From,

Date : 15.11.2008.

DR MOHAMMED IMRAN Place: Bellary

Post Graduate Student in M.D. (General Medicine)

Department of General Medicine,

Vijayanagar Institute of Medical Sciences, Bellary.

To,

The Principal,

Vijayanagar Institute of Medical Sciences,

Bellary.

THROUGH PROPER CHANNEL

Respected Sir,

Subject: Acceptance of registration and forwarding of my dissertation topic.

With reference to the above subject, I, the undersigned studying Post Graduate Course in M.D. General Medicine has been allotted the dissertation topic “CLINICAL STUDY OF DIAGNOSTIC EFFICACY OF ADENOSINE DEAMINASE(ADA) LEVELS IN TUBERCULAR PLEURAL EFFUSION AT VIMS COMBINED HOSPITALS”, under the guidance of DR. VISHNU N. HAYAGREEV Professor and Head of the Department, Department of Medicine, VIMS, Bellary.

I request you to kindly forward the dissertation topic in the prescribed form to the University for approval.

Thanking you,

Yours sincerely,

Signature of the guide :

(DR VISHNU N. HAYAGREEV) (DR. MOHAMMED IMRAN)

Professor and HOD, P.G.in General Medicine,

Department of Medicine, VIMS, Bellary.

VIMS, Bellary

From, Date : 15.11.2008.

The Professor and Head of the Department, Place: Bellary

Department of General Medicine,

Vijayanagar Institute of Medical Sciences, Bellary.

To,

The Registrar,

RajivGandhiUniversity of Health Sciences,

Bangalore.

THROUGH PROPER CHANNEL

Respected Sir,

As per the regulations of the University for Registration of Dissertation topic, the following Post Graduate Student in M.D. General Medicine has been allotted the dissertation topic as follows by the Official Registration Committee of all qualified and eligible guides of the Department of Medicine.

NAME / TOPIC / GUIDE
DR. MOHAMMED IMRAN.
Post Graduate Student in M.D. General Medicine,
VIMS, Bellary. / “ CLINICAL STUDY OF DIAGNOSTIC EFFICACY OF ADENOSINE DEAMINASE(ADA) LEVELS IN TUBERCULAR PLEURAL EFFUSION AT VIMS COMBINED HOSPITALS” / DR.VISHNU N. HAYAGREEV
Professor and HOD,
Department of Medicine, VIMS, Bellary.

Therefore, I kindly request you to communicate the acceptance of the dissertation topic allotted to the PG student at an early date.

Thanking you,

Yours faithfully,

Signature of the guide: ( DR. VISHNU N. HAYAGREEV)

Professor and HOD

Department of Medicine,

(DR. VISHNU N.HAYAGREEV) VIMS, Bellary.

Professor and HOD,

Department of Medicine,

VIMS, Bellary.

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KARNATAKA.

ANNEXURE – II

SYNOPSIS FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1 / Name of the candidate and Address
( In Block letters ) / DR. MOHAMMED IMRAN
POST GRADUATE STUDENT IN M.D .GENERAL MEDICINE
VIMS, BELLARY – 583104.
2 / Name of the Institution / VIJAYANAGAR INSTITUTE OF MEDICAL SCIENCES, BELLARY
3 / Course of study and subject / M.D. in GENERAL MEDICINE
4 / Date of admission to the course / 1st June 2008
5 / Title of Topic:
“ CLINICAL STUDY OF DIAGNOSTIC EFFICACY OF ADENOSINE DEAMINASE LEVELS IN TUBERCULAR PLEURAL EFFUSION AT VIMS COMBINED HOSPITALS ”
6 / Brief resume of the intended work:
  • 6.1 Need for the Study:
Tuberculosis is one of the oldest and commonest infectious diseases also known as “Master of Death or Captain of Death”.
Tuberculosis(TB) is major cause of pleural effusion.
Diagnosis of TB pleural effusion is important because tuberculosis is treatable cause of pleural effusion .
Tubercular pleural effusion diagnosis remains obscured even after implication of available diagnostic tools.
The diagnosis of pleural TB is generally established by analysis of pleural fluid
and pleural biopsy .
In recent years, numerous studies investigated possible biochemical markers
such as ADA, ADA isoenzyme, lysozyme, INF-  and other lymphokines to improve diagnostic efficiency.
Analysis of Adenosine Deaminase (ADA) activity is a very useful diagnostic approach to achieve a more rapid and precise diagnosis in cases of TB pleural effusion.
This study is aimed to evaluate the diagnostic efficacy of Adenosine Deaminase (ADA) levels in tubercular pleural effusion.
6.2 Review of Literature:
Hippocrates first described pleural effusion in 5th century B.C
The disease associated with cough, fever, blood spitting and emaciation was recognized as laoping in china and Rajayakshma in India, was called Phtisis by Hippocrates.(1)
Tuberculous (TB) pleural effusion occurs in approximately 5%of patients with Mycobacterium tuberculosis infection.
The HIVpandemic has been associated with a doubling of the incidenceof
extrapulmonary TB, which has resulted in increased recognitionof
TB pleural effusions even in developed nations.
The treatment of TB pleuraleffusions in patients with HIV/AIDS is essentially similar tothat in HIV negative.(2)
Most common cause of pleurisy with effusion in young adults in India is Tuberculosis(3)
The clinical presentation of TB pleurisy may be subtle or abrupt and severe..
The symptoms most commonly reported are:
cough (71-94%), fever (71-100%), chest pain (78-82%) and dyspnea.
The cough is usually nonproductive particularly when active pulmonary lesions are not present.
Night sweats, chill sensation, dyspnea, weakness and weight loss are common complaints.(4)
Definitive diagnosis of Tubercular pleural effusion can be difficult to
make because of low sensitivity and speficity of noninvasive
diagnostic tools.
Results of pleural fluid staining for Acid Fast Baccilli (AFB)are virtually always negative and pleural fluid cultures for mycobacteria are positive
in < 25% of cases.(5)
The pleural fluid in TB pleural effusion is straw coloured and at times hemorrhagic it is an exudate with a protein concentration >50% of that in serum(usually 4-6gm/dl), a normal to low glucose concentration, a ph of approximate 7.3(occasionally <7.2) and detectable white blood cells.
Neutrophils may predominate in the early stage,while mononuclear cells are the typical findings later.mesothelial cells are generally rare or absent.
Determination of the pleural concentration of Adenosine Deaminase(ADA) is a useful screening test;tuberculosis is virtually excluded if the value is very low.(6)
The diagnosis of pleural tuberculosis has been greatly improved by the use of biochemical markers, which are faster and can be more sensitive. The pleural fluid activity of adenosine deaminase (ADA) is one of the best, providing reliable basis for a treatment decision, particularly in excluding the diagnosis of tuberculosis, due to its high sensitivity.(7)
ADAis involved in the proliferation and differentiation of lymphocytes,especially T lymphocytes. They release ADA when stimulated inthe presence of live intracellular microorganisms.For thisreason,ADA has been looked on as a marker of cell-mediatedimmunity and, in particular, as a marker of the activation ofT lymphocytes(8)
An increase in ADA levels in pleural fluid has been proposed as a test with reasonably good sensitivity and specificity ,which may be a useful,simple and relatively inexpensive test under certain circumstances,particularly where resources are limited and TB is prevalent.(9)
Pleural fluid levels of interferon-gamma (IFN-gamma) and adenosine deaminase (ADA) have been found to be high in patients with tuberculosis (TB) The difference in the cost of performing the two diagnostic tests was compared with the cost of the treatment for a patient with TB.. Even though IFN-gamma estimation was more sensitive (97.1 vs. 91.4%), the extra cost of IFN-gamma estimation for detecting one patient with TB was found to be equivalent to the cost of a complete course of antituberculosis treatment for six patients. In developing countries, where TB is rampant and cost is a major concern, pleural fluid IFN-gamma estimation does not seem to be a cost-effective investigation method for differentiating TB from non-TB pleural effusion.(10)
6.3 Objectives of the study:
To study the diagnostic efficacy of Adenosine Deaminase(ADA) levels in tubercular pleural effusion.
7 / Materials and methods:
7.1 Source of data:

The study will be conducted for period of one year from December2008- December2009.

Inclusion criteria:
1)All patients diagnosed to have Tubercular pleural effusion.
2)Patient above the age of 14 years will be taken for study.
Exclusion criteria:
Diagnosed cases of pleural effusion due to malignancy and heart failure.
7.2 Method of Collection of Data:
Detailed history will be taken from patient and meticulous examination will be done according to prepared proforma.
1)Information regarding detailed history of symptoms including fever, cough, shortness of breath, weight loss, night sweat etc. will be taken.
2)Thorough physical examination of all the systems will be done .
3)Previous hospital records and investigation done will be recorded .
4)All patients will be subjected for routine blood investigation including blood sugar, urea, creatinine and complete haemogram and pleural fluid analysis.
7.3 Does the study requires any investigations or interventions to be conducted on patients or other humans or animals ? If so please describe briefly.
YES
Chest X-ray
Analysis of pleural fluid for
  • Colour
  • Specific gravity
  • Biochemical analysis(total protein,sugar
  • & Adenosine Deaminase.)
  • Cytological analysis(cell count & cell type)
  • Bacteriological analysis(Gram stain & AFB staining)
7.4 Has ethical clearance been obtained from your Institution in case of 7.3 ?
YES, Ethical clearance has been obtained from VIMS INSTITUTIONAL ETHICS COMMITTEE, Bellary.
8 / List of References:
1.P.S.Shankar. Pulmonary TB 2nd edition Newdelhi; oxford & IBH publishing co.pvt.ltd 1990;1-4

2.Diagnosis and Treatment of Tuberculous Pleural Effusion in 2006.

Arun Gopi, MBBS; Sethu M. Madhavan, MD; Surendra K. Sharma, MD, PhD and Steven A. Sahn, MD, FCCP ,From the Division of Pulmonary and Critical Care, Department of Medicine, All India Institute of Medical Sciences, New Delhi, India.
3.Dr.Siddarth.n shah. Association of physicians of India (API) Textbook 8th edition page no.440.
4. Herbert W. Berger, F.C.C.P, Eruido Mejia.
Tuberculouspleurisy.Chest1973;63:88-92.
5.Light,RW(1995)pleural diseases 3rd edition,William and Wilkins,Baltimore
Page.no.154-155
6.Mario.c.raviglione,Richard J O’Brein, Harrisons principles of internal medicine 17th edition,vol.1 page.no.1011.
7.Oliveira H.G., Rossatto E.R., Prolla J.C. Pleural fluid adenosine deaminase and lymphocyte proportion: clinical usefulness in the diagnosis of tuberculosis. Cytopathology 1994;5(1):27-32
8.Roth, BJ Searching for tuberculosis in the pleural space. Chest1999;116
9.Pathology of lung , by William M Thurlbeck,Andrew churg .page 238
10. Sharma SK, Banga Amit . Journal of clinical laboratory analysisISSN0887-8013CODENJCANEM2005,vol.19,no2,pp.40-46
9 / Signature of the candidate :
10 / Remarks of the guide :
11 / Name and Designation of :
( In Block Letters)
11.1 Guide: / DR.VISHNU N. HAYAGREEV
Professor and Head of the Department ,
Department of Medicine,
VIMS, Bellary.
11.2 Signature
11.3 Co – Guide, if any
11.4 Signature
11.5 Head of the Department / DR.VISHNU N. HAYAGREEV
Professor and Head of the Department,
Department of Medicine,
VIMS, Bellary.
11.6 Signature
12 / 12.1 Remarks of Chairman and Principal
12.2 Signature

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