Evidence-based Medicine: Time for a change? - Journal of Medical ...

EDITORIAL 

Evidence-based Medicine: Time for a change? 

1 

Sudheeranjan Thingbaijam, 2 A Devadutta Sharma 

The Evidence-based Medicine (EBM) 

movement emerged due to research-practice 

gap, poor quality of much research, 

information overload and clinical medicine 

which is not evidence-based, in the context 

of post-modern “risk society”, “managerialism” 

and “audit society” 1 . This movement 

also coincided with the rise of professionalism, 

empowerment and consumerism and has 

been aided by the information technology 

movement. Sackett and colleagues 2 describe 

EBM as the “conscientious, explicit, and 

judicious use of current best evidence in 

making decisions about the care of individual 

patients,…..integrating individual clinical 

expertise with the best available external 

clinical evidence from systematic research”. 

The traditional EBM tools are randomized 

controlled trial and systematic review, 

championed by the Cochrane Collaborations. 

While some critics define EBM as one which 

is purely guided by evidence from clinical 

research and some even brand it as “cookbook 

medicine” 3 , most subscribe to the 

definition of ‘the use of best external research 

evidence in the context of clinical experience, 

clinical situation, and patient values and 

1. Associate Professor of ENT,2. Associate 

Professor of GI Surgery, Regional Institute of 

Medical Sciences, Imphal 

Address for Correspondence: 

Dr A Devadutta Sharma, Associate Professor of GI 

Surgery, Department of Surgery, Regional Institute 

of Medical Sciences, Imphal 

e-mail: aribam.sharma@jipmer.net 

preferences for making clinical decisions’ 4 . 

Though the EBM movement has gained 

tremendous momentum in the last two 

decades, the gold-standard status of RCT, 

meta-analysis and systematic review remains 

less than certain. Evidence synthesis, a term 

expounded by Prof Thanos and Prof Ara 

Darzi 5 , applies to a group of assessment 

techniques that integrate the data from 

variable evidence sources, and is applicable 

to both clinicians and policy-makers. The 

ultimate maturation of EBM would be when 

genomics, proteomics and informatics lead 

us to “personalized medicine”. 

The prerequisites for a viable evidence-based 

practice (EBP) include clinicians educated 

and skilled in the fundamentals of EBM and 

ready to change; the system or organization 

whose board-level members and leadership 

are committed and geared toward rendering 

the best evidenced health care; a workable IT 

infrastructure; an informed and involving public 

and a sound EBM education module at hand. 

The decision making process of EBM 

essentially comprises of 1) designing an 

answerable clinical question directly relevant 

to one’s patient 2) searching the literature( 

including and mainly electronic) skill-fully for 

the right evidence from the right sources 3) 

critically analysing the identified evidence 4) 

examining if the evidence is closely similar to 

one’s patient or should be ignored and make 

the final presumptive decision 5) to evaluate 

the patient outcome and other audit 

parameters which will inform future EBM 

initiatives 2 . 

JMS * Vol 25 * No. 13 * June, September, 2010 2011 

1

EDITORIAL 

The main short-coming of EBM is that there 

is more diseases and clinical questions 

without evidence-base than those with a 

robust external evidence. While critics point 

out the statistical nature of most research 

evidence thereby making extrapolation to a 

particular patient rather difficult, this 

translational gap could be bridged by filtering 

all evidence through “clinical relevance”. Most 

important and worrying is the fact that these 

‘gold-standards’ are not without errors and 

thus are fallible. One of the main arguments 

on what constitutes “clinical judgement” 

arises from the fact that while critics seem to 

equate it with “ clinical experience” which is 

afflicted with psychological biases 6 , the EBM 

enthusiasts point out that best evidence is an 

important part of the decision-making process 

or “clinical judgement” for the patient. Clinical 

freedom and innovation are other potential 

collateral victims of EBM movement according 

to the critiques and some suspect it to be a 

“management Trojan-horse”. 

As pointed out by the Institute of Medicine 

(IOM) Roundtable conference on “ Learning 

health care system”, convened in 2006, the 

success of the EBM movement mandates 

involvement of all the stake-holders of 

healthcare delivery system. They include 

professionals, managers, leaders, policymakers, 

industry representatives and the 

public. Incidentally, evidence synthesis would 

help put the evidence into perspectives for 

different stake-holders, thereby preventing 

EBM policies and initiatives from getting out 

of context. 

Sadly, despite more than two decades of the 

movement, much headway has not been 

made in turning the fundamentals and the 

philosophy into practice so as to lift up patient 

outcomes. Some of the tested interventions 

include “feedback”, “ ownership”, “ 

administrative “, “detailing” which is a part of 

“social influence”, “ involvement of opinionleader”, 

“computerized decision-support 

systems” and “consumerism”. “Ownership” of 

which examples include professional 

guidelines means making the professional 

members feel they are part of ‘it’ and have 

contributed materially, resonates with the 

current managerial advances. Total quality 

management leads us to health care 

equivalent -continuous quality improvement 

(CQI). In short, it requires a system overhaul. 

In the USA for example, managed-care 

hospitals are put under the umbrella of payfor-performance(P4P) 

guidelines, which is 

basically a “financial penalties” intervention. 

The professionals are looking toward the IT 

revolution and beyond for solutions, and use 

of hand-held PDA and e-book reader for pointof-care 

evidence needs is a recent such 

example which seems to be working at least 

in the developed countries. But perhaps even 

more important for developing country is EBM 

“training the trainers” programs 7 . Globally 

present research is directed towards 

developing an adequate assessment tool after 

interventions to ensure positive patient 

outcomes. The “Fresno Test” is one such 

promising tool which has been validated in 

Spain 8 and is being tested in Australia starting 

this year 9 . The Spanish study found that 

framing a clinical question according to 

PICOTT guidelines is the most difficult 

outcome to achieve. The authors 

hypothesized that it could be due to the fact 

that during the rather short EBM course the 

participants were constrained by the 

multitudes of tasks. The Australian study is 

looking at institution of EBM skills as early as 

the 3rd clinical year. 

The situation back home is wanting especially 

in the peripheral and rural areas. The third 

world countries including India with its northeastern 

states are a fry cry from seeing a 

general acceptance of EBP sooner, probably 

because of lack of locally relevant evidence 

base; corrupted infrastructure and processes; 

heavy influence of the industry; lack of 

adequate IT solutions customized to the local 

needs; lack of a critical mass of concerned 

citizens, and resistance of the private sector 

to follow EBM principles for obvious reasons. 

Paradoxically we are actually in need of 

controlling the distribution of healthcare 

delivery demography-wise as well as 

geography-wise while doing away with the 

unnecessary cost of ineffective interventions. 

And mostly in this part of the world clinicians 

2 JMS * JMS Vol 25 * Vol * No. 25 3 * No. * September, 1 * June, 2010 2011

EDITORIAL 

are depraved of the much-needed evidencebase 

as well as the access to it, partly due to 

utter lack of IT infrastructure and partly 

because EBM has not gained a firm foothold 

yet. Possibly the Department of Medical 

Education in each institute can take a more 

pro-active role in EBM skills courses and CME 

and take up research on integration of EBM 

principles into medical curriculum and clinical 

rounds while the local or regional professional 

bodies or societies can take up leadership roles 

in EBP guidelines and awareness campaigns. 

We, both academicians and practitioners, 

cannot depend on wishful thinking but on being 

prepared for the inevitable health reforms and 

realities sweeping across the globe. 

References: 

1. Trinder L. Introduction: the Context of 

Evidence-Based Practice: In Trinder L, 

Reynolds S.eds. evidence-Based 

Practice: A Critical Appraisal. 

Oxford:Blackwell Science 2000. p.1-16 

2. Sackett DL, Rosenberg WMC, Gray 

JAM, Haynes RB, Richardson WS. 

Evidence based medicine: what it is and 

what it isn’t. BMJ. 1996;312:71–2. 

3. Straus SE, McAlister FA. Evidencebased 

medicine: a commentary on 

common criticisms. CMAJ. 

2000;163:837–41. 

4. Charlton BG. Restoring the Balance: 

Evidence-based medicine put in its 

place. J Eval Clin Pract 1997;3:87-98 

5. Ashrafian H, Darzi A, Athanasiou TH. 

Evidence Synthesis: Evolving 

Methodologies to Optimise Patient Care 

and Enhance Policy Decisions. In: 

Athanasiou TH, Darzi A (Editors). 

Evidence Synthesis in Healthcare : A 

Practical Handbook for Clinicians. 

London: Springer 2011.p.1-46 

6. Tversky A, Kahneman D. Judgment 

under uncertainty: Heuristics and biases. 

Science. 1974;185:1124–31 

7. Walczak J, Kaleta A, Gabryœ E, et al. 

How are “teaching the teachers” courses 

in evidence based medicine evaluated? 

A systematic review BMC Medical 

Education 2010, 10:64 

8. Argimon-Pallàs JM, Flores-Mateo G, 

Jimenez-Villa J et al. Effectiveness of a 

short-course in improving knowledge 

and skills on evidence-based practice 

BMC Family Practice 2011, 12:64 

9. Ilic D, Tepper K, Misso M. Teaching 

evidence based medicine literature 

searching skills to medical students 

during the clinical years – a protocol for 

a randomised controlled trial BMC 

Medical Education 2011, 11:49 


3

ORIGINAL ARTICLE 

Comparison of laparoscopic pyeloplasty and open pyeloplasty for the treatment 

of primary uretero pelvic junction obstruction 

1 

Ak. Kaku Singh, 2 N.P.Gupta, 

Abstract 

Objectives: To compare the complications , 

hospital stay , and functional results of 

laparoscopic and open pyeloplasty for primary 

uretero pelvic junction (UPJ) obstruction. 

Methods: From July 2004 to Dec. 2006, 56 

consecutive non randomized patients of 

primary UPJ obstruction who underwent open 

and laparoscopic pyeloplasty in All India 

Institute of Medical Sciences were included 

in the study.There were 31 cases of 

laparoscopic pyeloplasty and 25 cases of 

open pyeloplasty .The decision between the 

two techniques depended on patient‘s 

preference and surgeon‘s experience .The 

preoperative evaluation included history of 

clinical symptoms, ultrasound, X-ray IVP and 

renal dynamic scan . The patients were 

followed up at 3 months and 1 year after the 

surgery by evaluation of clinical symptom and 

renal dynamic scan. Success was 

considered if there was improvement of 

symptom and absence of an obstructive 

pattern during the washout phase of a renal 

scan. Result: The mean operating time was 

less in the open than in the laparoscopy group 

( 98 mins and 145 mins respectively). The 

mean blood loss was 85ml in the laparoscopy 

and 101 ml in the open pyeloplasty group. The 

mean analgesic requirement was less in the 

1. Associate Professor, Department of Urology, 

RIMS, Imphal, 2. Ex. Professor and Head 

Department of Urology AIIMS , New Delhi 

Address for correspondence 

Dr.Ak.Kaku Singh, Associate Professor, 

Department of Urology RIMS , Imphal 

Pin : 795004 e-mail : kakuakoijam@yahoo.com 

laparoscopy group than in the open group 

(75mg vs 127 mg of pethidine). No 

intraoperative complications occurred in either 

group. Post operative complications occurred 

in 2/31 cases in laparoscopic group and none 

in the open group.The mean hospital stay was 

5.8 days for laparoscopic pyeloplasty and 6.7 

days for open pyeloplasty. Of the 27 cases in 

the laparoscopy group, 25 cases were free of 

symptoms and all the 22 patients in the open 

group were free of symptoms. Renal scan 

shows good clearance in 23 cases, slow 

clearance in 3 cases and obstructed drainage 

in 1 in the laparoscopy group, and good 

clearance in19 cases and slow clearance in 

3 cases in the open group. At 1 year follow 

up, 14 cases were available in group I, all were 

free of symptoms and 12 showed good 

clearance and 2 showed slow clearance .And 

in group II, 10 cases were available for follow 

up , all were free of symptoms and 8 cases 

showed good clearance and 2 cases showed 

slow clearance on diuretic renogram. 

Conclusion: Laparoscopic pyeloplasty is 

associated with decreased hospital stay and 

early recovery from pain but takes longer 

operating time and has comparable functional 

results as open pyeloplasty. 

Key words: Laparoscopic pyeloplasty, open 

pyeloplasty. 

Introduction: Open Anderson Hyne’s 

dismembered pyeloplasty is the gold standard 

for the treatment of UPJ obstruction with the 

highest long term success rate with which 

other techniques should be compared 1. 

Laparoscopic pyeloplasty which was first 



described by Schuessler et al in 1993 has 

emerged as an alternative technique with 

comparable results to open pyeloplasty. 

Laparoscopic pyeloplasty producing 

comparable functional result with the open 

pyeloplasty and having the advantages of a 

minimally invasive procedure is gradually 

replacing open surgery as the gold standard 

in the treatment of UPJ obstruction , but the 

laparoscopic procedure requires significant 

laparoscopic surgical training and 

experience 2-6 . 

We report our results of a prospective nonrandomized 

study conducted to compare the 

clinical and functional result of laparoscopic 

and open pyeloplasty for primary UPJ 

obstruction. 

Materials and Methods: Between July 2004 

to December 2006, 56 patients underwent 

laparoscopic or open pyeloplasty for primary 

UPJ obstruction in our department. In the 

laparoscopic group (Group I) , there were 31 

and in the open group (Group II), there were 

25 patients. Symptomatic patients with 

primary UPJ obstruction proven with X-Ray 

IVP and diuretic renogram who has normal 

renal function and normal contralateral kidney 

unit were included in the study. 

Secondary UPJ obstruction, UPJ obstruction 

associated with other pathology or congenital 

anomaly were excluded. The operative time, 

estimated blood loss, type of pyeloplasty and 

the presence of crossing vessel were 

recorded . In the laparoscopy group, the route 

of approach was either Retroperitoneoscopic 

or Transperitoneal, the method of stenting 

either antigrade or retrograde and conversion 

to open with the reason were also recorded. 

In post operative period , mean analgesic 

requirement , period of hospital stay , start of 

normal daily activity, resumption of normal diet 

and postoperative complications were 

recorded. The DJ stent was removed 4-6 

weeks after the operation. In the follow up 

diuretic renogram was performed at 3 months 

and 1 year after the surgery and compared 

with the pre operative finding , the relieve or 

presence of symptoms because of the UPJ 

obstruction was also recorded. 

Result: Anderson Hyne’s dismembered 

pyeloplasty was performed in 26/31 

procedures in Group I and 21/25procedures 

in Group II . The age of the patients range 

from 12 -70 years in the laparoscopy group 

and 2 – 68 in the open group showing a 

tendency for open pyeloplasty in children. The 

mean operating time was less in the open than 

in the laparoscopy group , 98 mins and 145 

mins respectively.The mean blood loss was 

85 ml in the laparoscopy group and 101 ml in 

the open group .The average analgesic 

requirement was less in the laparoscopy 

group than in the open group . Crossing vessel 

was encountered in 7/31 cases in Group I and 

2/25 cases in Group II (Table I) . No 

intraoperative complications occurred in either 

group . One case in the laparoscopy group 

was converted to open pyeloplasty because 

of anastomotic tension . Post operative 

complications occurred in 2/31 cases in 

laparoscopic group and none in the open 

group.The patient who was converted to open 

surgery because of tension while 

anastomosing had wound infection and post 

operative fever . The other patient had 

misplaced DJ stent , coiled in the pelvis had 

post operative prolong drainage , ileus ,fever 

and jaundice .The mean hospital stay was 5.8 

days for laparoscopic pyeloplasty and 6.7 days 

for open pyeloplasty (Table I ). At 3 months of 

follow up 25/27 and 22/22 patients in group I 

and group II respectively are free of symptom. 

Renal scan shows good clearance in 23/27, 

slow clearance in 3/27 and obstructed 

drainage in 1 /27 in group I, and good clearance 

Table 1. Operative and Post operative parameters 

Laparoscopic Open pyeloplasty 

pyeloplasty 

Mean operating time 

in minutes (range) 145.32±26.83 97.80±18.15 

Mean blood loss in 

ml (range) 84.84 ±34.53 100.8±43.84 

Mean analgesic 

requirement 

(pethidine in mg) 75±15.81 127±53.97 

Mean length of 

hospital stay in 

days (range) 5.8±3.0 6.7 ±1.7 

Mean duration of 

recovery to routine 

activity in days (range) 15.0±7.4 20.2±5.8 


5


Table 2. Follow up at 3 months 

Lap Open 

pyeloplasty pyeloplasty 

` N=27/31 N=22/25 

Renal Dynamic Scan 

Good clearance 23 19 

Slow clearance 3 3 

Obstruction 1 

Symptom (Pain) 

Absent 26 22 

Present 1 0 

Table 3. Follow up at 1 years 

Lap Open 

pyeloplasty pyeloplasty 

` N=14/31 N=10/25 

Renal Dynamic Scan 

Good clearance 12 8 

Slow clearance 2 2 

Obstruction 

Symptom (Pain) 

Absent 14 10 

Present - - 

in19/22 and slow clearance in 3/22 in group II 

(Table 2). The one patient in Group I, who had 

obstructed drainage and was symptomatic 

underwent nephrectomy as it was found to 

be pyonephrotic when explored for redo 

pyeloplasty. At 1 year follow up 12/14 and 2/ 

14 patients show good and slow clearance 

respectively in group I and all the patients are 

free of symptom in this group and in group II 

,8/10 patients show good clearance and 2/10 

patients show slow clearance and all the 

patients are free of symptom (Table 3). 

Discussion: Open dismembered pyeloplasty 

is the gold standard for the treatment of UPJ 

obstruction with a success rate exceeding 

90%. Minimally invasive procedure like 

antegrade percutaneous endopyelotomy, 

endop-yeloplasty, retrograde endopyelotmy 

and balloon dilatation are associated with 

lower success rates and outcome is not 

favourable in the presence of a crossing 

vessel, severe hydronephrosis, poor renal 

function, long UPJ stricture or complete 

obliteration and severe periureteral fibrosis. 

These procedures are also associated with 

significant risk of hemorrhage, many cases 

requiring blood transfusion and sometimes 

postoperative embolization or nephrectomy 

7,8,9 . 

Laparoscopic pyeloplasty which was first 

reported by Schuessler et al became a 

minimally invasive technique having equal 

success rate as that of open surgery . 

Laparoscopic pyeloplasty can be performed 

by transperitoneal or retroperitoneal approach. 

We have performed laparoscopic pyeloplasty 

by both transperitoneal and retroperitoneal 

approaches. Both approaches has pros and 

cons but we preferred transperitoneal 

approach as it allows more working space 

which favour easy dissection and suturing . 

However , others recommend extraperitoneal 

approach as they do not find the smaller 

operating space hindering the dissection and 

anastomosis and also decreased risk of 

intraperitoneal organ damage, decreased post 

operative ileus and absence of contaminating 

the peritoneal cavity with blood, urine or 

carbonic acid 3,10 . Laparoscopic pyeloplasty 

has all the good quality of minimally invasive 

procedure like decreased length of hospital 

stay, decreased post operative pain, less 

analgesic requirement and faster recovery 

while it has comparable funtional results with 

open pyeloplasty. However , laparoscopic 

pyeloplasty require greater laparoscopic skills 

for reconstructive surgery involving 

intracorporeal suturing techniques with a 

steep learning curve which limited this 

procedure to become widely practiced 11,12,13 . 

With the advent of robot, which provides ease 

of intracorporeal suturing and shorter learning 

curve, robotic assisted laparoscopic 

pyeloplasty is becoming another minimally 

invasive technique for the treatment of UPJ 

obstruction. 

Anderson Hyne’s dismembered pyeloplasty 

was the commonest procedure performed 

and was preferred for patients with crossing 

vessel, bulky pelvis requiring subtraction 

pyeloplasty and in patients with poor renal 

function. Fenger pyeloplasty was performed 

if there was only a short stenotic ureteropelvic 

segment and the renal pelvis was not baggy. 

Foley Y-V pyeloplasty was done if the renal 

pelvis did not require reduction and ureter was 

inserted high into the renal pelvis .Scardino 

prince vertical flap pyeloplasty was performed 



in two cases of open pyeloplasty ,both cases 

having long obstructed UPJ segment . 

The mean operation time of 145 minutes in 

laparoscopic pyeloplasty was very much 

longer than in the open pyeloplasty group but 

is comparable to other series of laparoscopic 

pyeloplasty. The mean blood loss were 

comparable in both the groups and the mean 

blood loss in the laparoscopy group is 

comparable to other studies . In our study , 

there was not much difference in the mean 

length of hospital stay though it was less in 

the laparoscopy pyeloplasty group .The mean 

hospital stay of approximately 5. 8 days in the 

laparoscopy group is also longer in 

comparison with other series of laparoscopic 

pyeloplasty, this is because of two patients in 

this group , one patient who was converted to 

open surgery and got wound infection in the 

post operative period with a hospital stay of 

10 days. Another patient who got misplaced 

DJ stent , complicated with post operative 

fever, prolong drainage ,jaundice and 

abdominal pain with post operative hospital 

References: 

1. O’Reilly P H , Brooman P J , Mak S et al. 

The long-term results of Anderson-Hynes 

pyeloplasty . BJU Int 2001;87: 287- 289 . 

2. Schuessler W W, Grune MT, Tecuanhuey 

L V and Preminger G M. Laparoscopic 

dismembered pyeloplasty. J Urol 

1993;150: 1795-1799. 

3. Moon DA, El-Shazly MA, Chang CM, 

Gianduzzo TR, Eden CG. Laparoscopic 

pyeloplasty: evolution of a new gold 

standard. Urology 2006;67: 932-6. 

4. Klinger HC,Remzi M, Janetschek G et al. 

Comparison of open versus laparoscopic 

pyeloplasty technique in treatment of 

uretero-pelvic junction obstruction . Eur 

Urol 2003; 44: 340-345 

5. Brooks JD, Kavoussi LR, Preminger GM 

et al. Comparison of open and 

endourologic approaches to the 

obstructed uretero pelvic junction. 

Urology 1995; 45: 791-795. 

6. Motola JA, Badlani GH and Smith AD. 

Results of 212 consecutive 

endopyelotomies : an 8-year follow up. J 

Urol 1993;149: 453-456. 

7. Nadler B, Rao GS, Pearl MS et al. 

stay of 20 days.Moreover our patients prefer 

to get discharged from the hospital when they 

have recuperated fully and perurethral catheter 

and drain is removed .The mean analgesic 

requirement was less in the laparoscopic 

pyeloplasty group which is in consistence with 

other studies 4,5 .We are not performing 

statistical analysis of our results because of 

the small size of the study groups , multiple 

number of surgeons have performed the 

operations in both the groups and majority of 

the patients were lost to follow up at 1 year . 

Conclusion: Laparoscopic pyelpoplasty 

requires skilled intracorporeal suturing and it 

takes longer time to perform. But laparoscopic 

pyeloplasty has the advantage of minimally 

invasive procedure havingadvantages of less 

pain, less amount of analgesic required, 

shorter period of hospital stay, faster recovery 

and better cosmesis over open pyeloplasty. 

Short term functional results also shows that 

laparoscopic pyeloplasty is equally efficacious 

as open pyeloplasty. 

Acucise endopyelotomy: assessment of 

long-term durability. J Urol 1996;156: 

1094-1098. 

8. Van Cangh PJ. Wilmart JF, Opsomer RJ 

et al. Long-term results and late 

recurrence after endouretero pyelotomy: 

a critical analysis of prognostic factors. 

J Urol 1994;151: 934-937. 

9. Van Cangh PJ, Nesa S. Endopyelotomy. 

prognostic factors and patient selection. 

Urol Clin N Am 1998; 25 : 281 

10. Ben Slama M R, Salomon L, Hoznek A, 

et al. Extraperitoneal laparoscopic repair 

of uretero pelvic junction obstruction: 

initial experience in 15 Cases. Urology 

2000;56: 45-48. 

11. Eden CG, Cahill D, Allen JD. Laparoscopic 

dismembered pyeloplasty: 50 

consecutive cases. BJU Int 2001; 88: 

526-81. 

12. Jarett TW, Chan DY, Charambura TC, 

Fugita O, Kavoussi LR. Laparoscopic 

pyeloplasty the first 100 cases. J Urol 

2002;167: 1253-6. 

13. Inagaki T, Rha K H, Ong AM et al. 

Laparoscopy pyeloplasty : current status. 

BJU Int 2005;95: 102-105. 


7


Acute kidney injury in HIV-positive patients 

1 

Devi PS, 2 Singh Lk S, 2 Dhanaraj Ch, 3 Shreeniwas S, 4 Singh S 

Abstract 

Objective : To study the incidence, spectrum, 

prognosis and outcome of clinical renal 

disease with special emphasis on acute 

kidney injury in patients with HIV infection. 

Methods: A protocol of study was prepared. 

All HIV patients of both genders regardless of 

age attending Antiretroviral treatment (ART) 

Centre and those admitted in the wards of the 

hospital (Sir Sunderlal Hospital, Varanasi, Uttar 

Pradesh, India) were subjected for screening 

of clinical renal disease. HIV-seropositive 

patients with clinical renal diseases were 

included and divided into two groups: (A) 

Asymptomatic patients without manifestations 

of renal diseases but found to have a 

significant renal involvement on screening 

and (B) Patients with symptomatic renal 

diseases. HIV-associated renal disease were 

diagnosed using the following criteria: 1) 

Positive HIV Serology, 2) CD4 T-Lymphocyte 

count, 3) Proteinuria / Haematuria, 4) Elevated 

serum creatinine and 5)Quantitative 

proteinuria (24 hours urinary protein or spot 

urine Protein/creatinine ratio). National AIDS 

Control Organisation (NACO) Guidelines of 

India, 2007 were followed for the diagnosis of 

1 

Assistant Professor 2 Associate professor, Regional 

Institute of Medical Sciences, Imphal; 3 Consultant 

Nephrologist, ARTEMIS Hospital, Gurgaon; 4 Lecturer, 

Department of Nephrology, Institute of Medical 

Sciences, Banaras Hindu University, Varanasi (India). 


Dr Loukrakpam Sharatchandra Singh, Associate 

Professor (Medicine), Regional Institute of Medical 

Sciences, Imphal – 795004 (India). 

e-mail: lkbhu@sify.com 

HIV-seropositivity. Results: 47 HIVseropositive 

patients were found to have 

clinical renal disease during the study period 

of August 2007 and July 2009. During the two 

years study period, there were 3545 patients 

of HIV-seropositive patients and only 1725 

patients (611 females and 1114 males) were 

enrolled for ART as they fulfilled NACO 

guidelines. 47 (1.33%) patients (44 males and 

3 females) were found to have clinical renal 

disease. Most of the patients (45/47) had AKI 

(pre-renal-15, acute tubular necrosis-27, 

interstitial nephritis-3). Proteinuria, serum 

creatinine and serum albumin were 0.935± 

0.985 gm/day, 5.28± 5.64 mg% and 2.92± 0.58 

respectively. Renal biopsy were done on 2 

indicated patients who showed 

granulomatous glomerulonephritis, and 

Tubulointerstitial nephritis in one patient each. 

CD4 count was in the range of 43- 

842(170.36± 157.75) cells/µL. 9 patients 

(1.7%) having HIV-related clinical renal disease 

died due to sepsis (5), tubercular meningitis 

(3) and hypovolemia (2). Peritoneal dialysis 

could be done in 6 patients. Conclusion: AKI 

mostly related to acute tubular necrosis was 

the most common HIV-related clinical renal 

disease. Evidence of non-specific glomerular 

disease with or without interstitial nephritis 

was observed in 2 patients. HIV-associated 

nephropathy well documented in western / 

African-American literatures was not observed 

in our study 

Key words: HIV Infection, Acute Kidney injury, 

Mortality, CD4. 



Introduction : As early as 1984, physicians 

in New York and Miami recognized kidney 

disease as rare but devastating complication 

of the acquired immunodeficiency syndrome 

(AIDS) 1 . The association between HIV-1 

infection and kidney disease was made in 

1984 and much has been learnt over the last 

25 years. Renal disorders are encountered at 

all stages of HIV infection, and range from fluid 

and electrolyte imbalances commonly seen 

in hospitalised HIV infected patients to HIVassociated 

nephropathy (HIVAN), which 

progresses to end stage renal disease 2 . Acute 

kidney injury is also common among patients 

with HIV/AIDS. The exact pathogenesis of 

renal disease in HIV-associated nephropathy 

is not known in spite of intense research in 

the field. However, it is proposed that HIVassociated 

kidney disease is due to direct 

kidney infection with HIV or from medications 

used to treat HIV and their resulting adverse 

effects 3 . There are a few Indian studies on 

HIV-associated renal disease 4 . Most of the 

studies are from African population 5 . 

The aim of our proposed work is to study the 

incidence, spectrum, prognosis and outcome 

of clinical renal disease with special emphasis 

on acute kidney injury in patients with HIV 

infection in the Indian setting. 

Material and Methods: All HIV- seropositive 

patients of both genders regardless of age 

attending ART Centre of Sir Sunderlal 

Hospital, Institute of Medical Sciences, 

Banaras Hindu University, Varanasi, India and 

those admitted in the wards of the hospital 

were subjected to screening for clinical renal 

disease. HIV positive patients with clinical 

renal disease during August 2007 and July 

2009 were included in this prospective study. 

HIV-infected patients were divided into two 

groups: 

(1) Asymptomatic patients without 

manifestations of renal disease but found to 

have a significant renal involvement on 

screening and 

(2) Patients with symptomatic renal 

disease. The following procedures or 

methods were utilized: 

A. Informed consent from all patients 

B. Ethical clearance from the ethical 

committee of the institute 

C. Criteria for HIV-positivity based on National 

AIDS Control Organisation (NACO) 

Guidelines of India. 

D. Criteria for HIV-associated clinical renal 

Disease: 

1) Asymptomatic group: Mild proteinuria, 

elevated serum creatinine, normal or 

decreased CD4 count 

2) Symptomatic group: Hypertension, 

proteinuria, haematuria, elevated serum 

creatinine, decreased CD4 count d


Results: The two years prospective study 

included 3545 HIV-seropositive patients who 

were referred to the ART centre for further 

evaluation. Of 3545 HIV-seropositive patients, 

1725 (1114 males, 611 females) patients were 

enrolled or ART drugs as they fulfilled the 

NACO guidelines of India for the treatment of 

AIDS. The clinical renal disease was noted in 

47/3545 (1.33%) patients. The majority of HIVseropositive 

patients with clinical renal 

disease were males (93.61%) (Table 1). 

Maximum number of patients were in the age 

LEGENDS 

Table 1 : Demography of patients (n=47). 

Parameter Number % 

Sex Male 

Female 44 93.61 

3 6.38 

Age 15-20 2 4.25 

21-30 12 25.53 

31-40 23 48.93 

41-50 8 17.02 

>50 2 4.25 

Table 5 : 24 hours Urinary Protein, CD4 count 

and Mortality (n=47). 

Table 6 :Serum creatinine, CD4 count and 

Mortality (n=47). 

Table 2 : Spectrum of clinical renal disease in 

HIV-serpositive patients (n=47). 

Parameter Number % 

AKI 

Pre-renal 15 31.91 

ATN 27 57.45 

AIN 3 6.38 

CKD stage IV 2 4.26 

Proteinuria > 0.5 gm/day 32 68.06 

Nephrotic syndrome 2 4.25 

Table 3 : Causes of AKI (45/47). 

Cause Number % 

Hypovolemia 2 4.44 

Sepsis 4 8.89 

Urosepsis 3 6.67 

Drug induced 3 6.67 

*Mixed causes 33 82.23 

*Dehydration, drug induced, bleeding, etc. 

Table 4 : Outcome of AKI (n=45). 

Cause 

No. of patient (s) Percentage Status 

AKI of various causes 36 80 Alive 

Sepsis 4 8.89 Expired 

Tubercular meningitis 3 6.67 Expired 

Hypovolemia 2 4.44 Expired 

group of 31 to 40 years (48.9%) and the age 

of patients ranged between 16 and 58 

(36.34±9.33) years. 28/47(59.57%) were 

sexually active males having the occupation 

of driver. 44 patients were married and 3 were 

unmarried. Most of the patients were addicted 

to alcohol (31), smoking (29) and ganja/ 

bhang (16). 

Anemia (100%), weight loss (100%), oral 

candidiasis (61.70%), fever (68.08%), 

respiratory problems mostly due to pulmonary 

tuberculosis (23.79%) and decreased Urine 

output (27.65%) were the common 

manifestations in HIV-seropositive patients 

with clinical renal disease (Table not shown). 

Acute kidney injury (AKI) was the most 

common renal manifestation of HIVseropositive 

patients. Acute tubular necrosis 

(57.45%) was the prominent intrinsic renal 

lesion of AKI in these patients (Table 2). AKI in 

HIV-serpositive patients had mixed causes 

(82.23%) like dehydration, drugs, and bleeding. 

Sepsis (15.56%) was the common factor 



associated with HIV-related AKI (Table 3 &4). 

Of 47 HIV-serpositive patients, all patients 

were anemic with the hemoglobin level of 

7.87±2.62 gm/dl. Proteinuria, serum creatinine 

and serum albumin in these patients were 

0.935 ± 0.985 gm/day, 5.28± 5.64 mg /dl and 

2.92± 0.58 gm/dl respectively. 

Proteinuria more than 0.5 gm/day was found 

in 68.08% of HIV-serpositive patients (n=47). 

24 hour urinary protein excretion in HIVseropositive 

patients was in the range of 500 

mg/day – 1 gm/day in 24 (51.1%) patients. 

Urinary protein excretion was in the range of 

300-500 mg/day in 11 (23.4%) of cases. 9 

patients (19.14%) of AKI died due to sepsis 

(4), tubercular meningitis (3) and hypovolemia 

(2). Thus 80% of HIV-seropositive patients with 

AKI showed full recovery of renal function 

(Table 4). 6 symptomatic patients with AKI 

were subjected to peritoneal dialysis due to 

severe acute renal failure. Low CD4 count 


hyperuricosuria from tumor lysis syndrome, 

and extrarenal obstruction, including 

retroperitoneal fibrosis, pelvic 

lymphadenopathy, bladder dysfunction, 

fungus balls, and nephrolithiasis which have 

been observed by various groups. 14 Despite 

an observed association between ART 

exposure and AKI, individual antiretroviral 

agents rarely are implicated. 15 

Age, baseline serum creatinine level, and 

history of hypertension or diabetes were not 

associated independently with AKI in 2 recent 

studies including a large number of 

ambulatory patients. 15 Prognosis in AKI varies 

with severity and etiology. Studies have shown 

higher mortality in patients with AKI secondary 

to ATN and hemodynamic instability, 9-10 with 

similar overall mortality rates in AIDS versus 

non-AIDS patients. 10 Nevertheless, AKI 

remains a strong predictor of mortality in the 

ART era. Among hospitalized patients in New 

York State, a documented diagnosis of AKI 

was independently associated with a nearly 

6-fold increase in mortality among HIV-infected 

patients. 11 Rao et al reported a high incidence 

of mortality (60%) in HIV-associated clinical 

renal disease 2 . However we have observed 

only 20% mortality in HIV-associated AKI in 

the study. Further studies are needed to 

determine if AKI is an independent predictor 

of mortality or rather a marker for greater 

systemic illness. The acute and chronic 

impact of various medications used in the HIVinfected 

patient, including ART and antibiotic 

medications, also should be investigated 

further to decrease toxicity. Future studies of 

AKI in HIV-infected patients should attempt to 

use standard definitions to allow for 

comparison across studies. 

Poor prognostic markers in patients of HIVassociated 

AKI are related to a low CD4 count 

< 200 cells/µl, low serum albumin, systolic 

blood pressure, HIV-RNA level < 10000 copies/ 

ml and higher serum creatinine level. 2 Lower 

CD4 nadir < 200 cells/µl was associated with 

AKI, whereas hepatitis C virus (HCV) coinfection 

and intravenous drug use were 

associated with the development of AKI after 

the first 3 months of HIV care. 15 

We have observed most of the mortality 

related to sepsis and lower CD4 count as also 

observed by others. Hypertension, which is 

estimated to be present in 12% to 21% of the 

HIV-infected population, is an independent risk 

factor for mortality in women beginning ART. 16 

Mortality rates for HIV-positive patients on 

dialysis were initially quite high, approaching 

nearly 70% in 1991 and subsequently 

decreasing to 24% by 2002. 17 In the CDC 

sponsored HIV Epidemiology Research Study 

(HERS), the presence of proteinuria and / or 

elevated serum creatinine levels was 

positively associated with an increased rate 

of death (adjusted hazard ratio, 2.5) as well 

as having renal causes of death recorded on 

death certificates (26% of the total deaths). 

We have observed all deaths (19.14%) due 

to HIV-associated AKI with or without AIDS 

defining illnesses. 

Proteinuria in HIV-infected patients is defined 

as spot urinary protein/ creatinine ratio level 

more than 200 mg/g as per Kidney Disease 

Outcome Quality Initiative (KDOQI) 

guidelines 1,2 . Even in patients with normal 

renal function, the presence of proteinuria 

mainly indicates early kidney disease. And the 

presence of hypertension in such patients is 

12-21%.We have also observed 91.5% of the 

patients having proteinuria more than 0.3 g/ 

day. However all the nine deaths related to 

HIV-related clinical renal disease had 

proteinuria in the range of 0.3 – 1.0 g/day. It 

indicates the acuity of the disease. In the 

western and African counterparts heavy 

proteinuria (nephrotic range proteinuria) were 

found to be associated with CKD or 

ESRD. 5,8,9,18 

High serum creatinine is an independent risk 

factor for advancement of renal disease and / 

or mortality in HIV-associated renal 

disease. 10,12 We have got the mean serum 

creatinine of 5. 28 mg/dl (range, 2.1-37.4 mg/ 

dl) and all the deaths were related to patients 

with serum creatinine level of more than 5 mg/ 

dl. In one study, the mean serum creatinine 

level at presentation was 4.2 mg/dL (range, 2 

- 15 mg/dL), and proteinuria levels were 

variable with a median level of 1.76 g/24h 

(range, 0-4.5 g/24 h). 19 

Renal biopsy in the HIV-infected patient is 

required to establish a diagnosis of intrinsic 



renal disease, including a variety of HIV-related 

glomerular diseases, non–HIV-related renal 

diseases, and medication nephrotoxicity. We 

have come across only 2 patients of biopsy 

proven granumatous glomerulonephritis (1) 

and Intersitial nephritis (1). Our patients 

(95.74%) predominantly had AKI. We also had 

not found cases of HIVAN and HIV-associated 

immune complex disease (HIVICK) 

which was reported by the western 

counterparts 18,20 

Hepatitis co-infection and other forms of liver 

disease also have been associated with AKI 

in hospitalized and ambulatory patients with 

HIV infection. 21 We have come across only 

one case of HBV infection in the HIVseropositive 

case. Hepatitis C virus (HCV) coinfection 

is common among HIV-infected 

patients. In our study, there was no HCV coinfection 

of patients with HIV-associated 

clinical renal disease. 

Conclusion: Acute kidney injury mostly related 

to intrinsic renal injury was the most common 

renal disease in our HIV-seropositive patients. 

Evidence of non-specific glomerular disease 

with or without interstitial nephritis was 

observed in 2 patients. 

References 

1. Wyatt CM. Kidney Disease in HIV 

Infection: Introduction. Seminars in 

Nephrology. 2008; 28(6):511-12. 

2. Ahuja TS, Borucki M, Funtanilla M, 

Shahinian V, Hollander M, Rajaraman S. 

Is the prevalence of HIV-associated 

nephropathy decreasing? Am J 

Nephrol.1999;19(6):655-9. 

3. Salifu MO. eMedicine – HIV Nephropathy. 

2007. Available from : 

http://www.emedicine.com/med/topic 

3203. 

4. Anuradha S, Chatterjee A, Bajaj J, Singh 

NP, Agarwal SK, Kaur R. Trichosporon 

beigelli peritonitis in a HIV-positive patient 

on continuous ambulatory peritoneal 

dialysis. J Assoc Physicians 

India.2000;48(10):1022-4. 

5. Wools-Kaloustian K, Gupta SK, Muloma 

E, Willis O or, Sidle J, Aubrey RW,et al. 

Renal disease in an antiretroviral-naïve 

HIV infected outpatient population in 

Western Kenya. Nephrol Dialysis 

Transplantation. 2007;22(8):2208-12. 

6. Hilton R. Acute renal failure. BMJ. 

2006;333:786-90. 

7. Franceschini N, Napravnik S, Eron JJJ, 

Szczech LA, Finn WF. Incidence and 

etiology of acute renal failure among 

ambulatory HIV-infected patients. Kidney 

Int.2005;67:1526-31. 

8. Nochy D, Glotz D, Dosquet P, et al. Renal 

disease associated with HIV infection: a 

multicentric study of 60 patients from 

Paris hospitals. Nephrol Dial Transplant. 

1993;8:11-9. 

9. Valeri A, Neusy AJ. Acute and chronic 

renal disease in hospitalized AIDS 

patients. Clin Nephrol.1991; 35:110-18. 

10. Peraldi MN, Maslo C, Akposso K, 

Mougenot B, RondeauE, Sraer JD. Acute 

renal failure in the course of HIV infection: 

a single-institution retrospective study of 

ninety-two patients and sixty renal 

biopsies. Nephrol Dial Transplant. 

1999;14:1578-85. 

11. Wyatt CM, Arons RR, Klotman PE, 

Klotman ME. Acute renal failure in 

hospitalized patients with HIV: risk factors 

and impact on in-hospital mortality. 

AIDS.2006;20:561-5. 

12. Rao TK, Friedman EA. Outcome of 

severe acute renal failure in patients with 

acquired immunodeficiency syndrome. 

Am J Kidney Dis. 1995;25:390-8. 

13. Rastegar D, Claiborne C, Fleisher A, 

Matsumoto A. A patient with primary 


13


human immunodeficiency virus infection 

who presented with acute 

rhabdomyolysis. Clin Infect Dis. 

2001;32:502-4. 

14. Kalim S, Szczech LA., Wyatt CM. Acute 

Kidney Injury in HIV-Infected Patients. 

Seminars in Nephrology.2008;28(6) : 

556-62. 

15. Roe J, Campbell LJ, Ibrahim F, Hendry 

BM, Post FA. HIV care and the incidence 

of acute renal failure. Clin Infect Dis. 

2008;47:242-9. 

16. U.S. Renal Data System. USRDS 2007 

Annual data report: atlas of chronic kidney 

disease and end-stage renal disease in 

the United States. 2007. Available from: 

http://www.usrds.org/ 

17. Carter JT, Melcher ML, Carlson LL, 

Roland ME, Stock PG. Thymoglobulinassociated 

Cd4 T-cell depletion and 

infection risk in HIV-infected renal 

transplant recipients. Am J Transplant. 

2006;6:753-60. 

18. Agati VD, Suh JI, Carbone L, Cheng JT, 

Appel G. Pathology of HIV-associated 

nephropathy: A detailed morphologic and 

comparative study. Kidney Int 

1989;35:1358-70. 

19. Briggs WA, Tanawattanacharoen S, Choi 

MJ, et al. Clinicopathologic correlates of 

prednisone treatment of human 

immunodeficiency virus-associated 

nephropathy. Am J Kidney Dis. 

1996;28:618-21. 

20. Szczech LA, Anderson A, Ramers C, et 

al. The uncertain significance of antiglomerular 

basement membrane antibody 

among HIV-infected persons with kidney 

disease. Am J Kidney Dis. 2006;48:E55- 

9. 

21. Boccia RV, Gelmann EP, Baker CC, Marti 

G, Longo DL. A hemolytic-uremic 

syndrome with the acquired 

immunodeficiency syndrome. Ann Intern 

Med. 1984; 101:716-7. 



Clinical profile of chronic liver disease with reference to hepatocellular 

carcinoma in RIMS 

1 

N. Biplap, 2 Th. Bhimo, 1 Th. Suraj, 3 Th. Brojendro, 4 Lalbiakdiki 

Abstract: 

Objective: To study the clinical profile of 

chronic liver disease (CLD) with reference to 

hepatocellular carcinoma (HCC). Methods: 

The study was conducted on one hundred and 

thirty-two (132) CLD cases at Regional 

Institute of Medical Sciences (RIMS), Imphal. 

Routine investigations including hepatitis B 

surface antigen (HBsAg), hepatitis C antibody 

(HCV), and Ultrasound (USG) upper abdomen 

were done. Aspiration cytology was done for 

confirmation of HCC localized by USG, CT or 

MRI. Results: 20 (15.16%) CLD cases had 

HCC. Male to female ratio was 3:1. The 

maximum number of patients with CLD was 

found in the age group of 45-54 years and 

most of them were from Imphal west. The 

commonest risk factors associated with CLD 

are alcohol 67(50.75%), chronic HCV 61 

(46.21%) and HIV 31 (23.41%). There were 

20 cases of HCC (15.15%) including 9(45%) 

HCV associated HCC. These nine HCC 

cases had HIV-HCV (2 cases), HIV-HBV-HCV 

(1 case) as co-infection and chronic HCV with 

alcoholism (6 cases). Conclusion: The 

commonest risk factors for CLD associated 

with HCC are alcohol, HCV and co-infection 

with HBV, HIV. Routine screening of HCV, HBV 

and HIV must be done in CLD cases. 

Keywords: Chronic liver disease, 

Hepatocellular Carcinoma (HCC). 

1. Assoc. Prof. 2. Prof. 3. Asst. Prof. 4. PGT, Dept. of 

Medicine, RIMS Imphal 


Dr. N. Biplap, Assoc. Prof., Dept. of Medicine, RIMS 

Introduction: Hepatocellular Carcinoma 

(HCC) is among the commonest malignancies 

in the world, ranking the third most frequent 

cause of cancer mortality. It is up to 4 times 

more common in males than in women and 

usually arises in a cirrhotic liver. 1 The most 

clearly established risk factors for HCC are 

liver cirrhosis, chronic infection with hepatitis 

B and/or C virus, aflatoxin exposure, male 

sex, alcohol drinking, and cigarette smoking. 2 

A typical interval between HCV-associated 

transfusion and subsequent HCC is ~30 

years. HCV-associated HCC patients tend to 

have more frequent and advanced cirrhosis, 

but in HBV-associated HCC, only half the 

patients have cirrhosis; the remainders have 

chronic active hepatitis. 3 There are about 170 

million Hepatitis C Virus (HCV) infected and 

about 350 million hepatitis B virus (HBV) 

infected persons in the world, both of which 

are transmitted through parenteral route. 4,5 

There are about 33.2 million Human 

immunodeficiency virus (HIV) infected 

persons in the world, transmission of which 

is the same as HBV and HCV. 6 

HCC have been reported as one of the fatal 

complications of both hepatitis B and C. There 

are variations in the proportion and prevalence 

of these factors in association with and 

causation of HCC in different regions. There 

is so far no study in this part of the country 

about HCC and the associated risk factors. 

Therefore the present study was taken up to 

establish the clinical profile of HCC in chronic 

liver disease and its association with risk 

factors like alcohol, HBV, HCV and 

co-infection of both HBV and HCV. 


15


Materials and Methods: The study was 

carried out in 132 patients of CLD with or 

without HCC attending Medicine OPD in 

collaboration with Departments of 

Radiotherapy and Radiodiagnosis, Regional 

Institute of Medical Sciences, Imphal during 

September 2008 to August 2010. It is a cross 

sectional study. Patients of known underlying 

malignancy, un-cooperative and unwilling 

subjects were excluded. 

Informed written consent was taken for each 

case. Detail clinical examination was carried 

out for each case. Routine investigations 

including complete haemogram, urine routine 

examination, kidney function test, liver function 

test, prothrombin time, random blood sugar, 

hepatitis B surface antigen (HBsAg), 

HBeAntigen and HCV antibody were done. 

HBV and HCV were confirmed by PCR at 

Roche Lab, Mumbai. Computed Tomography 

(CT) or Magnetic resonance Imaging (MRI) 

was done when USG report and serum AFP 

level are suggestive of HCC. Ultrasound/CT 

guided aspiration cytology was done for 

confirmation of HCC. 

RESULTS AND OBSERVATIONS 

A total of 132 CLD were enrolled in the study, 

out of which 20 (15.16%) have HCC and 112 

(84.84%) were without HCC (p = 0.24). Of the 

112 CLD without HCC 83 (74.1%) were males 

and 29(25.9%) were females; of the 20 

subjects with HCC, 17 (85%) were males and 

3(15%) females (p = 0.43) as shown 

in Table 1. 

Table1.Profile of chronic liver disease 

Profile Male Female Total 

(N=100) (N=32) (N=132) 

CLD without HCC 83(83%) 29 (90.62%) 112 (84.84%) 

CLD with HCC 17(17%) 3 (9.38%) 20 (15.16%) 

The age-wise distribution of CLD with and 

without HCC is shown in table 2 and was 

found to be maximum in the age group 45-54 

years. The ages of the 20 HCC (15.15%) were 

all above 35 years. The maximum cases were 

from Imphal west which is also most thickly 

populated. 

Table 2. Age distribution: 

Age Group CLD without HCC CLD with HCC Total CLD 

64 yrs 7 (6.25%) 5 (25%) 12 

Total 112 (100%) 20 (100%) 132 

Of the 132 chronic liver disease subjects, 

69(52 presented with abdominal distension, 

49 with fever and 43 with jaundice. 21 had 

generalised weakness, 12 pain abdomen, 10 

upper GI bleeding, 4 hepatic encephalopathy 

and 2 with pulmonary tuberculosis. 18 had 

palpable hepatomegaly. 

The associated risk factors among the 132 

CLD were alcoholism (67 cases ie 50.75%), 

HCV (61 cases ie 46.21%) and HBV (11 ie 

8.33%). Twenty-six of the 67 chronic ALD were 

associated with HIV, chronic HCV, chronic 

HBV or combination of these. Of the 61 chronic 

HCV, 37(60.65%) were HCV mono-infection 

and the other 24 (39.35%) chronic HCV were 

associated with other risk factors like ALD (7 

cases), HIV (13 cases), HBV (3 cases) and 

HIV-ALD (1case). 

There were 20 cases of HCC (15.15%) 

amongst the 132 CLD cases. 9 of 61(14.75%) 

Graph showing risk factors of chronic liver 

disease and HCC 

chronic HCV and 3 of 11 (27.27%) chronic 

HBV were found to have HCC. 9 HCV 

associated HCC were associated with risk 



factors HIV (2 cases), HBV-HIV (1 case) and 

chronic alcoholism (6 cases). ALD is the 

predominant risk factor in all cases of CLD 

and HCV is the predominant risk factor 

amongst HCC (p = 0.04). Four (4) of 67 

chronic alcoholic cases (5.97%) were 

associated with HCC. The other associated 

risk factors with chronic alcoholism were 

chronic smoking (46%), multiple sexual 

partner (36%), and occasional sexual 

exposure (20%). 

Discussion: The present study was carried 

out in 132 patients with chronic liver disease 

who were admitted in medicine ward and those 

attending Medicine outpatient Department 

(OPD) and Radiotherapy OPD of Regional 

Institute of Medical Sciences, Lamphelpat 

from September 2008 to August 2010. 

Out of the total 132 patients, 100 (75.75%) 

were males and 32 (24.25%) were females, 

male to female ratio being 3:1. Khan et al 

found similar male:female ratio of hepatitis B 

and hepatitis C (73:27) in Hazara, Pakistan. 7,8 

In a study on precipitating factors of 

encephalopathy in chronic liver disease, Malik 

et al found that males comprises 64% cases 

of CLD. 9 In the analysis of patients who died 

with cirrhosis by Johnson et.al, 24% patients 

had developed hepatocellular carcinoma. 

Those patients with HCC showed a striking 

male preponderance (11:1). 10 Male dominance 

of chronic liver disease may be attributable to 

more common practice of alcohol drinking and 

substance abuse among males. 

The maximum numbers of patients with CLD 

with and without HCC were found in the age 

group of 45-54 years comprising of 38 

(33.93%) and 6(30%) patients each. This is 

more or less in accordance with the findings 

of Malik SH et al where chronic liver disease 

is most common among the age group 40-49 

followed by 50-59 years. 9 Bell et al also 

reported that age group of 45-54 years 

comprises maximum patients in their study 

of epidemiology of chronic liver disease in US 

population. 11 

The most commonly associated risk factor 

for CLD were ALD (67 cases i.e. 50.75%), 

Chronic HCV (61 cases i.e. 46.21%) and HIV 

(31 cases i.e. 23.48%). Twenty-six (26) of the 

67 chronic ALD cases were found to be 

associated with HIV, chronic HCV, chronic 

HBV or combination of these infections thereby 

showing that alcohol is one of the most 

common risk behaviors in the transmission 

of these infections. The findings of the present 

study are almost similar to those of others 

found in the literature. Garcia et al conducted 

a retrospective study among veterans in 

Puerto Rico and concluded that Alcoholic liver 

disease is the principal underlying liver 

disease, closely followed by HCV infection 

among 114 patients with biopsy proven HCC. 12 

Similarly, In France, ethanol is still the leading 

cause of cirrhosis and was responsible for 

60% of all HCC causes during the last 

decade. 13 

Chronic HCV is the second commonest factor 

(46.21%) associated with CLD. Of the 61 

chronic HCV, 37(60.65%) were only HCV 

infection with various features of chronic liver 

diseases like cirrhosis and portal hypertension. 

The other 24 (39.35%) cases of chronic HCV 

were associated with other risk factors like 

ALD (7 cases), HIV (13 cases) HBV-HIV (3 

cases) and HIV-ALD (1case). In a study 

conducted on 2,353 newly diagnosed CLD by 

Bell et al, Hepatitis C, either alone or in 

combination with ALD, accounted for twothirds 

of the cases. Other etiologies included 

nonalcoholic fatty liver disease (NAFLD), ALD, 

and hepatitis B. 11 In a study conducted by 

Laraba et al HCV infection was present in 

5.6% of patients with Chronic hepatitis and 

12.1% of patients with Liver cirrhosis. 14 A study 

by Lesi et al in Lagos, South-Western Nigeria 

found a HCV infection rate of 12.2% in patients 

with CLD. 15 Furthermore, Shehu in his study 

in Jos, North-Central Nigeria found that 11.8% 

of their patients with CLD had evidence of 

HCV infection. 16 The findings of these studies 

are much lower than that of the present study. 

In some countries, more than 10% of HCC 

cases were coinfected with both HBV and 

HCV viruses, thus hampering the attribution 

of a fraction of HCC cases to HBV or HCV. 17 

Coinfection with HIV is a frequent occurrence 

because of shared routes of transmission. A 

recent study of HCC in HIV-HCV coinfected 

patients indicated rapid development of HCC 

in these patients. 18 The combination of 


17


associated risk factors like HIV-HCV and HIV- 

HBV-HCV over and above alcoholic liver 

disease is an unique finding of this Northeastern 

state of India. 

There were 20 cases of HCC (15.15%) 

amongst the 132 CLD cases and 9 of 

61(14.75%) chronic HCV. Out of the 20 HCC 

cases, 9 were associated with HCV (45%). 

Other associated risk factors found in these 

9 HCC cases were HIV-HCV (2 cases), HCV- 

HBV-HIV (1 case) and HCV cirrhosis with 

chronic alcoholic (6 cases). Other studies by 

Olubuyide et al in Ibadan, Kirk et al in West 

Africa and Kew in his study among blacks in 

Southern Africa found HCV infection in 

18.7%,19%, 13.2% and 19.5% of their 

patients with HCC respectively. 19,20,21 These 

studies show lower percentage of HCV 

associated HCC cases than the present 

study. However, Chen in his study among 

natives in Taiwan, found that 70-80% of his 

patients with HCC had evidence of HCV 

infection. 22 Similarly, Tanaka et al found that 

78% of Japanese patients with HCC had 

evidence of HCV infection. 23 The higher 

prevalence of HCV associated HCC (45%) in 

the present study may be because of high 

prevalence of IDU and sexually transmitted 

HIV which shares similar route of 

transmission. 

Three (3) of the 11 cases (27.27%) of chronic 

HBV was found to be associated with HCC. 

In a prospective study conducted by Yang HI 

et al, the relative risk of HCC was 9.6 among 

men who were positive for HBsAg alone and 

60.2 among those who were positive for both 

HBsAg and HBeAg, as compared with men 

who were negative for both. 24 In the present 

study, 15% of the total HCC cases were 

associated with chronic HBV which include 

both HBeAg positive as well as negative 

cases. In Manipur AIDS Control Organisation 

report also, HBV coinfection with HIV is much 

lower than that of HCV though the real cause 

is not known so far. 

Four (4) of 67 chronic alcoholic cases (5.97%) 

were associated with HCC. Associated risk 

factors with chronic alcoholism were chronic 

smoking (46%), multiple sexual partner (36%), 

and occasional sexual relational relationship 

(20%) 

Presence of 31(23.48%) cases of HIV, HIV- 

HCV, HIV-HBV-HCV among 132 cases of CLD 

shows that there are multiple infections 

among CLD with or without HCC which can 

be an eye opener for the health care workers 

and the importance of prevention of these viral 

infections. Thus routine screening of HIV, HBV 

and HCV are important while managing CLD 

cases. The high prevalence of HCC amongst 

chronic HCV calls for the need of HCC 

screening among chronic HCV patients with 

nodular liver. 

Conclusion: The present study shows that 

the commonest risk factors for CLD are 

chronic alcoholism, (50.75%) and chronic 

HCV (46.21%). There were 20 (15.16%) cases 

of HCC. The most commonly associated risk 

factors for HCC are Chronic HCV (45%) with 

or without co-infection, chronic alcoholism 

(30%), etc. 

The limitations of the present study are small 

sample size, unvailability of facilities for HBV/ 

HCV genotyping and viral load and liver biopsy. 

A larger study with adequate sample size is 

needed to give us more insight about the 

clinical profile of Chronic liver disease with 

reference to hepatocellular Carcinoma in 

Manipur. 

Reference: 

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SD, Liu CJ. Familial Risk of 

Hepatocellular Carcinoma among 

Chronic Hepatitis B Carriers and Their 

Relatives. J natl cancer Inst 2000 Jul 19; 

92(14):1159. 

2. Sherlock S, Dooley J. Hepatic 

transplantation. In: Sherlock S, Dooley 

J, editors. Diseases of the liver and biliary 

system. 11 th ed. London: Blackwell 

Science; 2002. p. 657-76. 

3. Carr BI. Tumors of the biliary tree. In: 

Fauci AS, Kasper DL, Longo DL, 

Braunwald E, Hauser SL, Jameson JL, 

editors. Harrison’s principles of internal 

medicine. 17 th ed. New York: McGraw 

Hill; 2008. p. 581-82. 



4. WHO media centre. Fact sheet N o 164. 

WHO Hepatitis C [online]. Revised 2000 

Oct [cited 2008]. Available from: 

URL:http://www.WHO .int /W HO 

Hepatitis C.html. 

5. Custer B, Sullivan SD, Hazlet TK, Iloeje 

U, Veenstra DL, Kowdley KV. Chronic 

hepatitis B from a Global perspective: 

Epidemiology and costs of illness. J clin 

Gastroenterol 2004 Nov/ Dec; 38(10) 

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6. Knott SB. WHO media centre. Global HIV 

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seropositivity among chronic liver 

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patients in hazera, Pakistan. J Ayub Med 

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19


An insight on HIV-1 discordant couples-A RIMS study 

1 

K. Felix Jebasingh, 2 Robinson Ningshen, 3 Th. Shanti Devi, 2 N. Biplab Singh , 4 S. Bhagyabati Devi, 

Abstract: 

Objective: To discuss the characteristics of 

the patients with Human Immunodeficiency 

Virus-1(HIV-1) infection, who has discordant 

partners and the postulated mechanism for 

their persistent HIV seronegativity from various 

literatures. Methods: We retrospectively 

analyzed HIV-1 discordant infected partners 

who were admitted in Medicine ward, Regional 

Institute of Medical Sciences (RIMS), Imphal, 

Manipur from 2005 to 2010. Results: Out of 

the 25 infected patients with negative partners 

22 were male and 3 were female. 3 patients 

were of HIV WHO stage III and others were of 

stage IV. The mean CD4 count of our patients 

is 119. 84% of the patients had infection 

through IDU. Only 4 patients had infection 

through heterosexual behavior. Conclusion: 

This retrospective study is to highlight that 

discordant partners do exist in our population. 

Through proper counseling and by advising 

safe sex, we can prevent HIV transmission to 

the non infected partners. 

Keywords: HIV; IDU-Intravenous Drug User; 

Discordant couples; CD4 count. 

Introduction: India is one of the hubs of HIV 

infection in this modernized world. HIV 

1. P.G. Student , 2. Associate Professor, 3. Senior 

Resident, 4. Professor, RIMS, Imphal, Manipur. 

Corresponding author: 

Dr.Robinson Ningshen, MBBS., MD (General 

Medicine), Associate Professor, Department of 

Medicine, Regional Institute of Medical Sciences, 

Imphal, Manipur. Phone No: 9612159017. E-Mail: 

dr.ningshen@yahoo.co.in 

infection is predominantly a sexually 

transmitted disease worldwide .The most 

common mode of infection, particularly in 

developing countries, is heterosexual 

transmission 1 . According to NACO, in 2008 

there are about 2.27 million people between 

15 and 49 years of age, affected by HIV 

infection in India. Compared to the African 

countries the number of HIV infected is less. 

The major route of transmission is different in 

different parts of India. In India states like 

Andhra Pradesh, Karnataka, Maharashtra, 

Manipur, Nagaland and Tamil Nadu have high 

HIV prevalence than the National prevalence. 

Manipur has the highest prevalence of HIV 

infection in the country. In 2008, the adult 

prevalence of HIV infection in India is 0.29% 

.This figure is much less, as compared to 

2002 which was 0.45%. Manipur with a 

population of 0.2 percentage of total Indian 

population has 8 percent of the total HIV 

infected people in India. As per the 2008 report 

the overall HIV prevalence among different 

High Risk Groups were Intravenous Drug 

Users- IDU (9.2%), Male having Sex with Male 

-MSM (7.3%), Female Sex workers-FSW 

(4.9%) and STD clinic attendees (2.5%) .Low 

prevalence is seen among ANC clinic 

attendees (0.49%). Heterosexual behavior is 

the main route of transmission (87.1%) as per 

NACO 2008. But IDU is the main mode of 

transmission in North Eastern parts of India 2 . 

The prevalence of HIV infection among the IDU 

was 17.9%, FSW was 13% and MSM in 

Manipur was 16.4% in 2007 3 . We 

retrospectively studied the case files of HIV 



discordant couples, admitted in the Medicine 

Department, Regional Institute of Medical 

sciences (RIMS), Imphal. Our aim is to 

discuss the characteristic features and the 

possible postulated mechanism behind the 

discordance from the available literatures. 

Materials and Methods: This is a 

retrospective study of HIV-1 infected patients 

who have discordant partners, who were 

admitted under Medicine Department, 

Regional Institute of Medical Sciences (RIMS), 

Imphal from 2005 to 2010. HIV patients were 

diagnosed as per the NACO guidelines. The 

patients were all legally married and living 

together for not less than 2 years and the HIV- 

1 seropositive status was known before the 

marriage and were practicing unsafe sex and 

had multiple issues. Seronegative partners 

were repeatedly negative for HIV antibody, 

tested every 3 months. 

Results: 25 HIV-1 infected patients, who had 

discordant partners, were admitted in 

Medicine Department, RIMS, Imphal. Out of 

25 patients, 22 were male and 3 were female. 

The infected male: infected female ratio was 

7.3:1. The mean CD4 count was 119. The 

mean age of our patients was 39.9 years. At 

presentation all the patients had at least one 

Acquired Immune Deficiency Syndrome 

(AIDS) defining opportunistic infection.84 % 

were IDU’s and remaining 16 % were 

heterosexuals. Of the 22 males, only one 

patient was a heterosexual and the remaining 

were IDU’s. The patients with IDU habits were 

addicted to illicit drugs for a period of more 

than 15-16 years. All the 3 females who had 

discordant husbands got infected through 

heterosexual behavior. Their children were 

negative for HIV infection. Out of 25 patients 

one patient had Hepatitis and other had 

Hepatitis C co-infection. Of the 25 patients 14 

had Koch’s infection, 3 had pneumocystis 

carinii pneumonia (PCP) or pneumocystis 

jiroveci pneumonia, 3 had cryptococcal 

meningitis, 2 had cerebral toxoplasmosis, 1 

had disseminated candidiasis, 1 had chronic 

intestinal isosporiasis, as opportunistic 

infections and 1 had Progressive multifocal 

leukoencephalopathy (PML) (Table-1).3 

patients were of stage 3 HIV WHO staging 

and remaining were of stage 4 4 . Because of 

the non-availability of the viral load estimation 

for HIV -1, none of our patients had viral load 

estimation done. It is well defined that low 

CD4+ counts are associated with high levels 

of plasma viremia 1 . Since the CD4 count of 

all our patients was low and of WHO stage III/ 

IV infection at presentation, their viral loads 

were presumed to be high. All the patients 

were on antiretroviral therapy (ART) and were 

advised to practice safe sex. 

Table: 1. Characteristics of the HIV Infected Partners 

PCP-Pneumocystis carinii, IDU-Intravenous Drug User. 

PML- Progressive multifocal leukoencephalopathy. 

Discussion: Humans demonstrate significant 

variability in their susceptibility to Human 

Immunodeficiency Virus type 1 (HIV-1) 

infection. There are three groups of people, 

one with infection and disease manifestation, 

second who are persistently seronegative 

even after unprotected sexual behavior and 

third , though HIV infected but without the 

disease progression. Such variable HIV 

infective patterns have indicated that natural 

resistance to HIV-1 infection might be the 

reason behind 5 . 

In Pune, a prospective study was conducted 

to study the profile of HIV discordant couples 

and the secondary transmission rate. The 

study conducted from September 2002 for a 

period of 26 months found 457 discordant 

couples 6 .Kumarasamy et al did a cross 

sectional study to compare the clinical and 


21


behavioral characteristics of HIV-infected 

South Indian patients in concordant and 

discordant heterosexual relationships. 839 

concordant patients were compared with 996 

discordant patients in his study. Concordant 

patients had significantly higher CD4 cell 

counts than discordant patients at the time of 

enrolling to care. Their study concluded that 

couple-based interventions in addition to 

proper provision for HAART will decrease the 

HIV transmission among discordant South 

Indian married couples. 7 

A study from Canada has postulated that a 

cumulative effect due to cellular immunity, viral 

characteristics, and co receptor integrity could 

be the reason behind the seronegativity results 

after studying 11 discordant couples. There 

is no single reason behind the resistance to 

HIV infection 8 . Immunoglobulin A (IgA) 

responses found in the cervico-vaginal fluids 

of sex workers in Thailand as well as in other 

discordant groups, suggests that local 

mucosal immune responses might be the 

reason behind the persistent seronegativity . It 

has been studied that purified IgA from HIV 

resistant sex workers have a neutralizing effect 

towards HIV isolates from different clades and 

inhibit HIV infection of susceptible cells in vitro. 

This provides further evidence that IgA may 

be an important part of the immune defense 

against HIV 9, 10 . In literature there is evidence 

of elevated levels of IgA, IgG and IgM which 

are believed to suppress HIV, in the 

cervicovaginal secretions of a cohort of HIVseronegative 

African sex workers, suggesting 

that the immune response may not be limited 

to just IgA (Belec et al.) 11 . 

It is postulated that cytotoxic T-lymphocytes 

(CTLs) might have a role in resistance to HIV 

infection although the resistance is believed 

to be dependent on persistent exposure to 

HIV. 12 This type of responses have been 

found in babies born to infected mothers, 

regular sexual partners of HIV-infected 

individuals, and sex workers with high levels 

of exposure to HIV. 13 Rowland-Jones et al in 

their work on sex workers in Nairobi who were 

HIV seronegative had discovered CTL 

responses targeting epitopes defined by HIV 

clade B. 14 A study in HIV seronegative Kenyan 

sex workers, found that HIV-specific CD8+ T 

cells in the genital mucosa of the sex workers, 

suggesting that CTL responses were 

protective against heterosexual transmission 

of HIV infection (Kaul et al). 15 Another study 

by the same author among a cohort of 

exposed-uninfected Kenyan sex workers, a 

subset who seroconvert for HIV infection were 

found to have had lapses in sex work. This 

apparent interruption in HIV exposure might 

have lead to loss of HIV-specific CD8+ 

responses, suggesting that constant or 

frequent exposure to HIV is needed to 

maintain a protective CTL response. 16 

A study among the Chinese males had shown 

that 30% of the persistently negative 

individuals have HIV-1 specific T cell immune 

responses. 17 Though various studies explains 

the evidence for CTL involvement in resistance 

to HIV infection there is no conclusive 

evidence, leaving the possibility that CTLs are 

surrogate markers of some other 

mechanism. Thomas et al in their study have 

confirmed the reduced expression of CCR5 

in HIV-1 resistance. This reduced expression 

of CCR5 could be the reason for the 

seronegativity. 18 A study among high risk 

individuals of Indian origin had concluded that 

single nucleotide polymorphism (SNP) in 

Stromal Derived factor (SDF-1); a ligand for 

CXCR4 could be a protective factor towards 

HIV infection. 19, 20 Another study by Sangok et 

al showed a high expression of CD26/DPPIV 

enzymes in exposed seronegative individuals. 

This opens a new dimension of CD26/DPPIV 

in protection against HIV infection in vivo. 21 

DPPIV enzymes are the enzymes which are 

implicated in the carbohydrate metabolism. 

Stanford et al in their study had observed a 

strong non-cytotoxic CD81-cell anti-HIV 

response in discordant persons suggesting 

that this might be a contributing factor for the 

reason towards the persistent negativity 

Though various postulates have been given 

for the persistent seronegativity or HIV 

resistance /susceptibility, we could not 

evaluate the reason for the discordance in our 

patients due to lack of resources. An insight 

towards the resistance or susceptibility to HIV- 

1 infection is important in the context of future 

treatment modalities and research towards 



the HIV vaccine. Counseling regarding the 

safe sex is a challenge for the treating 

physician in discordant couples. 

Conclusion: Through our study we would like 

to highlight that HIV discordance among 

couples is prevalent in our population. Though 

research had been done in high risk Indian 

population who are seronegative, we could 

not find any study for the discordant or 

persistent negativity for HIV-1 infection in the 

discordant partners in India. Though we have 

25 discordant couples the reason could not 

be evaluated due to non-availability of 

resources. Such couples should be advised 

to practice safe sex and should be given 

proper counseling. This kind of study will be a 

boost for HIV vaccine research in future. 

References: 

1) Fauci AS, Lane C.Human 

Immunodeficiency Virus Disease: AIDS and 

related Disorders. In: Fauci AS, Kasper 

DL, Longo DL, et al, eds. Harrison’s 

Principles of Internal Medicine. 17th ed. 

New York: McGraw-Hill, 2008: 1137-1204. 

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management of common opportunistic 

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5) Marmor M, Hertzmark K, Thomas SM, et 

al. Resistance to HIV infection. J Urban 

Health. 2006 Jan;83(1):5-17. 

6) Mehendale SM, Ghate MV, Kishore Kumar 

B, et al. Low HIV-1 incidence among 

married serodiscordant couples in Pune, 

India. J Acquir Immune Defic Syndr. 2006 

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7) Kumarasamy N, Venkatesh KK, Srikrishnan 

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86. Epub 2009 Sep 24. 

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immunodeficiency virus type 1 (HIV-1) 

transmission in HIV-1-discordant partners. 

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2000 Jun 29. 

9) Beyrer C, Artenstein AW, Rugpao S, et al. 

Epidemiologiv and biologic 

characterization of a cohort of human 

immunodeficiency virus type 1 highly 

exposed persistently seronegative female 

sex workers in Northern Thailand. J Infect 

Dis. 1999;179:59–67. 

10) Broliden K, Hinkula J, Devito C, et al. 

Functional HIV-1 specific IgA antibodies in 

HIV-1exposed, persistently IgG 

seronegative female sex workers. Immunol 

Lett. 2001;79:29–36. 

11) Belec L, Ghys PD, Hocini H, et al. 

Cervicovaginal secretory antibodies to 

human immunodeficiency virus type 1 (HIV- 

1) that block viral transcytosis through tight 

epithelial barriers in highly exposed HIV- 

1-seronegative African women. J Infect 

Dis.2001;184(11):1412–1422. 

12) Kaul R, Rowland-Jones SL, Kimani J, et 

al. New insights into HIV-1 specific cytotoxic 

T lymphocyte responses in exposed, 

persistently seronegative Kenyan sex 

workers. Immunol Lett. 2001;79(1–2):3–13. 

13) Rowland-Jones SL, Pinheiro S, Kaul R, et 

al. How important is the Fquality_ of the 

cytotoxic T lymphocyte (CTL) response in 

protection against HIV infection? Immunol 

Lett. 2001;79:15–20. 

14) Rowland-Jones S, Dong T, Fowke KR, et 

al. Cytotoxic T cell responses to multiple 

conserved HIV epitopes in HIV-resistant 

prostitutes in Nairobi. J Clin 

Invest.1998;102(9):1758–1765. 


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15) Kaul R, Plummer FA, Kimani J, et al. HIV- 

1-specif ic mucosal CD8+ lymphocyte 

responses in the cervix of HIV-1-resistant 

prostitutes in Nairobi. J 

Immunol.2000;164(3):1602–1611. 

16) Kaul R, Rowland-Jones SL, Kimani J, et 

al. Late seroconversion in HIV-resistant 

Nairobi prostitutes despite pre-existing 

HIV-specific CD8+ responses.[comment]. 

J Clin Invest.2001;107(3):341–349. 

17) Liu HW, Hong KX, Ma J, et al. Identification 

of HIV-1 specific T lymphocyte responses 

in highly exposed persistently 

seronegative Chinese. Chin Med J (Engl). 

2006 Oct 5;119(19):1616-21. 

18) Thomas SM, Tse DB, Ketner DS, et al. 

CCR5 expression and duration of high risk 

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SIGNR and SDF-1 in high risk seronegative 

and HIV-1 patients in Northern Asian 

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Preloading versus prophylactic intravenous ephedrine in the prevention of hypotension 

following subarachnoid block in patients undergoing caesarean section 

1 

N. Anita Devi 2 L. Chaoba Singh 3 Prof. L. Kameshwar Singh, 1 Th. Rupendra, 2 L. Eshori 

Abstract 

Objective: The primary objective of this study 

was to compare the efficacy of preloading with 

ringer lactate and prophylactic intravenous 

ephedrine in prevention of hypotension 

following subarachnoid block in patients 

undergoing caesarean section. Methods: 

One hundred parturient of ASA I &II undergoing 

caesarean section in RIMS hospital during the 

period of 2006- 2008 were enrolled for the 

study. They were randomly divided into two 

groups of fifty each. 

Group I (preloading) – patients were preloaded 

with ringer lactate at the dose of 20ml/kg, 30 

mins before the spinal anaesthesia 

Group II (ephedrine) – patients were given inj 

ephedrine 10 mg intravenously just before the 

induction of spinal anaesthesia . 

Heart rate, systolic blood pressure , peripheral 

oxygen saturation were recorded at baseline 

and thereafter every 2min interval for the first 

10min and than at every 5min till the end of 

the study. Results: Preloading with ringer 

lactate did not absolutely prevent hypotension 

and the incidence of hypotension was 44% in 

the preloading group and 32% in the 

ephedrine group. This finding was not 

significant statistically between the groups. 

Conclusion: Preloading with crystalloid 

administration was a safe procedure, its 

1. Assistant Professor 2. Registar. 3. Prof. and 

Head. Dept. of Anaesthesia RIMS 

Address for correspondence 

Prof. L. Kameshwar Singh, Prof. & Head, Dept. of 

Anaesthesiology RIMS Imphal. 

effectiveness in preventing hypotension in 

parturient undergoing caesarean section 

under spinal anaesthesia was questionable. 

And at the same time prophylactic ephedrine 

had limited efficiency for the prevention of 

hypotension. 

Key words: Hypotension, preloading, 

ephedrine, spinal anaesthesia 

Introduction: Spinal anesthesia is commonly 

used for caeserian section as it has got rapid 

onset, profound sensory and motor blockade 

and avoidance of side effects of general 

anaesthesia. But hypotesion complicates 

spinal anaesthesia in about 80% of the 

parturient and if left untreated it produces 

foetal acidosis and a poor neonatal outcome. 

Hypotension is universally treated with 

preloading with either crystalloid like ringer 

lactated at a dose of 10-30ml/kg body weight 

before induction of spinal anaesthesia or with 

colloids like gelatine and starch. However rapid 

infusion of fluid causes pulmonary oedema in 

patients with heart diseases, hypothermia or 

dilutional coagulopathy 1, 2 . There is increase 

used of vasopressors 3,4 like ephedrine, 

phenylephrine with no preloading or minimal 

loading. Of the available vasopressors, 

ephedrine is most commonly used. IM 

ephedrine has been described, but its efficacy 

has been inconsistent 5,6 , and its use may be 

associated with unacceptable hypertension, 

particularly if spinal anesthesia is 

unsuccessful 7 . As an alternative, IV ephedrine 

given immediately after the induction of spinal 

anesthesia has been described 8,9 .The present 

study was conducted to compare the 


25


effectiveness of preloading with ringer lactate 

to the vasopressor ephedrine in the 

management of parturient undergoing 

caesarean section under spinal anaesthesia. 

Material and method: After obtaining written 

informed consent and approval of the institute 

ethical committee, one hundred (100) 

parturient of ASA I and II undergoing caesarean 

section under spinal anaesthesia were 

enrolled for the study. Patients with 

cardiovascular or respiratory disorders, 

abnormal cardiac anatomy, hypertension, preeclampsia, 

diabetes, electrolyte imbalance, 

patients with haemoglobin concentration less 

than 10 gm%, weight more than 80 kg, fasting 

for less than 6 hours and those on medication 

which have direct cardiac effects such as beta 

blockers were excluded from the study. All the 

patients were premedicated with inj ranitidine 

50mg and ondensetron 4mg intravenously 45 

min before induction of spinal anaesthesia . 

Patients were randomly divided into two 

groups 

Group A- patients were preloaded with ringer 

lactate at the dose of 20ml/kg body weight 30 

min before spinal anaesthesia 

Group B– patients were given inj ephedrine 

10mg intravenously just before the induction 

of spinal anaesthesia 

Spinal anaesthesia was given in L34 space 

with 25G spinal needle with 2.2 ml of 0.5% inj 

bupivacaine in left lateral position. A wedge 

was placed under the right hip for left uterine 

displacement in patients undergoing 

caesarean section. Supplemental oxygen 2 

Lmin-1 was given through face mask. The 

level of loss to pinprick sensation was 

assessed and surgery was started when 

sensory loss of T6 was achieved. Heart rate, 

mean arterial pressure, peripheral oxygen 

saturation were recorded just before induction 

of spinal anaesthesia and thereafter every 2 

mins interval for the first 10 mins and than at 

every 5mins till the end of surgery. 

Hypotension was defined as a decrease of 

systolic blood pressure more than 30% of the 

baseline or less than 90 mmHg. During an 

episode of hypotension Inj ephedrine 5mg iv 

was given. The data were collected and 

analyzed. 

Results and observations 

Patient Characteristics : Mean age in years 

of the patients in ephedrine group and 

preloading group were 28.50± 2.72 and 28.76 

± 2.52 respectively. The weight ranges from 

66.50 ± 30 kg in ephedrine group to 66.40 ± 

3.20 kg in preloading group. The variation in 

age and weight between the two groups were 

statistically not significant. 

Figure I: The mean systolic blood pressure 

The mean systolic blood pressure between 

the groups was shown in figure I. There was 

a significant fall in the mean systolic blood 

pressure throughout the study period in both 

the groups, compared to the baseline values. 

In preloading group significant decrease was 

seen during 10 and 15 minutes of the study. 

Table 1: The incidence of hypotension 

Groups No of patients X 2 Df P- value 

with hypotension 

Ephedrine 16 (32%) 1.528 1 0.216 

Preloading 22 (44%) 

Table I showed the incidence of hypotension 

in the two groups. Hypotension was observed 

in 16 (32%) patients in ephedrine group and 

22 (44%) patients in preloading group. These 

finding was statistically insignificant with p 

value of 0.216. 



Figure 2: The mean heart rate 

The mean heart rate was more in the preloading 

group than the ephidrine group in every stage 

of the time period of the study as shown in Fig. 

2. This difference was statistically significant 

with p value of less than 0.5. 

Discussion: Rapid administration of 

crystalloid solutions to correct hypotension 

was first advocated by Greiss and Crandell in 

1965 but they showed that intravenous fluid 

only partly restored uterine blood flow in gravid 

uterus rendered hypotension by spinal 

anaesthesia and at the same time Jackson R 

et al 1 also concluded that volume preloading 

was not essential to prevent spinal induced 

hypotension in caesarean section. Large 

volume of fluid also decrease decreses 

oxygen carrying capacity and also increase 

the risk of pulmonary oedema in susceptible 

patients. 

Vasopressors such as ephedrine maintains 

the systemic vascular resistance. They 

reduces the need for an increase in cardiac 

output and directly reverses the physiological 

changes produced by the block. 

In the present study incidence of hypotension 

in the preloading group was 44% and 32%of 

the patients in the ephedrine group . The 

decrease in blood pressure was rapid in the 

first 10 min and thereafter it was gradual in 

the prealoding group whereas it was more 

gradual in the ephedrine group. Our findings 

were in aggrement with Rout CC et al 10 where 

they found hypotension in 43% of the patients 

in preloading group and 44% of the patients in 

the nonloading group. In our study, patients 

were given “rescue” ephedrine as soon as 

hypotension occurred, and the total dose of 

ephedrine given was similar among groups. 

Because this caused the blood pressure in 

hypotensive patients to return toward baseline, 

it is a confounding factor in the repeated 

measures analysis, with the tendency to 

reduce the likelihood of finding a difference 

between doses. This explains the 

convergence of systolic blood pressure 

measurements in the latter part of the 

recording period. 

Our finding of hypotension in 32% of the 

patients in ephedrine group was different from 

Marcel PV et al 11 where they found 

hypotension in 25%of the patients. These 

difference might be because of prehydration 

with 1000ml of crystalloids in all their cases 

and used of small-dose (bupivacaine 6.6mg) 

spinal anesthesia for cesarean delivery in their 

study. 

In our study we did not encounter any case of 

reactive hypertension which was different 

from Ngan Kee WD 12 . We used 10mg 

intravenous ephedrine .They found that 

incidence of hypotension was reduced to 35% 

in the patients who received ephedrine 30 mg 

compared with the control rate of 95%, this 

was at the expense of an increased incidence 

of hypertension, which occurred in 45% of the 

patients. They suggested that 30-mg 

intravenous ephedrine may not be suitable in 

some patients such as those with 

cardiovascular or cerebrovascular 

disease. 

Conclusion : Although preloading with 

crystalloid administration is a safe procedure, 

its effectiveness in preventing hypotension in 

parturient undergoing caesarean section 

under spinal anaesthesia is questionable. And 

at the same time prophylactic ephedrine has 

limited efficiency for the prevention of 

hypotension. Further study are required to 

determine the optimal doses/technique of 

prophylactic ephedrine administration and 

trials of other prophylactic vasopressors are 

warranted. 


27


References 

1. Jackson R, Reid JA, Thorburn J. Volume 

preloading is notessential to prevent 

spinalinduced hypotension at caesarean 

section. Br J Anaesth 1995; 75: 262-5. 

2. Turner RJ ,Gatt SP, Ramzan I , Daley M 

. Administration of crystalloid fluid preload 

does not prevent the decrease inarterial 

blood pressure after induction of 

anaesthesia with propofol and fentanyl. 

Br J Anaesth 1988;8 : 737-41. 

3. Lee A, Ngan Kee WD, Gin T. Prophylactic 

ephedrine prevents hypotension during 

spinal anesthesia for cesarean delivery 

but does not improve neonatal outcome: 

a quantitative systematic review. Can J 

Anaesth. 2002;49:588–59 

4. Bhattacharya D, Chowdhury M, Biswas 

B, Nitish G, Rudra A, Banarjee A. 

Comparison of an ephedrine infusion with 

crystalloid administration for prevention 

of hypotension during spinal anaesthesia 

for elective caesarean section. Indian J 

Anaesth 2001; 45(4): 290-3. 

5. Gutsche BB. Prophylactic ephedrine 

preceding spinal analgesia for cesarean 

section. Anesthesiology 1976;45:462–5. 

6. Webb AA, Shipton EA. Re-evaluation of 

im ephedrine as prophylaxis against 

hypotension associated with spinal 

anaesthesia for Caesarean section. Can 

J Anaesth 1998;45:367–9. 

7. Rout CC, Rocke DA, Brijball R, 

Koovarjee RV. Prophylactic intramuscular 

ephedrine prior to caesarean section. 

Anaesth Intensive Care 1992;20:448–52 

8. Chan WS, Irwin MG, Tong WN, Lam YH. 

Prevention of hypotension during spinal 

anaesthesia for Caesarean section: 

ephedrine infusion versus fluid preload. 

Anaesthesia 1997;52:896–913. 

9. King SW, Rosen MA. Prophylactic 

ephedrine and hypotension associated 

with spinal anesthesia for cesarean 

delivery. Int J Obstet Anesth 1998;7:18– 

22. 

10. Rout CC, Rocke DA, Levin J. A reevaluation 

of the role of crystalloid 

preload in the prevention of hypotension 

associated with spinal anesthesia for 

elective cesarean section. 

Anesthesiology 1993;79:262–9. 

11. Marcel PV, Hilde CC, Vincent HH, 

Mertens E, Hugo AA. Prevention of 

hypotension by a single 5-mg dose of 

ephedrine during small-dose spinal 

anesthesia in prehydrated caesarean 

delivery patients. Anesth Analg 

1999;90(2):241-2. 

12. Ngan Kee WD, Khaw KS, Lee BB, Lau 

TK, Gin T. A dose-response study of 

prophylactic intravenous ephedrine for 

the prevention of hypotension during 

spinal anesthesia for cesarean delivery. 

Anesth Analg. 2000;90:1390–5. 



The effect of intrathecal clonidine on hyperbaric bupivacaine for postoperative 

analgesia 

1 

L. Chaoba Singh, 2 N. Anita Devi, 2 N. Ratan Singh, 3 Laithangbam PKS, 4 Kh. Maniram Singh 

Abstract 

Objective: To evaluate the postoperative 

analgesic effect and associated complication 

of intrathecal clonidine as an adjuvant to inj 

0.5% hyperbaric bupivacaine in patients 

undergoing lower abdominal surgeries. 

Methods: 60 (sixty) patients of ASA I and II 

Grades, age between 20–60 years, 

undergoing lower abdominal surgery were 

included in the study. Patients with 

neurological deficits or diseases, bleeding 

disorders, psychiatric disorders, chronic pain, 

obvious skeletal deformities and those 

patients on antihypertensive medication were 

excluded. The patients were randomly divided 

into two groups of 30 (thirty) each. 

a. Group I patients received 0.5% hyperbaric 

bupivacaine 0.3mg/kg. 

b. Group II patients received 0.5% hyperbaric 

bupivacaine 0.3mg/kg and 1 µg/ kg body 

weight of preservative free inj.clonidine 

hydrochloride. 

The hemodynamic parameters such as heart 

rate, NIBP, ECG and SpO2 were monitored 

periodically. Patients were observed for the 

presence of side effects (dry mouth, 

dizziness, anxiety, restlessness pruritus, 

sedation, nausea, etc) 

Duration of analgesia was taken as the pain 

free post operative interval between the end 

1. Registrar 2. Asst Professor 3. Assoc Professor 

4. Professor, Dept of Anaesthesia, RIMS, Imphal 

Address of correspondence:- 

Prof. Kh. Maniram Singh, Dept. of Anaesthesiology, 

RIMS Imphal 

of injection and patient’s first analgesic 

request and rescue analgesia was provided 

by inj tramadol hydrochloride 100mg 

intravenously. Results: Duration of postoperative 

analgesia in the clonidine group 

(360.83 ± 50.489 min) was significantly longer 

than control group(190.43 ± 23.942 min). 

There was no significant complication of 

intrathecal clonidine during the study. 

Conclusion: It may be concluded that 

intrathecal clonidine at the dose of 1µg/kg 

significantly prolongs the post-operative pain 

free period without significant cardiovascular 

changes and side effects. 

Key words: Bupivacaine, clonidine, spinal 

anaesthesia, postoperative analgesia 

Introduction: Spinal anaesthesia with 

hyperbaric bupivacaine is commonly used for 

lower abdominal and lower limb surgeries. 

Search is on for the ideal adjuvant drugs which 

may be added to local anaesthetic agents to 

prolong the duration of the block and also to 

provide post operative analgesia. Even though 

opioids administered intrathecally can provide 

profound postoperative analgesia, there are 

disadvantages like nausea, vomiting, pruritus, 

urinary retention, respiratory depression, etc. 

The use of clonidine - an alpha 2 adrenergic 

receptor agonist, has been of considerable 

and sustained interest for the last two 

decades. It has been shown that clonidine 

administered in the epidural space or 

intrathecally has a substantial antinociceptive 

effect by its action on the α 2-receptor in the 

dorsal horn of the spinal cord 1 . Several authors 

had used high doses of intrathecal clonidine 


29


in the range of 75µg-450 µg but they were 

usually associated with bradycardia 2 , 

hypotension 2,3,4 , sedation 4 , dry mouth 4,5 , etc. 

The present study was conducted in the 

Department of Anaesthesiology, RIMS, Imphal, 

to evaluate the postoperative analgesic effect 

and associated complication of intrathecal 

clonidine as an adjuvant to hyperbaric 

bupivacaine in patients undergoing lower 

abdominal surgeries. 

Materials and methods: After obtaining 

approval by Institutional Ethical Committee and 

informed written consent, 60(sixty) patients 

of ASA I and II Grades 6 , age between 20 – 60 

years, undergoing lower abdominal surgery 

at RIMS, Imphal, were included in the study. 

Patients with neurological deficits or diseases, 

bleeding disorders, psychiatric disorders, 

chronic pain, obvious skeletal deformities and 

those patients on antihypertensive medication 

were excluded. All patients were advised to 

fast after 2200 hrs and administered diazepam 

orally (10 mg) and tab ranitidine 150mg the 

night before surgery. Baseline pulse rate and 

blood pressure were recorded. Preloading 

was done with inj Ringer’s lactate 15 ml per 

kg body weight about 15 minutes before the 

intended time of intrathecal drug 

administration. Patients were given spinal 

anaesthesia with one of the drugs prepared. 

The study solution was prepared by a person 

not involved in the study 

The patients were randomly divided into two 

groups of 30 (thirty) each. 

a. Group I (control group) patients received 

0.5% bupivacaine (heavy) 0.3mg/kg. 

b. Group II (clonidine group) patients received 

0.5% bupivacaine (heavy) 0.3mg/kg and 

1 µg/ kg body weight 7,8 of preservative 

free inj.clonidine hydrochloride. 

The hemodynamic parameters such as Heart 

rate, NIBP, ECG and SpO2 were monitored 

periodically and recorded at 2 minutes interval 

for the first 10 min and thereafter at 5min 

intervals until the end of surgery. Patients were 

observed for the presence of side effects (dry 

mouth, dizziness, anxiety, restlessness 

pruritus, sedation, nausea, etc) 

Intravenous fluid was administered in the form 

of Ringer’s lactate (RL) at the rate of 10ml 

per kg body weight per hour. A decrease in 

mean arterial pressure (MAP) of >20% from 

baseline was treated with rapid infusion of 500 

ml of RL and 3mg of injection mephentermine 

intravenously if there was no response to fluid 

administration. Bradycardia (heart rate< 60/ 

minute) was treated with intravenous atropine 

sulphate 0.3mg. 

All the patients were observed in the post 

anaesthesia recovery room and then in the 

ward for 24 hours. Duration of analgesia was 

taken as the pain free post operative interval 

between the end of injection and patient’s first 

analgesic request and rescue analgesia was 

provided by inj tramadol hydrochloride 100mg 

intravenously. 

Results and observation 

Table 1. Comparison of patient characteristics 

(Age and Weight) between groups 

Table 2. Comparison of patient characteristic 

(gender) between groups 

Sex Clonidine Group Control group Total 

Female 24 25 49 

Male 6 5 11 

Total 30 30 60 

2 = 0.111; d.f. =1; P = 0.739 

Table-1 shows the comparison of mean age 

and weight of patients between clonidine group 

and control group. It was observed from the 

table that those persons who belong to 

clonidine group had older age (35.20±12.947 

vs 34.40±10.981) as well as heavier 

(57.00±8.052 vs 56.47±7.655 ) than those of 

the control group. But it was statistically 

insignificant even at 5% probability level. 

As shown in Table -2 gender distribution of 

the study subjects between the two groups 

were almost similar (p=0.739). However, both 

the groups had higher number of female 

patients. 



Table 3. Comparison of Mean±SD of Duration 

of Surgery & Analgesia between groups 

Fig. 1: Shows comparison of Mean Heart Rate 

Fig. 1 highlights the difference of average HR 

between the groups. On an average the heart 

rate in clonidine group was lesser than that of 

its counterpart control group which was true 

in all the stages except at 2 nd minute but was 

not statistically significant (P>0.01). 

Fig.- 2: Shows comparison of mean SpO2 

There was a much fluctuated trend of mean 

peripheral oxygen saturation (SpO2) was 

witnessed when comparison was made 

between clonidine and control groups for each 

stage. However, insignificant value of ‘t’ for 

every stage confirmed that SpO2 for clonidine 

group was almost alike with the control group. 

Fig.-3: Shows comparison of Mean Arterial Pressure 

The mean arterial pressure was higher in the 

control group, in all the stages considered 

except at 6 th and 30 th minutes, than the 

corresponding value for clonidine group but 

statistically it was insignificant as shown in 

Figure 3. 

Parameter Clonidine group Control group t- 

value d.f. P- 

No. Mean± No. Mean± 

value 

cases SD (min) cases SD (min) 

Duration of 

Surgery 

(min) 

Duration of 

analgesia 

(min) 

30 44.83± 

13.55 

30 306.83± 

50.48 

30 43.67± 

10.822 

30 190.43± 

23.942 

0.368 58 0.714 

11.410 58 0.000 

Duration of post-operative analgesia in the 

clonidine group (306.83 ± 50.489 min) was 

significantly longer than control group(190.43 

± 23.942 min) even though duration of surgery 

(44.83 ± 13.55 vs 43.67± 10.82 min) was 

statistically not significant. The maximum 

dose of clonidine used was 65 µg. There was 

no significant complication of intrathecal 

clonidine during the study (Table 3). 

Discussion: Clonidine is a selective partial 

agonist for α2 adrenoreceptors. It is known 

to increase both sensory and motor block of 

local anaesthetics. The analgesic effect 

following its intrathecal administration is 

mediated spinally through activation of post 

synaptic α2 receptors in substantia 

gelatinosa of spinal cord 1 . The rationale behind 

intrathecal administration of clonidine is to 

achieve a high drug concentration in the 

vicinity of α2 adrenoreceptors in the spinal 

cord and it works by blocking the conduction 

of C and A delta fibres. 

In the present study, duration of analgesia in 

the clonidine group (306 ± 50 min) was 

significantly longer than the control group (190 

± 23 min). This finding was in agreement with 

the study by Kaabachi O et al 7 wherein 1 µg/ 

kg of clonidine was added to 15mg of 0.5% 

bupivacaine intrathecally in patients 

undergoing orthopedic surgery. They 

observed that clonidine prolonged the duration 

of both the sensory and motor block, and time 

to first rescue analgesia was longer (461+/- 

147 min) in clonidine group. 

Interestingly, Sethi BS et al 8 had also 

demonstrated that addition of clonidine to 

bupivacaine in the dose of 1 µg/kg significantly 

increases the duration of analgesia (614 min) 

following its placement in subarachnoid space 


31


as compared to bupivacaine alone, which is 

comparatively longer than that of the present 

study finding. However more sedation, 

change in the heart rate and mean arterial 

pressure were observed in their study than 

ours. 

When the analgesic effects of 150µg of 

intrathecal clonidine were compared with 

placebo (saline) in cesarean section under 

general anesthesia, Filos KS and co-workers 3 

observed that clonidine provided pain relief for 

7 +/- 2.2 hr vs. 3+/- 2.8 hr of saline. They also 

investigated response to 150µg, 300µg, and 

450µg doses of intrathecal clonidine in a 

similar design and patient population and 

observed that clonidine produced dosedependent 

and long-lasting analgesia (7 +/- 

1.3, 10 +/- 1.3, and 14 +/-1.3 hr respectively). 

In both the studies, they found sedation was 

dose dependent and more pronounced after 

450 µg of intrathecal clonidine. The maximum 

dose used in our study was 65 ìg and this low 

dose of clonidine (1 µg/kg) might be cause 

for single incidence of sedation in this series. 

Our study also shows that moderate 

prolongation of duration of analgesia is 

possible with low dose clonidine without 

sedation. 

Many previous studies had used intrathecal 

clonidine combined with opioids and local 

anaesthetics for labour analgesia and 

orthopaedic surgery. However, the 

combination with opioids would seem less 

attractive for obvious reasons. Using 

intrathecal clonidine in place of opioids avoids 

problems of respiratory depression, pruritus, 

urinary retention and abuse liability. 

The works of Dobrydnjov I et al 1 , Filos KS et 

al 5 , Kock DM et al 9 , where clonidine was used 

more than 75 ìg, found prolongation of 

analgesia but at the expense of sedation. Even 

though sedation is a well known side effect of 

clonidine we had encountered only one case 

in our study of intrathecal clonidine (1 µg/kg). 

This might be because of low dose as 

suggested by Eisenach et al 10 which stated 

that clonidine produces dose dependent 

sedation of rapid onset at the range 50-900 

ìg, regardless of route of administration. Our 

findings were in agreement with Kaabachi O 

et al 7 which again underlines the safety of low 

dose intrathecal clonidine. 

Conclusion: It might be concluded that 

intrathecal clonidine at the dose of 1µg/kg 

significantly prolongs the post-operative pain 

free period without significant cardiovascular 

changes and side effects. 

Reference 

1. Dobrydnjov I, Axelsson K, Samartel J, 

Holmstrom B. Postoperative pain relief 

following intrathecal bupivacaine 

combined with intrathecal or oral clonidine. 

Acta Anaesthesiol Scand 2002; 46:806- 

14. 

2. Chiari A, Lober C, Eisenach JC, Wildling 

E, Krenn C, Zavrsky A et al. Analgesic and 

hemodynamic effects of intrathecal 

clonidine as the sole analgesic agent 

during first stage of labor:A doseresponse 

study. Anesthesiology1999; 

9:388-96. 

3. Filos KS, Goudas LC, Patroni O, Polyzou 

V. Intrathecal clonidine as a sole analgesic 

for pain relief after cesarean section. 

Anesthesiology 1992; 77:267-74. 

4. Benhamou D, Thorin D, Brichant JF, 

Dailland P, Milon D, Schneider M. 

Intrathecal clonidine and fentanyl with 

hyperbaric bupivacaine improve analgesia 

during cesarean section . Anesth Analg 

1998; 87: 609–13. 

5. Filos KS, Goudas LC, Patroni O, Polyzou 

V. Hemodynamic and analgesic profile 

after intrathecal clonidine in humans. A 

dose-response study. Anesthesiology 

1994; 81:591-601. 

6. Owens WD, Felts JA, Spitznagel EL Jr. 

ASA physical Status classification: a study 

of consistency of ratings. Anesthesiology 

1978; 49:239-43. 

7. Kaabachi O, Zarghouni A, Ouezini R, 

Abdelaziz AB, Chattaoui O,Kokki H. 

Clonidine 1 µg/kg is a safe and effective 



adjuvant to plain bupivacaine in spinal 

anesthesia in adolescents. Anesth Analg 

2007; 105:516-9. 

8. Sethi BS, Mary S, Deepak S. Efficacy of 

analgesic effects of low dose intrathecal 

clonidine as adjuvant to bupivacaine. In J 

Anesth 2007; 51: 415-9. 

9. Kock DM, Gautier P, Fanard L, Luc HJ, 

Lavandhomme P. Intrathecal ropivacaine 

and clonidine for ambulatory knee 

arthroscopy: a dose-response study. 

Anesthesiology 2001; 94:574-8. 

10. Eisenach JC, Kock MD, KlimschaW. 

Alpha sub 2- adrenergic agonists for 

regional anesthesia: a clinical review of 

clonidine (1984-1995). Anesthesiology 

1996; 85(3):655-74. 

11. Fogarty DJ, Carabine UA, Milligan KR. 

Comparision of the analgesic effects of 

intrathecal clonidine and intrathecal 

morphine after spinal anaesthesia in 

patients undergoing total hip replacement. 

Br J Anaesth 1993; 71:661-4. 

12. Bonnet F, Brun-Buisson V, Saada M, 

Boico O, Rostaing S, Touboul C. Doserelated 

prolongation of hyperbaric 

tetracaine spinal anesthesia by clonidine 

in humans. Anesth Analg 1989; 68:619- 

22. 

13. Racle JP, Benkhadra A, Poy JY, Gleizal B. 

Prolongation of isobaric bupivacaine 

spinal anesthesia with epinephrine and 

clonidine for hip surgery in the elderly. 

Anaesth Analg 1987; 66:442-6. 

14. Grace D, Bunting H, Milligan KR, Fee JPH. 

Postoperative Analgesia after coadministration 

of clonidine and morphine 

by the intrathecal route in patients 

undergoing hip replacement. Anesth Analg 

1995; 80:86-91. 

15. Heo GJ, Kim YH, Hyun Oh J, and Chul 

Joo J. Effect of intrathecal clonidine in 

hyperbaric bupivacaine spinal anesthesia. 

Korean J Anesthesiol 1997; 33:304-8. 

16. Alex THS. Optimal dose of intrathecal 

clonidine added to sufentanil plus 

bupivacaine for labour analgesia. Can J 

Anesth 2000; 47:875-80 

17. Maria DC, Juliao C, Gabriela RL. Lowdose 

intrathecal clonidine combined with 

sufentanil as analgesic drugs in abdominal 

gynecological surgery. J Cl Anesth 2000 

;12: 357-62 

18. Dobrydnjov I, Axelsson K, Thorn SE, 

Matthiesen P, Klockhoff H, Holmstrom B,et 

al. Clonidine combined with small-dose 

bupivacaine during spinal anesthesia for 

inguinal herniorrhaphy: a randomized 

double-blinded study. Anesth Analg 

2003;96:1496-503 

19. Brain DS, Micheal B, Russel B, Rohan C. 

Intrathecal clonidine added to a 

bupivacaine-morphine spinal anesthetic 

improves postoperative analgesia for total 

knee arthroplasty. Anesth Analg 

2003;96:1083–8 

20. Strebel S, Gurzeler JA, Schneider MC, 

Aeschbach A, Kindler CH. Small dose 

intrathecal clonidine and isobaric 

bupivacaine for orthopedic surgery: a 

dose-response study. Anesth Analg 2004; 

99:1231-8. 

21. Van IT, Klei VWA, Werff VD, Kalkman CJ. 

The effect of addition of intrathecal 

clonidine to hyperbaric bupivacaine on 

postoperative pain and morphine 

requirements after caesarean section: a 

randomized controlled trial. Br J Anaesth 

2006; 97:365–70 

22. Ogun CO, Kirgiz EN, Duman A, Kara I, 

Okesli S. The comparison of intrathecal 

isobaric ropivacaine and isobaric 

ropivacaine-clonidine for caesarean 

delivery. Internet J Anesthesiol 2007;15:(1). 

Available from: http://www.ispub .com / 

ostia / index. php ? xml File Path = 

journals/ija vol 15n1/intrathecal.xml. 

Accessed on June 15, 2008. 


33


Pretreatment with lidocaine and metoclopramide for the prevention of pain 

associated with propofol injection 

1 

Cherry JB Kharbudnah , 2 N. Ratan Singh, 3 Laithangbam PKS, 4 L. Deban Singh, 5 L.Kameshwar Singh 

6 

A. Jack Meitei 

Objective: To study the effectiveness of 

Pretreatment with lidocaine and metoclopramide 

for the prevention of pain associated 

with propofol injection Methods: Following 

ethics committee approval, 105 adult patients 

of either sex (ASA I & II, Aged 18 – 60 yrs) 

undergoing major elective surgery under 

general anaesthesia were randomly divided 

into three groups (n = 35) to receive injection 

20 mg of injection lignocaine 2% plus 

metoclopromide 10 mg (Group A), injection 

lignocaine 2% 20 mg alone (Group B) or saline 

(Group C) given over 10 seconds into a large 

antecubital vein after applying a rubber 

tourniquet (pressure of 50 mm Hg). After one 

minute, the tourniquet was released and 25% 

of the calculated dose of propofol (2 mg/kg) 

was given, and patient’s pain response was 

graded into four point scale (0 = no pain, 1 = 

mild pain/pain reported only on questioning 

without any behavioural sign; 2 = moderate 

pain/pain reported spontaneously/pain 

reported on questioning accompanied by 

behavioural signs; 3 = severe pain/strong 

vocal response/pain accompanied by facial 

grimacing, withdrawal or tears. Results: It 

was found that 12 (34.29%) patients in the 

control group had pain compared to 7 (20%) 

patients in the lignocaine group and 8 (22.86%) 

patients in the lignocaine - metoclopromide 

1. PGT, 2. Asst. Prof., 3. Assoc. Prof., 

4. Professor, 5. Professor & Head, 6. Registrar 

Deptt. of Anaesthesiology, RIMS, Imphal, Manipur. 


Dr L. Deban Singh, Professor, Department of 

Anaesthesiology; RIMS, Imphal, Manipur 

combination group (p < 0.05). Conclusion: 

We could not appreciate lignocaine and 

metoclopromide combination to be superior 

to lignocaine or placebo in reducing propofol 

injection pain. 

Key words: Injection pain, pre-treatment, pain 

attenuation 

Introduction: Propofol is a potent intravenous 

hypnotic agent widely used for induction and 

maintenance of general anaesthesia, for 

sedation in ICU, and also to provide sedation 

during surgery. However, pain on its injection 

remains a problem. Various strategies have 

been tried to reduce the incidence of propofol 

injection pain, which include injecting propofol 

into a large antecubital vein 1 ,cooling 2 , adding 

local anaesthetics 3 , diluting propofol solution 4 , 

or by administering opioids 5 ,metoclopramide 6 , 

non steroidal anti-inflammatory drugs 

(NSAIDS) 7 , etc. Interestingly, out of all these 

methods cited, several workers have 

advocated the use of lidocaine and 

metoclopramide for ameliorating the propofol 

injection pain, and some studies have shown 

that lidocaine & metoclopramide are equally 

effective in the reduction of propofol injection 

pain 8 . The present study was designed to 

investigate if lidocaine & metoclopramide 

combination is superior to lidocaine alone or 

a placebo (saline). 

Methods: This Study was conducted in the 

department of Anaesthesiology, Regional 

Institute of Medical Sciences, Imphal. After 

obtaining permission from the institutional 

ethics committee and written informed 



consent, 105 adult patients of ASA grade I & 

II, between 18 and 60 years of age of either 

sex who were scheduled to undergo major 

elective surgery under general anesthesia 

were included in this study. 

105 (One hundred and five) patients were 

randomly allocated into three groups (n=35) 

viz. Group A=Lidocaine + metoclopramide 

group received 20 mg lidocaine 2% along with 

10 mg of metoclopramide, Group B = 

Lidocaine group received 20 of lidocaine 2% 

and Group C = Saline group received 0.9% 

saline intravenously. 

On the morning of surgery, 20gauze IV 

cannula was inserted on the forearm vein for 

administering the study drugs. Premedication 

was provided with injection glycopyrrolate 0.2 

mg IM and inj. Ranitidine 50 mg IV, 1 hour 

before the induction of anesthesia. On arrival 

at the operation theatre, non invasive 

monitoring for blood pressure (BP), 

electrocardiogram (ECG), and pulse oximetry 

were started. A rubber tourniquet was applied 

to the arm for venous occlusion. The study 

drugs were administered over 10 seconds 

through the cannula (pretreatment). After 1 

minute, the tourniquet was released and 25% 

of the induction dose of the drug (2mg/kg) was 

injected, and the during this injection, the 

patients were asked standard questions 

regarding the comfort of injection, and were 

continuously observed for vocal responses, 

facial grimacing , arm withdrawal or tears 

suggesting severe pain. Pain was graded 

using a four point scale 9 : 0= no pain, 1= mild 

pain or pain reported only in response to 

questioning without any behavioral signs, 2= 

moderate pain or pain reported in response 

to questioning and accompanied by a 

behavioral sign or pain reported spontaneously 

without questioning and 3= severe pain with 

strong vocal response or response 

accompanied by facial grimacing, arm 

withdrawal or tears. 

Once the assessment of the injection pain had 

been made, induction of anesthesia was 

completed with the remaining dose of propofol 

and tracheal intubation was facilitated with 

vecuronium. Anaesthesia was maintained with 

halothane, nitrous oxide (66%) in oxygen and 

tramadol hydrochloride with controlled 

ventilation. 

Results: Table I shows the distribution of 

patients in relation to their age, weight, sex 

and ASA (American Society of Anesthesiologist) 

classification in Group A, Group B 

and Group C. The mean (± SD) age of group 

A was 40.26 ± 12.96, group B was 42.07 ± 

12.86 and group C was 39.75 ± 13.56; while 

the mean weight for Group A, B & C were 

53.54±8.26, 54.97±9.81 and 51.97±8.25 

respectively. So, statistically there are no 

significant differences between the three 

groups with respect to age and weight with 

an ‘F’-value of 1.00and P value of 0.37. 

Similarly, there was no statistically significant 

difference in the sex and ASA distribution in 

the three study groups as shown in the said 

table 1. 

Table 1. Demographic profile 

Group A Group B Group C 

(n=35) (n=35) (n=35) Test Level P value 

Age(yrs) 

Mean ±SD 40.26± 42.07± 39.75± F=1.00 0.37 

12.96 12.86 13.56 

Weight(kg) 

Mean ±SD 53.54± 54.97± 51.97± F=1.01 0.37 

8.26 9.81 8.25 

Sex(M:F) 11:24 14:21 9:26 × 2 = 0.82 0.4 

ASA(I:II) 35:0 34:1 32:3 × 2 = 1.83 0.15 

Table 2. Distribution of Pain during 

propofol injection 

Table 2 shows the distribution of the pain in 

the three groups during the injection of 

propofol. The number of patients with no pain 

were 27(77.14%) in group A, 28(80.00%) in 

group B and 23(65.71%) in group C. Mild pain 

was experienced by 8(22.86%), 5(14.29%) 

and 8(22.86%) of the patients in group A, group 


35


B and group C respectively. Severe pain was 

experienced by a few patients in all the groups. 

This distribution of pain grades is not 

statistically significant with a chi-square value 

of 5.40 and a P value of 0.49. 

Discussion: The mechanism of propofol 

injection pain is attributed to the activation of 

kallikren & kinin system and the release of 

bradykinin 10 . Propofol injection pain depends 

on the site of injection, size of the vein, age of 

the patient, temperature and concentration of 

propofol or the use of tourniquet inflation 11 . The 

idea of the use of tourniquet is to allow the 

exertion of local anesthetic effect of lidocaine 

or metoclopramide by allowing more direct 

contact with the free nerve endings after 

tourniquet inflation 12 . However, local 

anesthetic effect is not the only mechanism 

as some studies have shown that lidocaine 

causes inhibition of bradykinin 10 . This may 

explain why some investigators found 

lidocaine mixed with propofol is superior to 

pretreatment in attenuating pain 13 . In our study 

we could not demonstrate significant 

difference among the three groups. This is in 

sharp contrast to the findings of Fujii Y and 

Nakayama M 6 who found significant pain 

reduction (p


8. Liaw WJ, Pang WW, Chang DP, Hwang 

MH. Pain on injection of propofol: the 

mitigating influence of metoclopramide 

using different techniques. Acta 

Anaesthesiol Scand 1999 Jan; 43(1): 

24- 7. 

9. Memis D, Turan A, Karamanlioglu B, Sut 

N, Pamukcu Z. The use of magnesium 

sulfate to prevent pain on injection of 

propofol. Anesth Analg 2002; 95: 

606–8. 

10. Nakane M, Iwama H. A potential 

mechanism of propofol – induced pain 

on injection based on studies using 

nafamostat mesilate. British Journal of 

Anaesthesia 1999; 83(3): 397- 

404. 

11. Gupta M, Mishra S, Gupta D, Gujjar M, 

Bhatnagar S. Prevention of pain on 

propofol injection. A comparative 

randomized double blind study between 

lignocaine, pethidine, dexamethasone 

and placebo. The Internet Journal of 

Anesthesiology 2007; 11(2). Accessed 

on 25August 2010. 

12. Mangar D, Holak EJ. Torniquet at 50 

mmhg followed by intravenous lidocaine 

diminishes hand pain associated with 

propofol injection. Anesth Analg 1992 

Feb; 74(2): 250-2. 

13. Overbaugh R, Jones P, Nguyen A, Swaney 

G. Effect of mixed versus unmixed 

lidocaine with propofol. The Internet 

Journal of Anesthesiology 2003; 7 (2). 


37


Histological pattern of thyroid diseases in RIMS Hospital, Imphal: A report of 

ten years study. 

1 

Rajesh Singh Laishram, 1 O. Okendrajit Singh, 2 Janet Zoremnghaki, 3 Durlav Chandra Sharma, 4 S Thingbaijam 

Abstract 

Objective: The study was conducted to 

observe the different types of thyroid lesions 

in specimens received in Pathology 

department, RIMS, Imphal. Methods: This 

retrospective study was carried out on 

surgically resected thyroid specimens in 

RIMS Hospital, Imphal, during the period 

between January 2001 and December 2010. 

One hundred and eighty four 

histopathologically diagnosed thyroid lesions 

were reviewed and analysed in respect of age, 

gender and histological types. Cases with 

metastatic lesions in thyroid were excluded 

from the study. Results: In the study, of the184 

histologically diagnosed thyroid diseases, 

20(10.87%) cases were males and 

164(89.13%) were females and male to 

female ratio was 1:8.2. Age range was from 8 

to 88 years. Colloid goitre was the 

commonest thyroid lesion (45.11%) followed 

by follicular adenoma (8.70%).There were 13 

cases of thyroiditis, eight of whom were 

lymphocytic thyroiditis and five were 

Hashimoto’s thyroiditis. The overall 

malignancy was seen in 19.02%, papillary 

carcinoma was the commonest comprising 

1. Assistant Professor. 2. PGT. 3. Professor & Head, 

Deptt. of Pathology RIMS, IMphal. 4. Associate 

Professor Deptt. of ENT, RIMS, Lamphelpat, Imphal. 


Dr. O. Okendrajit Singh 

Assistant Professor, Department of Pathology, 

Regional Institute of Medical Sciences, Lamphelpat, 

Imphal- 795004, Manipur, India. 

Mobile: +919436025356 e-mail: okendradr@yahoo.com 

of 29(82.85%) cases followed by medullary 

carcinoma in 3(8.57%) cases and there were 

2.86% each of follicular carcinoma, anaplastic 

carcinoma and insular carcinoma. 

Conclusion: Thyroid diseases are more 

common in females than males. Colloid goitre 

is the most common lesion. Papillary thyroid 

carcinoma is the commonest malignant 

tumour and among the benign tumour, 

follicular adenoma is the commonest. 

Keywords: Thyroid diseases, Colloid goitre, 

Papillary carcinoma, Follicular adenoma 

Introduction: Thyroid diseases are 

progressively becoming one of the most 

frequent reasons for seeking medical advice. 

The worldwide prevalence of goitre in the 

general population is estimated to be 4-7% 

and most of them are colloid goitre with few 

malignancies mainly in solitary nodules. 1 

Thyroid cancer is the most common 

endocrine tumour and its annual incidence 

estimated worldwide from 0.5-10 per 

100,000. 2 It is more common in females than 

in males. There is a well-recognised spectrum 

of variable prognosis with different histological 

variants.Papillary carcinoma is the most 

common histological type of malignancy in 

most parts of the world. 3-5 

This study was carried out to observe the 

pattern of various histological types of thyroid 

lesions from the specimens received in 

Pathology department, Regional Institute of 

Medical Sciences(RIMS), Imphal, Manipur. 

Materials and Methods: This retrospective 

study was done in the cases treated surgically 



for thyroid lesions in RIMS hospital, Imphal, 

Manipur. Histologically diagnosed thyroid 

lesions during the period between January 

2001 and December 2010 were reviewed and 

analysed according to age, sex and 

histological types with the approval of the 

Institutional Ethics Committee. Cases with 

metastatic lesions in the thyroid were excluded 

from the study. All the slides had been stained 

with Hematoxylin and Eosin and special stains 

like Congo red were used when and where 

necessary. 

Result: In the present study, 184 histologically 

diagnosed thyroid diseases were reviewed. 

Table 1: Age and sex distribution of the cases 

Age Male Female Total Percentage(%) 

groups(yrs) 

0-10 2 1 3 1.63 

11-20 1 7 8 4.35 

21-30 5 41 46 25 

31-40 4 42 46 25 

41-50 4 35 39 21.20 

51-60 1 30 31 16.85 

61-70 3 7 10 5.43 

71-80 0 0 0 0 

81-90 0 1 1 0.54 

Total 20 164 184 100 

Table 2: Histopathological types of lesions 

Histopathological diagnosis Number Percentage 

Nodular goitre 11 5.98 % 

Multinodular goitre 12 6.52 % 

Adenomatous goitre 12 6.52 % 

Colloid goitre 83 45.11 % 

Toxic goitre 1 0.54 % 

Hashimoto’s thyroiditis 5 2.72 % 

Lymphocytic thyroiditis 8 4.35 % 

Follicular adenoma 16 8.70 % 

Hyalinising trabecular adenoma 1 0.54 % 

Thyroid malignancy 35 19.02 % 

Total 184 100 

Table 3: Histological types of thyroid malignancies 

Histopathological diagnosis Nos. % 

Papillary thyroid carcinoma 29 82.85 

Medullary carcinoma 3 2.86 

Follicular carcinoma 1 2.86 

Anaplastic carcinoma 1 8.57 

Insular carcinoma 1 2.86 

Total 35 100 

Table 4: Distribution of benign lesions in relation to 

age (years) 

Histopa- 0-10 11-20 21-30 31-40 41-50 51-60 61-70 71-80 81-90 

thological 

lesions 

Nodular 0 0 2 7 1 1 0 0 0 

goitre 

Multinodu- 1 1 0 3 4 3 0 0 0 

lar goitre 

Adenoma- 0 0 5 0 2 5 0 0 0 

tous goitre 

Colloid 0 3 19 19 23 15 4 0 0 

goitre 

Toxic 0 0 0 0 0 1 0 0 0 

goitre 

Hashim- 0 0 1 0 2 1 0 0 1 

oto’s 

thyroiditis 

Lympho- 0 0 0 0 0 0 1 0 0 

cytic 

thyroiditis 

Follicular 2 0 4 8 0 0 2 0 0 

adenoma 

Hyalini- 0 0 0 1 0 0 0 0 0 

sing 

trabecular 

adenoma 

Total 3 4 31 41 36 26 7 0 1 

% 2.01 2.68 20.81 27.52 24.16 17.45 4.70 0 0.67 

Out of which 20(10.87%) cases were males 

and 164(89.3%) were females, with a male to 

female ratio of 1:8.2. The ages ranged from 8 

to88 years. Table 1. shows the age and sex 

distribution of the cases. Thyroid diseases 

were rare below the age of 20 years and only 

11 cases were seen. The most common 

incidence was seen in the age group of 21-40 

years with 92(50%) cases followed by age 

group of 41-50 years in 39 (21.2%) cases. 

Among females, the highest incidence of 

thyroid disease was found in the age group of 

31-40 years and whereas in males it was 21- 

30 years. 

The histopathological types of thyroid lesions 

are shown in Table 2. Colloid goitre was the 

commonest thyroid lesion (45.11%), followed 

by follicular adenoma in 16(8.70%).Thyroiditis 

was found in 13 cases, eight of which had 

lymphocytic thyroiditis and the remaining five 

had Hashimoto’s thyroiditis. Hyalinising 

trabecular adenoma and toxic goitre were 

found in one case (0.54%) each. Among the 

184 patients, 35(19.02%) had thyroid 

malignancies,32 of these were in females with 

a male to female ratio of 1:10.67. Papillary 

thyroid carcinoma was the commonest 


39


Table 5: Distribution of malignant lesions in relation to 

age (years). Figures within the parenthesis indicate 

percentage & ca indicate carcinoma. 

Histolo- 0-10 11-20 21-30 31-40 41-50 51-60 61-70 >70 Total 

gical 

lesions 

Papillary 0 2 13 8 3 3 0 0 29 

ca (6.8) (44.8) (27.5) (10.3) (10.3) 

Medullary 0 1 1 0 0 0 1 0 3 

ca (33.3) (33.3) (33.3) 

Follicular 0 1 0 0 0 0 0 0 1 

ca (100) 

Anaplastic 0 0 0 0 0 1 0 0 1 

ca (100) 

Insular ca 0 0 0 0 0 0 1 0 1 

(100) 

Total 0 4 14 8 3 4 2 0 35 

% 0 11.43 40 22.86 8.57 11.43 5.71 0 100 

(82.85%) followed by medullary carcinoma 

(8.57%). One case each (2.86%) of anaplastic 

carcinoma, follicular carcinoma and insular 

carcinoma were also found as shown in 

Table 3. 

The age distributions of various thyroid lesions 

are shown in Table 4 and 5. Colloid goitre was 

commonest in the age group of 41-50 years, 

as also in cases of thyroiditis. Papillary 

carcinoma was commonest (44.8%) in ages 

between 21 and 30 years whereas in other 

types of carcinomas there were no specific 

age group. 

Discussion: Thyroid nodules which are 

surgically treated may be benign or malignant 

and their incidences varies widely. 3-6 From 

the 184 cases of thyroid lesions reviewed, we 

observed that there was higher incidence in 

females (89.13%) than in males (10.87%) with 

a male to female ratio of 1:8.2. This is 

compatible to studies done by Htwe et al and 

other workers who found that there is female 

preponderance for thyroid lesions. 1,3,7,8,9 

In our study, age ranged from 8 to 88 years 

and high incidence of thyroid lesion were in 

ages between 11 and 70 years and among 

the females, thyroid disease occur mostly in 

the age group between 31 and 40 years. Our 

observations are well comparable with many 

of the published figures. 1,4-8,10,11 

The present study showed colloid goitre as 

the commonest cause of thyroid nodule 

comprising of 45.11% whereas in the studies 

ofMemon W et al, Gandolfi PP et al and others 

reported the most common cause as 

multinodular goitre. 4-6,10 

The overall malignancy in this study was 

19.02% which was slightly higher than 

findings in Italy (13.7%), Yemen (17.7%) and 

Nigeria (15%). However, much lower 

incidence were reported in Malaysia (6.7%) 

and Pakistan (2.92%). 5,8,9,12 

Papillary carcinoma (82.85%) was the 

commonest malignant tumour and more 

common in the age group of 21-30 years 

which is similar to the findings of many 

workers. 1,3-6,8,10-15 In contrast to our finding, 

Mulandzi et al and Edino ST et al reported that 

follicular carcinoma was the commonest 

thyroid malignancy in the African countries. 7,9 

Medullary carcinoma(8.57%) was the second 

most common tumour in our study whereas 

it was follicular carcinoma as observed by 

some other workers. 1,7,10,14 Anaplastic 

carcinoma and insular carcinoma(2.86% 

each) had low incidence as also reported in 

various studies. 8,16,17 It was observed that all 

types of thyroid carcinomas are more 

common in females(91.4%). Similar findings 

have been reported in many studies done in 

different parts of the world. 4-7,10 

Conclusion: Thyroid disease is more 

common in females than males. Colloid goitre 

is the commonest finding in thyroid nodules. 

Papillary carcinoma is the most common 

thyroid malignancy and usually occurs in the 

second and third decade. 



References : 

1. Htwe TT, Hamdi MM, Swethadri GK, 

Wong JOL, Soe MM, Abdullah MS. 

Incidence of thyroid malignancy among 

thyroid lesions from the Sarawak General 

Hospital 2000-2004. Singapore Med J 

2009; 50(7):724-8. 

2. Chan JKC. The Thyroid Gland. In: 

Fletcher CDM. Diagnostic Histopathology 

of Tumors. 3 rd ed.Philadelphia: Elsevier; 

2007.p.997. 

3. Haq RN, Khan BA, Chaudhry IA. 

Prevalence of malignancy in goitre- A 

review of 718 thyroidectomies. J Ayub 

Med CollAbbotabad 2009; 21(4):134-6. 

4. Memon W, Khanzada TW, Samad A, 

Kumar B. Incidence of thyroid carcinoma 

in multinodulargoiters. Rawal Medical 

Journal 2010 Jan-Jun; 35(1)65-7. 

5. Gandolfi PP, Frisina A, Raffa M, Renda F, 

Rochetti O, Ruggeri C et al. The incidence 

of multinodular goitre: retrospective 

analysis. Acta Bio Medica Ateneo 

Parmense 2004; 75:114-7. 

6. Marjani A and Kabir MJ. Incidence of 

thyroid cancer in Golestan Province of 

Iran: some initial observations. Pak J Med 

Sci 2008; 24(6):887-90. 

7. Mulandzi TV, Ramdial PK, Madiba TE, 

Callaghan RA. Thyroid carcinoma at King 

Edward VIII hospital, Durban, South Africa. 

East African Medical Journal 2001 May; 

78(5):242-5. 

8. Hussain M, Anwar M, Nadia N, Ali Z. 

Pattern of Surgically treated thyroid 

disease in Karachi. Biomedica Jan-Jun 

2005; 21:18-20. 

9. Edino ST, Mohammed AZ, Ochicha O, 

Malami SA, yakubu AA. Thyroid cancers 

in nodular goitres in Kano, Nigeria. Niger 

J ClinPract 2010 Sep; 13(3):298-300. 

10. Larijani B, Aghakhani S, Kajeh-Dini H, 

BaradarJalili R. Clinicopahological 

features of thyroid cancer as observed in 

five referral hospitals in Iran. 

ActaOncologica 2003; 42(4):334-7. 

11. Arora R and Dias A. Iodine and thyroid 

cancer in Goa. Online J Health Allied Scs 

2006;4:3. 

12. Abdulmughni YA, Al-Hureibi MA, Al-Hureibi 

KA, Ghafoor MA, Al Wadan AH, Al-Hureibi. 

Thyroid cancer in Yemen.Saudi med J 

2004 Jan; 25(1):55-9. 

13. Ito Y and Miyauchi A. Thyroidectomy and 

lymph node dissection in papillary thyroid 

carcinoma. Journal of thyroid research 

2011. 

14. Tanton R and Gupta S. Pattern of 

malignant thyroid neoplasms in Ajmer. J 

Indian MA 1988 Aug; 86(8):212-3. 

15. Ahmed M, Alsaihati B,GreerW, Al-Nuaim 

A, Bakheet S, Abdulkareem AM et al. A 

study of 875 cases of thyroid cancer 

observed over a fifteen year period (1975- 

1987) at the King Faisal Specialist 

Hospital and Research Centre. Ann Saudi 

Med 1995 Nov; 15(6):579-84. 

16. Dorairajan N, Saravanakumar P, 

karthikayan S, Siddarth D, Kanna S. Review 

Analysis of Medullary carcinoma thyroid–a 

15 year Indian experience. J Indian Med 

Assoc 2005 Aug; 103(8):415-7. 

17. Jain R, Chaturvedi KU, Khurana N, 

Aggarwal AK. Insular Carcinoma of 

Thyroid-a case report. IndJ 

PatholMicrobiol 2004; 47(3):420-2. 


41


Bacterial profile of osteomyelitis cases at RIMS hospital, Imphal 

1 

Ksh. Mamta Devi, 2 Lyngdoh CJ, 3 Kh. Sulochana Devi, 4 Ch. Arunkumar Singh, 

Abstract 

Objective: To isolate and identify bacteria 

responsible for osteomyelitis, to study the 

changing pattern of bacterial flora and drug 

sensitivity of the bacterial isolates to the 

commonly used antibiotics. Methods: A 

cross-sectional study was undertaken from 

cases of orthopaedic wound infections in 

patients attending RIMS hospital for a period 

of two years from August 2006 to July 2008. 

Two samples were collected, one for aerobic 

culture and another for anaerobic culture. 

Anaerobic culture was done in a Gas Pak 

anaerobic chamber. Any growth was identified 

using standard biochemical tests. 

Antimicrobial susceptibility of the isolates was 

done by Kirby Bauer disc diffusion method in 

accordance with Clinical Laboratory Standard 

Institute (CLSI) guidelines. Results: The study 

subjects were predominantly males (66.7%) 

in the age group of 0-15 years (51.6%). The 

maximum number of cases was seen in the 

summer months of April to July. Positive 

culture of 52% of cases was seen with a 

predominance of gram-positive organisms 

(89.4%). Among the gram-positive organisms, 

the predominant isolate was Staphylococcus 

aureus (68.3%). Among the gram-negative 

organisms (10.6%), the isolated organisms 

1. Assistant Professor, 2. Post Graduate student; 

3. Professor, Deptt. of Microbiology, RIMS, 4. Professor 

& Head of Department, Department of Orthopaedics, 

RIMS Imphal, Manipur- 795004. 

Address for correspondence: 

Dr. Kh Sulochana Devi 3 Professor, Department of 

Microbiology RIMS, Imphal-795004 

E mail: sulo_khu@rediffmail.com 

were Pseudomonas aeruginosa and 

Acinetobacter baumannii. Most of the grampositive 

isolates were sensitive to 

Erythromycin and Gentamicin. 100% 

sensitivity to vancomycin is maintained. 100% 

of the isolates were found to be Methicillin 

resistant. A lower sensitivity to the 

Cephalosporin group of antibiotics was 

observed. Conclusion: High occurrence of 

resistance is seen in surgical and orthopaedic 

patients where antibiotic usage is the greatest. 

Hence therapy should be initiated following 

antimicrobial susceptibility testing to prevent 

the acquisition and spread of resistant strains 

of the organisms. 

Keywords: Osteomyelitis, Antimicrobial 

susceptibility, Staphylococcus aureus, 

Pseudomonas aeruginosa. 

Introduction: Florence Nightingale, more than 

100 years ago is believed to have said ‘No 

stronger condemnation of any hospital or ward 

could be pronounced than the single fact that 

infectious diseases has originated in it, or that 

such a disease has attacked other patients 

than those brought in with them. 

Bacteria and resultant infection have 

continued to inflict untold misery on humanity 

from time immemorial and even today, post 

operative infections have plagued us. 1 In spite 

of advances in medicine and surgery, wound 

sepsis is a dreadful complication that 

challenges every physician and surgeon. 

Moreover the patient suffers prolonged 

morbidity, economic loss, and often 

permanent disability. 2 



Bone and joint infections remain a formidable 

challenge to the orthopaedic surgeon. The 

high success rate obtained with antibiotic 

therapy in most bacterial disease has not 

been obtained in bone and joint infections 

because of the physiological and anatomical 

characteristics of bone. 3 

The most common causative organism in 

orthopaedic wound infections is 

Staphylococcus aureus. 4,5 Others include S. 

epidermidis, Streptococci and enteric gramnegative 

bacteria such as Escherichia coli 

and Pseudomonas aeruginosa. Anaerobic 

bacteria are recognized increasingly as an 

important cause in orthopaedic wound 

infections, particularly in osteomyelitis of 

bones of feet associated with diabetes and 

foot ulcers. 3, 4 

The Clinical Microbiology Laboratory is 

increasingly challenged by the spectrum of 

orthopaedic infection. The ever-expanding list 

of organisms underscores the need for careful 

microbiological studies that identify the 

infecting agent precisely. 

Hence this study was carried out to isolate 

and identify bacteria responsible for 

osteomyelitis, to study the changing pattern 

of bacterial flora and drug sensitivity of the 

bacterial isolates to the commonly used 

antibiotics. 

Methods : This study included 33 patients of 

Osteomyelitis from amongst the patients 

attending Orthopaedic OPD and those 

admitted in RIMS Orthopaedic ward. Cases 

clinically suspected to be suffering from 

tubercular infections were excluded. The 

study was conducted in the Departments of 

Microbiology and Orthopaedics, RIMS, Imphal 

from August 2006 to July 2008. 

Under strict aseptic and antiseptic 

precautions, pus or wound swabs were 

collected using sterile swabs or using a needle 

and syringe. Specimens for anaerobic culture 

were inoculated into Robertson’s cooked 

meat medium. The specimens were 

subjected to direct smear, gram staining and 

culture by inoculating on Nutrient agar, Blood 

agar and MacConkey agar media. The 

colonies were then subjected to a series of 

tests for identification. Anaerobic culture was 

done on selective blood agar containing 20µg 

of gentamicin in a Gas Pak anaerobic jar 

(Dynamicro labs). 6 

Antibiotic susceptibility testing was carried out 

by Kirby Bauer disc diffusion method in 

accordance with Clinical Laboratory Standard 

Institute (CLSI) guidelines. 

Results: In this study it was observed that 

the maximum number of cases were seen 

during the summer months of April ’07 to July 

’07 (18.2%) and April’08 to July ’08 (42.3%) 

constituting more than half of the cases. 

Fewer cases occurred during the autumn and 

winter season. Most of the patients of 

osteomyelitis were males (66.7%) especially 

of the age group of 0-15 years (51.6%) with a 

lower prevalence in females (33.3%). The 

percentage age and sex distribution among 

the different clinical groups was found to be 

insignificant (p> 0.05). 

Out of the total of 33 cases of osteomyelitis, 

positive culture was seen in 17 (52%) of the 

cases. Total number of organisms isolated 

was 19 as shown in Table 1. Two of the 

samples showed mixed infection 

(Staphylococcus aureus/ Coagulase negative 

Staphylococcus and Staphylococcus aureus 

/ Acinetobacter baumannii). 

Out of a total of 17 Gram-positive organisms 

which was isolated, the predominant organism 

was Staphylococcus aureus (68.3%) followed 

by Coagulase-negative Staphylococcus 

(21.1%). The gram-negative organisms 

isolated were Pseudomonas aeruginosa and 

Acinetobacter baumanii as shown in table 1. 

Table 2 shows that 100% sensitivity to 

vancomycin was seen in all the Gram-positive 

organisms. 76.9% of Staphylococcus aureus 

were sensitive to Erythromycin whereas 

61.5% and 69.2% of Staphylococcus aureus 

were sensitive to Gentamicin and 

Ciprofloxacin respectively. 53.8% of the 

isolates showed sensitivity to Piperacillintazobactam. 

Among the CONS, most of the 

isolates (75%) showed sensitivity to 

Erythromycin, Gentamicin and Piperacillintazobactam. 

All the Staphylococcal isolates 

were resistant to oxacillin. 


43


Among the gram negative organisms, both the 

Pseudomonas aeruginosa and Acinetobacter 

baumannii isolates were sensitive to Amikacin, 

Table 1: Number and types of bacteria from positive 

cultures 

Bacteria Organism Osteomyelitis 

n=19 

Gram positive S.aureus 13 

(68.3) 

CONS 04 

(21.1) 

Total 17 

(89.4) 

Gram negative Pseudomonas aeruginosa 01 

(5.3) 

Acinetobacter baumanii 01 

(5.3) 

Total 02(10.6) 

*Figures in parentheses indicate the percentage 

Table 2: Antimicrobial susceptibility pattern of Grampositive 

bacteria 

Antibiotics Staphylococcus CONS 

aureus (n=13) 

(n=04) 

S I R S I R 

Erythromycin 10 00 3 3 00 1 

(76.9) (23.1) (75) (25) 

Gentamicin 8 00 5 3 00 1 

(61.5) (38.5) (75) (25) 

Ciprofloxacin 9 00 4 1 1 2 

(69.2) (30.8) (25) (25) (50) 

Piperacillin- 7 1 5 3 00 1 

tazobactam (53.8) (7.7) (38.5) (75) (25) 

Vancomycin 13 00 00 4 00 00 

(100) (100) 

Cefotaxime 6 03 4 1 1 2 

(46.1) (23.1) (30.8) (25) (25) (50) 

Oxacillin 00 00 13 00 00 04 

(100) (100) 

*Figures in parentheses indicate the percentage 

Gentamicin, Piperacillin-tazobactam. 

The isolates showed resistance to 

Ceftazidime, Ceftriaxone, Ciprofloxacin and 

Co-trimoxazole. 

Discussion: According to Resnick D 7 , the 

distribution of osteomyelitis is greatly 

influenced by the age of the patient, the 

specific causative organism and the presence 

or absence of any underlying disorder or 

situation. In this study, the maximum patients 

belong to the age group of 0-15 years. In all 

the age groups, males (66.7%) were 

predominant over the females (33.3%) 

comparable to a study by Waldvogel FA et al 8 

and Duthie and Nelson. 9 

The maximum number of cases of 

osteomyelitis was seen in the summer 

months of April to July which constituted more 

than half the total number of cases. A similar 

finding was reported by Mukhopadhyay B 10 

wherein it was stated that osteomyelitis was 

more common in summer and rainy seasons. 

A culture positivity rate of 52% was observed 

in this study, consistent with findings of 

Vishwakarma and Lal 11 and Kundsen and 

Hoffman 12 . In this study, majority of the 

isolates were grampositive organisms 

(89.4%). Gram-negative organisms 

constituted 10.6%. Mixed infection was seen 

in 2 cases. 

Staphylococcus aureus (68.3%) was the 

commonest isolate comparable to studies by 

Gupta U and Bhattacharya AN 13 Ng 

Brajachand et al 14 and Dhawan et al 15 . 

However the relative rates of Staphylococcus 

aureus vary from centre to centre. Classen 

et al 16 reported as low as 16.3%. 

Staphylococcus aureus and Staphylococcus 

epidermidis are the 2 major pathogens 

responsible for most cases of osteomyelitis 

in the present study. 

There was no isolation of anaerobes. It could 

probably due to the fact that anaerobic 

organisms require very stringent conditions 

for isolation and transportation which could 

not always be maintained. 

Consistent susceptibility (100%) to 

Vancomycin is retained in this study. Most of 

the isolates of Staphylococcus were sensitive 

to Erythromycin. All the Staphylococcal 

isolates showed resistance to methicillin. 

Onche I and Adedeji O 17 also reported 

Staphylococcus aureus completely resistant 

to oxacillin in a hospital setting and inferred 

that this was not unconnected with abuse of 

antibiotics by the populace related to over the 

counter selling of antibiotics. 



Among the gram-negative bacteria, 

Acinetobacter showed resistance to 

Ceftazidime, Ceftrixone, Ciprofloxacin and 

Co-trimoxazole. Agarwal AC et al 18 however 

reported ceftriaxone to be most effective 

antibiotic against gram-negative bacteria in 

contrast to this study. Overuse of broadspectrum 

antibiotics may be an important 

factor in building resistant strains. 

The antimicrobial sensitivity pattern differs in 

different studies and at different times. Many 

studies implied a high level of resistance to 

the commonly used antibiotics due to MRSA 

and ESBL producers resulting from 

indiscriminate and inappropriate use of 

antibiotics. High occurrence of resistance is 

seen in surgical and orthopaedic patients due 

to overcrowding, workload and understaffing 

and where antibiotic usage is the greatest. 

Hence therapy should be initiated following 

antimicrobial susceptibility testing keeping in 

mind the condition of the patient, the side 

effects and practical considerations to prevent 

the acquisition and spread of resistant strains 

of the organisms. 

References 

1. Lidwell Om, Lowberry EJL and Whyte W. 

Bacteria isolated from deep joint sepsis after 

operation for total hip or knee replacement and 

the sources of infection with Staphylococcus 

aureus. I Hosp Infect. 1983; 4: 111. 

2. Ramon B. Gustilo. Evolving concepts in 

treatment of musculoskeletal sepsis, 

Orthopaedic inf ection- Diagnosis and 

treatment. 1 st Edn. Philadelphia: WB 

Saunders Company; 1989. p.1-6. 

3. Cleveland KB.General Principles of Infection, 

Campbell’s Orthopaedics. 10 th Edn. 

Philadelphia: Mosby; 2003. P.643-686. 

4. Jawetz E, Melnick JL and Adelberg EA. Cases 

and clinical correlations, Jawetz, Melnick and 

Adelberg’s Medical Microbioloby. 20 th Edn. 

New York: McGraw Hill; 1995.p.638-639. 

5. Schonholtz GJ, Borgia CA and Blair JD. Wound 

sepsis in orthopaedic surgery. J Bone Joint 

Surg Am. 1962; 44: 1548. 

6. Bhattacharya AN and Gupta U. Changing 

bacterial pattern in orthopaedic infections. 

Indian Journal of Orthopaedics. 1974; 8: 34- 

38. 

7. Resnick D. Osteomyelitis, Septic arthritis and 

Soft tissue infection, Resnick Diagnosis of 

Bone and Joint Disorders. 4 th Edn. 

Philadelphia: WB Saunders Company; 

2002.p.2375-2377. 

8. Waldvogel FA, Medoff G and Swartz MN. 

Osteomyelitis: A review of clinical features, 

therapeutic considerations and unusual 

aspects. N. Engl. J. Med. 1970; 282: 198-206. 

9. Duthie and Nelson. Inf ection of the 

musculoskeletal system, Mercer’s 

Orthopaedic Surgery. 9 th Edn. Great Britain: 

Arnold; 1996.p.549-645. 

10. Mukhopadhyay B. Pyogenic haematogenous 

osteomyelitis: Acute and chronic, Textbook 

of Orthopaedics and Trauma. 1 st Edn. New 

Delhi: Jaypee Brothers; 1999.p.161-196. 

11. Vishwakarma and Lal. Changing bacterial flora 

in osteomyelitis. Archives of Med. Sciences. 

1970; 1: 55. 

12. Kundsen CJM and Hoffman EB. Neonatal 

osteomyelitis. J Bone Joint Surg (Br). 1990; 

72-B: 846-57. 

13. Gupta U and Bhattacharya AN. Anaerobic 

organisms in osteomyelitis, Indian J. Surgery. 

1980; 1: 143. 

14. Brajachand Ng, Lokhendro H and Ibotomba 

Y. Bacteriological study of post-operative 

wound infections and antimicrobial 

susceptibility of the wound pathogens. Journal 

of Medical Science. 1988; 11: 19-22. 

15. Dhawan B, Mohanty S, Das BK and Kapil A. 

Bacteriology of orthopaedic wound infections 

in an Indian Tertiary Care Hospital. Indian J 

Med Res. 2005; 121: 784-785. 

16. Classen DC, Sott Evans R and Pestonik SL. 

The timing of prophylactic administration of 

antibiotics and the risk of surgical wound 

infection. N Engl J Med. 1992; 326: 281-285. 

17. Onche I and Adedeji O. Microbiology of postoperative 

wound infection in implant surgery. 

Nigerian Journal of Surgical Research. 2004; 

6: 37-40 

18. Agrawal AC, Jain S, Jain RK and Aza HKT. 

Pathogenic bacteria in an orthopaedic hospital 

in India. J infect Developing Countries. 2008; 

2(2): 120-123. 


45


Attention deficit hyperactivity disorder (ADHD) in a school sample in Manipur 

1 

R.K. Lenin Singh, 2 S. Gojendra Singh, 3 L. Roshan Singh, 4 N. Heramani singh, 5 M. Akshyakumar Singh 

Abstract 

Objective: To find out the prevalence of 

ADHD among the school children in a city 

school, Imphal, Manipur. Methods: A total of 

312 students within the age range of 5-12 

years were evaluated by using Vanderbilt 

ADHD Diagnostic Teacher Rating Scale and 

Vanderbilt ADHD Diagnostic Parents Rating 

Scale. Results: The prevalence of ADHD was 

estimated to be 4.17% and the rate was higher 

among boys than girls with a percentage of 

2.9% and 1.8% respectively. Conclusion: 

ADHD is common among the school children 

in Manipur. 

Keywords: Prevalence, attention deficit 

hyperactivity disorder, school children 

Introduction: Attention-deficit/hyperactivity 

disorder (ADHD) has defining features of 

inattention, over activity, and impulsivity 1 . It is 

the most frequently encountered childhoodonset 

neurodevelopment disorder in primary 

care settings. 

Symptoms frequently co-occur with other 

emotional, behavioral, and learning problems, 

including oppositional defiant disorder, 

conduct disorder, depression, anxiety, and 

learning disabilities. 

1. Associate professor, 2. Registrar, Dept. of 

psychiatry, 3. Assistant Professor, Dept. of Clinical 

Psychology, 4. Professor & Head, Dept. of 

Psychiatry 5. Professor, Dept. of Clinical 

Psychology 

Correspondence: Dr. R.K.Lenin Singh, Associate 

Professor, Department of Psychiatry, RIMS, Imphal 

Email Address: leninrk@yahoo.com 

Introduction: Attention-deficit/hyperactivity 

disorder (ADHD) has defining features of 

inattention, over activity, and impulsivity 1 . It is 

the most frequently encountered childhoodonset 

neurodevelopment disorder in primary 

care settings. Symptoms frequently co-occur 

with other emotional, behavioral, and learning 

problems, including oppositional defiant 

disorder, conduct disorder, depression, 

anxiety, and learning disabilities. The National 

Institute of Mental Health (NIMH), estimates 

that between 3% and 5% of preschool and 

school-age children have ADHD or 

approximately two million children in the 

United States. This means in a class of 25 to 

30 students, it is likely that at least one student 

will have this common condition 2 . The cause 

of ADHD is unknown, and multiple pathways 

may lead to the phenotypic expression of the 

disorder 3 . Some studies suggest that genes 

play a large role. Like many other illnesses, 

ADHD probably results from a combination 

of factors. In addition to genetics, researchers 

are looking at possible environmental factors, 

and are studying how brain injuries, nutrition, 

and the social environment might contribute 

to ADHD. Results from several international 

studies of twins show that ADHD often runs 

in families. Researchers are looking at several 

genes that may make people more likely to 

develop the disorder 4,5 . Children with ADHD 

who carry a particular version of a certain gene 

have thinner brain tissue in the areas of the 

brain associated with attention. This National 

Institute of Mental Health (NIMH) research 

showed that the difference was not 



permanent, however, and as children with this 

gene grew up, the brain developed to a normal 

level of thickness. Their ADHD symptoms also 

improved. 6 Other studies suggest a potential 

link between cigarette smoking and alcohol 

use during pregnancy and ADHD in children. 7,8 

In addition, preschoolers who are exposed to 

high levels of lead, which can sometimes be 

found in plumbing fixtures or paint in old 

buildings, may have a higher risk of developing 

ADHD. 9 Children who have suffered a brain 

injury may show some behaviors similar to 

those of ADHD. However, only a small 

percentage of children with ADHD have 

suffered a traumatic brain injury. Recent 

British research indicates a possible link 

between consumption of certain food 

additives like artificial colors or preservatives, 

and an increase in activity. 10 Research is under 

way to confirm the findings and to learn more 

about how food additives may affect 

hyperactivity. 

Treatments can relieve many of the disorder’s 

symptoms, but there is no cure. With 

treatment, most people with ADHD can be 

successful in school and lead productive lives. 

Researchers are developing more effective 

treatments and interventions, and using new 

tools such as brain imaging, to better 

understand ADHD and to find more effective 

ways to treat and prevent it. 

Methods: A cross-sectional study design was 

used. Primary data was collected through 

personal interview method from both the 

teachers of the City Montessori Higher 

Secondary School, Imphal and parents of the 

children studying in the school. The 

interviewer read out a prepared script that 

provided an overview of the study aims and 

objectives and also benefits for participation 

were explained. All the students belonging to 

classes between I to VII with an age range of 

5-12 years who were studying in the school 

were recruited. Based on purposive sampling 

technique, a sample of 312 children was 

selected. All the children were screened for 

ADHD by using Vanderbilt ADHD Diagnostic 

Teacher Rating Scale 11 and Vanderbilt ADHD 

Diagnostic Parents Rating Scale. 11 

Sociodemographic data were collected using 

a semi-structured proforma and the diagnosis 

of ADHD was made using DSM-IV-TR 

criteria. 

Procedure: To proceed with the study, 

necessary permission was sought from the 

school authority. The teachers of the school 

were educated and trained about ADHD. One 

day training programme for the teachers on 

ADHD screening tool were conducted by a 

specialist in the field. In the programme, all 

the 18 criteria for ADHD in Vanderbilt Teacher 

rating Scale was discussed and explained one 

by one. After the training, teachers were asked 

to screen the school children belonging to 

class I to VII using the particular scale. 

The parents of the students were also 

educated about ADHD by organizing one day 

awareness programme for parents at schools. 

Parents were explained about the Vanderbilt 

Parents Rating Scale. The scale is the 

parents’ version of teachers rating scale which 

has all the 18 DSM-IV criteria for ADHD. The 

scale was further simplified and translated into 

Manipuri and back translated, so that parents 

could understand at ease. After that, parents 

were also asked to screen and rate the severity 

of each behavior on a 4 point Scale. 

Result: The present study was based on a 

primary sample of study subjects. For the 

particular school 312 students, both boys and 

girls were screened. 

Table 1. Students screened for ADHD by Teachers 

Class students students with positive positive 

screened ADHD boys girls 

I 28 4 2 2 

II 55 11 6 5 

III 53 1 1 0 

IV 47 0 0 0 

V 47 0 0 0 

VI 43 0 0 0 

VII 39 1 1 0 

TOTAL 312 17 (5.45%) 10 (3.23%) 7 (2.22%) 

Table 2. Student screened for ADHD by Parents 

Class student No. of No. of Negative Miss out Total No. of 

screened boys girls students 

positive by positive of 

teachers ADHD 

I 4 1 2 1 0 3 

II 11 6 3 2 0 9 

III 1 1 0 0 0 1 

IV 0 0 0 0 0 0 

V 0 0 0 0 0 0 

VI 0 0 0 0 0 0 

VII 1 0 0 0 1 0 

TOTAL 17 8 5 3 1 13 


47


Table 3. Student found positive for ADHD in both the 

settings 

Class No. of No. of boys No. of girls No. of student 

student found found positive of 

screened positive positive ADHD in 

two settings 

I 28 1 2 3 

II 55 6 3 9 

III 53 1 0 1 

IV 47 0 0 0 

V 47 0 0 0 

VI 43 0 0 0 

VII 39 0 0 0 

TOTAL 312 8 (2.9%) 5 (1.8%) 13 (4.17%) 

Out of the 312 students belonging to classes 

from I to VII who were recruited and screened 

for the study (as shown in table-1). The data 

collected from teachers shown that out of 312 

students screened, 17 students were 

screened positive of ADHD with a percentage 

of 5.45%. Out of which 10 were boys and 7 

were girls with a percentage of 3.23% and 

2.22% respectively.. From the data collected 

by parents it was found that out of the 17 

positive students, 13 of them were again 

screened positive – 8 boys and 5 girls, 

whereas 3 of them were found negative and 

1 of the student could not be traced as he had 

already dropped out of the school. Special 

focus was given on the above mentioned 17 

positive students (shown in table – 2,3). 

Putting the above two data together, it was 

found that out of the total of 312 students 

screened, 13 students were diagnosed 

positive of ADHD. So, it stands that 4.17 % of 

the students were affected by ADHD. 

Discussion: Besides providing information 

that can be compared with the child’s behavior 

at home, school setting can be used as an 

alternative setting for carrying out interventions 

and allows sampling of a broader spectrum 

and area of behavior. 12 Moreover, externalizing 

problems get reported more often by teachers 

and internalizing problems more often by the 

parents. 13 Keeping these views in mind, school 

was chosen as a platform to obtain samples 

for study. This has been done in several other 

studies. 14, 15. The sample consisting of 312 

children that were screened comprised of an 

almost equal proportion of girls and boys. This 

ensured proportional representation of both 

sexes. In the present study, information from 

child, teacher and parents was used and the 

interviewer’s best judgment was applied to 

arrive at a final conclusion. 

The prevalence of ADHD in the current study 

was found to be 4.17 %. Though, the finding 

was agreed with several other studies. Studies 

by Kashani et al., 16 Cohen et al. 17 and 

Deivasigamani 14 have found higher rates while 

that by Esser et al 18 revealed lower rate of 

prevalence. This difference could be attributed 

to variations in age group, informants, 

diagnostic system, diagnostic tools and 

sampling techniques. The higher rate of ADHD 

among boys than girls were similar to findings 

of Rutter et al., 19 and Offord et al 20 . 

Conclusion: ADHD is not uncommon in 

school going children in Manipur. It is a barrier 

in the effective management of children at 

school and home. And yet many of the parents 

and teachers are not aware of the same. 

Present study could bring up awareness 

among the teachers and parents. 

Limitations: The present study had certain 

limitations. Inherent disadvantages of 

sampling in schools remained. Subjects with 

severe ADHD, being probable school 

dropouts, were automatically left out. Certain 

socio-demographic and clinical variables 

such as peer adjustment, environment in 

neighborhood, parenting style and intelligence, 

which were not probed, kept room for future 

improvement. 

References 

1. American Psychiatric Association. 

Diagnostic and Statistical Manual of Mental 

Disorders. 4th ed. Washington, DC: 

American Psychiatric Association; 1994 

2. National Institute of Mental Health. 

“Attention Deficit Hyperactivity Disorder.” 

Department of Health and Human 

Services. National Institutes of Health. 

2006. 



3. National Institutes of Health. Diagnosis 

and Treatment of Attention-Deficit/ 

Hyperactivity Disorder. Washington, DC: 

US Government Printing Office; 1998. 

4. Faraone SV, Perlis RH, Doyle AE, Smoller 

JW, Goralnick JJ, Holmgren MA, Sklar P. 

Molecular genetics of attention-deficit/ 

hyperactivity disorder. Biological 

Psychiatry, 2005; 57:1313-1323. 

5. Khan SA, Faraone SV. The genetics of 

attention-deficit/hyperactivity disorder: A 

literature review of 2005. Current 

Psychiatry Reports, 2006; 8:393-397. 

6. Shaw P, Gornick M, Lerch J, Addington A, 

Seal J, Greenstein D, Sharp W, Evans A, 

Giedd JN, Castellanos FX, Rapoport JL. 

Polymorphisms of the dopamine D4 

receptor, clinical outcome and cortical 

structure in attention-deficit/hyperactivity 

disorder. Archives of General Psychiatry, 

2007; 64(8):921-931. 

7. Linnet KM, Dalsgaard S, Obel C, Wisborg 

K, Henriksen TB, Rodriguez A, Kotimaa 

A, Moilanen I, Thomsen PH, Olsen J, 

Jarvelin MR. Maternal lifestyle factors in 

pregnancy risk of attention-deficit/ 

hyperactivity disorder and associated 

behaviors: review of the current evidence. 

American Journal of Psychiatry, 2003; 

160(6):1028-1040. 

8. Mick E, Biederman J, Faraone SV, Sayer 

J, Kleinman S. Case-control study of 

attention-deficit hyperactivity disorder and 

maternal smoking, alcohol use, and drug 

use during pregnancy. Journal of the 

American Academy of Child and 

Adolescent Psychiatry, 2002; 41(4):378- 

385. 

9. Braun J, Kahn RS, Froehlich T, Auinger 

P, Lanphear BP. Exposures to 

environmental toxicants and attentiondeficit/hyperactivity 

disorder in U.S. 

children. Environmental Health 

Perspectives, 2006; 114(12):1904-1909. 

10. McCann D, Barrett A, Cooper A, Crumpler 

D, Dalen L, Grimshaw K, Kitchin E, Lok 

E, Porteous L, Prince E, Sonuga-Barke 

E, Warner JO. Stevenson J. Food additives 

and hyperactive behaviour in 3-year-old 

and 8/9-year-old children in the 

community: a randomised, doubleblinded, 

placebo-controlled trial. Lancet, 

2007; 370 (9598):1560-1567. 

11. Wolraich ML, Feurer ID, Hannah JN. 

Obtaining systematic teacher reports of 

disruptive behavior disorders utilizing 

DSM-IV. Journal ofAbnormal Child 

Psychology, 1998; 26(2):141–152. 

12. Malhotra S. Child psychiatry in India: An 

approach to assessment and 

management of childhood psychiatric 

disorders. New Delhi: Macmillan India; 

2002. 

13. Banerjee T. Psychiatric morbidity among 

rural primary school children in West 

Bengal. Indian J Psychiatry, 1997; 39: 

1305. 

14. Deivasigamani TR. Psychiatric morbidity 

in primary school children: An 

epidemiological study. Indian J Psychiatry 

1990; 32:235-40. 

15. Offord DR, Boyle MH, Szatmari P. Ontario 

Child Health Study-II. Six month 

prevalence of disorder and rates of 

service utilization. Arch Gen Psychiatry 

1987; 44: 832-6. 

16. Kashani JH, Daniel AE, Sulzberger LA. 

Conduct disordered adolescents from a 

community sample. Can J Psychiatry 

1987; 32: 756-60. 

17. Cohen P, Cohen J, Kasen S. An 

epidemiological study of disorders in late 

childhood and adolescence-I: Age- and 

genderspecific prevalence. J Child 

Psychol Psychiatry, 1993; 34: 85167. 

18. Esser G, Schmidt MH, Woerner W. 

Epidemiology and course of psychiatric 

disorders in school-age children-results 

of a longitudinal study. J Child Psychol 

Psychiatry, 1990; 31: 243-63. 

19. Feehan M, McGee R, Raja SN, et al. DSM- 

III-R disorders in New Zealand 18-yearolds. 

Aust N Z J Psychiatry 1994;28: 87- 

99. 

20. Rutter M, Tizard J, Whitmore K. 

Education, health and behavior. London: 

Longmans; 1970. 


49


Clinical and endoscopic studies of dysphagia 

1 

G.S. Moirangthem, 2 Ch. Arun Kumar Singh, 3 Dathiadiam Tongper, 3 Dacto Gara 

Abstract 

Objective: The aim and objective of the 

present study was to evaluate the nature and 

frequency of different upper gastrointestinal 

conditions leading to dysphagia and to study 

the diagnostic potential of upper 

gastrointestinal endoscopy in relation with 

clinical symptoms. Methods: The present 

study was conducted in Surgical 

Gastroenterology and Minimal Access Surgery 

Unit, Department of Surgery, RIMS, Imphal, 

Manipur over the period of twenty four month 

(September 2008 to September 2010). The 

study population consisted of 50 patients 

presenting with dysphagia at our OPD or 

referred to our unit from various departments 

for endoscopic evaluation for dysphagia 

irrespective of age, sex, marital status, social 

caste, religion. Results: There was male 

preponderance of 56% (28 pts) as against 

44% (22 pts) of his female counterpart. The 

average age of the patients in the sample (n 

= 50) was 53± years. Nineteen patients out of 

50 patients were associated with a recent 

significant weight loss, rest 31 patients does 

not have any weight loss. Significant, 

1. Professor & Head; 2. Associate Professor; 

3. PGT, Surgical Gastroenterology & Minimal 

Access Surgery Unit, RIMS, Imphal-795004, 

Manipur (INDIA) 


Dr. Ch. Arun Kumar Singh, Surgical 

Gastroenterology & Minimal Access Surgery Unit, 

RIMS, Imphal-795004, Manipur e-mail: 

drcharun@yahoo.com 

Lymphadenopathy was found in 7 patients 

only. Endoscopic Biopsy for HPE was down 

in 16 out of 50 patients who were suspected 

of having Carcinoma of esophagus and 

carcinoma of oropharynx. 

Out of the sample of 50 patients presenting 

with dysphagia and associated complaints, 

10 patients (20%) were diagnosed as 

superficial esophagitis on upper GI 

endoscopy, in 10 patients (20%) no obvious 

pathological findings were demonstrated 

(Normal findings) and fourteen cases of 

carcinoma (6 Ca. esophagus, 5 Ca. 

oropharynx and 3 Ca. stomach), 5 cases of 

benign esophageal stricture (corrosive 

stricture), 5 cases of Grade III & IV esophageal 

varices, 2 cases of GERD, 3 achalasia, 1 case 

of hiatus hernia were detected. 

Conclusion: The present study shows that 

Upper GI endoscopy in conjunction with HPE 

and barium X ray is a good diagnostic modality 

in evaluating a case of dysphagaia. Different 

cases of dysphagia in a limited number of 50 

patients were evaluated. 

Keywords: Dysphagia, Upper GI Endoscopy 

and dysphagia, Barium swallow and 

dysphagia 

Introduction: Dysphagia is a Greek word and 

means ‘disordered eating’. Dysphagia 

typically refers to difficulty in eating as a result 

of disruption in the swallowing process. 

Dysphagia may be caused by a variety of 

upper GI conditions, it can be divided into high 

and low causes. 



High causes may be: 

Neurological 

• Stroke 

• Parkinsons disease 

• Cranial nerve palsy or bulbar palsy 

(such as multiple sclerosis, motor 

neurone disease) 

Anatomical or muscular 

• Myasthenia gravis 

• Oropharyngeal malignancy 

• Cricopharyngeal spasm 

• Pharyngeal pouch 

Low causes (oesophagial) 

• Carcinoma oesophagus 

• Reflux disease with or without stricture 

• Motility disturbance (such as 

achalasia, scleroderma, or 

oesophageal spasm) 

There are several diagnostic investigations 

available to evaluate dysphagia, including 

upper gastrointestinal radiography and 

endoscopy. OGD is an effective and an 

appropriate tool for the evaluation of patients 

presenting with dysphagia. Early OGD should 

be considered particularly in male patients > 

40 years old with dysphagia which often leads 

to the therapeutic intervention even in quite 

frail subjects. 

Materials and Methods: The study was 

conducted in the Surgical Gastroenterology 

and Minimal Access Surgery Unit, Department 

of Surgery, RIMS, Imphal, Manipur over a 

period of twenty four month (September 2008 

to September 2010) and included patients 

presenting with dysphagia. Before including 

the patients in the study group informed written 

consent was taken. A detailed clinical history 

was taken for each and every case. A thorough 

general, physical and systematic examination 

was done using a predesigned proforma. 

Investigations like blood routine examination, 

X-ray chest, LFT etc. were also included. 

Patients presenting with dysphagia 


caste, religion etc were also included. 

Patients presenting with dysphagia 


caste, religion etc. were included in the study. 

The cases were subjected to esophagogastroscopy 

under local anaesthesia, findings 

were noted and endoscopic biopsy was taken 

from any suspicious lesions. Barium swallow 

and meal wear also advised if necessary and 

the final diagnosis were made after reviewing 

those HPE reports and barium series. 

Results: Average age of the patients of 

sample (n=50) in the study was 53 years, with 

a minimum and maximum of 25 years and 78 

years and age range of 53 years. There was 

male preponderance of 56% as against 44% 

of his female counterpart in this study. 

Most of the patients had mean duration of 

onset of symptoms of 2-3 months. Significant 

weight loss was associated in 19 patients and 

clinically apparent lymphadenopathy found in 

only 7 patients. (Table 1) 

Table 1: Clinical profiles 

Parameters Numbers (50) 

Duration of the symptoms 1 month 10 

2-3 months 29 

> 4 months 11 

Significant wt lossPresent 19 

Absent 31 

Lymphadenopathy Present 7 

Absent 43 

Esophagogastroduodenoscopy performed, 

endoscopic biopsy for HPE were done in 16 

out of 50 patients who were suspected of 

carcinoma of esophagus and carcinoma of 

oropharynx and barium swallow studies for 

16 patients. (Table 2) 

Table2: Endoscopy with associated interventions 

Parameter 

Numbers (n=50) 

Endoscopy performed 50 

Endoscopy with biopsy 16 

Endoscopy with barium studies 16 

Superficial esophagitis and normal findings 

were the commonest findings demonstrated 

in Upper GI endoscopy 10 patients each in 

our study, commonly seen in 40 to 70 years. 

(Table 3) 


51


Table 3: Endoscopy findings and provisional 

diagnosis 

Diagnosis 

(Endoscopically) 

Total 

Carcinoma of esophagus 6 

Carcinoma of stomach 3 

(GE junction) 

Superficial esophagitis 10 

Corrosive stricture 5 

Esophageal varices Gr III & IV 5 

Carcinoma oropharynx 5 

GERD 2 

Achalasia 3 

Normal study 10 

Pharyngeal pouch/Hiatus Hernia 1 

Total 50 

Final diagnosis was made by collaborating the 

endoscopic findings with the barium study 

report and histophathodological reports. 

Table 4: Final diagnosis 

Final Diagnosis 

Total 

Carcinoma of stomach 3 

(GE junction) 

Carcinoma of esophagus 6 

Superficial esophagitis 10 

Corrosive stricture 5 

Esophageal varices Gr III & IV 5 

Carcinoma oropharynx 5 

GERD 2 

Achalasia 3 

Normal study 10 

Pharyngeal pouch/Hiatus Hernia 1 

Total 50 

Out of the sample of 50 patients presenting 

with dysphagia and associated complaints, 

10 patients (20%) were diagnosed as 

Superficial esophagitis on upper GI 

endoscopy, in 10 patients (20%) no obvious 

pathological findings were demonstrated 

(Normal findings), fourteen cases of 

carcinoma (6 Ca. esophagus, 5 Ca. 

oropharynx and 3 Ca. stomach), 5 cases of 

benign esophageal stricture (Corrosive 

stricture), 5 cases of grade III & IV esophageal 

varices, 2 cases of GERD, 3 achalasia and 1 

case of hiatus hernia. (Table 3) 

Discussion: Dysphagia, an important 

alarming symptom especially when 

associated with other upper gastrointestinal 

symptoms like dyspepsia, chronic 

gastrointestinal bleeding, progressive 

unintentional weight loss, persistent vomiting, 

iron deficiency anemia or epigastric mass. 

Dysphagia needs to be investigated on an 

urgent basis to establish a diagnosis early in 

the course of the patient’s management and 

to rule out any ongoing serious pathology such 

as a neoplastic process. A detailed medical 

history and clinical examination is the key to 

rule out various causes of dysphagia. Several 

diagnostic investigations are available to 

evaluate dysphagia, like upper gastrointestinal 

endoscopy, contrast imaging studies and 

manometeric studies. 

Several studies have been done to find the 

diagnostic potential of esophagogastroduodenscopy 

in evaluating dysphagia. 

Varadarajulu Shyam et al 1 conducted a study 

on a total of 1649 patients with dysphagia. 

(mean age 56.7 years, M:F=3:2). Abnormal 

findings at OGD were found in 70% (1150) of 

the patients and a major pathology was seen 

in 54% (898). Cancer was found in 4% (70) of 

the patients and was predicted by male 

gender, age and weight loss. The esophagus 

was normal in 29% (483) of patients. 

Nafees A Quereshi et al 2 also reported 

esophagus was abnormal in 678 cases 

(74%). Superficial esophagitis, Barrett’s 

esophagus, esophageal cancer and 

esophageal ulcer were main histological 

findings. Ahmed et al 3 reported in a survey of 

120 consecutive endoscopies on elderly 

patients with suspected obstructive dysphagia. 

Seventy eight patients had positive findings. 

Benign structure of the esophagus was the 

commonest findings; fifteen patients had 

upper GI malignancy (12 esophagus and 3 

stomach). Six patients with negative 

endoscopies had established by other means 

and in 14 no cause was not identified. Thus 

they concluded that upper gastro intestinal 

endoscopy is a safe and valuable procedure 

in elderly patients with dysphagia and often 



leads to positive therapeutic interventions even 

in quite frail subjects. 

Stephen M wildi et al 4 in a study of total 175 

patients with worsening symptoms of ongoing 

reflux performed upper GI endoscopy. Major 

esophageal finding were discovered in 95 

patients, in 10 patients major gastric or 

duodenal findings were detected as follows: 

erosive gastritis (n=8), gastric ulcer (n=2), 

duodenal ulcer (n=2), erosive duodenitis 

(n=2), and duodenal polyp (n=1). 

Gupta SD et al 5 conducted a study on 

endoscopic evaluation of dysphagia in the 

elderly. A survey of 100 consecutive 

endoscopies on elderly patients with 

suspected obstructive dysphagia is reported. 

Seventy eight patients had positive findings 

of 1 to 3 lesions. Benign structure of the 

esophagus was the commonest findings and 

15 patients had upper GI malignancy. Six 

patients with negative endoscopies had 

diagnosis established by other means and in 

14 patients, no cause could be identified. The 

study concluded that upper GI endoscopy is 

a safe and valuable procedure in elderly 

patients and often leads to positive therapeutic 

intervention even in quite frail subjects. 

In our series of 50 cases, superficial 

esophagitis, followed by carcinoma 

esophagus, corrosive stricture, esophageal 

varices Gr-III & IV and carcinoma oropharynx. 

In 10 patients (20%) no abnormality were 

detected, superficial esophagitis 10 patients 

(20%), Carcinoma of esophagus was found 

in 6 patients (12%), Corrosive stricture in 5 

patients (10%), Esophageal varices Gr-III & 

IV in 5 patients (10%), Carcinoma oropharynx 

in 5 patients (10%), carcinoma of stomach in 

3 patients (6%), GERD 2 patients (4%), 

Achalasia 3 patients (6%) and hiatus hernia 

in 1 patient (2 %). 

Conclusion: The study shows that Upper GU 

endoscopy is a good diagnostic modality in 

evaluating a case of dysphagia. It has the 

advantage of direct vision of the lesion and 

tissue biopsy if required for histopathological 

examination. The commonest cause of 

dysphagia in patients presenting at RIMS 

surgical OPD was superficial esophagitis 

followed by carcinoma of esophagus and 

carcinoma of oropharynx respectively. 

Malignancy was associated with significant 

loss of weight and lymphadenopathy. The 

normal study on the UGI endoscopy in the 10% 

patients having dysphagia is also another 

notable and significant finding of the study. 

These groups of patients may require further 

psychiatric evaluation. Therefore, while 

evaluating a case of dysphagia consideration 

for endoscopy should be correlated with 

clinical examination. 

References 

1. Shyam Varadarajulu, Mohamad A. 

Eloubeidi, Rig S. Patel, Hugh E. 

Mulcahy, Alan Barkun, Paul Jowell et 

al. The yield and the predictors of 

esophageal pathology when upper 

endoscopy is used in the initial 

evaluation of dysphagia. American 

Journal of Surgery 2005; 61:804-808. 

2. Nafees A Qureshi, Micheal T Hallissey 

ad John W Fielding. Outcome of index 

upper gastrointestinal endoscopy in 

patients presenting with dysphagia in 

a tertiary care hospital. BMC 

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Endoscopic evaluation of dysphagia in 

elderly. BMC surgery 2001;16:159- 

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Robert F Woolson, Wei Wang 

Roberts H Hawes, Micheal B Wallace. 

Is esophagoscopy alone sufficient for 

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of Dysphagia in the Elderly. Oxford 

Journals 1987; 16:159-164. 


53


Effect of ethyl acetate extract of black catechu (Acacia catechu) on oral glucose 

tolerance and hydrocortisone induced hyperglycemia 

1 

Ng. Gunindro, 2 Lakshman Das, 3 Kh. Krishna Pramodini, 4 Th. Imoba Singh 

Abstract 

Objective: To evaluate effects of ethyl acetate 

extract of black catechu (Acacia catechu) on 

oral glucose tolerance and hydrocortisone 

induced hyperglycemia in an attempt to 

explore the possible mechanisms of 

hypoglycemic activity of Acacia catechu, a 

plant reported to possess hypoglycemic 

property. Methods: Ethyl acetate extract of 

black catechu (Acacia catechu) was orally 

tested at the doses of 250 and 500 mg/kg for 

hypoglycemic activity in normal and alloxan 

induced hyperglycemic rats. Using the same 

doses, effects of the extract on oral glucose 

tolerance and hydrocortisone induced 

hyperglycemia were evaluated. In all the 

studies, the results of the extract treated 

groups were compared with those of the 

control and standard groups. The results were 

analysed for statistical significance. Results: 

The extract showed hypoglycemic activity. It 

reduced hydrocortisone induced hyperglycemia 

but not the hyperglycemia after oral 

glucose load. Conclusion: Reduction of 

hydrocortisone induced hyperglycemia by the 

ethyl acetate extract of black catechu 

Affiliations: 

1. Asst. prof., Dept. of Pharmacology, RIMS, Imphal, 

2. Asst. prof., Dept. of Pharmacology, Tripura 

Medical College & Dr. B.R. Ambedkar Teaching 

Hospital, Hapania, Agartala, 3. Professor Dept. of 

Pharmacology RIMS, 4. Prof. and Head, Dept. of 

Pharmacology, JNIMS, Imphal 


Ngangom Gunindro, Asst. professor, Dept. of 

Pharmacology, RIMS, Imphal PIN – 795004 

Email: pharrims @yahoo.co.in 

(Acacia catechu) suggested the possibility of 

inhibition of hepatic gluconeogenesis as one 

of the mechanisms contributing to its 

hypoglycemic activity. 

Key words: Black catechu, alloxan, oral 

glucose tolerance. hydrocortisone induced 

hyperglycemia 

Introduction: Black catechu (Kattha in Hindi) 

or cutch is an aqueous extract prepared from 

the heart wood of Acacia catechu Willd 

(Family – Leguminosae) and is mainly used 

as an ingredient of paan and paan masala. 1 

The plant Acacia catechu is a small thorny 

tree of up to 12 m in height, with crooked stem, 

straggling branches, compound, feathery 

leaves and pale yellow, fluffy flowers in dense 

heads. This tree is found in India, Burma, 

Thailand and China. In India, it is grown as a 

multipurpose tree in forestation schemes in 

dry parts of the country. The black catechu 

extract is used to a limited extent against 

diarrhoea, dysentery, chronic catarrh, 

haemorrhage and mouth inflammation. The 

diluted form is employed as gargle for sore 

throat, mouth and gum infections. Externally, 

it is applied to boils and ulcers. 2 Black catechu 

is odourless, light brown to black, friable and 

porous cake. 3 It contains catechin isomers, 

acacatechin (2-12%), catechu tannic acid or 

phlobatannin (25-35%), gum (20-30%), 

quercitrin, quercetin, catechu red and water, 1 

and tastes first somewhat bitter and 

afterwards sweetish. 4 

Acacia catechu is reported to show activities 

like hepatoprotective, 5,6,7 antidiarrhoeal, 

antipyretic ,7 and hypoglycemic. 7,8 However, 



there is hardly any study where the 

hypoglycemic action has been explored 

further to establish the mechanism of action. 

The present study is undertaken using ethyl 

acetate extract of black catechu (EBC) to 

reassess the hypoglycemic activity both in 

normal and hyperglycemic albino rats. Studies 

have been taken up to evaluate effects on oral 

glucose tolerance (OGT) and on 

glucocorticoid induced hyperglycemia. The 

study protocol is approved by the Institutional 

Animal Ethics Committee, and the study is 

carried out in the Department of 

Pharmacology, RIMS, Imphal. 

Materials and Methods: Animals: Healthy 

Wistar albino rats of either sex (110-150 g) 

were used in the present study. The animals 

were housed in standard rat cages and 

maintained on standard diet with free access 

to water. They were acclimatized at room 

temperature with natural light-dark cycle for 7 

days in the departmental animal house. The 

animals described as fasted, were deprived 

of food for 18 h with due care to prevent 

coprophagy, but with free access to water. 

Plant material and extract preparation: 

Black catechu (Kattha) was collected from the 

local market. It was identified and differentiated 

from pale catechu (Uncaria gambier), a 

closely alike preparation by Gambier fluorescin 

test. 3,4 Powdered catechu was defatted with 

petroleum ether (B.P 40 - 60 o C) in soxhlet 

apparatus and spread out to evaporate 

petroleum ether. The dried defatted product 

was repacked and extracted with 95% ethanol 

until the eluent was colourless. Dried ethanol 

extract was again extracted with ethyl 

acetate. 6 The ethyl acetate extract was spread 

on the drying tray and kept for use in the study. 

The yield at the end of the extraction was 4.5%. 

Dose of test drug: The LD 50 

of ethyl acetate 

extract of Acacia catechu in mice was 

reported to be 2500 mg/kg. 6 The LD 50 

of the 

extract in rats as calculated by extrapolation 

method 9 was 1750 mg/kg. Two doses of 250 

and 500 mg/kg of the extract were used as 

suspensions in 2% aqueous gum acacia and 

given per orally as single doses. 

Blood sample collection and glucose 

estimation: Blood samples were collected 

from orbital sinus puncture by using capillary 

tubes. 9 The samples were allowed to settle 

for 30 minutes, and then centrifuged at 2000 

rpm for 20 minutes. 6 The serum glucose 

estimation was done by enzymatic 

colorimetric test using commercial assay kit 

(Human, Germany). 

Induction of hyperglycemia: A single dose 

of 120 mg/kg s.c 10,11 of freshly prepared 

alloxan monohydrate (Sigma Ltd, USA) 

dissolved in normal saline was used for 

induction of hyperglycemia in fasted healthy 

albino rats. The animals were fed on standard 

diet and water ad libitum. The induction of 

hyperglycemia was confirmed 48 h after 

alloxan administration by blood glucose 

estimation, and rats showing blood glucose 

levels of 300-350 mg/dl were used for 

evaluation of the effect the test substance on 

blood glucose in hyperglycemic rats. 

Effect of ethyl acetate extract of black 

catechu (EBC) on blood glucose in normal 

rats: To evaluate the effect of EBC on blood 

glucose, the method of Babu V et al. 12 was 

followed. The healthy albino rats of either sex 

weighing 110 – 150 g were divided into four 

groups – I (control) II, III and IV (standard) of 

six rats in each group. After fasting for 18 h, 

the rats in group I received 2% aqueous gum 

acacia suspension at the dose of 10 ml/ kg. 

The group II and III rats were given the test 

substance i.e. EBC at the doses of 250 and 

500 mg/kg respectively. The group IV animals 

were administered glibeclamide at the dose 

of 0.5 mg/kg. 13 The test and standard drugs 

were prepared as suspensions in 2% aqueous 

gum acacia such that each ml of the 

suspension contained the required dose of the 

drug. Each treatment was given per orally as 

single dose. The glucose concentrations in 

the blood samples collected just prior to drug 

treatments, at 1 and 2 h after treatments were 

estimated. 


catechu (EBC) on blood glucose in alloxan 

induced hyperglycemic rats: The selected 

hyperglycemic rats with blood glucose levels 

between 300 – 350 mg/dl were divided into 

four groups – I (control), II, III and IV (Standard) 

of six rats in each group. After collection of 


55


the fasting blood samples, the animals in the 

different groups were treated in the similar way 

as in the study in normal rats. The glucose 

concentrations were estimated in the fasting 

blood samples, and samples collected at 1 

and 2 h after the treatments. 


catechu (EBC) on oral glucose tolerance: 

To study the effect of EBC on oral glucose 

tolerance (OGT), the principal adopted by Puri 

D and Baral N was followed. 14 Six healthy 

albino rats of either sex (110-150g) were kept 

fasted. After collecting fasting blood samples, 

each rat was administered 2% aqueous gum 

acacia at the dose of 10 ml/kg p.o, followed 

immediately by a glucose load of 3 g/kg p.o 

(30% D-glucose in D/W). The glucose 

concentrations were estimated in the fasting 

blood samples, and samples collected at 1 

and 2 h after glucose load. 

Using the same set of animals, the oral 

glucose tolerance (OGT) tests were repeated 

after single oral doses of 250 and 500 mg/kg 

of EBC, and 20 mg/kg of nateglinide. The drug 

wash out period of 10 days was maintained 

in between successive OGT tests. 15 The dose 

of nateglinide was obtained from human dose 

of 240 mg/day by extrapolation method. 9 


catechu (EBC) on gluconeogenesis: 

Twenty four healthy albino rats of either sex 

(110 – 150g) were divided into four groups of 

six rats in each – I (control) II, III and IV 

(standard) and given fasting. After collection 

of fasting blood samples, all the animals were 

injected hydrocortisone sodium succinate 

(240 mg/kg i.p) 16 and followed immediately 

by the treatments as follows: 

Group I: 2% aqueous gum acacia – 10 ml/ kg 

Group II: EBC - 250 mg/kg 

Group III: EBC - 500 mg/kg 

Group IV: Metformin -135 mg/kg 

The dose of metformin was extrapolated from 

human dose of 1.5 g/day. 9 The drugs were 

suspended in 2% aqueous gum acacia such 

that 1 ml of each preparation contained the 

required dose and given per orally as single 

doses. The blood samples were collected at 

1 and 2 h after the treatments. The glucose 

concentrations in the fasting and after 

treatment blood samples were estimated. 

Statistical analysis: All values were 

expressed as mean ± SD for each group. The 

data were analyzed using One - way ANOVA 

followed by Bonferroni test, and a P value less 

than 0.05 was considered statistically 

significant. 

Results: Effect of EBC on blood glucose 

in normal and alloxan induced 

hyperglycemic rats: In both the normal and 

hyperglycemic rats, the mean blood glucose 

changes (decrease) at 1 and 2 h after 

treatments from the fasting values in the 

different groups were compared. The glucose 

changes were increased in the EBC and 

glibenclamide treated groups, thereby, 

reflecting more reductions in glucose 

Table 1: Effect of EBC on blood glucose in normal albino rats 

Values are mean ± SD. n = 6 in each group. All preparations are suspended in 2% aqueous gum acacia and given per orally 

in single doses. *p


Table 2: Effect of EBC on blood glucose in alloxan induced hyperglycemic albino rats 

Values are mean ± SD. n = 6 in each group. All preparations are suspended in 2% aqueous gum acacia and given per orally 

in single doses. *p


concentrations from the fasting values. The 

EBC (500 mg/kg p.o) and glibenclamide (0.5 

mg/kg p.o) treated groups showed significantly 

different glucose changes (increase) when 

compared with the changes in the control 

groups (Table 1 and 2). 

Effect of EBC on hydrocortisone induced 

hyperglycemia: Following treatments with the 

different drugs just after hydrocortisone 

injection, the blood glucose concentrations 

increased in all the groups from the fasting 

values. The glucose changes (increase) at 1 

and 2 h from the fasting values in the different 

groups were compared. When compared with 

the glucose changes in the control group, the 

EBC treated groups showed significantly less 

(p


glucose induced hyperglycemia at 1 and 2 h 

after nateglinide when compared with 

corresponding values in the control group 

supports the fact that the drug acts as an 

insulin secretagogue. The failure on the part 

of the test substance to produce significant 

fall of glucose induced hyperglycemia shows 

that it is unlikely to act as an insulin 

secretagogue. 

Conclusion 

From the present study, it is evident that ethyl 

acetate extract of black catechu (Acacia 

catechu) exhibits hypoglycemic property. The 

extract possibly does not enhance insulin 

secretion, but inhibition of hepatic 

gluconeogenesis is one of the mechanisms 

which have contributed to its hypoglycemic 

effect. 

References 

1. Ali M. Black catechu. Text book of 

Pharmacognosy. 2 nd ed. New Delhi: CBS 

Publishers & Distributors; 1998.p142-43 

2. Wyk BE, Wink M. Acacia catechu 

Medicinal Plants of the World. 1 st ed 

(reprint). Portland: Timber Press; 

2005.p28. 

3. Kokate CK, Purohit AP, Gokhale SB. Pale 

catechu. Pharmacognosy. 43 rd ed. 

Mumbai: Nirali Prakashan; 2009.p9.16- 

9.17 

4. Evans WC. Phenols and Phenolic 

glycosides. Trease and Evans 

Pharmacognosy. 15 th ed (Indian reprint). 

New Delhi: Elsevier; 2006.p214-252. 

5. Subramoniam A and Pushpangadan P. 

Development of phytomedicines for liver 

diseases. Indian J Pharmacol 1999; 

31(3): 166-75. 

6. Jayasekhar P, Mohanan PV and 

Rathinam K. Hepatoprotective activity of 

ethyl acetate extract of Acacia catechu. 

Indian J Pharmacol 1997; 29(6): 426 – 

28. 

7. Ray D, Sharatchandra K and Thokchom 

IS. Antipyretic, antidiarrhoeal, 

hypoglycaemic and hepatoprotective 

activities of ethyl acetate extract of Acacia 

catechu Willd in albino rats. Indian J 

Pharmacol 2006; 38(6): 408 – 13. 

8. Singh KN, Mittal RK and Barthwal KC. 

Hypoglycemic activity of Acacia catechu, 

Acacia suma, Albizzia odoratissima seed 

diets in normal albino rats. Indian J Med 

Res 1976; 64(5): 754 – 57. 

9. Ghosh MN. Fundamentals of 

Experimental Pharmacology. 3rd ed. 

Kolkata: Hilton & Company; 2005. 

10. Shoka AAE. Effect of some oral 

antidiabetic drugs on glucose and mineral 

metabolism in alloxan diabetic rats 

pretreated with ethylene diamine tetra 

acetic acid disodium salt. Indian J 

Pharmacol 1992; 24(4): 201 – 6. 

11. Parmer NS, Prakash S. Screening 

methods in Pharmacology. New Delhi: 

Narosa Publishing House; 2006. 

12. Babu V, Devi TG, Subramoniam A. 

Antidiabetic activity of ethanol extract of 

Cassia klenni leaf in glucose fed normal 

rats and alloxan induced diabetic rats. 

Indian J Pharmacol 2002; 34(6): 409 – 15. 

13. Ignacimuthu S, Amalraj T. Effect of leaf 

extract of Zizyphus jujuba on diabetic rats. 

Indian J Pharmacol 1998; 30(2): 107 – 8. 

14. Puri D, Baral N. Hypoglycemic effect of 

Biophytum sensitivum in the alloxan 

diabetic rabbits. Indian J Physiol 

pharmacol 1998; 42(3): 401 - 6. 

15. Venkateswarlu V. Biopharmaceutics and 

Pharmacokinetics. Hyderabad: Pharma 

Book Syndicate; 2004. 

16. Marcus DF, Wales JK, Viktoria JK, Wolff 

FW. A comparative study of various 

hyperglycemic agents in potassium 

deficient rats. Proc Soc Exptl Biol Med 

1968; 127(2): 533 – 38. 

17. Brahmachari HD, Augusti KT. Isolation of 

orally effective hypoglycemic compounds 

from Ficus bengalensis Linn. Indian J 

Physiol Pharmacol 1964; 8(11): 60 – 64. 


59


18. Rerup CC. Drugs producing diabetes 

through damage of insulin secreting 

cells. Pharmacol Rev 1970; 22(4); 485 – 

81. 

19. Zastrow MV, Bourne HR. Drug receptors 

and pharmacodynamics. In: Katzung BG, 

Masters SB, Trevor AJ, editors. Basic 

and Clinical Pharmacology. 11 th ed. New 

Delhi: Tata McGraw-Hill education Pvt Ltd; 

2009. p 15 – 35. 

20. Schimmer BP, Parker KL. 

Adrenocorticotropic hormone; 

Adrenocortical steroids and their 

synthetic analogs; Inhibitors of synthesis 

and actions of adrenocortical hormones. 

In: Brunton LL, Lazo JS, Parker editors. 

Goodman & Gillman’s The 

Pharmacological basis of Therapeutics. 

11 th ed. New York: McGraw- Hill; 2006. p 

1587 – 1612. 

21. Gunindro N, Das L, Pramodini KK, Singh 

TI. Study of the ethyl acetate extract of 

Cutch (Acacia catechu) on peripheral 

glucose uptake and its interaction with 

insulin by using isolated rat 

hemidiaphragm. Indian Medical Gazette 

2008; CXLII (8): 306 – 9. 

22. Puri D, Prabhu KM, Murthy PS. 

Mechanism of action of a hypoglycemic 

principle isolated from Fenugreek seeds. 

Indian J Physiol Pharmacol 2002; 46(4): 

457 – 462. 

23. DeFronzo RA. Pathogenesis of type 2 

Diabetes mellitus. Med Clin N Am 2004; 

88(4): 787 – 835. 



Trends in blood component therapy – A RIMS experience. 

1 

A. Barindra Sharma, 2 O. Geetchandra Singh, 2 Pratima Khoyumthem, 2 K. Rachandra Singh, 3 Kh. Nando 

Singh, 4 Prof. A. Meina Singh, 

Abstract 

Aim of study: To evaluate the use of different 

types of blood components. Methods: The 

present study is based on the different types 

of blood components prepared and issued 

from the department of Immunohaematology 

and Blood transfusion, RIMS, Imphal during 

the five year period from January 2006 to 

December 2010. Blood components were 

prepared from whole blood collected in multiunit 

bags containing CPD-A solution and 

centrifuged in refrigerated centrifuge as per 

standard operating procedures (SOPs). The 

components were packed red cells, liquid 

plasma, platelet rich plasma, platelet 

concentrate, fresh frozen plasma and 

cryoprecipitate. Results: The total number of 

blood components issued were 11130 out of 

total 69512 blood units issued making a 

percentage of 16.01%. Packed red cells were 

utilized most (72.98%) followed by platelets 

(24.57%). The least utilized was 

cryoprecipitate (5 units only). The maximum 

numberof components were utilized in 2010 

(3701 units). Conclusion: The trend of 

component therapy is encouraging. Use of 

blood components has many advantages. 

Whole blood transfusion should be minimized 

as it has limited indications. 

1. Associate prof., 2. P.G. Trainee 3. Chief Medical 

Officer, 4. Prof. and Head, Dept. of Immunohaematology 

and Blood transfusion 


Dr. A. Barindra Sharma, Assoc. Prof. of Immunohaematology 

& Blood Transfusion, RIMS, Imphal 

E-mail: abarindras @ yahoo.co.in 

Key words: Blood components, whole blood, 

transfusion transmissible infections. 

Introduction: Blood is always in short supply 

both in developing and developed countries. 

Before component separation was not known 

the shortage of any of the blood components 

was treated by transfusing whole blood. This 

means the patient received a host of unwanted 

cells and components from someone else 

which the patient may not need, besides 

volume overload. Since blood transfusion 

involves the transplant of tissue from the donor 

to the recipient, there are risks to the recipient 

of transfusing transmissible infections and of 

immunological responses to the foreign cells 

and plasma proteins. 1 

These days blood transfusion therapy has 

been converted into component therapy 

because very few require transfusion of whole 

blood. This has become one of the effective 

methods of optimizing blood usage. 

Materials and methods: The study was 

conducted in the department of Immunohaematology 

and blood transfusion, RIMS, 

Imphal during the period from January 2006 

to December 2010. Data of whole blood 

collection, component separation and issued 

during the period were analysed and 

recorded. The components were prepared 

from whole blood collected in multi-unit bags 

containing CPD-A solution. The bags were 

centrifuged in the refrigerated centrifuge 

(Cryofuge 6000i, Heraeus, Germany) at 

different speeds and time as per standard 

operating procedures (SOPs) and the 

components prepared were packed red cells, 


61


liquid plasma, platelet rich plasma, platelet 

concentrate and fresh frozen plasma (FFP). 

Cryoprecipitate was further prepared from 

FFP by collecting the precipitate formed during 

controlled thawing and resuspending in 10- 

20ml plasma. 

Results: A total of 69512 blood units were 

issued during the five-year period, out of which 

11130 units were issued as components, 

making a percentage of 16.01 (Table 1). 

Packed red cells were the most utilized 

component (72.98%) followed by platelet 

component (24.57%), liquid plasma (1.46%) 

and FFP (0.93%) respectively and the least 

utilized was cryoprecipitate with only 5 units 

issued during the period (Table 2). The 

maximum number of components were 

utilized in 2010 (3701 units and a percentage 

of 26.89). 

Discussion: Blood component and derivative 

therapy began during the world war-II when 

Edwin J. Cohn and his collaborators 

developed the cold ethanol method of plasma 

fractationation 2 . 

Making components from whole blood not only 

serves more patients but also improves the 

storage of the individual blood elements. Red 

cells are best stored cold, platelets at room 

temperature with agitation and plasma 

frozen. 3,4 Whole blood when stored at 2-6 0 C 

has few viable platelets after 24 hours while 

after separation, platelets can be stored for 

five days at 22 0 C. Where plasma is frozen at 

-25 0 C or colder, it can be stored for at least 

one year or longer and heat labile coagulation 

factors (Factor V and VIII) are preserved 1,5 . 

Liquid plasma is plasma separated from a 

whole blood unit and stored at 4 0 C and is 

devoid of any labile coagulation factors 1 . 

Moreover the specific components could be 

given as required in adequate dose without 

danger of overloading or complications due 

to other portion of blood 6 . 

In India, 80 percent of blood is used as whole 

blood and only 20 percent units are utilized 

as components 7 . WHO also recommends 

that the ratio of the use of blood components 

and whole blood should be 90:10. As a national 

action plan, NACO has advocated under 

NACP-III (2007-2012) that at least 50% of all 

blood collections should be separated into 

components 7 . In Maharastra, 40% of the total 

blood units are separated into components 

and in Gujarat, 38% are given as components 8 . 

It was also suggested that promoting blood 

component therapy would not only bring down 

the requirement of whole blood by 60-70%, it 

would also ensure the optimum use of all 

resources 7,8 . The overall percentage of 

components in RIMS (16%) is still lower than 

the national average of 20%. Encouraging 

trends are emerging in RIMS Hospital since 

the availability of component separation facility 

since October 2002, and components issued 

reached 26% in 2010. Component therapy is 

now a better medicine and we should 

encourage this for better patient care services. 

Conclusion: Appropriate component therapy 

now provides more effective treatment and 

more complete use of blood products. By 

providing the right blood product, in the right 

quantity for the right patient, the gap between 

demand and supply can be bridged. 

AcknowleDgement: The authors sincerely 

express gratitude to Dr. Y. Bijoykumar Singh, 

Chief Medical Officer, Department of 

Immunohaematology and Blood Transfusion, 

RIMS for his various inputs and technical 

support in completion of the work. 



References: 

1. The clinical use of blood. WHO, Blood 

Transfusion Safety, Geneva, 2002. 

2. Cohn EJ. The separation of blood into 

fraction of therapeutic value. Ann Intern 

Med 1947; 26: 341-52 

3. Solheim BG, Hess JR: Red cell 

metabolism and preservation. In: Simon 

TL, Synder EL, Solheim BG, Stowell CP, 

Stauss RG, Petrides M, editors. Rossi’s 

Principles of Transfusion Medicine, 4 th ed. 

U.K. Wiley-Blackwell, 2009: 54-66. 

4. Transfusion Guidelines for blood 

components. Medical advisory committee 

of the American Red Cross Blood 

Services, New England, USA, December 

2003. 

5. Practice parameters for the use of FFP, 

cryoprecipitate and platelets. Task Force 

of American College of Pathologists. 

JAMA 1994; 271: 777-781. 

6. Saran RK. Transfusion Medicine 

Technical manual. 2 nd ed. Directorate 

General of Health Services, Ministry of 

Health and Family Welfare, Government 

of India, New Delhi. 2003. 

7. An action plan for blood safety. NACO, 

Ministry of Health and Family welfare, 

Government of India, New Delhi, 2007. 

8. Romani KV, Mavalankar DV, Govil D. 

Study of Blood transfusion services in 

Maharastra and Gujarat states, India. J 

Health Popul Nutr 2009 April : 259-270. 


63


Breast-feeding: patterns and correlates in Manipur 

1 

R.K. Narendra 2 N. Sharat Singh 3 N. Sanajaoba Singh 

Abstract 

Objective: To study the breastfeeding (BF) 

patterns and also to identify the determinants 

which may have profound effects on the 

duration of BF. 

Methods: A cross sectional study of 1225 

ever-married women of reproductive age with 

at least one live birth was conducted in four 

valley districts of Manipur under cluster 

sampling scheme. Survival analysis technique 

has been adopted through SPSS vs 16. 

Results: The median duration of BF is found 

to be 20.37 months. Among the seven 

explanatory variables of interest, only two 

factors – place of residence (urban, relative 

risk (RR) =1.35) and employment status 

(employed, RR=1.88) have highly significant 

effect (P


availability of supplementary foods, socioeconomic 

status etc. 10-13 So the study of 

behaviour and differential of BF is very 

important in a society where the fertility, 

woman as well as child health are becoming 

a serious problem. Therefore this study tries 

to touch these issues. The main objective of 

this paper is to study the breastfeeding (BF) 

patterns and also to identify the determinants 

which may have profound effects on the 

duration of BF by using survival analysis 

techniques. 

Materials and methods: A cross sectional 

study was conducted in four valley districts – 

Bishnupur, Thoubal, Imphal West and Imphal 

East – of Manipur during January1 to June 30, 

2009. Under cluster sampling scheme, house 

to house survey was carried out with pretested 

and semi-structural interview schedule 

on ever-married women of reproductive age 

with atleast one live birth. The clusters of 

randomly selected villages in rural area and 

wards in urban were completely enumerated 

which entailed a sample of 1225 women from 

1013 households 

Here, the duration of BF is taken as the 

response variable and is defined as the child’s 

age (in months) at the time of complete 

weaning, regardless of when consumption of 

other food began. For the children who have 

died or still being breastfed at the time of 

survey, the duration is the child’s age at death 

or at the time of survey. Such cases are 

treated as censored ones. 

The explanatory variables or so termed as 

covariates are socio-economic and 

demographic characters. The categorical 

variables are quantified by binary dummy 

variable (0, 1). The socio-economic variables 

include place of residence (urban=1, rural=0), 

educational level, employment status 

(employed=1, unemployed=0) and family 

income. The demographic variables are age 

at marriage, sex of previous child (male=1, 

female=0) and parity. 

As the study is confined in censored data, 

statistical analysis is therefore carried out 

using survival analysis techniques. Firstly, the 

survival function of BF (the proportion of 

women reported termination of BF within 6, 

12, 18 and 24 months) with respect to socioeconomic 

is estimated by life table technique 

14-15 

and log rank test 16 is employed to 

compare the survival experience between 

different groups under study. Secondly, the 

effects of various demographic and socioeconomic 

factors on the dynamics of duration 

of BF are investigated by utilizing Cox’s 

proportional hazard model. 17 

Results: Table 1 provides the overall median 

duration of BF of the study population which 

is 20.37 months. About 59 per cent, 35 per 

cent, 24 per cent, 16 per cent and 13 per cent 

of the mothers who have married during the 

age group of below 15 years, 15-20 years, 

20-25 years, 25-30 years, and 30 years and 

above respectively terminate BF within 12 

months. It also highlights that the median 

duration of BF increases with the increase in 

the age at marriage of mothers. By the Log 

rank test, the association between age at 

marriage and duration of BF is highly 

significant (x 2 = 26.181, P < 0.001). It could be 

examined that 59 per cent of mothers having 

parity zero terminate BF within 12 months. 

On contrary, 23 per cent of mothers having 

parity one, that of 22 per cent of parity two, 

20 per cent of parity three and 19 per cent of 

parity four and above terminate BF within 12 

months. The median duration of BF increases 

with the increase in parity and this variation is 

highly significant in the study population 

irrespective of other covariates (P < 0.001). 

Mothers residing in rural areas have longer 

duration of BF (20.85 months) than residing 

in urban areas (18.48 months) and relationship 

is found to be statistically significant 

(P


mothers (20.55 months) than employed 

mothers (15.40 months). About 22 per cent 

of unemployed mothers terminate BF within 

12 months while 41 per cent of employed 

mothers terminate BF within 12 months. Only 

15 per cent of mother having family income of 

below Rs. 2000 terminate BF within 12 

months. But 19 per cent of the study subjects 

having family income of Rs. 2000-4000, 21 per 

cent in the income of Rs. 4000-6000, 25 per 

cent in Rs. 6000-8000, 29 per cent in Rs. 8000- 

10000 and 34 per cent in Rs. 10000 and above 

terminate BF within the same period. The 

variation in the median duration of BF with 

respect to family income is highly significant 

(P


Table 2 

Cox’s regression analysis of covariates on the 

duration of BF 

Table 3 

Stepwise Cox’s regression analysis of covariates on 

the duration of BF 

0.090 

Discussion: The above result shows that the 

median duration of BF is 20.37 months, which 

is lower than the minimum of 24 months 

recommended by WHO for most children. 

The duration of about 20 months is also 

lacking behind the India’s national figure of 25 

months observed by National Family Health 

Survey-3 (NHFS-3). The findings arrived in the 

present study also highlight that different 

factors have different effects on duration BF. 

The duration of BF increases with the increase 

in parity. It might be due to the fact that mothers 

of high parity may be older and they produce 

less milk but they may be more traditional in 

orientation, and usually lower order births 

occur in quick succession than higher order 

births and hence the chance of voluntary 

termination of BF at an early age of child might 

be higher for the lower birth order babies than 

for the higher birth order. This view is 

consistent with the other findings observed 

by several researchers. 4,11,13,18 The 

educational level of mothers show an inverse 

relationship with the duration of BF, owing to 

the fact that educated mothers probably start 

giving food supplements to their children 

earlier and so a shorter period of lactation. 

Similar, findings have also been obtained by 

other researchers in developing countries . 1, 

8, 11 

Place of residence has a significant impact 

on the duration of BF. The risk of termination 

of BF of mothers residing in urban is higher 

than those in rural. The shorter duration of BF 

in urban areas is thought to be caused by 

higher educational level and higher income 

than that of rural. This view is incorporated 

with the past findings. 9, 13 Besides, employed 

mothers have shorter duration of BF than 

unemployed one. The reason may be that 

employed mothers do not get enough time to 

breastfeed their children as they work outside 

and thus tend to lactate for shorter period and 

probably also provide food supplements to the 

children much earlier. It is supported by the 

earlier findings too. 1, 12 Mothers of high income 

group have shorter duration of BF. It may 

perhaps be the fact that economically affluent 

families could afford to buy powder milk, other 

baby formulae, wet nurses etc. Similar views 

have also been reported by other researchers 

based on the data from developing countries. 12 

Conclusion: The present duration of 

breastfeeding, that is about 20 months, is 

lower than the WHO recommended figure of 

24 months and even lacking behind the all 

India’s figure of 25 months. This low status of 

breastfeeding may cause hazardous problem 

in reproductive and child health. Thus, we 

have to promote the breastfeeding practice 

among the educated and employed women 

having high income and the women residing 

in urban areas too through vigorous 

implementation of inter-sectoral operational 

strategies. Over and above, prolong breastfed 

mothers have to lengthen the duration of inter 

live-birth interval for reducing current fertility 

and to improve economic status of general 

community resulting into better way of life. 


67


References 

1. Huffman SL. Determinants of 

breastfeeding in developing countries: 

overview and policy implications. Studies 

in Family Planning 1984; 15(4): 144-54. 

2. Thapa S, Williamson NE. Breast-feeding 

in Asia: an overview. Asia-Pacific 

Population Journal 1990; 5(1): 7-25. 

3. Lechtig JAD, Jelliffe E. The first workshop 

on national breast-feeding programmes 

in Latin America: a personal view. Journal 

of Tropical Pediatrics; 1990. 

4. Mannan HR, Islam MN. Breastfeeding in 

Bangladesh: patterns and impact on 

fertility. Asia-Pacific Population Journal 

1995; 10 (4): 23-38. 

5. Chhabra P, Grover VL, Aggarwal OP, 

Dubey KK. Breastfeeding patterns in an 

urban resettlement colony of Delhi. Indian 

Journal of Pediatrics 1998; 65: 867-72. 

6. Lawrence RA. Peer support: making a 

difference in breastfeeding duration. Can 

Med Assoc J 2002; 166: 42-43. 

7. Yngve A, Sjostrom M. Breastfeeding in 

countries of the European Union and 

EFTA: current and proposed 

recommendations, rationale, prevalence, 

duration and trends. Public Health Nutr 

2001; 4: 631-45. 

8. Koosha A, Hashemifesharaki R, 

Mousavinasab N. Breast-feeding patterns 

and factors determining exclusive breastfeeding. 

Singapore Med J 2008; 49 (12): 

1002. 

9. Agrawal DK, Agarwal KN, Tiwari IC, 

Yadava KNS. Breast-feeding practices in 

urban slum and rural areas of Varanasi. 

Journal of Tropical Pediatrics 1982; 28. 

10. Aaryal TR. Some techniques to estimate 

child mortality in Nepal. Journal of Institute 

of Science and Technology 2004; 13: 48- 

61. 

11. Aaryal TR. Differentials of breastfeeding 

among rural women of Western Nepal: a 

survival analysis. Journal of Nepal Health 

Research Council 2005; 3(2): 58-64. 

12. Giashuddin MS, Kabir M. Duration of 

breastfeeding in Bangladesh. Indian J Med 

Res 2004; 119: 267-272. 

13. Islam S, Yadava KNS, Alam MA. 

Differentials and determinants of the 

duration of breastfeeding in Bangladesh: 

a multilevel analysis. Proc. Pakistan 

Acad. Sci. 2006; 43(1): 1-14. 

14. Berkson J, Gage RR. Calculation of 

survival rates for Cancer. Proceedings of 

staff meetings of the Mayo Clinic 1950; 

25: 250. 

15. Cutler SJ, Ederer F. Maximum utilization 

of the life table method in analyzing 

survival. Journal of Chronic Diseases 

1958; 8: 699-712. 

16. Peto R, Peto J. Asymptotically efficient 

rank invariant procedures. Journal of the 

Royal Statistical Society 1972; Series A, 

135: 185-207. 

17. Cox DR. Regression models and life 

tables. Journal of the Royal Statistical, 

Society 1972; Series B, 34(2): 187-220. 

18. Ahamed MM. Breastfeeding in 

Bangladesh. Journal of Biosocial Science 

1986; 18(4): 425-434. 



Clinical profile of nasopharyngeal Carcinoma with neurological complications 

1 

Lozinu J, 2 S. Thingbaijam, 1 Rino K, 3 Sobita P, 1 Das B, 4 W. Jatishwar 

Abstract: 

Objective: To study the clinical and 

radiological profile of nasopharyngeal 

Carcinoma with neurological complications. 

Method: Discriptive study of twenty eight 

newly diagnosed patients of nasopharyngeal 

carcinoma (NPC) with neurological 

complications admitted in the department of 

Otorhinolaryngology, Regional Institute of 

Medical Sciences, Imphal, Manipur during a 

two years period between September 2008- 

July 2010 were evaluated for clinical profile. 

Patients with histologically proven NPC with 

neurological complications of all age group 

were included in the study irrespective of age, 

sex, occupation, religion, race, socioeconomic 

status and address. Patients with 

recurrent or residual NPC or without 

neurological complications were excluded 

from the study. The diagnosis was made from 

the clinical findings, histopathological tests 

and radiological studies. Results: Cervical 

lymphadenopathy was the most common 

presenting complaint (75%). The most 

common neurological symptoms at diagnosis 

were facial pain/trigeminal neuralgia present 

in 19 patients (38.8%). The most commonly 

involved nerve was the trigeminal (V) nerve 

1. Post graduate trainee; 2. Associate Professor; 

3. Assistant Professor, Department of 

Otorhinolaryngology, RIMS 4. Prof. Dept. of 

Radiodiagnosis, RIMS, Imphal 


Dr. Thingbaijam S, Associate Professor, Dept of 

Otorhinolaryngology, RIMS, Imphal – 795004 

Email – dr_sthingbaijam@yahoo.in 

(67.9% of cases). The CT evaluation of NPC 

patients with cranial nerve involvement should 

include thin cuts of the skull base for detection 

of subtle bone erosion. Conclusion: NPC 

with neurological complications is not as 

uncommon as believed to be. Therefore it is 

important to do a thorough neurological 

examination and radiological imaging to know 

the exact extent of the primary tumour in a 

case of NPC. 

Key words: Nasopharyngeal carcinoma, 

neurological symptoms, cranial nerve, 

computerized tomography (CT) and MRI 

(Magnetic resonance imaging) 

Introduction: Nasopharyngeal carcinoma 

malignancies (NPC) frequently escape early 

recognition. This can be attributed to the 

insidious manner of growth, the lack of 

specificity of initial symptoms, and the relative 

inaccessibility of the nasopharynx to routine 

examination. Neurological manifestations may 

occur early or late in the course of the disease, 

and may at times be the earliest recognizable 

abnormalities. 1 This study on NPC presenting 

in advanced stage or with neurological 

complications was carried out with the 

purpose of calling attention to the disease as 

one cause of neurological symptoms and 

signs which may be puzzling at times. 

Materials and Methods: 28 cases of 

histologically confirmed cases Of NPC with 

neurological manifestations were studied in 

the Department of Otorhinolaryngology, 

Regional Institute of Medical Sciences, Imphal, 

Manipur during a period between September 


69


2008 and July, 2010. Detailed history with 

clinical examination was done and recorded 

in a prescribed proforma. Endoscopic 

examination with 0 0 and 30 0 Karl Storz 

endoscope, biopsy for histopathological 

examination along with computer tomography 

(CT) and magnetic resonance imaging (MRI) 

of the nasopharynx, head and neck were done. 

Patients with recurrent or residual disease or 

without neurological involvement were 

excluded from the study. Statistical analysis 

was done with Chi-square test in SPSS 17 

version. 

Results: The results of the study done on 28 

cases of NPC with neurological manifestations 

are presented below: 

Neck swelling was the most common clinical 

feature among 21(75%) patients; followed by 

facial pain in 19 ( 67.9%) patients. Otological 

symptoms: hearing loss and ear fullness in 

18 (64.3%) patients as shown in table 1. 

Table I: Clinical features of Nasopharyngeal carcinoma patients 

with neurological involvement 

Symptoms 

No. of patients(%) 

Neck swelling 21(75) 

Sticky sensation back ofnose/throat 

10(35.7) 

Epistaxis 9(32.1) 

Nasal obstruction 10(35.7) 

Tinnitus 10(35.7) 

Fullness of ears & Hearing loss 18(64.3) 

Otalgia 3(10.7) 

Otorrhea 3(10.7) 

Headache 16(57.1) 

Dysphagia 11(39.3) 

Nasal regurgitation 11(39.3) 

Diplopia 12(42.9) 

Diminished vision 7(25) 

Proptosis 1(3.6) 

Facial pain 19(67.9) 

Ptosis 7(25) 

Hoarseness 1(3.6) 

Loss of smell 1(3.6) 

Trismus 4(3.6) 

Facial asymmetry 2(7.1) 

Fig. 2 shows Cranial Nerve involvement 

among the Nasopharyngeal carcinoma 

patients with neurological complications. 

Trigeminal nerve (Cr. nerve V ) was found to 

be the most common cranial nerve involved 

in 19 (67.9%), followed by the Abducent nerve 

(Cr. nerve VI), which was since in 12 (43%). 

Figure 2: Bar chart representing the different 

types of cranial nerves involved 

Table-2: Histopathological report of the Nasopharyngeal 

carcinoma patients with intracranial complications 

Table-3: Computed Tomography nasopharynx findings among 

the Nasopharyngeal carcinoma patients with neurological 

involvement. 

Table-4: Magnetic Resonance Imaging study of nasopharynx 

findings of the nasopharynx carcinoma patients with intracranial 

complications. 

Non-keratinizing undifferentiated type was 

found to be the most common histopathological 

picture in Nasopharyngeal 

carcinoma patients with intracranial 

complications comprising of 23 (82.1%), 


Table 5: CT finding showing relation of skull base 

erosion, intracranial extension, and cranial nerve 

involvement (n=28) 

Table 6: MRI finding showing relation of skull base 

erosion, intracranial extension, and cranial nerve 

involvement (n= 23) 

follow by differentiated non-keratinising 

carcinoma 4 (14.3%) as shown in table 2. 

Skull base erosion was detected via CT in 14 

(50%) of the patients. Intracranial extension 

was detected in 14 (46.4%) of the patients 

as shown in table 3. MRI could detect 14 

(50%) of skull base erosion and 18 (64.3%) 

of intracranial extension of the nasopharyngeal 

carcinoma as shown in table 4. 

A significant correlation was found between 

skull base erosion and involvement of cranial 

nerves III-VI and either skull base erosion or 

intracrenial extension (p=0.000) as seen in 

both the CT and MRI findings (Table 5 & 6). 

The last four cranial nerves IX-XII are involve 


significantly (P=006,P=000) when there is no 

skull base erosion or intracranial extension 

detected by CT or MRI scans. 

Discussion: Cervical lymphadenopathy was 

the most common presenting complaint in 21 

(75%) patients. A study in Taiwan, reported 

75.5% (729 out of 966) of patients presented 

with neck mass. 2,3 Neurological complications 

associated with malignant tumours of 

nasopharynx range from 30 to 70% in large 

series 4 . In our study, the most common 

neurological symptoms at diagnosis was 

facial pain/trigeminal neuralgia present in 

19(67.9%) patients and the trigeminal was the 

most commonly involved nerve (67.9%). We 

have found that I and VIII nerves are rarely 

affected. These finding agrees with most of 

the studies. 5,6,7,8 The cranial nerves traversing 

the middle fossa are the most susceptible to 

injury because Rosenmûller’s fossa, the 

classic site of origin of primary 

nasopharyngeal malignant tumors, lies 

directly beneath the foramen lacerum. This 

aperture and the nearby foramen ovale are 

the preferred routes of entry into the cranial 

cavity. The structures in immediate proximity 

to these foramina are the tip of the petrous 

pyramid that is crossed by the abducents 

nerve, the gasserian ganglion, and emerging 

trigeminal branches, and the cavernous sinus 

with its contents. Thus there is a high 

incidence of patients with fifth and sixth nerve 

lesions. Cranial nerves leaving the skull 

through the posterior fossa are also 

susceptible to damage from such a tumor. 

As a rule, these lesions are extracranial and 

are caused either by spread of the tumor into 

the retroparotidean space, or by pressure 

from metastasis in the retropharyngeal lymph 

nodes. I, III and IV nerves are usually 

compromised when the tumor reaches 

forward to the anterior portion of the cavernous 

sinus and the superior orbital fissure. The VII 

nerve generally is involved in the neck after 

its emergence from the stylomastoid foramen, 

and the olfactory nerve is affected by 

expansion of the tumor into the nasal cavity 

or through the cribriform plate. 1 The VII and 

VIII nerves are protected by the petrous bone 

and hence are rarely injured in all series 9 , as 

seen in our case. In the present study non- 


71


keratinizing undifferentiated carcinoma was 

found as the most common histopathological 

picture (82.1%). This is comparable to the 

study done by McGuire LJ et al (82.1%). 10 

There were 14 (28.6%) patients who had skull 

base erosion and the 13 (26.5%) patients who 

had intracranial extension on CT scan. This 

is comparable to a study in Hong Kong which 

observed erosion of skull base in 31.3% but 

reported a lower percentage of intracranial 

extension (12.2%). 11 In the present study, 14 

(50%) patients had skull base erosion and 18 

(78.2%) had intracranial extension on MRI 

study of the 23 patients. All skull base erosion 

were detected by CT scan but intracranial 

extension was seen better by MRI particularly 

parasellar and cavernous sinus region. It was 

observed that patients having skull base 

erosion or widening of foramina may not 

necessarily have intracranial extension. This 

finding agrees with Sham JST at al. 11 A Hong 

Kong study of 67 patients reported that MRI 

showed intracranial extension in 38(56.7%) 

versus 24(35.8%) on CT. 12 A significant 

involvement of cranial nerve III-VI (p=0.000) is 

seen in patients who had either skull base 

erosion or intracranial extension, a finding 

References: 

1. Thomas JE, Waltz AG. Neurological 

manifestations of nasopharyngeal tumors. 

JAMA 1965;192: 95-8. 

2. Garandawa HI, Ahmad BM, Ngadda HA. 

Nasopharyngeal carcinoma in Northeastern 

Nigeria: clinical trends. Niger J Clin 

Pract 2009; 12(4):379-82 

3. Wong BYK. Nasopharyngeal carcinoma in 

Hong Kong- clinical features and diagnosis. 

Hong Kong Med J 1987;39:243-5 

4. Turgman J, Braham J, Modan B, 

Goldhammer Y. Neurological 

complications in patients with malignant 

tumors of the nasopharynx. Eur Neurol 

1978; 17:149-54. 

5. Neel HB III. Nasopharyngeal carcinoma: 

clinical presentation, diagnosis, treatment, 

and prognosis. Otolaryngol Clin North Am 

1985; 18:479-90. 

6. Godtfredson E. Ophthalmologic and 

neurologic symptoms at malignant 

nasopharyngeal tumors: clinical study 

comprising 454 cases with special 

similar to Sham JST et al. 11 The last four 

cranial nerves IX-X are found to be affected 

significantly (p=0.00 & p=0.000) in patients 

without either skull base erosion or intracranial 

extension. These nerves might have been 

involved in the retroparotidian space or in the 

retropharyngeal space outside the skull by 

either extension of the tumor or metastatic 

node. 

Conclusion: NPC with neurological 

manifestations is common as found in our 

study. V is the most commonly involved cranial 

nerve. Most of the patients with III-VI cranial 

nerve involvement had skull base erosion. 

Non-keratinizing undifferentiated carcinoma 

was found as the most common 

histopathological picture. Skull base erosion 

and intracranial extension are demonstrated 

well in CT and MRI and they are thus, 

important tools for the diagnosis, staging and 

treatment planning of nasopharyngeal 

carcinoma. Neurological manifestations 

should be paid attention to, in a case of NPC 

and proper otoneurological examination with 

CT and MRI should be for early diagnosis and 

treatment which would improve the prognosis 

of the disease. 

reference to histopathology and possibility 

of earlier recognition. Acta Otolaryngol 

1944; 59 suppl:19-323. 

7. Hoppe RT, Goffinet DR, Baghshaw MA. 

Carcinoma of the nasopharynx: eighteen 

years experience with megavoltage radiation 

therapy. Cancer 1976; 37:2605-12. 

8. Baker SR. Malignant tumours of the 

nasopharynx. J Surg Oncol 1981; 17:25-32. 

9. Brennan B nasopharyngeal carcinoma. 

Orphanet J Rare Dis 2006; 15:1765-77. 

10. McGuire LJ, Lee JC. The histopathologic 

diagnosis of nasopharyngeal. Ear Nose 

and Throat J 1990; 69:229-36. 

11. Sham JST, Cheung YK, Choy D, Chan FL, 

Leong L. Cranial nerve involvement and 

base of the skull erosion in 

nasopharyngeal carcinoma. Cancer 

1991;68:422-6. 

12. Ng SH, Chang TC, Ko SF, Yen PS, Wan 

YL, Tand LM et al. Nasopharyngeal 

carcinoma: MRI and CT assessment. 

Neuroradiology 1997;39:741-6. 


CASES SERIES 

A profile of renal tubular acidosis 

1 

K. Felix Jebasingh, 2 Salam Ranabir, 3 Lallan Prasad, 4 M.Bijoy, 5 Th. Premchand Singh 

Abstract: 

Objective: To Study the characteristic and 

biochemical feature of Renal tubular acidosis 

(RTA). Methods: Retrospective analysis of 4 

cases of RTA from the Department of 

Medicine, Regional Institute of Medical 

Sciences, Imphal. Results: Our case series 

comprised of 4 cases. The mean age of our 

series was 41+ 18 years. The male to female 

ratio was 1:1.Three patients had recurrent 

periodic paralysis and one had proximal 

muscle weakness. The mean arterial 

bicarbonate was 14.97+ 2.98.The mean 

potassium, chloride and fasting urine pH levels 

were 2.45+ 1.33, 117+ 1.41 and 7.07+1.22 

respectively. All the patients had distal RTA 

(d-RTA). Out of four patients, one had dRTA 

secondary to autoimmune disease. 

Conclusion: From our case series we would 

like to highlight that in the presence of 

recurrent periodic paralysis or persistent 

hypokalemia, RTA is a possibility. As these 

patients need bicarbonate, in addition to 

potassium supplements a proper evaluation 

is needed. 

Keywords: RTA, Metabolic acidosis, Periodic 

paralysis. 

Introduction: Renal tubular acidosis is the 

syndromic disorder characteristic by defect 

1. P.G. student, 2. Assistant Professor, 3. Associate 

Professor, 4. Senior Registrar, 5. Professor, 

Department of Medicine, RIMS, Imphal, Manipur. 

Corresponding Author: 

Dr.Lallan Prasad, Associate Professor, Department 

of Medicine, Regional Institute of Medical 

Sciences, Imphal, Manipur. 

in the urinary acidification, in the absence of 

defect in the nephron leading to metabolic 

acidosis and its systemic complication 1 . 

Patients who presents with hyperchloremic 

hypokalemic metabolic acidosis in the setting 

of normal renal function without 

gastrointestinal potassium loss, diagnosis of 

renal tubular acidosis (RTA) needs to be 

considered 2 . Unlike hypokalemia due to renal 

or gastrointestinal loss these patients need 

bicarbonate along with potassium 

supplements and calcium/vitamin D 

supplements depending upon the type of 

RTA 3 . 

There are three major type of renal tubular 

acidosis. 

1) Type 1 or distal renal tubular acidosis 

(dRTA) where there is failure of the kidney to 

lower the PH less than 5.5 in the presence of 

metabolic acidosis. Fractional excretion of 

bicarbonate is low and the patients may have 

nephrocalcinosis and nephrolithiasis. 

2) Type 2 or proximal renal tubular acidosis 

(pRTA) is characterized by glucosuria in the 

presence of normal plasma sugars, 

aminoaciduria, phosphaturia, with high 

fractional excretion of bicarbonate. The 

generalized defect in the proximal tubule is 

called Fanconi syndrome. 

3) Third type which is termed as Type 4 RTA 

may be due to hyporeninaemic 

hypoaldosteronism or secondary to 

obstructive uropathy 4, 5 . The patients will have 

high or high normal serum potassium with 

metabolic acidosis. This type of RTA is usually 


73

CASES SERIES 

seen in chronic renal failure, diabetes mellitus, 

hypoadrenalism, drugs such as ACE 

inhibitors, heparin, trimethoprim etc 6 . 

In this article we are presenting a series of 

patients with RTA admitted or attended the 

Regional Institute of Medical Sciences, Imphal, 

Manipur. Though RTA have been reported from 

the other parts of Indian subcontinent ,to best 

of our knowledge this is the first kind of case 

series from north eastern part of India. 

Materials and methods: This is a 

retrospective analysis of patients with clinical 

and biochemical features of RTA admitted or 

attended the Medicine department, Regional 

Institute of Medical Sciences, Imphal. All 

patients underwent serum sodium, potassium, 

chloride, calcium and phosphate analysis in 

biochemistry department. Arterial blood gas 

(ABG) was also done to look for metabolic 

acidosis. Anion gap was calculated using the 

formula (Serum Sodium+ Serum potassium) 

– (Serum chloride+ Serum bicarbonate). The 

normal anion gap is taken as 8±2 meq/l. 

Fasting urine pH was examined after a 

overnight fasting of at least 8 hours. Thyroid 

hormones were done to rule out thyrotoxicosis/ 

hyperthyroidism. Ophthalmology evaluation 

was undertaken to look for causes for RTA. 

Ultrasonography of the abdomen was done 

for nephrocalcinosis/ nephrolithiasis 

evaluation. All the biochemistry results were 

pronounced as mean+SD. 

Results: Four patients with clinical and 

biochemical features of RTA were analyzed 

in our case series. All our patients had 

hypokalemia with normal anion gap, 

hyperchloremic metabolic acidosis. The 

metabolic acidosis was diagnosed with 

arterial blood gas. The male to female ratio 

was 1:1.The mean age of our patients was 

41 ± 18 years. Three of our patients presented 

with history of recurrent periodic paralysis and 

one had proximal muscle weakness. The 

mean arterial bicarbonate was 14.97± 

2.98.The mean potassium, chloride and 

fasting urine PH levels were 2.45±1.33, 117± 

1.41 and 7.07±1.22 respectively. All patients 

had normal thyroid status. All patients had 

normal alkaline phosphatase levels 

suggesting no bony involvement. Our entire 

patient has type 1 RTA. Only One patient had 

nephrocalcinosis in the ultrasonography of the 

abdomen and hypercalciuria in 24 hour 

urinary calcium. One patient with the distal 

RTA is of secondary to autoimmune disease. 

The causes of RTA in other patients could not 

be found. All the patients were given oral 

potassium in addition to bicarbonate either 

made in-house or as potassium citrate. One 

of the patients had phosphaturia (Tubular 

Maximum of Phosphate Reabsoption per 

Glomerular Filtration Rate-TmPO4/GFR) less 

than 2.5 and she was advised to take 

phosphate solution. The details of our patients 

are shown in table 1. 

Table 1. Profile of Patients with RTA 

Discussion: RTA is characterized by a triad 

of generalized weakness or periodic paralysis 

with hypokalemia and systemic metabolic 

acidosis. The main objective is differentiating 

the type of RTA and the correction of metabolic 

acidosis 3, 4 . 

The diagnostic criteria for the RTA are as 

follows. 

1) Type -1 or dRTA- Fasting urine pH more 

than 5.5 in the presence of metabolic 

acidosis with Fractional excretion of 

Bicarbonate-FEHCO3 less than 15% 

2) Type -2 or pRTA- Fasting urine pH less 

than 5.5 in the presence of metabolic 

acidosis with FEHCO3 more than 15% 2 

FEHCO3= urine Bicarbonate × plasma 

creatinine Plasma Bicarbonate x urine 

creatinine 

When a diagnosis of d-RTA is made the 

diagnostic work-up should always include 

ultrasonography for nephrocalcinosis or renal 

calculi, and measurement of urinary calcium 

and citrate excretion. Hypercalciuria and 

hyperphosphaturia is due to calcium and 

phosphate release from the bones due to 

change in H + buffer and systemic acidosis 1- 


CASES SERIES 

5 

. Hypercalciuria with hypocitraturia and high 

urine pH contribute to occurrence of calcium 

phosphate renal stones. Hypercalciuria is 

suspected when the 24-hr calcium excretion 

exceeds 4 mg/Kg/day. Hypocitraturia is said 

to be present when the 24 hr urinary citrate is 

below 2 mg/Kg/day 1 . 

All patients with idiopathic dRTA should 

undergo a formal hearing evaluation, as they 

are prone for sensorineural deafness; 

deafness may not be present in infancy and 

can develop later 7 . Since dRTA in adults may 

be associated with systemic lupus 

erythematosus(SLE), Sjogren syndrome or 

chronic hepatitis, appropriate evaluation has 

to be done 3, 8, 9 . A subtype of RTA, caused by 

deficiency of carbonic anhydrase type II 

isoenzyme, is associated with 

osteopetrosis 10 . In suspected patients with 

incomplete dRTA, ammonium chloride loading 

test is done to confirm the diagnosis of dRTA. 

But it is not needed in patients who had 

systemic acidosis 11 . 

For the diagnosis of pRTA all the functions of 

the proximal tubules have to be studied. The 

proximal is a major site for the reabsorption 

of filtered bicarbonate and a decreased 

threshold of bicarbonate reabsorption results 

in bicarbonaturia. The proximal tubules of the 

kidney are also the site for the absorption of 

the aminoacids, glucose, anions such as 

citrate and phosphate. So the assessment for 

aminoaciduria, glucosuria (in the presence of 

normal plasma sugars) and osteomalacia 

have to be done in addition to phosphate 

excretion calculated using the Bijvoet 

nomogram 1-5 . Fractional excretion of 

phosphate (FePO4) is calculated first and 

using the slide-rule method recommended by 

Bijvoet, Tubular Maximum of Phosphate 

Reabsoption per Glomerular Filtration Rate- 

(TmPO4/GFR) is calculated. The normal 

value of TmPo4/GFR is 2.8-4.4 mg/dL. If the 

value is less than 2.5, it indicates phosphaturia. 

Such patients need oral phosphate 

supplementation 12 . 

Fepo4= urine phosphate × plasma creatinine 

Plasma phosphate x urine creatinine 

It is also important to determine whether the 

defect is isolated or complete/generalized 

which is defined as Fanconi syndrome. 

Patients with pRTA should undergo eye 

examination to rule out cystinosis and Wilsons 

disease. Congenital enzyme deficiency such 

as Fabry’s disease, Ehlers Darlos syndrome, 

galactosemia, etc should also be 

screened for 3 . 

There are various causes of both proximal 

and distal RTA’s. But in real practice it is 

difficult to come to conclusion on the etiology 

for RTA 3 . In our cases series too, further 

evaluation to find the etiology for RTA could 

not be done because of limited facility in the 

centre. 

The treatment aim in dRTA is providing 

adequate bicarbonate in order to balance the 

H+ production. Oral potassium has also has 

be supplemented for normalizing the 

extracellular potassium to prevent life 

threatening periodic paralysis. In patients with 

nephrolithiasis/nephrocalcinosis, oral 

potassium citrate/bicarbonate therapy 

reduces the urinary calcium excretion thereby 

preventing the progression of 

nephrocalcinosis/nephrolithiasis. Monitoring of 

24 urinary calcium and citrate should be done 

in the follow up. 

The treatment goal for pRTA is correction of 

chronic metabolic acidosis. Alkali treatment 

with potassium supplement is cornerstone in 

the treatment of pRTA to prevent systemic 

effects of metabolic acidosis. Some patients 

need massive dose of bicarbonate to maintain 

the bicarbonate levels and compliance is the 

problem in these patients as bicarbonate is 

an unpalatable compound. In such patients 

concomitant administration of a thiazide 

diuretic may help in reducing the quantity of 

alkali treatment required. Correction of 

acidosis in children with pRTA is particularly 

important in achieving normal linear growth 

rates. Supplemental calcium and activated 

vitamin D have to be given for these patients. 

For type IV RTA, treatment and prognosis 

depends on the underlying cause. The 

treatment for includes dietary modification and 

cation exchange resins, to reduce serum 

potassium and alkali administration 1-6 . 

In a retrospective analysis from Hyderabad, 

India 96 patients with distal RTA were 


75

CASES SERIES 

analyzed. Their series showed that majority 

of children with dRTA had urological problems 

in contrast to autoimmune disorders in 

adults 13 . In the hypokalemic case series 

published from CMC Vellore, India 42 % of 

patients had RTA. Out of the 13 patients with 

RTA, 10 had pRTA and 3 had dRTA 14 . In a 

case series from Malaysia they studied 16 

cases of RTA and emphasized on the long 

term follow up for such patients to prevent 

future life threatening complications 15 .From 

Kolkata, India 2 case reports of Wilsons’ 

disease presenting as periodic paralysis due 

to dRTA had been reported by two different 

authors 16, 17 . 

In children, RTA can present as short stature 

or with features of rickets/ osteomalacia. 

From CMC Vellore, a short Klinefelter’s 

syndrome with features of rickets was 

reported, where the short stature is due to 

pRTA .But Klinefelter’s syndrome patients are 

supposed to be tall. So RTA is a cause for 

short staure in children 18 . 

The long term management and follow up is 

important as it not only prevents future life 

threatening periodic paralysis but also 

prevents further complications due to 

metabolic acidosis and preserves the renal 

functions. Once the nephrocalcinosis sets in, 

it cannot be reverted back, but treatment with 

bicarbonate will prevent form further 

progression of nephrocalcinois 1-6 . 

Conclusion: In the presence of persistent or 

recurrent hypokalemia without any 

gastrointestinal loss of potassium the 

likelihood of RTA is high. Unlike the patients 

with isolated hypokalemia, patients with 

hypokalemia and RTA should be given 

potassium and bicarbonate supplementation. 

Proper evaluation for type and etiology of the 

RTA is important in these patients. Early 

diagnosis and adequate treatment prevents 

life threatening periodic paralysis and further 

deterioration of the renal functions. 

Reference: 

1) Bagga A, Sinha A. Evaluation of Renal 

Tubular Acidosis. Indian J Pediatr 

2007;74 (7):679-86. 

2) Kumar S, Vaswani M, Srivastava RN, et 

al.Urinary net charge in hyperchloremic 

metabolic acidosis.Indian Pediatr. 1998 

Jan;35(1):13-8. 

3) Penney MD, Oleesky DA. Renal tubular 

acidosis. Ann Clin Biochem 1999; 36: 

408-22. 

4) Booth BE. Renal tubular acidosis: 

pathogenesis, diagnosis and treatment. 

Indian J Pediatr 1988; 55:379-94 

5) Saborio P, Krieg RJ, Ahmad TM,et al. 

Renal tubular acidosis in children. Saudi 

J Kidney Dis Transpl. 1997 Jul- 

Sep;8(3):235-46. 

6) Reddy P. Clinical approach to renal 

tubular acidosis in adult patients. Int J 

Clin Pract. 2011 Mar;65(3):350-60 

7) Mythili A, Subrahmanyam KA, Kumar 

KD. Type 1 renal tubular acidosis with 

sensorineural deafness. J Assoc 

Physicians India. 2007 Apr;55:303-5. 

8) Comer DM, Droogan AG, Young IS, et al. 

Hypokalaemic paralysis precipitated by 

distal renal tubular acidosis secondary 

to Sjögren’s syndrome. Ann Clin 

Biochem. 2008 Mar;45(Pt 2):221-5. 

9) Gera C, Mohapatra D, Calton N. 

Hypokalaemic paralysis secondary to 

distal renal tubular acidosis as the 

presenting symptom of systemic lupus 

erythematosus. Singapore Med J. 2011 

Jan;52(1):e1-3. 

10) Soriano JR. Renal tubular acidosis, the 

clinical entity. J Am Soc Nephrol 2002; 

13: 2160-2170. 

11) Lash JP, Arruda JAL. Laboratory 

evaluation of renal tubular acidosis. Clin 

Lab Med 1993; 13: 117-29 

12) Walton RJ, Bijvoet OL. Nomogram for 

derivation of renal threshold phosphate 

concentration. Lancet. 1975 Aug 

16;2(7929):309-10. 

13) Jha R, Muthukrishnan J, Shiradhonkar S, 

et al.Clinical profile of distal renal tubular 

acidosis. Saudi J Kidney Dis Transpl. 

2011 Mar;22(2):261-7. 


CASES SERIES 

14) Rao N, John M, Thomas N, et al. 

Aetiological, clinical and metabolic profile 

of hypokalaemic periodic paralysis in 

adults: a single-centre experience. Natl 

Med J India. 2006 Sep-Oct;19(5): 

246-9. 

15) Zainal D. Renal tubular acidosis in 

Kelantan, Malaysia—a case review. 

Singapore Med J. 1994 Jun;35(3): 

303-5. 

16) Thapa R, Biswas B, Mallick D.Recurrent 

limb weakness in a 17-year-old boy.Clin 

Pediatr (Phila). 2009 Jun;48(5):555-7. 

17) Chakraborty PP, Mandal SK, 

Bandyopadhyay D, et al. Recurrent limb 

weakness as initial presentation of 

Wilson’s disease. Indian J Gastroenterol. 

2007 Jan-Feb;26(1):36-8 

18) Jebasingh F, Paul TV, Spurgeon R, et al. 

Klinefelter’s syndrome with renal tubular 

acidosis: impact on height. Singapore 

Med J. 2010 Feb;51(2):e24-6. 


77

CASES SERIES 

Head and neck malignancies in HIV infected persons-report of 9 cases 

1 

Rino K, 2 Thingbaijam S, 3 Sobita P, 1 Momin E, 1 Kalpana TH 

Abstract 

Objectives: To analyze the spectrum of head 

and neck malignancies in HIV infected cases 

registered at Regional Institute of Medical 

Sciences, Imphal. Methods: We have 

retrospectively reviewed records of head and 

neck malignancies in HIV infected persons 

registered at our hospital from Sept 2009 to 

October 2010 to analyze HIV associated head 

and neck malignancies. Results: Nine cases 

of HIV-associated head and neck 

malignancies were identified. All the patients 

were below 50 years (age range 18-43yrs). 

Five were males. There were three cases of 

NHL, two cases of NPC, one carcinoma ex 

pleomorphic adenoma parotid, one Kaposi 

sarcoma, one maxillary carcinoma and one 

SCC. NHL was the most common overall 

malignancy while NPC happened to be the 

most common non AIDS defining malignancy. 

All patients were in advanced stage of AIDS 

and 75% were in the advanced stage of 

malignancy (II&IV). One patient expired while 

the remaining patients are currently on followup. 

Conclusion: We believe that there is an 

urgent need to direct research efforts for timely 

prevention, screening and management of HIV 

1. Post graduate trainee; 2. Associate Professor; 

3. Assistant Professor; Department of 

Otorhinolaryngology, Regional Institute of Medical 

Sciences (RIMS), Imphal. 


Dr. S. Thingbaijam, Associate Professor, Dept of 

Otorhinolaryngology, Regional Institute of Medical 

Sciences, Imphal – 795004 

Email – dr_sthingbaijam@yahoo.in 

infected persons with Head and neck 

malignancies. Cancer screening in HIVinfected 

patients should be considered at an 

earlier age than in the general population. 

Key words: Head and neck malignancy in HIV 

infected persons, AIDS defining malignancy, 

Non AIDS defining malignancy. 

Introduction: According to NACO (2009) 33.4 

Million people are living with HIV and there were 

2 million HIV/AIDS deaths in 2008. India 

contributes 2.4 million whereas Manipur 

contributes 8%. Malignancies are the no 1 

cause of death in HIV+ persons. 1 AIDS 

associated carcinoma is clinically classified 

as AIDS defining carcinoma (ADC), non AIDS 

defining carcinoma (NADC) and other 

carcinoma in HIV-infected community like 

multiple myeloma, soft tissue sarcoma, etc 

including head and neck carcinoma (HNCA). 

ADC includes Kaposi sarcoma, non Hodgkin’s 

lymphoma(NHL) and invasive cervical 

carcinoma while NADC include Hodgkin’s 

lymphoma, anal carcinoma, lung carcinoma, 

testicular germ tumors. 2 With the advent of 

HAART ( highly active antiretroviral therapy), 

malignancies are increasing in importance as 

a cause of AIDS-Related morbidity and 

mortality. 3 HIV-Infected persons have higher 

incidence of developing NADC than among 

the general population. 4 NADC incidence have 

surpassed that of ADC in HIV infected persons 

and cancer prevalence ranges from 7-15 % 

as cause of mortality in HIV population. 5 ADC 

now cause 13% of deaths in HIV + persons 1 

whereas prevalence of HNCA is 27%. 6 

Although it remains unclear whether HIV-1 


CASES SERIES 

acts directly as an oncogenic agent, it may 

contribute to the development of malignancies 

through several mechanisms. Infection by 

oncogenic viruses (e.g., cytomegalovirus, 

Epstein-Barr virus, HHV-5, HHV-8, HPV-16 and 

HPV-18), impaired immune surveillance, 

dysregulation of cytokine pathways and growth 

factor production, chronic B cell stimulation, 

and imbalance between cellular proliferation 

and differentiation may all contribute to the 

development of HIV/AIDS-associated 

malignancies. 2 

Objectives: To review the number of HIV 

infected persons with Head and Neck 

malignancy admitted in Regional Institute of 

Medical Sciences Hospital and to find out the 

different types of head and neck malignancies 

HIV infected persons. 

Materials and Methods: It is a Retrospective 

review record of HNCA patients from Sept 

2009 – Oct 2010 to identify and analyze types 

of HIV-associated Head and Neck carcinoma 

(HNCA) encountered in the Regional Institute 

of Medical Sciences, Imphal. HIV diagnosed 

during the work up. Information about 

Histology, CD4 counts and stage of HIV status 

(according to WHO clinical staging of HIV 

disease) as well as the malignancies were 

recorded. 

Results: The results of the study done on 9 

cases of HIV infection with head and neck 

malignancy are presented below: 

Out of 9 patients 3(33.3%) presented with 

NHL, 1(11.1%) with Kaposi sarcoma (KS) and 

the remaining 5(55.5%) presented with Non 

AIDS Defining Carcinoma(NADC) like 

Nasopharyngeal carcinoma (NPC), Ex 

pleomorphic carcinoma parotid (EPC), 

carcinoma maxilla (CM) and Squamous cell 

Table 1. Profil of HIV infected patients with head and 

neck malignancies 

carcinoma (SCC). NHL was the most 

common overall malignancy comprising of 3 

patients (33.3%) as shown in table 1. NPC 

happened to the most common NADC 

comprising of 2 cases (40%). The age range 

among the patients was found to be 18-43 

years (mean 36 years) and male; female 

ration is 1.0.8 as shown in table 2. The 

youngest patient was of 18 yrs. with NHL and 

the oldest patient was 43 yrs. old with KS. 7 

patients (75%) were in stage III/IV of 

malignancy and all the patients were in stage 

III/IV of HIV disease as shown in table 3. 55.5% 

of the patients have NADC type of HNCA as 

seen in table 4. 

Table 2: Sex distribution of head and neck 

malignancies in HIV infected persons 

Table 3: WHO clinical staging of HIV among the HNCA 

patients 

Table 4: Types of head and neck malignancy among 

the cases 

ADC~ Aids defining cancer, NADC~ Non AIDS 

defining cancer 

Dicussion: In our review the age range was 

18-36 years and mean age 36 years. The 

patients here were of a younger age, this is in 

keeping with the findings of other studies. 6 We 

believe that HIV-infected individuals are at 

greater risk of acquiring HNCA at a younger 

age than their HIV-seronegative counterparts. 


79

CASES SERIES 

Male to female ratio is 1:0.8 and this 

complements the report in other studies 6 . 

Since the emergence of AIDS some ADC are 

said to be increasing even among females 

though no apparent reason has been found. 

75% of the patients were in Stage III/IV of 

malignancy. This indicates that HNCA among 

the HIV infected persons are diagnosed late. 

Although Kaposi sarcoma is considered as 

the most common AIDS Defining Carcinoma 

(ADC), by other literatures 6 , the present study 

found Non Hodgkin’s Lumphoma as the most 

common AIDS defining casinima which is 

comparable to the report of Rabkin C 3 . 

According to recent studies, HAART use may 

prevent most excess risk of ADC, but not that 

of NADC. 3,7 In the present study we found more 

number of HIV infected patients with NADC 

and the ratio of NADC: ADC was 1.2:1. This 

may be attributed to the advent of HAART 

which as reported in other studies decreased 

the occurrence of ADC. 7 Infact, very recent 

studies have shown that the incidence of 

many types of NADC is higher among HIV 

infected persons than among the general 

population from 1992 to 2003. 4 

Conclusion: From our review we conclude 

that NHL is the most common HIV associated 

Head and Neck malignancy encountered in 

our institute. NADCs in Head and neck are 

almost equally prevalent as ADC among the 

HIV patients. Head and neck NADC in HIV 

infected persons occurs in early age and are 

diagnosed late. We believe that there is an 

urgent need to improve collection of 

epidemiological data and to direct research 

efforts for timely prevention, screening and 

management of HIV infected persons with 

Head and neck malignancies. Cancer 

screening in HIV-infected patients should be 

considered at an earlier age than in the general 

population, keeping in mind not to overlook the 

NADC. 

Reference: 

1. Bonnet F, Lewden C, May T, Heripret L, 

Jougla E, Bevilacqua S, Costagliola D, 

Salmon D, Chêne G, Morlat P 

Malignancy-related causes of death in 

human immunodeficiency virus-infected 

patients in the era of highly active 

antiretroviral therapy.CANCER 2004 

101:317-324 

2. Barbaro G, Barbarini G. HIV infection and 

cancer in the era of highly active 

antiretroviral therapy. oncology reports 

2007; 17: 1121-26 

3. Rabkin C. AIDS and cancer in the era of 

highly active antiretroviral therapy 

(HAART). Eur j cancer 2001 July; 

37(10):1316-19. 

4. Patel P, Hanson DL, Sullivan PS, Novak 

AM, Moorman AC, Tong TC, et al. 

incidence of types of cancer among HIVinfected 

persons compared with the 

general population in the united states. 

Ann intern med 2008 May;148(10):728- 

36 

5. Ruiz M.Certain non-AIDS-defining 

cancers higher in HIV population. HIV 

clinicians winter 2009;21(4):13-16 

6. Butt F, Chindia M, F Rana, Machigo F. 

Pattern of head and neck malignant 

neoplasms in HIV-infected patients in 

Kenya. Int j oral maxillofac surg 2008 

Sept;37(10):907-11 

7. Berretta M, Cinelli R, Martellotta F, Spina 

M, Vaccher E, Tirelli U. Therapeutic 

approaches to AIDS-related 

malignancies. Oncogene 2003: 22: 

6646–6659. 


REFLECTED ARTICLES OF PREVIOUS ISSUES 

1. Title : Oral changes in diabetics - a review 

Authors - Ng. Sanjeeta, W. Robindro, T. Nabachandra Singh 

Published in JMS Vol. 25 (1) January, 2001 on page 55-58 as review articles 

The above article has been retracted due to dispute regarding the contribution and Authorship 

of one of the Authors. The article may further be resubmitted for publications in subsequence 

issues of JMS when the dispute is settled. 

2. Title : Herpes zodter in a hrlthy adult: Report of a case with oro-cutaneous presentations 

Authors - Ng. Sanjeeta, W. Robindro Singh, O. Brajachand Singh 

Published in JMS Vol. 25 (2) May, 2011 on page 99-101 as a case report 

The above article has been retracted due to dispute regarding the contribution and Authorship 

of one of the Authors. The article may further be resubmitted for publications in subsequence 

issues of JMS when the dispute is settled. 


81

CASE REPORT 

“Deltoid paralysis following post herpetic axillary nerve neuropathy: Review 

of literatures” 

1 

N. Romi Singh, 2 C. Zonunsanga, 2 Hmingthanmawii , 3 S. Langlunthang Simte, 2 S. Kharlukhi 

Introduction: Herpes zoster infection 

causing motor neuropathy is rarely reported. 

Broadbent 1 in 1866 was the first to describe a 

“case of herpetic eruption in the course of 

branches of the brachial plexus followed by 

partial paralysis in corresponding motor 

nerves.” Few cases have been reported about 

motor involvement 2-5 by this organism as it 

mainly causes sensory symptoms. Infection 

is usually limited to sensory ganglion and 

nerve roots but it may occasionally involve 

motor system leading to paresis of muscles 

supplied by the affected nerve segment 6 . 

Isolated axillary nerve involvement is rare in 

such infection and here, we report a case of 

axillary nerve motor neuropathy following 

herpes zoster infection in view of the rarity of 

such occurance and review of the 

contemporary literatures is be discussed. 

Case report: A 35 year old married male who 

is in active service by profession reported with 

complaints of inability to lift his right arm for 

two weeks of insidious onset. There was 

neither history of trauma nor fever. On 

examination, there was vesiculoerythematous 

rash / scar on right upper limb 

1. Associate Professor, 2. Postgraduate student, 

3. House Officer, Physical Medicine & Rehabilitation 

Department, Regional Institute of Medical Sciences, 

Imphal 


Dr. N. Romi Singh 

Associate Professor 

Department of Physical Medicine & Rehabilitation 

Regional Institute of Medical Sciences, Imphal – 795 

004 Manipur (India) 

E-mail:dr.romi.singh@gmail.com 

extending from the upper arm laterally to the 

dorsal aspect of forearm with a tattoo mark 

over the deltoid muscle (figures 1 a. ). 

Fig.1 (a) 

Fig.1 (b) 

Fig.1 (a) : Showing scar / rashes over shoulder 

Fig 1 (b): Showing inability to fully abduct the arm 

actively beyond 15 0 (Deltoid paresis) 

He had noticed the painful vesiculo- bullous 

rash two weeks back, which eventually dried 

up by the time he reported to us. Motor power 

of deltoid muscle was 1/5, other muscles 

around the shoulder were of good power. 

Range of movement (ROM) of shoulder 

(passive) was normal, but active abduction 

of shoulder ROM was limited to first 15 0 with 

the scapulo-thoracic participation (figure 1 b.). 

Sensory affection in form of hypo-esthesia 

was present over badge area of the arm. We 

consented the patient for retroviral antibody 

for human immuno-deficiency virus in view of 

his occu-pation and extensive tatoo mark, but 

was negative for retroviral antibody and no 

significant findings were observed for the 

routine investigations. No electro-physio- 


CASE REPORT 

logical test was performed as the tale-tale 

features of herpes zoster infection was already 

evident. His past illness was insignificant but 

he had affection with varicella zoster virus 

(VSV) during childhood. He was treated with 

supportive treatment like neurotropic 

vitamines and gabapantin only. No antiretroviral 

treatment was administered as there 

was no active vesiculo-bullous eruptive stage 

at the time of presentation. He was advised 

to undergo regular shoulder ROM exercise 

and has been put on physical therapy modality 

viz. electrical stimulation for the paralysed 

deltoid muscle, besides advice to support the 

shoulder with a sling support to the arm to 

prevent any possible traction subluxation of 

shoulder by weight of gravity. The patient is 

being followed up for motor recovery of the 

paralyzed deltoid. 

Discussion: The common affection of herpes 

zoster usually occurs in thoracic (53%), 

cervical roots viz. C , C , C ( 20%), 

2 3 1 

opthalmic division of trigeminal nerve (15%) 

and lumbo-sacral (11%) dermatomes of 

body 7 . Moschella 8 found most common 

involvement of C & L dermatomes. Herpes 

2 2 

zoster or shingles infection is the reactivation 

of dormant VZV in the dorsal root ganglia 3,9 . 

Segmental motor paresis is rare and only few 

cases of brachial plexitis have been reported 

in the literature. Axillary nerve is formed from 

the posterior cord of brachial plexus and 

supplies the deltoid muscle. We report this 

case with axillary nerve affection causing 

paralysis of deltoid muscle folowing herpes 

zoster infection in a normal immune status 

adult. The patient had history of childhood VZV 

infection but not suffering from any immunocompromised 

status viz. human immunedefficiency 

virus infection, myeloproliferative 

disorders under chemotherpeutic treatment, 

etc. The reactivation occurs when immunity 

to VZV declines because of aging or 

immunosuppression. Hence, herpes zoster 

infection can occur at any age but most 

commonly affects the elderly population or 

immunocompromized patients 9 . 

Bhargava R et al 10 also reported a case of 

isolated axillary nerve palsy following herpes 

zoster in a 52 year old man in a normal 

immune status patient with eruptive rashes 

completely healed by two weeks time. The 

deltoid paralysis with no improvement in 

motor power was persisting till three months 

post herpetic eruption. No significant post 

herpetic neuralgia was also reported. We also 

did not find any unbearable post herpetic 

neuralgia in the case reported herein except 

for the marked deltoid weakness. Probably the 

post herpetic neuralgia as normally 

encountered in the dorsal root involment is of 

less magnitude in such cases when there is 

predominant motor / anterior horn pathway 

involment leading peripheral nerve motor 

neuropathy. 

Eban R 11 also described a case of deltoid 

muscle paresis after cervical herpes zoster 

and subsequent painful shoulder with marked 

subluxation of head of humerus. Bhargava R 

et al 10 also had observed dropping and 

flattening of shoulder after 3 months of follow 

up, probably due to disuse atrophy following 

the deltoid paralysis. The present case has 

been given due care for prevention of any 

possible shoulder subluxation due to weak 

deltoid action by prescribing a shoulder 

support sling during early phase of recovery. 

Hopefully with the return of deltoid power and 

proper biomechanical advice, he may be 

prevented from further complication of 

shoulder subluxation as reported by the two 

authors 10,11 . 

The cause of motor neuropathy in case of 

herpes zoster infection is not exactly clear. 

However, there are probably few possible 

factors which have been proposed for the 

motor neuropathy like, (i) gangliomuscular 

disease subsequent to infection of 

propioceptive ganglion cells (ii) myositis 12 , 

(iii) acquired demyelination of the peripheral 

nerve 13 etc. Schmidbauer M et al 12 have 

demonstrated varice1la zoster virus in 

myositic masseter muscle in a case of 

trigeminal nerve affected by herpes zoster. 

Even if myositis occurs with herpes zoster, it 

is not clear, if myositis or some other factors 

were responsible for the muscle paralysis . 

Alshekhlee A et al 4 described three patients 

who exhibited classic symptoms of herpes 

zoster infection of the upper limb with various 


83

CASE REPORT 

neuropathic findings, including multiple 

neuropathies, radiculopathy, and brachial 

plexopathy. As the distribution of weakness 

and electrodiagnostic findings involved not only 

the concerned dermatome, further 

electrodiagnostic studies performed on one 

such patient showed evidence of acquired 

demyelination. Hence, spread of the infectious 

process to the axon and myelin sheath of 

peripheral nerve may probably be responsible 

for the motor weakness in case of herpes 

zoster infection. 

Conclusion: We have reported the case for 

the rare occurance of axillary nerve neuropathy 

causing deltoid palsy following post herpes 

zoster infection in a case of normal immune 

status adult individual. Early and prompt 

management with exercise therapy and 

biomechanical support intervention to prevent 

complications like subluxation of the shoulder 

will be the cornerstone for management for 

axillary nerve neuropathy following herpes 

zoster, besides antiviral and supportive 

medications. 

References: 

1. Taterka JH, O’Sullivan ME. Motor 

complications of Herpes Zoster JAMA. 

1943;122(11):737-739. doi: 10.1001/ 

jama.1943.02840280021006 [Pubmed] 

2. Aktas I, Akgun K, Gunduz OH. Axillary 

mononeuropathy after herpes zoster 

infection mimicking subacromial 

impingement syndrome. Am J Phys Med 

Rehabil. 2008 Oct;87(10):85961. 

3. Jeevarethinam A, Ihuoma A, Ahmad N. 

Herpes zoster brachial plexopathy with 

predominant radial nerve palsy. Clin 

Med. 2009;9(5):5001. 

4. Alshekhlee A, Tay E, Buczek M, Shakir 

ZA, Katirji B. Herpes zoster with motor 

involvement: discordance between the 

distribution of skin rash and localization 

of peripheral nervous system dysfunction. 

J Clin Neuromuscul Dis. 2011;12(3): 

153-7. 

5. Burkman KA, Gaines RW Jr, Kashani 

SR, Smith RD. Herpes zoster: a 

consideration in the differential diagnosis 

of radiculopathy. Arch Phys Med 

Rehabil. 1988;69(2):1324. 

6. Denny - Brown D, Adams R D, 

Fitzgerald,P J. Pathologic features of 

herpes zoster : a note on geniculate 

herpes. Arch Neurol Psychiatr 1944; 51 : 

216-31. 

7. Nagington J, Rook A, Highest AS. Virus 

and related infection : Varicella and zoster. 

In : Text book of Dermatology (Rook A, 

Wilkinson DS, Ebling FJG, et al eds), 4th 

edn. Bombay Oxford University Press, 

1987; 680-5. 

8. Burnett JW, Cruteher WA. Viral and 

Rickettsial infections: Herps zoster. In : 

Dermatology (Moschella SL, Hurley HJ, 

eds), 2nd edn. New Delhi: Jaypee 

brothers, 1985; 686-9. 

9. Sampathkumar P, Drage LA, Martin DP. 

Herpes zoster (shingles) and postherpetic 

neuralgia. Mayo Clin Proc. 2009 

Mar;84(3):274-80. 

10. Bhargava R, Agarwal US, Narayan R. 

Axillary nerve palsy following herpes 

zoster. Indian J Dermatol Venereol Leprol 

1994;60:97-8. 

11. Eban R. Cervical herpes zoster and 

shoulder Pain. Br Med J 1978; 177: 21. 

12. Schmidbauer M, Budka H, Pilz P, Kurata 

T, Hondo R. Presence, distribution and 

spread of productive varicella zoster virus 

infection in nervous tissue, Brain 1992; 

115 : 383-98. 


CASE REPORT 

Fibrocalculus pancreatic diabetes - a case report 

1 

Dhanaraj Singh Chongtham, 2 Sambhaji Raut, 3 Ranabir Salam, 4 S. Subhashchandra, 5 M. Kulachandra 

Case Report 

A twenty year unmarried, non-alcoholic 

female,from low socioeconomic status, 

Christian by religionfrom Khongsang, Manipur 

was admitted at Medicine ward of Regional 

Institute of Medical Sciences, Imphal with 

chief complaints of pain in abdomen since 

two years, significant weight loss and 

indigestion since last one year. Pain in 

abdomen was dull aching, present mainly in 

upper abdomen and aggravated after taking 

food. There was no history of cough, fever, 

night sweatsand previous history of 

tuberculosis or bleeding per rectum. She did 

not give any history of diabetes mellitus and 

tuberculosis in the family. Her bowel habits 

are disturbed and appetite is decreased.On 

general physical examination she was found 

to be malnourished (Body Mass Index 

16.43kg/m 2 ) with mild pallor, sparse hairs on 

head. Per abdominal examination revealed flat 

abdomen with tenderness in umbilical, 

epigastric and left hypochondrium. There was 

no guarding, rigidity or any lump, other 

systems were within normal limits. On 

investigation, random blood sugar (RBS) was 

350 mg%,complete hemogram was normal, 

kidney function tests were within normal limits, 

1. Asso. 2. Prof. P.G. Student, 3. Assist. Prof., 

Department of Medicine Assist 4. Prof. Department 

of Radiodiagnosis, 5. Professor and Head, 

Department of Medicine, Regional Institute of 

Medical Sciences, Imphal. 


Dr Dhanaraj Singh Chongtham, Department of 

Medicine, RIMS, Imphal 795004 

Email: dhanarajcardiology@yahoo.co.in 

alkaline phosphatase was364KAU, SGOT 

was 184Uand SGPT was 276U. Urinalysis 

showed glycosuria of 2%. Keeping in mind 

some chronic illness patient was started on 

symptomatic management followed by X-ray 

abdomen which showed multiple calcified 

lesions grouped together in linear fashion in 

upper abdomen centrally, in front of L1-L3 

lumbar vertebral level suggestive of pancreatic 

calcification (Fig. 1). 

Fig.1: Plain X-ray Abdomen showing pancreatic 

calcification 

Fig. 2: Contrast enhanced CT abdomen axial image 

showing ductal parenchymal and periductal 

calcification in head and uncinate process of 

pancreas. 


85

CASE REPORT 

Fig. 3: Contrast enhanced CT abdomen axial image 

showing ductal and parenchymal calcification in 

body and tail region of pancreas. 

Ultrasonography (USG) whole abdomen 

showed outline of pancreas with extensive 

parenchymal and ductal calcifications with 

loss of normal parenchymal echotexture. 

Major pancreatic duct diameter was 4.4 mm. 

(Fig. 2). These features were suggestive of 

chronic calcific pancreatitis. Fasting and post 

prandialblood sugar were 304 and 382mg% 

respectively. Montoux test was negative 

measuring 2×2mm. Fasting and post prandial 

blood sugar level and urine dipsticks charting 

were done for adjustment of Insulin doses. 

Contrast enhanced (CECT) abdomen 

showed pancreas measuring 16 mm at body 

with irregular margins (Fig. 3). There is 

multifocal extensive calcification in 

parenchyma and ducts causing irregular 

ductal dilatation. Main pancreatic duct 

measures 8mm in diameter these features 

suggestive of chronic calcific pancreatitis with 

parenchymal atrophy. 

Barium meal study was within normal limits, 

serum calcium was within normal limits, 

glycosylated Hb was 17.8%.Then patient was 

started on low dose mixed Insulin and 

pancreatic enzyme supplementation. Patient 

was receiving mixed insulin(50/50) 35/30 units 

with voglibose 0.3 mg and pancreatic 

enzymes at the time of discharge. Patient was 

symptomatically better and fasting post 

prandial blood sugar level was within normal 

limits at the time of discharge. 

Discussion: Tropical chronic pancreatitis 

(TCP) is a juvenile form of chronic, 

calcific,non-alcoholic pancreatitis seen 

almost exclusively in developing countries of 

the tropical world. The classical triad of tropical 

chronic pancreatitis is abdominal pain, 

steatorrhoea and diabetes. When diabetes is 

present the condition is calledFibrocalculus 

pancreatic diabetes (FCPD) which is thus a 

later stage of TCP. 1 Severalterms had been 

earlier proposed for this syndrome including 

tropicalcalcific pancreatitis, tropical chronic 

pancreatitis, tropical pancreatic diabetes, 

nutritional pancreatitis, endemic pancreatic 

syndrome, etc. As the term Fibrocalculus 

Pancreatic Diabetes was introduced by the 

World Health Organization Report this is the 

preferred term used by diabetologists, while 

the term Tropical Calcific Pancreatitis (TCP) 

is used by gastroenterologists. 2 The 

prevalence of FCPD very low, in one of study 

from southern urban areas of India was shown 

to be 0.36 % of total diabetic population. 3 The 

single largest series of cases of FCPD 

reported to date is from the southwestern state 

of Kerala in India, where Geevarghese and 

Pitchumoni observed this disease in endemic 

proportions in two major medical college 

hospitals. Indeed, Geevarghese collected one 

of the largest series in the world (over 1700 

patients) and two monogramson the subject 

were published by him and istherefore 

oftenreferred to as “Father of Pancreatic 

Diabetes”. 2 

The cardinal manifestations of TCP are 

recurrent abdominal pain in childhood, 

followed by onset of diabetes mellitus a few 

years later. Early reports on TCP identified 

patients only in the late stages of the disease 

when extreme emaciation and other obvious 

clinical signs of protein malnutrition, such as 

bilateral parotid gland enlargement as well as 

skin and hair changes of kwashiorkor, 

dominated the clinical picture. 4 

Diagnostic criteria for fibro-calculuspancreatic 

diabetes (FCPD) 

1. Occurrence in a “tropical” country. 

2. Diabetes by WHO Study criteria. 

3. Evidence of chronic pancreatitis: 

pancreatic calculi on X-ray or at least three 

of the following: 

a) Abnormal pancreatic morphology by 

ultrasonography 

b) Chronic abdominal pain since 

childhood 

c) Steatorrhoea 

d) Abnormal pancreatic function test. 


CASE REPORT 

4. Absence of other causes of chronic 

pancreatitisi.e. alcoholism, hepatobiliarydisease 

or primary hyperparathyroidism 

etc. 5 

The etiopathogenetic mechanisms of FCPD 

still remain unclear. Thereis no satisfactory 

experimental model for FCPD. The following 

hypotheses have been proposed based on 

epidemiological data: 

1. Malnutrition theory 

2. The cassava hypothesis and other dietary 

toxins 

3. Oxidant stress hypothesis and trace 

element 

4. Familial and genetic factors 1 

One of the characteristicclinical features of 

FCPD is that despite requiring insulin for 

control,patients rarely becomeketotic on 

withdrawal of insulin. This is attributedto the 

following factors: 

1. Partial preservation of beta cell functions 

as shown by C-peptidestudies. 

2. Decreased glucagon reserve. 

3. Reduced supply of non-esterified fatty 

acid (NEFA), the fuelneeded for 

ketogenesis, due to the loss of 

subcutaneous tissue. 

4. Resistance of subcutaneous adipose 

tissue lipolysis to epinephrine. 

5. Carnitine deficiency, affecting transfer of 

NEFA across mitochondrialmembrane. 2 

Complications due to chronic pancreatitis 

include pseudocysts, pancreaticabscesses, 

References 

1. Mohan V. Fibrocalculous pancreatic 

diabetes. In:Balakrishnan V, harishkumar, 

Sudhindran S, Unnikrishnan AG editors. 

Chronic Pancreatitis and Pancreatic 

Diabetes in India1 st ed. Bangalore: The 

Indian Pancreatitis Study Group; 

2006.p155-174 

2. Mohan V, Farooq S, Mohan D. Prevalence 

of Fibrocalculous Pancreatic Diabetes in 

Chennai in South India .J Pancreas 2008; 

9(4):489-92. 

3. Barman KK, Premalatha G, Mohan V. 

Tropical chronic pancreatitis. PostgradMed 

J 2003; 79: 606-15. 

4. Mahurkar S, Reddy DN, Rao GV, Chandak 

and ascites. Obstructive jaundice may also 

be occasionally seen, which can be due to 

common bile duct obstruction or associated 

carcinoma of the pancreas. 1 Microvascular 

complications like retinopathy and 

nephropathy was seen in FCPD patients. 

Renal failure due to diabetic nephropathy has 

also been reported in other forms of pancreatic 

diabetes. Peripheral neuropathy and 

autonomic neuropathy have also been 

reported in those with FCPD. Macrovascular 

complications are however,rare in FCPD. This 

is believed to be due to three reasons: the 

patients are young, lean, and have low lipid 

levels. 2 It was previously believed that chronic 

complications do not occur in subjects with 

FCPD but both acute and chronic 

complications have been documented time 

and again 6 . Although the frequency is low, 

diagnosis of Fibrocalculus pancreatic 

diabetes must be kept in mind in treating 

diabetic subjects in developing countries as 

its management would include management 

of pain,pancreatic enzyme supplements and 

periodic surveillance for pancreatic 

malignancy. 3 

An overall association was observed between 

FCPD and HLA-DQB1 (P = 0.003), that was 

largely due to a positive association with HLA- 

DQB1*0302 and a negative association with 

HLA-DQB1*0202, a novel protective 

association was found with HLA-DQB1*0202 

in Bangladeshi FCPD subjects. The genetic 

susceptibility to FCPD has features both 

similar and dissimilar to T1DM. 7 

GR. Genetic mechanismsunderlying the 

pathogenesis of tropical calcific 

pancreatitis. World Gastroenterology J2009 

January 21; 15(3): 264-269. 

5. Mohan V. Fibrocalculous pancreatic 

diabetes in indiaInt J Diab Dev Countries 

1993; 13: 14-21. 

6. ZargarAH,Bhat MH,Laway BA,Masoodi SA. 

Clinical and aetiological profile of early 

onset diabetes mellitus: data from a tertiary 

care centre in the Indian subcontinent. 

Postgrad Med J 2001; 47(1): 27-9. 

7. Chowdhury ZM, McDermott MF, Davey S, 

Hassan Z, Genetic susceptibility to 

fibrocalculous pancreaticdiabetes in 

Bangladeshi subjects: a family study. 

Genes and Immunity J (2002); 3:5-8. 


87

Colour Page 

CASE REPORT 

Jejunal GIST presenting as an exophytic mass with obscure lower gastrointestinal 

bleeding 

1 

D. Nilottpal, 2 Kh. Gojen Singh, 3 K. Lekhachandra Sharma, 2 L. Jaleshwar, 4 Th. Gojendra, 

Case report 

A 37 years old woman presented to us with 

complaints of a painless swelling in her left 

upper part of abdomen for the past three 

months followed by weight loss for the past 

one month (around 10kg). She also gave 

history of bleeding per rectum 6 years back 

for which she was hospitalised and two units 

of blood were transfused. There was no 

history of upper GI complaints like 

hematemesis,nausea,vomiting, alteration in 

bowel habits, or history of fever, upper 

abdominal discomfort or shortness of breath. 

Micturation habit was normal. On examination 

patient was pale but general examination 

including vital parameters were within normal 

limits. Systemic examination including 

abdominal examination, DRE and PV 

examinations were essentially normal. She 

had normocytic hypochromic anemia with Hb 

8.7mg%, TLC-6200/Cumm, SAKP-487U/L, 

S.bilirubin-1.2mg%, S. total protein - 6.4mg%, 

S. alb-3.1mg%, S.glb-3.3mg%, SGOT-134U/ 

L,SGPT-92U/L, stool was positive for occult 

blood .In barium studies no lesion was 

found.CXR PAview was normal. USGabdomen 

suggested a colonic mass 

9.4cm×6.7 cm at around spleenic flexure with 

suspected target lesions at 7 th and 8 th hepatic 

segments with mild hepato spleenomegaly 

and right sided renal cortical cyst, but in Upper 

GI endoscopy it was reported as antral 

gastritis. After transfusing two units of 

compatible blood ,she was subjected toFNAC 

which reported as Leiomyoma (benign 

spindle cells).In suspicion of Gastro intestinal 

stromal tumor, CECT abdomen was advised 

but the patient’s family could not affort.Thus 

the patient was subjected to MRI where a 

large exophytic cavity of small bowel mass 

(9.85×8.29cm)with evidence of communication 

with jejunal loop and showing 

intermediate signal intensity changes in all the 

sequence and necrotic lesion at segment 7 

of liver with minimal pleural effusion (Fig. 1). 

Fig: 1 MRI showing 

exophytic mass. 

Fig: 2 Cut section 

showing hemorrhagic 

1 PGT. 2.Registrar. 3. Professor. 4. Asst. 

Professor. Department of Surgery, RIMS, Imphal 


Dr.Kh.Gojen Singh, 

Registrar, Department of Surgery, 

Regional Institute of Medical Sciences, 

Imphal, Manipur -795004 

Fig: 3 Histopathology 

showing areas with 

cavitation spindle cells 

Fig : 4 Immuno 

histochemistry 

staining positive for 

CD-117. 


CASE REPORT 

CECT-abdomen/ MRangiography were also 

suggested but due to the economic constrains 

all these investigations were abandoned and 

after explaining the nature of the disease ,likely 

course and outcome the patient was put up 

for exploratory laparotomy on the 4 th of Nov. 

2008.At operation, a hypervascular exophytic 

jejunal mass (15×10×6 cm) 5cm away from 

DJ junction was noted which was resected 

with grossly tumor free mergin followed by end 

to end jejuno-jejunal anastomosis. Liver was 

found to be normal in appearance , the 

peritoneum, mesentry and omentum were 

also normal with no suspicious lymph node 

enlargement. Cut section showed firm gray 

white with central area of cavitation and 

hemorrhage (Fig. 2). After histopathological 

and immunohistochemical analysis it was 

confirmed to be a jejunal GIST(borderline 

malignancy) with mitoic figure (‹5/50hpf), 

CD117 – positive (score 4+) (Fig. 3&4) .The 

patient had an uneventful recovery and is 

asymptomatic with no features suggestive of 

recurrence in subsequent follow up clinically, 

till June 2011. Neither we could start imatinib 

mesylate therapy nor could investigate 

properly for recurrence as the cost of the 

investigation & therapy was beyond her 

affordability. 

Discussion: GISTS are rare nonepithelial 

primitive digestive tract tumours, first identified 

by Mazur and Clark in 1983, arising from the 

connective tissue of the digestive tract with 

an incidence of 0.1–1%of gastrointestinal 

malignancies. 1 GIST and leiomyosarcomas 

(LMS) of the abdominal cavity and 

retroperitoneum are unusual malignancies 

that until recently were classified histologically 

together as leiomyosarcomas because of their 

similarities on light microscopy. 2 

Phenotypicaly mesenchymal tumors can be 

classified in three catagories (1) Tumours with 

differentiation towards smooth muscle cells 

[I.H.C. – (alpha) smooth muscle actin and 

desmin] (2) Tumours with neural 

differentiation (I.H.C. – S 100 protein) (3) 

Tumours with no differentiation – GIST [2]. 

GISTS are believed to arise from the interstitial 

cells of Cajal (pacemaker cells of GIT) and 

hence were termed in the past as GANT 

(Gastrointestinal Autonomic Nerve Tumours). 3 

Age of onset is between 50–70 years without 

any sex predeliction, 25 % of GISTS are 

malignant. The clinical manifestations depend 

upon the site and size of the GIST. About 5 % 

are in oesophageal, 50–70 % are in the 

stomach, 25–40 % in the small intestine, 10– 

20 % in the duodenum, 27–37 % in jejunum, 

27–53 % in ileum and < 10 % are located at 

colorectal (50 % colonic 50 % rectal). 60 % 

are submucosal, 30 % are subserosal and 

some are intramural. 4 Small imtestinal GIST 

may remain silent till it become large enough 

to cause obstruction or causes GI bleeding 

due to ulceration of mucosa. Exophytic and 

extramural GISTS have been noted in 18–30 

% of cases. Small bowel GISTS have higher 

propensity to have malignant behaviour than 

gastric GIST. 5 It spreads mainly to adjacent 

organs, omentum, mesentery, retroperitoneum, 

liver, and to the lymph nodes, extra 

abdominally to lung and rarely to bone. 6 Upto 

30 % of GISTS are metastatic on presentation. 

Table 1 

Prognostic Criteria for GIST (Berman 2001; 

Fletcher et al 2002) 

Size in cm. 

Mitotic 

count/50 hpf 

Very low risk ‹2 ‹5 

Low risk 2-5 ‹5 

Intermediate risk ‹5 6-10 

High risk ›5 ›10 

Other proposed prognostic factors are 

mucosal and muscularis propria invasion, 

ploidy, proliferation markers (PCNA, Ki67), 

necrosis, hemorrhage, degeneration and 

calcification (which can be found in benign 

GISTS), cellularity, pleomorphism and 

immunophenotype. 7 No single factor is 

predictive enough to be used exclusively. CD 

117 positivity has become definitional in the 

diagnosis of GISTS. Metastasis may lose CD 

117 positivity. CD 34 positive GISTS have a 

more favourable prognosis. In 5% of the cases 

PDGFR-α may be positive with epitheloid 

histology picture. 8 

Preoperative diagnosis of GIST is difficult. CT 

and MR Angiography are helpful in clinching 

preoperative diagnosis. US endoscopy and 

FNA with subsequent immunohistochemical 

analysis along with c-kit gene mutation study 

offers the best diagnostic accuracy . 


89

CASE REPORT 

Resection offers the best treatment option. 

Unresectable and/or metastatic GISTS (CD 

117 +ve) are treated with Imatinib mesylate 

(tyrosine kinase receptor inhibitor). 9 Our 

patient presented as an obscure lower GI 

bleed due to an exophytic jejunal GIST, CD 

117 positive score+4 , with mitotic figures of 

‹5/50 hpfs, with suspected metastasis in the 

liver. In general gastric GISTS are spindle 

celled in 70 to 80 % of cases and epitheloid in 

20–30 %, while small intestinal GISTS are 

usually spindle celled, usually the benign ones. 

Esophageal and rectal GISTS are usually 

malignant and predominately spindle cells. 

Conclusion: GISTS are rare tumours of GIT, 

which are difficult to diagnose preoperatively. 

Surgery offers definitive treatment and regular 

follow up is required lifelong post resection. 

Their unusual presentations must be borne 

in mind. An unusual exophytic jejunal 

malignant stromal tumor with obscure lower 

GI bleed is being presented. 

References 

1. Pappillon E, Rolachon A, Calender A, et al 

(2001) A malignant GIST in a patient with 

multiple endocrine neoplasia type I. Eur J 

Gastroenterol Hepatol 13(2):207–211. 

2. Miettinen M, Kopczynski J, Makhlouf HR, 

et al (2003) Gastrointestinal stromal 

tumours, Intramural leiomyomas, and 

leiomyosarcomas in the duodenum. Am 

J Surg Pathol 27(5): 625–641. 

3. Crowther KS, Wlyd L, Yamani Q, Jacob 

G (2002) Case report: gastroduodenal 

intussussception of a GIST. BJR 

75(900):987–988. 

4. Mukhopadyay S, Gupta SD (2002) 

Gastrointestinal Stromal Tumours: Benchto-bedside 

review. GI Surgery Annual 9: 

101–148. 

5. Dubenec SR, Dawes-Higgs RJ, Truskett 

PG (2001) Haemoperitoneum caused by 

spontaneous rupture of a GIST. ANZ J 

Surg 71(10):612–614. 

6. Rizzo S, Bonomo S, Moser A, et al (2001) 

Bilateral phaeochromocytoma associated 

with duodeno-jejunal GIST in patient with 

von Recklinghausen’s disease: report of 

a clinical case. Chir Ital 53(2):243–46. 

7. Johnston AT, Khan AL, Beakney R, Keenan 

RA (2001) Stromal tumour within a 

Meckel’s Diverticulum: CT and ultrasound 

findings. BJR 74(888): 1142–1144. 

8. Miettinen M, Virolainen M, Sarlomo-Rikala 

M (1995) Gastrointestinal stromal tumours 

– Value of CD34 antigen in their identi. 

cation and separation from true 

leiomyomas and schwannomas. Am J 

Surg Pathol 19:207–16. 

9. Lattarulo S, Ugenti I, Ferrarese F, Fabiano 

G (2003) GIST : current issues. Chir Ital 

55(2):219–226. 


CASE REPORT 

Hypokalemic periodic paralysis in Grave’s disease 

1 Arvind G, 2 Robinson Ningshen, 3 S. Bhagyabati Devi, 3 Th. Bhimo Singh, 4 Th. Shanti Devi, 

Case Report 

A 33 year old male presented to the 

Emergency Room with sudden onset 

paraparesis without any sensory, bladder or 

bowel symptoms. He denied having diarrhoea 

or vomiting, use of alcohol, diuretics, exertion, 

a high carbohydrate intake or fever preceding 

weakness. He had no past history of similar 

weakness and family history for periodic 

paralysis was negative. There was no history 

of diabetes or hypertension. However he gave 

history of palpitations, heat intolerance, 

increased bowel frequency, weight loss with 

increased appetite and increased sweating 

since 6 months. However he had no history 

of intake of antithyroid medication. 

His examination revealed a Pulse rate of 120/ 

min, BP 130/80 and no dehydration. He was 

fully conscious with normal higher mental 

functions, no cranial nerve deficits, muscle 

power of 2/5 in both lower limbs with 

decreased reflexes, normal power and 

reflexes in both upper limbs, no sensory 

deficits. He had exophthalmos with lid lag, a 

firm enlarged thyroid gland with a bruit and 

his palms were moist and warm. His other 

system examination revealed nothing 

abnormal. 

1. PGT, 2. Associate Professor, 3. Professor, 

4. Registrar, Department of Medicine, Regional 

Institute of Medical Sciences, Imphal, Manipur. 


Dr.Robinson Ningshen, MBBS., MD (General 

Medicine), Associate Professor, Department of 

Medicine, Regional Institute of Medical Sciences, 

Imphal, Manipur. Phone No: 9612159017. 

E-Mail: dr.ningshen@yahoo.co.in 

On investigation serum electrolytes revealed 

K+ level of 1.9 mEq/l and normal serum 

sodium, chloride and bicarbonate. Serum 

calcium, magnesium, phosphate were within 

normal limits. Random blood sugar was 

148mg/dl.ECG revealed Sinus tachycardia 

with heart rate of 112/min and PR interval 0.20 

sec, presence of ST-T flattening with U wave. 

Urinary electrolyes were normal. 

Free T4 levels-270 nmol/L (66-181 nmol/L) 

Free T3 levels-3.0 (1.3-3.1 nmol/L) 

TSH level- 0-05 (0.3-6.0 microIU/ml) 

Patient was treated with intravenous 

potassium chloride at the rate of 10 mEq/hr 

in normal saline infusion with cardiac 

monitoring and was also given propranolol 40 

mg 8hrly orally. At the 8 th hour of KCl infusion 

patient’s paraparesis resolved completely and 

neurological examination was normal except 

for increased ankle jerks bilaterally. Repeat 

serum K+ was 5.3 mEq/L. KCl infusion was 

discontinued and K+ supplementation was 

given orally and propranolol continued. 

In view of the TPO antibody positivity patient 

was labelled to be suffering from Grave’s 

Disease and was treated with Carbimazole 

15mg 8 hourly with propranolol continued at 

40mg 8hrly. 

Patient had no recurrent episodes of 

paraparesis on follow up and serum T4 

normalised at 6 weeks and was put on 

maintenance Carbimazole at 10mg daily. 

Patient continues do well after 6 months 

follow up. 


91

CASE REPORT 

Discussion: Diagnosis of Thyrotoxic periodic 

paralysis (TPP) is a challenge to clinicians, 

the reason being in most cases it can present 

with only mild elevations of thyroid hormone. 

Thorough history with emphasis on age, 

previous similar weakness, family history of 

weakness, high carbohydrate intake,or acute 

gastroenteritis, drug and history of alcoholism 

needs to be elucidated. 

Hypokalemia in TPP results from an 

intracellular shift of potassium and not total 

body K+ depletion. It has been shown that the 

Na+/K+–ATPase activity in platelets and 

muscles is significantly higher in patients with 

TPP 1 . Hyperthyroidism may result in a 

hyperadrenergic state, which may lead to the 

activation of the Na+/K+–ATPase pump and 

result in cellular uptake of potassium. 

Thyroid hormones may also directly stimulate 

Na+/K+– ATPase activity and increase the 

number and sensitivity of beta receptors 2 . 

Patients with TPP have been found to have 

hyperinsulinemia during episodes of paralysis. 

This may explain the attacks after highcarbohydrate 

meals. 

The typical presentation of the disease is in 

Asian males 3 , generally in 2 nd -4 th decades 

occurring as sudden onset symmetrical lower 

limb weakness, affecting the proximal 

muscles more than the distal muscles.The 

weakness occurs at rest after exertion and a 

high carbohydrate meal. It may last for 3-96 

hours with resolution of weakness in an 

opposite direction to that of appearance. On 

rare occasions there may be respiratory 

muscle weakness needing ventilatory 

support 3 . 

Since TPP can be life threatening, prompt 

treatment with intravenous potassium should 

be initiated. Ahmed I et al recommend K+ 

doses of < 10 mEq/hr with close monitoring 4 . 

Prompt treatment results in prompt resolution 

of weakness. Propranolol, a nonselective 

beta-blocker, prevents the intracellular shift of 

potassium and phosphate by blunting the 

hyperadrenergic stimulation of Na+/ K+– 

ATPase 5 . Combination of low IV potassium 

and non selective B blockade appears to be 

the treatment of choice for recovery and 

reducing rebound hyperkalemia. 

Acetazolamide used in the the treatment of 

HPP is contraindicated in TPP 6 . 

However definitive treatment lies in treating 

Hyperthyroidism per se.TPP is curable once 

a euthyroid state is achieved. 

Conclusion: In the setting of hypokalemic 

periodic paralysis one should look out for 

secondary causes, particularly for a thyrotoxic 

cause in males of Asian origin 3 in 2-4 decades 

of life.TPP is a potentially treatable cause and 

further episodes can be prevented on 

achieving euthyroid status. 

Furthermore, low dose of IV potassium

CASE REPORT 

Giant condyloma acuminata: a case report 

1 

T.Y Babu Singh, 2 Ksh. Raju, 3 Manju Darang 

Case report 

A 40 years Hindu male from Lilong Chajing, 

mansion by occupation was admitted on 18- 

10-10 with chief complaint of swelling in the 

right scrotum for eight years. The swelling 

was gradual in onset and progressive in 

nature. It increased in size at a faster rate in 

the last 2 years. It was not associated with 

pain except some heavy/dragging sensation 

when not wearing undergarments. There were 

occasional oozing of blood when traumatized 

but there was no discharge as such. 

There was no discomfort during passing stool/ 

urine or sexual relationship. He was an 

occasional smoker and drank alcohol 

occasionally. There was no other significant 

history like 

STD in both the 

partners but 

his wife was 

m a r r i e d 

previously to 

another man 

who expired, 

and history 

couldn’t be Fig. 1 Giant condyloma acuminata 

traced regarding any STD. The patient also 

denies any history of extra marital contact 

before or after marriage. 

1. Prof. and Head of Department, Surgery, 

2. Asst. Prof. 3. Jr. Resident, Department Of 

Surgery, RIMS, Imphal. 


Dr. Ksh. Raju Singh, Assistant Professor, 

Department of Surgery, RIMS, Imphal. 

Local examination showed a pinkish grey 

white cauliflower like non pedunculated 

growth over the right scrotum, the surface 

was rough and showed papillations. Adjacent 

skin showed tortuous dilated veins radiating 

from the growth. The growth measured about 

14x7cm with no local rise in temperature and 

non tender. It was firm in consistency with well 

defined margin. The growth was fixed to the 

scrotal skin but free from the testes. There 

were bilateral inguinal lymphadenopathy which 

was slightly tender, firm, non matted and 

mobile .The left scrotum showed no change 

and the penis was normal though it was 

slightly pushed to the left by the scrotal growth 

(fig.1). Routine investigations for blood were 

normal. Incisional biopsy was done and 

showed hyperplastic verrucous epithelial 

lesion. FNAC of inguinal lymph nodes showed 

non specific reactive lymphadenitis. Growth 

was excised with free margin of 1cm under 

spinal anesthesia, haemostasis secured and 

wound was closed primarily after putting a 

corrugated drain. Histopathological 

examination of excised tissue showed skin 

with epidermis displaying broad irregular 

acanthosis, papillomatosis and 

hyperkeratosis. The underlying dermis 

showed proliferating capillaries with moderate 

pericapillary lymphocytic infiltration. No 

evidence of malignancy was seen. Features 

were of Giant Condyloma Acuminata. 

Postoperative period was uneventful except 

for some wound gapping for which secondary 

stitching were done and patient was put on 

oral antibiotic, analgesic and multivitamins. 


93

CASE REPORT 

Patient was discharged and advised to attend 

STD clinic with his wife after one week. 

Patient reported after one week and wound 

was found healthy and healing was 

satisfactory. 

Discussion: Giant condyloma acuminata also 

known as Buschke–Lowenstein Tumor or 

Verrucous lesion is a locally aggressive form 

of Condyloma Acuminata. Although these 

lesions do not metastasize, they can cause 

an extensive local tissue destruction and may 

be grossly indistinguishable from epidermoid 

carcinoma. Giant Condyloma Buschke 

Lowenstein is mostly located in glans penis 

however it can be found on any anogenital 

mucosal surface, including the vulva, vagina, 

rectum, scrotum, and bladder. 1 Co-localization 

with human papillomavirus (HPV) types 6 and 

11 2 , occasionally HPV types 16 and 18, and, 

on one occasion, HPV 54 has been shown. 

Giant Condyloma Buschke-Lowenstein 

(GCBL) is rare type of Condyloma Acuminata. 

Estimates of incidence shows that GCBL 

accounts for 5-24% of penile cancers, which, 

in turn, are 0.3-0.5%of male malignancies. 

Another review assessed that Verrucous 

carcinoma accounted for approximately 50% 

of all low grades squamous cell carcinoma 

(SCC) of the penis. GCBL located outside the 

penis is more frequent. GCBL typically starts 

on the prepuce as a keratotic plaque and 

slowly expands into a cauliflowerlike mass, 

as large as 15 cm. The lesion may ulcerate 

or form a penile horn and typically is 

associated with a foul odour. Expansion to the 

corpus cavernosum and urethra may occur, 

with subsequent fistulation. Regional 

lymphadenopathy is common, primarily due 

to secondary infection, not metastases. 

Biopsy is the diagnostic procedure necessary 

for evaluation. It must be sufficiently deep and 

generous to evaluate for possible foci of 

squamous cell carcinoma (SCC). Although the 

rate of regional lymph node involvement is 

low, sentinel lymph node biopsy should be 

considered if clinical findings suggest the need 

for it. The treatment of choice for GCBL is wide 

surgical excision. Surgery alone has resulted 

in a disease-free status in 45.5% of patients. 5 

In addition, oral and topical chemotherapeutic 

modalities have been used with mixed 

success as adjuvant to surgery or as 

treatment for recurrences. Inadequately 

treated GCBL has a relentless progression 

and is fatal by direct spread to pelvic organs. 

By definition, adequately treated GCBL has a 

low recurrence rate and, therefore, an 

excellent prognosis. 

Conclusion: Giant Condyloma Acuminata is 

a rare type of condyloma acuminata. In our 

case there was no history of STD exposure 

and there was no evidence of malignancy. 

Surgical excision is the treatment of choice. 

References: 

1 Wiedemann A, Diekmann WP, Holtmann 

G, Kracht H. Report of a case with 

giant condyloma (Buschke-Lowenstein 

tumor) localized in the bladder. J 

Urol. Apr 1995;153(4):12224. 

2 Dianzani C, Bucci M, Pierangeli A, 

Calvieri S, Degener AM. Association of 

human papillomavirus type 11 with 

carcinoma of the 

penis. Urology. Jun 1998;51(6):10468. 

3 Castren K, Vahakangas K, Heikkinen E, 

Ranki A. Absence of p53 mutations in 

benign and pre-malignant male genital 

lesions with over-expressed p53 

protein. Int J Cancer. Aug 

31 1998;77(5):6748. 

4 Crespo R, Puig F, Lanzon A, Borell 

A. Buschke Lowenstein tumor and 

pregnancy: a case report. Eur J 

Gynaecol Oncol. 2007;28(4):3289. 

5 Renzi A, Giordano P, Renzi G, Landolfi V, 

Del Genio A, Weiss EG. Buschke- 

Lowenstein tumor successful treatment 

by surgical excision alone: a case 

report. Surg Innov. Mar 2006;13(1): 

69-72.

Evidence-based Medicine: Time for a change? - Journal of Medical ...

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