Bombay Hospital Journal

ABSTRACTS OF PAPERS AT THE 84TH RESEARCH MEETING OF THE MEDICAL RESEARCH CENTRE OF BOMBAY HOSPITAL ON MONDAY, 12TH FEBRUARY 2001, 2.30 PM, SP JAIN CAFETERIA. (CONVENOR DR. HL DHAR)

1. A STUDY OF SERUM VITAMIN B12 DEFICIENCY IN DIFFERENT DISEASES

SR Kankonkar, RV Prabhu, SJ Tijoriwala, SC Raikar, SV Joshi, HL Dhar, RC Kankonkar
During attempts to unravel the mystery of anaemia almost about two centuries ago, Combe’s research made him believe that anaemia was disorder of digestive assimilative organs, while Thomas Addison observed that anaemia mostly occurred in fat people. Subsequent research on the subject by Flint, Castle, Will et al ultimately indicated that anaemic patients were deficient in serum vit. B12 levels. Now it has been revealed that serum vit. B12 deficiency mainly exists in patients having iron deficiency, normal near term pregnancy, vegetarian food habits, partial gastrectomy or ileal damage, consumption of oral contraceptives, parasitic competition, pancreatic deficiency in patients treated for epilepsy, older age etc. Naturally, serum vit. B12 deficiency was observed not only in anaemic patients but also many other disorders.
Hence it was decided to estimate serum vit. B12 levels in patients suffering from general debility, anaemia, diabetes, thyroid disorder, and dementia etc. in order to see if any correlation existed between serum vit. B12 level and a particular disorder and also the vegetarian and non-vegetarian food habits of patients. It was also of interest to see whether this study could be of any therapeutic significance for the clinician to decide about the line of treatment.

Five hundred patients that were referred to Tissue Typing Lab of Bombay Hospital between the period 1995-97 for the purpose of estimation of serum vit. B12 levels were chosen for this study. Patients were in the age group of 10-97 years, 54% of them (270 patients) were vegetarians and 46% (230 patients) were non-vegetarians.

The serum vit. B12 level deficiency was nearly 3.35 fold more in vegetarians viz. 43.70% as compared to that in non-vegetarians 13.04%. Vegetarians mostly belonged to Marwari (31.08%), Gujarati (27.7%) and Maharashtrian (20.94%) communities.

The higher number of serum vit. B12 deficient patients was seen in thyroid cases (55.5% viz. 10/18). This was followed by patients with gastrointestinal disorder 43.60% viz. 17/39), anaemia (42.55% viz. 20/47), general debility (29.60% viz. 59/200), neurological disorders (22.81% viz. 39/171) and the last in the list were diabetic patients (only 12.0% viz. 3/25).

Amongst the serum vit. B12 deficient neuropathic patients, 28% cases comprised patients with loss of memory, 20% patients with dementia, 21.74% patients with peripheral neuropathy and 22.22% patients with other neurological symptoms viz weakness of limbs, numbness etc.

Amongst patients with gastrointestinal disorders, 43.6% were found to be serum vit. B12 deficient. Parasitic infections are common in a developing country like ours and hence there is a possibility that the patients having serum vitamin B12 deficiency could have some parasitic infections too.

2. ENTERIC FEVER : CORRELATION OF BLOOD CULTURE AND WIDAL TEST IN PAEDIATRIC PATIENTS

Sweta Chomal, Lina Deodhar
The term enteric fever includes typhoid fever caused by Salmonella typhi and paratyphoid fever caused by S. paratyphi A, B and C. Typhoid fever is a common illness among children in developing countries. Though demonstration of the causative agent in blood is considered to be the most conclusive test in the diagnosis, a positive result depends upon several factors. The rate of isolation has been reported to vary from 45% to 80% in blood. With BACTEC 9050 system, identification of blood stream pathogens and results of antimicrobial susceptibility test can be made available to the clinicians in 48 hrs. The other most commonly used diagnostic procedure in typhoid fever is tube agglutination or Widal test. The test results are difficult to interpret in areas where typhoid and other Salmonellosis are endemic. In such cases a titre greater than 1:100 is considered significant.
In the year 2000, a total of 2712 blood samples were received for blood culture, out of which 370 samples were from paediatric patients, 90 samples, of the paediatric patients, were bacteriologically positive out of which 57 (63%) showed growth of S. typhi and 8 (8.89%) showed growth of S. paratyphi A. A total of 48 samples were received for both blood culture and Widal test, out of which one sample was positive for S. paratyphi A by both methods. Out of the remaining 47 samples, 25 samples were bacteriologically as well as Widal positive for S. typhi. 3 samples were bacteriologically positive but Widal negative and 4 samples showed a titre of less than 1:120. 15 samples were positive by Widal and negative by blood culture.

In the present study 60.8% strains of S. typhi were multidrug resistant that is resistant to ampicillin, choramphenicol, co-trimoxazole and tetracycline (ACCoT). Amongst quinolones 66% strains were resistant to nalidixic acid and none to ciprofloxacin. All the strains were sensitive to ceftriaxone.

3. NEUROENDOCRINAL CARCINOMAS

Deepak Dhatrak, AR Chitale
These are the carcinomas that share morphologic and biochemical features with cells of the dispersed neuro-endocrine cell system. Organs in which it can occur include lungs, breast, cervix, oesophagus, stomach, large bowel, urinary bladder, prostate, larynx etc. It originates in primitive cells of the basal epithelium which in the process of neoplastic change undergoes partial differentiation toward neuro-endocrine cells.
Morphologic features : (a) Light Microscopy - small round to oval cells, pattern of growth - trabecular, rosette, insular. Nuclei - finely granular and very hyperchromatic. Nucleoli - Inconspicuous. Cytoplasm - scanty.

(b) Immunohistochemistry shows positivity for neuroendocrine markers such as chromogramin, synaptophysin and neuron specific enolase. (c) Electronmicroscopy - dense core neurosecretory granules in the cytoplasm of tumour cells. Some endocrine disorders, such as cushing’s, syndrome, Eaton, lambert syndrome and myasthenia like syndrome are seen associated with these carcinomas. Prognosis is poor.

Case I - Neuro-endocrine carcinoma - cervix occurs most often in older age, but also < 40 years (In this case 35 years). Possible aetiologic agent - human papilloma virus (HPV).

Most cases - pure form. Other - combined with epidermoid carcinoma; adenocarcinoma or carcinoma in situ. Immunohistochemistry - in addition to neuroendocrine markers also express positivity for variety of peptide hormones, keratin, chorioembryonic antigen (CEA). Histologically and clinically aggressive. Prognosis is poor. Rarely live for more than 5 years.

Case II - Neuro endocrine carcinoma - large bowel occurs in 4 patients.

1. As scattered endocrine cells in otherwise typical adenocarcinomas (particularly of the mucinous type) occurs in 15-50% of all adenocarcinomas.

2. Mixed composition - typical adenocarcinoma intermingles with a component exhibiting clear cut endocrine differentiation. 3) Small cell carcinoma - Most are located in the right colon. Some of these arise on the basis of anadenoma, usually of villous type. Prognosis is poor with early metastasis to lymph nodes and liver. 4) Composed of larger cells than those of small cell carcinoma. It has a more organised appearance. Neuroendocrine carcinoma can occur in patients with ulcerative colitis.

Case III - Metastatic neuroendocrine carcinoma omentum - Primary carcinoma, head of pancreas. Males are more commonly affected. Age - 42-73 (Mean 60) years.

Clinical features - Generalised weakness, anorexia, weight loss and jaundice. General clinical and biochemical features of the ectopic ACTH syndrome are also seen. It arises in the islets of Langerhan’s and represent an unusually malignant form of islet cell carcinoma. Prognosis extremely poor. Patient died within 2 months from the onset of symptoms with extensive metastatic disease.

Thus, it is important to diagnose carcinomas with neuroendocrine differentiation because of their clinically aggressive behaviour and overall poor prognosis.

4. REPORTING OF HIV TEST

Maya Parihar Malhotra, Ramesh Shah
Methodology : Informal interactive session - experience sharing
Duration : 10 minutes

Mind Set : Most of us do not have the much required patience in our daily routine life e.g. (1) We cannot wait at the Xerox shop or PCO if there is a crowd. (2) When the train stops midway on the tracts, we criticize the motorman, inspite of knowing that he has to follow the signal system. With the background of this mind set we discuss the issue of ‘supposed delay’ in HIV reporting.

In our lab HIV testing is usually done by the Elisa method. The protocol of any Elisa reporting is to repeat any positive sample (above cut off value) in duplicate. This results in a time lag of one more shift, as it gets repeated in the second batch. Now in case of HIV we have to take further care and precaution in reporting due to social stigma and fear that is attached to the disease. Even if patient comes to know that the results are doubtful he will have severe mental trauma, as there is no cure for HIV.

To take this care another technician repeats the same sample in the second batch (to rule out human error). It is also tested by another kit (to rule out kit error if any). Now if we get the same reading or discrepancy we ask for a fresh blood sample of the patient (to rule out sample collection error). As and when patient gives fresh sample the test is again run on this fresh sample. Only after the sample is confirmed through this schedule is the final report issued to the patient. We feel that this is a very much required time lapse to minimise all known error areas. Many labs send their positive samples to our lab so that final positive reporting is done by us. We can say that we are almost treated as a reference centre.

Question : Why the delay in reporting of Negative cases?

Answer : Normally it takes maximum one shift time (8 hrs) as we have 24 hrs service but sometimes there can be a delay e.g. (1) Gadget/equipment failure (2) Insufficient blood sample goes for collection again (3) Haemolysed sample (4) Identification of sample is not proper. (5) Kit or accessories are not available (6) Natural or man-made calamities e.g. strikes, flooding or train problem.

Note A : For dire emergencies like accident or delivery we do have HIV spot facility max time 10 mins. Note B : Also in emergencies if test is run but report is not ready we give a hand written provisional report.

In my 25 years work experience no one (Hon. Dr., Resident doctor, patient or patients relative) has said "please take your time but give me an accurate report" (attitude !!). Every one is in a hurry which leads to nothing but necessary pressure.

In reality a negative report is more dangerous than a positive one as universal precautions are taken for the positive case but the patient with a negative HIV report is taken for granted even though he may be in the "Window period". Like we say "God save me from friends enemies that I can flight".

5. CHANGING AWARENESS AMONG BLOOD DONORS

Maya Parihar Malhotra, Radhika Nambiar
The blood bank caters mainly to indoor patients and therefore the majority of blood collection is made from non-remunerated replacement donors. We do have indoor voluntary donors who are well informed and committed to the cause; but their numbers are few.
The blood bank is continuously attempting to increase the indoor voluntary donor pool by spreading of better awareness among our routine donors. To enhance this process a survey of 100 donors was done to determine the existing level of awareness and information regarding blood, blood donation and its resulting impact on blood transfusion and patient safety.

Among the donors who were randomly selected and interviewed 74% were in the age group 21-40 years. 95% of the donors were males. Donors of female sex were often rejected due to low Hb, menstruation, pregnancy, lactation and abortion. However the number of females among the voluntary donors is definitely higher. Irrespective of their age and sex 70% of the respondents had at least a graduate qualification and their responses and general attitude towards blood donation was positive.

It was seen that people usually preferred and many times insisted to receive blood only from their family members and friends. They themselves were willing to donate blood if required by a patient admitted in a hospital. But were apprehensive regards safety and disposables used in a camp and therefore reluctant to donate at blood donation camps.

74% of the donors knew that the HIV and HbsAg tests are mandatory for donated units and 80% of them were definitely sure that HIV infection would not be contracted by donating blood. This was a welcome change because a similar survey done 4 years back revealed that blood donors avoided donation because of the fear of getting infected by HIV during the process of donation.

74% of the donors felt that a patient could get infected for HIV if untested blood is used and if the blood is brought from an unauthorized blood bank.

However only one donor was aware of the term "window period" and the rest of them were shocked to know that there was nothing like "100% safe blood". This information left them thinking about the safety of their own and their families blood requirement.

100% safe blood is something that doesn’t exist even in the western countries where better organised and sophisticated services are available. Existence of safe blood could be made possible only if people are made aware of the consequences of donating and receiving blood from unhealthy donors. Most often people bring their own relatives and friends considering them to be healthy donors. The irony is that these donors themselves could be infective.

At the Blood Bank elaborate pre-donation screening procedure with one to one contact with the donors is essential. Information should be made available to prospective donors on all aspects of the procedure. The only solution for this is that more and more voluntary donors have to be encouraged and we need to increase our voluntary donor pool and have committed regular, repeat blood donors, who are educated regards importance of their donation.

6. DIAGNOSTIC PROFILE OF HEPATITIS B

Maya Parihar Malhotra, PK Khadapkar
We have a random access fully automated machine where hepatitis markers i.e. HBsAg, Anti HBc-IgM, HBe-Ag, HBe-Ab, Anti-HBc-Total and Anti-HBs are tested and reported in a day. These markers aid the Clinician in the diagnosis of acute hepatitis infection, sero-conversion or chronic infection. The further treatment and decision for anti-viral treatment or vaccination can thus be taken.
During the period from December 2000 to January 2001, 122 HBsAg positive cases were referred to our lab for testing of various Hepatitis Markers (229 tests).

26 cases were tested for Anti HBc-IgM, HBe-Ag and HBe-Ab, 38 cases for HBeAg and HBe-Ab, 4 cases for HBc-Total, HBeAg and HBe-Ab, 19 for HBc-IgM alone, 28 for HBeAg 5 for HBe-Ab and 2 for HBc-Total. In addition Anti-HBs was asked for in 9 cases.

1. Out of 45 cases sent for Anti HBc-IgM test : 6 were positive indicating early acute Hepatitis B infection and 39 were negative i.e. potential chronic Hepatitis B cases.

2. 96 cases were referred for HBeAg test : 27 were positive indicating high infectivity of the patient and 69 were negative.

3. 73 cases were sent for HBe-Ab test : 51 were positive indicating low infectivity of the patient and the resolution of infection is likely and 22 were negative. We had one case where both HBeAg and HBe-Ab results were negative i.e. the "e-window". Here too the infectivity is low and resolution of infection is likely.

4. HBc-Total 6 cases referred : 4 were positive indicating ongoing or old infection and 2 were negative.

5. 6 out of 9 cases referred for Anti-HBs were positive. Four of these were post vaccination studies and 2 were relatives of carriers and indicates protection from the virus. The 3 negative cases were relatives of patients and is an indication of susceptibility of the patient to HBV infection. These individuals need to be vaccinated.

Thus the knowledge of the Hepatitis Marker’s status is important in diagnosis and treatment of Hepatitis. Our lab now offers this facility and the response we are getting is encouraging.

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