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Parimala (

International Journal of Medical Research

&

Health Sciences

www.ijmrhs.com Volume 2 Issue 2 April - June Coden: IJMRHS Copyright @2013 ISSN: 2319-5886 Received: 8

th Jan 2013 Revised: 2

nd Feb 2013 Accepted: 10

th Feb 2013

Research article

ASSESSMENT OF PHARMACOLOGY TEACHING - A CRITICAL APPRAISAL BY

MEDICAL SCHOOL LEARNERS

*Parimala K 1, Subash KR 2, Jagan N1, Vijay Kumar S1, Viswanathan S1, Chandrasekhar M3

1Department of Pharmacology, 3Medical Education Unit, Meenakshi Medical College and Research

Institute, Enathur, Kanchipuram, Tamil Nadu, India2Department of Pharmacology, Sri Padmavathi Medical College, Hospital and Research Centre, Sai ram

Nagar, Tirupati Airport Road, Renigunta, Tirupati-517520, Andhra Pradesh, India

*Corresponding author email:[email protected]

ABSTRACT

Background: Students feedback is an indicator of the success of any teaching methodology followed in

a department. Aim: To identify strengths and weaknesses in the current teaching-learning and evaluation

methodology in pharmacology using feedback from second MBBS students in Meenakshi Medical

College and Research Institute. Materials and Methods: Questionnaire was designed and finalised

after a departmental discussion in concurrence with the Medical Education Unit. The study subjects

were 115 (2011batch) second-year medical students. They were requested to fill the questionnaire. A 10-

item multiple choice questionnaires were used to explore the student’s opinion on teaching. The

questionnaires were analyzed. Results: 115 II M.B.B.S students participated and descriptive statistics

was used for analysis of data. The analysis revealed 82.82%, 72.17% and 93.64% student’s interest

towards writing classification of drugs, weekly test and viva-voice respectively. Conclusion: The

present study has helped us to elicit the student preference regarding pharmacology teaching and its

outcome would be helpful in modifying undergraduate pharmacology teaching patterns.

Keywords: Medical education, Pharmacology Assessment, Medical school learners.

INTRODUCTION

The primary aim of teaching pharmacology to

medical students is to train them on rational and

scientific basis of therapeutics. Pharmacology

teaching is facing a major challenge in the

medical science due to constant reformation.

Generally, there is an opinion that teaching

pharmacology in medical schools has failed tokeep in pace with the rapid changes in medical

practice. Attempts have been made all over India

to make the teaching of pharmacology more

interesting and relevant1. To make pharmacology

teaching more innovative and interesting learning

experience, efforts have been made by

formulating new educational strategies to meet

the educational objectives. Educational

objectives can be evaluated by assessment procedures and timely feedback to achieve the

learning goal.

10.558/.2315886.2.2.001


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In Meenakshi Medical College and Research

Institute, Pharmacology teaching comprises

mostly of a series of didactic lectures using

power point presentations covering general,

systemic pharmacology and practical

pharmacology which includes animalexperiments and clinical pharmacology sessions

spread over the academic year. To evaluate the

student’s progress we conduct monthly internal

assessment tests consisting of multiple choice

questions, essay questions, short notes and ultra

short notes for 3 hr time duration including

model practical exams conducted twice in a year.

Regular viva voce exams follow the monthly

internal assessment test to develop theircommunication and interaction skills.

Apart from this regular schedule of assessment,

we also introduced a method of assignment on

classification of drugs after each system. To

reinforce the learning process, we implemented

weekly test on the first hour of every week based

on the lectures delivered over the previous week.

The test was conducted for one hour which

covered various portions of the chapter in detail

testing the levels of knowledge.

After completing the above schedule

meticulously, at the end of the year to understand

the beneficiaries’ opinion we planned to collect

the student’s feedback. Currently the student’s

feedback represents the primary means used by

different programs to assess their methodology2.

Feedback helps in correcting mistakes,

reinforcing good performances and incorporating

students view in teaching methodology. It isaccepted that reviewing the teaching and

evaluation methods by feedback from students

and modifying of methodologies accordingly is

very important for the undergraduate medical

teaching3&4. Thus the present study is an effort to

obtain and analyze critical appraisal on,

• The student attitude toward teaching and

learning pharmacology in Meenakshi

Medical College and Research Institute,Enathur, Kanchipuram.

• Assessment of pharmacology teaching using

student feedback.

• Methods to improve teaching Pharmacology.

MATERIALS AND METHODS

A questionnaire was designed to obtain feedback

and finalized after a departmental discussion

with the concurrence of Medical Education Unit.

The study subjects were 115-second year MBBS

students of 2011 batch studying in the Meenakshi

Medical College and Research Institute, Enathur,

Kanchipuram.

All the students enrolled in the study were

requested to fill up the questionnaire. The study

was conducted at the end of their academic year

in the Department of Pharmacology. A ten-item

multiple choice questionnaires and an open

ended question for suggestion were provided to

explore the student’s opinion on teaching and

learning methods imparted. The questionnaire

was analyzed by two observers. The

questionnaire was designed in such a way to

assess the knowledge, their attitude and skillsdeveloped during their one and half year course

in pharmacology. Both the theoretical and

practical pharmacology practiced by different

methods during their study period were evaluated

from the feedback form.

Statistics: Descriptive statistics was used for

analysis of data. Frequency was shown as a

percentage.

RESULTS

One hundred and fifteen students of II MBBS

participated and responded in the questionnaire

study. Based on the pattern of studying

pharmacology, 48.69% studied pharmacology

once or twice a week on a regular basis and

34.78% opted studying only for monthly tests

and viva voce exams which reflects on their

regular preparation for monthly internal

assessment test (Fig.-1). 54.75% of students preferred lecture notes and textbooks as the

source of studying pharmacology.


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Fig: 1. Ph

The majo

writing an53.91% ha

improved

Fig: 2. Stu

Among th

students f

test for th

academic

%

%

rmacolog

ity (87.82

maintainive opined

in better

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) of stu

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e. In th

ing Habit

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ds, 54.78

nal assess

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s

oved

rugs.had

the

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eported ieproduce i

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&

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72.17% o

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(

ugs.43.47

ess tond also to

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ave

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Fig: 3. We

The majo

regular tes

when c

pharmacol

have me

following

improved t

%

Fig: 4. Te

ekly test i

ity (66.95

ts in clini

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) of stu

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(93.64%)

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ills.

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Fig.4).

%

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Parimala (

DISCUSSION

Feedback is defined as a response within a

system that influences continuous activity or

productivity of that system. In the present study

on educational context, it would mean a response

from the learner about the teaching learning

process. Feedback is essential to find out the

effectiveness of the process, the need to change

it, as well as, to evolve strategy for its

improvement.

From the feedback evaluation obtained, it is

observed that students like to study

pharmacology by regular test / viva and

interactive classes so by these way students

understand the subject properly5. This very much

correlates in the present study feedback results.

It was found that students preferred writing and

maintaining classification of drugs throughout

their academic year, which were corrected

periodically by the faculty, who played the role

of mentor for the given group of students to

cultivate and sustain the habit. Writing

classification of drugs by medical school learners

has helped them to understand the differentclasses of drugs and also to systematically

memorize and reproduce in the written test as

well as the knowledge application in clinical

rotations.

Students opined that monthly internal assessment

test was mostly useful than the weekly written

test for their academic performance in theory

exams, the reason for the following may be a

monthly internal assessment pattern is similar to

that of university examination. The weekly

written test has definitely kept the students in

pace with the portions being completed every

week. By answering the weekly test their

preparation, facing and performing a monthly

internal assessment had become extremely

comfortable and confident . The weekly test had

various parts, students considered true or false

part of the weekly test has created interested in

them, the fact to get such a feedback may be thechances of getting the wrong answer is only

50%. Also they have mentioned that, Match the

following with extended responses have

stimulated their thought process to find the

correct response. The feedback also emphasized

the student’s interest towards more interactive

sessions on Clinical pharmacology exercises and

felt it should be given regular emphasis than the

animal experiments. According to Gibbs G et al,

19876active review during the lecture, involving

students in structured discussions, using

questionnaires and asking them to summarize are

the three most important things to be followed

and practiced for an effective teaching-learning

process.

To conclude though the teaching learning

method implemented in the present study

required a lot of strenuous hard work from the

faculty particularly preparing questions,

organizing test and more importantly correcting

all the papers in a week period, it has created an

interest in learning pharmacology among

students. The feedback from learners has clearly

exhibited their likeliness for the variety or

different methodological approach instead ofregular didactic lectures offered by the

department of Pharmacology.

ACKNOWLEDGEMENTS

We sincerely thank our II M.B.B.S Students of

Meenakshi Medical College & Research Institute

for the participation.

REFERENCES

1. Gitanjali B and Shashindran CH. Curriculum

on clinical Pharmacology for medical

undergraduates of India. Indian J Pharmacol.

2006;38: 108-14.

2. Richardson BK. Feedback Acad. Emerg

Med. 2004; 11th Edn, 1-5.

3. Ruth N. Communicating student evaluation

of teaching results: rating interpretation

guides (RIGs) Assess Evaluation Higher

Edu. 2000;25:121–34.

4. Victoroff KZ, Hogan S. Students

perceptions of effective learning experiences


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in dental school: A qualitative study using a

critical incident technique. J. Dental

education.2006; 70: 124-32.

5.

Nilesh Chavda, Preethi Yadav, Mayur

Chaudhari, Kantharia ND. Second year

students feedback on teaching methodologyand evaluation methods in Pharmacology.

National Journal of Physiology, Pharmacy

and Pharmacology. 2011;1: 23-31

6. Gibbs G, Habeshaw S & Habeshaw T.

Improving student learning during lectures.

Medical teacher. 1987; 9:11-20.


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&

Health Sciences



th Feb 2013 Accepted: 18

th Feb 2013

Research article

ACUTE TOXICOLOGICAL EVALUATION OF PET – ETHER EXTRACT OF PORTULACA

OLERACEA (LINN.) ON RODENTS.

*Siva Reddy1, Somasundaram G2

1Department of Forensic medicine, Sri Venkateshwaraa Medical College Hospital & Research Centre,

Ariyur, Pondicherry. India.2Department of Pharmacology, MGMCR&I, Pilayarkuppam, Puducherry, India.

*Corresponding author email: [email protected]

ABSTRACT

Introduction: Portulaca oleracea is a common plant used in South Indian culinary; recently there is

increase in research publication on various biological activities of the medicinal herb. The safety of the

medicinal herb well accounted by its widespread accepted use of natives yet scientific evaluation on the

safety of the herb is not reported. Aim To scientifically evaluate the toxicity profile of the pet - ether

extract of Portulaca oleracea by standardized methods. Method A 24hour acute toxicity study followed by 14 day sub-acute toxicity study with serum haematological, biochemical and histopathological

analysis’s is evaluated in rodents. Result No observable serious side effects are recorded in acute and

sub acute toxicity study for 0.5gm/kg and 1gm/kg pet-ether extract of Portulaca oleracea. There are

statistically significant rising (p


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belongs to family Portulacaceae . The plant is

reported to have protective biological effect

against bacterial and fungal infection1. Towards

treatment of infertility and preclinical scientific

research on various inflammatory conditions2.

Despite the uses traditionally, there is much lessscientific evidence in established literature on the

safety of this plant. Information concerning

toxicity of Portulaca oleracea from traditional

use has also been scarce. The literature search

also revealed no scientific evidence available

regarding safety of this plant. The present study

is an effort to provide preliminary information on

the acute and subacute toxicological profile of

the Pet - Ether extract of Portulaca oleracea inrodents the reports were supported with

biochemical, isolated organ and histopathological

observations .


Plant Material: The leaves of Portulaca

oleracea are used in traditional medicine

similarly in the present study the leaves of the

plant is collected from botanical garden during

the month of May 2009; the collected leaves are

authenticated by Department of Botany,

Annamalai University, Chidambaram.

Extract Preparation: The leaves of Portulaca

oleracea were sold dried for seven days and

pulverized one kg of coarse powder was filtered

through a fine mesh and collected powder is

soaked in 4 litres of petroleum-ether for 3 days at

room temperature. The collected extract is

evaporated to dryness using a rotary vacuumflash evaporator and the yield was stored in

airtight container for further research.

Animals : Sprague-Dawley rats weighing 200-

250gms were used for toxicity studies. The

animals are kept in standard conditions of a 12

hour day and 12 hour night cycles at 22º C room

temperature, in polypropylene cages. The

animals were fed on standard pellet’s (Hindustan

Lever Pvt Ltd., Bangalore) and provided tapwater ad libitum. To acclimatize to laboratory

conditions the animals were housed in

polypropylene cages prior to the experiments for

one week. The experiment was conducted in

Rajah Muthiah Medical college, Department of

Forensic medicine and Toxicology and the

protocol was approved by the Institutional

Animal Ethical Committee (IAEC). All procedures and techniques used in these studies

were in accordance with accepted principles for

laboratory animal use and care of Annamalai

University.

Acute toxicity : Sprague-Dawley rats of either

sex were randomly divided into four groups, six

animals in each group (n=6). The rats were kept

in the experimental environment for an

acclimatization period of 1 week before startingthe experiment. The animals were fasted

overnight with access to water ad libitum. The

study design included three treatment groups and

one control group, the treatment group received

orally pet-ether extract of Portulaca oleracea in

doses of 0.50,1.00, and 2.00 gms/ kg of body

weight. The control group received 10 ml/ kg

p.o. of Normal saline. The rats were observed up

to 24 hours for general changes in behaviour and

physiological function as well as mortality. The

assessment of behaviour and physiological

function was carried out by procedures

originally4 described by Irwin (1968)3.

Sub-acute toxicity : Sprague-Dawley rats, 6 per

group, were treated orally with Portulaca

oleracea daily for 14 consecutive days. The

study design included four groups. Group -1 the

control, received 10 ml kg p.o. of Normal saline

daily. Group 2, 3 and 4 were treated with dailydoses of the extract i.e. 0.5, 1 and 2 gm/ kg

respectively. The extract of three different

concentrations was prepared such that not more

than 2 ml was given orally. The animals were

monitored closely for signs of toxicity.

Appearance, toxicity signs, cage side observation

and behaviour pattern were assessed daily and

any abnormalities in food and water intake were

registered.Preparation of serum and isolation of organs:

After fourteen days of observation the rats were

sacrificed on the fifteenth day by cervical


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dislocation, the jugular vein was cut and blood

samples were collected for hematological assay

in vacuum tubes containing 2.5 µg of ethylene

diamine tetra acetic acid (EDTA). Hematological

parameters including haemoglobin (HGB), red

blood cells (RBC), white blood cells (WBC),mean corpuscular volume (MCV), mean

corpuscular haemoglobin (MCH), and mean

corpuscular haemoglobin concentration (MCHC)

were determined by an automatic analyzer.

Another sample of blood was collected into tubes

without anticoagulant to obtain serum was

collected and stored at -20°C until assayed for

biochemical parameters the next day.

Biochemical analyses were performed on serumcollected for the determination of the following

parameters: fasting blood glucose, aspartate

transaminase (AST), alanine transaminase

(ALT), alkaline phosphatase (ALP), urea, Blood

urea nitrogen (BUN) and Cholesterol. All

analyses were carried out using the Automated

Clinical Chemistry Analyzer. After collecting

blood, the rats were quickly dissected to remove

and isolate the organs which were blotted with

clean tissue paper and then weighed on a

balance.

Effect of extract on body and organ weights in

rats : Body weights of the rats in each group

were recorded on day 1 and 15. The relative

organ weight (ROW) of each organ was

calculated as follows:

ROW = Absolute Organ Weight (g) / Rat body

weight on sacrifice day X 100.

Histopathological examination :

Histopathological examinations were carried out

on the tissue obtained from liver, kidney, spleen

and stomach of each group. Tissues were fixed in10 % neutral buffered formalin (pH 7.2) and

dehydrated through a series of ethanol solutions,

embedded in paraffin and routinely processed for

histological analysis. Sections of 2 µm thickness

were cut and stained with haematoxylin Eosin for

examination.

Analysis of data

The recorded data were statistically analyzed for

the presence of significant differences amongmeans of groups using one-way ANOVA

followed by Newman-Keuls multiple comparison

test.

Data were presented as mean ± SEM (n=6).

Graph Pad Prism (GraphPad Software, San

Diego, CA, USA) statistical software was used.

RESULTS AND DISCUSSION

Acute toxicity : All animals in each group are

observed continuously for first four hours

followed by 8th hour and 24th hour. In control and

Portulaca oleracea 0.5 gm there were no signs

of toxicity, whereas the Portulaca oleracea 1gm

and 2gm exhibited Asthenia, defecation,

salivation, urination more than that of control

group (Table-1)

Table.1: Acute Toxicity observation of Portulaca oleracea Extract .

S.No Group Mortality Toxicity Signs D/T Latency (hrs)

1 Control N.S 10ml/kg 0/6 - None

2 Portulaca oleracea 0.5gm/kg 0/6 - None

3 Portulaca oleracea 1gm/kg 0/6 - Asthenia, defecation, salivation,

urination

4 Portulaca oleracea 2gm/kg 0/6 - Asthenia, defecation, salivation,

urination

N.S-Normal Saline, D/T – Death/Treatment


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Sub-acute toxicity

Similar observation as seen in acute toxicity

studies was present for initial two days, later

Asthenia, increased defecation, salivation,

urination were not observed. The cage side

observations for 14 days on general behaviour,respiratory pattern, cardiovascular signs, reflexes

are normal. The Portulaca oleracea 2gm/kg

group exhibited decreased motor activity and

there were no change in skin and fur. All animals

survived for 14 days. The decreased motor

activity is probably due to the extract effect on

skeletal muscle, a similar observation was made

by Parry O et al, and reported to muscle relaxant

activity4. The analysis of hematological

parameter revealed in all treatment groups the

haemoglobin (p


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Though the all animals in each group were fed

with the common diet pattern there a significant

increase in total cholesterol level, the total

cholesterol level signifies low density

lipoproteins, very low density lipoproteins, high

density lipoproteins and triglycerides. The probable rise in cholesterol level without a rise

in body weight and fat free food could be due to

omega 3 free fatty acid. Already there are

investigating reports on Portulaca oleracea as a

rich source of omega 3 fatty acids 6. The body

weight was measured on day 7 and day 14 of sub

acute toxicity study did showed increase in body

weight in all groups, but when compared to

control group the treatment group did not have

any statistical difference. The animals in each

group after euthanasia were carefully dissected

and observed for gross macroscopic tissue/organ pathology. Necropsy observation revealed no

gross anatomical abnormalities in all the groups.

The organs liver, spleen, stomach and kidney are

dissected and checked for relative organ weights

(Fig; 1, 2, 3 & 4)

Fig.1: Relative organ weight-Liver

Fig2: Relative organ weight-Spleen

There was no statistical relative weight difference for spleen, liver and stomach when compared to that

of control (fig; 1, 2 & 3.).

Control P.ole 0.5gm/kg P.ole 2 gm/kg P.ole 2 gm/kg

R e l a t i v e o r g a n w e i g h t

( % )


R e l a t i v e o r g a n w e i g h t

( % )


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Fig.3: Relative organ weight-Stomach

Fig.4: Relative organ weight-Kidney

The weight of the kidney of Portulaca oleracea 1gm/kg and 2gm/kg treated group had increased relative

weight of organ by 0.2% but not statistically significant (fig 4).

Fig.5. A – Control group with arrow indicating normal glomerular structure and Renal tubules,B – P.oleracea 2gm/kg treated group arrow pinpointing oxalate renal stone and tubular dilation.

Control P.ole 0.5gm/kg P.ole 2 gm/kg P.ole 2 gm/kg R e l a t i v e o r g a n

w e i g h t ( % )


Portulaca oleracea Pet-Ether Extract


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Hence all the dissected organs with particular

interest of isolated kidney from Portulaca

oleracea 1gm/kg and 2gm/kg were taken for

histopathological studies. The histopathological

studies revealed the presence of epithelial

inflammation and oxalate stones andhemorrhagic spots (fig; A, B). Earlier studies on

nutrition content of Portulaca oleracea revealed

half a cup of leaves contain 910 mg of oxalate

which explains the increase in relative organ

weight and histopathalogical appearance of

oxalate stones7. The phytochemical screening of

pet-ether extract of Portulaca oleracea can

reveal the major active constituents responsible

for biological activity of the extract

8

.

CONCLUSION

The pet-ether extract of Portulaca oleracea

0.5gm/kg, 1gm/kg and 2gm/kg evaluated for

acute toxicity and sub-acute toxicity has no

observable side effects, except for the renal

calculi formation at 1gm/kg and 2gm/kg for 14

days. The study has also provided other

important finding such as the ability of the

Portulaca oleracea pet-ether extract in

increasing the hemoglobin and anticipated High

density lipoprotein level. The observed finding

can be extrapolated for further research of potent

hematinic compound.

ACKNOWLEDGEMENTS

The authors are grateful for the technical

assistance offered by the staff Department of

Pharmacology, Botany and Department ofForensic medicine and toxicology (Rajah

Muthiah Medical College) Annamalai

University.

REFERENCES

1. Oh KB, Chang IM, Hwang KI, Mar W.

Detection of anti-fungal activity in Portulaca

oleracea by a single cell bioassay system. J

Phytother Res; 2002, 14:329-32.2.

Jagan Rao N., Jayasr ee T., Mallikarj una

Rao B., Sandeep Kumar K., Vijay Kumar S..

Evaluation of the anti-nociceptive and anti-

inflammatory activities of the pet: ether

extract of portulaca oleracea (linn.). Journal

of Clinical and Diagnostic Research;

2012,6:226-230.

3.

Irwin S. Comprehensive observationalassessment: Ia. A systematic, quantitative

procedure for assessing the behavioral and

physiologic state of t h e m o u s e . P s y c

h o p h a r m a c o l o g i a . 1968;13(3) :

222-57

4. Parry O, Marks JA, Okwuasab FK. The

skeletal muscle relaxant action of Portulaca

oleracea: Role of potassium ions. J.

Ethnopharmacol. 1993;49:187-94.5. Ezekwe MO, Omara-Alwala TR,

Membrahtu T, (1999). Nutritive

characterization of the purslane accessions

as was influenced by the planting date. Plant

Foods Hum Nutr ; 54:183-91.

6. Simopoulos AP, Norman HA, Gillaspy JE,

and J. A. Duke. Common purslane: a source

of omega-3 fatty acids and antioxidants.

Journal of the American College of

Nutrition. 1992; 11(4) 374-82.

7. Moreau A.G, Savage G.P. Oxalate content

of purslane leaves and the effect of

combining them with yoghurt or coconut

products. Journal of Food Composition and

Analysis. 2009;22(4):303-06

8. Subash KR, Muthulakshmi Bhaarathi G,

Jagan Rao N, Binoy Vargheese Cheriyan.

Phytochemical screening and acute toxicity

study of ethanolic extract of Alpinia galangain rodents. 2013;2(1):93-100.


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th Feb 2013

Research article

ANTI DIABETIC EFFECT OF MOMORDICA CHARANTIA (BITTER MELONE) ON

ALLOXAN INDUCED DIABETIC RABBITS.

*Yakaiah Vangoori1,Mishra SS2,Ambudas B

3, Ramesh P4, Meghavani G4, Deepika K 4, Prathibha A4

1Assistant Professor and 4PG of Pharmacology, Santhiram Medical College, Nandyal, AP, India

2Professor of Pharmacology, IMS & SUM Hospital, Bhubaneswar, Odisha, India3Lecturer in Pharmacology, BLDEU’s Sri BM Patil Medical College Hospital & Research Centre,

Bijapur, Karnataka, India

* Corresponding author email: [email protected]

ABSTRACT

Objective: to investigate the anti diabetic effect of the bitter melon on Alloxan induced diabetes in

experimental animals (rabbits). Materials and Methods: the alcohol extract of whole fruit was tested

for its efficacy in Alloxan (150mg/kg) induced diabetic rabbit. The diabetic rabbits were divided into

5groups. Group I (control) received 2% gumacasia, groupie (positive control) received standard drug

Metformin (62.5mg+2%GA), group III, IV, V (T1 T2 T3) were treated orally with a daily dose of 0.5(gm)

1gm, 1.5gm respectively for 35 days, for all diabetic rabbits after giving TEST,NC,PC preparations, the

blood samples were collected and determined the blood glucose level 0,1,3,24hrs intervals. 0hr reading

is before drug giving and remaining 3 readings after drugs giving. 24th her reading is considered as 0hr

reading for the next day. Results: administration of alcohol of an extract of bitter melon produced a dose

dependent decrease in blood glucose levels in Alloxan induced rabbits. There was a significant fall in

blood sugar level in High dose (1.5GM/kg) in comparison to low dose (0.5gm/kg) and median dose

(1gm/kg) shown by LSD test. This is comparable to the effect of Metformin. Conclusion: the results of

this study show that chronic oral administration of an extract of Momordica charantia fruit at an

appropriate dosage may be good alternative anti diabetic agent.

Keywords : Hyperglycemia, Metformin, Alloxan, Momordica charantia

INTRODUCTION

Diabetes mellitus is the world largest endocrine

disease with deranged carbohydrate, fat and

protein metabolism. The diabetes mellitus is

mainly classified into two major groups, Type-1(insulin dependent diabetes mellitus), Type-2

(non-insulin dependent diabetes mellitus. As per

WHO report, approximately 150 million people

have Diabetes mellitus worldwide, and this

number may well double by the year 2025.

Statistical projection suggests that the number ofdiabetics will rise from 15 million in the year

1995 to 57 million in 2025 in India. This number


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is making India the country with the highest

number of diabetics in the world.1 Long-term

complications of diabetes are micro vascular

(neuropathy, retinopathy, nephropathy) and

macro vascular (heart complications)2 diseases.

The anti diabetic drugs are mainly used for toreplace the insulin deficiency or to enhance the

action of insulin and/or decrease the insulin

resistance. Although many drugs and

interventions are available to manage diabetes,

these are expensive for the large diabetic

population of developing countries like India,

apart from their inherent adverse effects.3 So it is

necessary to look for new cheep alternatives to

manage this major health problem. Differentindigenous drugs have been used in this

subcontinent for several centuries for the

treatment of Diabetes mellitus with conflicting

reports of their efficacy because of lack of

scientific investigation in a laboratory setting.

One such plant, Momordica charantia (Karela)

whose fruit has long been used traditionally in

the treatment of Diabetes mellitus in South Asian

countries and has rich Ayurvedic reference to

select for the study. In this study, the anti

diabetic potential of this unripe fruit extract of

Momordica charantia (Karela) was screened on

laboratory animal model.4,5


Institutional Animal Ethics Committee (IAEC)

permission was obtained before starting the

study. The study was conducted strictly in

accordance with the protocol.

Plant material: Fresh green fruits of bitter

gourd popularly known as karela was obtained in

sufficient quantity from a local market in

Nandyal, A.P. in November 2012. They were

carefully washed to remove dust particles and

other foreign materials and dried in shaded areas.

The completely dried fruits were powdered with

electric grinder and stored in well closed bottles.

Alcohol extract preparation: The extract is aconcentrated preparation of vegetables or animal

source Extract: The extract is the process or act

of pulling or drawing out the active principle of a

particular material like plants or animal organs.

In the present study the percolation method was

selected to extract the active principle of bitter

gourd plant material.6 Cold percolation

method: This is a traditional method ofextraction used by the herbalists throughout the

world. This is the original extraction method, and

it's continuing to be the backbone of the present

extracting technology. The distillation devices

are “modified Soxhlet extractions” made by

Eden Labs 7,8 Extraction procedure: The dried

fine powder of the bitter gourd was weighed in

balance 25g and taken into the sac like cloth

material and placed in the Soxhlet basket. 250mlof ethyl alcohol was taken as solvent into the

Soxhlet flask. The extract laden solvent falling

from the Soxhlet basket is dark in color and it

becomes clearer, that indicates the extraction

process is finished9. At the end of the extraction

process the solvent is then evaporated and the

remaining mass is measured. The percentage

yields are calculated as mg per gm dried powder

in 250ml of alcohol, 25gms powder was

suspended. 5gms (20%) of extract was obtained.

The extract was suspended in 5ml of 2% Gum

acacia and used for the oral administration in

diabetic rabbits.

Animals used: 25 Rabbits of either sex, adult,

healthy albino rabbits of local strain weighing

between 1 to 4 kg were used in this experiment.

All the animals were kept in an air-conditioned

animal house in the Pharmacology Department at

the Santhiram Medical College, Nandyal,Kurnool Dist. AP. The animals, rabbits were

offered a natural food like grass and leaves and

allowed a tap water to drink.10

Preparation of diabetic rabbits: the 25 rabbits

weighing between 1 to 4 kg were made diabetic

by injecting intravenously 150mg/kg body

weight of Alloxan monohydrate11,12 Before

giving Alloxan, the normal blood glucose levels

of all rabbits were estimated. After 2hours ofAlloxan injection the Dextrose (5gm) mixed with

water fed to the all-diabetic rabbits orally to

prevent a hypoglycemic condition of rabbits with


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Alloxan.7 After 72hours of Alloxan injection, the

blood glucose levels of all surviving rabbits were

determined by the glucose oxidase method. The

rabbits with blood glucose levels of 220 to

500mg/dl were considered as diabetic and were

employed to further study. 13

Table.1: Grouping of animals

All Alloxan diabetic rabbits were randomly divided into five groups (n=5).

For all the diabetic rabbits after giving test,

negative control and positive control

preparations, the blood samples were collected

and determined the blood glucose 0, 1 & 3hrs

intervals. ‘0’ hour reading is before drug

giving.‘1 & 3’ hours reading is after drug giving.

After administration of drugs to the diabetic

rabbits the blood was collected 1,3 and 24-hour

interval daily up to 35 days and blood glucose

level was determined by the glucose oxidase

method by using Glucometer for 15 days andthen weakly for 3 weeks. The

glucose oxidase method is more accurate, rapid

and time saving method. It requires only a small

amount of blood. So this method is popularly

used in India people suffering from diabetes for

self-monitoring of blood glucose levels.14

RESULTS

In the present study, alcohol extract of the unripe

fruit of the Momordica charantia (Bitter gourd)

was assessed for its anti diabetic activity in

Alloxan-induced diabetic rabbits. The results

obtained were recorded (Table 2).

Table.2: Average Blood Glucose levels (mg/dl) of groups I to V before and after treatment up to 35th

day.

After 35 days of treatment, there is a significant

decrease in blood glucose levels was seen with

the standard drug Metformin and Ethanolic

extract of M-Charantia but there is no significant

reduction in the control group treated with gum

acacia.

Groups Animals Drug Remarks

I Control (2% gum acasia) 5ml Placebo

II Positive control (Metformin 62.5mg+2% ga) 5ml Positive

III Test (low dose 0.5gm) Alcohol extract+2%ga 5ml ExL

IV Medium dose (1gm) Alcohol extract+2%ga 5ml ExM

V High dose (1.5gm) Alcohol extract+2%ga 5ml ExH

S.No. Group – I Group – II Group – III Group – IV Group - V

Before

Alloxan 78.2 75 86 88 89

After Alloxan

(72 hrs.) 311 293 310 300 305

AfterTreatment

0 Hr 1

Hr

3 Hr 0

Hr

1

Hr

3

Hr

0

Hr

1

Hr

3

Hr

0

Hr

1

Hr

3

Hr

0 Hr 1 Hr 3 Hr

Day 1 311 308 307 293 283 279 301 307 308 300 292 292 314 319 312

1st week 312 287 278 254 238 244 277 274 283 260 275 279 251 244 247

2n week 307 298 298 184 173 171 228 224 225 198 204 203 145 158 157

3r Week 289 286 299 158 149 153 227 232 228 169 175 145 147 141 146

4th Week 293 276 295 150 144 153 202 194 191 166 161 165 145 143 148

5th

Week 272 278 274 109 112 130 184 194 199 149 151 146 120 127 131


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Table 3: Mean blood sugar level of different groups:

Group I Group II Group III Group IV Group V

0 Hour 27216.1 109.2±3.3**

184±13.3*

149.6±5.7**

120±7.8***

1st Hour 278.4±8.3 112.2±2.6***

194±13.4** 151.8±14.2*** 127.6±5.2***

3rd Hour 274.8±11 130.2±16.1***

199.6±15*

146±4.6*** 131±10.2***

*P


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difference with that of Metformin in the doses

used in this study. This result was checked by

two post-ANOVA multiple comparison tests like

LSD test of Fisher accommodates a lot of Type I

error) and FSD test of Scheffe (accommodates a

lot of Type II error). Both the tests gave anidentical result. It gave a strong hint that the

Extracts of M. charantia were as efficient as

Metformin in lowering the blood sugar in

diabetic rabbits and that was achieved in a broad

range of doses ranging from 0.5 gm / Kg to 1.5

gm / Kg, so it might be a much safer alternative

to the established drugs.

Comparison between different doses of the

Extract : There was significant fall in bloodsugar level in ExH dose in comparison to ExL

and ExH dose in comparison with ExM as shown

by LSD test. But such difference was not found

in with Scheffe’s test.

The present study, the hypoglycemic effect of M.

Charantia fruit extract was compared with

metformin. Similar studies by Akhtar MS et al,

in 1981 and Biyani MK et al (2003) the acute

hypoglycemic effect was compared with

sulphonylureas and concluded positive effect.

So the present study showed the hypoglycaemic

effect of the alcoholic extract of the unripe fruit

of M. charantia in the dose ranging from 0.5 gm

/ Kg to 1.5 gm / Kg body weight of diabetic

rabbits given orally. The hypoglycemic effect

was comparable to that of the standard anti-

diabetic drug Metformin in the dose of 62.5 mg /

Kg body weight of rabbits. The broad dose range

of hypoglycemic effect of M. charantia may bean interesting finding which may prove it safer in

comparison to the established hypoglycemic

drugs.

CONCLUSION

M. charantia or Karela was taken traditionally

for control of diabetics in India and in other

countries for long time. Three doses of alcoholic

extract of the powder of unripe fruit of M.

charantia were taken to study the hypoglycemiceffect of in 5 groups of alloxan-induced diabetic

in Rabbits. It was a placebo-controlled open

study where blood sugar levels were recorded

daily for 5 weeks. The study showed

hypoglycemic effect of the extract in the oral

dose range of 0.5 to 1.5 gm / kg body weight of

rabbits. The hypoglycemic effect was

comparable to that of established anti-diabeticdrug Metformin in the dose of 62.5 mg / Kg. The

broad dose range of the extract producing a

hypoglycaemic effect in diabetic rabbit was an

interesting observation, we believe that extract of

M-Charantia has the potential to be used as an

adjuvant in the treatment of Diabetes but which

requires further study.

ACKNOWLEDGMENTS: we are grateful to

Santhiram Medical College management anddepartment staff for their cooperation throughout

this study.

REFERENCES

1 Ying ZD, Xiwen Q, Fengjie C, Qin G,

Xinghua Z, Yun Wang. Effect of Superfine

Grinding on Antidiabetic Activity of Bitter

Melon Powder. Int. J. Mol. Sci. 2012;13,

14203-182 Yi Zhang and Zhiyu Xiong Satosker RS.

Pharmacology & Pharmacotherapeutics. 19th

Edition, 2005, Pub. Popular Prakashan Pg,

886-93

3 Walters and Deeker,Indian herbal drug

development-problems, prospects. Pharma

times. 1988;34:13-14

4 Khanna P. Jain SC, Panagariya A and Dixit

VP. Hypoglycemic activity of Polypeptide P

from Plant source. J.Nat. Prod.1981;44(6) :

648-55

5 Sharma VN. Sogani RK. Some observations

on Hypoglycemic activity of Momordica

charantia. IJMR 48:471-77, 1960.

6 Lodikar MM and Rajaramarao MR. Note on

Hypoglycemic principle isolated from

Momordica charantia Linn. Indian Journal of

Pharmacology.1966:28(5) : 129-133

7 Bell BT-experimental production of diabetesin animals with alloxan. Diabetes

times.1986;74:11-18


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8 Okey and Ojiako. http:www.endenlabs.org/

extraction methods.html.

9 Aisle Semiz. Various extraction procedures.

African journal of Biotechnology.2007: 6(3).

273-77

10 Vogal. Drug discovery & EvaluationPharmacological Assays. 2nd Edition 2002.

Pub.. Springer. Medical Publishers, Page

948-50.

11 Akthar AK. Effect of Momordica Charantia

on blood sugar level of Normal and Alloxan

rabbits. Planta Medica. 1981;42;205-212.

12 Butt TA. The hypoglycemic response to

glucagon in Normal, Alloxan Diabetic

rabbits. University of Karachi, JPP-Pakistan.1962.15:1-6

13 Vijaya. Drug Interaction of Naphroxen with

Tolbutamide. Journal of Pharma.sci.

1987;42:51-52

14 Desai J. Somani R, Jain K. Anti-diabetic

effect of karela in mice. Indian Journal of

Pharmacology. 2006, S66; 44-47.


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&

Health Sciences




th Feb 2013

Research article

THE EFFECT OF VERAPAMIL AND DILTIAZEM ON CARDIAC STIMULANT EFFECT OF

ADRENALINE AND CALCIUM CHLORIDE ON ISOLATED FROG HEART

Lakhavat Sudhakar 1, Naveen Kumar T2, Tadvi NA3, Venkata Rao Y4

1 Non Medical Assistant, Kakatiya Medical College, Warangal, Andhra Pradesh, India2

Associate Professor, Department Pharmacology, Apollo Medical College, Hyderabad, A.P, India3Associate Professor, 4Professor and Head, Department Pharmacology, Kamineni Institute of Medical

Sciences, Narketpally, Andhra Pradesh, India


ABSTRACT

Background: Calcium channel blockers block voltage dependent L-type of calcium channel and thus

reduce the frequency of opening of these channels in response to depolarization . The result is a marked

decrease in transmembrane calcium current associated with long lasting relaxation of vascular smooth

muscle, reduction in contractility in cardiac muscle, decrease in pacemaker activity in the SA node and

decrease in conduction velocity in the AV node. Among Calcium channel blockers verapamil, is cardio

selective, nifedipine is vascular smooth muscle selective, while diltiazem exhibits intermediate

selectivity. Methods: In the present study, the effect of two Ca++ channel blocker, Verapamil and

Diltiazem were compared on the isolated frog heart by using adrenaline & calcium chloride as standard

on frog heart contractility. Results and conclusion: Adrenaline and calcium chloride increased the

amplitude of contraction of isolated perfused frog heart. The L- type of Ca2+ channel blockers

verapamil and diltiazem produced dose dependent (2µg, 4µg, 8µg, and 16µg) reduction in the amplitude

of contraction produced by calcium chloride in isolated perfused frog heart. There was no statistical

significant difference (p > 0.05) between the inhibitory effect of diltiazem and verapamil on calcium

chloride induced contraction of isolated frog heart.

Keywords : Verapamil , Diltiazem,Cardiac stimulant effect, Adrenaline, Cacl2

INTRODUCTION

The incidence of ischemic heart diseases is high

all over the world especially in urban

population1. Risk factors are age, male sex,

hyperlipidemia, smoking, hypertension, diabetes

and family history2. Calcium channel blockers

are used for treatment of heart diseases which

include angina, hypertension & arrhythmia 3.

Among Calcium channel blockers verapamil, is

cardio selective (↓HR, contractility,& conduction

velocity), nifedipine is vascular smooth muscle

selective, while diltiazem exhibits intermediate

selectivity.4 so this study was planned to


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compare the cardiac depressant effect of the two

calcium channel blockers verapmil and

diltiazem.

Aims and Objectives The aim of the present

study was to compare cardiac depressant effects

of two L-type of calcium channel blockers,verapamil & diltiazem in Calcium chloride-

induced inotropic effect on isolated frog ( Rana

tigrina) heart preparation.

MATERIAL AND METHODS

The study was conducted in the Amphibian

Laboratory in the department of Pharmacology,

Kamineni Institute of Medical Sciences,

Narketpally during the period from 13/10/2009

to 12/04/2011.5 Frogs ( Rana tigrina) 12 in

numbers, weighing about 150 – 250g, reared in

the Central animal house of the Kamineni

Institute of Medical Sciences (KIMS) were used.

The present study was approved by Institutional

Animal Ethcs Commeette.

Double pithed frog was fastened over the frog

board and the heart was removed and mounted

using standard procedures described by Ramesh

KV et al5

The Normal contraction of the heartwas recorded for 3 minutes by using frog ringer

solution. Adrenaline 2µg was added into the

vertical limb of the Syme’s cannula and response

was recorded to test the sensitivity of the tissue.

Calcium chloride 2 mg was added to symes

cannula and increase in responses were recorded.

Then 2 µg verapamil was added to the Syme’s

cannula and the contraction of the heart was

recorded and the difference from normal

contraction (inhibition in height of contraction)

was recorded. The procedure was repeated by

adding calcium channel blocker verapamil in the

dose of 4, 8, 12, and 16 µg respectively. The procedure was repeated in six frog hearts. The

above procedure was repeated with diltiazem in

the same dose (2, 4, 8, 12, and 16 µg)

respectively.

Calcium chloride solution (standard) 2 mg was

added each time in to ringer solution because

calcium channel blockers verapamil & diltiazem

act on calcium chloride induced heart

contraction.

6

Drugs used in the experiment:

Diltiazem 5mg/ml vial ( Dilgard cipla)

Verapamil 5mg/2ml amp (Samarth life

science pvt. Ltd.)

Adrenaline 1mg/ml amp (Neon laboratories

pvt. Ltd.)

Calcium chloride (1%) 10mg/ml (Accord

labs)

RESULTS

The effect of diltiazem (2µg, 4µg, 8µg, 16µg)

pretreatment on calcium chloride induced

increase in the amplitude of contractions was

also calculated. Diltiazem pretreatment reduced

the CaCl2 produced increase in amplitude of

contraction in dose dependent quantity, i.e 2µg,

4µg, 8µg, 16µg.

Fig.1: Inhibitory effect of Diltiazem.


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Adrenaline (2µg) was added to the biophase to

conform the normal functioning of heart as

adrenaline is a standard drug which increases the

contraction of heart. Subsequently 2 mg of

calcium chloride was added to the biophase and

the increase in contraction of heart compared tothe normal contraction was recorded.

Verapamil pretreatment reduced the CaCl2

produced an increase in amplitude of contraction

in dose dependent quantity, i.e. 2µg, 4µg, 8µg,

16µg.

Pre-treatment with diltiazem and Verapamil in

the above quantities had not modified the

adrenaline induced increase in amplitude of

contractions suggesting more doses of Verapamil

and diltiazem pre-treatment for blocking the

adrenaline response or probably L type ofCalcium channels may not be involved in

adrenaline response in isolated perfused frog

heart.

Fig.2: Inhibitory Effect of Verapamil

Table 1: Comparison of antagonist effect of diltiazem versus verapamil

Sr.No Dose

(µg)

Diltiazem Height of

contraction (mm)

Verapamil Height of

contraction (mm)

t value p value

1 2 30.83±2.37 24.00±2.76 1.87 0.09

2 4 29.16±2.30 23.33±3.38 1.42 0.18

3 8 27.33±2.40 20.50±3.17 1.71 0.11

4 16 23.16±4.05 20.83±3.02 0.461 0.65

*Data presented as mean ±SD

Comparison of antagonism of CaCl2 produced an increase in amplitude of contraction by diltiazem and

Verapamil showed no statistical significance (P>0.05) by applying student unpaired‘t’test

DISCUSSION

Adrenaline (2µg) and CaCl2 (2mg)

administration through the Symes cannula in the

biophase produced an increase in amplitude of

contraction of isolated perfused frog heart

preparations. Pre-treatment with the known L-

type Ca++ channel blockers diltiazem and

verapamil reduced the CaCl2 responses in dose

dependent quantity. Both diltiazem and

verapamil in the doses of 16µg completely

blocked CaCl2 induced increase in the amplitude

of contractions.

Comparison of antagonism of CaCl2 produced an

increase in amplitude of contraction by Diltiazem


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and Verapamil showed no statistical significance

(P>0.05) by applying student unpaired “t” test.

SUMMARY AND CONCLUSION

Adrenaline and calcium chloride increased the

amplitude of contraction of isolated perfused

frog heart. The L- type Ca++ channel blockers

verapamil and diltiazem produced dose

dependent (2µg, 4µg, 8µg, and 16µg) reduction

in the calcium chloride produced increase in

amplitude of contraction of isolated perfused

frog heart. There was no statistical significant

difference (p > 0.05) between the inhibitory

effect of Diltiazem and Verapamil on CaCl2

induced contraction on isolated frog heart.Further studies are needed to explore the role of

calcium channels in the adrenaline induced

positive inotropic effect (increase in amplitude of

contraction)

REFERENCES

1. Fuster V, Kelly BB, editors. Promoting

Cardiovascular Health in the Developing

World: A Critical Challenge to AchieveGlobal Health. Washington (DC): National

Academies Press (US); 2010;2:

2. Gupta R, Guptha S, Gupta VP, Agrawal A,

Gaur K, Deedwania PC. Twenty-year trends

in cardiovascular risk factors in India and

influence of educational status. Eur J Prev

Cardiol. 2012;19(6):1258-71

3. Sharma HL,KK. Drugs Therapy of

Hypertension, Angina Pectoris, Arrythmias.In Principles of Pharmacology by 2011, 3rd

Ed; pg:279- 307

4. Sharma HL,KK. Drugs Therapy of Angina

Pectoris . In Principles of Pharmacology by

2011, 3rd Ed; pg:284.

5. Ramesh KV, Ashok S, Mukta NC. Practical

Pharmacology; 1st ed. Himachal Pradesh:

Arya Publishing Company; 2008. Pg 89.

6. Ghosh MN, Fundamentals of Experimental

Pharmacology, Hilton and Company , 3rd

ed.2009.Pg26


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Nidhi Bansal et al., Int J Med Res Health Sci.2013;2(2):147-155


&

Health Sciences


st Jan 2013 Revised: 20


th Feb 2013

Research article

AN AUDIT OF INDICATIONS AND COMPLICATIONS ASSOCIATED WITH ELECTIVE

HYSTERECTOMY AT SVMCH AND RC, ARIYUR, PONDICHERRY

*Nidhi Bansal1, Hiremath PB2, Meenal C3, Vishnu Prasad4

1Assistant Professor, 2Associate Professor, 3Professor, 4CRRI, Dept. of OBG SVMCH & RC

Ariyur,India


ABSTRACT

Background: Hysterectomy is the most common gynaecological surgery performed worldwide

Menorrhagia secondary to uterine fibroids and abnormal menstrual bleeding are the two most common

indications for hysterectomy. An important factor impacting on the incidence of complications of

hysterectomy, apart from the indication for surgery, is the surgical approach. Majority of the

hysterectomies are performed by the abdominal route. The incidence of LAVH performed for benign

lesions has progressively increased in recent years. Methods : Surgical indications and details,

histological findings, and postoperative course were reviewed and analysed for 340 patients who

underwent hysterectomy in 2011 and 2012.Results : In our study, fibroid uterus (27.9 %) was the

leading indication for performing hysterectomies followed by a Dysfuctional uterine bleeding (DUB)

22.9% and uterovaginal prolapse (UVP) 21.8%. During the study period (2011-2012), most

hysterectomies were performed abdominally (54.4%). Overall post operative complications including

major and minor, are significantly higher in the abdominal surgery group as compared to the vaginal and

laparoscopic group ( p value= 0.001). Conclusion: We need to ensure that trainees acquire competency

in performing hysterectomies vaginally, which is clearly safer than the abdominal approach.

Keywords: Hysterectomy indications, LAVH, TAH, Intraoperative, Postoperative complications

INTRODUCTION

Hysterectomy is the most common gynecological

surgery performed worldwide. After caesarian

delivery, hysterectomy is the major surgical

procedure most frequently performed in women1,

2. With increasing advancement in technology

and acquisition of better skills and experience the

abdominal route is fast being replaced by vaginal

and laparoscopic for majority of indications as

many of the surgeons now consider that descent

of the cervix and not the uterine size predicts the

success of the vaginal route of hysterectomy.

Over the past 2 years various hysterectomies

were performed in our hospital through different

routes for a variety of indications.

More than half of the hysterectomies are carried

out due to abnormal uterine bleeding, which is

associated with a wide range of diagnoses that

include uterine fibroids, endometriosis,


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adenomyosis and dysfunctional uterine bleeding

(DUB). Menorrhagia secondary to uterine

fibroids and abnormal menstrual bleeding are the

two most common indications for hysterectomy.

An important factor impacting on the incidence

of complications of hysterectomy, apart from theindication for surgery, is the surgical approach.

The type of hysterectomy depends on the

disorder be treated, the size of the uterus, and the

skills and preference of the surgeon. The

abdominal approach is indicated in most cases of

uterine cancer, in cases of emergency

hysterectomy, and in patients with large fibroids.

Laparoscopic assisted vaginal hysterectomy

(LAVH) and Vaginal hysterectomy (VH) isclinically and economically comparable with

Total abdominal hysterectomy (TAH), with

patients' benefits of less estimated blood loss,

less analgesia use, less intra- and postoperative

complication rates, less postoperative pain, rapid

patient recovery and shorter hospital

stay3.Studies have reported fewer unspecified

infections or febrile episodes in the vaginal group

versus the abdominal group4. The number of

doses of injectable analgesics used per patient

was significantly more in the TAH group in

comparison to LAVH group. Overall

complication was 14% in LAVH and 10% in

TAH though the differences were not

significant5.

In LAVH, greater total uterine weight and

morcellation are associated with longer operative

times. Blood loss correlates with uterine weight

when vaginal morcellation is also used. Anincrease in the operative time and a higher blood

loss can be expected as the uterine weight

increases and can be predicted taking

morcellation methods into account6.

Assessing surgical approaches according to the

type and severity of complications identifies the

risk factors most strongly associated with each

approach. Further, by giving rise to technical

improvement, such assessment will result in safer patient treatment.


Surgical indications and details, histological

findings, and postoperative course were reviewed

and analysed for 340 patients who underwent

hysterectomy in 2011 and 2012 at SVMCH &

RC, Ariyur, Pondicherry. Institutional Research,Science and Ethical committee approval was

obtained and informed consent was taken from

each patient prior to surgery.

The patients are admitted 2-3 days before surgery

and a complete work up of the case is done. Co

morbid medical conditions like diabetes,

hypertension, heart disease, thyroid disease if

any, are looked into and cardiologist or

physician’s opinion is sought for the same.Patients with Hb


26/197


for 24 hrs routinely for abdominal hysterectomy

and 48hrs for VH/LAVH/NDVH and extended

bladder drainage is considered in patients who

had required difficult bladder dissection during

surgery. Romovac drain is removed when the

drain output is < 25ml.Patients with abdominal hysterectomy are

discharged on the 7th or 8th day after suture

removal, while NDVH/VH/LAVH patients are

discharged on the 4th postoperative day. All

patients are advised to review after 6 weeks or

earlier in the event of any unforeseen

complications.

Histopathology reports are routinely reviewed at

6 weeks. However, in patients whom malignancyis suspected the same is reviewed after 2 weeks.

RESULTS

Statistical analysis of the data was done by using

SPSS version 17. Considering the age wise

distribution pattern of patients who underwent

hysterectomy the majority of women were in the

age group of 40 -49 years (193). However, the

second leading age group was that of youngwomen 30-39 years (68). The younger women

hysterectomised were about 30 years of age, for

varied indications like fibroid uterus or

adenomyosis. The overall mean age was 46.9

years. Considering the varied pre operative

diagnosis for hysterectomy, the highest mean age

was 57.8 years in cases of genital malignancies

followed by 55.7 years in cases of UVP, whereas

the lowest was 40.7 years in cases of pre

malignant conditions and Adenomyosis .

Preoperative diagnosis showed in Table 1. In our

study, fibroid uterus (27.9 %) was the leadingindication for performing hysterectomies

followed by a DUB (22.9%) and uterovaginal

prolapse (UVP-21.8%)

During the study period (2011-2012), most

hysterectomies were performed abdominally

(54.4%), an approach that is associated with

higher incidence of complications. However, in

2012, the percentage of hysterectomies done

abdominally reduced to 26.8 %( 40/149).On thecontrary, 73.2% of hysterectomies were

performed vaginally (LAVH – 61/149, NDVH –

10/149, VH – 38/149) [Table II, Figure I]

On analysis of 185 patients, who underwent

hysterectomy by an abdominal approach over a

period of 2 years, 5 were for malignant( cervical,

endometrial, ovarian), 29 were for suspected

large adnexal masses and 40 for large fibroid

uterus (uterine size > 20weeks). Remaining

111 abdominal hysterectomies were done for

benign indications like DUB, fibroid uterus or

Adenomyosis, which could have been considered

for LAVH or NDVH. This is explained by lack

of laparoscopy expertise at our centre during the

early part of our study period.

Table. 1: Preoperative diagnosis

S.No Diagnosis No of patients Percentage (%)

1. Dysfunctional uterine bleeding 78 22.9%2. Fibroid uterus 95 27.9%

3. Adenomyosis 33 9.7%

4. Utero vaginal prolapse 74 21.8%

5. Adnexal mass 29 8.5%

6. Chronic cervicitis 8 2.4%

7. Pre malignant conditions 8 2.4%

8. Genital malignancy 5 1.5%

9. Post menopausal bleeding 10 2.9%

Total - 340 100%

The route of hysterectomies was performed showed in the Table 2.


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Table. 2 : Route of surgery

S.No Route No of patients 2011 (%) No of patients 2012 (%) Total (%)

1. TAH 142(74.3%) 35(23.5%) 177(52.1%)

2. VH 38(19.9%) 38(25.5%) 76(22.4%)

3. NDVH Nil 10(6.7%) 10(2.9%)

4. LAVH 8(4.2%) 61(40.9%) 69(20.3%)

5. Wertheim’s 2(1.0%) 2(1.3%) 4(1.2%)

6. Subtotal 1(0.5%) Nil 1(0.3%)

7. Staging

laparotomy

Nil 3(2.0%) 3(0.9%)

Total 191 149 340

Fig 1 : Trend of hysterectomies in 2011 & 2012

Table.3: Correlation of age, Preoperative & Histopathological Diagnosis

∗

Dysfunctional uterine bleeding,†

Post menopausal bleeding,∗∗

Endometrial Hyperplasia

I n d i c a t i o n

M e a n a g e

N o p a t h o l o g y

F i b r o i d

A d e n o m y o s i s

B e n i g n

O v a r i a n

C h r o n i c

c e r v i c i t i s / S I L

E H ∗ ∗∗ ∗ ∗ ∗∗ ∗

C a O v a r y

C a u t e r u s

C a c e r v i x

E n d o m e t r i o s i s

T o t a l

DUB 43.8 40 7 15 - - 14 - 1 - 1 78

Fibroid 41.2 5 75 15 - - - - - - - 95

Adenomyosis 40.7 6 5 22 - - - - - - - 33

Prolapse 55.7 70 2 - 1 - 3 - - - - 74

Adnexal mass 47.7 1 - - 24 - - 2 - - - 29

Chronic cervicitis 45.2 - - - - 8 - - - - - 8

Premalignant

conditions

40.7 - - 1 - 1 5 1 - - - 8

Genital Malignancy 57.8 - - - - - - 1 - 4 - 5

PMB† 49.6 3 - 3 - - 4 - - - - 10

Total 46.9 125 89 56 25 9 26 4 1 4 1 340


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An analysis of Histopathological reports, 125 out

of 340 women (36.8%), revealed no significant

pathology. Out of these women, a majority of the

70 women (56%) underwent hysterectomy for

UVP, while in 40 women (32%); the indication

for surgery was DUB. In the remaining 15 patients, the indications were fibroid uterus,

Adenomyosis or postmenopausal bleeding

(PMB) [Table 3 ]

Out of 78 women hysterectomised for DUB, a

majority of the 40 women (51.3%) had no

pathology in the uterus, while 15 (19.2%) had

Adenomyosis, 14 had endometrial hyperplasia

(EH-17.9%) and 7 patients (9%) were diagnosed

with fibroid uterus. One patient with a preoperative diagnosis of DUB, aged 52 years

was diagnosed as having endometrial cancer on

HPR (Not diagnosed on Fractional curettage).

One case of DUB surprisingly showed HPR of

Degenerated products of conception.

95 women (27.9%) in our study underwent

hysterectomy for fibroid uterus, out of which a

majority of 75 women (79%) had

histopathologically proven fibroids.

In the remaining 20 patients, 15 had

Adenomyosis, while 5 patients had normal uteri

with no definitive pathology. 14 other patients

with incidental findings of leiomyoma on HPR

were operated for varied indications like DUB,

Adenomyosis or prolapse uterus.

In the 74 women with UVP, who underwent VH,

majority of 70 women had no pathology on HPR.

Operated 33 cases with a preoperative diagnosisof Adenomyosis of which only 22 had proven

Adenomyosis on HPR. Total number of HPR

showing Adenomyosis was 56 in our study, out

of which, in 34 patients, the preoperative

diagnosis was not Adenomyosis. This indicates

that the true incidence of Adenomyosis is higher

compared to clinical or sonological diagnosis.

We operated 29 cases of adnexal masses, out of

which 24 were benign tumours, while 2 weremalignant.

In our study, 5 bladder injuries (1.4%) were

noted over a period of 2 years, out of which 2

were in TAH (1.1%) & VH (2.6%) each and 1

was seen in LAVH (1.4%). All were identified

on the table and bladder repair was done. In

addition 3 ureteric injuries were noted, all in the

abdominal hysterectomy group for large adnexal

mass, carcinoma cervix and carcinoma ovary

respectively. These injuries were identified post

operatively. The difference was however not

significant statistically ( p value= 0.84) [Table 4]

Table.4: Intraoperative complications

Hysterectomy Diagnosis Haemorrhage

with transfusion

Bladder

Injury

Bowel

Injury

Ureteric

Injury

Total

TAH/Subtotal 4 / 178

1. DUB - Yes - -

2. Chr cervicitis - Yes - -

3. Adenomyosis Yes - - -4. Adnexal mass - - - Yes

LAVH 2/69

1. Adenomyosis - Yes - -

2. Fibroid uterus Yes - - -

VH/NDVH 2/86

1. UVP - Yes - -

2. UVP - Yes - -

Wertheim’s ¼

1. Ca Cervix Yes - - Yes

Staging Lap 2/3

1. Ca Ovary Yes2. Ca Ovary Yes

Total No. of

complications

5 Nil 3 11/340

(3.2%)


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Considering the immediate postoperative

complications, pyrexia was noticed in 14.1% of

patients with TAH. On the contrary, 3.2% of

patients in the vaginal group (LAVH, NDVH,

and VH) had significant post operative fever

[Table 5].

Table 5: Immediate postoperative complications

Immediate postoperative complications like

haemorrhage, wound sepsis, pain, urinary

complaints were noticed in 20.1% of patients

with abdominal surgery as compared to 5.2% of

patients in the laparoscopic and vaginal group.

Relaparotomy was done in 2 cases of abdominal

hysterectomy and 5 cases were taken for wound

resuturing. No such complications were noticed

in the vaginal group.

Vault exploration had to be done for 4 patients

out of which 3 were following abdominal

hysterectomies.

An analysis of major complications in

hysterectomised patients from the time of

discharge up to 6 weeks post op, 1 patient with

abdominal surgery had Deep vein thrombosis, 4

patients had vesico vaginal fistula (2%) and 1

patient had uretero vaginal fistula (0.5%). On the

contrary, only 1 patient of vaginal hysterectomy

had a vault granuloma on 6 weeks follow up. No

patients in the LAVH or NDVH group had any

of the above complications on follow up.

However the difference in the rates of fistula

formation in abdominal vs. vaginal route is not

statistically significant (p value =0. 12) [Table 6]Table.6: Complications from discharge upto 6 weeks post surgery

Complication No. of occurrences

Pain 15(TAH) + 2(LAVH)

Poor wound healing 5(TAH)

Vault prolapse 1(TAH)

Deep vein thrombosis 1(TAH)

Vesico vaginal fistula 4(TAH)

Uretero vaginal fistula 1(TAH)

Vault granuloma 1(VH)Total no of patients 30/340 (8.8%)

Complication Approach to hysterectomy No

complicationsTAH LAVH VH/NDVH Wertheim’s Staging

laparotomy

Pyrexia 25 3 2 Nil Nil 30

Haemorrhage 3 Nil Nil 1 8

Wound sepsis 9 Nil Nil 1 1 11

Pain 12 1 Nil 1 Nil 14

Urinary complaints 8 Nil 3 1 Nil 12

Second laparotomy 2 Nil Nil Nil Nil 2

PulmonaryEmbolism

Nil Nil Nil Nil Nil 0

Death Nil Nil Nil Nil Nil 0

Resuturing 5 Nil Nil Nil Nil 5

Vault exploration 3 Nil 1 Nil Nil

Total no of pts. With

complication

67

(37.8%)

4

(5.8%)

10

(11.6%)

3

(75%)

2

(66.6%)

86/340

(25.3%)


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Overall post operative complications including

major and minor, are significantly higher in the

abdominal surgery group as compared to the

vaginal and laparoscopic group ( pvalue= 0.001 )

In our series, the incidence of carcinoma ovary

and carcinoma cervix was 1.17% each whereascarcinoma endometrium and endometriosis were

least i.e. 0.29% each.

In pre malignant conditions, one case was

cervical dysplasia, 26 were endometrial

hyperplasia, out of which two showed

hyperplasia with atypia.

DISCUSSION

Hysterectomy is the major surgical proceduremost frequently performed in women, after

caesarian delivery.1, 2 In our series, 20% of

hysterectomies were done in the age group of 30-

39 years. An Indian study in 2010 showed that

33% of hysterectomies were performed in

women less than 35 years of age7. These

numbers could have been further reduced by

using alternative therapeutic options like

levonorgestrel-releasing intrauterine system,endometrial ablation or fibroid embolisation.

Kripalani et al found that Ormeloxifene was an

effective and a safe therapeutic option for the

medical management of menorrhagia8 . This

would further decrease the number of

hysterectomies for DUB. These figures stress

upon the need for encouraging the treatment of

benign conditions conservatively and offering

hysterectomies more often to women with

defined pathologies in the perimenopausal or

menopausal age group.

Fibroid uterus (27.9%) was the most common

indication for hysterectomy, followed by DUB

and UVP. A Nigerian tertiary hospital

retrospective study showed that uterine fibroid

was the leading indication in 38.7% of patients9.

We do not have the data to analyze the

percentage of women with fibroids who were

symptomatic to justify hysterectomy as the onlytreatment modality in our study group. Few

hysterectomies were performed for genital

malignancies at our centre over the study period

of two years.This is due to the non availability of

the onco-surgeons. We deny hysterectomy for

chronic cervicitis, hence the incidence is low at

2.4%.

Most surgeons perform up to 80% of procedures

by the abdominal route 10 . The incidence ofLAVH performed for benign lesions has

progressively increased in recent years11. During

our study period, 54.4% of surgeries were

performed abdominally. However, in the later

part of the study, this was reduced to 26.8%, in

favour of 73.2% of hysterectomies that were

performed vaginally. This is explained by lack of

laparoscopy expertise at our centre during the

early part of our study period .This also indicatesa favourable trend towards adopting a vaginal

approach for hysterectomy in contrast to

abdominal approach at our institute.

The high incidence of abdominal hysterectomies

can in part be explained by personal preference,

but is mainly due to lack of training and

experience leading to reluctance to perform VH

in nulliparous women in the presence of uterine

enlargement or in women with previous pelvic

surgery or previous caesarean section. The above

factors should not be considered

contraindications to VH, and there are

publications that support this view 12, 13. The

rationale for LH is to convert an abdominal

hysterectomy (AH) into a laparoscopic/vaginal

procedure and thereby reduce trauma and

morbidity10.

Urinary tract injuries are reported in

approximately 1 percent of women who undergo pelvic surgery14 . Studies have reported that the

rate of injuries varies by indication and

procedure, being highest following radical

hysterectomy for cervical cancer (1 in 87; 95%

CI 61-128) and lowest following vaginal

hysterectomy for prolapse (1 in 3861; 95% CI

2550-6161).

After total abdominal hysterectomy, risk was

lower after hysterectomy for benign conditions

15

.In our series, 2.4% of women had urinary tract

injuries (5 bladder injuries, 3 ureteric injuries).

On analysis of these, we noted that amongst the


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bladder injuries, 2 were in TAH(1.1%), 2 in

VH(2.6%) and 1 in LAVH(1.4%).In a study by

Babak Vakili et al, there were 8 cases of ureteral

injury (1.7%) and 17cases of bladder injury

(3.6%) There was no diff erence in the rate of

bladder injury among TAH, TVH, and LH (2.5%

vs. 6.3% vs. 2.0%, respectively; P = .123),

although there was a trend toward a higher

incidence of bladder injury with vaginal

hysterectomy16.A similar trend was observed in

our study.

Vakili et al have also reported, that abdominal

hysterectomy was associated with a higher

incidence of ureteral injury as compared to VH

or LH (2.2% vs. 1.2% vs. 0%) but this was notsignificant.Vakili et al have concluded that

surgery for prolapse or incontinence increases

the risk of urinary tract injuries. Thus routine use

of cystoscopy during hysterectomy should be

considered16.However, this is difficult to accept

in routine gynaecology practice.

On analysis of surgical fistulas, 4 patients had

VVF (2%) and 1 patient had uretero vaginal

fistula (0.5%).All fistulas were noted in

abdominal surgeries and all patients presented

with urinary leak 10-14 days post surgery.

Surprisingly, all of them were seen in surgeries

performed in a particular unit. The contribution

of surgical fistulas to the total fistula prevalence

in developing countries is small, however it is

often supposed that this complication results

from direct injury to the lower urinary tract at the

time of operation but this is certainly not always

the result of careless, hurried, or rough surgicaltechnique. In a study on Vesico-vaginal fistulas

in developing countries, of the 165 urogenital

fistulas over the last 12 years, 117 were

associated with pelvic surgery, and 91 followed

hysterectomies; of these only 4% presented with

leakage of urine on the first day post operatively.

In the other cases it was presumed that tissue

devascularization during dissection, inadvertent

suture placement, or pelvic hematoma formationor infection developing postoperatively resulted

in tissue necrosis with leakage usually

developing 5–14 days later. Over distension of

the bladder postoperatively may be an additional

factor in many of these latter cases .It is likely

that patients with a habit of infrequent voiding,

or those with inefficient detrusor contractility,

may be at increased risk of postoperative urinary

retention; if this is not recognized early andmanaged appropriately, the risk of fistula

formation may be increased. The use of

prophylactic catheterization in the first 24–48 h

might be expected to reduce the risk of post-

operative fistula formation, but this has never

been proven17.

CONCLUSION

Hysterectomy is a major gynecologic operationand more cases of hysterectomy should be

performed vaginally, considering the numerous

benefits it has over the abdominal route. We need

to ensure that trainees acquire competency in

performing hysterectomies vaginally, which is

clearly safer than the abdominal approach.

The prophylactic use of antibiotics to reduce

infection and fever, the adequacy of analgesic

regimens, and the correct dosage of prophylacticheparin treatment are some of the other issues

that should be audited to reduce post operative

complications. Ideally, we should be able to

provide more medical options, such as the

levonorgestrel intrauterine system, whenever

appropriate, and to have available the equipment

and collective skill necessary to provide any

patient with the most appropriate surgical

treatment.

Because, few studies have recently been

conducted regarding the indications for and

complications of elective hysterectomies, the

present study may provide a basis for a future

audit of our gynaecological practice and for the

comparison of our practice with others.

ACKNOWLEDGEMENT

We would like to extend our sincere gratitude to all

our patients who were a part of this study.


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