A study on genetic polymorphism of RET proto-oncogene in Hirschsprung's disease in children.

BACKGROUND: Hirschsprung's disease (HD) is a genetic disorder with a complex pattern of inheritance. Some single-nucleotide polymorphisms (SNPs) are identified to be associated with the risk of Hirschsprung's Disease (HSCR). AIMS AND OBJECTIVES: The aim of this study is to know the association between the rearranged during transfection (RET) proto-oncogene polymorphism and HD and to characterize the SNPs of RET proto-oncogene affecting HD. MATERIALS AND METHODS: The study was conducted in the Department of Pathology in association with the Department of Pediatric Surgery. Blood samples were collected from the patients diagnosed with confirmed HD and from age- and sex-matched controls. This case-control study consisted of 53 HSCR cases and 50 controls. Genotypes of rs1800860 and rs1800861 were analysed in by polymerase chain reaction amplification and sanger sequencing. Associations with the risk of HSCR were estimated by odds ratio (OR) and their 95% confidence intervals (95% CI) using. RESULTS: We observed that in the case of rs1800860A > G genotype AG was not associated with the increasing risk of disease (OR with 95% CI = 0.568 [0.238-1.356]) while genotype GG was associated with increasing the risk of the disease (OR with 95% CI = 2.278 [0.967-5.366]). In the case of rs1800861G > T genotype GT was associated with lowering the risk of the disease (OR with 95% CI = 0.230 [0.0981-0.539]) while genotype TT was associated with increasing the risk of the disease (OR with 95% CI = 9.647 [3.830-24.302]). The difference in the genotypic distribution of GT and TT at rs1800861G > T between Short segment disease (SSD) cases and Long Segment Disease (LSD) and total colonic aganglionosis was made by Fisher's exact test and it was statistically significant (P = 0.0476 and 0.0054). CONCLUSION: The results of this study support the hypothesis that variations in RET pathway might play an important role in the development of HSCR.

Incidence of Fanconi anaemia in phenotypically normal aplastic anaemia patients in West Bengal.

OBJECTIVES: Fanconi anaemia (FA) is a rare inherited bone marrow failure and autosomal recessive blood disorder. FA patients have a higher risk of cancer, including acute myeloid leukaemia and squamous cell carcinoma. Maximum, but not all, affected individuals have one or more somatic abnormalities, including skin, skeletal, genitourinary, gastrointestinal, cardiac and neurological anomalies, etc. Positive stress cytogenetics has immense implications for the treatment and management of FA. The aim of our study was to find out the incidence of FA in the population of phenotypically normal aplastic anaemia (AA) patients in West Bengal. METHODS: Ethical clearances were obtained from the corresponding institutional committees. A total of 117 AA cases was selected. Stress cytogenetics was performed from peripheral venous blood (PVB) samples of 63 AA patients (age ≤ 50 years) and 63 age- and sex-matched healthy individual (control) using Mitomycin C (MMC). RESULTS: Out of 63 AA patients, 6 (9.25%) cases showed positive stress cytogenetics suggestive of FA, which is statistically significant (p-value - 0.000532), analysed by chi-square test. DISCUSSION: A considerable percentage of patients showing sensitivity towards MMC, even if they are phenotypically normal and did not have any distinguishable features which are generally found in FA. CONCLUSION: This observation may indicate that stress cytogenetics analysis of phenotypically normal AA patients (≤50 years) is essential for the improvement of the treatment procedure.

Spectrum of Hemoglobinopathies in West Bengal, India: A CE-HPLC Study on 10407 Subjects.

Hemoglobinopathies are common genetic disorders of haemoglobin. Identification of these disorders is immensely important epidemiologically and they can be prevented by population screening. The present study was carried out to evaluate the spectrum of hemoglobinopathies in the state of West Bengal by the cation-exchange high-performance liquid chromatography (CE-HPLC). A retrospective, single-center, cross-sectional study was conducted on consecutive 10,407 participants. Out of 10,407 subjects, 8,898 (85.5 %) were diagnosed as normal, 579 (5.6 %) were as ß-thalassemia trait (BTT) and 522 (5.0 %) were detected as HbE carrier on HPLC study. Apart from BTT and HbE carrier ten additional variants were encountered. The present study showed that CE-HPLC is a convenient, high-throughput, labour-saving and objective screening tool for early detection and management of hemoglobinopathies.

Impact of iron deficiency anemia on cell-mediated and humoral immunity in children: A case control study.

OBJECTIVE: The precise role of iron in immune regulation especially in children vulnerable to iron deficiency is not fully known. Hence, this study was conducted to evaluate the effects of iron deficiency anemia (IDA) and its treatment with oral iron supplementation on cell-mediated immunity (CMI) and humoral immunity (HMI) in children. MATERIALS AND METHODS: A total of 40 children (<15 years) with IDA and 40 age-matched healthy children after satisfying the inclusion criteria were enrolled for this case-control study. Flow cytometric evaluation of absolute and relative numbers of cluster of differentiation 4 (CD4) and CD8 (cluster of differentiation 8) lymphocyte subgroups was carried out to assess the CMI and serum Immunoglobulin G (IgG), Immunoglobulin A (IgA), Immunoglobulin M (IgM) were measured to assess the HMI at baseline and 3 months post oral iron supplementation. RESULTS: Significantly lower levels (P < 0.05) of CD4+ T-cells and decreased CD4:CD8 ratios were observed in the iron deficient children. Iron supplementation significantly improved the CD4+ cell counts and CD4:CD8 ratios. However, immunoglobulin levels weren't different between the two groups. CONCLUSIONS: Although IDA did not influence HMI, it significantly impaired CMI, which was improved following iron supplementation for 3 months.

Endometrial hyperplasia: a clinicopathological study in a tertiary care hospital.

OBJECTIVE: To evaluate the clinical as well as histomorphologic features in different cases of endometrial hyperplasia along with its relative occurrence. MATERIALS AND METHODS: A one-and-a-half-year prospective study was conducted on histopathologically diagnosed cases of endometrial hyperplasia in a tertiary care hospital. Apart from relevant clinical findings, histomorphologic details were noted and statistically analyzed. OBSERVATIONS: Maximum number (46.5 %) of endometrial hyperplasia occurred in patients of 41-50 years age group. Majority (55.2 %) of the patients were found to be premenopausal. Menorrhagia was the most common (49.6 %) clinical presentation followed by postmenopausal bleeding (30.8 %). Simple hyperplasia without atypia was the most common type (95.6 %) followed by complex hyperplasia without atypia (3.6 %) and complex hyperplasia with atypia (0.8 %), respectively. The study of gland-stroma ratio revealed 65:35 to be the most frequent (34 %) ratio; variable-sized glands with cystic dilatation (60.4 %) was the commonest gland architecture and most of the cases (99.2 %) showed the absence of atypia. Associated histopathological findings included a case each of endometrial adenocarcinoma and undifferentiated endometrial stromal sarcoma along with the common leiomyoma and progesterone effects. CONCLUSION: Menorrhagia was the most common presenting complaint in cases of endometrial hyperplasia. The cases were mostly in the premenopausal age group. Simple endometrial hyperplasia without atypia was the commonest type diagnosed histopathologically. Histopathological examination along with clinical details is essential to give the final opinion regarding the diagnosis.

CT guided fine needle aspiration cytology of thoracic mass lesions: a prospective study of immediate cytological evaluation.

To evaluate the role of CT guided FNAC as diagnostic and supportive investigation for thoracic lesions, 190 patients were studied during two years period from March 2003 to February 2005 in our institution. A total number of 163 (85.8%) lung lesions, 22 (11.6%) mediastinal lesions and 05 (2.6%) pleural lesions were obtained; only neoplastic lesions were categorized as per WHO classification. The diagnostic sensitivity for malignancy was 97.71% and specificity 100%. Though our priority was cytological assessment, the cytological diagnosis was corroborated with clinico-radiological parameters and transbronchial biopsies whenever applicable.

A study of fine needle aspiration cytology of salivary gland lesions with histopathological corroboration.

The diagnostic utility of fine needle aspiration cytology as initial work up of salivary gland enlargement was assessed in one hundred and eighty-five salivary gland specimens over three years period and corroborated with histopathology, whenever feasible. All smears were evaluated according to cell size, amount of cytoplasm, cytologic atypia and presence of lymphocytes. (a) Variable cytologic appearances of pleomorphic salivary adenoma were observed. (b) Cellular pleomorphic adenoma and adenoid cystic carcinoma showed basaloid cell features. (c) Tumours with intermediate size cells and bland cytology included low grade muco-epidermoid carcinoma and cystic lesions. (d) Warthin's tumour, oncocytoma, salivary duct carcinoma and high grade muco-epidermoid carcinoma revealed large cells and abundant cytoplasm with or without atypia. A major diagnostic categories were inflammatory lesions (n = 7 5), cystic lesions (n = 9), benign tumours (n = 81), malignant neoplasms (n = 1 8) and normal acinar pattern (n = 2). Malignant tumours included muco-epidermoid carcinoma (n = 5), adenoid cystic carcinoma (n = 3), acinic cell carcinoma (n = 2), adenocarcinoma (n= 2), squamous cell carcinoma (n = 1), undifferentiated carcinoma (n= 4) and malignant lymphoma (n = 1). Histopathological correlation was possible in 40% of benign and 80% of malignant neoplasms. The overall sensitivity, specificity and diagnostic accuracy were very high. So it can be concluded that fine needle aspiration cytology can play important role in early diagnosis and subsequent therapeutic planning of salivary gland lesions.