Cellular mesenchymal epithelial transition (C-MET) gene copy number variation in gastric adenocarcinoma: A pilot search for new marker for targeted therapy in HER-2/neu resistance

Increasing HER-2/neu resistance in gastric carcinoma has encouraged search for new biomarkers for targeted therapy. Cellular mesenchymal epithelial transition (C-MET) is one such tyrosine kinase inhibitor proposed for personalized salvage treatment. We determined frequency of C-MET gene copy number variation (CNV) by Fluorescent in-situ hybridization (FISH) in gastric adenocarcinoma (GAC) and sought its correlation with conventional clinicopathologic parameters. Dual-coloured FISH was done on 32 GAC cases. C-MET gene and centromere 7 signals were counted under fluorescent microscope and ratio was calculated for each case. Correlation between C-MET CNV and conventional clinic-pathologic parameters was done by Fischer exact test. CNV was identified in the form of amplification and polysomy (3.1% each) and associated with poorer prognostic parameters. Our pilot study highlights limited subset of patients that may benefit from anti-C-MET-targeted therapy and thus could be a novel biomarker for targeted intervention in GAC.

Clinical Profile of MDR-TB patients with special reference to kanamycin induced ototoxicity in a tertiary care hospital of eastern India

Introduction: MDR-TB is defined as resistance to isoniazid and rifampicin, with or without resistance to other anti-TB drugs. Multidrug-resistant TB (MDR-TB) remains a public health crisis and a health security threat. Kanamycin, is an aminoglycoside antibiotic used to treat multi-drug resistant TB in the intensive phase. Objective: To analyze the patients of MDR-TB with respect to age, sex and presence of comorbidities like diabetes mellitus. Also to study the incidence of hearing impairments among patients of MDR-TB receiving injectable Kanamycin. Methods: 40 patients of MDR-TB diagnosed by sputum culture and drug susceptibility testing (DST) have been classified on the basis of age, sex and presence of diabetes mellitus. All have received injectable Kanamycin for 6months in their intensive phase (IP). Patients giving history of auditory impairments underwent pure tone audiometry (PTA) for detection of sensory neural hearing loss, if any. Result: Out of 40 patients of MDR-TB, 30 were males and the rest 10 were females. Age ranges from 12 to 70 years among which maximum patients fell in the age group of 21-30 years (12 patients). 16 patients were diabetic. After getting Kanamycin, 8 patients gave the history of auditory disturbances and only 1 patient found to have severe sensory neural hearing loss confirmed by pure tone audiometry. Conclusion: Prevalence of MDR-TB has been found more among males and in younger age group. Diabetes Mellitus play a major role here. Kanamycin induced hearing loss is not a very serious concern in our study.

Focal nodular hyperplasia of the liver in children: A report of 2 cases

Focal nodular hyperplasia (FNH) is a benign non-neoplastic lesion of the liver usually found in adults. It is uncommon in children, comprising 2-10% of all pediatric liver tumours. In children, it can occur at all ages, with increased frequency between 6-10 years. We present two cases of FNH in childhood- the first being that of a 5-month-old infant, and the second in a 6-year-old boy. The possibility of congenital FNH had been excluded in the first case. The second case posed diagnostic difficulty initially and was wrongly treated for hepatoblastoma by neoadjuvant chemotherapy, but later correctly diagnosed to be FNH. Both the children are doing well on follow-up. Paediatric FNH though rare, should be kept in mind while dealing with a hepatic mass. Radiological features can be variable and needle sampling may not be sufficient to reach to a diagnosis. Histological examination with glutamine synthetase immunostaining should be performed in doubtful cases to differentiate FNH from other paediatric liver masses, as management differs.

A study of pulmonary tuberculosis in the elderly.

The incidence of tuberculosis (TB) is increasing globally. The diagnbsis of TB in elderly is often delayed due to the atypical presentation. There is also therapeutic problems because of presence of comorbidity, nutritional and socio-economic factors and increased incidence of adverse drug reactions and mortality. A prospective study was conducted among patients presenting with pulmonary tuberculosis at the department of TB and respiratory medicine in a tertiary care hospital between January, 2006 to July, 2006. Thirty patients aged more than 65 years were studied for their clinical characteristics, comorbid illnesses, sputum status, radiological features and adverse drug reactions. They were contrasted against the same parameters in 40 patients aged 65 years or less. The study showed that pulmonary TB in the elderly is characterised by (a) atypical symptoms, (b) more extensive radiological lesion with lower zone preponderance, (c) higher sputum positivity, (d) more frequent comorbidity, (e) more frequent side-effects and (f) higher mortality.

Evaluation of mercury toxicity by some cytological indices in leucocyte cultures.

The genotoxicity induced by different levels of inorganic mercury was evaluated by chromosome metaphase analysis in human leucocytes, treated in vitro for 72 hr. Mitotic index gradually decreased with an increase in concentration of mercury but the reverse phenomenon was observed with respect to chromosomal aberration due to its probable interaction with protein and DNA.

Impact of modified leprosy elimination campaign in a MDT pilot project district of India.

A study was carried out based upon the data available from National Leprosy Eradication Program of Purulia district in West Bengal. The result showed that the disease was in a declining trend up to the year 1998 and was inclining during the year 1998-1999 due to more case detection through MLEC-I, then followed by declining trend during the year 2000 as it was observed by MLEC-II. Single skin lesion rate was higher, MB rate was same and reduced deformity rate indicates early detection of cases due to better awareness of the community about the disease.

Role of paucibacillary leprosy in the transmission of disease.

The objective of this study was to establish that paucibacillary leprosy also carried increased risk of infection to the community. All members of 100 families with an index paucibacillary case were clinically, bacteriologically and immunologically examined. The "comparison" group was sampled from suspect register. Fifty-six cases occurred among 944 contacts of index paucibacillary cases; of these, four were multibacillary and 52 were paucibacillary. In the "comparison" group, two contacts out of 760 developed paucibacillary leprosy. This difference, between the two groups, was statistically significant. All the 56 cases in the index case families were under 20 years of age; and 50 of them were aged under 15 years. Male/female ratio was 2.1:1. Of the 56 cases, 28 shared the same bed with the index patient, 20 shared the same room and eight lived in the same house. Lepromin positivity rate was higher in "comparison" families (92.2%) than in index case families (74.6%), the difference being statistically significant (x = 6.09, P < 0.001). Contacts of index case families, therefore, were immunologically at higher risk than contacts of "comparison" families.

Identification of the appropriate tissue from formalin fixed perinatal autopsy material for chromosomal ploidy detection by interphase FISH.

We have evaluated the suitability of different formalin fixed paraffin embedded tissues i.e., brain, bone, liver and placenta, for fluorescence in situ hybridization (FISH) efficiency and chromosomal ploidy detection employing directly labelled repetitive sequence probes for chromosome X, Y and 1. The study was carried out on four foetal autopsy specimens. Cells from 50 mu thick tissue sections were dissociated before performing mono and multicolour FISH with directly labelled probes. Hybridization efficiency was maximum with brain tissue (81, 55 and 24% for mono, dual and triple colour FISH, respectively), followed by bone (45 and 34% for mono and dual colour FISH), liver (38, 19 and 0% for mono, dual and triple colour FISH) and placenta (14, 5 and 0% for mono, dual and triple colour FISH). These results indicated that brain is the most efficient material followed by bone, liver placenta for chromosome ploidy detection by FISH in formalin fixed tissues.

Nutritional status of pavement dweller children of Calcutta City.

Pavement dwelling is likely to aggravate malnutrition among its residents due to extreme poverty, lack of dwelling and access to food and their exposure to polluted environment. Paucity of information about nutritional status of street children compared to that among urban slum dwellers, squatters or rural/tribal population is quite evident. The present study revealed the magnitude of Protein Energy Malnutrition (PEM) and few associated factors among a sample of 435 underfives belonging to pavement dweller families and selected randomly from clusters of such families, from each of the five geographical sectors of Calcutta city. Overall prevalence of PEM was found almost similar (about 70%) to that among other 'urban poor' children viz. slum dwellers etc., but about 16% of them were found severely undernourished (Grade III & V of IAP classification of PEM). About 35% and 70% of street dweller children had wasting and stunting respectively. Severe PEM (Grade III & IV) was more prevalent among 12-23 months old, girl child, those belonged to illiterate parents and housewife mothers rather than wage earners. It also did increase with increase of birth rate of decrease of birth interval.

Does autopsy of antenatally diagnosed malformed foetuses aid genetic counselling?

BACKGROUND: Many pregnancies are terminated because of ultrasonographic diagnosis of malformation in the foetus. A detailed foetal autopsy is needed to arrive at a definite diagnosis on the basis of which genetic counselling can be provided. METHODS: Sixty-one foetuses, terminated because of antenatal diagnosis of congenital malformations by ultrasound, were autopsied. The ultrasound diagnosis was compared with the diagnosis reached after autopsy. RESULTS: In 31 cases (51%) the autopsy provided additional findings. In 21 cases (34.4%), the autopsy changed the primary diagnosis. The revised diagnosis led to a change in the risk of recurrence in 18 cases (29.5%). CONCLUSION: Genetic counselling depending solely on ultrasonographic foetal diagnosis may be erroneous. For appropriate genetic counselling, a detailed foetal examination should be carried out after termination in cases with ultrasonographically detected congenital malformations.

Analysis of meiotic segregation in human nondecondensed interphase spermatozoa by triple colour rapid direct fluorescent in situ hybridization.

Meiotic segregation of chromosomes X,Y and 1 was analyzed by triple colour rapid fluorescent in situ hybridization (FISH) with directly labelled probes on 4506 non-decondensed and non-cleaned interphase spermatozoa from four healthy male donors to test the possibility of rapid sperm FISH by omitting the conventional sperm decondensation and cleaning steps. Only 0.15 per cent of sperms were without any signals which suggested high hybridization success. An abnormal number of signals was seen in 1.6 per cent of sperms. Chromosome specific as well as donor specific segregation error was seen similar to previous reports. There was a wide variation in the ratio of normal X and Y bearing sperm from donor to donor. This study indicated that for segregation studies sperm FISH can be carried out in three hours with directly labelled probes without the steps for separation of sperm from somatic cells (cleaning), sperm swelling and sperm DNA decondensation.