimicrobial
medications were prescribed according to standard
regimens. Of the 226 patients, 63 came for follow-up
and 22 of them received antimicrobials on follow-up.
Antimicrobial agent was changed in 15% patients on
follow-up. Out of all the antimicrobial items
prescribed, 44% were available at the pharmacy of the
Urban Health Centre. Most common antimicrobial
prescribed from outside the Urban Health Centre was
doxycycline. The WHO Essential Drug List was
available at the Urban Health Centre. Fifty eight
percent of antimicrobials prescribed were from WHO
Essential Drug List. Of the antimicrobials prescribed
from WHO Essential Drug checklist, 46% were
available at the pharmacy of the Urban Health Centre.
89
Fluoroquinolones (norfloxacin, ciprofloxacin) were

administered to 5 children, of which three had the
diagnosis of diarrhea, and two were diagnosed with
fever and chills.
Table 1: Some common disease conditions and
corresponding antimicrobial prescribed
Most common diagnosis
Most common
antimicrobials
prescribed
Upper respiratory tract Cotrimoxazole
infection (URTI)
Loose Motion
Metronidazole
Urinary Tract Infection Norfloxacin
(UTI)
Injury
Cotrimoxazole
Folliculitis
Cotrimoxazole
48.20%
14.60%
URTI
Loose motion
23.40%
9.60%
UTI
4.20%
Injury
Others
Fig 1: Diagnosis observed in percentage:

URTI- Upper respiratory tract infection, UTI- Urinary
tract infection
40.00%
36.20%
32.20%
30.00%
20.00%
15.70%
10.00%
11.20%
4.70%
0.00%
Fig 2: Antimicrobials prescribed

DISCUSSION
There is a widespread use of antimicrobials all over
the world. In a study from rural clinics in Western
China, almost half of the prescriptions contained
antimicrobial agents.9
This figure was 54.8% in
Lagos, Nigeria, 67% in Hai Phong Province, Vietnam,

27.1% in a primary healthcare centre in Lebanon,
15.3% in United States, and 32% in Spain.9 In a study
from India, 69% prescriptions contained one or more
antimicrobial agents.4 In the present study, 46%
prescriptions contained one or more antimicrobial
agents. The difference is statistically significant.
(Z=8.08, p<0.001). Upper respiratory tract infection
was the most common diagnosis, and cotrimoxazole
was the most commonly prescribed antimicrobial
agent (36%) followed by metronidazole, norfloxacin,
and amoxicillin. Two other studies also found
cotrimoxazole as the most commonly prescribed
antimicrobial agent (36% prescriptions).4, 7 The results
are comparable with our study. In a study conducted in
Kyrgyz Republic, penicillin G was the most common
antimicrobial agent prescribed3. Now-a-days the
cephalosporins are one of the most commonly
prescribed antimicrobials in various countries. A study
in South India reported cefixime to be the most
commonly prescribed antimicrobial agent2. In the
present study there were 26 different antimicrobials
prescribed of which 4 were prescribed most
commonly; however, the cephalosporins were
infrequently prescribed. In a study conducted in China,
there were 49 antimicrobials prescribed in total, 17 of
them were prescribed frequently.9 In the present
study, prescriptions with one antibiotic comprised 81%
of all prescriptions, those with two antimicrobials
represented 17%. In the study conducted in China,
prescriptions with one antibiotic comprised 40.6% of
all prescriptions, and those with two antibiotics
represented 7.08%9. The frequency and proportion of
prescribed antimicrobials in the present study are
higher compared with the other studies. 9 The average
number of medicines per encounter (2.8%) is higher
than the range of 1.32.2 found in similar studies in
other countries conducted at the district or regional
levels, either in hospitals or health centers. 1 Though a
significant number of antimicrobials were prescribed
by the non-proprietary name, the physicians prescribed
majority of the antimicrobials by brand (proprietary)
name. It was found in the prescriptions that the doses
of the antimicrobial medications were appropriate in
context with the medical conditions and the patient
factors. Almost one third of the patients taking
antimicrobials returned for follow up. Less than half of
the antimicrobials prescribed were available at the
Urban Health Centre. Majority of the antimicrobials
90
were prescribed from the WHO Essential Drug List

(58%). When this figure was compared with those
from other studies, it was found that the percentage of
antimicrobials prescribed from WHO Essential Drug
List was higher in other studies, e.g. being 79% in a
study done in Lesotho and with the WHO study
showing that the adherence to the Essential Medicine
List in Tanzania was 88% (Ofori-Adjei, 1992) and in
Nepal 86%.1 It was suggested that improvements in
the prescribing pattern can be made by prescribing the
drugs to a larger extent by their non-proprietary name.
More antimicrobial agents should be prescribed from
the WHO Essential Drug List. We suggest that more
drugs which are prescribed and included in the WHO
Essential Drug List should be available in the Urban
Health Centre pharmacy. In the present study, it was
noticed that fluoroquinolones were administered to 5
patients less than 18 years of age. Fluoroquinolones
may damage growing cartilage and cause arthropathy.
Therefore these drugs are not routinely recommended
for patients less than 18 years of age.11
3.
4.
5.
6.
7.
CONCLUSION
Prescription audit of prescriptions over a period of 1
year at the Urban Health Centre of a rural hospital
showed that antimicrobials were widely prescribed.
Cotrimoxazole was the most common antimicrobial
prescribed. There were antimicrobial items found to be
prescribed by the proprietary name in significant
number
of
prescriptions.
Suggestions
and
recommendations from this particular audit would be
useful to improve the prescribing trends for the benefit
of the recipients.
8.
9.
ACKNOWLEDGEMENTS
I sincerely thank the Urban Health Centre staff and the
Department of Preventive and Social Medicine for
extending help in providing all the necessary
information of the patients visiting the Urban Health
Centre.
REFERENCES
1. Antibiotics prescribing pattern at 6 hospitals in
Lesotho.
Retrieved
from
apps.who.int/
medicinedocs/documents/s21028en/s21028en.pdf.
(Accessed on November 15, 2013).
2. Khade A, Shakeel M, Bashir M, George S,
Annaldesh S, Bansod K. Prescription pattern of
antimicrobial agents in a teaching hospital of
10.
11.
South India. Int J Basic Clin Pharmacol 2013;

2(5): 567-70.
Baktygul K, Marat B, Ashirali Z, Rashid H,
Sakamoto J.
An assessment of antibiotics
prescribed at the secondary health care level in the
Kyrgyz Republic. Nagoya J. Med. Sci. 2011;73:
157-68.
Indira K, Chandy S, L Jeyaseelan, Kumar R and
Suresh S. Antimicrobial prescription patterns for
common acute infections in some rural and urban
health facilities of India. Indian J Med Res
2008;128:165-71.
Kumari R, Idris M, Bhushan V, Khanna A,
Agrawal M, Singh. S.K. Assessment of
prescription pattern at the public health facilities
of Lucknow district. Indian J Pharmacol.
2008;40(6):243-7.
WHO Essential Drug List. Retrieved from:
www.who.int/medicines/publications/essentialmed
icines. (Accessed on February 24, 2013)
Furones J A. Drug utilization Study related to
Antibiotics in Primary Health Care; INABIS98.
Retrieved from: www.mcmaster.ca/inabis98/
occupational/furones0821/index.html. (Accessed
on November 15, 2013).
Introduction to Drug Utilization and Research/
WHO International Working Group forDrug
Statistics Methodology, Drug Utilization Research
and Clinical Pharmacological Services. Retrieved
from:
http://apps.who.int/medicinedocs
/en/d/Js4882e/8.4.html#Js4882e.8.4. (Accessed on
February 25, 2013).
Dong L, Yan H, Wang D. Antibiotic prescribing
patterns in village health clinics across 10
provinces of Western China. J Antimicrob
Chemother. 2008;62(2):410-15.
WHO. How to investigate drug use in health
facilities: selected drug use indicators, Geneva,
World Health Organisation, 1993, WHO/DAP/93
1993;1:1-87. (Accessed on February 24, 2013)
Deck DH, Pharm D, Lisa G, Winston, MD.
Sulfonamides, trimethoprim, and quinolones. In:
Katzung BG, Masters S, Trevor A. Basics and
clinical
pharmacology.
Tata
McGrawHill;2012;12th edition:836
91
DOI: 10.5958/j.2319-5886.3.1.019

&
Health Sciences
www.ijmrhs.com
th
Research article
Copyright @2013
ISSN: 2319-5886
Accepted: 23rd Dec 2013
PREVALENCE
AND
FUNGAL
PROFILE
OF
PULMONARY
ASPERGILLOSIS
IN
IMMUNOCOMPROMISED AND IMMUNOCOMPETENT PATIENTS OF A TERTIARY CARE
HOSPITAL
Prakash Ved1, *Mishra Prem P2, Verma Shashi K3, Sinha Shivani4, Sharma Mahendra5
1
Associate Professor, 2Assistant Professor, 4MD student Department of Microbiology, RMCH, Bareilly, UP, India
3
Professor, Department of Physiology, RMCH, Bareilly, UP, India
5
Statistician cum lecturer, Dept of community Medicine; RMCH, Bareilly, UP, India
*Corresponding author email: prem6284@gmail.com
ABSTRACT
Background: Aspergillus is a fungus which may present an array of pulmonary manifestations, depending on the
patient's immunological and physiological state. Although the incidence of pulmonary aspergillosis occurs primarily
in immunocompromised patients but the incidence is also rising in immunocompetent individuals, especially in
developing countries. Aim: The objective of the study was to determine the prevalence and predisposing factors of
pulmonary aspergillosis along with species identification. Materials and Methods: One hundred and three patients
admitted to the Department of Chest and Tuberculosis and in the Department of Medicine from Jan 2012 to Jan
2013 were included in this study. The patients were epitomized on the basis of clinical signs and symptoms,
physical examination, chest radiography, CT scans, histopathological examination, bronchoscopy and fungal
examination including potassium hydroxide mount, fungal culture of sputum and bronchoalveolar lavage. Species
identification was done by colony characteristics, slide culture and Lactophenol Cotton blue mount. Results: Out of
the 103 patients, (63 males and 40 females) Aspergillus species has been isolated from 17 (16.5%) males and 07
(6.79%) females. Various predisposing factors of pulmonary aspergillosis have been identified in which pulmonary
tuberculosis, chronic smoking and environmental exposure to asbestos, cement its tops the list. Many of the patients
had multiple predisposing factors. Aspergillus species were isolated in 24 (23.3%) cases. Aspergillus fumigatus was
the predominant species isolated in 13 (54.16%) cases followed by Aspergillus flavus in 07 (29.16%) cases,
Aspergillus niger in 03 (12.5 %) and Aspergillus terrus in 1 (4.16%) cases. Conclusion: It is concluded that the
prevalence of pulmonary Aspergillosis is quite high in immunocompromised individuals and low in
immunocompetent individuals. An adequate and efficient evaluation of the etiological agents has a crucial role in
the management of such patients.
Keywords: Aspergillus, Tuberculosis, Sputum, Immunocompromised.
INTRODUCTION
In recent years fungal infections are one of the
important cause of pulmonary infections.1 Aspergillus
primarily affects the lungs, causing a variety of
manifestations, including allergic bronchopulmonary
aspergillosis (ABPA), aspergilloma, and invasive
Prakash et al.,
aspergillosis. Invasive pulmonary aspergillosis is an

increasingly common fungal infection with high
morbidity and mortality in immunocompromised
patients. The incidence and clinical impact of these
infections is on the rise in the developed countries,
92
which is possibly related to increased number of

immunocompromised patients, owing to improved
survival from AIDS, malignancies and more intensive
cytotoxic therapy, organ transplantation and better
treatment and prophylaxis for other fungal infections.2
Immunocompromised individuals are susceptible to
pulmonary aspergillosis, but invasive aspergillosis is
extremely uncommon in individuals with intact
immunity. Immunocompetent persons seldom develop
this infection and do so only in the presence of other
pulmonary and systemic abnormalities such as fibrotic
lung disease,3 suppurative infection4 or treatment with
corticosteroids.5 Pulmonary aspergillosis shows a
variable inimitable pattern of lung disease that
primarily depend on the patient's immune status.
Preexisting lung diseases acts as a significant
predisposing cause for pulmonary aspergillosis.6,7
Pulmonary aspergillosis is generally presented as a
wide range of pulmonary manifestations, from
aspergilloma with a comparatively benign course, to
invasive pulmonary aspergillosis, which can be
terminal. Pulmonary aspergillosis is one of the main
causes of pulmonary infections and creates a
complicated diagnostic challenge due to lack of
pathognomonic clinical features. The diagnosis of
aspergillosis is frequently missed as the diagnostic
tests for their detection is not done in routine
diagnostic laboratories and/or is not suspected by the
physician.
Therefore, the present study aims to a) detect the
prevalence
of
pulmonary
aspergillosis
in
immunocompromised
and
immunocompetent
individuals. b) To study the various predisposing
factors. c) Isolation and differentiation of
Aspergillus species from clinical specimens of patients
suffering from pulmonary infections.
METHODS
This study was conducted on 103 patients with
different chronic pulmonary infections admitted in the
wards of Department of Chest and Tuberculosis, and
Department of Medicine between the period of
January 2012 to January 2013. The cases are the
patients with various chronic pulmonary infections of
more than one year on whom bronchoscopy, radio
imaging was done. This work has been approved by
the Institutional Ethical Committee.
Data were collected regarding age, sex, detailed
medical history (immunosuppressive conditions like
Prakash et al.,
pulmonary tuberculosis, Diabetes mellitus, AIDS etc,

chronic smoking and environmental exposure to
asbestos, cement etc smoking), physical examination
(vital signs, cyanosis, pallor, clubbing etc), chest
radiography, Computed Tomography (C.T) scan,
bronchoscopy etc. A complete blood picture and
histopathological examination were done. We have
considered the infections/diseases as a prime risk
factor in patients with multiple risk factors.
The sputum and bronchoalveolar lavage was
homogenized and direct microscopy was performed by
using 10% KOH mount. It was inoculated on one set
of Sabouraud's Dextrose Agar (SDA) [HIMEDIA,
MUMBAI] plain and SDA with Chloramphenicol
(0.05 mg/mL) [HIMEDIA, MUMBAI] and also on
Czapek Dox agar [HIMEDIA, MUMBAI]. The
inoculated SDA were incubated at 25C and at 37C.
The colony morphology of obverse as well as reverse
was studied.8 Tease Mount Preparation (TMP) of the
mould isolated was prepared in Lacto Phenol Cotton
Blue (LPCB) for identification detailed morphology
including hyphae, phialides, vesicles and spores. The
confirmation of fungal species was done by slide
culture.9
Statistical analysis: The data were analyzed by using
SPSS version 17. The descriptive analysis and chi
square test were applied. The results obtained were
presented by using appropriate tables and charts.
RESULTS
A total of 103 patients {63 (61.16%) males and 40
(38.83 %)} of various age groups with indications of
chronic pulmonary infections were admitted in the
wards of the Hospital during the study period as shown
in Table 1 and Table 2. The chi square test is
appropriate at 5% level which shows no significance
among culture positive males and females while
significant in age group > 40 years (Elderly).
Aspergillus species have been isolated from 17
(16.5%) males and 07 (6.79%) females. The elderly
patients (>40 years) had a higher incidence of
pulmonary aspergillosis in males as well as females.
There are 17 culture positive cases among
immunocompromised and 07 cases
among
immunocompetent cases. Based on the data of the
clinical history, the various risk factors like pulmonary
tuberculosis, diabetes mellitus, HIV infection, chronic
smoking, recurrent respiratory tract infections,
Bronchial Asthma, Pleural effusion, environmental
93
exposure to asbestos, cement and other chemicals are

documented in Figure 1.
Aspergillus fumigatus was the predominant species
isolated from 13 (54.17%) cases significant by chi
square test, followed by Aspergillus flavus which was

isolated in 7 (29.17%) cases, 3 (12.5%) cases of
Aspergillus Niger and 1 (4.7 %) case of Aspergillus
terrus as depicted in Table 3 and figure 2.
Table 1: Distribution of culture positive and culture negative patients on the basis of sex.
SEX
Culture Positive Patients Culture
Negative Total
P value
Patients
MALE
17
46
63
=1.231
FEMALE
07
33
40
P= 0.2671
TOTAL
24
79
103
Table 2: Age group of culture positive and culture negative patients.
Age Group
Culture Positive
Culture Negative
Total
0-20 YRS
21-40 YRS
>40 YRS
TOTAL
01
08
15
24
23
24
32
79
24
32
47
103
P value
=6.92
P= 0.0314*
*Significant
Table 3: The incidence of Aspergillus species isolated among patients of chronic lung disease.
SPECIES
No. of Positive Cultures
Percentage
P value
Aspergillus fumigatus
Aspergillus flavus
Aspergillus niger
Aspergillus terrus
45
40
35
30
25
20
15
10
5
0
13
07
03
01
54.17%
29.17%
12.5%
4.7 %
= 6.92
P= 0.0314*
*Significant
42
33
31
24
22
21
15
9
3
total no of patients
no of positive culture
Fig 1: The various risk factors in the patients that may be associated with pulmonary aspergillosis
Note: various patients had multiple risk factors.
Prakash et al.,
94
Aspergill
Aspergill us terrus
us niger
4%
13%
Aspergill
us flavus
29%
Aspergill
us
fumigatu
s
54%
Fig 2: Percentage of Aspergillus species in culture

positive patients.
DISCUSSION
Aspergillus species are common saprobic in the soil,
and their vegetative spores are ever present. Generally,
only immunocompromised patients or the individuals
who suffer from other chronic lung conditions are
susceptible. Recently, reports of invasive pulmonary
aspergillosis in immunocompetent patients have
increased
in
the
clinical
literature.10,11
Immunocompetent
patients
are
generally
asymptomatic and only incidentally they are found to
have aspergillosis.12-14 Though, the rare cases of
pulmonary aspergillosis in patients with intact immune
system have been documented.11 In recent time,
reports about invasive pulmonary aspergillosis in
COPD
patients
and
apparently
non15-22
immunocompromized patients
have been reported.
In our study, the prevalence of pulmonary aspergillosis
was 23.3%. The prevalence was higher than
Henderson et al23 who reported an incidence of 11%,
Pepy et al24 reporting 8% and Campbell and Clayton
8.2 % respectively.25 This might be due to the more
exposure of the patients to the predisposing factors and
environmental conditions favouring the growth of the
fungus.
Among the risk factors pulmonary tuberculosis,
chronic smoking, bronchial Asthma, bronchogenic
carcinoma was seen. Multiple risk factors were also
found in patients admitted. Risk factors such as
COPD, systemic corticosteroid therapy, nonhaematological malignancy, chronic renal disease,
liver failure, diabetes mellitus, near-drowning, HIV
infection, etc have been described in earlier studies.2629
The incidence of aspergillosis was more common in
Prakash et al.,
males as compared to females, more in adults as

compared to children which may be due to increased
exposure to risk factors. Our study showed a higher
incidence
of
Aspergillosis
among
immunocompromised individuals and low in
immunocompetent individuals. More recently, reports
have described
patients with normal immunity and invasive or semiinvasive infections caused by Aspergillus species,
most commonly Aspergillus fumigatus, involving the
chest wall30, brain, middle ear31, and lung10,14.
Methods of prompt diagnosis of pulmonary
aspergillosis are based on isolation of Aspergillus in
culture, serological methods and histopathological
examination which is an invasive method, for which
both clinicians and patients may be reluctant to
undertake. The culture was positive in 24 (23.3%)
samples. Aspergillus fumigatus was the predominant
species isolated in 13 (54.17%) cases which is in line
with the findings of Bordane et al and Shahid et al.32, 33
The other species isolated were Aspergillus flavus,
Aspergillus niger and Aspergillus terrus in 7 (29.17%),
3 (12.5%), and 1 (4.7 %) cases respectively.
CONCLUSION
Finding of Aspergillus species in respiratory tract
samples in the patients should not be routinely
discarded as colonization, even if the patients are
immunocompetent[27]. It is concluded from the present
study that the prevalence of pulmonary Aspergillosis
in immunocompromised as well as immunocompetent
patients is rising in our country; hence, any patient of
chronic lung infection not responding to regular
antibiotic therapy should be investigated for infection
by Aspergillus. Any indication of aspergillosis, by
positive sputum culture, serological tests, should
compel the physician to initiate anti-fungal treatment.
ACKNOWLEDGMENT
We would like to express our special thanks to our
teachers who made us capable to do this wonderful
project which also helped us to gain the knowledge
from experience. Secondly, we would also like to
thank Miss Vandana Thakur and other technicians who
helped us to carry out our work smoothly.
Thanks again to all who helped us.
Disclaimer: None
95
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Disseminated aspergillosis in intensive care unit
patients: an autopsy study. J Chemother
2003;15:7175
28. Vandewoude KH, Blot SI, Benoit D, et al.
Invasive aspergillosis in critically ill patients:
attributable mortality and excesses in length of
ICU stay and ventilator dependence. J Hosp Infect
2004;56:269276.
29. Meersseman W, Vandecasteele SJ, Wilmer A.
Invasive aspergillosis in critically ill patients
without malignancy. Am J Respir Crit Care Med.
2004;170:62125
30. Fisher MS. Case report 750: aspergillosis of the
chest wall in an apparently immunocompetent
host. Skeletal Radiol. 1992;21:41013
31. Kim DG, Hong SC, Kim HJ. Cerebral
aspergillosis in immunologically competent
patients. Surg Neurol 1993;40:32631
32. Bordane EJ Jr. The clinical spectrum of
Aspergillosis. Part II: Classification and
description. Rc Crit Rev Clin Lab Sci. 1980;13:85
33. Shahid M, Malik A, Bhargava R. Prevalence of
aspergillosis in chronic lung diseases. IJMM 2001;
19(4): 201-205.
Prakash et al.,
97
DOI: 10.5958/j.2319-5886.3.1.020

&
Health Sciences
Received: 7th Dec 2013
Research article
Coden: IJMRHS
Copyright @2013
ISSN: 2319-5886
th
Revised: 19 Dec 2013
SOCIODEMOGRAPHIC PROFILE OF SPEECH AND LANGUAGE DELAY UP TO SIX YEARS OF

AGE IN INDIAN CHILDREN
*Abraham Binu1, Raj Sunil1, Stephenson Baburaj2, Mohandas MK2
1
Assistant Professor, 2Professor, Department of Pediatrics, Dr SMCSI Medical College, Trivandrum, Kerala
*Corresponding author email: abramb@gmail.com

ABSTRACT
Background: Speech and language is the most important skill for the childs development and scholastic
performance. Awareness of the delay is important in the programs for early identification. Purpose: to assess the
prevalence of speech and language delay in children from age group 0 to six years of age. Methodology: The
speech and language development of children coming in the well baby clinic and daily pediatric clinic of age group
from birth to 6 years were evaluated using Language Evaluation Scale Trivandrum (LEST). The prevalence of
speech and language delay in each age group was calculated and also analyzed in the sociodemograhic profile.
Results: A total of 102 children were studied in which 13.7% had language delay. 18% had questionable language
delay and 15.7% had suspect language delay. Though among language delay mixed type was more, children had
more difficulty in doing expressive items. Language delay was also found to be more prevalent in males, single
child, first born child and children of working mothers. Parental age, education or socioeconomic status was not
found to be related to language delay. Conclusion: The 13.7% prevalence of language delay in the children
indicates the need of early identification and for it a simple screening tool like LEST is a must during the routine
evaluation of young children in pediatric clinics. Health care givers and parents should ensure that babies grow up
in a language rich, nurturing and stimulating environment right from birth onwards.
Key words: LEST, Language delay, Speech delay, First born child
INTRODUCTION
Speech and language is the most useful and most
widely used form of communication. Communication
is integral to overall developmental progress in young
children mainly in cognitive, social emotional and
adaptive development. Speech helps the children to
get attention from others, to satisfy their needs, to
influence the behavior of others, to develop social
relations and as they grow, it plays an important role in
their academic achievements.1
Language typically develops in a very predictable
fashion, and assessment of language development
should be a central part of every well-child visit.
Pediatricians are in an excellent position to identify

children's speech and language problems early and to
make appropriate referrals for further evaluation and
treatment services.
The children who have communication problems may
develop behavior problems and difficulty to read and
write later in life.2 Childrens capacity to communicate
and the vocabulary power when they enter preschool
are important for good scholastic performance.
Children with language problems in preschool are at
risk of poor educational achievement in school age and
are at increased risk to develop emotional and
98
Abraham et al.,
behavioral disorders.3 Early intervention may prevent

or decrease the severity of language delays in school
age and increase later academic success in school. To
underline this fact, there is increasing number of
evidences coming up that intervention given or started
during infancy or preschool age has a greater positive
effect than services provided at school age.4
The language development of a child may be a good
marker of developmental delay. Delay in acquiring
language development is often an early indicator of
pervasive developmental problems and future learning
disability. This indicates the need for assessment of all
babies less than 2 years.
This study is planned to evaluate the prevalence of
language and speech delay in children from birth to 6
years of life as preschool years are the most ideal time
for the early identification of communication delay
which will help to start the early intervention. It will
also be useful to evaluate the prevalence of expressive
and receptive type of delay among the children which
help to focus our attention to that part.
This study also tries to evaluate the communication
delay in the context of maternal and paternal education
and occupational status. There is a scarcity of studies
involving all these factors. So this study is aimed to
involve all these factors which will help to know the
multiple factors influencing the language and speech
development.
Aims and Objectives: The aim of the present study
was to assess the speech and developmental outcomes
in children from age group 0 to six years. The
objectives were to find the prevalence of speech and
language delay in children from age birth to six years
of age and to find the sociodemographic characteristics
associated with it.
The Study was conducted by Department of Pediatrics
after getting ethical clearance from the institutional
ethical committee of Dr SMCSI Medical College,
Trivandrum, Kerala, also taken informed consent from
parents.
Study design: A descriptive study of cross sectional
design.
Study population: The children attending well baby
clinic and daily pediatric clinic of a tertiary care
centre, Dr SMCSI Medical College, Karakonam of age
group birth to six years. Considering the prevalence of
developmental delay as 6.6%(p) as per the study done

by Nair MKC et al5, margin of error at 5%(m),
confidence level as 95%(t=1.96), the minimum
sample size is estimated to be 102 using the formula
t2xp(1-p)/m2
Selection of cases: The inclusion criteria consist of
children in the age group 0-6 years coming in the
outpatient and well baby clinic of Pediatric
Department for routine checkups, minor illnesses and
also for vaccination. Those children with severe
sickness and those with developmental delay in other
domains like gross motor, fine motor and social were
excluded.
Tools for the study
The study is done by using a performa consisting of
the socio demographic parameters like age, sex, family
order, living with parents or not and sibling details.
Details of paternal age, education and occupation are
assessed. The socioeconomic class is assessed using
Modified Kuppuswami Scale.6 Maternal details of age;
education and occupational status as house wife or
working mother were also assessed. The speech and
language assessment is done using Language
Evaluation Scale Trivandrum (LEST) which was
developed
by
Child
Development
Centre,
7
Trivandrum . Other tests are Receptive Expressive
Emergent Language Scale (REELS) and Early
Language Milestone Scale (ELM Scale 2).7 But LEST
is a culturally appropriate locally relevant simple
language development screening tool which can be
used both to professionals, those who are working in
the field of child development and even with the
mothers to pick up speech delay in the early years of
life. The assessment of language delay was done by
assessing if the child is able to do all items on the left
side of their corresponding age in the LEST Chart. The
interpretation is done in four ways as in Table1
Table1: Interpretation of
LEST7
Normal
All items
done
Questionable One item
not done.
language delay using

Suspect
Two
items not done
Delay
Three or
more items not done
The distribution of children in different age groups are

calculated in 0-1 year, 1-2 year, 2-3 year, 3-4 year, 4-5
year and 5-6 years and the speech and language
developmental pattern was assessed in these age
99
Abraham et al.,
groups. The prevalence speech and language delay

was calculated as normal, questionable, suspect and
delay which were the outcome variables. Each item is
compared in the sociodemographic schedule with
different age groups. The type of delay was also
assessed as expressive, receptive or mixed type. The
delays were compared with different age groups.
Statistical analysis: Mean, standard deviation and
Student t tests were used for analysis of continuous
variables and Chi Square test was used for categorical
variables. A p value below or equal to 0.05 was
considered to be statistically significant for a 95%
Confidence Interval. The Statistical software SPSS
16.0 was used for the analysis of the data and
Microsoft Excel was used to generate tables.
RESULTS
The study was conducted in children attending the
well baby and pediatric clinics of Department of
Pediatrics, Dr SMCSI Medical College Trivandrum,
Kerala. A total of 102 children were assessed for the
study in which 49(48%) were females and 53(52%)
were males and the difference was not statistically
significant (P value 0.73). Depending on the age of
children they were divided into 6 groups 0-1 year, 1-2

year, 2-3 year, 3-4 year, 4-5 year and 5-6 years.
Among the 102 children studied, the total percentage
of children with language delay was 13.7%. 15.7%
children were in the suspect and 18 % were in the
questionable group. The prevalence of language delay
in each age group is given in table 2
Among the total 14 of 102 children who had language
delay, 10.8% children were having a mixed type of
delay, 1% was having receptive and 2% were having
an expressive type of delay. Regarding the type of
items children could not do during assessment, 20%
had difficulty in doing both items.
Comparing expressive and receptive type of language
items individually, 16% could not do expressive items
only compared to 9.1% who could not do receptive
items only. This shows that children had more
difficulty in doing expressive items.
The percentage of males having delay were found to
be more compared with that of females (15.1% males
with 12.2% females) and the difference was not found
to be statistically significant (p value 0.67). The sub
analysis of children with language delay according to
delay, questionable and suspect group is given in table
3.
Table 2: Language delay in each age group

Age Group (yr) Normal (%) Questionable (%) Suspect (%) Delay (%) Total
0-1
14(70.0)
4(20.0)
1(50)
1(5)
20
1-2
11(52.4)
6(28.6)
3(14.3)
1(4.8)
21
2-3
7(46.7)
1(6.7)
3(20)
4(26.7)
15
3-4
6(40)
3(20)
3(20)
3(20)
15
4-5
7(43.8)
2(12.5)
4(25)
3(18.8)
16
5-6
9(60)
2(13.3)
2(13.3)
2(13.3)
15
Total
54(52.9)
18(17.6)
16(15.7)
14(13.7)
102
Table 3: Gender related variation in language delay
Sex
Normal (%)
Questionable (%)
Female
30(61.2)
6(12.2)
Male
24(45.3)
12(22.6)
Total
54(52.9)
18(17.6)
The majority of the children were of the first order
which was 67 (61.8%). Of the rest, 37 children
(36.3%) were 2nd order. Language Delay was found to
be more prevalent among the first born child in this
present study. 17.5% delay was seen in the first child
compared to 8.1% seen in the second born child.
Language delay was found also to be more prevalent
Suspect (%)
7(14.3)
9(17)
16(15.7)
Delay (%)
6(12.2)
8(15.1)
14(13.7)
Total
49
53
102
in the single child in the family. 17.3% of 52 single

children were having delay compared to 10% of 50
children who were not single kids in the family and it
was significant (p value -0.033)
In the present study no association could be made with
the parental age and language delay. Among the 14
children with language delay, fathers of half children
100
Abraham et al.,
had passed 10th class and other half were degree

holders. Similarly of those 14 children, 5 mothers had
passed 10th class and 9 mothers were degree holders.
This shows that all the parents of children with
language delay were educated.
It has been found that among the children of house
wife mothers, 4 children (11.2%) had language delay.
But among the children of working mothers, 10
children (30.8%) had language delay.
Among the 14 children who had language delay, 11
children were living with parents. For 2 children their
fathers were not in the state and for one child, both
parents were not in the state. No association could be
made about the language delay in children not living
with both their parents as the number of children in
those groups was very less.
The socioeconomic class grading was also done
among the children studied using Modified
Kuppuswami Grade and the socioeconomic class of
the children with language delay was analyzed and
shown in table 4.
Table 4: Socioeconomic class and language delay
Social
No Delay
Delay
Total
Class
(%)
Present (%)
Class 1
1(100)
1
Class 2
19(86.4)
3(13.6)
22
Class 3
50(86.2)
8(13.8)
58
Class 4
17(85)
3(15)
20
Class 5
1(100)
1
Majority of children belonged to 2, 3 and 4
socioeconomic grades. No significant association was
seen with lower or higher socioeconomic class and
language delay.
DISCUSSION
A cross sectional study in 102 children was conducted
using Language Evaluation Scale Trivandrum (LEST
0-6) from the age group birth to 6 years of age to find
out the prevalence of language and speech delay.
The total percentage of children with language delay
was 13.7. In the study done by Nair MKC et al5, 6.6 %
of language delay was observed for the age group 0-12
months using LEST against 4% prevalence for the
same using Receptive Expressive Emergent Language
Scale (REELS). In the present study it was 5% below
1 yr age was comparable.
For the age group 13 to 24 months, the study done by
Nair MKC et al5, prevalence of speech and language
delay among at risk babies was 29.7% using LEST as
Abraham et al.,
against 6.6% by using REELS and 5.7% using both

tests. In the present study it was found to be 4.8%. The
difference may be due to the factor that in the present
study the babies coming to the well baby clinic were
observed and at risk babies were not included in the
study.
In a study done by James et al in 1980 the speech and
language delay in the age group 0 to 2 years was
around 5%8. In the present study, it was 4.87% which
was comparable.
For the age group 2-3 years, the speech and/or
language delay was 6.9% in the study done by Burdon
et al, it was 6.9%9. The language delay was 2.6 % in
the study done by Silva et al in 1983.10 But in the
present study it was 26.7% which was significantly
higher that the other studies.
For the age group 3-4 years, in the study done by
James et al the speech or / and language delay was
5%.6 In our study it was 20% which was higher.
For the age group 5-6 years, in the study by Beitchman
et al, the speech and/or language delay was 11.78%.11
In another study by Stevenson et al it was 6.8%.12 In
the present study the speech delay was 13.3% which
can be compared to the study done by Beithchman et
al.
In a study done by Nair MKC et al5 in children of age
13 to 24months, 24% had a language delay in the
receptive area using LEST as against 5.1% using
REELS. Similarly 42% had a language delay in
expressive area by using LEST as against 7.4% using
REELS. In the study done by James et al the mixed
language delay was 2.14%8, expressive delay was
4.27% and receptive delay was 3.95%. In the present
study the mixed language delay was found to be more.
Among the items not done by children in our study,
16% could not do expressive items and 9.1% could
not do receptive items. This showed that children have
more difficulty in doing the expressive items. In the
study done by Nair MKC et al5 in children of age 13 to
24months, 24% had delay in the receptive language
and 42% had delay in expressive language by using
Language Evaluation Scale Trivandrum (LEST).
In the study done by Tomblin13 et al 87% of children
with articulation disorders were boys and in the study
done by Choudhary et al 70% of the children were
males.14 In the present study though the number of
males with language delay was more (57%), the
difference was not significant.
In the study done by Broookerhouser et al15 children
born late in family birth order was a significant factor
101
for language delay. In another study by Nelson et al

single child in the family was also found to be a
factor.16 In the present study also first born children
had a more language delay. Similarly a single child in
the family was also found to be a significant factor.
In the study done by Nelson et al, older parents and
younger mother age was found to be a significant
factor16. From the present study no such association
could be made with parental age. The study done by
Campell et al showed an association between lower
maternal education and language delay.17 The
systematic evidence review done by Nelson et al also
showed similar picture.. Another study done by Tallal
et al also showed an association between lower
paternal education level and language delay.18 This
study does not support that fact and all the parents of
the children were educated.
Children of house wife mothers had significantly less
language delay than children of working mothers.
Similarly those living with both the parents had less
delay but the difference were not significant. In the
study done by Tallal et al18 lower socioeconomic class
was a risk factor for language delay. In our study there
was no significant association between socioeconomic
status and language delay.
CONCLUSION
The study showed that language delay was more
prevalent in below 2 years of age, in first born child
and single child in the family. This reveals the
importance of early screening and the importance of
the stimulation they get from the whole family. The
language development does not depend on the age,
educational or socioeconomic status of the parents but
the quality time the care givers spend with the child.
The prevalence of 13.7% speech and language delay in
the normal children enlightens the need for early
screening programs. Because communication is central
to personal development, social interaction and
learning ability of child, delay in the language and
speech development should be identified as early as
possible. Health workers should make sure that the
babies are growing in a language rich environment and
parents should be educated about it as well.
ACKNOWLEDGEMENT
The authors are very thankful to the Department and
Management of Dr SMCSI Medical College for their
generous support and encouragement during the period
of study. The authors also acknowledge Mr Sanu

Johnson for computer work and Mrs Deepa S Mony
for her contribution in data collection.
REFERENCES
1. Elizabeth B Hurlock. Child Development. 6th
Edition, Tata McGraw Hill Publishers: 1942;13549
2. Backer l, Cantwell D. A prospective psychiatric
follow up of children with speech/language
disorder. Journal of the American Academy of
child and Adoslescent psychiatry.1987; 26 :546-53
3. Prizant B. Communication disorders and
emotional /behavioural disorders in children.
Journal
of
Speech
and
Hearing
Disorders.1990;55:179-92
4. Barnett W, Escobar C. Economic costs and
benefits of early intervention, Hand book of early
childhood Intervention,3rd Edn, In SJ Meisels & J
P Shoukoff:1990; 560-82
5. Kavitha SR, Nair MKC. Validation of LEST (1-2
years) against REELS Language Evaluation Scale
Trivandrum (1-2 Research Form 2006) Against
Receptive Expressive Emergent Language Scale.
Teens .2006; 1(2):29-31
6. Sushama Bai S. History taking. Clinical
Evaluation of New borns, Infants and Children 2nd
Edition. Jaypee Brothers Medical Publishers.
2009; Chapter 3:13
7. MKC Nair ,GS Harikumaran Nair, AO Mini, S
Indulekha,S Letha and PS Russel.Development
and Validation of Language Evaluation Scale
Trivandrum for Children Aged 0-3 years - lest (03). Indian Pediatr. 2013;50:463-67
8. James Law, James Boyle. Francis Harris.
Prevelance and natural history of primary and
language delay: findings from a systematic review
of literature. Int J Lang Comm Dis. 2000;35(2):
169-72
9. Burden V, Stott CM, Forge J, Goodyer I. The
Cambridge Language and Speech Project
(CLASP): I. Detection of language difficulties at
36 to 39 months. Dev Med Child Neurol.
1996;38:61331
10. Silva PA, Williams SM, McGee R. A longitudinal
study of children with developmental language
delay at age three: later intelligence, reading and
behaviour problems. Developmental Medicine and
Child Neurology. 1987;29:63040
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11. Beitchman JH, Nair R, Clegg M. Prevalence of

psychiatric disorders in children with speech and
language disorders. J Am Acad Child Adolesc
Psychiatry 1986; 25: 528-35
12. Stevenson J. Developmental changes in the
mechanisms linking language disabilities and
behaviour disorders. In JH Beitchman, Cohen NJ,
Konstantareas MM, Tannock R. Language,
Learning and Behavior Disorders: Developmental,
Biological and Clinical Perspectives Cambridge
University Press;1996;5th edition:234-45
13. Tomblin JB, Smith E, Zhang X. Epidemiology of
specific language impairment: prenatal and perinatal risk factors. Journal of Communication
Disorders.1997;30:32544
14. Choudhury N, Benasich AA. A family aggregation
study: the influence of family history and other
risk factors on language development. J Speech
Lang Hear Res. 2003;46:26172
15. Brookhouser PE, Hixson PK, Matkin ND. Early
childhood language delay: the otolaryngologists
perspective. Laryngoscope. 1979;89:189813
16. Nelson HD, Peggy Nygrien, Miranda Walker, Rita
Panoscha. Screening for speech and language
delay in preschool children: systematic evidence
review for the US Preventive Services Task Force.
Pediatrics. 2006;117(2):301-02
17. Campbell TF, Dollaghan CA, Rockette HE. Risk
factors for speech delay of unknown origin in 3year-old children. Child Dev. 2003;74:34657
18. Tallal P, Ross R, Curtiss S. Familial aggregation
in specific language impairment. J Speech Hear
Disord. 1989;54:16773
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DOI: 10.5958/j.2319-5886.3.1.021

&
Health Sciences
www.ijmrhs.com
Volume 3 Issue 1 (Jan- Mar)
Coden: IJMRHS
th
Received: 8 Dec 2013
Research article
Copyright @2013
ISSN: 2319-5886
URIC ACID AND HYPERTENSION: DOES URIC ACID LICK THE JOINTS AND BITES THE HEART?
* Vittal BG1, Bhaskara K2, Naveenkumar GH3
1
Associate Professor of Biochemistry, 2 Associate Professor of Orthopaedics, 3 Assistant Professor of Community

Medicine, Bidar Institute of Medical Sciences, Bidar, Karnataka, India
* Corresponding author email: vittal.bg@gmail.com
ABSTRACT
Background: Uric acid a metabolic end product of purine degradation is implicated in gout as aetiology. Its
increased levels have also been associated with hypertension, cardiovascular morbidity and mortality. Few studies
have been conducted, especially in India to elucidate association of uric acid with prehypertension.
Aims: This study intends to assess the association of serum uric acid levels with blood pressure in normotensive,
prehypertensive and hypertensive population. It also intends to check whether there is an incremental rise of serum
uric acid with increasing blood pressure. Material and methods: Two hundred outpatients who met inclusion and
exclusion criteria and consented formed study population. Blood pressure of each participant was measured
followed by venipuncture to collect venous blood for measurement of serum uric acid. Participants were categorised
into 4 groups as Normal, Prehypertension, Hypertension Stage 1, Hypertension Stage -2 as per Joint National
Committee 7 classification. Data was analysed to know levels of serum uric acid among the four categories and to
verify association of uric acid with blood pressure. Results and Conclusions: Stepwise increase in serum uric acid
levels was observed along with increasing blood pressure. Strong positive linear correlation was observed between
serum uric acid levels and mean blood pressure (Pearsons correlation coefficient r = 0.74; p< 0.0001). Uric acid
was associated (r = 0.442) with blood pressure in prehypertension population. Serum uric acid levels are associated
with prehypertension and hypertension and are independent and strong predictors of cardiovascular mortality.
Keywords: Blood pressure, Prehypertension, Uric acid.
INTRODUCTION
Uric acid is an end product of purine degradation in
humans and is primarily excreted through urine.
Serum uric acid levels are regulated by dietary purine
intake, endogenous metabolism of purines, and its
urinary excretion rate. In the process of evolution 15
million years ago, two mutations rendered uricase
gene non-functional in humans and great apes.
Consequently uric acid is not converted to readily
water soluble and easily excreted product allantoin,
thus resulting in higher serum uric acid levels in
humans and great apes.1
Vittal et al.,
As early as in 1848 AD, Sir Alfred Garrod

demonstrated that Gout, an inflammatory disease of
joints was associated with Hyperuricemia i.e,
increased levels of serum uric acid (>7mg/dl in males
and >6mg/dl in females).2 Gout is a disease of joints
characterised by the deposition of monosodium urate
crystals in joint space causing inflammation and
painful joints.
A few years later, in 1874 AD, Frederick Mohamed
postulated for the first time that People with high
blood pressure belong to gouty families suggesting
104
the possible association of Hyperuricemia with high

blood pressure. 3
Association of elevated serum uric acid with
hypertension was further reported by many
researchers. At the end of the 19th century many
studies demonstrated that uric acid was also associated
with cardiovascular morbidity. However, lack of
possible mechanism by which hypertension and uric
acid are associated led to conclusion that uric acid is
not a true risk factor for cardiovascular disease. 4-9
Amidst contradicting reports, Mohameds hypothesis
that uric acid has a causative role in hypertension
remains controversial even after over 130 years.
Recent animal studies and clinical observations
indicate the possible direct causal role of uric acid in
pathogenesis
of
hypertension
by
various
10
mechanisms. Of late, increasing evidence is being
gathered suggestive of association and causal role of
uric acid in hypertension and cardiovascular
morbidity. 11
Hitherto studies conducted have not assessed the
association of serum uric acid levels blood pressure in
prehypertensives and its incremental rise with
increasing blood pressure. So in this study we intend
to assess the association of serum uric acid levels with
blood pressure in normotensive, prehypertensive and
hypertensive participants. We also intend to check
whether there is an incremental rise of serum uric acid
with increasing blood pressure.
Our study was conducted at Regional Diagnostic
Laboratory of District Hospital, Bidar, a teaching
hospital affiliated to the Bidar Institute of Medical
Sciences, Karnataka, India. Study spanned over a
period of 3 months from August to October 2013.
Institutional Ethical committee approval was taken
before commencement of study and our procedures
were in accordance with the Helsinki Declaration of
1975, as revised in 2000.12
The subjects for this prospective study were
outpatients who visited regional diagnostic laboratory
for routine investigations. Two hundred participants
(103 men and 97 women) of age group 20 to 60 years
formed the study population.
Subjects who fulfilled below mentioned inclusion and
exclusion criteria were informed and explained about
the study and after their informed written consent were
included in the study.
Vittal et al.,
Inclusion and exclusion criteria: Paediatric and

psychiatric patients, pregnant women, diagnosed cases
of essential secondary hypertension, medications like
uricosuric drugs and antihypertensive drugs were
excluded in the study.
Study participants were made to sit comfortably on a
chair for five minutes. Systolic and diastolic blood
pressures were measured twice by auscultatory method
with a mercury sphygmomanometer (cuff size, 12.5 x
40 cm) on the right arm. The first and fifth phases of
Korotkoffs sounds were taken as the criteria for SBP
and DBP respectively. The mean of two consecutive
readings was recorded and used for analysis.13 Mean
of systolic and diastolic blood pressure was calculated
(SBP+DBP/2) and noted as mean blood pressure.
As per Joint National Committee (JNC)7 classification
of blood pressure, Participants were categorised as
normal if systolic blood pressure (SBP) was <120mm
of Hg and Diastolic blood pressure (DBP) was <80mm
of Hg; prehypertensive if SBP/DBP is 120-139/or 8089 mm of Hg; Stage 1 Hypertensive if SBP/DBP is
140-159/or 90-99mm of Hg and were categorised as
Stage 2 hypertensives if SBP/DBP is 160/or 100
mm of Hg.14
Under aseptic precautions, venipuncture was
performed on median cubital vein and 2ml of blood
was collected into a sterile evacuated plastic tube with
red stopper with no additives. Blood samples were
allowed to clot at room temperature for 30 minutes.
Samples were centrifuged at 1500g for 15 minutes for
serum separation.15
Serum uric acid levels were measured by modified
Trinders method16, 17 using ERBA XL 300 fully
automated analyser. To ensure quality, daily internal
quality control samples were run and day to day
coefficient of variance (CV) was <5%. The laboratory
also had an external quality assurance programme in
place.
Statistical Analysis: Statistical analysis of participant
data was performed using IBM SPSS Statistics 20
software. The data was analysed to measure age-sex
distribution of participants, to categorise participants
as normal, prehypertension, Stage-1 hypertension and
stage-2 hypertension along with their mean blood
pressures and mean serum uric acid levels. Pearsons
correlation coefficient was calculated to elucidate the
statistically significant association between serum uric
acid levels and blood pressure.18
105
RESULTS
Characteristics of study population: The demographic
characteristics of the study population are summarised
in table 1. Study population comprised of 200
participants of whom 103 were men and 97 were
women..
Table: 1. Age sex distribution of study population
with mean blood pressure
Age
(years)
Number
of Males
Number
of females
20 - 30
35
44
31 - 40
14
14
41 - 50
17
15
51 - 60
37
24
* mean standard deviation
Blood pressure*
(mm of Hg)
98.08 9.09
101.96 13.13
107.21 14.27
112.23 12.69
Mean age of the study population was 40.0613.8

years and mean age of males and females was 41.98
13.48 years and 38.03 13.91 years respectively. The
mean blood pressure of study population showed an
increasing trend with age
The prevalence of undiagnosed hypertension in
population was 22% (n = 44) and of undiagnosed
prehypertension was 42% (n = 84), put together
comprising nearly 65% of study population. A
stepwise increase in serum uric acid levels was
observed when study population was categorised into
four groups namely, Normal, Prehypertension,
Hypertension stage-1, Hypertension stage-2 based on
the JNC 7 classification of blood pressure. Similar
increasing trend in mean serum uric acid level was
observed along with mean blood pressure of the study
population. (Table-2)
Table: 2. Serum uric acid and blood pressure in normotensives, prehypertensives and hypertensives
JNC 7 BP classification14
Serum Uric acid* Blood Pressure* (mm
Males
Females
(SBP/DBP mm of Hg)
(mg/dl)
of Hg)
Normal
30
42
5.09 0.65
92.95 4.7
(<120/ and <80)
Prehypertension
47
37
5.70 0.73
104.08 5.21
(120-139/ or 80-89)
Hypertension Stage-1
18
14
6.81 0.77
119 6.94
(140-159/ or 90-99)
Hypertension Stage-2
8
4
7.59 0.57
136.41 6.86
(160/ or 100)
* mean standard deviation
Statistically highly significant (p<0.0001) difference in
mean serum uric acid was observed between normal
and prehypertension categories; and also between
prehypertension and hypertension stage-1 JNC 7
categories. Similar but less profound, statistically
significant difference (<0.01) was noted between
Stage-1 and Stage-2 hypertension categories.
A strong positive linear correlation was observed
between serum uric acid levels and mean blood
pressure (Pearsons correlation coefficient r = 0.74).
Correlation is highly significant at the 0.05 level (2tailed) and the P-value is < 0.0001. (Figure 1). Similar
correlation was also noted between serum uric acid
and systolic blood pressure (r = 0.746) and diastolic
blood pressure (r = 0.609). Uric acid was associated
strongly (r = 0.442) with blood pressure in the
prehypertension population while a weak correlation (r
= 0.113) was observed in normal population.
Vittal et al.,
Fig 1: Scatter diagram showing correlation of

serum uric acid levels with mean blood pressure.
DISCUSSION
Our prospective study consisting of 200 participants
showed an association of serum uric acid with blood
pressure
in
apparently
healthy
individuals,
undiagnosed
prehypertensive
subjects
and
106
hypertensive individuals. This is the first study

conducted in India to elucidate the association of
serum uric acid levels with blood pressure in
prehypertensive population.
Study population comprised of adult individuals from
20 years to 60 years. Mean age of the study population
was 40.0613.8 years comparable to other similar
studies that had a mean age of 42.30.2 years19 and
41.6 years.20
Although known hypertensive patients were excluded
from the study, 22% (n = 44) of participants were
hypertensivses and 42% (n = 84) were
prehypertensives.
Similar
prevalence
of
21
prehypertension (39%) among adults in India and
Unitesd states of America22 was reported by separate
researchers. It is noteworthy that, a large percentage of
the population who are at risk of developing
hypertension (42%) and undiagnosed hypertensives
(22%) who may develop cardiovascular morbidity go
unnoticed.
Serum uric acid levels were positively (r = 0.740) and
significantly (p < 0.0001) associated with blood
pressure in our study. A similar positive and
statistically significant correlation was observed by
other researchers. 19, 20, 22, 23
A stepwise incremental rise of serum uric acid was
observed with increasing blood pressure when
participants were categorised as per JNC7
classification as normal, prehypertension, hypertension
stage-1, and hypertension stage-2. A similar
incremental increase of uric acid was observed in a
cross sectional study conducted in Japan. However this
study categorised the participants based on Japanese
society guidelines JSH-2009 rather than JNC 7
classification.19
A similar association (r = 0.15; p < 0.001) was
demonstrated by a study on large prospective male
cohort. They also demonstrated that serum uric acid
was independently related to mortality from
congestive heart failure and stroke. 20
Positive association (r = 0.32) of serum uric acid with
prehypertension independent of smoking BMI and
other confounding factors was observed in a study.22
A study demonstrated significant (p < 0.0001)
correlation between uric acid and prehypertension in
adults but the study also noted, unlike our study, that
the association was not statistically significant in older
individuals over 65 years of age. 23
Vittal et al.,
In a nine year follow-up study, association of serum

uric acid with incident hypertension was observed and
stronger association was noted among blacks. 24
PIUMA study, with a cohort of 1720 patients with
follow-up of 12 years noted that, subjects with higher
uric acid levels were at higher risk of developing
cardiovascular events (relative risk 1.73; 95%
confidence interval) than the subjects with lower uric
acid levels. 25
A study on 125 children (age group 6-18 years) with
primary hypertension demonstrated the association of
serum uric acid with systolic blood pressure (r = 0.80)
and diastolic blood pressure (r = 0.66). 26 Another
study in paediatric age group also observed the
association of serum uric acid levels with ambulatory
diastolic blood pressure (r = 0.29; p = 0.0033). 27
Serum uric acid has long been associated with
hypertension, the primary aetiology of cardiovascular
morbidity. Several large cohort studies have
demonstrated that serum uric acid was predictive of
mortality due to ischaemic heart diseases in women. 28
Few studies demonstrated the independent and
significant association of uric acid with risk of
cardiovascular mortality29 and myocardial infarction.
30
It was observed in a study that serum uric acid level
was a strong and independent predictor of
cardiovascular mortality in middle aged men. 31
Increased serum uric acid levels have been associated
with elevated blood pressure and cardiovascular
morbidity and mortality. But the causal role of uric
acid in hypertension and pathogenesis of
cardiovascular events has not been clear. 5- 9
Recent studies have elucidated the plausible
mechanisms that explain how elevated uric acid causes
hypertension. Studies on animal models have shown
that increased uric acid levels cause renal
microvascular and tubular interstitial injury. Uric acid
also increases juxtaglomerular renin production and
decreases nitric oxide synthase expression in macula
densa; collectively contributing to blood pressure
elevation.10
CONCLUSION
Serum uric acid levels are associated with
hypertension and are independent and strong
predictors of cardiovascular mortality, myocardial
infarction and coronary artery diseases in both sexes of
different ethnic groups. So it may not an exaggeration
107
to state that Uric acid licks the joints and bites the
heart
Limitations of the study: The study population was
drawn from outpatients of a hospital that may not form
a representative sample of the general population.
Confounders like serum creatinine, serum uric acid,
serum albumin, history of alcohol intake, and dietary
protein and sodium consumption that alter serum uric
acid and /or blood pressure were not taken into
consideration.
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16. Trinder P. Determination of blood glucose using
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17. Trivedi RC, Rebar L, Berta E, Stong L. New
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Clin Chem. 1978; 24 (11): 1908-11.
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19. Kansui Y, Ohtsubo T, Goto K, Sakata S, Ichishima
K, Fukuhara M, Ohta Y, Matsumura K.
Association of serum uric acid with blood pressure
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J, Guptha S, Sharma KK. Normotension,
prehypertension, and hypertension in urban
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Syamala S, Li J, Shankar A. Association between
serum uric acid and prehypertension among US
adults. J Hypertens. 2007; 25 (8): 1583-9.
Liang J, Xue Y, Zou C, Zhang T, Song H, Qi L.
Serum uric acid and prehypertension among
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Mellen PB, Bleyer AJ, Erlinger TP, Evans GW,
Nieto FJ, Wagenknecht LE etal., Serum uric acid
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Verdecchia P, Schillaci G, Reboldi G, Santeusanio
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T. Relation of serum uric acid to mortality and
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109
DOI: 10.5958/j.2319-5886.3.1.022

&
Health Sciences
www.ijmrhs.com
Coden: IJMRHS
nd
Research article
Copyright @2013
ISSN: 2319-5886
Accepted: 22nd Dec 2013
STUDY OF PRESCRIBING PATTERN OF ANTIMICROBIAL AGENTS IN AN IPD OF A TERTIARY

CARE HOSPITAL IN AHMEDNAGAR
*Kapure NL, Nayak BB, Raul AR, Vijaykumar AN, Vijayprasad S, Vakade KP, Jadhav AR
Department of Pharmacology, PDVVPFS Medical College, Ahmednagar, Maharashtra
*Corresponding author email: nitin.farmac@gmail.com
ABSTRACT
Objectives: To evaluate the pattern of use of Antimicrobial drugs in IPD patients admitted for various illnesses.
Materials and Methods: It is a retrospective and observational study, conducted during the period of January, 2011
to December, 2011. Prescription record of 252 patients admitted in IPD of Medicine & Surgery departments of the
PDVVPFs Medical College & Hospital, Ahmednagar were studied. These data were obtained from Medical Record
Departmeent (MRD) of the hospital. The study was conducted after obtaining permission from the Institutional
Ethics Committee (IEC) of the college. Data were analyzed for- average number of antimicrobials prescribed per
prescription, the relationship between patient age and sex, percentage usage of various antimicrobial groups and
percentage use of individual antimicrobials. Results: It was observed that 75 % of patients were prescribed 1-2
antimicrobial agent and 25 % were prescribed 3 or more than 3 antimicrobials. Cephalosporins were the most
preferred antimicrobials followed by quinolones and aminoglycosides. Fluconazole was found to be most
commonly prescribed antifungal whereas Artesunate and Metronidazole were most preferred antimalarial and
antiamoebic drugs. Conclusion: It can be concluded from the present study that physicians preferred to prescribe 2
or more than 2 antibacterial agents in a prescription. To treat various infections Cephalosporins and quinolones were
observed to be most prescribed antibacterials. Fluconazole, Artesunate & Metronidazole were found to be
commonly prescribed antifungal, antimalarial and antiamoebic agents. Uses of Macrolides, Tetracyclines &
Vancomycin were very low. However, aminoglycosides were commonly prescribed to young males and
Cepahalosporins to young female patients.
Keywords: Drug utilization, Antimicrobial agent, Prescription
INTRODUCTION
As per data by All India Origin Chemists and
Distributors-Advance Working, Action & Correction
S y s t e m ( AIOCD-AWACS) m a r k e t research firm,
antibiotics therapy rank as the 1st in all the super
groups in pharmaceutical market with 14.8% growth
in the month of February 2012. It occupies around 19
% in over 60,000 cr market. However they are the
least studied drugs in terms of drug utilization studies.1
The principal aim of drug utilization research is to
facilitate appropriate use of drugs in patient
Kapure et al.,
populations, minimize the adverse event and drug

interactions leading to better patient outcome. Drug
utilization studies are powerful exploratory tools to
ascertain the role of drugs in the society. They create a
sound sociomedical and health economic basis for
making health care decisions.2 Drug utilization is
defined as marketing, distribution, prescription and the
use of drugs in society, with special emphasis on the
resultant medical, social and economic consequences.3
Often, drugs are not used, keeping in mind their safety
110
and efficacy.4 Rational drug prescribing is the use of

the least number of drugs to obtain the best possible
effect in the shortest period and at a reasonable
cost .5 Irrational prescribing and disparity between the
prescription and the consumption of medicines may
offset the benefits which are demonstrated by
randomized controlled trials on drug efficacy.6-9
The present study was planned to examine the
patterns of drug prescription of Antimicrobials in the
IPD of the internal medicine and surgery in the
PDVVPFs Medical C o l l e ge Hospital, Ahmednagar
a tertiary care hospital.
Study Design: A retrospective, observational study.
Study Duration: 1 year from 01/01/2011 to
31/12/2011
Study Population: Medical Record (MR) data were
obtained from MRD department; consisting of
prescription records
of 252 patients that admitted
in the internal medicine and surgery in the PDVVPFs
Medical College Hospital, Ahmednagar a tertiary
care hospital in Ahmednagar district.
Procedure: The study was conducted after the
permission from the Institutional Ethics Committee.
Total 327 patients data were screened and analyzed
as per the inclusion and exclusion criteria and 252
patients were selected for this study. Patient related
information like age, gender, diagnosis, month of
admission, drug related information like number of
drugs prescribed were collected on a customized
data collection sheet.
Inclusion criteria: All patients who were admitted in
the IPD of the Medicine and Surgery departments and
were prescribed on the antibiotics for various
infections.
Exclusion criteria: Incomplete data.
Parameters studied: Following parameters were taken
in the study
1.Average number of antimicrobials prescribed per
prescription.
2.Percentage usage of various antimicrobials
3.Percentage usage of drugs in each antimicrobial
group
4.Frequency of systemic infection at different
months
5.Relationship between patient d e mo gr aph i cs and
prescription pattern
Statistical analysis: The data were subjected to
descriptive analysis using Microsoft Excel. Utilization
Kapure et al.,
of different classes of drugs as well as individual drugs

was analyzed and presented as a percentage.
RESULT
The total number of prescriptions analyzed was
252 .The numbers of drugs per prescription varied
from one to more than four (Table-1)
Table 1: Number of antimicrobials per
prescriptions in number and percentage
Number of antimicrobials per No of pts ( % )
prescriptions
One
112(44.44)
Two
80 (31.74)
Three
36(14.28)
Four or more than four
24( 9.52)
Total no of prescriptions studied 252
Table 2: Percentage usage of
antimicrobial group
Drug class
Drug
Cefuroxime
Cefotaxime
Ceftriaxone
Cefoperazone
Cefixime
Cefepime
Ciprofloxacin
Quinolones
Ofloxacin
Levofloxacin
Norfloxacin
Aminoglycosides Amikacin
Gentamicin
Streptomycin
Amoxicillin
Penicillins
Penicillin - V
Ampicillin
Fluconazole
Antifungals
Itraconazole
Ketoconazole
Artesunate
Antimalarials
Chloroquine
Primaquine
Metronidazole
Antiamoebics
Tinidazole
Ornidazole
Macrolides
Others
Tetracyclines
Vancomycin
Cephalosporins
drugs in each
(%)
of
prescriptions
33.3
25.3
6.32
1.58
1.58
1.58
14.28
12.69
7.92
4.75
20.62
4.75
3.17
11.1
4.75
3.17
4
2.7
1.3
2
1.7
0.8
13.6
6.4
4
3.17
3.17
1.58
111
PERCENTAGE
Table 3: Frequency of systemic infection in

different months
System
Highest
Lowest
Involved
frequency
frequency
GIT
Sep (70%)
Feb (15%)
CVS
May (85%)
Jan (10%)
CNS
Feb (50%)
July (5%)
RS
Oct (70%)
Jan (10%)
OTHER
Aug (60%)
March (10%)
80
70
60
50
40
30
20
10
0
Fig 1: Prescribing frequency of antimicrobial group of

drugs
76
80
70
0-15
60
16-30
31-60
>60
48
50
36
28
20 20
16
1412 12
40
30
16
20
10
1616
0
8
4
43 322
0 0 02
0
Fig 2: Age-wise prescribing frequency of antimicrobials

in males
0 -15
1 6-30
3 1-60
>60
25
20
20
15
88
10
10
8 8
12
4
0
4
0
6
2
3 3
2
344
0
2
0 11
It was observed that 1, 2, 3 & 4 or >4 Antimicrobials

were prescribed to 44.44%, 31.74%, 14.28% & 9.52%
respectively (Table-1). Among the Antimicrobials
Cephalosporins was found to be prescribed to the
largest number (71.42%) of patients, followed by
Quinolone (39.68%), Aminoglycoside (28.57%),
Antiamoebic (24%), Penicillins (19.04%), Antifungal
(8%), Antimalarial (4.5%) & others were 8% (Fig-1).
Among the cephalosporins use of cefuroxime was
highest (33.33%), followed by cefotaxime (25.39%),
ceftriaxone (6.32%), Cefoperazone, Cefixime,
Cefepime each were 1.58% respectively. Among the
fluoroquinolones it was found Ciprofloxacin was
mostly preferred (14.28%), followed Ofloxacin
(12.69%), Levofloxacin (7.9%), Norfloxacin (4.79%).
Amikacin among the Aminoglycosides was the most
chosen drug (20.62%) followed by Gentamicin
(4.75%), streptomycin (3.75%). Among Penicillins
Amoxicillin was used to the extent of 11.1%, followed
by Benzyl Penicillin 4.75% and Ampicillin 3.17%.
Among the oral antifungal drugs Flucanazole was
observed to be the most favoured to the extent of 4 %
followed by Itraconazole 2.7% and Ketoconazole
1.3% . Artesunate was prescribed to 2 %. Chloroquine
1.7 % & Primaquine 0.8% as antimalarials. Among
Antiamoebic drugs Metronidazole was used to the
extent of 13.6% , followed by Tinidazole 6.4% &
Ornidazole 4 % .
Macrolides, Tetracyclines,
Vancomycin were used in 3.1%, 3.1% & 1.5%
respectively (Table-2) . Patients admitted due to CVS
disease were observed highest among all the diseases
(85%) in the month of May & lowest in the month of
January (10%). Infections of the nervous system
caused to the extent of 15 % in the February & 5 % in
the July. Other infection were found 60% in August
and the lowest occurrence was in March (10%) (Table3). In young male patients Aminoglycisides &
Antimalarials were found to be highest & lowest
prescribed drugs respectively whereas Cephalosporins
& Quinolone were highly preferred for younger as
well as older female patients .Younger age male
patients were mostly admitted for the CVS &
endocrine disorders. However in younger & adult
female patients were commonly associated with CVS
& GI disorders. (Fig 2 & 3)
DISCUSSION
Fig 3: Age-wise prescribing frequency of antimicrobial

in females
Kapure et al.,
The clinical setting in the medical ward w a r r a n t s

the use of drugs from various drug classes. Rational
prescription of drugs is essential for better patient
112
care. The first step in any intervention programme to

improve drug utilization is to assess the extent of
existing problem in prescribing. The objective of our
study was to evaluate the drug utilization patterns
among patients admitted to the IPD of a tertiary care
hospital.
The demographic results of patients admitted to the
IPD over a period of 12 months revealed a male
preponderance with a mean age of around 50 years,
10
similar to a study carried out in Nepal in 2005. In
contrast, Smythe et al (1993) showed an equal number
of male and female patients admitted to the hospital
11
with a mean age of 65 years. Previous Indian studies
also documented male predominance which suggests
that more males are admitted in an Indian setting for
12
infections. The probable reasons for this finding
could be the male to female ratio is higher in the state
of Maharashtra and overall in the India. In the Indian
scenario it is noticed that female populations are
reluctant to utilize health care facilities even if
they are critically ill and especially from lower
socioeconomic strata.
A wide spectrum of clinical diagnoses was observed
including sepsis, renal failure, acute respiratory
distress syndrome, multi organ dysfunction, head
injury, cvs related disorder and diabetes complication.
Debilitating condition of the patients due to underlying
disease, invasive diagnostic and therapeutic
procedures and prolonged utilization of life support
equipment predisposes these patients to infections
It was noticed that most of the antimicrobial agents
were prescribed by brand name (60%) which requires
revision of current prescribing practice. Extensive
polypharmacy (> 90 %) that is more than five drugs
were prescribed in all the patients. Polypharmacy is
defined as concomitant use of five or more drugs and
it could enhance drug interactions and drug related
13
problems. It is difficult to treat patients in the IPD
with multiple comorbidities with less number of
drugs as they require drugs for treatment of specific
conditions as well as for prophylaxis, but it is also
essential to keep a balance between the number of
drugs and effective pharmacotherapy.
High antimicrobial prescribing frequency was
observed in our study inconsistent with earlier studies
14
from Nepal which documented 30%. More than one
antimicrobial agent was prescribed among (69%) of
the prescriptions. This could be expected since
Diabetes, multi organ dysfunction, IHD, respiratory
Kapure et al.,
tract infections was prevalent among the patients of

the present study necessitating therapeutic as well as
prophylactic
utilization
of
antimicrobials.
Antimicrobial protocol and guidelines; formulary
based antimicrobial restrictions can be used to
improve rational usage of antimicrobials. A
multidisciplinary approach can be adopted in the ICU
and IPD set up involving intensive care specialist;
infectious disease control s p e c i a l i s t , pharmacists
and microbiologists can work together for more
rational antimicrobial pharmacotherapy.
CONCLUSION
It can be concluded from the present study that
physicians preferred to prescribe 2 or more than 2
antibacterial agents in a prescription. To treat various
infections Cephalosporins and quinolones were
observed to be most prescribed antibacterials.
Fluconazole, Artesunate & Metronidazole were found
to be commonly prescribed antifungal, antimalarial
and antiamoebic agents. Use of Macrolides,
Tetracyclines & Vancomycin was very low. However,
aminoglycosides were commonly prescribed to young
males and Cepahalosporins to young female patients.
In conclusion, a wide spectrum of clinical diagnosis
and a variety of drugs were utilized for various drug
classes. Overall, the scope for improving rational use
of antimicrobial agents exists. Antibiotic resistance is
increasing at an alarming rate leading to increasing
morbidity, mortality and treatment cost. A key factor
in the development of an antibiotic resistance is
inappropriate use of antibiotics. The medical
fraternity needs to understand that antibiotics are
precious and finite resources, and unless conscious
efforts are made to contain the problem of drug
resistance, multidrug resistant organism untreatable
by ever known antibiotic may emerge reversing the
medical progress by ranking and returning as back to
pre-antibiotic. Pharmacoeconomic studies in the
hospital can encourage cost effective antimicrobial
drug therapy.
This will help in rationalizing
prescribing practices based on the feedback from these
studies and practices between institutions, regions and
countries can be compared.
REFERENCES
1. Mukherjee R. Antidiabetic drugs post highest
growth in Feb. Times o f I n d i a . Mumbai
edition. 5th April 2012: 36.
113
2. Bakssas I, Lunde PKM. National drug policies;

the need for drug utilization studies. Trends
Pharmacolo Sci 1986; 7: 331.
3. WHO, The selection of essential drugs. WHO
technical report 1977; 615: 36.
4. Lunde PKM, Levy M. Drug utilization
geographical differences and clinical implications.
Introductory remarks. In: Duchene-Marullaz, P,
ED.
Advances in pharmacology and
therapeutics. Oxford, Pergamon Press 1978;6:7982.
5. Gross F . Drug utilization therapy a n d practice.
The present situation in the Federal Republic of
Germany. Eur J Clin Pharmacol 1981; 19:387-94.
6. Cochrane AL. Effectiveness and efficiency
Random reflections on health services. London, the
Nuffield Provincial Hospitals Trust, 1982.
7. Stolley PD, Lasagna L. Prescribing patterns of
physicians. Journal of chronic diseases 1969;
22:395-405.
8. Westerholm B. Therapeutic auditing at the national
and international levels. Br J Clin Pharmacol,
1986;22:55S-9S.
9. Pullar T, Kumar S, Tindall H, Freely M. Time to
stop counting the tablets? Clin Pharmacol Ther
1989;46:163-8
10. Srishyla MV, Krishnamurthy M, Nagarani MA.
Prescription audit in an Indian hospital setting
using the DDD (Defined Daily Dose) concept.
Indian J Pharmacol 1994; 26:238.
11. Smythe MA, Melendy S, Jahns B. An exploratory
analysis of medication utilization in a medical
intensive care unit. Crit Care MED 1993; 21 (9):
31923.
12. Biswal S, Mishra P, Malhotra S. Drug utilization
pattern in the intensive care unit of a tertiary care
hospital. J Clin Pharmacol 2006; 46:94551.
13. Viktil KK, Blix HS, Moger TA. Polypharmacy as
commonly defined is an indicator value in the
assessment of drugrelated problems. Br J Clin
Pharmacol 2007; 63(2):18795.
14. Shankar PR, Partha P, Dubey AK. Intensive care
unit drug utilization in a teaching hospital in
Nepal.
Kathmandu Univ Med J 2005;
3(10):1307.
Kapure et al.,
114
DOI: 10.5958/j.2319-5886.3.1.023

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Research article
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MORPHOMETRIC STUDY OF THE SACRAL HIATUS IN NIGERIAN DRY HUMAN SACRAL BONES
*Ukoha Ukoha U1, Okafor Joseph I2, Anyabolu Arthur E1, Ndukwe Godwin U3, Eteudo Albert N4,
Okwudiba Nchedo J2
1
Department of Anatomy, College of Health Sciences, Nnamdi Azikiwe University, Nnewi, Nigeria.
Department of Anatomy, Anambra State University, Uli, Nigeria.
3
Department of Anatomy, Ebonyi State University, Abakaliki, Nigeria.
4
Department of Anatomy, College of Medicine and Health Sciences, Abia State University, Uturu, Nigeria.
2
*Corresponding author email: drukohaukoha@yahoo.com

ABSTRACT
Background: The sacrum is a large triangular bone formed by the fusion of the five sacral vertebrae and forms the
caudal region of the vertebral column. Aims: This was aimed at studying the morphometry of the sacral hiatus
noting its anatomical variations that is useful in caudal epidural anaesthesia. Materials and Methods: Eighty three
intact adult sacra of unknown sex were measured with vernier callipers and the various shapes of the sacral hiatus
were also noted. Results: The findings revealed that inverted U (48.2%) was the most predominant shape; followed
by inverted V (34.9%), dumbbell (4.8%), bifid (4.8%) and irregular (4.8%). The mean anteroposterior diameter at
the apex was 5.52 1.89mm. The mean length of the sacral hiatus was 20.05 9.22mm and the transverse width at
base of hiatus was 12.35 3.12mm. There was complete spina bifida in 1.2% and absence of sacral hiatus in
another 1.2%. Conclusion: The knowledge of anatomical variations of sacral hiatus is important in the
administration of caudal epidural anaesthesia in the studied population and may help to reduce its failure rate.
Keywords: Sacral hiatus, caudal epidural block (CEB), sacral vertebra.
INTRODUCTION
The sacrum is a large triangular bone formed by the
fusion of five sacral vertebrae and it also forms the
caudal region of the vertebral column. It forms the
posterosuperior wall of the pelvic cavity, wedged
between the innominate bones.1 Due to its great size,
the sacrum is usually the last bone of a buried body to
rot. The ancients may thus have believed the sacrum to
be the focal point, around which the body could be
reassembled in the after-life.1 The opening at the
caudal end of the sacral canal is the sacral hiatus
formed due to failure of fusion of laminae of the fifth
(occasionally 4th) sacral vertebrae.
The sacral hiatus is an inverted V-shaped space
located at the distal part of the sacrum. This space is
formed by incomplete midline fusion of the posterior

elements of the distal portion of the fifth or sometimes,
the fourth sacral vertebra. The sacral hiatus is covered
posteriorly by the posterior aspect of the
sacrococcygeal membrane and is an important
landmark in caudal epidural block.2
Sacral approach to epidural space is used for giving
analgesics and anaesthesia for a variety of operations.
Caudal epidural block (CEB) has been widely used for
the treatment of lumbar spinal disorders, management
of chronic back pain, in obstetrics,3 and orthopaedic
practice.4 The technique of CEB depends upon
accurate localization of sacral hiatus through which
access to sacral epidural space is gained. Some authors
115
Ukoha et al.,
have reported that one of the anatomic reasons of

caudal epidural anaesthesia failure is the absence of
sacral hiatus. One of the important key factors for
successful caudal epidural anaesthesia may be clear
understanding of the normal anatomy of sacral hiatus
and surrounding structures.4
Sacral hiatus exhibits variations in morphology which
differ among populations and the reliability and
success of epidural anaesthesia depend upon these
anatomical variations. These variations have not been
well documented in the Nigerian population, hence
this study is meant to address this.
The parameters studied were the following:

i.
Shapes of the sacral hiatus.
ii.
Level of apex with respect to the sacral
vertebrae.
iii.
Level of base with respect to the sacral
vertebrae.
iv.
The length of the sacral hiatus measured from
the apex to the midpoint of the base.
v.
The anteroposterior diameter at the apex.
vi.
The transverse width at the base measured
between the inner aspects of the inferior limits
of sacral cornua.
Only sacra with complete sacral hiatus were used for
the study and damaged, mutilated and deformed sacra
were excluded.
Data Analysis: Data were expressed as mean and
standard deviation for continuous variables, and
percentage for categorical variables. Comparative
analysis was done using Analysis of variance
(ANOVA). The statistical software used was SPSS
Version 16.0.

The study was conducted on 83 intact adult dry human
sacra obtained from various Anatomy museums in the
South-East and South-South zones of Nigeria. Bones
of undetermined age and gender were used. They were
preserved in dry conditions free from moisture, dust,
insects or moths. Direct measurements were taken
with vernier callipers (God Marc Tools, Japan;
accurate to 0.02mm).
RESULTS
Table 1: Frequency distribution of the shape of sacral hiatus
Shape of Sacral Hiatus

Absent
Bifid
Complete spina bifida
Dumbbell
Inverted U
Inverted V
Irregular
Total
Frequency
1
4
1
4
40
29
4
83
Percentage
1.2
4.8
1.2
4.8
48.2
34.9
4.8
100
Table 2: Frequency distribution of the level of apex with respect to the sacral vertebrae.
Level of apex with respect to the sacral vertebrae
Frequency
Percentage
None
S2
S3
S4
S5
Total
2
2
17
58
4
83
2.4
2.4
20.5
69.9
4.8
100
Table 3: Frequency distribution of the level of base with respect to the sacral vertebrae
Level of base with respect to the sacral vertebrae
Frequency
Percentage
None
Coccyx
S4
S5
2
6
2
73
2.4
7.2
2.4
88
116
Ukoha et al.,
Total
83
100
Table 4: The length, transverse width and anteroposterior diameter of the sacral hiatus
Variables
MeanSD
Median
Range
Length (mm)
20.05 9.22
20.50
6.10 57.0
Transverse Width (mm)
12.35 3.12
13.00
5.0 20.50
Anteroposterior Diameter (mm)
5.52 1.89
5.10
0.40 11.10
Table 5: Mean and standard deviation of the length, transverse width and anteroposterior diameter according to the
shape of sacral hiatus
Shape of Sacral Hiatus
Length (mm)
Transverse
Width (mm)
11.03 2.48
13.50 1.08
12.45 2.80
12.81 3.52
8.20 2.51
Bifid
11.03 2.48
Dumbbell
13.50 1.08
Inverted U
22.17 8.42
Inverted V
20.91 9.88
Irregular
8.20 2.51
Data are expressed as means and standard deviations.
Anteroposterior
Diameter (mm)
4.60 1.73
4.78 0.52
5.26 1.83
6.07 2.06
5.80 1.70
Table 6: Mean and standard deviation of the length, transverse width and anteroposterior diameter of sacral hiatus
according to the level of apex with respect to the sacral vertebrae
Level of apex with respect to

sacral vertebrae
S2
Length (mm)
49.55 10.54
S3
26.59 8.27
S4
17.81 6.52
S5
10.0 1.15
Transverse
Width (mm)
14.05 1.34
Anteroposterior
Diameter (mm)
8.60 3.54
12.35 2.55
11.99 3.05
16.78 4.25
5.43 1.85
5.42 1.82
5.78 1.71
Table 7: Mean and standard deviation of the length, transverse width and anteroposterior diameter of the sacral hiatus
according to the level of base with respect to the sacral vertebrae
Level of base with respect to

Length (mm)
sacral vertebrae
S4
28.0 4.24
S5
19.48 9.24
Coccyx
24.35 8.64
Transverse
Width (mm)
15.0 2.83
12.18 3.14
13.57 2.80
Anteroposterior
Diameter (mm)
6.50 2.12
5.44 1.90
6.18 1.82
DISCUSSION
The detailed morphometric study of sacral hiatus is of
great relevance, since this route is frequently utilized
for caudal epidural anaesthesia in perineal surgery, and
caudal analgesia for painless delivery. Edward and
Hingson in 1942 for the first time took advantage of
this natural gap in the lower end of the sacral canal for
continuous caudal analgesia during labour.3 Since
then, the sacral hiatus has been an important landmark
in caudal epidural block. However, failures have often
been encountered in caudal epidural block owing to
anatomical variations in the sacral hiatus. In 1999,
Tsui et al reported that the failure rate was about 25%.5
Shape
Table 1 showed the frequencies of the various shapes
of sacral hiatus in the study population. The inverted U
shape (48.2%) was most dominant, followed by the
inverted V shape (34.90%), both of which were
considered normal. The results were similar to studies
by Seema et al6 and Shewale et al.7 In a study by
Vijisha and Baskaran,8 the inverted U and inverted V
had equal frequencies of 35% each. The abnormal
shapes constituted 15.6% and 1.2% were absent.
Comparison with studies by other authors (
117
Ukoha et al.,
Table 8) showed similarities in the normal shapes, but

the present study had lower frequencies in the
abnormal shapes. Only the population under study
presented with a bifid sacral hiatus.
Level of Apex
The level of apex of sacral hiatus in relation to sacral
vertebrae in the study population is shown in Table 2.
It was quite variable and extended between the middle
of S2 and mid-S5. The S4 vertebra (69.9%) was the
most dominant level. In 2.4%, the wall was open. The
results of the present study in comparison (Table 9)
agreed with studies by Ramamurthi and Anil9 and
Seema et al6 as well as standard Anatomy textbooks.1
Level of Base
In the study population, Table 3 showed the various
levels of base with respect to the sacral vertebrae. The
most dominant level was the S5 (88%) vertebra. In
2.4% of the sacra, the sacral hiatus was completely
obliterated and the lower end of the canal was closed
due to bony undergrowth. Comparison with other
studies supported the fact that the level of base was at
the S5 vertebra in most of the population (Table 10).
Length, transverse width and anteroposterior diameter
at apex
The results are shown in Table 4. The mean length and
mean transverse width were 20.05mm and 12.35mm
respectively. The anteroposterior diameter at apex of
sacral hiatus is important as it should be sufficiently
large to admit a needle, and varying diameters could
cause subcutaneous deposition of anaesthetic drug. In
the present study, mean anteroposterior diameter was

5.52mm.
Table 5 showed the mean length, transverse width and
anteroposterior diameter of the sacral hiatus according
to its shape. Analysis of variance (ANOVA) indicated
significant variations in length (F = 4.32; P = 0.003)
among the different shapes. On the other hand, no
significant differences were observed in transverse
width (F = 2.41; P = 0.057) and in the anteroposterior
diameters (F = 1.22; P = 0.309) of the various shapes.
The mean length, transverse width and anteroposterior
diameter of sacral hiatus according to the level of apex
is seen in Table 6. Analysis of variance (ANOVA)
showed significant variations in length (F = 22.37; P =
0.000) and transverse width (F = 3.42; P = 0.021)
among the different levels. No significant difference
(F = 1.93; P = 0.132) was observed in the
anteroposterior diameter of the various levels.
In
Table 7, the mean length, transverse width and
anteroposterior diameter of the sacral hiatus according
to the level of base is determined. Analysis of variance
(ANOVA) indicated no significant variations in length
(F = 1.56; P = 0.217), transverse width (F = 1.29; P =
0.280) and the anteroposterior diameter (F = 0.70; P =
0.498) among the different levels.
Table 8: Incidence of various shapes of sacral hiatus in dry human sacral bones by various authors
Shape
Inverted U
Inverted V
Irregular
Dumbbell
Bifid
Complete
spina bifida
Elongated
Absent
Seema et al (2013)
42.95%
27.52%
16.11%
13.42%
-
Shewale et al (2013)
40.69%
32.35%
9.31%
5.89%
0.98%
Anil et al (2013)
31%
25.80%
20.60%
5%
-
Current Study (2013)

48.20%
34.90%
4.8%
4.8%
4.8%
1.2%
9.31%
0.98%
17.20%
-
1.2%
Table 9: Incidence of level of apex of sacral hiatus in dry human sacral bones recorded by various authors
Level
S2
S3
S4
S5
Anil et al (2013)
7.76%
41.38%
50.86%
-
Seema et al (2013)
4.03%
35.57%
56.37%
4.03%
4%
15%
66.50%
14.50%

2.40%
20.50%
69.90%
4.80%
Table 10: Incidence of level of base of sacral hiatus in dry human sacral bones reported by various authors
Level
S4
Anil et al (2013)
18.97%
Seema et al (2013)
13.42%
2%

2.4%
118
Ukoha et al.,
S5
72.41%
Coccyx 8.62%
CONCLUSION
70.47%
16.11%
Information obtained from studies on anatomical

variations of the sacral hiatus is important in caudal
epidural block (CEB). In the present study, 83 dry
human sacra were studied and the irregular, bifid and
dumbbell shapes were 4.8% each. The sacral hiatus
was completely absent in 1.2% and 1.2% had spina
bifida, bringing the total rate of sacral hiatus
abnormalities to 16.9%. The rate should be kept in
mind when administering caudal epidural anaesthesia
in the Nigerian population.
82%
16%
88%
7.2%
10. Ramamurthi KS, Anil KR. Anatomical study of

sacral hiatus for successful caudal epidural block.
Int J Med Res Health Sci, 2013; 2(3):496-500
REFERENCES
1. Williams PL (ed). Grays Anatomy, 38th edition,
Churchill Livingstone, 2000; 592-31, 673-74.
2. http://www.MedicineNet.com. The Sacrum The
Holy Bone, 2003. Accessed 15th June, 2013.
3. Senoglu N, Senoglu M, Oksuz H, Gumusalan Y,
Yuksel KZ, Zencirci B et al. Landmarks of the
hiatus for caudal epidural block: An anatomical
study. British Journal of Anaesthesia. 2005; 95
(5):692- 695.
4. Edwards WB, Hingson RA. Continuous caudal
anesthesia in obstetrics. American Journal of
surgery. 1942; 57:459-464.
5. Sekiguchi M, Yabuki S, Satoh K, Kikuchi S. An
Anatomic study of the sacral Hiatus: A Basis for
successful caudal epidural Block. Clinical Journal
of Pain. 2004; 20(1): 51-54.
6. Tsui BC, Tarkkila P, Gupta S, Kearney R.
Confirmation of caudal needle placement using
nerve stimulation. Anaesth Analg 1999; 91:374-8.
7. Seema, Singh M, Mahajan A. An anatomical study
of variations of sacral hiatus in sacra of North
Indian origin and its clinical significance. Int. J.
Morphol., 2013; 31(1):110-114.
8. Shewale SN, Laeeque M, Kulkarni PR, Diwan
CV. Morphological and Morphometrical Study of
Sacral Hiatus. International Journal of Recent
Trends in Science And Technology. 2013;
6(1):48-52.
9. Vijisha P, Baskaran S. Morphometrical analysis of
sacral hiatus and its clinical significance. The
Health Agenda, 2013; 1(1): 10-14.
119
Ukoha et al.,
DOI: 10.5958/j.2319-5886.3.1.024

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Research article
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ISSN: 2319-5886
COMPARISON OF HEMATOLOGICAL PARAMETERS BETWEEN PLASMODIUM FALCIPARUM,

PLASMODIUM VIVAX AND CONTROL GROUP
*Ashis Kumar Saha1, Somnath Maitra2, Subhas Chandra Hazra3
1
Assistant Professor, 2Senior Resident, 3Professor and Head, Department of General Medicine, K P C Medical
College & Hospital, Kolkata, India
*Corresponding author email: asissaha2008@gmail.com
ABSTRACT
Aims: Malaria, a morbid disease of Tropical countries, may harmful if it cannot be diagnosed at its early phase, by
observing the changes in hematological parameters. Our aim was to compare the hematological parameters between
Plasmodium falciparum and vivax in relation to control healthy group in West Bengal. Methods and materials: In
total 238 slide or dual antigen positive patients (120= Plasmodium vivax, 118=plasmodium falciparum) clinical
hematological, renal parameters were compared. Results: In Plasmodium vivax and falciparum, male to female
ratio was 3:1 and 1.3:1 respectively. Significant elevation in erythrocyte sedimentation rate (ESR),differential
lymphocyte count, creatinine and significant lowering of platelet count, fasting blood sugar (FBS) were observed in
plasmodium vivax group, whereas, significant elevation of hemoglobin, differential monocyte count, mean
corpuscular hemoglobin concentration were seen in plasmodium falciparum group. Haemoglobin and FBS were
significantly lower, whereas, ESR, creatinine, differential monocyte count were high in vivax group, total white
blood cell and platelet count, hematocrit were low in both Plasmodium infection and mean corpuscular hemoglobin,
differential lymphocyte count were significantly low in falciparum group as compared to control group.
Conclusion: Combination of low hemoglobin, fasting blood sugar and significantly raised ESR is highly significant
in predicting severity of Plasmodium infection in patients of malaria endemic areas, which was evidenced in our
present study. P. falciparum and vivax suffered from lymphopenia and thrombocytopenia respectively.
Keywords: Hematological parameters, Plasmodium falciparum, Plasmodium vivax, West Bengal
INTRODUCTION
Malaria, a morbid disease of Tropical countries, like,
India, Pakistan, Bangladesh, is now of global
importance; because, it is responsible for 1.5 to 2
million of deaths yearly in the world1, and three fourth
of cases were suffered in India amongst 2.48 million
of malarial cases of South-East Asia.2 In Tropical
countries, where malaria is endemic, it is very
essential to differentiate malaria from other viral or
bacterial infections by symptoms and signs3 to prevent
future fatal complications, like, cerebral, renal, and
gastrointestinal. Hence in these areas, unnecessary
antimalarial treatment to treat the possible cases before

diagnosis is one of the causes of drug resistance. 4 In
India, Plasmodium falciparum (p. falciparum) and
Plasmodium vivax (p. vivax) are responsible for
malaria. This disease is transmitted by the bite of the
anopheles mosquito. Incubation period in malaria is
ten to fifteen days. After entry, the sporozoites in the
circulation in the human body, attach to the
hepatocytes through the receptors for thrombospondin
and properdin.5 In the hepatocytes, sporozoites are
transformed to schizonts. Each schizont produces a
large number of merozoites in the hepatocyte. Most of
120
Ashis et al.,
the merozoites are released into circulation. In the

circulation, each merozoite is entered in the red blood
cell (RBC) and produces 24 to 32 merozoites during
the asexual stage of the life cycle. As p. falciparum
enters the RBC, following thing things may occur.
Firstly, increased secretion of inflammatory cytokines
(tumor necrosis factor , interleukin 1, 10 and
interferon ), secondly, due to over expression of cell
adhesion molecule, endothelial cell become activated,
thirdly, coagulation cascade activation as a result of
platelet activation and endothelial damage, fourthly,
sequestration of parasitized RBC due to over
expression of cell adhesion molecule, iNOS.6-10 As a
result, there are changes in the morphology and
number in different cell lines. Now-a-days, in case of
p. vivax malaria, biochemical and hematological
parameters occur. Hematological changes include
hemoglobin, packed cell volume (Hct), total white
blood cell count (WBC), platelet count, blood glucose,
Creatinine. These changes may vary with the
nutritional status, demographic factors, individual and
environmental immunity.11 Our aim was to compare
the hematological and renal parameters between p.
falciparum and p. vivax affected patients in relation to
healthy group in West Bengal.
Inclusion criteria: Total 238 patients [120
plasmodium vivax (males 90 and females 30) and 118
plasmodium falciparum ( males 68 and females 50)]
between the ages of 2 to 80 years who were admitted
in our hospital from 2011 to 2013 years with
symptoms and signs suggestive of malaria, like, fever
with chill and rigor, headache, nausea with or without
vomiting, arthralgia, diarrhea, weakness, drowsiness,
confusion, stupor, anemia, jaundice, signs of
dehydration, hepatomegaly, and slpenomegaly, whose
blood were positive for malaria parasite in thick or thin
blood film stained by Giemsa stain and/or dual antigen
positive for plasmodium vivax or plasmodium
falciparum. They were subdivided into 2 groups
according their antigen positive type (Group A:
Plasmodium vivax (N=120), Group B: Plasmodium
falciparum (N=118)
Exclusion criteria: We excluded the patients
suffering from different infection producing sepsis,
dengue infection, viral hepatitis, Leptospirosis during
this period.
Ethical clearance: This three years study was

conducted only after getting permission from the
ethics committee of our hospital and informed consent
obtained from our patients parties.
Detailed clinical history was taken from the patient,
followed by, thorough clinical examination. Then
blood was used for thick and thin blood film, stained
with Gimsa stain, for detection of malaria parasite
under microscope and for detection of malarial antigen
of both p. falciparum and p. vivax. If at least, one
asexual form of parasite was detected in 100
microscopic fields of thick blood film examined under
microscope
using
oil
immersion
lens
(100xmagnification) it is considered as positive.
After confirmation of the diagnosis, 5 ml. of blood was
collected from each patient aseptically in a vial
containing ethylene diamine tetra acetic acid (EDTA)
and was promptly analyzed for routine hematological
parameters, which included, the following, like, total
WBC count, hemoglobin (Hb) estimation, hematocrit
(Hct), Mean Corpuscular Hemoglobin (MCV), Mean
Corpuscular Hemoglobin (MCH), mean corpuscular
hemoglobin (MCHC), erythrocyte sedimentation rate
(ESR), platelet count.
Another 2 ml. of blood was collected in a vial and
serum was separated and estimated Creatinine, blood
sugar. Hemoglobin was estimated by the acid hematin
method, PCV by Wintrobes method, blood sugar by
enzymatic method, Creatinine by the alkaline picrate
method. These are all conventional methods.
Similarly, blood from 100 patients in the healthy group
(Group C: n=100), which consist of patients party, lab
technicians having no history of disease in the recent
past or present were done of same parameters. Data
were collected and analyzed statistically.
Statistical analysis : The data were expressed in terms
of meansSD (standard deviation). Then, all the means
were compared between p. vivax and p. falciparum
group and control group separately at 95% confidence
interval using student ttest and, p value were
extracted. p value of less than 0.05 was considered as
statistically significant. In statistics, a confidence
interval (CI) is a type of interval estimate of
a population parameter and is used to indicate the
reliability of an estimate. It is an observed interval. In
applied practice, confidence intervals are typically
stated at the 95% confidence level.
121
Ashis et al.,
RESULTS
Table:1 Comparison between p. vivax and p. falciparum affected patients as compared to control group
Parameters
P. vivax
(Group A )
P. falciparum
(Group B )
Age (years)
42.8288.4
27.214.2
101.720.20
100.90.19
11.7852.1
12.321.52
ESR mm/1st hour
75.186.42
68.787.79
MCV (fl)
82.748.41
83.147.85
MCH (pg)
27.728.21
28.946.45
MCHC (g/dl)
34.181.62
35.471.48
Hematocrit
34.884.346
33.1793.136
6653.161999.0
6008.921393.5
42.1412.42
36.3915.45
10.102.17
13.596.80
42.6721.02
46.3918.18
3.014.19
4.124.79
1.452.12
1.721.64
1.61.0.61
1.81.0.91
Creatinine mg/dl
0.940.57
0.710.45
Fasting
blood
sugar mg/dl
93.818.67
100.3510.89
Temperatures
(oF)
Hemoglobin
(gm%)
Total WBC count

/cc
Differential count
lymphocyte
(%)
Monocyte
(%)
Neutrophil
(%)
Eosinophil
(%)
Basophil
(%)
Platelet
Lack/ cc
count
count
count
count
count
count
Control
Group C(100)
32.494.15
98.10.31
12.510.45
15.755.56
84.628.56
32.644.52
35.101.98
41.455.2
8096.2135.4
44.1315.87
8.684.95
43.7721.31
2.927.1
0.570.12
2.51.0.81
0.710.25
98.2511.92
95% CI$
-0.61
31.85
0.75
0.84
-1.008
-0.07
4.57
8.22
-2.47
1.67
-3.10
0.66
-1.58
-0.79
0.73
2.669
203.50
1084.98
2.17
9.32
-4.77
-2.205
-8.74
1.302
-2.25
0.04
-0.75
0.21
-293.95
39410.8
0.098
0.361
-10.46
-2.63
P value$
0.059
0.00**
0.02*
0.000***
0.704
0.204
0.000***
0.000***
0.00**
0.00**
0.00**
0.145
0.58
0.27
0.053
0.00**
0.00**
95% CI@
-7.11
27.77
3.55 3.68
P
value@
0.24
0.00**
95% CI^
P value^
-8.18
-2.39
2.73 2.86
0.00**
-0.50
0.12
51.87
55.54
-3.67
0.71
-5.21
-2.18
-0.09
0.83
-9.39
-7.14
-2362.13
-1812.44
0.22
0.00**
-1.14-- -0.30
0.00**
43.01
77.20
-4.14 0.38
0.00**
-6.73 -- 3.10
-1.14 0.70
0.00**
-7.84 -- 5.29
-1837.23
-1048.86
0.00**
-5.75 1.77
0.29
-0.57 1.77
0.01*
- 6.14 5.14
0.86
- 1.43 1.61
0.90
-0.39 2.79
0.14
-0.01 1.07
0.055
0.82 1.47
0.00**
-1.851241--70602.88
0.1090.35
0.00**
-93244 -- 46753.37
0.09-0.09
0.00**
-8.70-0.19
0.04*
-0.94
5.14
0.17
0.10
0.64
0.00**
0.00**
0.00**
0.18
0.00**
0.11
0.00**
--
- 11.93
- 3.54
2.29 5.52
-2.65 7.89
0.00**
0.000***
0.00**
0.32
1.0
$= Comparison with P.Vivax vs P. Falciparum, @= Comparison with P. Vivax vs Control, ^= Comparison with P. Falciparum
vs Control, *Significant, **Very significant, ***extremely significant
A. Characteristics of the studied population In case

of p. vivax, affected male (n=90) to female (n=30)
ration was 3:1, whereas, in case of falciparum
(male=68, female=50), it was 1.36:1. Temperature
in both p. vivax and p. falciparum groups were
significantly raised as compared to control group.
B. Comparison of hematological parameters between
p. vivax (120) and p. falciparum (n=118) group
P. vivax showed a significant elevation in ESR
(75.186.42 vs. 68.787.79 mm / 1st hour,
p=0.00),
differential
lymphocyte
count
[(42.1412.42) % vs. (36.3915.45) %, p=0. 00],
creatinine (0.940.57 vs. 0.710.45 mg/dl, p=0.
00) and significant lowering of platelet count
(161792.4561165.62
vs.
181350.8791122.45/cc, p=0. 05) Fasting blood

sugar level (93.818.67 vs. 100.3510.89 mg/dl,
p=0. 00) as compared to p. falciparum group.
Whereas, p. falciparum group showed a significant
elevation in hemoglobin (12.321.52 vs.
11.782.1 gm/dl, p=0.02), differential monocyte
count [(13.596.80) % vs. (10.102.17) %], and
MCHC (35.471.48 vs. 34.181.62 g/dl, p=0.00),
and significant lowering of WBC count
(6653.161999.01 vs. 6008.921393.56 /cc,
p=0.00), as compared to p. vivax group.
C. Comparison of hematological parameters between
p. vivax group (n=120) and control group (n=100)
In p. vivax group, hemoglobin (11.782.1 vs.
12.510.45 gm/dl, p=00), MCH (27.728.21 vs.
122
Ashis et al.,
32.64 4.52 pg, p=0.00), Hct (34.884.34 vs.

41.455.2,
p=0.00),
total
WBC
count
(6653.161999.01 vs. 8096.2135.41 /cc, p=0.00),
total platelet count (161792.451165.62 vs.
251350.1081315.62 / cc, p=0.00), fasting blood
sugar level (93.818.67 vs. 98.2511.92 gm/dl,
p=0.04) were significantly low as compared to
healthy control group. Whereas, in former group
showed significantly raised ESR (75.186.42 vs.
15.755.56 mm / 1st hour, p=0.00), differential
monocyte count [(10.102.17) % vs. (8.684.95)
%, p=0.01] and serum creatinine (0.940.57 vs.
0.710.25 mg/dl, p=0.00) as compared to later
group.
D. Comparison of hematological parameters between
p. falciparum group (n=118) and control group
(n=100) -- MCH (28.946.45 vs. 32.644.52 pg),
Hct (33.173.13 vs. 41.455.2, p=0.00), total
WBC
count
(6008.921393.56
vs.
8096.211035.41), differential lymphocyte count
[(36.3915.45) % vs. (44.1315.87) %, p=0.00]
total platelet count (181350.8791122.45 vs.
251350.1081315.62 /cc, p=0.00) were reduced
significantly in p. falciparum group, whereas, ESR
(68.787.79 vs. 15.755.56 mm /1st hour),
differential monocyte count[(13.596.80) % vs.
(8.684.95) %, p=0.00], basophil count
[(1.721.64) % vs. (0.570.12) %, p=0.00] were
raised significantly as compared to control group.
DISCUSSION
After the development of the microscope by Antonie
Van Leeuwenhoek in the 15th century, diagnosis of
many parasitic diseases including malaria was
possible. Moreover, in the last three decades, many
more investigation methods have come into action,
thus refine and modify our diagnosis. Due to huge cost
for development Newer tests based on serology
(Falkon assay screening test ELISA (FAST-ELISA,
Rapid antigen detection systems (RDTs), real-time
polymerase chain reaction, loop-mediated isothermal
amplification
(Lamp
and
Luminex),
mass
spectrometry12 to diagnose accurately the malaria
infection at its earliest phase, direct microscopy and
sociological methods and hematological parameters
for supporting diagnosis are still the gold standard for
the diagnosis of malaria infection.
Ashis et al.,
In our present study, male to female ratio were 3:1,

1.36:1 in p. vivax and p. falciparum respectively. But,
when we considered the total number of affected
patients, the ratio was 1.97:1, whereas, in the study
done by Muwonge H et al. The ratio was 2.5:1.13 In a
study done by Hussain M M et al14. The ratios were
1.73:1 and 2:1 at p. vivax and p. falciparum
respectively. Our study showed the extreme male
preponderance over female in case of p. vivax
infection than p. falciparum infection.
Mean age of incidence of malaria in our study in p.
vivax, p. falciparum and control group were
42.8888.4 years, 27.214.2 years and 32.494.15
years respectively, which showed an age incidence in
p. falciparum was close to the control group. But in a
study done by Hussain M M et al14 age incidence were
29.251.9 years, 27.982.4 years and 29.482.6 years
in p. vivax, P. falciparum and control group
respectively, which showed an age incidence in the
case of p. falciparum group was nearer to the our value
(, 27.214.2 years), whereas, in the case of p. vivax
group, age incidence was much higher in our study
than the study of Hussain M M et al14 (42.8888.4
years vs. 29.251.9 years).
P. vivax, p. falciparum and control groups in our study
showed mean axillary temperature of 101.70.01o F,
100.90.1o F and 98.10.31o F respectively, which
was higher as compared to the study done by Hussain
M M et al (99.650.1o F, 98.910.3o F and 97.680.1o
F in p. vivax, p. falciparum and the control group
respectively). 14
In malaria, anemia is multifactorial in originlike,
hemolysis of parasitized and non-parasitized RBC,
depressed or ineffective erythropoiesis15, nutritional
deficiency, especially in case of females, blood due to
hook worm infestation (which is most common in
West Bengal), decreased erythrocyte production. 16
Present study demoed significantly low hemoglobin in
p. vivax group (11.7852.1 gm/dl) as compared to the
p. falciparum group (12.321.52 gm/dl, p=0.02) and
control group (12.510.45 gm/dl, p=0.00). This
observation is not consistent with previous reports of
Plasmodium infection, in which, hemoglobin
degradation resulting anemia had a good correlation
with severity of infection due to p. falciparum.17 In
present study, low hemoglobin may be due to
nutritional deficiency or increased blood loss in
association with hemolysis of parasitized or nonparasitized RBCs.
123
In our present study, ESR was significantly raised in p.

vivax than in p. falciparum (75.186.42 mm/1st hour
vs. 68.787.79 mm/1st hour) as shown in other study
done by Hussain M M et al (82.195.1 mm/1st hour vs.
77.794.5 mm/1st hour).14 Again, combination of low
hemoglobin and raised ESR, as shown in our study,
was highly significant hematological parameters in
predicting p. vivax malaria infection in endemic areas
in patients who are symptomatic, but false smear
negative or serologically negative due to very low
parasitemia, as shown in other studies done by Erhart
et al18 and Gerardin et al.19
Mean value of total WBC count was significantly low
in p. falciparum group as compared to p. vivax group
(6008.921393.56/cc vs. 6653.161999.01, p=0.00).
Commonly, the total WBC count is within normal
range20, 21, except, in a few studies, where there was
evidence of leucopenia. 21, 22 In our present study, in p.
falciparum group, there was also leucopenia, which
was also consistent with other Indian study done in
malaria endemic area, where there was also evidence
of leucopenia.23 In Panama22 and Turkey24, also there
were evidences of leucopenia in cases of p. vivax, p.
falciparum and dual infection.
In our present study, there was significant reduction
differential lymphocyte count in p. falciparum
((36.3915.45) %, p=0.00) as compared to p. vivax
(42.1412.42) % and control group (44.1315.87) %.
Usually, differential lymphocyte count in acute
malaria, varies with the increase or decrease in
differential WBC lines. Hence, in respect to
differential lymphocyte count, varying reports
(increase, decrease or normal) were observed in
different studies in case of acute malaria infection21.
According to recent literature, lymphopenia may occur
in non-immune adult21, 25 and in children in endemic
areas. 17, 21 In the present study, though, the differential
lymphocyte count was within normal range, but, it was
in the low range of normal in p. falciparum group. The
factors responsible for transient lymphopenia are:
firstly, tissue distribution of lymphocytes26 from freely
flowing blood stream to the endothelial lining of the
blood vessels to adhere27, secondly, lymphocyte
destruction due to Fas-induced apoptosis. 28 Owing to
the high rate of lymphocyte destruction in p.
falciparum affected patients, both absolute and
differential count will be low.29 This may explain why
mean total lymphocyte counts was in lower range of
normal in p. falciparum group.
Ashis et al.,
Usually, phagocytes (Neutrophil and macrophages)

and/or natural killer [NK] cells are the effector cells,
been activated as a result of an immune response to
blood borne pathogens. So, obviously, an early
pathological hall-mark in acute malaria is reticuloendothelial cell hyperplasia involving macrophages.21
Monocytosis was the constant hematological finding
in different studies of acute malaria17, 30-32 as well as, in
our present study, where significant monocytosis were
observed in both p. vivax and p. falciparum groups
[(10.102.17)%, vs. (13.596.80)%,], as compared to
control group[ (8.684.95)% p =0.01].
In our study, mean neutrophil count was within normal
range as compared to control group [p. vivax=
(42.6721.02) %, p. falciparum= (46.3918.18) %,
control group = (43.7721.31) %], which was
consistent with the other study in India31, where 85%
of patients had normal Neutrophil count, as well as,
study done in Singapore.33 Though, few studies
demonstrated neutropenia27, which may be the result
of increased margination and sequestration of
neutrophils due to increased expression of cell
adhesion molecules [ICAM1 and VCAM1]
occurred in acute malaria. Some earlier studies
demonstrated neutrophilia also.17
Though our study showed no difference in eosinophil
count in p. vivax and p. falciparum [(3.014.19) %,
(4.124.79) % ] as compared to control (2.927.1) %,
but few studies in the world34, showed evidence of
eosinopenia, whose significance was not explained.
But, during recovery, these patients showed rebound
neutrophilia34, which was explained as the result of
enhanced T-helper2 cell response, which occurred
during this period.
Now-a-days, lots of work have been going on
regarding the platelet hemostasis in acute malaria,
because of the fact that, complexes of platelet and
coagulation factors surround the flowing and
sequestrated parasitized RBCs and enclose vascular
endothelium.21 The different studies on acute malaria
in the world17,23, 31, 35, 36 showed that the magnitude of
thrombocytopenia varied according to species and
severity of infection. It was also shown that p. vivax
group was associated with severe thrombocytopenia
than p. falciparum group. Similarly, our present study
showed thrombocytopenia in p. vivax group was more
severe than that in p. falciparum group
(161792.4561165.62
/cc.
vs.
181350.8791122.45/cc), though the count was within
124
normal limit, as compared to control group

(251350.1081315.62/cc). This thrombocytopenia
stimulates bone marrow to produce an increased
number of megakaryocytes, which ultimately produce
megaplatelets and leave the bone marrow to enter the
circulation;
the
stimulating
factor
being
thrombopoietin, a key platelet growth factor, which
was described in the study done by Cyril et al37. As a
result of increased number of megaplatelets, mean
platelet volume will be increased during acute malaria
infection.17, 23.
The pathophysiology of thrombocytopenia is
multifactorial. Firstly, splenic sequestration of RBC,
secondly, antibody mediated platelet dysfunction,
thirdly, release of adenosine diphosphate (ADP) as a
result of hemolysis of parasitized RBCs, fourthly,
abnormal megakaryocytosis, fifthly, invasion of
platelets by parasites, sixthly, phagocytosis of
platelets, seventhly, oxidative stress.21, 38
In our present study, MCHC was significantly reduced
in p. vivax group as compared to p. falciparum group
(34.181.62 g/dl. Vs. 35.471.48 g/dl, p=0.00), but,
only MCH were reduced in both groups as compared
to control group (p. vivax = 27.728.21 pg., p.
falciparum = 28.946.45 pg., control = 32.644.52
pg.). But, all the RBC indices were within normal
limits, which may be due to the following factors:
firstly, low production of cytokines, secondly, less
endothelial cell activation; thirdly, milder changes in
coagulation profile, fourthly, diminished sequestration,
fifthly, decreased hemolysis in less severe malaria.
Our present study demoed significantly raised serum
creatinine level in p. vivax group as compared to p.
falciparum (0.940.57 mg/dl, vs. 0.710.45 mg/dl.,
p=0.00) and control group (0.710.25 mg/dl.). This
study was consistent with the study done by Ogdaboyl
E O et al39 and Delanghe J et al40, in which, raised
creatinine was seen in the Nigerian population. The
elevated serum creatinine is probably due to
ineffective filtration ability as a result of renal
functional impairment.
In our study, plasma glucose level was lower in p.
vivax group (93.818.67 mg/dl) as compared to p.
falciparum group (100.3510.89 mg/dl) and control
group (98.2511.92 mg/dl). This low blood glucose
levels as well as low hemoglobin level are the two
most reliable indicators and hematological parameters
in predicting the presence of p. vivax malaria as shown
in other studies also18, 19.
CONCLUSION
Malaria infection was twice more common in males
than females. Younger age group was the victim of
plasmodium falciparum, whereas, plasmodium vivax
affected higher age group.
Plasmodium
vivax
affected patients were more anemic. The combination
of low hemoglobin, low fasting blood sugar and
significantly raised ESR is highly significant in
predicting severity of Plasmodium infection in patients
of malaria endemic areas, which was evidenced in our
present study. Lymphopenia was observed in
Plasmodium falciparum affected patients, whereas,
thrombocytopenia in Plasmodium vivax affected
patients, but, significant monocytosis was observed in
both groups. Significantly reduced MCHC was
observed in Plasmodium vivax groups, whereas, MCH
was reduced in both groups.
Conflict of interest: Nil.
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dysfunction in malaria patient in Minna, North
Central Nigeria. Online J. Health Allied Sci. 2009;
8(3):8
40. Delanghe J, De Slypere JP, De Buyzere M,
Robbrecht J, Wieme R, Vermeulen A. Normal
reference values for creatine, creatinine and
carnitine are lower in vegetarians. Clin. Chem.
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NONLINEAR DYNAMIC ANALYSIS OF VOICE: A NORMATIVE STUDY IN THE INDIAN

POPULATION
Jacqueline B. Fernandes1, *Radish Kumar Balasubramanium2, Arivudai Nambi Pitchaimuthu2, Jayashree S. Bhat3
1
II MASLP, 2 Associate Professor, 3Professor & Head, Department of Audiology and Speech Language Pathology,
Kasturba Medical college (Manipal University), Mangalore, India.
*Corresponding author email: radheesh_b@yahoo.co.in
ABSTRACT
Background: The aim of this study was to establish normative data for the Indian population using Nonlinear
dynamic analysis. In this study, correlation dimension, a measure of nonlinear dynamic analysis was performed for
normophonic young, middle aged and elderly voices. Materials and Methods: For this purpose, normophonic
young, middle aged and elderly individuals were selected without a history of voice/respiratory problems and
vocal abuse/ misuse. 60 participants were selected in each group. All of these individuals had a normal voice as
evaluated through GRBAS scale. Sound Recorder, on a computer desktop was used for voice recording and
convert code in MATLAB as well as D2.ini.writer software based on TISEAN package (Hegger, Kantz &
Schreiber, 1999) was used for the calculation of Correlation dimension (D2). Correlation dimension measures
were obtained for each participant, for both steady vowel phonations (/a/, /i/, /u/) as well as narration samples.
Results: The correlation dimension measures across the group revealed a significant main effect of the groups
indicating correlation dimension increases with increase in age. Conclusions: The application of nonlinear dynamic
measures in the assessment of voice is a novel venture and thus this study provides normative data for
correlation dimensions in the Indian population for future comparisons against the disordered voice samples.
Further studies are warranted to investigate the same in the clinical population. Also other nonlinear dynamic
analysis methods need to be investigated to obtain the normative data in the Indian population.
Keywords: Nonlinear dynamic analysis, Correlation dimension, Normophonic voice,
INTRODUCTION
Acoustic analysis does not appraise completely the
true nature of the underlying vocal fold function. Yet,
acoustic analysis is still used in the voice assessment
due to some level of correspondence between voice
production and voice acoustics. Though not perfect,
much can be inferred about the vocal physiology
based on the acoustic analysis. A normal voice signal
is said to be quasi periodic and must have very
minimal cycle to cycle variability in frequency as
well as amplitude. When the voice is periodic and/or
nearly periodic, measures such as Jitter and Shimmer

are reliable whereas they are unreliable in the case of
severely perturbed voices due to the difficulty in
identifying cycle boundaries. Due to this reason,
traditional measures such as jitter, shimmer have lost
their value in the assessment of aperiodic voices.
Nonlinear dynamic analysis endeavor to recognize
and explain the presence of rules underlying the
random nature of a severely perturbed voices. This
approach considers the severely perturbed voices as
128
Jacqueline et al.,
Int J Med Res Health Sci. 2014;3(1);128- 132
chaotic in nature. Chaos theory believes that

erratic looking temporal behavior does not arise
randomly, but is deterministic in nature i.e., initial
condition(s) determines the end result based on some
law/rule.1 A potential advantage of this method,
when compared with traditional perturbation
measures of the voice signal, is the possibility of
objectively quantifying dysphonia severity without
the requirement of cycle boundary detection. Also,
non linear methods have the capability of analyzing
all the types of voice signal (periodic as well as
aperiodic voice). There are two most commonly
used nonlinear methods which include phase space
portraits and the subsequent computation of
correlation dimension.2
Usually, voice waveform data are entrenched in phase
space and then reconstructed using the method of lag
variables or delay coordinates.3 A periodic signal will
show a closed trajectory in phase space, with
increasing perturbation resulting in irregular or
chaotic trajectories.3-5 Though vocal fold vibration is
graphically represented as a trajectory in phase space
with time,2 further computation is required to
objectively quantify the complexity of the signal in
space.
Correlation dimension (D2) is one such measure that
quantifies the complexity of the signal by specifying
the number of degrees of freedom (ie, dimensions)
needed to describe a dynamic system like voice.5 If
the dynamics of a system can be determined to be low
dimensional, then a complex determinism may exist,
which is responsible for the observed signal profile.6
Alternatively, more complex the system, greater the
number of degrees of freedom are required to
describe its dynamic state, and the higher the
correlation dimension. These nonlinear dynamic
methods have been analyzed in both pathological and
non pathological voice samples5, 7-9 in several studies.
In the modern clinical outlook, its popularity is
limited. Also, there are no normative available in the
Indian context. Hence, the present study is an attempt
in this direction. Results of this study would guide the
speech language pathologist in a more efficient
assessment and management of voice disorders.
Aim of the study: To obtain a normative data for
voice using Non Linear Dynamic Analysis.
METHOD
This study followed a cross sectional normative
study design, with Non Random Convenient
Sampling. The institutional ethical approval was
obtained prior to the conduct of the study. Participants
were alienated into three different groups based on
age10 which are as follows:
Table 1: Age Range Classification10
AGE RANGE
GROUP NAME
18 40 Years
Young Adults
41- 60 Years
Middle Aged Adults
61 Years & Above
Older Adults
Each group consisted of 60 individuals out of which
30 were females and 30 were males. All the
participants were normal healthy individuals
without any history of vocal abuse/misuse,
smoking, neurological, organic and non organic
vocal pathological conditions. All the participants
had a normal voice as evaluated perceptually by
three trained speech pathologists using the GRBAS
(Grade Roughness Breathiness Asthenia Strain)
scale.11 Prior to the study an informed consent was
obtained from all the participants.
Instrumentation: Sound Recorder, a computer device
was used for recording of the voices. A dynamic
microphone was used to record voice. Adobe
Audition (version 3.0) was used for noise reduction
from the samples. Correlation Dimension was
o bt ai ned by means of M AT L A B (matrix
laboratory) developed by Math Works and
D2.ini.writer software based on TISEAN package.12
Procedure:
During the voice sample recording, the participants
were seated in a comfortable chair. All the voice
samples were directly recorded in Sound Recorder
using a dynamic microphone. The distance between
the microphone and the participants mouth was
constantly maintained at 10 cm. After a brief period
of familiarization, the participants were instructed to
phonate vowel /a/ at their habitual loudness and pitch
as if the vowel was a word in a conversation, and
were also instructed to avoid singing it. The task
was demonstrated to each participant and
instructions were repeated as and when required. The
task was repeated if the experimenter felt that the
voice produced did not sound like their habitual voice
production. The recordings were carried out in a
129
Jacqueline et al.,
sound treated room in a single sitting for all the

participants. Similarly, a narration sample was also
recorded using the same set up. A common topic that
was maintained for narration was home.
Analysis: The pre recorded voice samples collected
for each participant was individually analyzed by
means of a code written using MATLAB. The
recorded voice samples were stored in .wav format.
The voice samples were then fed into MATLAB by
means of a convert code in order to transform it
into .txt file format. Once the .txt format was
obtained the file was then fed into a D2.ini.writer
based on the TISEAN package12 in order to obtain the
embedding
dimension
values.
(Correlation
Dimension, D2). A total of 15 correlation dimension
values were obtained for each sample. The mean
values for every dimension were calculated in
order to obtain a normative range across the three
age groups as well as to compare the variation
amongst the three age ranges.
RESULTS
The present study was carried out with an aim to
obtain normative data for the acoustic analysis of
voice using Non Linear Dynamic Analysis. Age
related differences were analyzed using one way
ANOVA with bonferronis post hoc test.
Fig. 1: Mean dimension values for sustained vowel

/across the three groups.
The above figure depicts no significant change
amongst the three groups until the 7th dimension at
p>o.05. However, a gradual increase in the mean
dimension values was observed in older adults beyond
the 8th dimension at p<0.05. Young and middle aged
adults displayed similar profiles in the mean
correlation dimension values.
Fig. 2: Mean dimension values for narration across

the three groups.
The above figure indicates differences in the
correlation dimension values across the three
groups. Older adults showed a higher dimension
value in comparison to young adults at p<0.05. The
middle aged adults depicted a comparatively reduced
mean value when compared with younger and older
adults at p<0.05.
The results revealed significant differences for
phonation of vowel /a/, and narration at p < 0.05.
DISCUSSION
With the development of nonlinear vocal fold models,
studies have put forward the means of assessing
nonlinearity in the voice signal through various
methods. These methods provide quantifiable data
by considering the chaotic components in a voice
signal. Various nonlinear dynamic analysis methods
have been described in the literature. These include
the development of phase space portraits, attractors,
and the use of correlation dimension, all of which
have produced variable results. In the present study,
correlation dimension was used to characterize the
normal voice samples across adults and geriatric in
Indian population. Results of one way ANOVA
revealed that the correlation dimension measures
across the group revealed a significant main effect
of the groups i.e., as the age increases, correlation
dimension values increases. This suggests that as the
age increases, complexity in the laryngeal mechanism
also increases thereby providing chaos in the vocal
fold vibration.
Sulica reported that the age related anatomical
changes occurs in the laryngeal system such as
degenerative changes to the lamina propria and the
130
Jacqueline et al.,
mucosal glands in the larynx, all of which results in

reduced production of laryngeal mucus which further
causes intermittent alteration in vocal fold vibratory
patterns thereby inducing changes in pitch, loudness
and quality as well.13 Thus, it can be stated that non
linearity is inherent in the laryngeal mechanism with
the presence of chaos in the voice production.
Higher correlation dimension values were reported in
systems that have more chaos or deterministic noise.
They suggest that the anatomical alterations in the
vocal mechanism that occur for any pathological
conditions result in higher values of correlation
dimension. Hence, we can opine that anatomical
alterations in the vocal mechanism that are exhibited
by aged individuals could be the underlying cause for
obtaining higher correlation dimension measures in
this study.14 Baken reported that the Fractal dimension
values are representative of the vibratory function of
the vocal folds.15 Baken considered vocal folds to be
oscillators whose movements if affected by means of
any change in the vocal mechanism be it due to aging
or organic pathology results in irregularity or chaos in
the regular oscillations of the vocal folds. This
irregularity in oscillation caused an increase in the
value of the fractal dimension.15
Alternatively, a study carried out by Nicollas et al16
in children aged 6-12 years using nonlinear dynamic
analysis reported that correlation dimension measure
decreased with increasing age in children. Their
results were attributed to several factors. The main
factor considered amongst them was the evolution of
the pediatric larynx.14,17 In support of this view, Eckel
et al17 reported that the subglottic airway rapidly
increases during the first 2 years and then follows a
linear mode. During the same period, fundamental
frequency decreases from 450 to 300 Hz, while
membranous vocal fold increase by 1 mm.
Histologically, it is well known that the collagen
distribution in the vocal folds varies with age, with
large variations in collagen fiber type occurring
during the period between 6 years and mutation,
corresponding to the pre mutation.18 These
histological changes, though not measured in the
present study would have contributed to increased
correlation dimension values in the older adults.
However, it is interesting to note that correlation
dimension values were more for young adults in
comparison to middle aged adults. The explanation for
this was unclear.

Thus, nonlinear dynamic analysis of voice
provided a quantifiable data on the age related
changes in the voice production. It was evident that
as the age increases, complexity of dimensions also
increases with the decreased predictability of geriatric
voices. This effect was pronounced in both phonation
as well as the narration samples. Thus, it can be
considered as a useful tool in the assessment of voice.
However, it cannot replace the existing voice analysis
techniques available to the voice clinician. Yet, it
may add to the battery of voice assessment
procedures.
CONCLUSION
The application of nonlinear dynamic measures in the
assessment of voice is a novel venture and thus, this
study provides normative data for correlation
dimension in the Indian population for future
comparisons with disordered voice samples. The
correlation dimension measures across the group
revealed a significant main effect of the group
indicating that, correlation dimension values increases
with increase in age. Further studies are warranted to
investigate the same in the clinical population.
Moreover, another nonlinear dynamic analysis
methods need to be investigated to obtain the
normative data in the Indian population.
ACKNOWLEDGMENT: We thank our Dean,
Kasturba Medical College (Manipal University),
Mangalore for permitting us to carry out the study.
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DC: Joseph Henry Press; 1997.
2. Jiang JJ, Zhang Y, McGilligan C. Chaos in
voice, from modeling to measurement. Journal of
Voice. 2006; 20: 2-17
3. Herzel H, Berry D, Titze IR, Saleh, M. Analysis
of voice disorders with methods from nonlinear
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Zanaret M, Triglia JM. Nonlinear Behavior of
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5. Zhang Y, Jiang JJ, Wallace MS, Zhou L.

Comparison of nonlinear dynamic methods and
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Perturbation and nonlinear dynamic dnalysis of
different singing styles. Journal of Voice.
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the normal swallow: characterization by age,
gender, and bolus volume. Annals of Otology
Rhinology and Laryngology. 2002;111: 623-32.
11. Hirano M. Clinical examination of voice. New
York: Springer verlag; 1981.
12. Hegger R, Kantz H, Schreiber T. Practical
Implementation of Nonlinear time series
methods: The TISEAN package, CHAOS: An
interdisciplinary Journal of Nonlinear Sciences.
1999: 9; 413 - 17.
13. Sulica L. Voice Medicine: The Ageing Voice.
Voice and Aging Sciences. ; 2009 [cited].
Available
from:
http://www.voicemedicine.com/aging.htm.
14. Jiang JJ, Zhang Y, Stern J. Modeling of chaotic
vibrations in symmetric vocal folds. Journal of
Acoustical Society of America. 2001; 110: 212028
15. Baken RJ. Irregularity of Vocal Period and
Amplitude: A first approach to Fractal Analysis
of Voice. Journal of Voice. 1994; 4: 185 97
16. Nicollas R, Garrel R, Ouaknine M, Giovanni
A, Nazarian B, Triglia, MJ. Normal Voice in
Children Between 6 and 12 Years of age:
Database and Nonlinear Analysis. Journal of
Voice. 2008; 22: 671-75
17. Eckel HE, Koebke J, Sittel C, Sprinzl GM,
Pototschnig C, Stennert, E. Morphology of the

human larynx during the first five years life
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Otology, Rhinology and Laryngology. 1999; 108:
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18. Hacki T, Heitmuller S. Development of the
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COMPARISON OF THE EFFECT OF MIME THERAPY VERSUS CONVENTIONAL THERAPY ON

THE SUNNYBROOK FACIAL GRADING SYSTEM IN PATIENTS WITH ACUTE BELLS PALSY
*Mistry Gopi S1, Sheth Megha S2, Vyas Neeta J3
1
Post graduate student, 2Lecturer, 3Principal, SBB College of physiotherapy, Ahmedabad, Gujarat, India
*Corresponding author email:gtgopi2007@gmail.com

ABSTRACT
Background: Facial resting symmetry and expressions are determinants of facial attractiveness & being a marker of
good health. Mime therapy is a combination of mime and physiotherapy and aims to promote symmetry of the face
at rest and during movement. The objective of this study is to compare the effect of Mime therapy and conventional
therapy on the facial functions in patients with acute Bells palsy. Method: The quasi-experimental study was
conducted at SBB College of physiotherapy. A convenience sample was taken consisting of 30 participants, 10 in
each group. Group A received Mime therapy. Group B, conventional therapy and Group C received home exercise
program. Facial symmetry at rest and movement was assessed through Sunnybrook facial grading scale (FGS) after
completion of 10 sessions to each group. At the end of treatment, response to treatment was assessed by the
Patients global impression of change scale (PGIC). Level of significance was kept at 5%. Result: Analysis of
variance was used to compare all outcomes. At the end of 10 sessions, scores on Sunnybrook FGS (p<0.001) and
PGIC (p<0.001) shows significant difference within and between groups. Post hoc Bonferroni test was used for
multiple comparisons. FGS shows significant differences between groups A&B (p<0.001) and groups A&C
(p<0.001). But no significant difference was seen between groups B&C(p=1.00). PGIC scale shows significant
differences between groups A&B (p<0.001) and A&C (p<0.001) but no significant difference was seen between
groupsB&C (p=1. 00). Conclusion: Mime therapy improves facial symmetry and functions more than conventional
therapy and home exercises in people with acute Bells Palsy. No difference was found between conventional
therapy and home exercise program.
Key words: Bells palsy, Mime therapy, Sunnybrook facial grading system, Patients Global Impression of change
scale, electrical stimulation.
INTRODUCTION
The term Bells Palsy is defined as an idiopathic, acute
and unilateral paresis or paralysis of the face which
may be partial or complete occurring with equal
frequencies on right and left sides of the face.1 The
major cause of Bells Palsy is idiopathic, accounting
for 50% of all cases. Other few suggested causes are
exposure to cold, middle ear infections, dental and
ENT surgeries and traumatic.2 The problems faced in
acute phase of Bells palsy include difficulty in closing
the affected side eye, facial deviation to the unaffected

side, difficulty in drinking, eating and speaking along
with psychological problems and facial appearance is
the main concern in any phase of Bells palsy.2,4 Facial
palsy is classified according to House and Brackmann
score into 6 grades, where grade 1 is normal, grade 2
has slight dysfunction, grade 3 has moderate
dysfunction, grade 4 has moderate to severe
dysfunction, grade 5 has severe dysfunction and grade
Gopi et al.,
133
6 has total paralysis.3 Mime therapy consists of auto

massage, stretching with facilitation exercises,
relaxation, inhibition of synkinesis and coordination
and emotional expression exercises.4
A Cochrane review done by Teixeira LJ et al in
February 2011 has concluded that there is only very
low quality evidence that facial exercise reduces
sequel in acute cases.5 Facial symmetry is a
determinant of facial attractiveness, it is a marker of
good health and it influences interpersonal attraction.6,
7
Bells palsy can dramatically affect, patients general
quality of life and expressions and interpersonal
communications. Patients with bells palsy suffer not
only the functional consequences of impaired facial
motion but also the psychological appearance of
skewed facial deviations.8 Less evidences are available
for the effectiveness of mime therapy in improving
facial symmetry in acute phase management in Bells
palsy, so arises the need of the student. The objective
of this study is to assess and compare the effect of
Mime therapy and conventional therapy on the facial
symmetry and functions in patients with Bells palsy
in the early stage of paresis.
METHODOLOGY
A Quasi experimental study was conducted at SBB
College of physiotherapy and convenience sampling
was used. The study consisted of 30 participants, 10 in
each group. The study was carried out from June 2013
to October 2013. Inclusion criteria: Males and
females diagnosed with Bells palsy in the age group
of 18-70 years with acute onset (1-3wks) and no other
neurological deficit involving the face were included.
Exclusion criteria: Subjects with a history of surgical
intervention for the ear and facial nerve palsy, pain of
any other origin and non co-operative patients were
excluded. Materials used were powder, mirror,
standard electrical stimulator with accessories and
infra red lamp. Outcome measures used were 13-item
Sunnybrook facial grading system (SBFGS) 8 and the
Patients' Global Impression of Change (PGIC) scale. 9
SBFGS includes 3 components resting symmetry,
symmetry of voluntary movement and synkinesis.
Resting symmetry of 3 components are checked eye,
cheek (naso labial fold) and mouth. In symmetry of
voluntary movements there are 4 components for
standard expressions and grades are given according to
the symmetry during movements; in synkinesis again
Gopi et al.,
there are 4 grades according to the amount of

synkinesis.
The study was reviewed & approved by the
Institutional Ethics Committee, SBB College of
Physiotherapy, V S General Hospital, Ahmedabad,
Gujarat.
Subjects were explained the procedure and purpose of
the study & written informed consent was taken.
After initial neurological examination the participants
were assigned randomly into three groups, Group A:
Mime therapy group, Group B: Conventional therapy
group and Group C: Home exercise group. Then
severity of the condition was measured by Sunnybrook
Composite Score (SBC) pre treatment and post
treatment.
Group A was given 10 sessions of Mime therapy
which included auto massage- effleurage and kneading
for 10 to 15minutes on both the sides of the face,
stretching exercises of the muscles of the affected side
followed by facilitation, specific low intensity
exercises to co-ordinate both the halves of the face,
active assisted exercises for affected side of the face,
exercises of mouth and eye with simultaneous
inhibition of synkinesis if present. A mirror was used
for biofeedback. Exercises to increase participants
awareness of lip movements such as a,e,i, o etc.
GroupB was given Electrotherapy (Conventional
therapy) for 10 Sessions. It included
Infrared
radiations (up to 7 days from the date of onset) to
affected side followed by electrical stimulation
(Surged Faradic current) of affected muscles with 3
sets of 30 contractions for each nerve trunk. Exercise
program to all facial muscles was given as below.
Group C was a control group. They were given 10
Sessions of home exercise program including,
massage, facial muscle exercise program in front of
mirror, 5-6 times in a day and home advices.
Level of significance was kept at 5%.
RESULTS
Analysis of results was done with SPSS version 16.0.
ANOVA (Post Hoc Bonferroni test) was used to
analyze the difference in facial symmetry post
intervention in 30 patients with acute Bells palsy. The
mean age of the participants was 44.1 years in group
A, 46.2 years in group B and 41.9 years in group C.
There were 6 females and 4 males in groups A and B
and 5 males and 5 females in group C.
134
Post hoc analysis of SBFGS showed that there was

B (p<0.001) and group A & C (p<0.001) but no
statistically significant difference between group A
significant difference between group B & C (p=1.00).
and B (p<0.001) and Group A and C (p<0.001) but no
Table 1 show that differences in mean Sunnybrook
significant difference between group B and C
Composite (SBC) scores in all three groups is
(p=1.00). Post hoc analysis of PGIC showed there was
statistically significant. (p<0.001)
statistically significant difference between group A &
Table 1: Comparison of mean composite score of SBFGS (Mean SD)
Variable
Group A
Group B
Group C
F value
p value
SBC(Pre)
38.514.5
33.615.79
38.512.31
SBC(Post)
86.26.81
53.812.79
60.919.5
SBC(Diff)
48.215.31
23.010.88
**- Very significance, SBC- Sunnybrook composite score
Table 2: Comparison of total score of PGIC (Mean SD)
Groups
MeanSD
23.413.06
A
B
C
6.600.699
3.700.675
4.001.15
11.935
F value
p value
33.498
<0.001**
<0.001**
**-very significance
DISCUSSION
The present clinical trial was conducted to study the
effect of Mime therapy on facial symmetry in patients
with acute Bells palsy. The SBFGS used to evaluate
severity of facial nerve paresis, included three
components resting symmetry, voluntary movements
and synkinesis.10
In the present study, asymmetry has reduced in all
three groups but more in a Mime therapy group than
others. This improvement may be because massage
improves circulation and maintains muscle properties.
Visual feedback has shown to control muscle activities
in facial muscles.11 Also miming demands highly
refined sense of body and muscle control. A study
done by Ryan J, 2009 has concluded that massage
done in mime therapy has shown to create new growth
and increase production of collagen and connective
tissue in facial muscles and restore facial muscle
action.12 Study done on mime therapy efficacy in
patients with long term facial nerve paresis shows that
mime therapy improves facial symmetry13. In
accordance with a study of Cronin and Steenerson
(2003) biofeedback by surface electromyography
results revealed improvement in facial symmetry.14
Ahmad SJ and Rather AH (2012) did a prospective
study of physical therapy in facial nerve paralysis and
found that physiotherapy in the form of electrotherapy
Gopi et al.,
and facial exercises has an effective role in the early

management of peripheral facial paralysis. 15
Because the effectiveness of therapeutic changes
differs greatly among patients, it is essential that
effectiveness of trials directly measure patient related
improvement and satisfaction with treatment. 15 The
PGIC is patient-reported, and asked the subject to
indicate how you feel now, compared to how you felt
before receiving treatment in this study on a 7-point
scale.
The cost of the treatment is low as along with therapy
at physiotherapy center, home program is an integral
part of the treatment. 9 So mime therapy is a good
choice of treatment for people with bells palsy.
Thus Mime therapy can be used in the treatment of
people with acute Bells palsy to get improvement in
facial asymmetry within a shorter period of time.
Limitations of the study are that subjects were not
followed up for a longer period of time.
Randomization was not done. Home exercise protocol
was not supervised.
CONCLUSION
Mime therapy improves facial symmetry and functions
more than conventional therapy and home exercises in
people with acute Bells Palsy. No difference was
135
found between conventional therapy and home

exercise program.
Conflict of interest: Nil
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136
DOI: 10.5958/j.2319-5886.3.1.027

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Health Sciences
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Coden: IJMRHS
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Received: 26 Aug 2013
Research article
Copyright @2013
ISSN: 2319-5886
CARDIOVASCULAR RESPONSES DURING DEEP WATER RUNNING VERSUS SHALLOW

WATER RUNNING IN SCHOOL CHILDREN
Anerao Urja M 1, Shinde Nisha K2, Khatri S M3
1
Postgraduate student, 2Associate Professor, 3 Principal, Department of Cardio-respiratory Physiotherapy,

College of Physiotherapy, Pravara Institute of Medical Sciences, Pravara Medical Trust, Loni.
*Correspondence author email: physiourja@gmail.com
ABSTRACT
Overview: As the school going children especially the adolescents need workout routine; it is advisable
that the routine is imbibed in the schools class time table. In India as growing number of schools provide
swimming as one of the recreational activities; school staff often fails to notice the boredom that is caused
by the same activity. Deep as well as shallow water running can be one of the best alternatives to
swimming. Hence the present study was conducted to find out the cardiovascular response in these
individuals. Methods: This was a Prospective Cross-Sectional Comparative Study done in 72 healthy
school going students (males) grouped into 2 according to the interventions (Deep water running and
Shallow water running). Cardiovascular parameters such as Heart rate (HR), Saturation of oxygen (SpO2),
Maximal oxygen consumption (VO2max) and Rate of Perceived Exertion (RPE) were assessed. Results:
Significant improvements in cardiovascular parameters were seen in both the groups i.e. by both the
interventions. Conclusion: Deep water running and Shallow water running can be used to improve
cardiac function in terms of various outcome measures used in the study.
Keywords: Deep water running, Shallow water running, cardiovascular responses.
INTRODUCTION
The importance of regular physical exercise, as part of
therapy in everyday life, has a favorable influence on
the important parameters of the cardiovascular system.
A number of studies have also shown that regular
physical exercise can decrease risk of the development
of many cardiovascular diseases and also other health
problems of both adults as well as children.1 People
who are physically active live longer. Regular exercise
reduces the risk of dying prematurely.2
Recommendations for appropriate amounts of
physical activity for the young population, including
school-age youth, have been developed by several

organizations and agencies. Although recent reviews
have summarized the benefits of regular physical
activity on the health of youth and its potential for
reducing the incidence of chronic diseases that are
manifested in adulthood, a more systematic approach
is indicated. 1-9 These reports present results of a
systematic evaluation of evidence dealing with the
effects of regular physical activity on several health
and behavioral outcomes in school-age youth, with the
goal of developing a recommendation for the amount
137
Anerao et al.,
of physical activity deemed appropriate to yield

beneficial health and behavioral outcomes.
According to the current worldwide survey, childhood
and adolescent health problems are one of the top five
problems in the world in the year 2012. 3 They also
identified that this health issue is important not only
for the health care industry but also for the health of
the children as they mature into adults. The health
industry has recognized this problem and is beginning
to mobilize with new programs aimed specifically at
children. Numerous health risks have been associated
with adolescent overweight, including hypertension,
respiratory disease, several orthopedic disorders,
diabetes mellitus and elevated serum lipid
concentrations. 4, 5 Development of specialized
physical activity programs are necessary as school
systems face the reality of cutting programs, such as
physical education and recess, to spend more time
preparing for the standardized tests and examinations.
Also; due to recent advances in technology; video
games and gaming consoles have become more
popular than outdoor sports activities thus; limiting
the regular physical exercise.
Current recommendations indicate that school-aged
youth should participate daily in 60 minutes or more
of moderate-to-vigorous physical activity that is
appropriate and enjoyable; and involves a variety of
activities including resistance training, aerobic
activities such as swimming, bicycling, running and
jogging. 1, 3, 10 Program developed should be such that
it helps boys and girls develop competence and
confidence in their abilities to engage in different
types of physical activities. Fitness professionals who
incorporate such training into kid-friendly classes and
personal training sessions need to understand and
appreciate the physical and psychosocial perspective
of children and adolescents. 11 Therefore, program
design considerations for developing successful
programs should be such that regular participation in a
training program has the potential to positively
influence many health and fitness measures.
As the school going children especially the
adolescents need workout routine; it is advisable that
the routine is imbibed in the schools class time table.
In India as a growing number of schools provide
swimming as one of the recreational activities; school
staff often fails to notice the boredom that is caused
by the same activity. Deep as well as shallow water
running can be one of the best alternatives to

swimming. If the program is supervised and well
taught it can be beneficial for both physical as well as
psychological perspectives in the growth of the
children. But; the change following the water running
that would occur in terms cardiovascular parameters is
still unidentified are not expressed. The evidence
shows that there are many benefits of both deep water
running and shallow water running. Since there were
no prior studies performed to compare both the above
groups; hence, its very important to study the changes
in the cardiovascular responses and document them.
Hence; the aim of the study was to compare
cardiovascular responses after deep water running and
shallow water running. Accordingly the hypotheses
were formulated.
METHODS
There were 100 students who were screened for age,
symptoms, and/or risk factors for any medical
contraindications to exercise or any risk for disease.
After finding their suitability as per inclusion and
exclusion criteria were requested to participate in the
study.8 students did not meet the inclusion criteria.
The students were randomly selected for the study
with the use of random table numbers. Thus, out of 92
students 72 were selected to participate in the study.
These 72 students were explained about the study and
intervention. A written informed consent form
previously approved by the Institutional Ethical
committee (IEC) was obtained and was signed by the
School Principal and each student. The 72 students
participated in the study. The demographic data for
each student was filed. Pre treatment assessment of
HR; SpO2, RPE, VO2max were done.
In group A(N=35) students were receiving Deep
Water Running. It takes place in water deep enough
for students to be submersed to the neck. The use of
flotation aids, such as a buoyancy belt was used to
suspend the student so a lack of ground contact occurs
during the exercise. In Group B (N=37) students were
receiving Shallow Water Running. It was performed
in shallow water typically below the xiphoid level,
where students run/walk propelling themselves
through the water. 12
Both the interventions were given for the duration of 6
weeks (3 times/ week) for 45minutes. At the end of 6
weeks post test measurements of the students were
138
Anerao et al.,
taken. Data was collected and recorded. All the

students completed the study. The data was recorded
on the 1st day of the intervention and on the 18th day of
intervention for each participant.
subjected to statistical analysis. Various statistical

measures such a mean, standard deviation (SD) and
test of significance such as paired and unpaired t test
were utilized to analyze the data. The results were
concluded to be statistically significant with p <0.05
and highly significant with p < 0.001 and not
significant with p>0.05. Paired t test was used to
compare the differences of scores on pre-intervention
and post-intervention within a single group. Unpaired
t test was used to compare differences between the
two groups i.e. the control group (Group A) and the
study group (Group B).
RESULTS
The results of the study were analyzed in terms of
increase or decrease in Heart Rate, VO2max, RPE, SpO2
and comparison was made between the first and 18th
day of the treatment. Statistical analysis was done by
GraphPad InStat (Trial version) software. The data
were entered into an excel spreadsheet, tabulated and
Table 1: Table showing demographic data

Demographics
Group A
Age (years)
16.51+ 1.269
Height (mts)
1.5+ 0.0943
Weight (kgs)
54.17+ 6.853
2
BMI(kg/m )
22.12+1.773
100
98.14
Group B
16.40+ 1.116
1.57+ 0.064
52.10+ 4.408
21.02+ 1.323
98.37
98.54
80.1
79.37
98.64
74
73.25
80
58.46
56.51
60
40.1
39.77
SpO2
40
0
5.67
5.6
20
Group A
Group B
Heart rate
1.5
Group A
Day1
RPE
1.45
VO2max
Group B
Day18
Fig.1.The following graph shows the mean of parameters of participants in group A and group B on 1st day &
18th day.
Table.2: Showing mean difference of outcome measures in Group A and Group B and their Statistical
inference
Outcome Measure
MEAN DIFFERENCE
df
Inference
Heart Rate(b/m)
SpO2
RPE
VO2max(ml/kg/min)
Group A
6.123.47
0.40.14
4.060.63
16.414.32
0.018
4.338
1.142
2.202
70
70
70
70
0.9851
<0.0001
0.2575
0.0310
Not Significant
Highly Significant
Not Significant
Significant
Group B
6.1081.70
0.270.11
4.220.55
18.694.45
The difference between parametsers for DWR on day

1 and on day 18 were found to be extremely significant
for HR (p= <0.0001) and RPE (p=<0.0001) and
VO2max (p=<0.0001), very significant for SpO2
(p=0.0058). This indicates that the interventions in
form of Deep water running in school children was

effective in improving cardiovascular parameters in
terms of Heart rate, SpO2, RPE, and VO2max.
The difference between parameters for SWR on day 1
and on day 18 were found to be extremely significant
139
Anerao et al.,
for HR (p= <0.0001) and RPE (p=<0.0001), VO2max

(p=<0.0001), and SpO2 (p=0.0004). This indicates that
the interventions in form of Shallow water running in
school children was effective in improving
cardiovascular parameters in terms of Heart rate,
SpO2, RPE, and VO2max.
The results between SWR and DWR on day 18 were
not significant in improving VO2max (p=0.2032), RPE
(p=0.5090), SpO2 (p=0.3224), HR (p=0.2253). This
indicates that both the interventions in form of Deep
water running and Shallow water running in school
children were effective in improving cardiovascular
parameters in terms of Heart rate, SpO2, RPE, and
VO2max.
The results of mean differences of the outcome
measures indicate that both Deep Water running and
Shallow water running improve Heart rate and RPE
similarly. The VO2max is improved more in Deep
Water running as compared to Shallow Water Running
and SpO2 is best improved during Shallow Water
Running as compared to Deep Water Running.
DISCUSSION
The study conducted in Loni; to compare Deep water
running to Shallow water running. It is also believed to
be the first study in India to compare the two water
running techniques in hydrotherapy. This study titled
cardiovascular responses in deep water running versus
shallow water running in school children was
performed in school boys aged between 15 to 19 years.
This population was chosen to generalize the results
for this age group. This study was conducted at
Pravara swimming pool, Loni, was completed in the
month of November 2012. The results of the study
indicated that the intervention in the form of Deep
water and shallow water running in school children
was effective in improving cardiovascular parameters
in terms of Heart rate, Spo2, RPE, and VO2max and
were also comparable to other studies.
In a study by Chu KS et al in 200213 measured
maximal physiological responses to Deep-Water and
Treadmill Running in Young and Older Women, they
observed Lower HRmax values in DWR for both age
groups (p < .05). Another study by Town GP and
colleagues14 concluded that HRmax values for SWR and
DWR were 88.6% and 86% of TMR, respectively. In a
Comparative study the authors Michaud et al15 found
that heart rate were significantly greater (p < 0.05) for
treadmill running. These results when compared with

the present study; the mean heart rate of participants
during Shallow water running and deep water running
at the end of the study were 73.25+2.201 and
74.13+3.66 respectively.
Authors noted that heart rate has been reported to
decrease during head-out water immersion exercise
compared with air. 16-19 The mechanism responsible for
the lower heart rate during immersion is the
redistribution of blood volume from the periphery to
the central region. The increased hydrostatic pressure
of the water, concomitant with peripheral
vasoconstriction to reduce heat loss forces peripheral
blood into the thorax. This results in an enhanced
venous return and a decreased stroke volume while
maintaining cardiac output. 17 The possible explanation
for reduction of heart rate in this present study was in
accordance with an explanation given by Sophie
Heywood.20 According to Sophie Heywood; the
hydrostatic pressure which is depth dependent; there is
increased stroke volume and cardiac output. The
Cardiac output (CO) is the product of Stroke volume
(SV) and Heart rate. Thus, during water immersion it
is found that heart rate is reduced.20 The hydrostatic
pressure causes an immediate increase in venous
return, right atrium pressure and, hence, stroke
volume. Increased stroke volume allows for the
maintenance of cardiac output with lower HR as stated
by Christie et al. in 1990. 18 A reflex response of the
cardiovascular system to the cold receptors in the skin
could also have contributed to the depressed HR in the
water as the water temperature of 32.5 C is slightly
lower than thermo-neutral for the resting condition.21
This study showed extremely significant difference
between the SpO2 in SWR group at the start of the
study and SPO2 on at the end of the study (p<0.0001).
The mean SpO2 of participants in SWR at the end of
the study was 98.540.5054. The difference between
the SPO2 in DWR group at the start of the study and
SpO2 on at the end of the study were very significant
(p<0.0001). The mean SpO2 of participants in DWR
on at the end of the study was 98.65 (SD= +0.4808).
These results are comparable with other studies.
Bishop et al.22 reported a higher O2 pulse during DWR
compared with TMR. Results of O2 pulse during
DWR was 4.34 and 3.81 during TMR (p<0.01). The
higher O2 pulse during DWR was largely a result of
lower VO2 not that of higher HR.
140
Anerao et al.,
The rate of perceived exertion measured in this study

was on the Borgs (CR10) scale. In a study by authors
Hall et al studied the cardio-respiratory responses to
underwater treadmill walking in healthy females;
found that the Borg scale of perceived exertion(6-20)
showed that walking in water at 4.5 and 5.5 km/hr was
significantly harder than on land (p<0.001). 23 It was
also concluded that walking in chest-deep water yields
higher energy costs than walking at similar speeds on
land. 23 These responses were similar to the present
study. The difference between the RPE on at the start
of the study and RPE on at the end of the study were
extremely significant (p<0.0001) for both the groups.
The difference between the VO2max on at the start of
the study and Vo2max on at the end of the study were
extremely significant (p=<0.0001) for both the groups.
These results where comparable with a study by
Davidson K and McNaughton DK who examined the
ability of deep water running training to improve
cardiovascular fitness in a young sedentary population.
24
Ten untrained female subjects were allocated into a
DWR and road running (RR) group. Subjects
underwent pre-test VO2max testing which was repeated
after each training program. Results indicated both
methods produced a significant increase in VO2max
compared with the pre-test without a significant
difference between the two.
Authors studied the intensity of exercise in deep-water
running and found that VO2 during the last session of
deep-water running (73% of maximum VO2) was not
significantly different from that of the treadmill hard
run (78%), but was significantly higher than that of the
treadmill normal run (62%).25 In a comparative study
it was found that peak oxygen consumption was
significantly greater (p < 0.05) for treadmill running.15
Although at a similar relative exercise intensity
treadmill running VO2, was significantly greater than
deep-water running. Several studies have shown that
maximal oxygen uptake (VO2max) attained during
treadmill running is lowered during DWR. 16, 26-29
Town and Bradley in 1991 found that the highest
values reached for VO2 and HR were 73.5 and 86% of
VO2 max and HR max on land, respectively.28 A study
found VO2 and HR during DWR to be 86 and 91% of
those obtained on land. 27 These findings are similar to
those reported in other studies. 27, 30 Responses to sub
maximal exercise on the treadmill and when immersed
to the neck have also been investigated. 30-32 A study
reported lower HR during DWR than treadmill

running at any given VO2.30
Implications for practice: In the participants of this
study; it was found that both DWR and SWR serve as
effective tool in improving cardiovascular responses.
The above results point out that such form of exercise
if given as a form aerobic training may improve
cardiovascular indexes and so increases cardiorespiratory endurance and parameters. The results also
indicate that both Deep Water running and Shallow
water running improve Heart rate and RPE similarly.
The VO2max is improved more in Deep Water running
and SpO2 is best improved during Shallow Water
Running so the intervention can be modified s per the
requirements of the participant.
In addition to benefits that physical activity has on
physical health and fitness, physical activity also has a
positive influence on academic performance and selfesteem. Because of the protective and health benefits
of habitual physical activity, it is important that
children are physically active and that they continue
this behavior through adolescence into adulthood.
Aquatic therapy is justifiably a rapidly expanding,
beneficial form of rehabilitation. Understanding the
theory of water techniques is essential in implementing
an aquatic therapy program. The success of the
program depends on the pleasure and benefits
achieved by the patients. The environment should also
be conductive to family and social interaction that
ultimately encourages the compliance of long-term
exercise programs.
In the current study; all the boys who participated
successfully completed the study without missing a
single session with the same enthusiasm, eagerness,
zeal and keenness throughout the study. The goals
established at the initial and subsequent evaluations
were met as quickly and as sensibly as possible.
Limitations of the study: Certain limitations of the
present study include small sample size, relatively
short term intervention, little follow up and the present
study has focused only on boys so the findings are
applicable to patients within this category only.
Suggestions for future research: Healthy school
going boys who were between the age group of 15 to
19 years were included in this study. Since the study
included regular participation for continuous 6 weeks
girls were not included for the same. Therefore; further
study can be conducted to generalize the results for
141
Anerao et al.,
female population. Also; this study was the first to

measure the cardiovascular parameters changes during
water running. Since the study was conducted in a
rural area, adequate instruments to measure VO2max;
were not available. Hence, future authors who are
interested in research can use a VO2max analyzer for
their study. Moreover; as the above mentioned results
cannot be generalized to all the types of age groups in
both the genders; the same intervention must be
studied in another age group to see the effect of this
intervention in both the genders.
CONCLUSION
Thus accepting the alternate hypothesis and rejecting
the null hypothesis, we conclude that 6 weeks of
training given in terms of DWR and SWR is effective
in improving cardiovascular responses when measured
on PACER test, Borgs Scale and Pulse oxymeter.
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DOI: 10.5958/j.2319-5886.3.1.028

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Health Sciences
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th
Accepted: 28th Dec2013
Research article
A CADAVERIC STUDY ON ANATOMICAL VARIATIONS OF THE SUPERFICIAL PALMAR ARCH
Vidhya Ramakrishnan1, Anil kumar Reddy Y 2, Aruna. S3, Balaji Thotakura4, Suba Ananthi5
1,2
Department of Anatomy, KFMS&R, Coimbatore, Tamilnadu, India.

Department of Anatomy, Indira Gandhi Institute of Medical Sciences, Pondycherry, India
4
Department of Anatomy, Chettinad Hospital and Research Institute, Padur, Chennai, India
3
*Corresponding author email: Kumarlucky48@gmail.com

ABSTRACT
Background: The Superficial Palmar arch (SPA) is an anastomosis between the ulnar and radial artery in the palm.
Maximum contribution in the arch is by an ulnar artery and it is completed by superficial palmar branch of radial
artery or arteria princeps pollicis or arteria radialis indicis or median artery. The SPA develops as a terminal plexus
of axis artery which is later joined by median, ulnar and radial arteries as these arteries develop. Materials &
Methods: Present study conducted in the Department of Anatomy, Chettinad Hospital and Research Institute on 50
(28 right and 22 left) formalin fixed hands were used. The variations observed were classified as per Coleman and
Anson, 1961, classification of the superficial palmar arch. Results: As per Coleman and Anson classification,
complete arch of type A was seen in 43 hands (86%) and of type B in 3 hands (6%). In this study incomplete arch
was seen in 4 hands (8%, 1 right and 3 left), persistent median artery type H supplying the radial side of the palm
and digits was seen in only one hand (2%). Conclusion: The data regarding the study on variations of SPA is
helpful in crushing injury of hand, arterial grafting, and vascular trauma of the upper extremity.
Keywords: Superficial Palmar arch, Radial artery, Ulnar artery, Median artery, Coronary artery bypass graft
INTRODUCTION
A hand or manus is a prehensile, multi fingered body
part located at the end of upper limb or forelimb of
primates and some other vibrates used for both gross
and fine motor skills. In order to perform its various
functions, it is richly supplied with blood vessels and
nerves1. The radial and ulnar arteries provide most of
the blood supply to the hands. Additional circulation
may come from the median artery or the interosseous
arterial system.
The superficial palmar arch (SPA) is an anastomosis
fed mainly by the ulnar artery. About a third of the
SPA are formed by the ulnar artery alone, a further
third are completed by the superficial palmar branch
of the radial artery and a third by the arteria radialis
indicis, a branch of either arteria princeps pollicis or

the median artery2.
The radial and ulnar arteries form 4 circuits in the
hand; anterior and posterior carpal arches at the level
of carpal bones, superficial and deep palmar arches at
the mid of palmar level3. Among these the superficial
and the deep palmar arches are the most important
circuits because they provide the principal blood
supply to all the structures in the hands. The SPA
develops as a terminal plexus of axis artery which is
later joined by median, ulnar and radial arteries as
these arteries develop4.
According to one of the extensive studies conducted
on 1200 formalin fixed hands, by Coleman and Anson
in 1961, the variations in the SPA were classified as
Vidhya et al.,
144
complete and incomplete arches which were further

subdivided into various subtypes as follows3.
GROUP I Complete Arch : Type A: classical radio
ulnar arch , Type B: Ulnar arch, Type C : medianoulnar arch ,Type D: radio-mediano-ulnar arch, Type E:
ulnar artery & a branch from deep arch
GROUP II Incomplete Arch : Type F: radial and
ulnar arteries without anastomosis, Type G; only ulnar
artery without supply to thumb and index finger, Type
H : ulnar and median arteries without anastomosis,
Type I: Median, radial and ulnar arteries without
anastomosis
incomplete arches, 3 were of type F (6%) and 1 was of

type H (2%) (Tab. 1)
Table 1: Incidence percentage of variations in the
current study
Arch type
No. of hands Percentage
Complete arch
46
92
Type A
43
86
Type B
3
6
Incomplete arch 4
8
Type F
3
6
Type H
1
2
Most of the arches seen in the current study were of
type A (Fig. 2), formed by the ulnar artery and
completed on the radial side either by the superficial
branch of the radial artery or princeps pollicis artery or
radialis indicis artery, branches of radial artery. Only
ulnar artery formed the arch (Fig. 3) in only 3 hands
and ulnar & radial without anastomosis (Fig. 4) in 3
hands. Persistent median artery supplying the radial
side of the palm and digits (Fig. 5) was seen in only
one hand.
Fig 1: Coleman and Anson classification

Hence the frequent anatomic variations encountered in
the formation of the SPA and increasing incidence of
taking radial arterial grafts for coronary bypass
attracted the interest in checking its incidence.
For the current study 50 human cadaveric hands (28
right and 22 left) fixed in formalin (10%) solution,
hands in the Department of Anatomy, Chettinad
Hospital and Research Institute were used.
Macroscopic dissection of the palm was done
according Cunninghams manual of practical anatomy
and variations in the formation and branching pattern
of the SPA were studied, variation were noted and
compared with similar studies conducted previously.
Fig. 2: Complete arch, Type A Classical radio

ulnar arch. (RA: Radial artery, UA: Ulnar artery)
OBSERVATION
Out of the 50 hands, complete arch was seen in 46
hands (24 right and 22 left) and incomplete arch in 4
hands. As per Coleman and Anson classification,
complete arch of type A was seen in 43 hands (86%)
and of type B in 3 hands (6%). Between the
Vidhya et al.,
Fig. 3: Complete arch, Type B Ulnar arch . (UA:

Ulnar artery)
145
Fig. 4: Incomplete arch, Type F Radial and ulnar

arteries without anastomosis (UA: Ulnar artery, RA
: Radial artery).
Fig. 5: Incomplete arch, Type H Mediano-ulnar

arch (2%), MA Median artery, UA Ulnar artery.
DISCUSSION
Advanced methods in Microsurgical techniques for the
reconstructing surgery of the hand and Upper
extremity and the choice of using a radial artery graft
during Coronary artery bypass grafting (CABG) have
necessitated the understanding of vascular architecture
in the palm.
Developmental the anomalies of blood vessels may be
due to: (i) The choice of unusual paths in the primitive
vascular plexuses. (ii) The persistence of vessels
normally obliterated. (iii) The disappearance of vessels
normally retained. (iv) Incomplete development.
The normal arterial blood supply to the human hand is
well documented, although the vascular supply to the
hand and digits via the SPA is known to be variable
(Al-Turk & Metcalf, 1984; Iossifidis, 19954, Ikeda et
al, 1988, Onderoglu et al, 19975). The systematic
arterial patterns of the hand were first described by
Jaschtschinski, 18976. Various anomalous patterns in
the arterial arches have been studied and various
Vidhya et al.,
classifications based on the contribution from the

formative branches, mainly superficial branches of the
radial artery and ulnar artery have been proposed by
various authors.
SPA was seen in all the 50 hands (100%) dissected (25
right, 25 left) unlike Brent et al7 (2010) who reported a
case of unilateral absence of the SPA in one hand he
observed. Complete arch was seen in 92% of the
hands (46, 22 left and 24 right) in the current study.
These results are similar to those reported by
MariosLoukas et al (2005)8, who observed the
presence of 90% complete arches in his study.
Although complete arches seem to be more prevalent,
as observed in the present study, in most of the studies
done by Coleman and Anson, 1961 (78.5%),
Suleyman et al, 2007 (75%) 9, Silvia et al, 2003 (60%)
10
, Nicolas et al, 2010 (58%) 11; some authors like
Valeria et al, 2004 (47.5%) 12 and Elizabeth O
Sullivan et al, 2002 (46.8%) 13 lesser incidence of
complete arches was reported.
The classical radio-ulnar arch formed by ulnar artery
and the superficial branch of radial artery or princeps
pollicis artery or radialis indicis artery (Coleman and
Anson, 1961, Type A) was seen in 43 hands (86%, 21
left and 22 right) in the current study unlike other
authors (Silvia et al, 2003, 67%; Suleyman et al, 2007,
40%; MariosLoukas et al, 2005, 40% and Coleman
and Anson, 1961, 34%) who have reported a lesser
incidence of the same type.
The ulnar type of arch formed by the ulnar artery
alone (Coleman and Anson, 1961, Type B) was seen
in 3 hands (6%, 2right and 1 left) in the present study.
In comparison such an arch was more prevalent in
other studies such as Coleman and Anson, 1961, 37%;
Suleyman et al, 2007, 35%; MariosLoukas et al, 2005,
35%; Silvia et al, 2003, 23%.
In this study incomplete arch was seen in 4 hands (8%,
1 right and 3 left) in par with Marios Loukas et al,
2005, who reported it in 10% of his study and unlike
other authors (Elizabeth O Sullivan et al, 2002,
53.2%; Valeria et al, 2004, 52.5%; Nicolas et al, 2010,
42%; Silvia et al, 2003, 40%; Suleyman et al, 2007,
25% and Coleman and Anson, 1961, 21.5%, who have
reported increased occurrence of the same (Fig. 6).
146
60%
50%
40%
30%
20%
10%
0%
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
Type Type Type Type Type Type Type Type Type
A
B
C
D
E
F
G
H
I
Coleman and Anson 1961
Fig. 6: Incomplete superficial Palmar arch Current study VsVarious authors

The most consistent incomplete arch was ulnar and
radial arteries without anastomosis (Coleman and
Anson, 1961, Type F), seen in 3 hands in this study
(6%, 2 left and 1 right hands). This type was seen in
3.2% of the hands by Coleman and Anson, 1961; in
20% of the hands by Suleyman et al, 2007 and in
33% of the hands by Silvia et al, 2003 (Fig. 7).
35.00%
30.00%
25.00%
20.00%
15.00%
10.00%
5.00%
0.00%
Coleman & Suleyman Silvia et al Current
Anson et al 2007
2003
study
1961
Fig. 7: Type F of incomplete superficial palmar

arch - Current study Vs Various authors
Only one of Coleman and Anson, Type H, in which
median and ulnar arteries supplied the palm without
anastomosis, was observed in the current study (2%,
left hand). Whereas Coleman and Anson reported
3.8% of the same type and Silvia et al, 10 % ( Fig 8).
The other types of arches described by Coleman and
Anson (Types C, D, E, G and I) were not observed in
the current study.
Vidhya et al.,
Fig. 8: Various types of arches - Current study Vs

Coleman & Ansons
CONCLUSION
The superficial and deep palmar arches account for a
rich anastomosis between arteries of the palm.
Wounds of the palm bleed profusely but heal rapidly
because of this anastomosis. An injury in the ulnar
artery or the SPA may compromise the arterial supply
of the fingers, particularly if there is an insufficient
anastomosis between the superficial and deep palmar
arches.
The sound knowledge about the vascular patterns in
the palm is crucial in microsurgical procedures of
hand and in amputations and in the choice of using the
radial artery for coronary bypass graft and in
preventing possible complications during hand
surgery. Identifying the presence of median artery and
its participation in the arch completion is important in
ligation of radial or ulnar artery in case of vascular
trauma.
In addition, the identification of any variation in the
arterial pattern of the hand using Doppler
ultrasonography,
photoplethysomography
and
oximetric techniques acquires great importance in
various surgical interventions in the hand.14 The
present study gives necessary information to
understand the vascular architecture and its common
and rare variations in the hand.
147
REFERENCES
1. Al-Turk M, Metcalf WK. A study of the
superficial palmar arteries using the Doppler
Ultrasound Flowmeter. Journal of Anatomy. 1984;
138:2732
2. Susan Standring. Williams and Warwick Editors
Grays Anatomy 38th Edition.
3. Coleman S, Anson J. Arterial pattern in handbased upon a study of 650 specimens. Surgery.
Gynaecology. Obstetrics, 1961; 409-24
4. Iossifidis. Aneurysm of the superficial palmar
arch. International Orthopaedics (SICOT). 1995;
19:403-404.
5. Onderoglu S, Basar R, Erbil KM, Cumhur M.
Complex variation of the superficial palmar arch
case
report.
Surgical
and
Radiology
Anatatomy.1997; 19:12325
6. Jaschtschinski SN. Morphology and topography of
the Arcusvolarissublimis and profundus of the
person. Anatomy notebooks. 1897; 7:161-88.
7. Brent AC, Paula Ferrada, Roger Walcott.
Demonstration of unilateral absence of the palmar
arch without collateral circulation. British Journal
of Surgery. 2006; 60: 652-55
8. Marios Loukas. Anatomical variations of the
superficial land deep palmar arches. Folia
Morphology.2005; 64( 2); 115-18
9. Sleyman Murat Tagil. Variations and clinical
importance of the superficial palmar arch. S.D..
TpFak. Derg. 2007; 14(2):11-16.
10. Silvia.
Morphologic
variations
of
the
superficialpalmar arc. Acta Cir Bras. 2003;18(3):
46-49
11. Nicols Ernesto Ottone. Analysis and clinical
importance of superficial arterial palmar irrigation
and its variants over 86 Cases. International
Journal of Morphology. 2010; 28(1):157-64
12. Valria Paula, SassoliFazan. Superficial palmar
arch: an arterial diameter study. J Anat.
2004;204(4): 30711.
13. Elizabeth OSullivan, Barry S Mitchell.
Association of the absence of palmaris longus
tendon with an anomalous superficial palmar arch
in the human hand. Journal of Anatomy. 2002;
202(2): 253.
14. Takkallapalli Anitha. Variations in the formation
of superficial palmar arch and its clinical
Vidhya et al.,
significance in hand surgery. Int J Biol Med Res.

2011; 2(2): 543-46
148
DOI: 10.5958/j.2319-5886.3.1.029

&
Health Sciences
www.ijmrhs.com
Coden: IJMRHS
th
Research article
Copyright @2013
ISSN: 2319-5886
COMPARATIVE STUDY OF GONADOTROPIN LEVELS AND CLINICAL PRESENTATION IN

SURGICAL AND NATURAL MENOPAUSE
*Naik Raviraj R, Chandel Rittu S, Abichandani Leela G
Department of Biochemistry, Grant Government Medical College and Sir JJ Group of Hospitals, Mumbai,
Maharashtra, India
*Corresponding author email: raviraj_40@yahoo.com
ABSTRACT
Introduction: Menopause means complete stoppage of menses for last one year due to failure of follicular
activities of the ovaries. This can be determined by the various hormones secreted by ovary such as LH and
FSH. As these hormones are responsible for normal maintenance of basic ovarian function in reproductive
life; there occurs considerable alteration in their levels in menopause. Aims and Objectives :- 1] To study
and compare ovarian function by determining levels of LH and FSH in Surgical and Natural menopause. 2]
To study and compare ovarian function in Surgical and Natural menopause. Brief Methodology: - Case
study: - 50 women with surgical menopause between 45 50 years of age. Control study: - 50 women with
natural menopause between 45 50 years of age. Material & Methodolgy :- Fasting serum samples of all women
with surgical and natural menopause were analysed for LH and FSH on Immulite 1000 chemiluminiscence
based analyser in special investigation lab. Summary of the Results :- Mean levels of LH and FSH were
higher in surgical menopausal women as compared to natural menopausal women. Women in surgical
menopause suffered from more vasomotor symptoms and cognitive decline as compared to women in natural
menopause group
Keywords: Surgical menopause, Natural menopause, LH, FSH, Chemiluminiscence
INTRODUCTION
Follicle stimulating hormone (FSH) and Luteinizing
Hormone (LH) is secreted by beta cells of the
adenohypophysis. FSH controls the ripening of
primordial follicles and in conjugation with LH
activates secretion of estrogen. FSH is suppressed by
estrogen secretion through a negative feedback
mechanism. 1 In conjugation with FSH, LH activates
secretion of estrogen, brings about the maturation of
the ovum
and
causes
ovulation. Following
ovulation LH produces luteinization of granulosa
and theca cells and initiate progesterone secretion.
LH also stimulates the secretion of testosterone
and androstenedione in ovarian stroma which
diffuses into follicular fluid and are aromatized

into estradiol.1 Menopause is defined as that point
in time when permanent cessation of menstruation
occurs following loss of ovarian activity.2 It takes
12 months of amenorrhoea to confirm menopause.
Sixty million women in India are above the age
of 55 years . It is therefore important to address all
these menopause related impairment and apply
prophylactic measures so that these women can
have an enjoyable and healthy life.3 Menopause
normally occurs between the ages of 45 and 55
years ; the average being 47 years3. Surgical
menopause is the cessation of menses resulting
149
Naik Raviraj et al.,
from surgical removal of the uterus, leaving one or

both ovaries, or the removal of both ovaries.4Women
who have undergone hysterectomy with ovaries
preserved will experience menopausal symptoms
because of hypoestrogenism caused by depletion of
oocytes. Hysterectomy is surgery to remove a
womans uterus. In physiological or natural
menopause, the ovaries gradually lose function,
secreting less hormones over time. With surgical
menopause, the loss of ovarian hormones happens
instantly with no adaptation time. The onset of
menopausal symptoms is therefore much quicker
and symptoms are usually more severe. 6 Symptoms
associated with surgical menopause are often more
severe than with natural menopause, particularly
the vasomotor symptoms of hot flushes and night
sweats.6 Hot flushes are the most common
symptom of the climacteric and occur in 75% of
postmenopausal women in whom it is more common
after Hysterectomy.7 Hot flushes tend to last longer
and be more severe in women who have had a
surgically induced menopause.8 It is recognized
that hot flushes occur with the pulsatile release of
LH.9 The symptoms are characteristic of a heat
dissipation response , and consist of sweating on
the face , neck and chest as well as peripheral
vasodilation. 10 There is an acute rise in the skin
temperature of several degrees centigrade,11 a
transient increase in heart rate , fluctuations in the
electrocardiographic baseline and a pronounced
decrease in skin resistance.12 Tataryn IV et al13
conducted a study on LH , FSH and skin
temperature during the menopausal hot flush and
found positive correlation of simultaneous skin
temperature and circulating LH levels. These data
suggest that LH or the factors that trigger its
pulsatile release are related to the mechanism
responsible for the initiation of hot flushes.
Depressed mood is more common after a
hysterectomy, as it results in a greater frequency and
severity of vasomotor symptoms.14 It could be a
'domino effect' of vasomotor symptoms, causing sleep
disturbance and tiredness, which in turn precipitate
depression.15 Cognitive decline is directly related to
hot flushes in women who have undergone
hysterectomy, but natural menopause itself does
not necessarily result in significant cognitive
dysfunction.16 During a hot flush , blood flow
decreases in the hippocampus , possibly impairing
memory and cognition. 16 Such reductions in blood

flow may contribute to the decreased mental
clarity and short-term verbal memory problems
experienced by postmenopausal women.16Symptoms
of menopause are irritability, mood swings, sudden
tears,
anxiety,
depression,
memory
lapses,
headaches, vaginal tissue atrophy that can lead to
more urinary tract or vaginal infections and
urinary incontinence, loss of skin tone and
osteoporosis.
Other
symptoms
include heart
palpitations, insomnia, loss of libido, vaginal
dryness and painful intercourse, fatigue, weight
changes and difficulty in losing weight, itchy skin
and difficulty in concentrating.6
Aims & Objectives
1.To study and compare hormonal levels of LH ,
FSH in Surgical and Natural menopause.
2.To compare the symptoms like hot flushes and
cognitive decline in Surgical and Natural menopause.
Place of study: Special investigation laboratory of
Department of Biochemistry, Grant Medical College
& Sir JJ group of hospitals. Samples were collected
from female patients and staff of the hospital.
Study design: Prospective study. Institutional Ethical
Committee clearance was taken.
Study population: Present study includes 50 women
(cases) belonging to surgical menopausal group and
50 women (controls) belonging to Natural menopausal
group.
Ethics: Institutional Ethical Committee approval,
Informed consent were taken from all the women
included in the study.
Period of study: July 2011 September 2013.
Inclusion criteria:
1. Women aging between 44 to 50 years who have
undergone Total Hysterectomy in past one to two
years.
2. Women aging between 44 to 52 years who were
experiencing natural menopause since past one to
two years.
Exclusion criteria - women with:
1. Hormonal intake in any form e.g.: Drugs,
Soyaflavons.
2. Endocrine disorder. eg: Hyperpituitarism.
3. Ovarian Tumors.
Blood Sample Collection- 5 ml blood sample was
collected by venipuncture in plain tube. All blood
150
samples were centrifuged at 4500 revolutions per

minute for 5 minutes to obtain clear serum. Serum
samples are then stored between 2-80C before
analyzing on Immulite 1000 chemiluminiscence
machine.
Biochemical Analysis: All the hormonal parameters
(LH, FSH) were measured by Solid Phase
Competitive Chemilumniscent Enzyme Immunoassay.
The solid phase (bead) is coated with rabbit antihormonal polyclonal antibody. The reagent contains
alkaline phosphatase conjugated to respective
hormone. This hormone-enzyme conjugate competes
with respective hormone in patients blood sample
for limited antibody binding sites on bead. The
excess sample and reagent are removed by centrifugal
wash. Finally chemiluminiscent substrate is added
to the bead and the signal is generated in
proportion to the bound enzyme. Fully automated
enzyme amplified chemiluminescent immunoassay
based Immulite 1000 analyzers was used.
Measurement of these blood hormonal parameters was
done by using commercial kits from Siemens Medical
Solutions Diagnostics, Los Angeles, CA, USA.
Statistical analysis: Numerical variables were
reported in terms of mean and standard deviation. An
independent (unpaired) sample t-test was used to
compare the difference of means for independent
quantitative variables following normal distribution.
Pearson chi-square test was used to test the
significance of qualitative variables like symptoms.
Variables showing P-value less than 0.05 were
considered to be statistically significant and less than
0.01 as very significant. The SPSS software was used
for data analysis.
RESULTS
The present study included 50 women with surgical
menopause and 50 women with Natural menopause,
thus a total of 100 subjects fulfilling the inclusion
criteria were enrolled in this study.
Age at Menopause: In this study the mean age at
menopause in the study group was 46.76 years 1.43,
while that in the control group was 50.9 0.83
years. On applying independent (Unpaired) sample t
test, the difference in mean age at menopause
between two groups was found significantly
different at the 0.01 level of significance.
Table:1. Mean Age statistics of surgical and

natural menopausal.
Menopause N
Mean Age at menopause
Standard Deviation (Years)
Surgical
50
46.76 1.437
Natural
50
50.9 0.839
Mean Difference= -4.14 Years

Table 2: Serum mean LH level of surgical and
natural menopausal females
Menopause LH[mIU/ml] FSH [mIU/ml]
Surgical
37.322.924
104.62 12.952
Natural
22.964.389
66.49.216
P Value
< 0.001
< 0.001
Note: Reference values in Postmenopausal women

LH: 11.3 39.8 mIU/ml, FSH 21.7 153 mIU/ml
LH: In this study the mean level of Luteinizing
hormone in study group was found to be 37.322.92
while that in control group was 22.964.38. On
applying independent (Unpaired) sample t test, the
difference between mean LH levels in both the groups
was found to be very significant with P value < 0.001.
FSH: In this study the mean level of Follicle
stimulating hormone in the study group was
104.6212.95 while that in the control group was
66.49.21. On applying independent (Unpaired)
sample t test, the difference in mean FSH level in
both the groups was found to be very significant with
P value < 0.001. (Independent Sample t test:- t value
17, df-88.49, P value <0.001)
Table 3: Clinical feature of surgical and Natural
menopause
Mood Swings
Osteoporosis
Hot Flushes
Irritability
headache
Memory lapses
anxiety
depression
Sudden tears
Vaginal tissue
atrophy
Surgical
menopause
32 (64%)
35 (70%)
44 (88%)
44 (88%)
30 (60%)
33 (66%)
34 (68%)
30 (60%)
31 (62%)
35 (70%)
Natural
menopause
20 (40%)
27 (54%)
28 (56%)
28 (56%)
18 (36%)
18 (36%)
20 (40%)
20 (40%)
15 (30%)
16 (32%)
151
Hot flushes: In the present study 88% of the women

in surgical menopausal group had hot flushes as
compared to only 56% of women in natural
menopausal group. On applying Pearson Chi-square
test, the frequency of hot flushes in surgical
menopause was significantly higher than that in
natural menopause with P < 0.001.
Mood Swings : In the present study 64% of the
women in surgical menopausal group had mood
swings as compared to only 40% of women in
natural menopausal group. On applying Pearson Chisquare test, the frequency of mood swings in surgical
menopause was significantly higher than that in
natural menopause with P < 0.05. Women with hot
flushes are more likely to experience disturbed
sleep, depressive
symptoms and
significant
reductions in quality of life. Women in surgical
menopause suffer more from hot flushes thus are
more affected by mood swings. LH and FSH levels
were found to be significantly increased in surgical
menopause as compared to natural menopause.
Women belonging to surgical menopause group suffer
more from hot flushes and mood swings as compared
to women in the natural menopause group.
DISCUSSION
In the present study the mean age of the surgical
menopausal group was significantly lesser than that
of the natural menopausal group; which was well
supported by another study done by Ozdemir S et al.
17
Ovarian function was indeed depressed in the
natural menopausal women but was still preserved
for 1 to 2 years after menopause. 18
In the present study, serum LH and FSH levels
in the group of women within 2 years after
surgical menopause were significantly higher than
those in the group of natural menopausal women
at a comparable period after menopause. Similar
finding were suggested by Nobuaki Furuhashi et
al18 who reported significantly increased levels of LH
and FSH within 2 years after surgical menopause as
compared to their levels in natural menopause.
Similarly Edward.E et al19 also found a significant
increase in LH and FSH levels in surgical
menopause. Carina C.W. Chan et al20 found that
women with hysterectomy had significantly
elevated serum FSH level and lower stromal
blood flow indices as compared to healthy natural
menopausal women. S.Muttukrishna et al21 reported
that ovarian inhibin A & B were cleared from

circulation within short period of surgical
menopause which was responsible for early rise
of FSH in surgical menopause.
The ovaries are the predominant source of Inhibin
A and B22 which are characterized for their
inhibitory effect on pituitary follicle-stimulating
hormone (FSH) secretion23, by a negative feedback
regulation24,25. It has been speculated that after
surgical menopause and the fall in inhibins ;
estradiol and progesterone stimulates increase in
the synthesis as well as secretion of FSH and
LH.21 It is well established fact that estradiol
demonstrate a direct pituitary site of estrogen
negative feedback on LH and FSH responsiveness
to GnRH but the effect of estradiol on FSH
responsiveness is greater than that on LH and this
effect is attenuated with aging and menopause.26
This negative feedback is disrupted in surgical
menopause because of abrupt deficiency of
estradiol which may also contribute to more
increase in levels of LH and FSH when compared
with natural menopause.27 In the present study the
percentage of surgical menopausal women
experiencing hot flushes , mood swings was
significantly
higher
than
that
of
natural
menopausal women. Pearce J et al28 and Bachmann
GA et al29 reported similar significant difference in
hot flushes percentage between two menopausal
groups and concluded that hot flushes tends to last
longer and be more severe in women who have
had a surgically induced menopause. Nachtigall et
al30 reported that 100% of surgically menopausal
women had vasomotor symptoms, and 90% had
severe symptoms which lasted an average of 8.5
years after menopause. Another study done by
Tataryn IV et al13 found a positive correlation of
simultaneous skin temperature and circulating LH
levels. So it may suggest that LH or the factors
that trigger its pulsatile release relate to the
mechanism responsible for the initiation of hot
flushes.13 Depressed mood is more common after
surgical
menopause, as it results in a greater
frequency and severity of vasomotor symptoms. 31 So
it could be a 'domino effect' of vasomotor symptoms,
causing sleep disturbance and tiredness, which in turn
precipitate depression. 15
152
CONCLUSION
LH and FSH levels were found to be significantly
increased in surgical menopause as compared to
natural menopause. Significant increases in the levels
of these hormones are seen in surgical menopause due
to sudden decline in the function of ovarian activity.
These women suffer more from hot flushes, cognitive
decline and mood swings as compared to women in
the natural menopause group.
ACKNOWLEDGMENT
Technical help at special investigation laboratory, JJ
Hospital

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Premature Menopause and Postmenopausal
bleeding. Chapter 5; p:52-55.
4. Kate MB. Can Hysterectomy Be Considered a
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5. Pratap Kumar, Narendre Malhotra. Jeffcoates
principle of gynaecology. 7th ed. New Delhi :
Jaypee Brothers Pvt.Ltd ; 2008. Menopause;
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6. Crystal
Hannan.
Surgical
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7. Pearce J, Hawton K, Blake F. Psychological and
sexual symptoms associated with the menopause
and the effects of hormone
replacement
therapy. Br J Psych 1995; 167: 163-73.
8. Bachmann GA. Vasomotor flushes in menopausal

women. Am J Obstet Gynecol 1999; 180: S312
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9. Rebar RW & Spitzer IB. The physiology and
measurement of hot flushes. Am J Obstet Gynecol
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10. Freedman RR. Physiology of hot flushes. Am J
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11. Sturdee DW, Reece BL. Thermography of
menopausal hot flushes. Maturitas 1979; 1: 201
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12. Sturdee DW, Wilson KA, Pipili E. Physiological
aspects of the menopausal hot flush. BMJ 1978; 2:
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13. Tataryn IV, Meldrum DR, Lu KH, Frumar AM ;
LH , FSH and skin temperature during the
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14. Avis NE, Brambilla D, McKinlay SM, Vass K. A
longitudinal analysis of the association between
menopause and depression. Results from the
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15. Maoz B, Shiber A, Lazer S. The prevalence of
psychological distress among postmenopausal
women attending a menopausal cliic and the effect
of hormone replacement therapy on their mental
state. J Menopause. 1994; 1:137-41.
16. Shepherd JE. Effects of estrogen on congnition
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Kaya,B. Compared effects of surgical and natural
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longitudinal analysis of the association between
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154
DOI: 10.5958/j.2319-5886.3.1.030

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EFFECT OF PACLITAXEL ALONG WITH DI ALLYL SULFIDE ON IMMUNO COMPETENT CELLS,

IMMUNE COMPLEXES AND IMMUNOGLOBULINS CHANGES IN 7,12 DI METHYL BENZ(A)
ANTHRACENE INDUCED SKIN CANCER IN WISTAR RATS.
*Muninathan N1, Ursula Sampson2, Prashanth Talikoti3, Uma Maheshwari4, Archana5, Kumar6
Department of Biochemistry, Meenakshi Medical College and Research Institute, Enathur, Kanchipurm, Tamil
Nadu, India
*Corresponding author email: muninathanpappaiya@gmail.com
ABSTRACT
Our recent studies have shown that naturally occurring dietary organo sulfure compounds such as di allyl sulfide
and paclitaxel are capable of inhibiting polycyclic aromatic hydrocarbon (PAH) metabolism and subsequent PAHDNA adduct formation in Wistar rats. In this study these plant phenols were tested for their effects against PAHs
and 7,12 Di Methyl Benz (A) Anthracene -induced skin tumorigenesis in rats. Each compounds was evaluated as a
possible anticarcinogen in an initiation and promotion and a complete skin tumorigenesis protocol. In the two-stage
tumor protocol in Wistar rats using 7,12-dimethylbenz(a)anthracene as the initiating agent followed by twice
weekly applications of acetone as tumor promoter each plant compounds afforded significant protection against skin
tumorigenicity. The protective effects were verified both by prolongation of latency period and by subsequent tumor
development. Our results suggest that these plants compounds have substantial though variable potential for
modifying the risk of skin tumorigenicity induced by a wide variety of chemicals and of these combinations of
Paclitaxel and Di allyl sulfide was shown to have maximal chemo protective effects.
Keywords: Paclitaxel, Di allyl sulfide, DMBA, Skin cancer.
INTRODUCTION
Skin cancer is the most common form of human
cancer. It is estimated that over 1 million new cases
occur annually.1,2 The annual rates of all forms of skin
cancer are increasing each year, representing a
growing public concern. It has also been estimated that
nearly half of all Americans who live to age 65 will
develop skin cancer at least once3. The most common
warning sign of skin cancer is a change in the
appearance of the skin, such as a new growth or a sore
that will not heal. In India, skin cancers constitute
about 1-2% of all diagnosed cancers. Basal cell
carcinoma is the commonest form of skin cancer
worldwide, but various studies from India have
consistently reported SCC as the most prevalent skin

malignancy4. Although complete data of incidence is
not available, various cancer registries in India
reported cumulative incidence of skin cancer varying
from 0.5 to 2 per 100 000 population5. Although, the
incidence of skin cancers in India is lower as
compared to the Western world, because of a large
population, absolute number of cases is estimated to be
significant. Skin cancer patients have stage IV
receive chemotherapy and /or hormonal therapy to
suppress cancer cells and control the disease. The goal
of chemotherapy is to destroy, shrink primary tumors,
slow the tumor growth, and to kill cancer cells that
155
Muninathan et al.,
may have spread (metastasized) to other parts of the

body from the original tumor. Chemotherapeutic drugs
elicit some toxicity towards normal cells also, that
limits its usage.
Paclitaxel is a naturally occurring antineoplastic agent
has shown great promise in the therapeutic treatment
of certain human solid tumors particularly in
metastatic breast cancer, skin cancer, lung cancer and
refractory ovarian cancer6. Paclitaxel's antitumor
activity was discovered in1960s during a large scale
35,000 plants-screening program sponsored by the
National Cancer Institute (NCI), USA. Paclitaxel is a
most effective drug in skin cancer, it has several
important side affects particularly neutropenia,
peripheral neuropathy and hypersensitivity reactions7.
Myelo suppression or neutropenia is the principal dose
limiting toxicity of paclitaxel on all administration
schedules. It is undeniable that the need for new agents
with both improved activity and acceptable safety
profile is urgent. Nausea, vomiting, thrombocytopenia,
mucositis, decreased appetite and diarrhea are the less
common side effects of administration of paclitaxel.
Ongoing clinical trials suggest that combining
paclitaxel with other anticancer drugs may be an
effective treatment for patients with skin cancer.
Researchers are exploring ways to reduce the side
effects of treatment improve the quality of patients'
lives, and reduce pain.
The chemotherapeutic and antitumor activity
associated with garlic has been attributed to the
presence of various organosulfide-based active
compounds including Di Allyl sulfide6. A topical
application of Di allyl sulfide is the most promising
approach for treating skin tumors as it leads to a
localized effect at the desired site with minimal side
effects. Polycyclic aromatic hydrocarbons (PAHs)
are
commonly
occurring
environmental
contaminants and are widely distributed in the
environment as pollutants of air, water and soil8.
Benzo (a) pyrene is the most toxic compound of
PAHs.9
The purpose of the present study is to evaluate the
combined effect of Paclitaxel and Di allyl sulfide
against the DMBA induced skin carcinogenesis.
Chemicals: 7,12 Dimethyl benz (a) anthracene and Di
allyl sulfide were purchased from Sigma chemical
company, USA. All the other chemicals used were of

analytical grade.
Animal care and housing: Male Wistar rats, 6-8
weeks of age and weighing 150-200g, were used. The
animals were procured from Central Animal House
Block, Meenakshi Medical College and Research
institute, Kanchipuran, Tamil Nadu, India and
maintained in a controlled environmental condition of
temperature and humidity on alternatively 12 h
light/dark cycles. All animals were fed standard pellet
diet (Gold Mohor rat feed, Ms.Hindustan Lever Ltd.,
Mumbai) and water ad libitum. This research work on
Wistar male rats was sanctioned and approved by the
Institutional Animal Ethical Committee
Experimental Design
The animals were divided in to six groups of 6 animals
each.
Group I animals served as control,
Group II as animals treated with DMBA (5 g/kg of
body weight) per animal in acetone (100 L), three
times a week for 28 weeks to induce skin cancer.
After tumor induction:
Group III animals were treated with Paclitaxel
(33mg/kg b.wt) once in a week for 4 weeks in intra
muscular.
Group IV animals were treated with garlic extract of
Di allyl sulfide (250g/animal) for 30 days daily.
Group V animals were treated with both Paclitaxel and
Di allyl sulfide (as in group III and group IV) daily.
After the experimental period of 32 weeks, the animals
were sacrificed by cervical dislocation. Blood sample
was collected via cardiac puncture, and add 2-3drops of
EDTA anticoagulant.
The following Biochemical analysis was done:
1. Estimation of total white blood cells:
Enumerated by the method of John (1972)10
2. Differential Leucocyte count: By the method of
John (1972) 10
3. Soluble immune complex was estimated by the
method of Seth and Srinivas (1981) 11
4. Nitro blue tetrazolium (NBT) reduction test:
was carried out by the method of gifford and
malavista (1970) 12
5. Neutrophil function test: By the method of
Wilkinson (1977) 13
6. Ig G was quantitatively measured: by Tenant et al
(1979) 14
156
Muninathan et al.,
7. Phagocytic index: by the method of Wilkinson

(1977) 13.
8. Avidity index: by the method of Wilkinson
(1977) 13.
RESULTS
Immunocompetent cells : Fig. 1 represents the effect
of paclitaxel and Di allyl sulfide on the status of
immunocompetent cells in various experimental
groups. Group II cancer bearing animals show a
significant (p<0.001) decrease in the cell counts when
compared with group I control animals. Paclitaxel and
Di allyl sulfide treatment caused a significant decrease

in leucocytes (p<0.05), lymphocyte (p<0.01),
neutrophils (p<0.01), absolute lymphocyte count
(p<0.05) and absolute neutrophil count (p<0.05). Di
Allyl Sulfide along with paclitaxel treated group V
animals caused a considerable changes (p<0.001;
p<0.01) in cell count. However the effect was more
pronounced in the group VI animals treated with both
paclitaxel and Di allyl sulfide when compared with
group I control animals.
Units - Total leucocyte count : cu mm x 102 ; Lymphocyte : % ; Neutrophils : %; Absolute lymphocyte count :
mm3 x 102
Absolute neutrophil count : no/mm3 / 102

Fig 1: Effect of paclitaxel and Di allyl sulfide on the status of immunocompetent cells
Immune complexes: Fig. 2 depicts the effect of
paclitaxel and Di Allyl Sulfide on immune complexes
like phagocytic index, avidity complex, NBT
reduction and SIC in various experimental groups.
Group II cancer bearing animals showed a significant
(p<0.001) decrease in the immune complexes when
compared with group I control animals. Paclitaxel

treatment caused a significant (p<0.01; p<0.05)
decrease in the levels of immune complexes. Upon
paclitaxel and Di allyl sulfide treatment there found to
be a significant (p<0.001; p<0.01) increase in the
levels of immune complexes.
Fig 2: Effect of paclitaxel and Di Allyl Sulfide on immune complexes

157
Muninathan et al.,
Immunoglobulins
Fig 3 display the levels of immunoglobulins like IgG,
IgA, and Ig M in various experimental groups. IgG
and IgM levels were decreased considerably (p<0.001)
in cancer bearing group II animals with an increase
(p<0.001) in IgA level when compared with group I
control animals. Upon paclitaxel treatment the levels
of IgG, IgM were significantly (p<0.05) decreased
where as IgA level was increased (p<0.01) in group III

animals. Di allyl sulfide along with paclitaxel treated
group V animals showed considerable alterations in
the levels of Immunoglobulins (p<0.001) when
compared with group II cancer bearing animals. In
group VI animals treated with both paclitaxel and Di
allyl sulfide show no significant changes when
compared with group I control animals.
Fig 3: Levels of immunoglobulins like IgG, IgA, and Ig M in various experimental groups.
DISCUSSION
Immunomodulatory
activities:
Chemotherapy
remains the major hope for the treatment of cancer and
is always associated with some degree of haemopoietic
tissue toxicity and immune suppression. Although
cancer itself is immunosuppressive, cytotoxic
antineoplatic therapy is the primary contributor to the
clinical immunodeficiency observed in cancer patients.
Severe leucopenia, thrombocytopenia alterations in
circulating platelets, white and red blood cells are the
main side effects of chemotherapy leading to the
decrease of chemotherapy dose or discontinuation of
treatment.15 The most common complication
associated with cytotoxic antineoplatic therapy occurs
with the onset of neutropenia.16 Though paclitaxel is a
potent anticancer agent the major limiting side effect is
myelosuppression. It induces troublesome neutropenia
of grade 3-4 with decrease in WBC count in more than
50% of the patients.
Abnormal content of immunoglobulin indicate the
concised humoral immunity and reduction in immune
response. Thompson et a.l17 have reported decreased
levels of IgG and IgM in skin cancer conditions. The
levels of IgG and IgM were also decreased in various
other cancerous conditions.18-20 IgA content alone was
Muninathan et al.,
found to be increased in the skin cancer bearing rats.

Chandy et al21, have reported that the elevated serum
IgA levels may be due to the failure of clearance
mechanism by the damaged liver. This indicates the
severity of liver damage which directly correlates with
the progression of the disease.
A significant alteration in the neutrophil functions has
been observed in all our study. The killing ability of
the neutroplil as indicated by the NBT reduction and
phagocytic ability of the neutrophils as indicated by
the phagocytic index and the avidity index has been
significantly decreased in the cancer bearing animals
which was further decreased upon treatment with
paclitaxel.
Soluble serum immune complexes serve as an
indicator of immune responses either due to presence
of excess antigens or antibodies. This may be due to
decreased antibody production during cancer.
Immunomodulation through natural or synthetic
substances may be considered as an alternative for the
prevention and cure of neoplastic diseases.22, 23
Flavanoids are polyphenol substances of plant origin,
having biological and antioxidative properties.24
Several reports have demonstrated the beneficial effect
158
of flavanoids in preventing toxicity of different

agents.25-27
Flavanoids display a remarkable array of biochemical
and pharmacologiocal actions some of which suggest
that certain members of this group of compounds
significantly affect the function of the immune system.
They also affect the function of enzyme system
critically involved in the immune system. Di allyl
sulfide contains organo sulfur compounds that play a
very important role in scavenging free radicals. In our
study also Di allyl sulfide exhibited positive effect on
the immune system which can be attributed to its
flavanoid content. Ali et al. (2000) have reported that
Di allyl sulfide stimulates immune response in rats.
Mesbah Lahouel28 have reported the effect of Di allyl
sulfide on haemotoxicity of chemotherapeutic drugs.
Considering the possible mode of antitumor action of
Di allyl sulfide it is likely that it could be mediated by
immunomodulatory activity of Di allyl sulfide. The
present study has given the hope that Di allyl sulfide
can confer in the reduction of side effects due to
chemotherapeutic agents and may be used in humans
in future.
CONCLUSION
From the present study, the effect of Paclitaxel- DAS
combination proved to be effective chemotherapeutic
agent against DMBA induced skin cancer in wistar
rats compared to that of paclitaxel or Di allyl sulfide
confirmed analyzing the total white blood cells,
Differential leukocyte count, Soluble immune
complex, neutophil function tests, IgG, IgM, IgA
levels and Phagocytic , Avidity indexs in blood
samples
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edition, CV Mosby Co ST louis .1972. pp 11981204.
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15. Lahowel M, Viotte G. and Sumereau E. Haemato

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A STUDY ON EARLY DETECTION OF CHANGES IN VISUAL PATHWAY DUE TO DIABETES

MELLITUS BY VISUAL EVOKED POTENTIAL
Rajesh Kumar1, Sundararajan D2, Rajvin Samuel Ponraj3, M Srinivasan4
1
Post graduate student, 2 Associate Professor, 3Post graduate student,4 Professor, Department of Ophthalmology,
Meenakshi Medical College and Hospital, Kancheepuram, Tamil Nadu, India
*Corresponding author email: samuelpnrj25@gmail.com
ABSTRACT
Electrical potentials have been recorded by surface Evoked Potentials namely the Somatosensory Evoked Potential,
Auditory Brainstem Response and Visual Evoked Potential [VEP]. Visual conduction disturbance can be evaluated
by these instruments. A mass response of cortical and possibly subcortical may be represented, visual areas to visual
stimuli. Diabetic patients without a past history of cerebrovascular accidents diagnosed with Non- Proliferative
Diabetic retinopathy[DR] with a best corrected visual acuity at least 6/9.This study was done to assess whether a
delay in VEP latency observed in diagnosed type II DM patients could be ascribed to dysfunction of the retinal or
post retinal structures or by both. It is to find out whether the VEP latencies are altered in diabetes or not, if altered
and to correlate duration of the diabetes mellitus with visual evoked potential changes. Visual evoked potentials are
useful as a non invasive investigatory method in establishing central nervous system neuropathy developing in
diabetes. This study clearly shows that changes in VEP may be detected in diabetics before the onset of retinopathy.
Future studies should be focused on evaluation of the time that elapses between the appearance of the first
detectable pathologic electrophysiologic changes and the first ophthalmoscopically detectable retinal changes in
patients with Diabetes Mellitus [DM].
Keywords: Pattern reversal, Photostress, electrodes.
INTRODUCTION
Electrical potentials that occur in the cortex after
stimulation of a sense organ, which can be recorded by
surface electrodes, are known as Evoked Potentials
[EP]. e.g. Somatosensory Evoked Potential (SEP),
Auditory Brainstem Response (ABR) and Visual
Evoked Potential (VEP).
A change has been observed over time with the
clinical use of Electric potentials. There have been
advances in imaging technology, especially in
magnetic resonance imaging (MRI), have reduced the
use of EP testing in clinical practice. MRI largely
remains an imaging, structural, or anatomic test and
therefore gives more accurate information about
structural problems. EP testing assesses functionality

and thus supplies information about the physiology of
a certain anatomic pathway, providing much less
spatial or localizing information than MRI does.1
These electric potentials are used in the detection of
anterior visual conduction disturbance. A mass
response of cortical and possibly subcortical may be
represented, visual areas to visual stimuli.2,3 VEP
affection is related to age of onset of diabetes and

glycemic control. Any abnormalities in the visual
pathway can be detected with the help of VEP
much prior to appearance of visual symptoms or
changes in fundus examination.4
161
Rajesh et al.,
These equipments permit one sectioning of

structures which help in visual pathway neural
conduction.5 Evaluation of bioelectric activity of
the retinal layers is done with the help of
electroretinographic
signals with patterned stimuli (PERG)6.
The aim of this study is to evaluate the visual pathway
abnormalities in diabetic patients without retinopathy
and with non-prolierative diabetic retinopathy (NPDR)
and to determine abnormal frequency and to
investigate the relationship between other variables
such as duration of diabetes and degree of metabolic
control.
Fig 1: Visual evoked potential3

Aim & Objectives
Aim: Aim of this work is to assess whether a delay
in VEP latency observed in diagnosed type II DM
patients could be ascribed to dysfunction of the retinal
or post retinal structures or by both.
Objectives: 1. To find whether the VEP-PR latencies
are altered in diabetes or not. 2. To correlate duration
of the diabetes mellitus with visual evoked potential
changes.
Experimental design: A cross sectional study.
Subjects: Patients were selected from the outpatient
of Ophthalmology Department of Meenakshi Medical
College & Hospital, Kanchipuram . An informed
consent and ethical committee clearance have been
taken for this study.
Inclusion criteria:
1. No past history of cerebrovascular accidents
2. Diabetic patients with duration of 1-10 years.
3. Non- Proliferative Diabetic retinopathy
4. Best corrected visual acuity at least 6/9
Exclusion criteria:
1.
Cataract, 2. Glaucoma 3. Vitreous opacities or
any evidence of optic atrophy 4. Peripheral nervous
system disease 5. Proliferative diabetic retinopathy
General examination and systemic examination:
General examination was done in the Department of
Ophthalmology and a detailed history of
Cerebrovascular diseases, Cataract, Glaucoma, any
Optic nerve pathology and TB was taken.
Visual evoked potentials were recorded using
pattern reversal stimulation
Study Group: The study groups were divided into
Group I, Group II and Group III.
Group I: 40 normal age and sex matched subjects,
were selected as control group.
Group II: 40 subjects with DM Type II without
retinopathy, with duration of diabetes varying from 1
year to 10 years
Group III: We evaluated 40 subjects with DM type II
with non-proliferatve retinopathy with duration of
diabetes varying from 1 year to 10 years.
In this study waveform pattern latencies which are P
100 and N 75 and amplitude of VEP were chosen as
the parameters. Visual Evoked Potential used from the
Diopsys Nova Company with the electrodes placement
on the scalp as shown in Fig 2: The diffuse light flash
stimulus is rarely used due to the high variability
within and across subjects. The checkerboard patterns
utilize alternate light and dark squares and stripes,
respectively. These squares and stripes which are
equal are then presented one at a time via a computer
screen.
Fig 2: Placement of Electrodes, Scalp electrodes was

used: 1.Frontal (FP2), 2. Occipital (O2), 3. Grounding
(C2) electrodes6
Statistical Analysis: Studentt test (Independent

sample t test") was used for comparison of VEP
between control and diabetes group. One way analysis
of variance (ANOVA) was used for comparing the
VEP latencies and amplitude with duration of DM and
different level of glycemic control
162
Rajesh et al.,
RESULTS
Table 1: Tabulation comprising 40 patients studied over period of 10 years
No. of Age
Duration of DM
Subjects
Group I
Group II
Group III
40
40
40
49.13 4.52
52.70 3.87 4.00 1.76
53.334.39 5.47 2.25
Table 2: Comparison of P100 latency, N75 latency of Visual Evoked Potential

No. of Subjects P100 latency (ms)
N75 latency (ms)
40
93.82 2
67.46 5.28
Group I
40
100.30 4.91
70.76 6.77
Group II
40
107.30 4.54
73.81 4.58
Group III
* The mean difference is significant at the < 0.05 level
P value
< 0.0001*
< 0.0001*
< 0.0001*
Table 3: Comparison of Amplitude of Visual Evoked Potential between the groups

No.
of Amplitude (v)
p value
Subjects
40
7.52 1.18
Group I
<0.0001*
40
3.61 1.24
Group II
40
2.77 1.56
Group III
Table 4: Relationship of various glycemic levels of Diabetes Mellitus with Visual Evoked Potential Latency
(P100).
FBG
No.
of P100
latency Amplitude (v) p value
(mg/dl)
Subjects
(ms)
25
97.81 4.25
<126
4.35 2.04
20
126-145
> 0.0001*
103.60 3.07
2.92 1.39
108.40 3.70
3.28 1.90
>145
35
Table 5: Analysis of P100 Latency in regard with different durations of Diabetes Mellitus:
Duration (yrs)
No. of Subjects
P100 latency (ms)
Amplitude(ms)
p value
28
<3
< 0.0001*
96.31 6.38
5.54 1.61
102.29 1.72
3.30 0.98
< 0.0001*
105.79 2.92
1.83 0.45
< 0.0001*
37
7 10
28
24
Relationship between duration of diabetes and VEP

latency and amplitude: Among the subjects, the
duration of type II diabetes mellitus was found to be
between 1 year and 10 years with a mean of 4.73
1.42 years. The subjects were distributed into 3 groups
based on the duration of diabetes - Subjects > 3 years,
3 7 years and < 7 years duration of diabetes mellitus.
Amplitude of VEP and duration of diabetes: The
mean P100 N145 amplitude was significantly
Rajesh et al.,
reduced with the increasing duration of diabetes.

(p.value <0.05)
DISCUSSION
Peripheral and central neuropathy in diabetic patients
can be determined by Electrophysiological
investigations. Many patients who were clinically
examined showed a decrease of nerve conduction
velocity.
10
In our study it appears that pattern stimulated VEP

(P100 and N75 latencies) in people with diabetes
mellitus shows a distinct prolongation of the latency
period which could be explained with findings of
Karlica et al.3
In our study VEP latencies and amplitude was
correlated with duration of diabetes and we found
there was a significant changes in VEP. This could be
explained from the basis of poor metabolic control,
diabetes duration, dislipidemia and diabetic
nephropathy and the probable physiological
mechanism could be that VEP abnormalities for both
eyes is associated with parasympathetic autonomic
neuropathy and the hyposthetic form of lower-limb
sensory neuropathy.
The mean N75 latency, P100 latency and P100-N145
amplitude were prolonged in those with HbA1c >7%
but the difference were not statistically significant.
2.
3.
4.
5.
CONCLUSION
Visual evoked potentials are useful as a non invasive
investigatory method in establishing central nervous
system neuropathy developing in diabetes.
This study clearly shows that changes in VEP may be
detected in diabetics before the onset of retinopathy.
This study also shows that the VEP changes may be
related to the poor control and long duration of the
disease, both of which were associated with significant
VEP latency prolongation and decreased amplitude.
Thus VEP measurement is essential for the detection
of pre retinopathy changes and has the potential to
reduce DM complications.
Furthermore, it can be performed whenever a patient
with diabetes without retinopathy shows a worsening
of metabolic control, to evaluate the impairment of
visual pathways. It is important to emphasise that,
when tight metabolic control is achieved, these
abnormalities disappear, suggesting that VEP
impairment is only functional and completely
reversible.
Future studies should be focused on evaluation of the
time that elapses between the appearance of the first
detectable pathologic electrophysiologic changes and
the first ophthalmoscopically detectable retinal
changes in patients with DM.
6.
pathways function , Impaired saccadic eye

movement in diabetic patients: Documenta
Ophthalmologica 1999;99: 11-20
Andrew BE, Jane G Boggs. Clinical Utility of
Evoked Potentials. Journal name. 2010;vol:pgnos
Dobrila Karlica, Davor Galetovi, Milan Ivanisevi,
Veselin Skrabi, Ljubo Znaor and Darija Juri.
Visual Evoked Potential in the Detection of
Prediabetic Form of Diabetic Retinopathy in
Patients with
Diabetes- Mellitus. Antropol.
2010;34(2): 525-29
Samahy RM, Matter AM, Nassef, Osman AF.
VEP in children and adolescents with type l
diabetes mellitus. Pediatric Diabetes, 2010,Suppl.
14: 35
Vincenzo Parisi, Luigi Uccioli, Giovanna
Monticone, Leoluca Parisi, Gianluca Manni,
Daniel Ippoliti, etal.,
Electrophysiological
assessment of visual function in IDDM patients.
Electroencephalography
and
clinical
Neurophysiologjy. 1997;104, 171 -79
Vincenzo Parisil, Luigi Uccioli. Visual
electrophysiological responses in persons with
type l diabetes. Diabetes/Metabolism Research and
Reviews, 2001; 17: 125:18
REFERENCES
1. Marco Alessandrini, Vincenzo Parisi, Ernesto
Bruno, Pier Giorgio. The relationship with visual
164
Rajesh et al.,
DOI: 10.5958/j.2319-5886.3.1.032

&
Health Sciences
www.ijmrhs.com
Coden: IJMRHS
th
Research article
Copyright @2013
ISSN: 2319-5886
EFFECT OF 30AND 60 HEAD UP TILT ON CARDIOVASCULAR RESPONSES IN NORMOTENSIVE

AND HYPERTENSIVE INDIVIDUALS
*Badwe AN1, Soodan KS2, Kulkarni NB3, Latti RG4
1
Associate Professor, 3Professor, 4Professor & HOD, Department of Physiology, Rural Medical College, Pravara
Institute of Medical Sciences, Loni, Rahata, Ahmednagar, Maharashtra, India
2
Ex-Principal Rural Medical College, Pravara Institute of Medical Sciences, Loni, Rahata, Ahmednagar,
Maharashtra, India
*Corresponding author email: anand.badwe@gmail.com, Mob: +91-9096035553
ABSTRACT
Since 50 years, head up tilt table testing is being used by physiologists and physicians for different purposes. Many
investigators have studied the effect of head up tilt at a specific angle on cardiovascular and autonomic functions in
healthy individuals and reported usefulness of HUT in assessing the integrity of cardiovascular and autonomic
functions. In present study effect of 30 and 60 head up tilt is studied on cardiovascular parameters (systolic blood
pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), mean arterial blood pressure (MAP), heart
rate/min (HR), rate pressure product (RPP)) in normotensive and hypertensive individuals. METHODS: Effect of
30 and 60 head up tilt on cardiovascular parameters was studied in normotensive (n=50) and hypertensive
individuals (n=50) aged 15-70 years. Blood pressure and heart rate were determined by using electronic blood
pressure apparatus. RESULTS: 30 and 60 HUT produced decrease in SBP, PP, MAP and increase in DBP, HR,
RPP in both groups. The results were significant at selected different time intervals. The changes produced by 60
HUT were more significant than 30 HUT. The changes produced in the hypertensive group were more prominent
than normotensive group. In conclusion significant changes in HR and RPP in hypertensive individuals indicated
more myocardial oxygen consumption and myocardial work at both angles of HUT.
Keywords: Hypertensive, head up tilt, cardiovascular parameters
INTRODUCTION
Since 50 years, head up tilt table testing is being used
by physiologists and physicians for different purposes.
This includes effect of head up tilt (HUT) on heart rate
and blood pressure changes in posture, for modeling
responses to haemorrhage, as a technique for
evaluating orthostatic hypotension, as a method to
study haemodynamic and neuroendocrine responses in
congestive autonomic dysfunction and hypertension,
as well as tool of drug research.1-6
Many investigators have studied the effect of head up
tilt at a specific angle on cardiovascular and autonomic
functions in healthy individuals and reported
Badwe AN et al.,
usefulness of HUT in assessing the integrity of

cardiovascular and autonomic functions. 7,8
From literature survey conducted, it is found that,
there are few studies conducted to study the effect of
head up tilt on cardiovascular responses in
hypertensive individuals. The studies conducted so far,
have studied the effect of head up tilt mainly on
cardiovascular parameters such as Systolic blood
pressure (SBP), Diastolic blood pressure (DBP), heart
rate variability (HR), Cardiac output (CO). 9-10 Hence
in the present study we decided to study the following
objectives in selected hypertensive patients from the
165
Medicine department and the Family Medicine

Department of Pravara Rural Hospital, Loni.
Objectives:1. To study the effect of 30 and 60 head
up tilt on cardiovascular parameters
2. Comparison of investigated parameters in
normotensive group and hypertensive group
MATERIALS AND MEHTODS
It was a case control study conducted in the
department of Physiology at Rural Medical College,
Pravara Institute of Medical Sciences. The male
subjects selected for the study were between the age
group of 20-70 years (n=100) and were grouped in two
groups as:
1. Normotensive (control group n=50)
2. Hypertensive (Study group n=50)
Control group: Age matched normotensive healthy
subjects were selected as control and were selected
from clerical, teaching staff and students of our
institute, who fulfilled following criteria, were
included as control subjects in the study:
No signs of cardiac, vascular or neurological
involvement
No history of diabetes mellitus, hypertension
No history of drug treatment
No history of systemic illness
Their normal blood pressure status was considered
according to guidelines of, Seventh Report of the Joint
National Committee (JNC7) 11 on Prevention,
Detection, Evaluation and Treatment of high blood
pressure and Indian Hypertension Guidelines II, 2007
with optimal value as <120/<80 mm Hg and further
variations in systolic blood pressure was considered in
the range of 120-139 mmHg.Diastolic blood pressure
variation was considered in the range of 80-89 mmHg.
Study group (Hypertensive): Study group included
the hypertensive patients attending to Medicine
department and the Family Medicine Department of
Rural Medical College on outpatient basis.
Hypertensive subjects suffering from major illness
such as severe diabetic condition, congestive heart
failure, coronary artery disease, arrhythmias were
excluded from the study.
Same type of exclusion criteria was used for inclusion
of normotensive subjects in the proposed study. The
study protocol was approved by the Institutional
Research Ethical Committee.
In this group also patients were between the age group
of 20-70 years with diagnosed hypertension (i.e.,
history of hypertension less than 1 year).Hypertensive

subjects were considered as, having systolic blood
pressure of 140-159 mmHg and diastolic blood
pressure of 90-99 mm Hg (Grade I hypertension =
According to Joint National committee VII and Indian
Hypertension Guidelines II, 2007).11-14
These subjects were under treatment or on blood
pressure lowering medication with controlled
hypertension (target blood pressure value 140/90) at
the time of study. Their hypertensive status was
determined by consulting physician of Medicine
department and Family Medicine department.
METHODS
All subjects were called by appointment in the
laboratory, 2 hours after light brake fast in the morning
(09.00am-12.00pm). Subjects were instructed not to
consume caffeinated beverage and to avoid smoking
before 12 hours of the test. Subjects were informed in
detail about study protocol and written consent was
obtained before the study.
Before beginning of the test, anthropometric
characteristics such as height (cm), weight (Kg), body
mass index (BMI, Kg/m2), percent fat (%), fat mass
(FM, kg), fat free mass (FFM, kg) were recorded in all
subjects.
Percent fat (%), fat mass (FM, kg), fat free mass
(FFM, kg) parameters were determined by method of
measurements of girth as described by McArdle et al.15
Subjects were made to lie comfortably on tilt table for
20 minutes in the supine position. Three straps were
applied at the level of knee, waist and head. After 20
minutes of rest baseline cardiovascular parameters
(SBP, DBP, PP, MAP, HR/MIN, RPP) were recorded
at 1,5,10 minutes of interval by using digital blood
pressure monitor (Digicheck, Japan).
Thereafter subjects underwent gradual head up tilt at
30, 60 angles of tilt with the speed of 5/Sec. During
head up tilt manoeuvre passive head up tilt protocol
was followed only for 10 minutes. Tilt table with foot
board was used in the study to support body weight.
The following sequence of recording was followed.
1. Basal: 20 minutes of rest on tilt table in supine

position
2. After 30 HUT
3. After 60 HUT
Cardiac parameters were recorded immediately after
1,5,10 minutes of HUT. Between each HUT the
166
Badwe AN et al.,
subject was tilted back to horizontal position and

allowed to rest for 10 minutes.
Statistical analysis: For each parameter of both
groups-mean and standard deviation (SD) were
calculated. To find any significant change the data was
analyzed for the same group by applying Student t

test and between two groups by applying unpaired ttest. The P values less than 0.05 (P<0.05) were
considered as statistically significant.
RESULTS:
Table:1. Anthropometric characteristics of subjects
Parameter
Normotensive
Hypertensive
Age(yrs)
Height (cm)
Body weight kg
BMI (Kg/m2)
% Fat
Fat Mass (Kg)
Fat Free Mass (Kg)
35.721.88
163.861.01
55.261.20
20.810.48
23.891.01
13.470.67
41.760.92
49.281.94
164.741.10
65.561.71
24.210.57
31.101.05
21.021.18
43.940.82
Values are Mean SE

Higher values of anthropometric characteristics were
recorded in hypertensive individuals as compared to
control group, which were non significant (Table: 1).
All results are presented graphically for better

understanding of the effect produced by both angles of
head up tilt in both study groups.
Table: 2. Effect of 30, 60head up tilt on cardiovascular parameters in normotensive

Basal
30HUT
1 Min
5 Min
10 Min
1 Min
SBP
121.41.66
117.441.80* 118.422.03
119.641.79 116.942.13*
DBP
76.261.30
77.041.30
77.221.21
78.11.57
78.81.43
PP
45.881.29
40.41.64***
41.21.70*
41.71.71*
38.341.66***
MAP
91.511.60
90.431.79
89.531.82
90.241.80
91.491.51
HR/MIN
75.61.60
78.141.79* 80.521.82*** 79.61.80*
89.242.01***
RRP
9.02.74
9.092.30
9.482.59*
9.721.16**
10.430.31***
Parameter
60 HUT
5 Min
10 Min
121.841.78
117.662.14*
80.262.25
80.541.58*
40.241.90*
37.41.67***
93.092.31
92.881.62
91.561.93***
89.622.56***
11.350.41***
10.640.33***
Values are Mean SE. Pressure values are in mmHg. Basal values are before tilt. SBP: systolic blood pressure,
DBP: diastolic blood pressure, PP: pulse Pressure, MAP: mean arterial blood pressure, HR/MIN: heart rate/min
RPP: rate pressure. (Paired t test:*P<0.05significant, **P<0.01 highly significant ***P<0.001 very highly
significant, Comparison between 30 and 60 head up tilt: P<0.05significant, P<0.01 highly significant
P<0.001 very highly significant, Unpaired t test: P<0.05 significant, P<0.01 highly significant <0.001
very highly significant)
Normotensive:
30 HUT caused minimal and
significant decrease in SBP after 1 min of HUT. After
1 minute of tilt, there was minimal decrease in SBP,
which remained insignificantly lower than basal value
for a total duration of 10 minutes of HUT.
DBP showed a marginal increase than basal value after
1 minute of HUT and remained almost constant
throughout the 10 minutes duration of HUT.
PP registered very highly significant decrease
(P<0.001) in its value than the basal value after 1
minute of tilt and showed a further significant decrease
(P<0.05) at 5 and 10 minutes of HUT.
MAP (=DBP+1/3 PP) showed insignificant decrease

after 1 minute of HUT and the same pattern was
continued for 5 and 10 minutes of HUT.
HR also registered increase in its value, which was
more than basal value. This change was significant
after 1minute (P<0.05) and at 5 (P<0.001), 10
(P<0.05) minutes of HUT.
RPP showed a marginal insignificant increase in its
value after 1 minute of HUT, however after 5 (P<0.01)
and 10 (P<0.001) minutes of HUT, RPP registered a
significant increase in its value.
167
Badwe AN et al.,
60 HUT: 60 HUT produced more significant

changes in cardiovascular parameters as compared to
30 HUT. SBP decreased significantly (P<0.05) after 1
and 10 minutes (P<0.05) of HUT. Insignificant
increase was observed at 5 minutes of HUT, than basal
value.
DBP registered a marginal insignificant increase at 1
and 5 minutes of HUT, however at 10 minutes of HUT
significant (P<0.05) increase in DBP was recorded. PP
registered significant decrease at 1(P<0.001),
5(P<0.05), 10(P<0.001), minutes of HUT. This
decrease was lower than basal value. MAP showed

insignificant decrease in its value after 1,5,10 minutes
of HUT. HR registered very highly significant
(P<0.001) increase as compared to basal values
throughout the duration of 10 minutes of HUT. RPP
also recorded very highly significant (P<0.001)
increase in its value as compared to basal values
throughout the duration of 10 minutes of HUT
Table: 3 Effect of 30 and 60head up tilt on cardiovascular parameters in hypertensive

Basal
30HUT
60 HUT
1 Min
5 Min
10 Min
1 Min
5 Min
140.43.59
141.722.48
142.482.70 140.52.58 137.43.04
136.583.83
SBP
93.841.99
93.922.54
96.361.99
96.481.84
95.581.74
95.001.92
DBP
49.782.15
45.501.99
45.882.00*
43.92.56*
46.662.90
43.781.99**
PP
109.332.16
111.251.81
111.652.02
111.031.73 100.603.18*
109.562.11
MAP
75.481.96
75.802.31
76.821.78 79.821.95** 84.261.74*** 83.721.85***
HR/MIN
10.70.36
10.980.38
10.820.39
10.840.38
11.740.43***
11.580.40*
RRP
Parameter
10 Min
132.623.49
94.141.70
40.681.96***
107.711.78
84.802.33***
11.400.41*
Values are Mean SE .Pressure values are in mmHg. Basal values are before tilt.SBP: systolic blood pressure,
DBP: diastolic blood pressure, PP: Pulse pressure, MAP: mean arterial blood pressure, HR/MIN: heart rate/min,
RPP: rate pressure product. (Paired t test:*P<0.05significant, **P<0.01 highly significant ***P<0.001 very highly
significant, Comparison between 300 and 600 head up tilt : P<0.05significant, P<0.01 highly significant
P<0.001 very highly significant, Unpaired t test: P<0.05 significant, P<0.01 highly significant <0.001
very highly significant)
Hypertensive: All cardiovascular parameters recorded
in hypertensives registered increase its value, as
compared with normotensives at 30and 60 HUT at
different time intervals.
30 HUT: SBP registered a marginal insignificant
increase in its value than the basal value after 1and 5
minutes of HUT. After 10 minutes of HUT decline in
SBP was observed and returned to baseline values.
DBP also registered a marginal insignificant increase
in its value than basal value after 1 minute of HUT and
this insignificant increase was followed for 5 and 10
minutes of HUT.
PP showed an insignificant increase after 1 minute of
HUT and increase at 5 and 10 minutes of HUT, was
found to be more significant (P<0.05) than basal value.
MAP recorded insignificant increase in its value after
1,5,10 minutes of HUT
HR recorded initially decrease in its value as
compared to basal value, however at 10 minutes of
HUT significant (P<0.01) increase in HR was
observed. RPP recorded a marginal insignificant
increase than basal value after 1,5,10 minutes of HUT.
60HUT: HUT SBP decreased insignificantly and

remained lower than basal value during 1, 5, 10
minutes of HUT.
DBP recorded a marginal increase in its value than
basal value at 1,5,10 minutes of HUT
PP recorded insignificant decrease after 1 minute of
HUT, however this decrease was significant at 1
minute (P<0.01) and 10 minutes (P<0.001) of HUT
than initial basal value. MAP registered a significant
increase in its value after 1minute (P<0.05) of
HUT.MAP showed further a marginal decrease at 1
and 5 minutes of HUT, than basal value. HR recorded
a highly significant increase (P<0.001) at 1,5,10
minutes of HUT. RPP also registered very highly
significant (P<0.001) increase in its value after 1
minute of HUT and remained significant (P<0.05)
increased at 5 and 10 minutes of HUT.
DISCUSSION
In the present study, we studied effect of 30 and 60
HUT on cardiovascular parameters in normotensive
and hypertensive subjects.
168
Badwe AN et al.,
Normotensive:
SBP, PP and MAP parameters
decreased, while DBP, HR/MIN, RPP increased
gradually as the angle of HUT increased. At 30 HUT
changes recorded in SBP, PP, HR/MIN, RPP were
significant.
Similarly same pattern of decrease in SBP, PP, and
MAP was observed in normotensive at 60 HUT and
significant pattern of increase in DBP, HR/MIN, and
RPP was observed. Except decrease in MAP other
findings of our study agree with the study conducted
by Vijayalaxmi et al15.It is important to note that,
autonomic functions vary with ageing 16 and
parasympathetic 17 is also reduced, since our subjects
were selected from different age group (20-70 yrs). In
normotensive subjects, significant fluctuations were
not observed, since, during the initial phase of HUT
intact
autonomic
activity18
stabilized
the
cardiovascular parameters during the total duration of
HUT.
Hypertensive: In hypertensive individuals, SBP, PP,
MAP showed decrease at 300 and 600 HUT. Similarly
DBP, HR/MIN, RPP showed increase in their value at
both angles of HUT. However, these changes were
more significant at higher angle of 60 HUT, in both
groups.
MAP is dependent on heart rate (HR), stroke volume
(SV) and total peripheral resistance (TPR), which can
be correlated as MAP=HR X SVX TPR. During HUT,
changes like pooling of blood in lower parts of the
body and low carotid pressure in the carotid sinus
occur.19
These gravity induced changes produced decreases in
venous return, stroke volume, pulse pressure, mean
arterial pressure which cause tachycardia and
vasoconstriction, due to baroreceptor reflex20. In this
upright posture increase in heart rate and peripheral
resistance regulate blood pressure. This mechanism is
more effective in younger individuals than older ones
in maintaining blood pressure in upright posture.
21
This was the major factor to cause a decrease in SBP,
PP and MAP during HUT.
Increase in HR, as reported by other studies is tilt
dependent, which remained elevated throughout the
period of HUT. However, this increase in HR may be
due to increase in sympathetic stimulation and
withdrawal of vagal tone, which is the prominent
finding in hypertensive.22
HUT 30 and 60 produced an increase in RPP in both
groups, but this increase was more in the hypertensive
group than normotensive group. HUT of 60 produced

a more significant increase in its value throughout the
duration of HUT. The increase in RPP was caused due
to increase in SBP and HR.RPP (Robinson Index) was
expressed as RPP= SBP X HR X10-3. 23RPP indicates
myocardial oxygen consumption and cardiac work in
normal subjects as well as patients with heart
diseases.24 It also indicates onset of ischaemia in
patients undergoing surgery or the onset of coronary
pain during exercise.25,26 Higher values of RPP
recorded in hypertensive than normotensive indicate
more oxygen consumption, coronary blood flow and
more myocardial work.
CONCLUSION
The results of this study indicate a significant effect of
HUT on cardiovascular parameters in hypertensive
group. It is worth noting that, significant changes in
HR and RPP in hypertensive individuals indicated
more myocardial oxygen consumption and myocardial
work at both angles of HUT. These are more
prominent at higher angles of HUT than the lower
angle of HUT.
REFERENCES
1. Severe K, Lefrandt, Nordby G, Os I. Autonomic
function in hypertensive and normotensive
subjects. Hypertension 2001; 37:1351-56
2. Chakko S, Muligtapang RF, Huikuri HV.
Alterrations in heart rate variability and its
circardian rhythm in hypertensive patients with
left ventricular hypertrophy free of coronary artery
diseases. American Heart Journal 1993;126:136472.
3. Guzzeti S, Piccgluger E, Casati R. Sympathetic
predominance in essential hypertension: a study
employing spectral analysis of
heart rate
variability. J Hypertens 1988;6:711-17.
4. Singh JP, Larson NG, Tuji H. Reduced heart rate
variability and new onset hypertension: The
Framingham
heart
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Hypertension
1998:77:93-297.
5. Huikuri HV, Ylitalo A, Pikkujamsa SM. Heart rate
variability in systemic hypertension. Am J Cardiol.
1996;77(12): 1073-1077.
6. Pikkujamsa SM, Huikuri HV, Airaksinen KE.
Rate variability and baroreflex sensitivity in
hypertensive subjects with and without metabolic
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features of insulin resistance syndrome. Am J

Hypertens 1998;11:523-31.
Vaz M, Kulkarni RN, Rodrigues D, Shetty PS.
Immediate heart rate responses to head up tilt in
healthy human subjects: response characteristics
and variability. Indain J Physiol Phramacol
1993:37(4):323-27.
Jahan N, Deepak KK, Kaushal Navita, Paudel BH.
Effect of graded head up tilt on parasympathetic
reactivity.
Indain
J
Physiol
Phramacol
1996:40(4):309-17.
James MA, Robinson G T, Potter JF. The effect of
systemic blood pressure on cardiovascular reflexes
in
elderly
subjects.Clinical
Physiology
2008:21(1):67-76.
Wahbha MMAE, Wilson , Hainsworth R.
Cardiovascular response to upright tilting in
hypertensive patients with and without renal
impairment and before and following nisoldopine
treatment. Br. J. Clin. Pharmac 1990;29:733-39.
Guidelines sub committee. 1993 Guidelines for the
management of mild hypertension:memorandum
from a World Health Organization/ International
Society of Hypertension meeting.J Hypertens
1993;11:905-918.
Joint National Committee on prevention, detection
and treatment of high blood pressure .The sixth
report of the Joint Committee on prevention,
detection and treatment of high blood
pressure.(JNC VI). Arch Intern Med 1997;157:
2413-46.
Chobanian AV, Bakris GL, Black AR. Joint
Committee on prevention, detection and treatment
of high blood pressure. National Heart, Lung and
Blood Institute, National high blood pressure
programme coordinating
committee. Seventh
report of the Joint Committee on prevention,
detection and treatment of high blood pressure.
Hypertension 2003;42:1206-52.
Shah Siddharth, convenor. Practical guidelines for
physicians: Indian hypertension guidelines 2007.
Supported by unrestricted educational grant Pfizer,
India. Website address
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assessment. In Exercise Physioloy: energy,
Nutrition
and
Human
Performance.5th
Ed,Lippincott
Williams
and
Wilkins,
Baltimore:2001:772-776.
16. Collins KJ, AN Exton-Smith. Functional changes

in autonomic responses with ageing. Age and
Ageing 1980:9:17-24.
17. Vita GP, Calabro R, Toscano. Cardiovascular
reflex test: Assessment of age adjusted normal
range. J. Neural Sci 1986;75:263-74.
18. Guyton AC, Hall JE. Nervous regulation of the
circulation and rapid control of arterial pressure. In
T.B of Medical Physiology.11th Ed ,Saunders,
Philadelphia. 2006:204-14.
19. Neto JAN, Gallo L, Manco JC. Mechanism of
tachycardia on standing: Studies in normal
individuals and in chronic changes in heart
patients. Cardiovas Res. 1980;14:541-50.
20. Florica V, Kem DC. Plasma norepinephrine, blood
pressure and heart rate response to graded change
in body position. Aviat Space Environ Med
1985;56:1166-71.
21. Luutonen S, Antila K, Errko M. Haemodynamic
response to head up tilt in elderly hypertensive and
diabetic. Age and ageing 1995;24(4):315-20.
22. Langewitz W, Ruddel H, Schachinger H. Reduced
parasympathetic cardiac control in patients with
hypertension at rest and mental stress. Am Hear J
1994;127:199-204.
23. Pepper MG, Crawley BE.Technical note:
Calculation and display of the rate/pressure
product during anaesthesia using binary rate
multipliers.
Med
and
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and
Comput.1985;23:187-89.
24. Globel FL, Nordstrom LA, Nelson RR. The rate
pressure product as an index of myocardial
oxygen consumption during exercise in patients
with angina pectoris. Circulation 1978;57:549-56
25. Cokkinos DV, Vorodis ES. Constancy of pressure
product in pacing induced angina pectoris. British
Heart Journal 1976;38:39-42.
26. Robinson BF. Relation heart rate and systolic
blood pressure to the onset of pain in angina
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DOI: 10.5958/j.2319-5886.3.1.033

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Letter to Editor
Copyright @2013
ISSN: 2319-5886
PEDAGOGY TO ANDRAGOGY
Darshana Bennadi
Senior Lecturer, Dept. of Public Health Dentistry, Sree Siddhartha Dental College and Hospital, Tumkur, India.
Corresponding author email: darmadhu@yahoo.com
Dear Sir,
I would like to congratulate Muneshwar JN, Mirza
Shiraz Baig, Zingade US, Khan ST for highlighting a
very important issue regarding the teaching methods
for health care professionals.1 Study has proved the
Chinese proverb: If I hear, I forget; if I see, I
remember; if I do, I know. Along with this I want to
focus little on podcast as new teaching method.
At present, education trend have changed from
pedagogy to andragogy i.e. from a teacher-centered
learning to a student-centered learning. These methods
of education trends have identified many different
learning styles as well. So, now it has become
necessary for educators to train themselves to
upcoming teaching methods. 2
Many new teaching methods are evolving in the
current electronic world. In which Podcasts as a
supplement to live lectures is one of the teaching
method, which have been adopted by many
universities. Podcasting is user friendly, where
information is recorded, then uploaded to a website or
published through programs like iTunes and made
accessible to students. The file can then be played on a
computer or digital player.3,4
Recently many studies have been conducted using
podcast as a new aid and its effectiveness. Studies
have shown that audio podcasts as an effective aid for
review before exams, enhancing student performance;
acceptability and perceived utility of podcasts was
good among students. Introduction of podcasts in the
beginning will offer the students a lot of flexibility in
learning, with regard to place and time.4
Darshana Bennadi,
Podcasts as a supplement to live lectures as teaching

method has open up for future research to assess their
utility on a long-term basis so as to pave the way for
introducing podcasts as one of the teaching method.
REFERENCES:
1. Muneshwar JN, Mirza Shiraz Baig, Zingade US,
Khan ST. A questionnaire based evaluation of
teaching methods amongst MBBS students. Int J
Med Res Health Sci.2013;2(1):19-22
2. Poonam Kharb, Prajna Paramita Samanta,
Manisha Jindal, Vishram Singh. The Learning
Styles and the Preferred Teaching Learning
Strategies of First Year Medical Students. Journal
of Clinical and Diagnostic Research. 2013;7(6):
1089-92
3. Burns TM. The forecast for podcasts: sunny skies
but not necessarily with clear visibility.
Neurology. 2007; 68(15):E19-20.
4. Kalludi SN, Punja D, Pai KM, Dhar M. Efficacy
and perceived utility of podcasts as a
supplementary teaching aid among first-year
dental students. AMJ 2013; 6(9): 450-57
Int J Med Res Health Sci. 2014;3(1):171
171
DOI: 10.5958/j.2319-5886.3.1.034

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www.ijmrhs.com Volume 3 Issue 1 (Jan - Mar) Coden: IJMRHS
Received: 4th Dec 2013
Review article
Copyright @2013
ISSN: 2319-5886
EMERGING ROLE OF VITAMIN D IN HEALTH

*Deepanjali Lomte
Associate Professor, Department of Pharmacology, Dr.Vasantrao Pawar Medical College, Hospital & Research
Centre, Nashik, Maharashtra, India.
*Corresponding author email: dlomte@gmail.com
ABSTRACT
Vit. D is a steroid prohormone. It is synthesized in the skin under ultra violet light exposure. Traditionally, Vit.D3,
cholecalciferol and calcitriol were known to have a role only in calcium and bone mineral metabolism. This article
takes an account of the current view on the impact of Vit D deficiency on human health. Research has now shown
the indisputable role of Vit D in prevention/treatment of some cancers, osteoporosis, rheumatoid arthritis, multiple
sclerosis, tuberculosis, hypertension, and diabetes mellitus. In addition lower maternal Vit. D levels are associated
with Pregnancy Induced Hypertension (PIH), suggesting that Vit. D deficiency may be a modifiable risk factor for
PIH. Greater awareness of the problem of a high prevalence of vitamin D inadequacy is required among researchers,
clinicians, and patients. Special efforts on the medical and social fronts are necessary to combat this preventable
epidemic of vitamin D deficiency.
Keywords: Vitamin D, 25-Hydroxyvitamin D, PIH, Pregnancy, Hypervitaminosis D, Cholecalciferol, Calcitriol.
INTRODUCTION
Vitamin D is more important nutrient for health.
Vitamin D is actually a hormone rather than a vitamin.
Despite its discovery 100 years ago, Vit D has
emerged as one of the most controversial nutrients and
prohormones of the 21st century, and a lot of research
has been in place on this molecule. Traditionally,
Vitamin D was viewed as a permissive factor in
calcium and bone mineral metabolism. It works with
the Parathyroid hormone (PTH), acts on the kidneys,
bone & intestine and influences gene expression. The
research leads us to newer therapies with newer
concepts.1 Research has now shown Vit D's indisputable role in both inherent and adaptive immunity.
Vit D is a Steroid prohormone and it is synthesized in
the skin under ultra-violet light exposure. 7Dehydrocholesterol present in the skin absorbs UV
light over wavelengths of 290-300 nm [UVB] to
synthesize Vit D3. Synthesis in the skin epidermis
takes place over several days; the quantity (intensity)
and quality (appropriate wavelength) of sunlight are

both important this biosynthesis can be inadequate due
to poor dietary intake, absorption, or poor exposure to
sunlight [UVB]. The deficiency can occur because of
fat malabsorption, anticonvulsant use, chronic kidney
disease and obesity and is seen in high-risk groups like
elderly women, dark-skinned people, people from
areas with a thick layer of ozone, women using
sunscreen lotions, and people from urban areas.2
In urban and polluted areas, the UV light of 290-300nm wave length gets filtered out; hence, skin may not
get enough of this light. Therefore, there is a high rate
of Vit D deficiency even among the urban population.
Hence, foods and dietary supplements are necessary.
Cod liver oil, salmon and sardines, fortified milk, egg,
fortified yogurt, mushrooms, fortified soy products,
oysters, and fortified cereals are rich sources of Vit D.
Activation of Vitamin D: It takes place in the
following manner: 1
Deepanjali,
172
Fig 1: Activation of Vitamin D

Under situations of minimal exposure to sunlight, a
specific recommendation of a daily supplement of 400
IU (10 g) is retained for the Indian population. RDA
for pregnant women is 200 IU per day and the
maximum safe daily dose is 2,000 IU. Due to
increased deficiency screening for vitamin D levels is
important for most individuals. A serum concentration
of 25 (OH) D is the best indicator of vitamin D.
The Emerging Roles of Vit D: It is now considered
important in cell differentiation, proliferation, and
immune function. It is an important factor in
prevention/treatment of some forms of cancer,
osteoporosis, rheumatoid arthritis, multiple sclerosis,
hypertension, cardiovascular disease, obesity, psoriasis,
and psychiatric diseases. The role of vitamin D in
pregnancy is also taking new dimensions.
Vit. D and Pregnancy: Maternal Vit.D deficiency is
common during pregnancy and throughout gestation.
If a women is Vit. D deficiency, it leads to a number
of serious health problems likes poor bone
mineralization in infants, low birth weight baby and
other adverse pregnancy outcomes.3-5 There are
different deficiency levels. The risk of rickets
increases significantly when the total circulating
25(OH)D falls below 10 ng/mL (25 nmol/L), whereas
cathelicidin mRNA expression as a marker of immune
function continues to be suppressed until 25(OH)D
circulating levels reach at least 20 ng/mL (50
nmol/L).6
The recently revised Institute of Medicine's (IOM)
2010 criterion for Vit D deficiency of total circulating
25(OH) D is <20 ng/mL (50 nmol/L), Optimal serum
concentrations of 25(OH) D3 are at or above 30 ng/mL
(>75 nmol/L), and Vit D toxicity is present when
levels are at or above 150 ng/mL (374 nmol/L).7
Rates of deficiency of Vit D are more with women

who have darker pigmentation and women who have
limited access to sunlight, through limited outdoor
activity.8 Vit D deficiency exists in a higher percentage
in obese women. Women including pregnant women,
with a BMI >30, are at increased risk of Vit D
deficiency.8 The adipose tissue serves as a repository
for Vit D that does not get into the circulation.
As per recent guidelines Recommended Daily
Allowance (RDA) of Vit. D during pregnancy is 200400 IU/day and more than 2,000 IU/day has been toxic
not just to the pregnant women but to the any one. As
per recent research, higher dosages of Vit D are not
just safe during pregnancy, but increased dosage may
actually reduce the risk of complications.
In a study, 500 women who were at least 12 weeks
pregnant took 400, 2000, or 4000 IU of Vit D per day.
The women who took 4,000 IU were less prone for
preterm labour or infections during pregnancy. Vit D
intoxication is extremely rare and easy to treat.
Pregnant women who get too little Vit D are more
likely to develop PIH (Pregnancy induced
hypertension) and are also more likely to require a
Cesarean section. They concluded that giving 4,000 IU
a day to pregnant women may not only improve birth
outcomes but also does not cause toxicity.9
Pregnant women with a serum level of 25-OH Vit D
<75 nmol/L are considered to be Vit D3 deficient.10
Until recently, it was thought that Vit D deficiency
was common only in high-risk women (women with
dark skin and those with minimal exposed skin), but it
is quite high even in low-risk women.
All women therefore should be offered testing for Vit
D status in early pregnancy and recommended
supplementation if deficient.11
Women with a 25-OH Vit D3 <75 nmol/L are
considered Vit D deficient and should have a dietary
assessment for calcium intake. They should receive a
higher dose up to 1000 IU. They should be offered
retesting at 28 weeks of pregnancy. If the higher dose
of Vit D does not improve the serum Vit D levels, then
malabsorption syndrome (such as celiac disease)
should be ruled out or else the patient may be noncompliant.
Pregnant women should have enough Vit D at the time
of delivery to insure sufficient Vit D levels in their
baby for the first 4-6 months of life.
The transplacental passage of maternal 25-OH Vit D3
is the sole source of Vit D in the developing fetus.
173
Deepanjali,
Therefore, infants are wholly dependent on their

mother for their Vit D status. Infants born to Vit Ddeficient mothers will be Vit D deficient and hence
will require supplementation in the form of
cholecalciferol bolus (50,000 IU) dose orally. The
obstetricians must understand the importance of
vitamin D supplementation to pregnant and nursing
mothers, which will go a long way in preventing
rickets.
Emerging Role of Vitamin D in Other Diseases: The
role of Vit D in osteoporosis and muscle weakness is
indisputable. But, there is a recent trend to give a
higher dose of Vit D to prevent the osteoporotic
fracture.
In a placebo controlled study, oral Vit.D (700-800
IU/d) with or without calcium supplementation was
given to elderly persons. The results show that there
was statistically significant (23-43%) reduction in risk
of a hip fracture and any non-vertebral fracture.12-15
Multiple sclerosis is an autoimmune disease which is
more prevalent in temperate climates than the tropics
and is also seen much more commonly in women. It is
associated with lower serum vitamin D levels, and Vit
D supplementation may have a preventive role in
multiple sclerosis.
The protective role of optimal Vit.D status and lower
risk of cancer has been reported in many studies.
Seven decades ago, Pellers and etal first time reported
that sunlight exposure may reduce the risk of cancer.16
In another study it has been reported that when the
concentration of 25 OH Vit.D > 32 ng/ml, there was
50% reduction in breast and colorectal cancer.17-18 The
higher the Vit D level, the lower the risk of cancer.
Vitamin D acts as an immunosuppressant in
rheumatoid arthritis as well.
Vit.D has a preventive role in development of diabetes
mellitus. Pittas AG and et al studied on high dosage of
calcium and Vit.D over 2-4 years in 83779 women
with no history of diabetes. In this study for group one
calcium >1200 mg/day and Vit. D >800 IU/day was
given. For group two calcium <600 mg/day and Vit.
D <400 IU/day was given. The results show that in
group one there was 33% lower risk of type 2 diabetes
as compared to group two.19 In another study in
Finland over 31 years Vit. D in a dose of 2000 IU/day
was administered to 10366 children during their first
year of life and result show that the risk of type 1
diabetes reduce by 80%.20
Tuberculosis is associated with lower Vit D levels.

Before the antikoch's treatment was available, high
dosages of Vit D were given to patients. We see this
disease in urban areas in women with a specific
dressing style which prevents adequate sunlight
exposure.
Adverse Effects of Vit D Therapy: The primary
toxicity associated with Calcitriol is to increase
intestinal calcium and phosphate absorption, along
with the potential to mobilize osseous calcium and
phosphorus concentrations.
Hypervitaminosis D is treated by immediate
withdrawal of the vitamin, a low calcium diet,
administration of glucocorticoids and vigorous fluid
support. Forced saline diuresis with loop diuretics for
hypercalcemia is useful. With this plasma Ca2+
concentration fall to normal and Ca2+ in soft tissue
tends to mobilize. Conspicuous improvement in renal
function occurs.1
Deepanjali,
CONCLUSION
To summarize, Vit D deficiency is highly prevalent
and contributes to women's health greatly. Getting too
little vitamin D is worse than getting too much. Newer
reports are changing our ideas about the optimal Vit D
status and the role of Vit D in health, especially in
relation to modern chronic diseases affecting women.
It must be remembered that some populations are still
very much under treated, and pregnancy-associated
complications can be reduced with correction of the
deficient state.
In spite of the close relation of vitamin D to human
health, vitamin D deficiency is not widely recognized
as a problem by doctors and patients. Greater
awareness of the problem of a high prevalence of
vitamin D inadequacy is required among researchers,
clinicians and patients. Women in the underprivileged
sections, both in urban and rural India, are battling
inadequate resources, multiparty, imposed customs of
clothing, and social vulnerability of the fairer sex
which coupled with the urban environmental decay
will continue to pose the threat of Vit D deficiency.
Special efforts on the medical and social fronts are
necessary to combat this preventable epidemic of
vitamin D deficiency.
174
REFERENCES
1. Peter A. Friedman, Agents affecting Mineral Ion.
Homeostasis and Bone Turnover. Goodman and
Gillmans Pharmacological basis of Therapeutics.
12th Ed:1280-94
2. Adams JS, Chen H. Chun R. Substrate and
enzyme trafficking as a means of regulating 1,25dihydroxyvitamin D synthesis and action: the
human innate immune response. J Bone Miner Res.
2007;22:V20
3. Viljakainen HT. Saamio E, Hytinantti T. Maternal
vitamin D status determines bone variables in the
newborn. J Clin Endocrmol Metab. 2010;95:l74957
4. Mahon P, Harvey N, Crozier S, et al. Low
maternal vitamin D status and fetal bone
development: Cohort study. J Bone Mincr Res.
2009;25:l4-9.
5. Pasco JA, Wark JD, Carlin JB. Maternal vitamin
D in pregnancy may influence nol only offspring
bone mass but other aspects of musculoskeletal
health and adiposity. Med Hypotheses.
2008;71:266-69
6. Walker V, Zhang X, Rastegar I. Cord blood
vitamin D status impacts innate immune responses.
J Clin Endocrinol Mctab. 2010;96:l835-43
7. Standing Committee on the Scientific Evaluation
of Dietary Reference Intakes. Dietary reference
intakes for vitamin D and calcium. Washington,
DC:
National
Academy
Press;
2010.
www.ncbi.nlm.nih.gov. NCBI Literature Books
helf
8. Johnson DD, Wagner CL, Hulsey TC. Vitamin D
deficiency and insufficiency is common during
pregnancy. Am J Pcrinatol. 2011:28:7-12
9. Hollis B, Johnson D, Hulsey T. Vitamin D
supplementation during pregnancy: Double-blind,
randomized clinical trial of safety and
effectiveness. J Bone Miner Res. 201l;26:2341-57
10. National Institute for Health and Clinical
Excellence. Antenatal Care Routine care for the
Healthy Pregnant Women. NICE Clinical
Guideline 62, London. 2009
11. Southern Health. Vit D and calcium in pregnancy
and breast feeding information sheet for women
(to be developed) clinical protocols and guidelines,
Maternity. 2009: http://www.monashhealth.org/
icms_docs/6643_Vitamin_D_in_pregnancy_a
nd_the_term_newborn.pdf
12. BischoIT-Ferrari HA, Willett WC. Wong JB.
Fracture
prevention
with
vitamin
D
supplementation: a meta-analysis of randomized
controlled trials. JAMA. 2005;293:2257-64
13. Chapuy MC, Arlot ME, Duboeuf F. Vitamin D3
and calcium to prevent hip fractures in the elderly
women. N Engl J Med. 1992;327:1637-42
14. Chapuy MC, ArJot ME, Delmas PD. et al. Effect
of calcium and cholecalciferol treatment fot 3
years on hip fractures in elderly women. BMJ.
1994:308:1081-82
15. Lips P, Graafmans WC, Ooms ME. Vitamin D
supplementation and fracture incidence in elderly
persons: a randomized, placebo-controlled clinical
trial. Ann Intern Mcd. 1996:124;400-06
16. Peller S, Stephenson CS. Skin irritation and cancer
in the United States Navy. Am J Vied Sci. 1937;
194:326-33
17. Lappc JM. Travers-Gustafason D, Davies KM.
Vitamin D and calcium supplemcnlation reduces
cancer risk: results of a randomized trial. Am J
Clin Nutr. 2007:85:1586-91
18. Dembrow M. High vitamin D: Rx for cancer
prevention? Clin Advisor. 2007;10:54-57
19. Pittas AG, Dawson-Hughes B, Li T. Vitamin D
and calcium intake in relation to type 2 diabetes in
women. Diabetes Care. 2006:29:650-56
20. Hypponen E, Laara E, Reunanen A.. Intake of
vitamin D and risk of type 1 diabetes: a
birthcohort study. Lancet. 2001;358: 1500-03
175
Deepanjali,
DOI: 10.5958/j.2319-5886.3.1.036

&
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th
Revised: 23rd Oct 2013
Case report
Copyright @2013
ISSN: 2319-5886
KIMURAS DISEASE: A RARE CASE REPORT

*Nagarekha Kulkarni
Professor, Department of Pathology, Vijayanagara Institute of Medical Sciences, Bellary, Karnataka, India
Corresponding author email: nagarekhaphaniraj1970@gmail.com
ABSTRACT
Introduction: Kimuras disease is of unknown etiology. Case report: This report describes an interesting case of
Kimuras disease in an 18 years old male manifesting as a unilateral left sided parotid swelling with multiple
cervical lymphadenopathy. There was eosinophilia and increased levels of circulating IgE. Patient was treated
with surgical excision and corticotherapy, cetrizine was prescribed. Histologically there were numerous follicles
with prominent germinal centres. Interfollicular area was infiltrated with eosinophils and plasma cells.
Conclusion: Any swelling in the head and neck region associated with eosinophilia should make one to suspect
the Kimuras disease.
Keywords: eosinophilia, lymphadenopathy, angiolymphoid hyperplasia
INTRODUCTION
The history of Kimuras disease dates back to 1937
when HT Kimm and C Szeto first described about it.1
Kimura et al in the year 1948 was the pioneer to
describe the microscopic features of the disease.
Hence, the disease is recognised by his name.1 This
disease is seen in young Asian males and the cause of
this rare entity is not known. Only 200 cases are
reported since its histological description and
sporadic in the rest of the world.2 Clinically the
disease presents as swelling in the head and neck
region characterised by eosinophilia in blood and
tissue with marked elevated serum immunoglobulin E
(IgE) levels.3 This report describes a rare case of
Kimuras disease in a 18 years old male who
presented with parotid swelling
CASE REPORT
An 18 years old male presented to the ENT outpatient
department with the swelling on the left side of the
face below the left ear. It was sudden in onset and
progressed gradually to attain the size of 12X10cms.

There was no past history of prolonged fever, cough,
loss of weight and loss of appetite. He was nonalcoholic and non-smoker. The family history was
unremarkable. On palpation the swelling was diffuse,
non-tender, firm, multiple over left parotid region
The swelling was measuring 12x10cms, mobile, skin
over the swelling was pinchable and hyperpigmented.
Other groups of the lymph nodes were not enlarged.
There was no hepatosplenomegaly. Bilateral ear and
facial nerve examination were within normal limits.
The vital signs and laboratory investigations were
normal except there was eosinophilia and elevated
IgE levels as shown in table-1. Neck ultrasonography
revealed enlarged parotid gland with altered
echotexture, multiple enlarged pre and post auricular
lymphnodes. Fine needle aspiration biopsy revealed
features of reactive lymphadenitis. After a course of
antibiotics the swelling was excised and sent for the
histopathological examination. He was treated with
179
Nagarekha
levofloxacin, acclofenac, cetrizine and B- complex

tablets.
The specimen was received in the histopathology
section. Macroscopic examination revealed a well
circumscribed mass measuring 12X8X5cms. External
surface was unremarkable and cut section showed
grey white homogenous areas as shown in figure - 1.
The specimen was processed routinely in the
histopathological section and the sections were
stained with haematoxylin and eosin stain (H/E).
Microscopic examination revealed the architecture of

the lymph nodes with numerous follicles showing
hyperplastic feature with germinal centers. Many
eosinophils and plasma cells were present in the
interfollicular area. Also seen are perifollicular
fibrosis, prominent blood vessels with endothelial
proliferation and mild hyaline change as shown in
figure 2. The diagnosis of Kimuras disease was
made.
Table 1: Shows vital signs and laboratory findings

Vital Signs: Pulse Rate: 86/minute, Blood Pressure: 130/80 mm of Hg, Respiratory Rate: 28/minute
Temperature: 38.5oc
Laboratory Investigations:
Hb%: 11.8g/dl (normal:12.5-14.5g/dl)
RBC Count: 3.8millions/cmm (normal:4.5-5.5millions/cmm)
Haematocrit: 34% (normal: 35% to 45%)
WBC Count: 9800 cells/cmm (normal: 4000 to 11,000/cmm)
Differential Count: Neutrophils: 65%, Lymphocytes: 23%, Eosinophils: 10%, Monocytes: 02%
Basophils: 00%
Bleeding Time-3 minutes 30 seconds (Normal:2-6minutes)
Clotting Time-4 minutes 30 seconds (Normal: 2-8minutes)
Absolute eosinophil count: 600 cells/cmm (Normal:40-440cells/cmm)
Serum IgE:4.4mg/dl (Normal: 0.01 0.04 mg/dl)
Stool tests: negative for parasites
Random Blood Sugar: 90mg/dl (normal: 80 to 110mg/dl)
Blood Urea: 19mg/dl (normal: 5 to 25mg/dl)
Serum Creatinine: 0.8mg/dl (normal: 0.8 to 1.2mg/dl)
Serological Investigations: HIV-1 & 2:Negative , HBsAg : Negative
Routine Urine Examination: Albumin: Nil, Sugar: Nil, Urine micro: 1-2 pus cells/HPF
Table 2: Shows the difference between kimuras disease and angiofollicular hyperplasia with eosinophilia1
Kimuras disease
Young man (2nd-3rd decade)
Oriental
Voluminous subcutaneous
salivary gland involvement
mass,
adenopathy,
Angiofollicular hyperplasia with eosinophilia

Middle aged woman (3rd-5th decade)
Westerner
Subcutaneous or dermal cervical papules or nodules;
overlying skin is erythematous or pigmented; rare
adenopathies
Same aspect. Histiocytoid vessels with particular
endothelial cells (different sized nuclei and protrusion
into the vessel lumen)
Follicular hyperplasia, eosinophil infiltration of

interfollicular and perivascular zones with abcess
formation and lysis, postcapillary venule
proliferation
Elevated total IgE, hypereosinophilia, benign No increase in IgE, hypereosinophilia. Benign form of a
pathology
group of vascular proliferation diseases ranging from
hemangioendothelioma to epitheloid angiosarcoma
180
Nagarekha
Fig 1: Cut section of the specimen showing

homogenous grey white areas.
Fig 2: Showing the microscopic picture of

Kimura's disease 40X(H/E).
syndrome), benign and malignant lesions of the gland

and cysts should be differentiated. However the
following conditions like lymphoma, metastasis,
ALHE, Langerhans cell histiocytosis, florid follicular
hyperplasia, Castlemans disease, drug reaction,
dermatopathic
lymphadenopathy,
parasitic
lymphadenitis and allergic granulomatosis of Chung
and Strauss are to be considered in differential
diagnosis.3
Laboratory analysis showed peripheral blood
eosinophilia and increased serum total IgE
concentration. There was no proteinuria. Regional
lymphadenopathy, peripheral blood eosinophilia and
increased IgE levels are commonly seen in Kimuras
disease, but not in ALHE. Renal involvement is
found in half the patients of Kimuras disease. Yuen
et al 6 reported that renal involvement is about 60%.
Table-2 reveals the differences and similarities
between Kimuras disease and ALHE.1
Surgical excision of the lesion is the first line therapy.
Corticosteroids therapy is partly unsuccessful.
Radiation and cytotoxic therapy has to be considered
for the refractory lesions which do not respond to
surgery. Cetrizine (histamine [H-1] receptor blockers)
induced a complete remission in a corticosteroid
dependent patient within 2 months of treatment.
DISCUSSION
CONCLUSION
Kimuras disease is a chronic inflammatory condition

where in the etiology may not be established. Hence,
there was a misconception between this disease and
angiolymphoid hyperplasia with eosinophilia
(ALHE). But later it was proved that they were two
separate disorders. Autoimmune/allergic response
was seen in Kimuras disease as against benign
vascular hyperplasia in ALHE.4
There is no age preponderance to this disease.
However 2nd and 3rd decade have been reported in
many literature, which also collaborates with the
present case.5 Won Jun Choi et al reviewed 54
patients and found that the mean age of the patients
was 33.1 years with head and neck region being more
commonly involved5. Other areas to be involved are
kidneys, orbit, ears, spermatic cord and median
nerve.5 Clinical differential diagnosis should include
chronic inflammatory disorder of the salivary glands,
granulomatous gland disease (cat-scratch disease,
sarcoidosis) and autoimmune disease (Sjogrens
This rare case report underlines the importance of

taking into account Kimuras disease when there is
eosinophilia in the peripheral blood and swelling in
the head and neck region.
ACKNOWLEDGEMENT
I thank the Director, Principal, Head of the
Department & all staff members of the Department of
Pathology & ENT, VIMS, Bellary for their support &
encouragement to prepare this report.
REFERENCES
1. Larroche C, Bletry O. Kimuras disease.
Orphanet
encyclopedia.
February
2005:
http://www.orpha.net/data/patho/GB/ukkimura.pdf
2. Veerendra Kumar, Salini, Savida Haridas.
Kimuras disease: An uncommon cause of
lymphadenopathy. Indian J Med Paediatr Oncol.
2010;31(3):89-90.
181
Nagarekha
3. Savage NW, Vucicevic Boras V. Unilateral

intraparotid swelling: a case report of Kimuras
disease and review of differential diagnosis. Case
reports
in
Otolaryngology.
2013;3:
http://dx.doi.org/10.1155/ 2013/ 795921.
4. Mariatos G, Gorgoulis VG, Laskaris G and Kittas
C. Epitheloid hemangioma (angiolymphoid
hyperplasis with eosinophilia) in the oral mucosa
: a case report and review of the literature. Oral
Oncology. 1999;35(4):435-38
5. Won Jun Choi, Jae Hur, Joo Yeon Ko, Kwang
Yeoll Yeo, Joung Soo Kim, Hee Joon Yu. An
unusual clinical presentation of Kimuras disease
occurring on the buttock of a five year old
boy.Ann Dermatol. 2010;22(1):57-60.
6. Yuen HW, Goh YH, Low WK, Lim- Tan SK.
Kimuras disease: a diagnostic and therapeutic
challenge. Singapore Med J. 2005;46:179-83.
182
Nagarekha
DOI: 10.5958/j.2319-5886.3.1.036

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Revised: 23rd Oct 2013
Case report
Copyright @2013
ISSN: 2319-5886
KIMURAS DISEASE: A RARE CASE REPORT

*Nagarekha Kulkarni
Professor, Department of Pathology, Vijayanagara Institute of Medical Sciences, Bellary, Karnataka, India
Corresponding author email: nagarekhaphaniraj1970@gmail.com
ABSTRACT
Introduction: Kimuras disease is of unknown etiology. Case report: This report describes an interesting case of
Kimuras disease in an 18 years old male manifesting as a unilateral left sided parotid swelling with multiple
cervical lymphadenopathy. There was eosinophilia and increased levels of circulating IgE. Patient was treated
with surgical excision and corticotherapy, cetrizine was prescribed. Histologically there were numerous follicles
with prominent germinal centres. Interfollicular area was infiltrated with eosinophils and plasma cells.
Conclusion: Any swelling in the head and neck region associated with eosinophilia should make one to suspect
the Kimuras disease.
Keywords: eosinophilia, lymphadenopathy, angiolymphoid hyperplasia
INTRODUCTION
The history of Kimuras disease dates back to 1937
when HT Kimm and C Szeto first described about it.1
Kimura et al in the year 1948 was the pioneer to
describe the microscopic features of the disease.
Hence, the disease is recognised by his name.1 This
disease is seen in young Asian males and the cause of
this rare entity is not known. Only 200 cases are
reported since its histological description and
sporadic in the rest of the world.2 Clinically the
disease presents as swelling in the head and neck
region characterised by eosinophilia in blood and
tissue with marked elevated serum immunoglobulin E
(IgE) levels.3 This report describes a rare case of
Kimuras disease in a 18 years old male who
presented with parotid swelling
CASE REPORT
An 18 years old male presented to the ENT outpatient
department with the swelling on the left side of the
face below the left ear. It was sudden in onset and
progressed gradually to attain the size of 12X10cms.

There was no past history of prolonged fever, cough,
loss of weight and loss of appetite. He was nonalcoholic and non-smoker. The family history was
unremarkable. On palpation the swelling was diffuse,
non-tender, firm, multiple over left parotid region
The swelling was measuring 12x10cms, mobile, skin
over the swelling was pinchable and hyperpigmented.
Other groups of the lymph nodes were not enlarged.
There was no hepatosplenomegaly. Bilateral ear and
facial nerve examination were within normal limits.
The vital signs and laboratory investigations were
normal except there was eosinophilia and elevated
IgE levels as shown in table-1. Neck ultrasonography
revealed enlarged parotid gland with altered
echotexture, multiple enlarged pre and post auricular
lymphnodes. Fine needle aspiration biopsy revealed
features of reactive lymphadenitis. After a course of
antibiotics the swelling was excised and sent for the
histopathological examination. He was treated with
179
Nagarekha
levofloxacin, acclofenac, cetrizine and B- complex

tablets.
The specimen was received in the histopathology
section. Macroscopic examination revealed a well
circumscribed mass measuring 12X8X5cms. External
surface was unremarkable and cut section showed
grey white homogenous areas as shown in figure - 1.
The specimen was processed routinely in the
histopathological section and the sections were
stained with haematoxylin and eosin stain (H/E).
Microscopic examination revealed the architecture of

the lymph nodes with numerous follicles showing
hyperplastic feature with germinal centers. Many
eosinophils and plasma cells were present in the
interfollicular area. Also seen are perifollicular
fibrosis, prominent blood vessels with endothelial
proliferation and mild hyaline change as shown in
figure 2. The diagnosis of Kimuras disease was
made.
Table 1: Shows vital signs and laboratory findings

Vital Signs: Pulse Rate: 86/minute, Blood Pressure: 130/80 mm of Hg, Respiratory Rate: 28/minute
Temperature: 38.5oc
Laboratory Investigations:
Hb%: 11.8g/dl (normal:12.5-14.5g/dl)
RBC Count: 3.8millions/cmm (normal:4.5-5.5millions/cmm)
Haematocrit: 34% (normal: 35% to 45%)
WBC Count: 9800 cells/cmm (normal: 4000 to 11,000/cmm)
Differential Count: Neutrophils: 65%, Lymphocytes: 23%, Eosinophils: 10%, Monocytes: 02%
Basophils: 00%
Bleeding Time-3 minutes 30 seconds (Normal:2-6minutes)
Clotting Time-4 minutes 30 seconds (Normal: 2-8minutes)
Absolute eosinophil count: 600 cells/cmm (Normal:40-440cells/cmm)
Serum IgE:4.4mg/dl (Normal: 0.01 0.04 mg/dl)
Stool tests: negative for parasites
Random Blood Sugar: 90mg/dl (normal: 80 to 110mg/dl)
Blood Urea: 19mg/dl (normal: 5 to 25mg/dl)
Serum Creatinine: 0.8mg/dl (normal: 0.8 to 1.2mg/dl)
Serological Investigations: HIV-1 & 2:Negative , HBsAg : Negative
Routine Urine Examination: Albumin: Nil, Sugar: Nil, Urine micro: 1-2 pus cells/HPF
Table 2: Shows the difference between kimuras disease and angiofollicular hyperplasia with eosinophilia1
Kimuras disease
Young man (2nd-3rd decade)
Oriental
Voluminous subcutaneous
salivary gland involvement
mass,
adenopathy,
Angiofollicular hyperplasia with eosinophilia

Middle aged woman (3rd-5th decade)
Westerner
Subcutaneous or dermal cervical papules or nodules;
overlying skin is erythematous or pigmented; rare
adenopathies
Same aspect. Histiocytoid vessels with particular
endothelial cells (different sized nuclei and protrusion
into the vessel lumen)
Follicular hyperplasia, eosinophil infiltration of

interfollicular and perivascular zones with abcess
formation and lysis, postcapillary venule
proliferation
Elevated total IgE, hypereosinophilia, benign No increase in IgE, hypereosinophilia. Benign form of a
pathology
group of vascular proliferation diseases ranging from
hemangioendothelioma to epitheloid angiosarcoma
180
Nagarekha
Fig 1: Cut section of the specimen showing

homogenous grey white areas.
Fig 2: Showing the microscopic picture of

Kimura's disease 40X(H/E).
syndrome), benign and malignant lesions of the gland

and cysts should be differentiated. However the
following conditions like lymphoma, metastasis,
ALHE, Langerhans cell histiocytosis, florid follicular
hyperplasia, Castlemans disease, drug reaction,
dermatopathic
lymphadenopathy,
parasitic
lymphadenitis and allergic granulomatosis of Chung
and Strauss are to be considered in differential
diagnosis.3
Laboratory analysis showed peripheral blood
eosinophilia and increased serum total IgE
concentration. There was no proteinuria. Regional
lymphadenopathy, peripheral blood eosinophilia and
increased IgE levels are commonly seen in Kimuras
disease, but not in ALHE. Renal involvement is
found in half the patients of Kimuras disease. Yuen
et al 6 reported that renal involvement is about 60%.
Table-2 reveals the differences and similarities
between Kimuras disease and ALHE.1
Surgical excision of the lesion is the first line therapy.
Corticosteroids therapy is partly unsuccessful.
Radiation and cytotoxic therapy has to be considered
for the refractory lesions which do not respond to
surgery. Cetrizine (histamine [H-1] receptor blockers)
induced a complete remission in a corticosteroid
dependent patient within 2 months of treatment.
DISCUSSION
CONCLUSION
Kimuras disease is a chronic inflammatory condition

where in the etiology may not be established. Hence,
there was a misconception between this disease and
angiolymphoid hyperplasia with eosinophilia
(ALHE). But later it was proved that they were two
separate disorders. Autoimmune/allergic response
was seen in Kimuras disease as against benign
vascular hyperplasia in ALHE.4
There is no age preponderance to this disease.
However 2nd and 3rd decade have been reported in
many literature, which also collaborates with the
present case.5 Won Jun Choi et al reviewed 54
patients and found that the mean age of the patients
was 33.1 years with head and neck region being more
commonly involved5. Other areas to be involved are
kidneys, orbit, ears, spermatic cord and median
nerve.5 Clinical differential diagnosis should include
chronic inflammatory disorder of the salivary glands,
granulomatous gland disease (cat-scratch disease,
sarcoidosis) and autoimmune disease (Sjogrens
This rare case report underlines the importance of

taking into account Kimuras disease when there is
eosinophilia in the peripheral blood and swelling in
the head and neck region.
ACKNOWLEDGEMENT
I thank the Director, Principal, Head of the
Department & all staff members of the Department of
Pathology & ENT, VIMS, Bellary for their support &
encouragement to prepare this report.
REFERENCES
1. Larroche C, Bletry O. Kimuras disease.
Orphanet
encyclopedia.
February
2005:
http://www.orpha.net/data/patho/GB/ukkimura.pdf
2. Veerendra Kumar, Salini, Savida Haridas.
Kimuras disease: An uncommon cause of
lymphadenopathy. Indian J Med Paediatr Oncol.
2010;31(3):89-90.
181
Nagarekha
3. Savage NW, Vucicevic Boras V. Unilateral

intraparotid swelling: a case report of Kimuras
disease and review of differential diagnosis. Case
reports
in
Otolaryngology.
2013;3:
http://dx.doi.org/10.1155/ 2013/ 795921.
4. Mariatos G, Gorgoulis VG, Laskaris G and Kittas
C. Epitheloid hemangioma (angiolymphoid
hyperplasis with eosinophilia) in the oral mucosa
: a case report and review of the literature. Oral
Oncology. 1999;35(4):435-38
5. Won Jun Choi, Jae Hur, Joo Yeon Ko, Kwang
Yeoll Yeo, Joung Soo Kim, Hee Joon Yu. An
unusual clinical presentation of Kimuras disease
occurring on the buttock of a five year old
boy.Ann Dermatol. 2010;22(1):57-60.
6. Yuen HW, Goh YH, Low WK, Lim- Tan SK.
Kimuras disease: a diagnostic and therapeutic
challenge. Singapore Med J. 2005;46:179-83.
182
Nagarekha
DOI: 10.5958/j.2319-5886.3.1.037

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Case report
Copyright @2013
ISSN: 2319-5886
SCOLIOSIS CORRECTION IN CHILDREN-ANAESTHETIC CHALLENGE: A CASE REPORT

* Amarjeet D Patil1, Sivashankar KR2, Arpan Sashankar3, Shikha A Malhotra4, Nitin Kapoor5, Charu Sudan6
1
Assistant Professor, 2Professor & Head, 3Assistant Professor, 4,5,6Resident, Department of Anaesthesiology,
MGM Medical College and Hospital, Kamothe, Navi Mumbai, India
* Corresponding author email: amarjeetpatil999@yahoo.co.in
ABSTRACT
Kyphoscoliosis is a challenging surgery to surgeons but even more challenging to anaesthesiologist to give
anaesthesia and maintain it throughout the surgery and post operative pain relief and ventilation. Here we are
describing the case of 3 years old male child weighing 9kg for surgical correction of spine deformity with
instrumentation.
Keywords: Scoliosis, Children and Anaesthesia
INTRODUCTION
Scoliosis is defined as a curvature in the vertebral
column from side to side and kyphosis is a curvature
from anterior to posterior.1 Kyphoscoliosis can be
congenital, idiopathic or postural. Surgical correction
is usually attempted from the age of 10. Advances in
paediatric anaesthesia and expertise of the surgeons
are allowing this correction to be attempted at the
very early stage. Positioning of the infant for surgery,
gross fluid shifts and manipulation of neural
structures pose a challenge to the anaesthesiologist.
Surgical correction with instrumentation in a boy of
nine kilos is described in this paper.2,3
instrumentation with complete preaparedness for

invasive monitoring and replacement of blood and
blood products.
CASE REPORT
Nine kgs, 3 years, boy was admitted in our tertiary
care hospital, MGM Medical College & Hospital,
Navi Mumbai, for surgical correction of deformity of
spine since one year. Clinical examination revealed
no other congenital anamoly and cardiorespiratory
system not deranged apart from the positional change.
Radiological findings revealed the extent of
angulation of the vertebral column in all directions.
The child was planned for surgical correction with
Amarjeet et al.,
Fig 1: Pre-operative X-ray of patient AP & Lateral

views
TECHNIQUE4
The infant was assessed, prepared, premedicated as
per standard protocol.5 Intravenous induction,
intubation with non depolarizing blocking agents was
resorted to once the peripheral iv line was secured.
Central line (Rt internal jugular canulation 4.5 fg) and
183
left radial artery canulated Positioning of the infant

for surgery was supplemented by cotton bundles apart
from standard bolsters. Proper eye padding given.6
Standard monitoring of oxygen saturation, end tidal
carbon dioxide (EtCO2), invasive blood pressure
(IBP), central venous pressure (CVP) and urine
output was being done, neuromuscular monitoring
was not possible because the instrument was
defective on that day.7
Anaesthesia was maintained with intermittent
neuromuscular
blocking
agents,
inhalational
anaesthetic and opiod analgesia. We took care to
avoid hypothermia by warming mattress,warm
fluids.8 Surgery was uneventful for 480 minutes.9
Elective postoperative mechanical ventilation was
done for 24 hours.10
DISCUSSION
Very few cases have been reported of infants below
10 kgs undergoing surgical correction and
instrumentation of gross Kyphoscoliosis. Positioning
of the child should be preferably with 9 poster
frame.11 We had resorted to cotton bundles for the
same, canulation of Internal jugular vein and radial
artery in children needs experienced hands. Proper
monitoring of effects of gross fluid shifts is
mandatory along with correction of the same.
Monitoring of spinal cord functions could not be done
in this surgery. No complications were noticed in the
form of brachial plexus injury and ocular changes or
air embolism.
CONCLUSION
With clinical experience of the Anaesthesiolgist,
expertise of the surgeon, surgical correction of
kyphoscoliosis even in children is possible now-adays12-14.
ACKNOWLEDGEMENT
We would like to extend our heartfelt gratitude to the
Department of Orthopedics, Department of
Pediatrics, Radiology and Physiotherapy.
Fig 2: Post operative X-ray AP view
Fig 3: Post operative X-ray AP & Lateral view
Amarjeet et al.,
REFERENCES
1. Weinstein SL, Dolan LA, Spratt KF, Peterson
KK, SpoonamoreMJ, Ponseti IV. Health and
function of patients with untreated idiopathic
scoliosis. A 50 year natural history study. JAMA
2003; 289:559-67.
2. Michael AE, Davandra Patel. Contin Educ
Anaesth. Crit Care Pain 2006;6 (1): 13-16.
3. Ogilvie JW, Winter RB, Bradford DS, Lonstein
JE, Ogilvie JW, eds. Historical Aspects of
Scoliosis. Moes Textbook of Scoliosis and other
Spinal deformities 3rd Edition. WB Saunders
Company. Philadelphia, USA, 1995; 1-4.
4. Salem MR, Klowden AJ, Gregory GA, ed.
Pediatric Anesthesia. Anesthesia for Orthopedic
Surgery Churchill Livingstone, New York, USA,
2002; 617-61.
5. Standards, Guidelines, Statements and Other
Documents. www.asahq.org
6. Myers M, Hamilton SR, Bogosian A, Smith CH,
Wagner TA. Visual loss as a complication of
184
7.
8.
9.
10.
11.
12.
13.
14.
spine surgery: A review of 37 cases. Spine 1997;

22:1325-29.
Ramirez N, Richards BS, Warren PD, Williams
GR. Complications after posterior spinal fusion
in Duchennes muscular dystrophy. J Pediatr
Orthop 1997; 17:109-14.
Sessler DI. Mild perioperative hypothermia. N
Engl J Med 1997; 336:1730-37.
Tsirikos AI, Chang W, Dabney KW, Miller F.
Comparison of one stage versus two stage
anteroposterior spinal fusion in pediatric patients
with cerebral palsy and neuromuscular scoliosis.
Spine 2003; 28:1300-05.
Rawlins BA, Winter RB, Lonstein JE.
Reconstructive spine surgery in pediatric patients
with major loss in vital capacity. J Pediatr Orthop
1996; 16:284-292.
Winter RB, Lonstein JR, Herkowitz H, Garfin
SR, Balderstone RA, Eismont FJ, etal., Juvenile
and Adolescent Scoliosis. Rothman-Simeone,
The Spine 4th Edition. WB Saunders Company,
Philadelphia, USA, 1999; 325-72.
Wazeka AN, DiMaio MF, Boachie-Adjei O,
Oheneba MD. Outcome of pediatric patients with
severe restrictive lung disease following
reconstructive spine surgery. Spine 2004; 29:528534
Merola A, Haher T, Brkaric M. A multicenter
study of the outcomes of the surgical treatment
of adolescent idiopathic scoliosis using the
Scoliosis Research Society (SRS) outcome
instrument. Spine 2002; 27:2046-2051.
Shapiro G, Green DW, Fatica NS, Boachie-Adjei
O. Medical complications in scoliosis surgery.
Curr Opin Pediatr 2001; 13: 36-41.
Amarjeet et al.,
185
DOI: 10.5958/j.2319-5886.3.1.038

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Health Sciences
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Case report
Copyright @2013
ISSN: 2319-5886
Accepted: 22nd Nov 2013
AGGRESSIVE ANGIOMYXOMA PRESENTING AS HUGE BROAD LIGAMENT TUMOR- A RARE

CASE REPORT
*Krishna Mandade1, Kashika singh1, Aptulkar2, Angarkar3, Bhavthankar DP4
1
Junior resident, Department of OBGY, 2Asso. Prof, Department of Surgery, 3Professor, Department of Pathology,
Prof & Head, Department of OBGY, Pravara Rural hospital Loni, Maharashtra, India.
*Corresponding author email: kmandade@gmail.com

ABSTRACT
Aggressive angiomyxoma was first described in 1983 by Steeper and Rosai, and fewer than 150 cases have been
reported in the world medical literature. Aggressive angiomyxoma is a rare mesenchymal tumor occurring
predominantly in the pelvic-perineal region of females of age group 30 to 50 yrs. These tumors are benign and often
reach too large dimensions before becoming clinically symptomatic. We report such a case presented as broad
ligament tumor, a very unusual presentation. Patient underwent laprotomy and tumor was successfully excised.
Keywords: Aggressive angiomyxoma, Pouch of Douglas.
INRTODUCTION
Aggressive angiomyxomas (AA) are rare, slow
growing benign tumors which are, predominantly,
located on the perineum of reproductive age
women.1,2 These lesions are characterized as soft,
non-encapsulated
tumors
with
finger-like
projections infiltrating the surrounding soft tissues.
The tumour presents as a large multilobular or
polypoid mass or swelling. It is important to
diagnose this condition because a tumor is locally
infiltrative and surgery is usually the first line of
treatment, radical surgery with wide margins and
long-term follow-up is advised.3
CASE
40 yrs female came to OPD with complain of pain in
abdomen, difficulty in passing stools and urine and
feeling of abdominal mass since 2 months in OPD of
Pravara Rural Hospital, Loni. Dist. Ahmednagar in
Maharashtra in India.
Mass associated with pain and bowel complain was
initially small and gradually progressed to present size.
Krishna et al.,
There was no history of fever, cough, cold, nausea,

vomiting, and bleeding per-vaginal, apparent weight
loss. Last menstrual period was 10 days back.
Past menstrual history was regular with cycle and
flow and there were no clots and no dysmenorrhea.
Patient was Para 2 Live
2. Both were full term
normal deliveries & history of tubal ligation done 15
yrs back.
Past, personal and family history was insignificant.
On examination, general condition of the patient was
good and vitals were stable. No peripheral
lymphadenopathy and other signs of malignancy
found.
Per abdomen: Non tender abdominal mass felt
corresponding to 24-26 weeks; oval, on Rt. side of
lumbar spine, arising from pelvis, slightly mobile, firm
in consistency, around 20*15cm. Rt. iliac fossa
completely obliterated.
Per vaginal examination: Uterus normal size, firm,
mobile, separately felt from the mass which was felt in
Rt. Adnexa.
186
Rt. Adnexa was fixed; bogginess felt in Rt. fornix, Lt.

Fornix was relatively free.
Per Rectal examination: large firm mass felt
anteriorly free from rectal mucosa, POD was
obliterated & mass compressing rectal lumen.
All hematological investigations were done and the
investigation reports were within normal limits.
USG suggestive of a large tumor of size 21*20*8cm
arising from Rt. Adnexa. Ovaries seen separately from
tumor on Transvaginal
sonography examination.
Uterus of normal size with normal ecotexture of
ovaries.
Tumor with some cystic and some hyper lucent areas
in between. On Color Doppler vascularity set in.
Fine needle aspiration cytology (FNAC): suggestive
of Tumor cells cytologically bland and have a
spindled, ovoid or stellate appearance with ovoid
nuclei and evenly dispersed chromatin. CT scan and
MRI evaluations could not be done due to no
affordability. CA125 levels was 9IU.
On the basis of the clinical picture and Ultrasound
review patient diagnosed as large Rt. Sided Broad
ligament tumor.
Exploratory laprotomy under General anesthesia
performed. Large whitish shiny tumor nearly of 20*20
cm drawn out of peritoneal cavity which was arising
from Rt. Adnexa of the uterus and its extension as
peduncle in POD and also in the ischiorectal fossa
noted.
With combined surgical approach Tumor excised
completely by securing bowel, bladder and ureters.
Along with the tumor uterus with bilateral ovaries
which were observed to be normal removed by the
conventional method of Hysterectomy. Haemostasis
achieved completely with moderate intraoperative
loss. No remnants of tumor left.
Fig 2: External appearance with pedunculated

extension of tumor.
Post-op was uneventful. Repeat haemogram was
11gm%. Patient discharged on 10th Post operative day.
Histopathology gross: Shiny white brown Tumor
mass measuring 22*20*7cm arising from lateral Wall
of body of uterus. Cut surface: Myxomatous &
hemorrhagic areas. Tumor is extended as pedunculated
globular 8.5*7*3cm attached to the lower side of
uterus near Cervix. Another extended mass 9 *7*2.
5cm noted on the posterior aspect of the Uterus.
Fig 3: Cut Surface of tumor.

Section from tumor show sparsely cellular tumor
composed of numerous haphazardly arranged small to
large blood vessels set in myxoid stroma.
Stroma shows collagen fibrils, scattered smooth
muscle bundles.
The Tumor cells cytologically bland and have a
spindled, ovoid or stellate appearance with ovoid
nuclei and evenly dispersed chromatin.
Stroma is distinctly myxoid.
Fig 1: Tumor attached to broad ligament seen.

187
Krishna et al.,
Fig 4: Section from pelvic mass showing varying

sized blood vessels surrounded by cells with ovoid
to spindle nuclei & a myxoid stroma (H & E x 280).
DISCUSSION
Aggressive angiomyxoma is a rare tumor of
mesenchymal origin first described in 1983 by Steeper
and Rosai.
The age distribution is wide, with the peak incidence
at 31 to 35.4 Female to male ratio of slightly more than
6:1 . The size may vary from 1-60 cm.5
On gross examination it is rubbery and white or soft
and gelatinous. The tumor presents as a large
multilobular or polypoid mass or swelling.5
Locally infiltrative but non-metastasising; that may
present as a vulval mass, vaginal polyp, bartholin or a
vaginal cyst, ovarian cyst, etc. These lesions are
characterized as soft, non-encapsulated tumours with
finger-like projections infiltrating the surrounding soft
tissues.6 The tumor grows slowly, and its benign
nature is suggested by the histology and by the fact
that it shows no tendency to metastasize. However it
usually tends locally to recure.6 The rarity of this
condition makes the preoperative diagnosis fairly
difficult, It has been also related to hormonal activity
which explains female dominance.7
The diagnosis can be made considering the clinical
presentation aided by ultrasound, CT or MRI shows a
hypodense mass with translevator extension,
displacing rather than invading the pelvic organs.
FNA reduces the diagnostic possibilities but
histopathology alone gives the definite diagnosis.8
Differential diagnosis:
Benign: myxolipoma, myxoid neurofibroma and
myxoid leiomyoma to myxofibrosarcoma, myxoid
variant of liposarcoma, leiomyosarcoma.
Malignant: fibrous histiocytoma and botryoid
rhabdomyosarcoma.
The distinctively striking vascular component in

aggressive angiomyxoma helps in ruling out most of
the above mentioned neoplasms as differentials.
The optimal treatment for AA is wide local excision
with tumor free margin, as this tumor is locally
invasive and tends to infiltrate deep into pelvic soft
tissues.9
Pre-operative knowledge of tumor extent is important
in determining surgical approach and MRI features of
AA are characteristic.9
Recurrence is local and reported in 36-72%.
This surgery is challenging because of the infiltration
and the difficult dissection and value of extensive
surgical resection to obtain clear margins has been
questioned.10 In the past, most authors advocated wide
excision even if genitourinary and digestive tract
resections were necessary.
Radiotherapy and chemotherapy may not have much
role due to the low mitotic activity seen.
GnRH agonist and tamoxifen have been used
successfully in few patients.11
The response can be assessed by clinical assessment,
patient's symptomatology and radiographic findings.
Because of the abdominal and pelvic organ
manipulation, hospital stays are generally longer, and
patients are at higher risk of developing problems such
as deep venous thrombosis and pulmonary embolism
while they await the return of bowel function after the
procedure.
There are many unanswered questions about treatment
and follow-up strategies for this rare disease; because
this tumor is slow growing and is often symptomatic
only when the tumor is large, radiographic follow-up
is best.
CONCLUSION
Although a rare diagnosis, aggressive angiomyxoma
can present with unusual features. Detailed
radiological examination is helpful in suspecting the
problem, but histology is the gold standard for
diagnosis. It should be distinguished from benign
myxoid tumors with low risk of local recurrence.
Therefore, recurrence of tumor may be avoided by
wide local excision which is curative and prognosis of
such tumor is good.
188
Krishna et al.,
REFERENCES
1. Steeper TA, Rosai J. Aggressive angiomyxoma of
the pelvis and perineum: report of nine cases of a
distinctive type ofgynaecologic soft tissue
neoplasm. Am J Clin Pathol 1983; 7:453
2. Chan YM, Hon E, Ngai SW, Ng TY, Wong LC.
Aggressive angiomyxoma in females: is radical
resection the only option? Acta Obstet Gynecol
Scand 2000;79(3): 216-20.
3. Wiser A, Korach J, Gotlieb WH, Fridman E.
Importance of Accurate Preoperative Diagnosis in
the Management of Aggressive Angiomyxoma:
Report of Three Cases and Review of the
Literature, Abdominal Imaging. 2006;31(3):38386.
4. Gungor T, Zengeroglu S, Kaleli A, Kuzey GM.
Aggressive angiomyxoma of the vulva and vagina.
A common problem: misdiagnosis. Eur J Obstet
Gynecol Reprod Biol 2004; 112: 11416.
5. Fetsch JF, Laskin WB, Lefkowitz M, Kindblom
L,
Meis-Kindblom
JM.
Aggressive
angiomyxoma. A clinicopathologic study of 29
female patients. Cancer 1996; 78: 7990.
6. H. Adwan, P.D Kamel and G. Glazer, A Solitary
Encapsulated Pelvic Aggressive Angiomyxoma,
Annals of The Royal college of Surgeons of
England, vol. 86, No. 6, November 2004, pp. W1W3.
7. Htwe M, Deppisch LM, Saint-Julien JS. Hormonedependent, aggressive angiomyxoma of the vulva.
Obstet Gynecol 1995; 86(4 Pt 2): 697-99.
8. Amezcua CA, Begley SJ, Mata N, Felix JC,
Ballard CA. Aggressive angiomyxoma of the
female genital tract: a clinicopathologic and
immunohistochemical study of 12 cases. Int J
Gynecol Cancer 2005; 15: 140-145.
9. Kaur A, Makhija PS, Vallikad E, Padmashree V,
Indira HS. Multifocal aggressive angiomyxoma: a
case report. J Clin Pathol 2000; 53: 79899.
10. Siassi RM, Papadopoulos T, Matzel KE.
Metastasizing aggressive angiomyxoma. N Engl J
Med 1999;341:1772.
11. Behranwala KA, Thomas JM. 'Aggressive'
angiomyxoma: a distinct clinical entity. Eur J Surg
Oncol 2003; 29(7):559-63.
189
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ANGIOMYOLIPOMA OF A KIDNEY: A CASE REPORT

*Manish Shah, Mrunal N. Ketkar, Sudhir J. Kothari, Shilpa S. Patankar, Ravi M. Swami
Department of Surgery, Bharati Hospital and Research Centre, Pune Satara road, Dhankawdi, Pune, Maharashtra,
India
*Corresponding author email: manishshah37@gmail.com

ABSTRACT
Angiomyolipoma is a rare benign tumour of the kidney. They are composed of abnormal vasculature, smooth
muscle and adipose elements. They may be associated with Tuberous sclerosis. The unilateral presentation is
uncommon. Angiomyolipoma is presented as an enlarge lump in the abdomen may mimic malignant lesion such as
renal cell carcinoma, yet malignancy has to be ruled out. The diagnosis of this condition may not be straight forward
with imaging alone. Excision is recommended for definite histopathological diagnosis (in symptomatic patients) and
to prevent the potential risk of haemorrhage and malignancy. A case of benign giant Angiomyolipoma is presented
here because of its uncommon occurrence.
Keywords: Angiomyolipoma , Unilateral, Kidney

INTRODUCTION
Angiomyolipoma is a rare benign tumour of the
kidney. It is found in approximately 45-80% of
patients with tuberous sclerosis and are typically
bilateral and asymptomatic. In patients without
tuberous sclerosis, renal angiomyolipomas can be
unilateral and tend to be larger.1Angiomyolipoma is a
benign clonal neoplasm consisting of varying amounts
of mature adipose tissue, smooth muscle, and thickwalled vessels. It is most likely derived from the
perivascular epithelioid cells, and its growth may be
hormone dependent. It shows female predominance
and rarity before puberty.2 It may mimic renal cell
carcinoma. Diagnosis is done with the help of
ultrasonography, CT scan and histology.
CASE REPORT
A 75 yr. an old woman from rural area presented with
lump in right side of the abdomen that the patient had
noticed 1 year previously. (Bharati Hospital). The
lump had gradually increased in size over a period of
time. She had complaints of pain since 1 day. On
examination, she was anaemic (8.3gm %) with large

retroperitoneal lump that occupied right side of
abdomen, the lump was firm in consistency and
tender. She had no lymphedema or other palpable
lymph node. Ultrasonography revealed a well defined
echoic lesion noted of size 14.6 X 8.7 cm, associated
with upper pole of the right kidney extending upto the
epigastric region and midline on right side. CT scan
revealed a large well defined mass lesion showing
density with peripheral soft tissue component seen in
right hypochondriac and right lumbar region
measuring 13 X 11 X 10 cm. The mass is seen in
medial to pancreas and (Inferior vena cava) displacing
it superolaterally. Superiorly mass extending to liver
and inferiorly to the right iliac fossa. The mass
completely encasing right kidney and displacing it
inferiorly, most likely liposarcoma. (figure 1) A
malignant tumour was suspected based on the imaging
and clinical features. In view of above finding and
pain, malignancy needed to be ruled out. The patient
underwent surgery and tumour was excised intact
190
Manish et al.,
(figure 2). Its weight was 1800 grams. A nephrectomy

was done due to inability to differentiate it from renal
cell carcinoma. 4 units of blood were transfused
preoperatively and in addition 3 units were given
(blood group AB positive) She made an uneventful
recovery. An angiomyolipoma was confirmed by
histopathological assessment. Post operatively, a
single large well circumscribed an encapsulated firm
mass measuring 20 X 15 X 9 cm weight 1800grams.
The cut section appears yellowish brown with areas of
hemorrhage (figure 3). Microscopy- tumour showed
mature adipocytes, separated by fibrohyalinisedseptae
showing vascular proliferation and area of smooth
muscle cell in bundles (figure 4).
Fig 1: CT scan showing lesion
Fig 2 : Intra operative photograph
Angiomyolipoma
Fig 3 : Specimen showing renal Angiomyolipoma.
Blood
vessel
Fat
Smooth
Muscle
Fig 4: Histopathology - Angiomyolipoma
DISCUSSION
Angiomyolipoma is a rare benign tumour of the
kidney. It is found in approximately 45- 80% of
patients with tuberous sclerosis and are typically
bilateral and asymptomatic with F: M predominance
of 2:I. The mean age of presentation is 30 years. In
contrast, of the 60 -70% of patient with AML who do
not have tuberous sclerosis present later in life, during
5th or 6th decade and this tumour can be unilateral and
tend to be larger than those associated with tuberous
sclerosis. Tuberous sclerosis is an autosomal dominant
disorder comprising adenoma sebaceum, mental
retardation and epilepsy .1
Angiomyolipoma consists of varying amount of
mature adipose tissue, smooth muscle and thick walled
vessels. It is mostly likely derived from perivascular
epitheloidcell. Extrarenal occurrence have been
reported in hilarlymphatics, retroperitoneum and liver
and direct extension into the venous system. 2
On diagnostic imaging, it may mimic a malignancy.
On ultrasonography, it gives a well circumscribed,
highly echogenic often associated with shadowing. On
CT scan, well defined mass is seen (confined by a
value of -20 to-80 Hounsfield units). 2
Differential diagnosis for this are subtypes of sarcoma
including fibrosarcoma, leiomyosarcoma, liposarcoma
and renal cell carcinoma.3 Positive immunoreactivity
for HMB-45 is characteristic for angiomyolipoma and
can be used to differentiate it from sarcoma.4, 5
The patient with tumour with intermediate features or
calcification should be managed proactively because
the likely diagnosis in most such cases is renal cell
carcinoma. Patients with isolated lesions less than 4
cm, can be followed up with a yearly CT scan or
Ultrasonography to define the growth rate and clinical
significance. Similarly, Patients with asymptomatic or
mildly symptomatic lesions greater than 4 cm should
191
Manish et al.,
be followed up with semiannual ultrasonography.

Patients with lesions greater than 4 cm with moderate
or severe symptoms (bleeding or pain) should undergo
surgical intervention either in the form of tumour
excision with or without nephrectomy, renal-sparing
surgery or renal arterial embolization.2
Complications are as follows, Retroperitonal
hemorrhage,
hematuria,
hypovolemic
shock,
hypertension, abscess formation.
CONCLUSION
Angiomyolipoma is a rare tumour of the kidney.5 They
may be confused with malignant tumours especially
when the presentation is unilateral. CT Scan and
ultrasonography helps in diagnosis. Symptomatic
patient requires surgical intervention.
REFERENCES
1. Smith and Tanaghos. General urology. McGrawHill & Lange. 18th ed. Chapter 22: 330-31,.
2. Campbell - Walsh Urology. Renal Tumours. WB.
Saunders; Philadelphia, PA. 9th edition.Chapter47:1578-80
3. Steiner MS, Goldman SM, Fishman EK, Marshall
FF. The natural history of renal angiomyolipoma.
J Urol. 1993, 150:1782-86.
4. De la Cruz Ruiz M, Rivero M, Fernandez DL.
Giant renal angiomyolipoma. Arch EspUrol 1999;
52: 3815
5. Hostis HL, Deminiere C, Ferriere JM. Renal
angiomyolipoma:
a
clinicopathologic,
immunohistochemical, and follow-up study of 46
cases. Am J Pathol 1999; 23: 101120.
192
Manish et al.,
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RIGHT SIDED CONGENITAL DIAPHRAGMATIC HERNIA: A RARE CASE REPORT

*Amit Narkhede1, Shrikhande DY2, Prasant Nigwekar3, Santosh Yadav1, Haresh Kasodariya1
1
PG Student, 2Professor and Head, 3Asso. Professor, Department of pediatrics, Rural Medical College, Pravara
Institute of Medical Sciences (DU), Loni, Maharashtra, India
*Corresponding author email: amit333n@gmail.com
ABSTRACT
A diaphragmatic hernia is defined as a communication between abdominal and thoracic cavity with or without
abdominal contents in the thorax. The true incidence of Congenital diaphragmatic hernia is 1 in 5000 live births
while right side diaphragmatic hernia (15%) is rare comparing to left side diaphragmatic hernia (85%) because
liver plugs the opening. Congenital diaphragmatic hernia typically refers to Bochdalek form, other forms are rarer.
Despite advances in neonatal intensive care, congenital diaphragmatic hernia is associated with high mortality and
morbidity. The posterolateral right congenital DH is a rare diaphragmatic defect. Females are twice affected than
that of males. The symptoms are non characteristic and patients with this disease maybe without symptoms for a
long period. The main tool for diagnosis of congenital DH is radiography. Surgical correction is required.
Keywords: Right sided congental diaphragmatic hernia, Posterolateral, Liver plugs at right side
INTRODUCTION
A diaphragmatic hernia is defined as a
communication between abdominal and thoracic
cavity with or without abdominal contents in the
thorax. Right side diaphragmatic hernia (15%) is rare
comparing to left side diaphragmatic hernia (85%)
because liver plugs the opening. Congenital
diaphragmatic hernia typically refers to Bochdalek
form, other forms are rare. The posterolateral right
congenital DH is a rare diaphragmatic defect.
Females are twice affected than that of males. The
symptoms are non characteristic and patients with this
disease maybe without symptoms for a long period.1
CASE REPORT
age, preterm, appropriate for gestational age (birth

weight 2300 gms, was brought to our hospital on 1
day of life with complaints of respiratory distress and
noisy breathing. Patient had tachypnea, grunting, air
entry absent over the right hemithorax along with
Peristaltic sounds heard over right hemi thorax. Chest
X ray shows Presence of bowel loops and liver in
the right hemi-thorax. Left lung showed nearly
complete expansion, Arterial Blood gas analysis
showed features of respiratory acidosis, other
investigations were within normal limits. The
neonate was referred to neonatal surgical unit for
surgical correction, after stabilization.
A male neonate, born in a private hospital to nonconsanguineous parents 36th week of gestational
Amit et al.,
193
early diagnosis is necessary in such situation; surgical

correction is the treatment modality.
REFERENCES
Fig 1: Chest X ray shows Presence of bowel loops

and liver, in the right hemi-thorax. Left lung
showed nearly complete expansion
DISCUSSION
A diaphragmatic hernia is defined as a
communication between abdominal and thoracic
cavity with or without abdominal contents in the
thorax. The true incidence of Congenital
diaphragmatic hernia is 1 in 5000 live births.1 Rightsided diaphragmatic hernia (15%) is rare, compared
to left-sided diaphragmatic hernia (85%) because
liver plugs the opening. Congenital diaphragmatic
hernia typically refers to Bochdalek form, other forms
are rarer.2 Malformation of diaphragm allows the
abdominal organs to push into proper lung formation
despite advances in neonatal intensive care;
congenital diaphragmatic hernia is associated with
high mortality and morbidity due to two
complications namely pulmonary hypoplasia and
pulmonary hypertension.2 The posterolateral right
Congenital Diaphagmatic Hernia is a rare
diaphragmatic defect. Females are twice affected than
that of males.1 Newborns with CHD often have
severe respiratory distress which can be life
threatening unless diagnosed and treated early.3,4 The
symptoms are non characteristic and patients with this
disease maybe without symptoms for a long period.
The main tool for diagnosis of congenital DH is
radiography. Surgical correction is required. ECMO
has been used as a part of treatment strategy in some
hospitals.3
1. Akhil maheshwari and waldermar A carlo.

Diaphragmatic hernia. Nelson textbook of
pediatrics,19th edition,:594-96
2. George BM. Report of a Case Strangulated RightSided Diaphragmatic Hernia. AMA Arch Surg.
195,72(2):273-74.
3. Bryner BS, Kim AC, Khouri JS, Drongowski
RA, Bruch SW, Hirschl RB et al., Right-sided
congenital diaphragmatic hernia: high utilization
of extracorporeal membrane oxygenation and
high survival. J Pediatr Surg. 2009;44(5):883-7.
4. Christopher VVM, Canino JE, Jules RC, James
JR. Congenital Right Diaphragmatic Hernia.
Misericordia Hospital Philadelphia, Penna
congenital right diaphragmatic hernia associated
with Thorax. Thorax. 1950;5:133
CONCLUSION
Diaphragmatic hernia is the congenital anomaly that
manifests itself since birth in the form of severe
respiratory distress. Suspicion of the condition and
Amit et al.,
194
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Case report
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CAPILLARY HEMANGIOMA OF THE COLUMELLA OF NOSE

*Muthubabu K, Sakthivel M, Srinivasan MK, Kalpana G, Twinkle Radhakrishnan, Ancy Anthony
Dept. of ENT, Meenakshi Medical College and Research Institute, Kanchipuram, Tamilnadu, India
*Corresponding author email: muthubabu67@gmail.com
ABSTRACT
Capillary hemangioma is a common condition but a capillary hemangioma arising from the columella of the nose is
rare. Here we report a 24 year old man who presented with a pedunculated swelling in the nasal columella. This was
excised. Histopathological examination showed features suggestive of capillary hemangioma, the case was
presented here due to rare occurrence in the nasal columella. Patients present with epistaxis and cosmetic
alterations. Wide excision and cauterization of the base gives excellent results.
Keywords: Columella, capillary hemangioma.
INTRODUCTION
Capillary hemangioma arising from the columella of
the nose is rare. Capillary haemangiomas can occur
anywhere in the nasal cavity and has even been
reported in the ethmoids.1 Congenital lesions of
capillary haemangioma have been reported in
children.2 Capillary haemangiomas can grow in size to
produce nasal obstruction, hence earlier surgical
intervention is advisable.3 Frequent nose picking with
fingers has been cited as etiological factor. Cryo
application is one modality of treatment.5 Wide
excision and cautery is the treatment of choice.
CASE REPORT
A 24 year old person presented with complaints of
swelling hanging from the nose of one month duration.
He gave history of frequent nose picking with his
fingers. To start with the swelling was small in size
and has attained the present size (fig 1). He gave
history of bleeding from the mass at times. It was not
painful. He was also bothered about the cosmetic
alteration. On examination a reddish pedunculated
mass was seen arising from the columella of the nose
on the right side. The stalk was narrow. The size of the
mass was about 2 cms. It was nontender, bled on
Muthubabu et al.,
touch, hanging and freely mobile. Anterior rhinoscopy

was done. The septum, turbinates and nasal mucosa
was found to be normal. Postnasal space was normal.
Under Local anaesthesia, infiltration with 2%
xylocaine in the columella of nose around the mass
was done. The pedunculated mass was excised
completely and the base was cauterized with bipolar
cautery. A wide excision of the mass was done. The
specimen was sent for histopathology which
confirmed capillary hemangioma ( fig 2&fig 3). The
wound was sutured with 3 0 chromic catgut. There
was no recurrence on follow up.
Fig 1: Capillary hemangioma arising from the nasal

columella.
195
argon laser has also been considered by some for the

removal of this hemangiomas.10
CONCLUSION
Capillary hemangiomas are a common tumour. But
occurrence in the nasal columella is rare. Patients
present with epistaxis and cosmetic alterations. Wide
excision and cauterization of the base gives excellent
results.
REFERENCES
Fig 2: Photomicrograph showing lobular arrangement of
thinned out capillaries lined by plump endothelium and
thinned out squamous epithelium. (10 X)
Fig 3: Photomicrograph showing proliferation of

thinned out capillaries lined by plump endothelial cells.
(40 X)
DISCUSSION
Capillary hemangiomas are benign tumours arising
from the vascular tissues of skin and mucosa. They are
made up of small capillaries which are normal in size
but more in number. These tumours may be either flat
to the skin, raised or protrude out as a nodule. In our
case the hemangioma protruded out as a nodule. They
are usually typically bright red in colour. Large
capillary hemangioma arising from the nasal columella
has been rarely reported.6
Adult capillary
hemangiomas have also been reported in the upper
eyelid.7
In the nasal cavity, cases with capillary
hemangioma involving the middle turbinate8 and in the
nasal septum has also been identified.9 Previous nasal
trauma and nose picking has been implicated as
possible etiological factors.4 In our case the cause of
the capillary hemangioma could be his persistant nose
picking habit. Small tumours like the one reported
here can be easily excised and the base cauterized. An
Muthubabu et al.,
1. Swapan K Gosh, Rajkumar Chathurvedi.

Capillary haemangioma of the ethmoid. Indian
Journal of Otolaryngology. 2004; 56(2): 148-49
2. Nedev P. Lobular capillary haemangioma of the
nasal cavity in children. Trakia Journal of
Sciences. 2008; 6(1): 63-67.
3. Milton Waner, Julie Kastenbaum, Kathrin Scherer.
Haemangiomas of the nose Surgical
management using modified subunit approach.
Arch Facial Plast Surg 2008; 10(5):329-334.
4. Puxeddu R, Berlucchi M, Ledda GP, Porado G,
Farina D, Nicolai P. Lobular capillary
hemangioma of nasal cavity. Ann J Rhinol. 206 ;
20 (4): 480 4.
5. Mohammed Maqbool, Suhail Maqbool. Tumours
of the nose and paranasal sinuses. Textbook of ear
nose and throat diseases 2013; Chapter 38, page
169.
6. Bora H, Bandyapadhyay SN, Sinha R, Bhuria R,
Mukherjee S, Das KK,Mukherjee PB. Large
capillary hemangioma arising from the nasal
columella: A case report. Journal of Indian
Medical Association 2001; 99(5):269 70.
7. Robert JP, Thomas I, Warner, Heather AD, Potter,
Daniel M, Albert. Adult capillary hemangioma.
Archives of ophthalmology 2012;130 (8):999
8. Kartaran H, Uraldi C, Arl N, Aktas D. Lobular
capillary hemangioma of the middle turbinate .
Acta otolaryngol 2006; 126: 442 444.
9. Ayotunde J Fasunla, Oluwatasin S Adebola,
Clement A Okolo ,Adereni AA. Nasal septal
lobular hemangioma in West Africa sub region ; A
case report. Case journal 2009 ; 2 : 8952.
10. Lemarchand VF. Indications for laser in the
treatment
of
capillary
hemangioma.
J.Mal.Vasc.1992:17(1) 41 3.
196
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Volume 3 Issue 1(Jan- Mar) Coden: IJMRHS
th
Case report
DELTO-PECTORAL FLAPS FOR SECONDARY
RECURRENT PAROTID TUMORS: CASE SERIES
DEFECTS
Copyright @2013
ISSN: 2319-5886
FOLLOWING
EXCISION
OF
*Adedeji Taiwo O1, Tobhi James E1, Olaosun Adedayo O1, Oseni Oyeniran G2, Idowu Julius A1, Olaitan Peter B2
1
Department of Ear Nose and Throat, Ladoke akintola University of Technology Teaching Hospital, Osogbo
Department of Surgery, Ladoke akintola University of Technology Teaching Hospital, Osogbo
*Corresponding author email: adedejitaiwo2003@yahoo.com

ABSTRACT
Background: Extensive infiltration of the skin by parotid gland tumors often lead to the surgeon seeking various
options that will lead to good cosmetic appearance and reduced donor site morbidity. Materials and Methods: This
is a report of two patients with extensively enlarged parotid tumors with associated skin loss and depth that was
difficult to close. Consent/permission was obtained from the patients. The case notes of the patients were reviewed
and it shows that apart from local tissues and skin grafts, delto-pectoral flaps could come handy. Outcome is
reported in this report. Results: Two patients who had a deltopectoral flap cover of their defects following excision
of huge parotid tumors involving the infiltration of the overlying skin are reported in this study. There was good
aesthetic outcome with minimal and acceptable donor site morbidity. Conclusion: Delto-pectoral flaps should be
considered an option in covering defects following parotid tumour excision.
Keywords: Recurrent parotid tumours, Delto-pectoral flaps, Secondary defects, Cosmesis
INTRODUCTION
Parotid gland tumors are not common.1-3 Generally,
salivary gland tumors represent about 1-3% of head
and neck tumours.2 In our environment, it constitutes
1.7% of head and neck tumours3. Seventy eight to
eighty percent of parotid tumours are benign.2, 3
Parotid tumours elicit considerable medical interest
because of their multifaceted clinical presentation,
varied histological appearances and the associated
difficulties in predicting their prognosis.1,3 In most
cases, therapy consists of parotidectomy and adjuvant
therapy mainly radiotherapy which is reserved for
cases with malignancies.2 Surgical intervention varies
from limited excision to extensive parotidectomy with
facial nerve sacrifice with or without neck dissection2.
Factors that influence surgical therapies include facial
nerve invasion, tumour extension, histological
characteristics and positive limits of the tumor.2
The recurrent parotid gland tumor is a challenge to

both the patient and the surgeon. Factors responsible
for tumor recurrence include histological grade, extent
of the tumour, invasion of adjacent structures and poor
surgical technique. Recurrence is more common in
malignant tumors4 but in pleomorphic adenoma (a
benign tumour), if the capsule ruptured during
removal, tumour may implant and cause recurrence.4
Management of recurrent parotid tumour is
challenging.4 There is a need for wide surgical
excision4 and facial nerve as well as the surrounding
soft tissues including skin sacrifices is inevitable.
Wide defects are therefore produced necessitating a
flap cover or a skin graft. The significant depression
created by complete tumour excision is a source of
concern for the patient about cosmesis and challenge
to the doctor about its closure.
197
Adedeji et al.,
Various options available for repairing the defect

include fat grafts, sternocleidomastoid muscle rotation
flaps, cellular dermal graft and free vascularized facial
graft.4 The deltopectoral flap is a useful, reliable and
versatile regional flap that can be used in selected
circumstances
for
major
head
and
neck
5
reconstruction. This article reports two cases of
recurrent parotid gland tumours that were managed by
the use of deltopectoral flaps in repairing the defects
created following wide surgical excision.
over to fill the defect. This was transferred under the

skin of the lateral neck. The result was functionally
and cosmetically accepted by the patient.
CASE NO 1
A.I. was a 69yr old male Nigerian referred from a
private hospital on account of left sided parotid
swelling. Progressive left sided parotid swelling
noticed about a year prior to presentation. No
associated swelling in other parts of the body, no pain
and no facial weakness. Examination at presentation
showed left sided parotid swelling which measured
6cm x 8cm in its widest dimension. It was firm, non
tender with no associated parapharyngeal /
oropharyngeal extension and no facial nerve
involvement.
Full blood count, electrolyte and urea and chest
radiograph were normal. An ultrasound revealed a
cystic mass 4.5cm x 4.7cm in widest dimension. Fine
needle aspiration for cytology suggested a benign
lesion. Patient had superficial parotidectomy under
general anesthesia. Findings at surgery were a cystic
mass about 6x6cm which contained sero-sanguinous
fluid. Patient was noticed to have developed House
and Brachman grade II facial palsy. Histology of the
tumour showed adenoid cystic carcinoma on account
of which he was referred for radiotherapy and
discharged to clinic but was lost to follow up.
He however re-presented two years later on account of
2 months history of recurrent parotid swelling with
associated pain and worsening of facial weakness.
Examination revealed 8cm x8cm left parotid swelling,
firm, non tender and no differential warmth. There was
grade III facial palsy. Full blood count, electrolyte and
urea, chest radiograph and clotting profile were
normal. He had a total parotidectomy. Operative
findings were tumour with a cystic cavity that had
infiltrated the root of zygoma, facial nerve, posterior
wall of external auditory canal and ramus of the
mandible. There was a big cavity of about 6 cm depth
created. A deltopectoral flap was then designed and
raised and de-epithelialised and the distal part turned
Fig 1: Huge left parotid tumour infiltrating the skin

and ear lobule.
Fig 2: Case 1 at surgery (filling the defect with

delto-pectoral flap)
Fig 3: Post operative appearance

CASE NO 2
A 73yr old widow who presented on account of left
sided progressive parotid swelling of five years
duration. No associated swelling in other part of the
body, no history of pain, trauma or facial weakness
and no alteration in the size of the tumour during food
intake. Examination revealed an elderly woman with
198
Adedeji et al.,
12x 11cm left sided parotid mass, firm, non tender and
no differential warmth. Full blood count, electrolyte
and urea and chest radiograph were normal,
electrocardiograph
showed
left
ventricular
hypertrophy, neck ultrasound revealed a non
homogenous mass with multi-septated cystic masses
measuring 10x20mm. Fine needle aspiration for
cytology was suggestive of pleomorphic adenoma. She
had superficial parotidectomy. Findings at surgery
were multi-nodular cystic mass about 25x18cm in its
widest dimension. Histology of the tumour showed
adenoid cystic carcinoma on account of which she had
54 cGy of radiotherapy. Three years later, patient
represented with 6 months history of recurrence. The
recurrence was associated with pain, facial weakness,
and ulceration and bleeding. Examination revealed an
elderly woman with a left parotid mass about 16x8cm
in widest dimension which had involved lobule of the
ear with a central area of ulceration. Full blood count,
electrolyte and urea, and chest radiograph were
normal. She had total parotidectomy. Operative
findings were multi-nodular masses which had
invaded the lobule of the ear and infiltrated the
branches of the facial nerve and associated facial
weakness. (Fig 4). A wide defect of 10 x 12cm) was
created. (Fig 5). Delto-pectoral flap of 24cm length
and 8cm width was designed, raised and partly deepithelialised. It was transferred by tunneling
subcutaneously into the defect. It covered the defect
completely and healed perfectly. The result was
functionally and aesthetically acceptable to the patient
Fig 4: Extensive recurrent left parotid tumor

infiltrating the skin and ear lobule
Fig 5: Defect after excision
Fig 6: Postoperative appearance of case 2.

DISCUSSION
The delto-pectoral flap remains a useful, reliable, and
versatile regional flap that can be used alone or in
combination with other flaps in selected circumstances
for major head and neck reconstruction5. It has
provided an excellent source of thin and pliable tissue
that form appropriate source of donor tissue for
reconstruction of limited defects of the pharynx,
esophagus, and skin of the neck6. The flap has become
the most commonly used pedicle regional flap for head
and neck reconstruction while providing coverage for
most defects of the head and neck from the scalp and
skull base to the cervical region and hypopharynx7. It
continues to play an important role in head and neck
reconstruction, reflecting its versatility, reliability, and
ease of harvest7. The current reports show the
versatility of this flap in covering secondary defects
from parotidectomy especially in our environment
where patients present rather late with tumours that
may leave a defect that may not close directly. While
Microvascular procedure might have given a better
result, facility for this is often not available in most
developing countries. This flap therefore comes handy
in managing this difficult and extensive defect
199
Adedeji et al.,
especially with the attending cosmetic problem that

might arise following the use of inappropriate tissue
for the closure.
Head and neck surgeries present unique challenges
because of the variety of functions that head and neck
are responsible for, including speech, swallowing,
sensation, oral continence, airway protection and facial
expression. Deformities of the head and neck region
can have devastating effects on the appearance and
function of the patient and are among the most
disabling and socially isolating defects with significant
impact on the patients quality of life. Reconstruction
of such defects continues to be an extremely
demanding challenge for surgeons who aim to restore
form and function with minimal surgical morbidity.
These reconstructive surgeries must always be
performed in a way that preserves these functions as
much as possible. The surgery may be done to restore
function, improve cosmetic appearance, or a
combination of both.
In the cases presented here, both function and
aesthesis were preserved with the flaps-one covering
the wide defect smoothly and the other occluding a
depth created by the excision of the tumors.
Gardiner et al.8 reported three cases of recurrent head
and neck carcinoma viewed as challenging
reconstructive problems because of the extent of the
extirpative surgery necessary and the substantial risk
of complications that would be associated with
previous treatment techniques. They showed that
myocuteneous flaps were quite versatile and useful in
head and neck reconstructive process8. Hurvitz et al.9
reported that although defects of the head and neck
region present a challenge, successful cosmetic and
functional results have been achieved with both local
and free tissue flaps.
In the first of the cases presented in this article, deltopectoral flap was designed, raised and deepithelialised. It was transferred by tunneling
subcutaneously into the defect to fill the cavity created
while in the second case, the flap with 24cm by 8cm
was designed, raised and partly de-epithelialised. It
covered the defect completely and healed perfectly.
Both results were functionally and aesthetically
acceptable to the patients. Delto- pectoral flap is
therefore useful in the reconstruction of defects and
restoration of cosmetic value to the patients following
surgical excision of recurrent parotid tumours.
While the flap functions effectively for aesthesis and

function, the limitation of the flap is in the fact that it
was bulky and needed to be divided secondarily to
remove the bulkiness on the side of the neck in one of
the patients. This was in a woman with thick
subcutaneous fat. The second problem arose as a result
of the fact that the secondary defect was closed
directly and this led to about 2-3cm lift of the
ipsilateral breast compared to the contralateral side.
Although the 73 year old woman was satisfied and did
not bother about the disparity in the breasts as a result
of the flaps, caution is suggested in raising these flaps
in women. Indeed, this problem of lift and the
bulkiness that may need a second procedure must
always be explained to the patients. Deltopectoral
flaps are therefore part of the armamentaria that can be
considered for parotidectomy defects.
CONCLUSION
Delto-pectoral flaps should be considered an option in
covering defects following parotid tumour excision. It
is useful in the reconstruction of defects, restoration of
cosmetic value to the patients with minimal and
acceptable donor site morbidity.
REFERENCES
1. Somefun OA, Oyeneyin JO, Abdulkarrem FB, da
Lilly- Tariah OB, Nimkur LT, Esan OO. Surgery
of parotid gland tumours in Lagos: a 12 year
review. Niger Postgrad Med J. 2007; 14(1): 72-75.
2. Mag A, Cotulbea S, Lupescu S et al. Parotid Gland
Tumours. J Exp Med Surg Resear. 2010; 4: 259263.
3. Nzegwu MA, Ngozi NR, Ugochukwu AI et al. A
Review of Salivary Gland Neoplasm in Eastern
Nigeria for A Five- Year Period from January 1,
2000 to December 31st 2004. Adv in Bioresear
2011; 2(1): 28 32
4. Carrol WR, Morgan CE. Diseases of the Salivary
Glands. In Ballengers Otorhinolaryngology Head
and Neck Surgery, sixteenth edition (Snow JB,
Ballenger JJ eds) BC Decker Inc. Hamilton,
Ontario, 2003; 1441 1454.
5. Gilas T, Sako K, Razack MS et al. Major Head
and neck reconstruction using deltopectoral flap.
A 20 year experience. Am J Surg 1986; 152(4):
430 434.
6. Mortensen M, Genden EM, Role of the island
deltopectoral flap in contemporary head and neck
200
Adedeji et al.,
reconstruction. Ann Otol Rhinol Laryngol. 2006

;115(5):361-364
7. Yang JY, Rosen MR, Keane WM. Flaps and
Grafts in the Head and Neck. In Ballengers
Otorhinolaryngology Head and Neck Surgery,
sixteenth edition (Snow JB, Ballenger JJ eds) BC
Decker Inc. Hamilton, Ontario, 2003; 972- 996.
8. Gardiner LJ, Ariyan S, Pillsbury HC.
Myocuteneous flaps for challenging problems in
head and neck reconstruction. Arch Otolaryngol.
1983; 109(6): 396- 399.
9. Hurvitz KA, Kobayashi M, Evans GR. Current
options in head and neck reconstruction. Plast.
Reconstr. Surg. 2006; 118(5):122e-133e.
201
Adedeji et al.,
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RABIES: NEED FOR ACTIVE AND PASSIVE IMMUNISATION

G N S Sangeetha Lakshmi
Dept of General Medicine, Baptist Christian Hospital, Tezpur, Assam
Corresponding author email: asangeethalakshmi@yahoo.co.in
ABSTRACT
Rabies is an acute highly fatal viral disease of the CNS caused by Lyssavirus Type-I. It has a long and variable
incubation period. It is a communicable disease of man that is always fatal. The combined administration of a single
dose of anti rabies serum with a course of vaccine, together with local treatment of the wound is the best specific
prophylactic treatment after exposure of man to rabies. Here, we report a case of rabies, who developed the disease
in spite of having taken three doses of anti rabies vaccine (Post exposure).
Keywords: Rabies Immunoglobulin, Human Diploid Cell Vaccine, Post-exposure Prophylaxis, Intra-dermal
Regimen.
INTRODUCTION
Rabies is a zoonotic disease of warm blooded
carnivore animals. It is transmitted to man usually by
bites or licks of rabid animals on broken skin and
mucous membrane.
Human Rabies is endemic in India. According to a
recent WHO estimate, 55000 deaths occur annually
due to human rabies globally 20,000 (36%) of which
occur in India.1
CASE REPORT
A female patient aged 55 years presented to the
Casualty of a secondary care hospital in Assam with
history of feeling feverish, headache, vomiting and
increased irritation since the morning of 29.05.2012.
She was admitted to the hospital with a provisional
diagnosis of Acute Sinusitis / Headache for evaluation.
At admission on physical examination vitals were
stable, mild frontal sinus tenderness was seen, and rest
of the systemic examination was normal. Complete
blood count, Random Blood Sugar, Serum Creatinine,
Serum Electrolytes, Liver Function Test, complete
Urine examination were within normal limit. Tests for

the peripheral smear of malaria and Rapid test for
Scrub Typhus was Negative. Chest-X-Ray and ECG
were within Normal limit.
After admission, in the ward she was found to be
reluctant to drink water. Further examination revealed
agoraphobia, hydrophobia and a healed wound on the
nasal bridge.
On reviewing history, the patients attendant revealed
that the patient had been bitten by a street dog on the
nasal bridge 2 weeks ago. The patient was taken to a
local physician and given HDC vaccine-Rabipur on 0
day - 1st dose, 3rd day - 2nd dose, 7th day - 3rd dose ;
post exposure. The 4th dose was not taken, as the
patient developed symptoms of rabies two days prior
to the 4th dose. The patient was however not RIG
advised.
The patient was well until 27.05.2012 (14 days after
the dog bite) doing all household work. The neither
relatives nor patient could tell about the fate of the
dog. A clinical diagnosis of rabies was made. The
202
Sangeetha.,
patient was discharged on request and advised to go to

a higher Centre.
DISCUSSION
The prophylaxis of rabies is with an Anti rabies
vaccine and rabies Immunoglobulin.
The Post
exposure Prophylaxis depend on the category of the
wound.2
Approach to Post-exposure Prophylaxis (PEP):
Management of animal bite wound:
Wound Toilet: Rabies virus enters the human body
through a bite or scratch. An efficient wound toilet can
be done by prompt and gentle washing with soap and
flushing the wound with running water for 10 minutes.
Considering the importance of this step all clinics that
are likely to encounter patients with dog bites should
have wound washing facilities.
Passive immunization rabies Immunoglobulin
(RIG): RIG should also be administered as passive
immunisation for immediate protection before the
development of immunity from the vaccine, It should
be given at the same time as the first dose of vaccine
and no later than 7 days after the first dose.2 Rabies
vaccine and RIG should never be administered at the
same site or in the same syringe.
Two types of Rabies antibody preparations are
available: Human rabies immunoglobulin (HRIG) and
Equine rabies immunoglobulin (ERIG).
The recommended dose of ERIG is 40 International
units (IU) /Kg 3 up to a maximum of 3000 IU 2, ERIG
may be occasionally associated with anaphylaxis. A
skin test may be performed prior to the administration
of ERIG but WHO does not advocate skin sensitivity
test (SST) anymore.4 The recommended dose of HRIG
is 20 IU/Kg3 up to a maximum of 1500IU.2 Adverse
effect of HRIG includes local pain and low grade
fever.
The wounds should be infiltrated with RIG (if
anatomically feasible) and the remainder of the dose
should be given intramuscularly (IM) in the gluteal
region. If the exposure involves a mucous membrane,
the entire dose should be administered IM. With
multiple or large wounds, the RIG may need to be
diluted for adequate infiltration.
Active Immunisation Anti rabies Vaccine: HDC
vaccines are mostly used as they are generally safe and
highly potent. All age groups of animal bite victims of
category II and III require the same number of
injections and dose per injection. The category III

exposures in addition require administration of rabies
immunoglobulin.
The
vaccination
schedule
recommended for Post exposure Prophylaxis consist of
6 doses (1 ml each) on days 0, 3, 7, 14 and 28 and a
booster dose on day 90. Injections are given
intramuscularly (deltoid).2
Intra-dermal (ID) Regimens: The use of this route
leads to considerable savings in terms of the total
amount of vaccine needed for a full Post-exposure
vaccination. A vaccine which has been approved by
Drug Controller General of India (DGCI) for use by
intra-dermal route have to be used [2] .The vaccines
used are same; however route, dose and site of
administration differ. The Regimen approved by DGCI
has updated Thai Red Cross schedule (2-2-2-0-2).2
Approach to a patient requiring RIG when none is
available: In circumstances when no immunoglobulin
is available greater emphasis should be given to proper
wound toileting followed by Essen schedule. 2
RIG is life saving biologic in patients with severe
exposure to rabies, but scarce and expensive.
Worldwide less than 3% of risk exposure cases receive
RIG and it is often not injected into wounds.5,6 Fear of
anaphylaxis with ERIG and the cost of HRIG are the
main barrier. ERIG is indigenously produced, less
expensive, more widely available. ERIG should be
promoted as an institutional product7 and given by
trained persons in all first referral unit (FRU)
hospitals. The safety profile of ERIG is good in many
studies.8 Post exposure prophylaxis applied adequately
is highly effective in prevention of human disease but
its use is low in India (2.1%).9 The compliance to
vaccine in India is 40.5%.9
After recognition of a rabies exposure, when a patient
approaches a local physician, exposure has to be
assessed to see which category it falls into. The need
for RIG and active immunisation has to be stressed
and informed to the patient by the local physician. In
our case, the patient should have been administered
RIG along with the first dose of rabies vaccine or been
informed of the need to enable the patient to approach
a higher centre for the same.
Rabies can be confirmed in patients early in the illness
by antigen detection using immuno fluorescence of
skin biopsy, and by virus isolation from saliva and
other secretions. These tests are not available in our
hospital, therefore they were not done.
203
Sangeetha.,
CONCLUSION
The approach to the management of rabies consists of
wound toilet, active and passive Immunisation should
be made available at the Primary Health Centres
(PHC) across the country.
As HRIG is expensive, ERIG can be used as it is less
expensive and more widely available. WHO has
recommended the use of intra-dermal (ID) route of
administration of HDC vaccine which not only reduces
the cost of Post-exposure Prophylaxis, but also allows
wider coverage in available quantity of vaccine?
This case shows the need for the combined
administration of RIG and Anti rabies vaccine in every
case of exposure of man to rabies. Every instance of
human exposure should be treated as a medical
emergency.
REFERENCES
1. Haniv J, Gdalenich M, Mimouni D, Gross E,
Shpilberg O. Successful post exposure rabies
prophylaxis after erronous starting treatment. Prev
Med 1999; 29(1): 28-31
2. National guidelines for rabies Prophylaxis and
Intra-dermal Administration of Cell Culture rabies
Vaccines
2007.
www.ncdc.gov.in/Rabies_Guidelines.pdf
3. World Health Organisation 2005: WHO expert
consultation on rabies. First report (First Report
Edition),
Geneva,
WHO,
2005.
http://apps.who.int/iris/bitstream/10665/85346/1/9
789241209823_eng.pdf
4. Rabies Vaccines: WHO Position paper. Wkly
Epidemiol Record 2010; 85:309-20.
5. David Anderson. WHO guidelines dealing with
immunoglobulin use impede rabies prevention.
Asian Biomed. 2007; 1:103-7.
6. Association for Prevention and Control of Rabies
in India (APCRI), assessing the burden of rabies in
India: WHO Sponsored National Multi Centric
rabies Survey, 2004. http://rabies.org.in/rabiesjournal/rabies-06/SpecialArticle1.htm
7. Sudarshan MK, Ashwath Narayana DH, Ravish
HS. Is skin sensitivity test required for
administering equine rabies immunoglobulin ?
The National Medical Journal of India.
2011;24(2):80-82
8. Chawan VS, Tripathi RK, Sankhel L, Feravdes
AC, Dastary GV Safety of equine rabies
9.
10.
11.
12.
immunoglobulin in Grade-III bites. Indian J

Community Med 2007; 32:73-74
Sudarshan MK. Assessing the burden of rabies in
India. WHO sponsored national multi-centric
rabies survey 2003. Final report August 2003.
Bangalore, Association for Prevention and control
of Rabies in India (APCRI), 2003.
Tapan Ranjan, Durga Madhab Sathapathy,
Ashiwini Kumar Pradhan. Safety of Equine rabies
Immunoglobulin into fingers and toes. Asian Bio
medicine. 2012;6(3):429-32.
Wilde H, Chutivongse S. Equine rabies
immunoglobulin : a product with a underserved
poor reputation. An J Trop Med Hyg.
1990;42(2):175-8.
Sudarshan MK, Madhusudan SN, Mahendra BJ,
Rao NS, Aswath Narayana DH Abdul Rahman S,
Assessing the burden of human rabies in India.
Results of a national multi-centre epidemiological
survey. Int J Infect Dis 2007, 11:29-35.
204
Sangeetha.,
DOI: 10.5958/j.2319-5886.3.1.044

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SPONTANEOUS NEPHROCUTANEOUS FISTULA IN TUBERCULOUS PYELONEPHRITIS: AN

UNUSUAL OCCURRENCE
Apoorv Sharma1, *Zeeshanuddin Ahmad1, Arpan choudhary1, Moolchand Songra2
1
MS Senior Resident, Department Of Surgery, GMC Bhopal, Madhya Pradesh, India

HOD and Professor, Department Of Surgery, GMC Bhopal, Madhya Pradesh, India
*Corresponding author email: zee_kmc03@rediffmail.com

ABSTRACT
Nephrocutaneous fistula has an uncommon incidence and occur usually as a complication of operative procedures
on kidneys, renal injuries (penetrating or iatrogenic), renal uroliths, renal tumors and chronic UTI with resultant
perirenal abscesses. The most common causes identified are renal calculi and chronic renal tuberculosis. We intend
to highlight a case of a woman aged 35years, complaining of watery discharge through the skin in the right lumbar
region for the past six months. A fistulogram was done which showed the passage of contrast dye in the collecting
system. The patient underwent a simple nephrectomy on the concerned side and recuperated without any
complication in the postoperative period.
Keywords: Kidney, Fistula, Renal tuberculosis, Nephrocutaneous.
INTRODUCTION
Spontaneous nephrocutaneous fistula (NCF) is a rare
condition.
Majority
develop
secondary
to
postoperative, trauma, chronic urinary tract infection,
renal stones1. Few cases as a complication of
xanthogranulomatous pylonephritis has also been
reported to the literature2, however occurrence of this
condition due to renal tuberculosis is a rare
phenomenon. The fistula may be internal (the fistulous
communication between kidney and adjacent viscera
like colon, duodenum, or jejunum) or external, like
nephrocutaneous fistula.3We report a rare case of
Spontaneous nephrocutaneous fistula due to renal
tuberculosis.
CASE REPORT
Complaints - A 35 year old female presented with
complaint of insidious onset watery discharge from her
right flank for 6 months. There was no history of loin
pain, back pain, lump in abdomen, fever, frequency of
urination or burning micturition at any time during the

course of illness. She never underwent any surgical
intervention in the past. There was also no history of
previous purulent discharge.
Examination -The physical examination revealed a
fistulous orifice in the skin on the right lumbar region
with surrounding induration. Examination of chest,
abdomen, spine and genitourinary systems was
unremarkable. There was no lymphadenopathy. On
examination watery discharge was of ammoniacal
smell. Culture and sensitivity of the discharge and
urine were sterile. X-ray chest, spine and KUB were
normal. Routine blood tests including renal functions
were normal and patient was not found diabetic.
Investigation - A fistulogram was done which showed
the passage of contrast dye in the right collecting
system travelling down freely up to the ureter and
bladder (Figure 1). Excretory urography revealed
nonfunctioning right kidney with normal function
205
Apoorv et al.,
opposite side. Ultrasound abdomen revealed small

right kidney with significant cortical loss and fistula
site biopsy was inconclusive.
Treatment- In view of non functioning right kidney,
nephrectomy was planned with excision of the fistula.
Intraoperatively shrunken, atrophic kidney was found
adhered to the surrounding tissue and perinephric fat
with caseous material filled in (Putty kidney). After
careful separation from surrounding tissue simple
nephrectomy was performed by excision of the entire
fistulous tract including skin and subcutaneous tissue.
Histopathology - Histopathological examination of
the specimen showed tuberculous pyelonephritis. The
postoperative period was uneventful. Patient was
started on antitubercular drugs and was discharged on
the seventh post-operative day.
Fig 1: Fistulogram showing passage of contrast agent to

the right collecting system freely up to the bladder
DISCUSSION
Spontaneous nephrocutaneous fistula without previous
surgical history is rare.4 Most of the cases reported in
the literature was associated with chronic UTI, renal
tumors, renal tuberculosis and nephrolithiasis. Patients
often overlook minor complaints of backache and
flank pain; such neglected cases often harbor an
underlying perinephric abscess5 that may lead to the
genesis of a spontaneous NCF. A review of literature
suggests renal calculus being the most common cause
followed by tubercular and xanthogranulomatous
pyelonephritis and reflux disease. 6,7 However some
reports favor open surgical procedure being

commonest. 8
Tuberculous pyelonephritis usually starts in renal
parenchyma and ureters and bladder are secondarily
involved. The mode of spread is hematogenous. Three
pathological stages have been described. At any stage,
when there is significant fibrosis and outlet
obstruction, the pus may find its way along the path of
least resistance-forming renocutaneous, reno-colic or
reno-pleural fistula. The case under discussion had
total outlet obstruction in proximal ureter due to
progressive fibrosis and obstruction causing atrophic,
putty kidney and renocutaneous fistula.
The clinical features related to renal tuberculosis are
variable and range from simple fatigue, anorexia and
weight loss, to the attacks of loin pain and haematuria.
Other features depend upon the stage of disease and
extent of involvement. Apart from routine
investigations, culture and sensitivity of urine,
abdominal ultrasound, fistulography, excretory
urography and DTPA renal scintigraphy are important
diagnostic tools.
Early changes are best detected by excretory
urography / pyelography while chronic changes are
evaluated with the help of ultrasound or CT scan. Plain
films are helpful in detecting lesions in the lungs and
areas of calcification in kidneys, adrenals and adjacent
lymph nodes. The standard treatment of
nephrocutaneous fistula is nephroureterectomy with
complete debridement of affected perirenal fat,
muscles, and subcutaneous tissue. The surgery is
followed by anti-TB regimen and long-term follow-up.
Classification of TB Pyelonephritis
I: Nondestructive (infiltrate) tuberculosis of kidney
II: Initial destruction (papillitis or small, by diameter
about 1 cm, single cavity);
III: Marked destruction (caverns or policavernosial
tuberculosis one of kidney segments);
IV: Total or subtotal destruction (policavernose
tuberculosis, tubercular pyonephrosis, calcification).
They distinguish three forms of tuberculosis:
tuberculoinfiltrative, ulcerous and scar.
CONCLUSION
We highlight here the rarity of spontaneous
nephrocutaneous fistula and renal tuberculosis as an
important differential diagnosis to be kept in mind in
the Indian scenario.
206
Apoorv et al.,
REFERENCES
1. Singer AJ. Spontaneous nephrocutaneous fistula.
Urology 2002; 60(6): 110910.
2. Biyani CS, Torella F, comford PA, Brough SJ.
Xanthogranulomatous pyelonephrins with bilateral
Nephrocutaneous fistulae. Urol Int 1997: 59: 4647.
3. Ansari MS, Singh I, Dogra PN. Spontaneous
nephrocutaneous fistula2 unusual case reports
with review of literature. Int Urol Nephrol.
2004;36:23943.
4. Alberto A, Antunes, Adriano A, Calado, Evandro
F.
Spontaneous
nephrocutaneous
fistula.
International Braz J Urol 2004; 30: 316-18.
5. Karfopoulos AS, Murray W, Stone FJ.
Nephrocutaneous fistula. J Med Soc NY 1981; 78:
379.
6. Iseki T, Kawamura M. Spontaneous passage of
renal calculi through nephrocutaneous fistula due
to
calculous pyelonephritis. Br J Urol 1987;
59(3): 28586.
7. Lewi HJE, Scott R. Calculocutaneous sinus.
Urology. 1986;28:23234.
8. Das S, Ching V. Nephrocutaneous sinus: a case
report. J Urol 1979; 122: 232.
9. Hargreave TB. The kidney and ureter. In: Cusheiri
A, Giles GR, Moosa AR, (edi). Essential surgical
practice, 3rd ed. Oxford. Butterworth- Heinemann;
1995:1487.
207
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DOI: 10.5958/j.2319-5886.3.1.045

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CONGENITAL GIANT MELANOCYTIC NEVI TIP OF THE ICEBERG

*Veena G1, Sathish Selva Kumar2, Meenakshisundaram3, Rajalakshmi V4
1
Senior Resident, 2Assistant Professor, 3Associate Professor, 4Professor & HOD, Department of Pathology, ESIC
Medical college & PGIMSR , K. K. Nagar, Chennai.
*Corresponding author email: drveenasailesh@gmail.com
ABSTRACT
Congenital Giant Melanocytic Nevus (CGMN), pigmented lesion present since birth, occurs in 1 % of infants
worldwide. Fifteen percent of CGMN are localized in the head and neck region and it can also have a bathing trunk
distribution. It grows proportionally to the size of the body as the child matures and grows with variation in colour
and surface texture. A 29 years old female presented to the Gynecology Out Patient Department for infertility. She
also had multiple large nevi of varying sizes present since birth. The lesion was distributed all over the body. She
also complained of sudden appearance of swellings at the back which were later excised and the histopathological
examination showed the presence of neural nevus involving the dermis and subcutaneous tissue. This case is being
reported for its rarity, the higher risk for melanoma transformation, its association with meningeal melanosis and
few benign / malignant tumors.
Keywords: Congenital, Nevi, Melanoma
INTRODUCTION
Melanocytic nevus refers to any congenital/acquired
lesion of melanocytes. They are common and they
present with numerous clinical and histologic types.
This variation in clinical and histologic presentations
necessitates thorough knowledge to differentiate from
malignant tumors. Congenital Giant Melanocytic
Nevus, classified according to the size of the nevus,1-4
are present since birth.1 These pigmented lesions are
to be followed up regularly because of their
association with melanoma transformation, meningeal
melanosis and few benign / malignant tumors.
CASE REPORT
A 29 years old female presented to Gynecology
Department for infertility. Incidentally, she brought
to the notice of the gynecologist about multiple
blackish lesions of varying sizes all over the body
Veena et al.,
since birth. She also complained of sudden

appearance of multiple nodules on her back of three
months duration. On examination multiple large
pigmented lesions were seen in the upper part of
chest, back and face. Few areas of the pigmented
lesions showed hair. The pigmented areas of the back
showed three nodules measuring 5x4cm, 7x5cm and
8x5cm each with wrinkled skin (Fig 1). All other
laboratory parameters were within normal limits. The
clinical differential diagnosis of the nodules was
neurofibroma. One of the nodules was excised and
sent for histopathological examination.
Gross Specimen of skin with soft tissue mass
measuring 10x8x5 cm. The skin showed wrinkling
and hyperpigmentation. The cut section showed many
specs of black discoloration of less than 0.3 cm,
involving the subcutis (Fig 2).
208
Microscopy -Sections showed structure of skin with

dermis showing interlacing fascicles of spindle
shaped cells with elongated nuclei interspersed with
collagen fibers, melanophages containing melanin
pigments (Fig 3). The skin appendages were also
surrounded by similar cells. Melanin bleach was done
and it confirmed that the pigments were melanin.
Immunohistochemistry showed positivity for HMB
45 and S 100 (Fig 4). Final diagnosis of congenital
giant melanocytic nevus was made.
Fig 3 b): shows dermis with interlacing fascicles of
spindle shaped cells interspersed with collagen fibres
and theques of melanocytes (40 X)
Fig 1: CGMN involving the back, is hair borne.

Nodules are seen (arrow).
Fig 4: Immunohistochemistry a) Melanocytes showing

positivity for HMB 45 (100 X)
Fig 2: GROSS- Cut section shows multiple black

pigmented specs extending upto the subcutis.
Fig 4: IHC b) Melanocytes showing positivity for

S100 (100 X)
DISCUSSION
Fig 3: a) epidermis and underlying dermis showing

melanocytes (100 X)
Veena et al.,
Melanocytes are of neural crest origin and they

migrate along nerves that emerge from the spinal cord
and merge with the skin. As they reach the skin, they
spread out evenly among the epidermal cells. These
melanocytes produce pigments, which protect the
skin from damage by the ultraviolet rays from the
sunlight.
Congenital Melanocytic Nevi (CMN)
209
reflects a failure of the normal process of migration of

melanocytes into the skin. Instead of spreading out
evenly into the skin, many cells collect at the same
spot .
Majority of the CMN are sporadic as our case, but
few familial cases have also been reported.
Congenital melanocytic nevi are present at birth in
1% to 2% of newborns.1-3 Large CGMN are rare
occurring 1 in 20,000 to 1 in 500,000 newborns.1
CMN are classified according to their size, as smallless than 1.5cm , medium 1.5-19.9cm and large more than 20 cm.1,3,4 Zeal LH et al recommended
defining CGMN as nevi covering 1% body surface
area in the face and neck and 2% elsewhere in the
body. . Hence our case according to this can be
classified as CGMN. The size is significant as it
determines the therapeutic options and risk for
malignancies.
CGMN can occur in both sexes4 with a slight female
predilection5. Majority of Congenital melanocytic
nevi, increase in size during first trimester of
pregnancy.5,6
Clinically the CMN are tan to brown, small,
uniformly pigmented, flat to elevated with well
defined, round borders. Giant melanocytic nevus is
darkly colored and well delineated from the normal
skin. Giant CMN are often covered with hair or
proliferative nodules.7 CGMN can occur at any site,
may involve whole extremity, scalp or the trunk and
may extend into the placenta. CGMN is associated
with meningeal or cerebral melanosis.
The majority of these patients lead normal life
without any complications. CGMN is at an increased
risk for the development of melanoma and is as high
as 5-7 % by age 60 years, and Arif et al suggested the
incidence as 2% to 31 % for melanoma
transformation.5,8
In another study,
70% of
melanomas occur in patients with giant CMN before
puberty.5 Hence there is no age limitation for the risk
of melanoma transformation. The risk of melanoma
may be greater in those with giant congenital
melanocytic nevi with larger diameter.1,9 Another
study suggests multiple nevi alone or with associated
posterior midline location of large congenital
melanocytic nevi may be complicated by underlying
cranial or spinal leptomeningeal melanocytosis.10
Crowe et al11, in their study of 223 patients with
neurofibromatosis found that 3 patients had extensive
CMN. Von Recklinghausen in his monograph
Veena et al.,
described 1 of 28 patients as having giant CMN. Few

benign conditions like diffuse lipomatosis,
hamartomas,
hemangiomas,
lymphangiomas,
mastocytomas, schwannomas, Von-Recklinghausen's
disease, vitiligo, structural brain malformations,
hypertrophy of skull bones, skeletal asymmetry,
hydrocephalus are associated with CGMN. The
explanation for these mixed neoplasms is that CMN
precursor cell, at least in some cases, is pluripotent
stem cell which has the capacity to give rise to
multiple cell types.12 Similarly malignant conditions
associated with CGMN are neuroectodermal tumors,
malignant melanoma (6% to 12%), neurocutaneous
melanosis, rarely rhabdomyosarcoma. One of the
syndromes known as Epidermal Nevus syndrome,
also known as Feuerstein syndrome/ Solomon's
syndrome, consists of extensive congenital nevi with
abnormalities of central nervous system (CNS),
musculoskeletal system, cardiovascular, genitourinary
and eyes.12
A study of 57 patients with CMN, suggests that
somatic mosaicism for NRAS codon 61 mutations in
a progenitor cell within the neuroectoderm cause
multiple CMN and neuromelanosis (including
nonmelanocytic CNS lesions).13
Treatment is usually to obtain an acceptable cosmetic
result to decrease the psychosocial inconvenience to
the patient and to minimize the risk of malignancy.
Curettage is an alternative to surgical excision if
performed in the first 2 weeks of life.14 Even after
complete removal of the nevi, the risk of malignancy
persists as the melanoma can occur at extracutaneous
sites, especially in CNS.5, 15
CONCLUSION
Long term follow up of the CGMN patients helps in
early diagnosis of malignant melanoma and various
benign/malignant tumors. Regular follow up of the
patient with magnetic resonance imaging is essential
for early detection of CNS complications. Anxious
couples need to be counseled, as there is no risk
associated with pregnancies. This case reported for its
rarity and its associated complications.
REFERENCES
1. Mary Wu Chang, Vourch-Jourdain M.The Risk
for Melanoma in large, congenital melanocytic
nevi,
J
Am
Acad
Dermatol
2012,
210
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
www.jwatch.org/./risk-melanoma-largecongenital-melanocytic-nevi.
Alper JC, Holmes LB. The incidence and
significance of birthmarks on a cohort of 4641
newborns, Pediatric Dermatology. 2012;1(1):5868
James WD, Berger TG. Andrews Diseases of the
skin: clinical Dermatology, Saunders Elsevier.
2006; 10th edn ; Philadelphia, pg 678-79
Karthik Natarajan. Congenital Melanocytic Nevi :
Catch Them Early!. J Cutan Aesthet Surg.
2013;6(1) :38-40.
Bhagyalakshmi A. Giant Congenital Melanocytic
Nevus of Scalp: a rare case. International Journal
of Research in Medical Sciences. 2013;1(3):31719
Timothy
McCalmont, Dirk
M
Elston.
Melanocytic Nevi. Updated Jun 3, 2013,
emedicine.medscape.com/article /1058445.
Price HN, Schaffer JV. Congenital Melanocytic
Nevi-when to worry and how to treat: Facts and
controversies.
Clinics
in
Dermatology.
2010;28(3):293-302
Arif Turkmen, Ebopras, DaghanIsik, Mehmet
Bekerecioglu. Comparison of Classification
Systems for Congenital Melanocytic Nevi.
Dermatologic Surgery 2010;36:1554-62
Hale EK, Stein J, Ben- Porat L. Association of
melanoma and neurocutaneous melanocytosis
with large congenital melanocytic nevi- results
from the NYU-LCMN registry. Br J Dermatol.
2005;152(3): 512-17
Lovett A, Maari C, Decarie JC. Large congenital
melanocytic
nevi
and
neurocutaneous
melanocytosis: one pediatric centers experience.
J Am Acad Dermatol. 2009;61(5):766-74
Crowe FW. A Clinical,Pathological and Genetic
study
of
multiple
Neurofibromatosis.
Springfield,IL,Charles C Thomas,1956,p 181.
Fitzpatricks Dermatology in General Medicine.
Klaus Wolff. Melanocytic tumors, Benign
neoplasia and hyperplasia of melanocytes,1;7the
ed: C1099-1101.
Veronica A. Multiple Congenital Melanocytic
Nevi and Neurocutaneous Melanosis Are Caused
by Postzygotic Mutation in codon 61 of NRAS,
Journal of Investigative Dermatology. 2013;133,
2229-36
Veena et al.,
14. Linda E . De Raev. Curettage of Giant Congenital

Melanocytic Nevi in Neonates. Arch Dermatol.
2002;138(7) 943-47
15. Marghoob AA, Schoenbach SP, Kopf AW. Large
Congenital nevi and the risk for the development
of malignant melanoma. Arch Dermatol
1996;132:170
211
DOI: 10.5958/j.2319-5886.3.1.046

&
Health Sciences
Case report
Coden: IJMRHS
Copyright @2013
ISSN: 2319-5886
th
PRIMARY UROTHELIAL CARCINOMA OF PROSTATE: A RARE CASE REPORT

*
Vandana Gangadharan1, Geetha Prakash2, Eswari V3, Indhu Kannan4
Assisstant Professor, 2Professor and HOD, 3Associate Professor, 4 Post Graduate, Department of Pathology,
Meenakshi medical college, hospital and Research institute, Enathur, Tamilnadu, India
*Corresponding author email: vandanagangadharan@gmail.com
ABSTRACT
Primary urothelial carcinoma of the prostate is a rare clinicopathological entity which as a rule bears an
unfavourable prognosis. We report a case of a 75 year old male who presented with a history of voiding difficulty.
With a provisional diagnosis of Benign Prostate Hyperplasia both clinically and by needle biopsy a Trans Urethral
Resection was undertaken. Histopathology showed acini lined by malignant transitional epithelial cells with stromal
invasion. No primary in the bladder was detected on the investigation. A CK 7/ CK 20 copositivity on
Immunohistochemistry confirmed our diagnosis of Primary Urothelial Carcinoma of Prostate.
Key words: Urothelial, carcinoma, prostate, primary
INTRODUCTION
Transitional cell carcinoma of prostate is carcinoma of
urothelial origin. The reported incidence of prostatic
transitional cell carcinoma ranges from 21.8 36.7%
depending mainly on the manner of examination.1,2
Urothelial carcinoma of the prostate is rarely primary
and usually represents synchronous or metachronous
spread from carcinoma of bladder and urethra.3 The
frequency of primary urothelial carcinoma, ranges
from 1- 4% of all prostate tumours in adults.3,4 Most
patients are older with a similar age distribution to
urothelial carcinoma of the bladder i.e. 45 to 90 years.4
The primary prostatic transitional cell carcinoma
involves the entire prostatic urethra particularly areas
near the verumontanum, the large prostatic duct and
nearby acini. They presumably arise from urothelium
lining the prostatic urethra and the proximal portion of
prostatic ducts. It has been postulated that these may
develop through a hyperplasia dysplasia sequence,
possibly from reserve cells within the urothelium.5
Stephen et al 6 also suggests that tumour originating in
the prostate may be the result of malignant
Vandana et al.,
transformation of prostatic urothelium. On the other

hand secondary prostatic transitional cell carcinoma
mainly involves the bladder neck or posterior prostatic
tissue and results from the direct pagetoid spread of
urothelial carcinoma in situ or a direct pathologic
invasion of bladder urothelial carcinoma. However
whether primary or secondary transitional cell
carcinoma of prostate is believed to have a poor
prognosis.7
CASE REPORT
A 75yr old male patient presented with a 3 month
history of voiding difficulty, symptoms of nocturia and
very few episodes of dysuria. This was not associated
with significant anorexia or weight loss. No other
positive history was elicited. Serum PSA done was
within normal limits.
Ultrasonography revealed
prostatic enlargement without any nodules.
Int J Med res Health Sci. 2014;3(1):212-215
212
Initial prostatic biopsy with a provisional diagnosis of

Benign Prostatic Hyperplasia reported focal acini
showing hyperplasia with low grade PIN changes.
The patient was followed with Trans Urethral
resection of prostate which revealed prostatic acini
with adenomatous hyperplasia and a focus of ducts
lined by malignant transitional epithelial cells with
mitotic figures and areas of necrosis and stromal
invasion. suggesting Transitional cell carcinoma of
prostate.
Fig 1: Urothelial Carcinoma Prostate 40x
Fig 2: High grade cytological features (40x)
Fig 3: Cytokeratin 7 positivity (40x)
The urinary bladder was evaluated with clinical and

ultrasonography to rule out secondary TCC prostate
Vandana et al.,
from a bladder primary carcinoma. This turned out to

be negative. Immunohistochemisty with CytoKeratin
7 (CK 7) and Cytokeratin 20 (CK 20) was positive
while Prostate Specific Antigen (PSA) was negative
which confirmed our diagnosis.
DISCUSSION
Prostate cancer is one of the most common cancers in
men. Prostatic cancer occurs microscopically in up to
50% men by the age of 50 and almost all men aged 80
years showed some microscopic evidence of prostate
cancer. 8 Besides the garden variety of prostatic
adenocarcinoma many variants and a wide histological
spectrum have been described. These include
mucinous carcinoma, neuroendocrine carcinoma,
sarcomatoid carcinoma, squamous cell carcinoma,
urothelial carcinoma etc.3
Primary urothelial carcinoma of prostate is rare with
an incidence ranging from 1-4%3,4 and arises either
from prostatic urethra or from the urothelial lining of
the larger periurethral prostatic ducts.9 Patients usually
present with symptoms of haematuria, urinary
obstruction or prostatitis as was seen in our case.3,10
Wadhwa et al 11 describes an atypical case presenting
as bleeding per rectum due to a rectal ulcer. Digital
rectal examination is abnormal in the majority of cases
but is rarely the presenting sign.10 Clinically urothelial
carcinoma of prostate may be mistaken for nodular
hyperplasia or prostatitis which was the provisional
diagnosis in our case too.3 Serum prostate specific
antigen (PSA) which is the cornerstone in the
diagnosis of prostatic adenocarcinoma is not elevated
in primary urothelial carcinoma of prostate (< 4
ng/dl).3 Radiological findings can overlap and play
limited role in the diagnosis of unusual neoplasms of
prostate including urothelial carcinomas.12 Most cases
are diagnosed by TUR or less often by needle biopsy.13
TURP is preferred due to more false negative reports
with needle biopsy as seen in our case as well.
However, in all suspected cases of primary urothelial
prostate cancer the possibility of secondary
involvement from an apparent or occult bladder
primary must be excluded. This may require random
biopsies of urinary bladder mucosa.14
Histologically the diagnostic criteria for primary
prostatic urothelial carcinoma are identical to those for
urothelial cancer of the bladder; most cancers are
moderately or poorly differentiated and usually
associated with prominent chronic inflammation.
213
Squamous metaplasia is rare.3 They may be seen to

spread by invasion of prostatic stroma initially. Local
spread beyond prostate gland as well as metastasis
may occur.10 Distinguishing urothelial carcinoma from
prostatic adeno carcinoma is clinically important
because of the oestrogen unresponsiveness of the
former.3 Prostatic adenocarcinoma may respond to
hormonal therapy and cystoprostatectomy may not be
needed. Diagnosis also determines the stage for
prognostication.15 Urothelial Carcinoma is usually
distinguished from poorly-differentiated Prostatic
AdenoCarcinoma
by
its
histopathological
characteristics (Fig 1) including the presence of solid
nests of cells associated with dense or abundant
cytoplasm and striking nuclear pleomorphism, with the
absence or rarity of glandular lumina. The serum free
PSA level is a main marker for prostate
adenocarcinoma screening 15 .In difficult cases IHC
may be mandatory. The sensitivity and specificity of
PSA are high in prostate cancer, at 100% sensitivity.
In poorly-differentiated prostate cancer and PAC, the
expression levels of PSA may reach 8595%. PSA is
the
oldest
and
most
commonly
used
immunohistochemical marker to identify cancers of
prostatic origin.16 CK7 and CK20 are also useful
markers to distinguish PAC from UC. Bassily et al17
studied the expression of CK7 and CK20 in PAC and
UC, and estimated their usefulness for distinguishing
between the two tumors. In the prostatic and metastatic
tumors, neither was positive for the markers. However,
61% of the UC cases were positive for CK7 and
CK20.
CONCLUSION
Primary urothelial carcinoma is a rare type of prostatic
carcinoma which as a rule bears an unfavourable
prognosis. As a primary tumor it makes only 1-4 % of
tumors of the prostate. It originates in the poorly
differentiated reservoir cells of the prostatic
periurethral ductus which explains why diagnosis is
most often obtained in advanced stages thus limiting
its management to radical surgery. Its distinction from
prostatic adenocarcinoma is pertinent for both
treatment and prognostication. Thus Transitional Cell
Carcinoma should be considered as a differential
diagnosis in cases with obstructive symptoms and
normal PSA.
Vandana et al.,
REFERENCES
1. Lerner SP, Shen S. Pathologic assessment and
clinical significance of prostatic involvement by
transitional cell carcinoma and prostate cancer.
Urol Oncol. 2008; 26(5):481-85
2. Shen SS, Lerner SP, Muezzinoglu B, Truong LD,
Amiel G, Wheeler TM. Prostatic involvement by
transitional cell carcinoma in patients with bladder
cancer and its prognostic significance. Hum Pathol
Jun 2006; 37(6):726-34
3. Bostwick DG, Eble JN (eds): Urologic surgical
pathology. St Louis Mosby, 2000 Pgno
4. Greene LF, ODea MF, Dockerty MB. Primary
transitional cell carcinoma of prostate. J Urol
1976; 116:235-37
5. Karpas CM, Moumgis B. Primary transitional cell
carcinoma of the prostate: possible pathogenesis
and relationship to reserve cell hyperplasia of
prostatic periurethral ducts. J Urol 1969;101:20105
6. Stephen W. Hardeman and Mark S Soloway.
Transitional cell carcinoma of prostate :
Diagnosis, staging and management. World J
Urol. 1988;6:170-74
7. Varghese SL, Grossfeld GD. The prostatic gland :
malignancies other than adenocarcinomas. Radiol
Clin North America 2000; 38 : 179-202
8. Cho JY. Prostate In: Kim S H editor. Radiology
Illustrated:
Uroradiology.
Philadelphia,
P
A:Saunders, 2003:571-606
9. Pickup M, VanTH, Der Kwast. My approach to
intraductal lesions of the prostate gland. J clin
Pathol 2007;60(8):856-65
10. David J Grignon. Unusual subtypes of prostate
cancer. Modern Pathology. 2004;17:316-27
11. Wadhwa P, Mandal AK, Singh SK, Goswami AK,
Sharma SC, Joshi K et al., Primary transitional cell
carcinoma of the prostate presenting as a rectal
ulcer. Urol Int. 2004; 72(2):176-77
12. Chang JM, Lee HJ, Lee SE, Byun SS, Choe GY,
Kim Sh etal., Unusual tumours involving the
prostate : radiological pathological findings.
British journal Of Radiology.2008;81: 907-15
13. Oliai BR, Kahane H, Epstein JI. A
clinicopathologic analysis of urothelial carcinomas
diagnosed on prostate needle biopsies. Am J surg
pathol 2001;25:794-801
214
14. Young RH, Sringley JR, Amin MB. Variants of

prostatic
adenocarcinoma,
other
primary
carcinomas of prostate and secondary carcinoma.
In: Tumours of the prostate gland, seminal
vesicles, male urethra and penis. Armed forces
institute of pathology: Washington D C, 2000,21755
15. Xiaoqing Yang, Chen Xu, Jianing Guo, Chunrui
Yang, Yuming Yang, and Ruifa Han. A novel
subtype of primary prostatic adenocarcinoma : A
case report. Oncol Lett. 2013; 6(5): 130306
16. Epstein JI., PSA, PAP as immunohistochemical
markers in prostate cancer. Urol Clin North Am.
1993;20:75770
17. Bassily NH, Vallorosi CJ, Akdas G, Montie JE,
Rubin MA. Coordinate expression of cytokeratins
7 and 20 in prostate adenocarcinoma and bladder
urothelial carcinoma. Am J Clin Pathol.
2000;113:38388
Vandana et al.,
215
DOI: 10.5958/j.2319-5886.3.1.047

&
Health Sciences
Case report
Coden: IJMRHS
Copyright @2013
ISSN: 2319-5886
th
EARLY OCULAR FINDINGS IN A PATIENT OF MAROTEAUX-LAMY SYNDROME

*Haldipurkar Tanvi S1, Misra Somen2
1
Post graduate student, 2Professor, Department of Ophthalmology, Pravara Institute of Medical Sciences, Loni,
Maharashtra, India
*Corresponding author email: tanuh8@gmail.com
ABSTRACT
The Maroteaux-Lamy disease or mucopolysaccharidosis type VI is an inherited severe metabolic disorder which is
very rare. It is caused by a deficiency of the enzyme Arylsulfatase B and characterized by a heterogeneous clinical,
radiological and genetic presentation. We report a case of Maroteaux-Lamy syndrome in a child aged 9 years whose
diagnosis was suspected clinically by the combination of a dysmorphic syndrome, prominent ophthalmological
signs, hepatomegaly and normal intelligence.
Keywords: Maroteaux- Lamy, cloudy cornea, retinopathy
INTRODUCTION
The mucopolysaccharidoses (MPSs) are a group of
disorders caused by inherited defects in lysosomal
enzymes resulting in widespread intra- and extracellular accumulation of glycosaminoglycans (GAG).
Mucopolysaccharidoses are caused by a reduction in
the activity of specific lysosomal enzymes involved in
the breakdown of GAG, which results in a wide
spectrum of clinical manifestations. They may present
as a mild type which is compatible with a normal
lifespan or may be fatal in the first few months of life.1
They have been subdivided according to the enzyme
defect and systemic manifestations. They include MPS
IH (Hurler), MPS IS (Scheie), MPS IH/S
(Hurler/Sheie), MPS II (Hunter), MPS III (Sanfilippo),
MPS IV (Morquio), MPS VI (Maroteaux-Lamy), MPS
VII (Sly) and MPS IX (Natowicz). The
Mucopolysaccharidoses have a spectrum of systemic
manifestations, including airway and respiratory
distress, skeletal deformities, ophthalmological,
intellectual and neurological impairment, cardiac
abnormalities, and gastrointestinal problems1. Ocular
findings are common in mucopolysaccharidosis and
occasionally can manifest with significant visual
Tanvi et al.,
impairment. Corneal opacification of varying severity

is frequently seen which prompts the paediatrician to
refer a patient to the ophthalmologist. Other ocular
findings may include retinopathy, optic nerve swelling
and optic atrophy, ocular hypertension, and glaucoma.2
CASE
A 9 year old male child presented to our out-patient
department (OPD) with complaints of diminution of
vision in the eyes, stunted growth and coarse facial
features (Fig 1). His father had noticed the stunted
growth and coarse facial feature since two years. On
inquiry, the child had mild bone aches, joint pain and
restricted joint movements in the region of wrists and
neck. He gave complaints of diminution of vision for
the past two years for both distance and near. The
patients father also noticed whitening of both corneas
which prompted him to bring the child to the
ophthalmology OPD. The parents of the boy had a
second degree consanguineous marriage. He had an
elder male sibling with no similar complaints and no
positive family history suggestive of a metabolic
216
disorder. The boy had previously visited more than

one general practitioner for stunted growth but was
misdiagnosed as malnutrition.
We did a complete ophthalmological and systemic
examination of the child along with blood
investigations which revealed the diagnosis of
mucopolysaccharidosis type VI (Maroteaux-Lamy).3
On ophthalmological examination we found the vision
to be 6/36 and 6/60 in the right and the left eye
respectively. Best corrected vision was 6/9 in both
eyes with a refractive error of +0.75/-1.00 X 55o,
+1.00/-1.50 X 105o in right (RE) and left (LE) eye
respectively. On external examination with slit lamp
biomicroscopy, patient had bilateral diffuse epithelial
haze (Fig 2) with reduced central convexity of the
corneas. Corneal topography with Allegro Oculyzer
(Wavelight AG, Germany) showed central corneal
flattening (Fig. 3) with a keratometry values as
follows: RE -K1: 39.6D K2: 40.2D, LE -K1: 39.3D
K2: 40.4D. Intraocular pressure (IOP) with an
applanation tonometer was 16 and 18mm Hg in the
right and left eyes respectively. Central corneal
thickness noted was 555m and 520m respectively.
On electrophysiological testing, the electroretinogram
(ERG) showed a bilateral reduced sensitivity of
photoreceptors especially cones. Optical coherence
tomography (OCT) of the retinal nerve fibre layer and
macula was within normal level.
On systemic evaluation the child showed the most
signs of MPS, namely stunted growth, skeletal
deformity
with
skeletal
dystosis
multiplex
demonstrated on X-ray (Fig 4), and cardiac
involvement with non-rheumatic affection of the
cardiac valves which was confirmed by 2D
echography.
Urine
was
positive
for
mucopolysaccharidosis and a confirmatory diagnosis
was done by assessing the arylsulphatase B enzyme
levels in the blood3. Spectrophotometric assay using
para nitro catchecol sulphate and flurimetric assay
using 4-methyl umbelliferone showed a low level of
aryl sulphatase B 12.6 nmol/hr/mg (normal-115-226).
Fig 1: Stunted growth with coarse facial features

(Photograph taken after consent from of the patients
father)
SUBEPITHELIAL DEPOSITS
SEEN AS CLOUDING
Fig 2: Subepithelial haze seen under slit lamp

examination (cloudy cornea)
Fig 3: Corneal topography showing central

lattening
Fig 4: X-ray showing skeletal dystosis multiplex

with short, broad metacarpals and phalanges
Tanvi et al.,
217
DISCUSSION
Maroteaux- Lamy syndrome (mucopolysaccharidosis
type VI) is a disorder of lysosomal storage. It is
characterised by a defect in the production of the
enzyme arylsulphatase B. This causes abnormal
deposition of the GAG, dermatan sulphate. The
mucopolysaccharidoses are caused by a specific
deficiency of lysosomal enzymes which lead to the
deposition of glycosaminoglycans in various organs in
the body. This may give rise to a wide spectrum of
clinical phenotypes.
The deposition of the GAG is seen in many organs and
tissues in the body. Patients with the severe form of
MPS I, MPS II and MPS VI present early to the
clinician, as their respiratory, cardiac and skeletal
deformities make the diagnosis straight forward. In
case of mild forms of MPS I, MPS III, MPS IV,
careful examination may reveal the corneal clouding
and thereafter a paediatric reference is often made. The
deposition of GAG within the layers of the cornea
gives
it
a
cloudy
appearance.2
Detailed
ophthalmological examination often becomes difficult
owing to the corneal opacification, thickening and due
to the physical and mental capabilities of most
patients.
MPS VI may present as a wide spectrum of clinical
features, but all the affected children are intellectually
normal. This was true in our case which prompted the
child to complain about his poor vision. Individuals
with Maroteaux- Lamy disease have short stature,
coarse facial features, restrictive joint problems and
hepatosplenomegaly. Some other features include
middle ear disease, sensorineural deafness, upper
airway problems and cardiomyopathy.
Ocular findings in MPS VI are progressive increased
corneal opacification and corneal thickening. Patients
may however present with clear corneas. Raised IOP
and both acute and chronic angle closure glaucoma
have been reported in MPS VI.4 Optic nerve
involvement in the form of swelling and optic atrophy
has also been seen.5, 6 However among the various
MPS syndromes, Maroteaux- Lamy disease has a less
severe phenotype with mild skeletal deformities and a
longer lifespan. Since the ocular findings are
progressive in nature, the role of the ophthalmologist
becomes paramount. The increased life span of these
children due to the advent of the bone marrow
transplant and the enzyme replacement therapy has
widened the scope for their ocular treatment.7
Tanvi et al.,
Our case was unique due to isolated ophthalmological

symptoms. On examination, we found the other signs
suggestive of MPS VI and then further reference was
made.8 The child had a normal intellect with coarse
facial features and skeletal deformities. Cardiac
involvement was seen however the respiratory system
is unaffected at this time. Ocular involvement with
corneal opacification with corneal flattening was seen.
On investigation delayed cones response was seen on
ERG testing suggesting a retinopathy.9 The child
needs to be tested on a regular basis for any
development of glaucoma4, worsening of the corneal
clarity or other complications which may reduce his
quality of life and require appropriate treatment.
CONCLUSION
Mucopolysaccharidoses are a complex group of
diseases which are rare and difficult to diagnose as
well as treat. The patient may present to any specialty
of medicine due to its varied presentation. It becomes
imperative on the clinicians part that a careful and
meticulous examination is done which can help
diagnose this disease. Ophthalmological involvement,
although rare as an initial finding, should definitely be
kept in mind when facing a case of
mucopolysaccharidosis.
REFERENCES
1. Muenzer J. The mucopolysaccharidoses: a
heterogeneous group of disorders with variable
pediatric presentations. J Pediatr 2004;144(5
Suppl): 27-34
2. Ashworth JL, Biswas S, Wraith E, Lloyd IC. The
ocular features of the mucopolysaccharidoses.
Eye.2006;20 :55363
3. Lehman TJA, Miller N, Norquist B, Underhill L,
Keutzer
J.
Diagnosis
of
the
mucopolysaccharidoses. Rheumatology 2011;50
(Suppl 5):v41-v48
4. Cantor LB, Disseler JA, Wilson FM 2nd. .
Glaucoma in the Maroteaux-Lamy syndrome. Am
J Ophthalmol 1989;108:426-30
5. Ashworth JL, Biswas S, Wraith E, Lloyd IC.
Mucopolysaccharidoses and the eye. Surv
Ophthalmol.2006;51 :117
6. Summers CG, Ashworth JL. Ocular manifestations
as
key
features
for
diagnosing
(Suppl 5):v34-v40
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7. Giugliani R, Harmatz P, Wraith JE.. Management

guidelines
for
mucopolysaccharidosis
VI.
Pediatrics.2007;120(2):405-18
8. Muenzer
J.
Overview
of
the
(Suppl 5) :v4-v12
9. Suppiej A, Rampazzo A, Cappellari A, Traverso
A, Tormene AP, Pinello L et al. The Role of
Visual
Electrophysiology
in
Mucopolysaccharidoses.
J
Child
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2013;28(10):1203-09
Tanvi et al.,
219
DOI: 10.5958/j.2319-5886.3.1.048

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th
Case report
SYNCHRONOUS OCCULT METASTASISING DUODENAL CARCINOID AND OVARIAN MUCINOUS
CYSTADENOCARCINOMA MULTIPLE PRIMARY MALIGNANCIES IN THE SAME PATIENT
*Devadass Clement W1, Sridhar Honnappa1, Aarathi R Rau1, Sharat Chandra2
1
Department of Pathology, M.S. Ramaiah Medical College, Bangalore, India

Department of Surgical Oncology, M.S. Ramaiah Medical College, Bangalore, India
*Corresponding author email: clement.wilfred@yahoo.com

ABSTRACT
Gastrointestinal carcinoid tumors are uncommon neuroendocrine tumours that may be associated with synchronous
or metachronous primary tumours of other histological type, most frequently colorectal adenocarcinomas. Primary
ovarian mucinous adenocarcinomas have been reported to coincide with few other ovarian tumours and minority of
these tumours may occur in association with Lynch syndrome. However association of duodenal carcinoid with
ovarian mucinous adenocarcinoma is distinctly unusual and, to our knowledge, has not been previously described.
We report a case of occult metastasising duodenal atypical carcinoid that was incidentally detected during surgical
intervention performed for left ovarian mucinous cystadenocarcinoma in a middle aged female. The carcinoid
tumour was Stage IIIB with regional nodal metastasis and the ovarian tumour was Stage IA with low grade
histology.
Key words: Duodenal carcinoid, multiple primary malignancies, synchronous tumours.
INTRODUCTION
Synchronous and metachronous Multiple primary
malignancies (MPM) are relatively rare with an
overall occurrence rate between 0.73% to 11.7%.1-3
About 20-29% of small intestinal carcinoid tumours
(CTs) are associated with synchronous or
metachronous primary non-carcinoid tumours, with
colorectal adenocarcinomas being the commonest.4, 5
Primary ovarian mucinous carcinoma have been
reported in conjunction with other ovarian tumors like
teratoma, Brenner tumour, and Sertoli-Leydig cell
tumour and some occur in the setting of Lynch
syndrome.6 However the simultaneous occurrence of
duodenal CT, which is rare, and ovarian mucinous
cystadenocarcinoma, which according to recent studies
constitutes only 3% all ovarian cancers, in the same
patient is unusual. We present a case of metastasising
duodenal CT that was incidentally detected during
Devadass et al.,
treatment of ovarian mucinous cystadenocarcinoma in

middle aged female.
CASE REPORT
A 40 year old female presented with pain and mass per
abdomen of one year duration. She also complained of
progressively increasing intermittent episodes of
respiratory distress, diarrhoea, palpitations and weight
loss. She denied history of prolonged therapy with H2
blockers and family history of malignancies.
Abdominal examination revealed firm lobulated
central pelvic mass. Abdomino-pelvic computed
tomography revealed a large complex cystic ovarian
mass [Figure 1]. A complete digestive tract endoscopy,
chest X-ray and gastric and colonic biopsies were
normal. Laparotomy showed a left ovarian tumour, the
frozen sections of which revealed mucinous
220
adenocarcinoma. In addition an area of intramural

thickening was present in D1 duodenal segment with
associated serosal puckering, omental adhesions and
enlarged adherent sub-pyloric nodes suggestive of
metastasis/implants. The paraaortic lymphnodes were
also enlarged. A clinical FIGO Stage IIIC was
assigned and total abdominal hysterectomy, bilateral
salpingoophorectomy and pelvic lymphadenectomy,
omentectomy, appendicectomy and sampling of
duodenal serosal nodularity, sub-pyloric and paraaortic
nodes was performed.
Fig 1: Abdomino-pelvic computed tomography showing

a large complex cystic ovarian mass.
Pathological findings: Gross examination revealed a

tensely cystic, bosselated left ovarian mass, measuring
23x18x10 cm with intact capsule and multilocular
mucoid cut surface with mural ragged solid and
nodulocystic areas exhibiting foci of necrosis and
haemorrhage [Figure 2]. Microscopy revealed a well
differentiated mucinous cystadenocarcinoma with
expansile pattern of invasion, grade 1 (Universal
grading system) [Figure 3].
2: Multiloculated left ovarian mass with mural

ragged solid and nodulocystic areas (O), enlarged
subpyloric nodes (SP) with greater omental adhesions
(GO) and unremarkable appendix (A).
Fig
Devadass et al.,
Fig 3: A- Ovarian mucinous adenocarcinoma with

architecturally complex papillary cystic areas, BExpansile pattern of invasion; C- Glandular formations
lined by disorderly epithelium exhibiting moderate
nuclear atypia (x400 H&E).
The pathological examination of the uterus, right
ovary, bilateral fallopian tubes, bilateral pelvic and
paraortic lymphnodes, appendix and peritoneal
washings revealed no significant abnormality.
The microscopy of the duodenal serosal nodularity
revealed a histologically different tumour composed of
organoid formations of relatively monotonous
cuboidal cells exhibiting stippled chromatin and
mitotically active nuclei (4-5/10HPF) consistent with
Neuroendocrine tumour, grade II (Atypical carcinoid)
[Figure 4]. This was further confirmed by
immunohistochemistry which revealed positive
staining of pan-cytokeratin and chromogranin in the
tumour cells with a 40% Ki67 index [Figure 5]. The 3
subpyloric lymphnodes isolated revealed metastasis of
the neuroendocrine tumour (pN1)
Fig 4: A- Subpyloric lymph node (LN) with metastatic

carcinoid tumour (CT); B- Duodenal serosal nodule
showing Atypical carcinoid; C- Atypical carcinoid
showing monotonous cells exhibiting stippled
chromatin and mitotically active nuclei (arrows) (x400
H&E).
221
Fig 5: Duodenal tumour showing A- positivity for

Pan Cytokeratin; B- positivity for Chromogranin; CNuclear positivity for Ki-67 [x400].
Further, extensive sampling of the ovarian tumour
failed to reveal any teratomatous/ carcinoid
component.
A final diagnosis of Left ovarian mucinous
cystadenocarcinoma, pT1aG1 pN0 pM0, TNM/FIGO
Stage IA with synchronous duodenal Neuroendocrine
tumour, grade II, TNM Stage IIIB was made.
DISCUSSION
CTs are relatively uncommon slow growing
neuroendocrine
tumours,
derived
from
enterochromaffin cells, that are capable of secreting
vasoactive substances and 73-85% of these tumours
occur in the gastrointestinal tract (GIT).7 Duodenal
carcinoids are rare , accounting for < 2% of all GIT
carcinoids, with an annual incidence of 0.07/100,000.5
About 91% have metastasis at time of detection
presumably because they are difficult to diagnose and
majority are asymptomatic and behave in an indolent
form.5 Clinical features are varied and depend on the
anatomic location, tumour size and metastasis and
majority are incidentally detected. 8 They may present
as carcinoid syndrome with cutaneous flushing,
diarrhoea
palpitations, abdominal pain and
bronchospasm. G-cell tumours followed by D-cell
tumours account for majority of duodenal CTs, the
former may occur with multiple endocrine neoplasia
type 1 and the latter may occur with neurofibromatosis
type 1. Unlike their midgut and hindgut counterparts,
proximal duodenal CT are less well characterized and
exhibit variable biological course necessitating
individualised treatment strategy for each patient.9
Devadass et al.,
In the present case the patient had palpitations,

diarrhoea and respiratory distress, all of which were
attributed to the huge ovarian tumour. The duodenal
CT was detected incidentally during the surgical
treatment of the associated ovarian malignancy.
CTs may be associated with other synchronous
primary malignant tumours. Berner M et al reported
that out of 270 GIT CTs analysed 7.8% had
synchronous primary malignancy, two thirds of which
were colorectal adenocarcinomas and 80% of which
were detected during the treatment of the other
associated malignancy. 10 Mullen et al reviewed 24
duodenal CTs and found that 38% had synchronous
or metachronous non-carcinoid malignancies, 77.8%
of which were adenocarcinomas. 9 Associated ovarian
malignancies were not detected in these studies. We
describe the first case, to our knowledge, of a duodenal
CT and a simultaneous ovarian mucinous
cystadenocarcinoma.
The mechanisms involved in the occurrence of MPM
have not been fully explained. Genetic susceptibility,
failure of immunological surveillance and exposure to
carcinogens has been implicated.1, 2, 4 Some authors
have hypothesised that CTs produce growth factors
which may determine neoplastic transformation or
influence tumour growth at other sites.4
It has been reported that prognosis of patients with
synchronous CTs and non-carcinoid tumours is
determined by the stage of the non-carcinoid tumour
rather than the CT. 10 This probably is applicable for
those cases wherein the CT component is nonmetastasising.4, 5 In the present case the ovarian
malignancy was well differentiated and FIGO stage I,
with an excellent prognosis and 5 year survival rate of
95%.6 The CT had regional node metastasis with Stage
III B, and logically will determine the survival of this
patient. The five year survival rate for CTs with only
local spread is 88% in contrast to 25% for those with
metastasis.5
Combined curative resection is the treatment of choice
for synchronous MPM.1, 2 However, in this case a
second malignancy was not suspected pre-operatively.
Pancreaticoduodenectomy is the subsequent treatment
in the management, which will be done after she
recovers from the first surgery.
CONCLUSION
The possibility of MPM should always be considered
in the pre-operative evaluation. The association of
222
CTs with colorectal adenocarcinomas and ovarian

mucinous adenocarcinomas with other primary ovarian
tumours and Lynch syndrome have been described.
As the management may differ in the finding of a
second primary, we should not limit ourselves to these
known associations. The clinicians should be aware of
this rare entity so that pre planned stage specific
treatment may be delivered resulting in better
outcome.
REFERENCES
1. Irimie A, Achimas-Cadariu P, Burz C, Puscas E.
Multiple Primary Malignancies- Epidemiological
Analysis at a Single Tertiary Institution. J
Gastrointestin Liver Dis 2010;19:69-73
2. Anania G, Santini M, Marzetti A, Scagliarini L,
Vedana L, Resta G, et al. Synchronous primary
malignant tumours of the breast, caecum and
sigma. Case report. G Chir 2012;33:409-10
3. Demandante CG, Troyer DA, Miles TP. Multiple
primary malignant neoplasms; case report and a
comprehensive review of the literature. Am J Clin
Oncol 2003;26:79-83
4. Gurzu S, Bara T Jr, Bara T, Jung I. Synchronous
intestinal tumours: aggressive jejunal carcinoid
and sigmoid malignant polyp. Rom J Morphol
Embryol 2012;53:193-96
5. Gao L, Lipka S, Hurtado-Cordovi J, Avezbakiyev
B, Zuretti A, Rizvon K, et al. Synchronous
Duodenal Carcinoid and Adenocarcinoma of the
Colon. World J Oncol 2012;3:239-42
6. Soslow RA. Mucinous Ovarian Carcinoma:
Slippery business. Cancer 2011; 117:451-53
7. Babovic-Vuksanovic D, Constantinou CL, Rubin
J, Rowland CM, Schaid DJ, Karnes PS. Familial
Occurrence of Carcinoid Tumors and Asssociation
with Other Malignant Neoplasms. Cancer
Epidemiol Biomarkers Prev 1999;8:715-19
8. Erbil Y, Barbaros U, Kapran Y, Yanik BT,
Bozbora A, Ozarmaoan S. Synchronous Carcinoid
Tumour of the Small Intestine and Appendix in the
Same Patient. West Indian Med J 2007;56:187-89
9. Mullen JT, Wang H, Yao JC, Lee JH, Perrier ND,
Pisters PWT, et al. Carcinoid tumours of the
duodenum. Surgery 2005;138:971-78
10. Berner M. Digestive carcinoids and synchronous
malignant tumors. Helv Chir Acta. 1993;59:75766
Devadass et al.,
223
DOI: 10.5958/j.2319-5886.3.1.049

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Health Sciences
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Coden: IJMRHS
th
Case report
Copyright @2013
ISSN: 2319-5886
SYNCHRONOUS POORLY DIFFERENTIATED GASTRIC ADENOCARCINOMA WITH GASTROINTESTINAL

STROMAL TUMOR: A CASE REPORT
Magdalene K. F.
Professor in Pathology, Sree Narayana Institute of Medical Sciences, Chalaka, Kerala, India
*Corresponding author email: magdalenekf@gmail.com
ABSRACT
Gastrointestinal stromal tumor (GIST) is categorized as a mesenchymal tumor. In the abdomen more than half occur
in the stomach. Adenocarcinoma is the most common epithelial malignancy of stomach comprising over 90% of all
gastric cancers. The simultaneous occurrence of both these tumors together is rare. This is an interesting case report
of a 54 year old lady with synchronous occurrence of GIST and poorly differentiated adenocarcinoma of intestinal
type. A brief review of literature is done regarding the reported cases and proposed hypothesis.
Keywords: Poorly differentiated carcinoma, GIST, Synchronous
INTRODUCTION
The most common gastric tumors are epithelial tumors. Adenocarcinomas constitute the most common type of
epithelial gastric tumors. Gastrointestinal stromal tumors (GIST) are non epithelial tumor which can occur in the
stomach. In the gastrointestinal tract 1% of all malignancies1, 2 and 5.7% of sarcomas3 are accounted by GIST. GISTs
and adenocarcinomas have two separate histogenesis. It is extremely rare for the co-existence of GIST and
adenocarcinoma. GISTs have been reported in the literature to coexist with tumors of different histogenesis such as
adenocarcinomas, carcinoids, MALT lymphomas and Burkitts lymphomas 4,5,6, as well as with different mesenchymal
tumors.7-13 Here is a case report of a 54 year old lady with poorly differentiated adenocarcinoma and synchronous
gastrointestinal stromal tumor which was incidentally detected.
CASE REPORT
A 54 year old lady was admitted with vomiting,
following food intake, of 3weeks duration. There was
associated abdominal discomfort and belching. She
gave a history of loss of appetite and weight loss
which was of 3 months duration. On general
examination the patient was emaciated and pale. The
systemic examination was unremarkable. Blood
routine was normal except for the low hemoglobin
level (5gm%). Urine routine was normal.
Ultrasonograghy showed diffuse thickening of the
gastric pyloric antral wall.
Magdalene
Oesophagogastroduodenoscopy showed multiple

ulcerations with hypertrophied margins in the lesser
curvature and antrum and the impression was gastric
outlet obstruction. Endoscopic biopsy done showed
microscopic features of a poorly differentiated
carcinoma. A lower radical gastrectomy was done and
the specimen was received in the histopathology lab.
An ulcerating infiltrating neoplasm measuring
30x25mm was detected in the lesser curvature adjacent
to which another nodular firm grey white
mesenchymal neoplasm measuring 25x20mm was also
224
noted [Figure1]. The microscopy of the ulcerating

tumor showed features of a poorly differentiated
intestinal type adenocarcinoma [Figure 2]. The tumor
was infiltrating the full thickness of the gastric wall
and extended to the serosal fat of the lesser curvature.
Four out of nine lymph nodes showed evidence of
metastasis.
Fig 3b: Microscopy of gastrointestinal stromal tumor

showing the sheet- like and fascicular arrangement of
spindle shaped cells (H&E X 40x)
Fig 1: Ulcerating infiltrating gastric carcinoma in the

lesser curvature of stomach (blue arrow) with adjacent
nodular firm grey white gastrointestinal stromal tumor
(red arrow)
Fig 2: Microscopy of poorly differentiated intestinal type

adenocarcinoma in the gastric wall (H&E X 10x)
The adjacent nodular firm white neoplasm showed

microscopic feature of a submucosal spindle cell
mesenchymal neoplasm which was circumscribed. A
fascicular and sheet like arrangement of plump spindle
shaped cells were noted [Figure 3a,b]. Mitotic activity
was less than 5/50 HPF. No areas of necrosis were
found. Based on the mitotic count of less than 5/50
HPF and size of the tumor less than 5 cm, the
histological diagnosis was GIST-low risk type.
Immunohistochemical markers were advised for
confirmation of GIST.
Immunohistochemical markers were done for the
identification of origin of the tumors. The
mesenchymal neoplasm was CD 117 (c-kit protein)
moderately to strongly positive demonstrating a
combined membranous and diffuse cytoplasmic
staining pattern. Additionally, CD 34 protein was
observed to be membranous stain positive, whereas S100, desmin and SMA demonstrated negative or very
weak reactivity. The poorly differentiated intestinal
type adenocarcinoma was cytokeratin positive. A final
report of synchronous poorly differentiated intestinal
type adenocarcinoma and GIST (low risk type) was
arrived. Since intestinal type adenocarcinomas could
be due to Helicobacter pylori they were searched in the
gastric mucosa but were not detected microscopically.
The resected gastric margins and omentum were free
of neoplasm. The postoperative course was uneventful.
Following surgery the patient received adjuvant
chemotherapy, but unfortunately died of progressive
disease 16 months later.
Fig 3a: Microscopy of circumscribed submucosal

spindle cell gastrointestinal stromal tumor (H&E X 10x)
Magdalene
225
DISCUSSION
GIST was named in the earlier literature as
leiomyomas, schwannomas, leiomyosarcomas and
leiomyoblastomas.
Electron
microscopy
and
immunohistochemical stains recognized it as a distinct
entity.14 Mazur and Clark15 introduced the term GIST
in 1983.
The synchronous occurrence of GIST and gastric
carcinomas are rare. A few reports of simultaneous
presence of poorly differentiated adenocarcinoma and
GIST have been reported.7-13 Most of the
adenocarcinomas were detected after endoscopic
biopsies. GIST was diagnosed as an incidental finding.
No high risk types of GIST have been reported in
association with gastric carcinoma .The tumors were
mostly less than 5cm.Recently Karahan N et al.16 have
reported in a neurofibromatosis type-1 patient with
development of simultaneous multiple GIST and
signet ring cell carcinoma. The synchronous
occurrence of these two tumors has excited many and
it raises the question as to why they occur together.
The reason for the simultaneous origin of GIST and
adenocarcinoma may be due to coincidence. Gene
mutations were another reason that was proposed.
Recently Yan Y et al 17 conducted molecular analysis
and clinicopathological profile of KIT/PDGFRA in
both these tumors. No relationship was obvious
according to this study.
H. pylorus is another cause that may be considered. H.
pylori can cause simultaneous development of gastric
carcinoma and lymphoma 7. Such a relationship with
GIST is not proved yet. In the present case study no H.
pylori could be detected.
Another hypothesis is the role of carcinogenic agent. It
may act on neighboring tissues and may lead to the
development of tumors in the same organ with
different histogenesis.18, 19
CONCLUSIONS
The synchronous occurrence of a GIST with gastric
carcinoma is rare, and little is known about this
association. Coexisting GISTs are in most cases small,
asymptomatic tumors and are detected incidentally
during surgery for gastric carcinomas. Hence
specimens should be handled cautiously to detect
associated lesions. Since most of the cases were poorly
differentiated adenocarcinomas further studies are
needed to know whether the associated GIST
Magdalene
influenced the differentiation of the tumor. Molecular

studies are also further needed to explain the
simultaneous development of tumors of different
histogenesis.
Disclosure of conflicts of interest: The author
declares that there is no financial relationship with any
organization in this case study and that there is no
conflict of interest.
REFERENCES
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primary adenocarcinoma and gastrointestinal
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cases. Turk J Gastroenterol 2004;15:187-91.
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Synchronous occurrence of gastrointestinal
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case report. J Pak Med Assoc 2006;56:184-86.
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the Stomach. A case report of Mixed Stromal
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Fano R: Synchronous occurrence of epithelial and
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Vallachira, and Praveen S. Mahadev.Synchronous
Adenocarcinoma and Gastrointestinal Stromal
Tumor in the Stomach.Saudi J Gastroenterol 2010
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targeted therapy. J SurgOncol 2005;90:195-207.
15. Mazur MT, Clark HB. Gastric stromal
tumors.Reappraisal
of
histogenesis.Am
J
SurgPathol 1983;7:507-19.
16. Karahan N, Bapinar , Bozkurt KK, Devrm T,
Kapucuolu
FN.Coexistence
of
multiple
gastrointestinal stromal tumors and signet ring cell
carcinoma of stomach in a patient with
neurofibromatosis
type-1:
case
report.TurkPatolojiDerg 2013;29(1):64-68.
17. Yan Y, Li Z, Liu Y, Zhang L, Li J, Ji
J.Coexistence of gastrointestinal stromal tumors
and gastric adenocarcinomas.TumourBiol 2013
Apr;34(2):919-27.
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Werther JL. Experimental models for gastric
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1984;53:108892.
19. Shitkov KG, Talalaeva AV. Gastric sarcomas
induced in rats by DMBA and cellophane.
VoprOnkol 1979;25:6265.
Magdalene
227

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DOI: 10.5958/j.2319-5886.3.1.

International Journal of Medical Research

A STUDY OF LUMBARISATION OF FIRST SACRAL VERTEBRA AMONG THE SOUTH INDIANS

Assistant Professor, Department of Anatomy, MES medical college, Perinthalmanna, Kerala

*Corresponding author e-mail: amee2amee@yahoo.co.in

the sacrum have been reported like sacralisation of

Int J Med Res Health Sci. 2014;3(1):1-4

Bertolotti observed for the first time that,

male and the other one is female. Incidence of sacrum

MATERIALS AND METHODS

Fig 1. Dorsal surface of sacrum

Fig 2: Pelvic surface of sacrum.

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presenting such a variation which emphasize on its

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6. Wellik DM, Capecchi MR. Hox 10 and Hox 11

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facilities and poverty, the PD is a cheaper option in

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only at around 15% of the ESRD population.5,6 Both

transplantation. Those patients who had access and

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diabetic nephropathy (n=18). The adult polycystic

Reasons for choosing peritoneal dialysis

Table 4: Reasons for choosing peritoneal dialysis

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(ARF: Acute renal failure, CRF: Chronic renal failure)

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Complications during peritoneal dialysis

Most patients with peritonitis had pyrexia (77%),

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The causes of CRF findings suggested that a broader

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11. Neugarten J, Acharya A, Silbiger SR. Effect of

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23. Johnson RJ, Couser WG. Hepatitis B infection

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International Journal of Medical Research

Received: 6 Sep 2013

Revised: 9 Oct 2013

Accepted: 4th Nov 2013

Tutor, Departments of Biochemistry, G.C.S. Medical College, Ahmedabad, Gujarat, India

*Corresponding author email: pautalk@gmail.com

transfer of the gamma-glutamyl moiety of glutathione

Int J Med Res Health Sci. 2014;3(1):12-15

This work was aimed at investigating the diagnostic

and sex. Exclusion criteria: Age < 20 or >60 years,

In this study we measured Serum activity of Gamma

Graph 1: Study Group

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Graph 2: Control Group

on the gastrointestinal tract and damage to the liver

It is concluded from the present study that the

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investigations. Addiction Biology 2002; 7:443

chronic alcoholic patients during

8. Bergmeyer H-U, Horder M, Rej R. IFCC

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International Journal of Medical Research

EFFECT OF GONADAL HORMONES ON HYPOPHAGIC PROPERTY OF OPIOID ANTAGONIST

This energy balance and fuel utilization are

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