Effect of vitamin D supplementation on sustained virological response in genotype 1/4 chronic hepatitis C treatment-naïve patients from India

Background & objectives: The effect of vitamin D supplementation on response to antiviral therapy in hepatitis C virus (HCV) genotype 1 and 4 infection still remains unclear, with studies yielding inconsistent results. The aim of the present study was to assess the effect of vitamin D supplementation on treatment outcome in patients with genotype 1/4 chronic hepatitis C (CHC) infection. Methods: Sixty consecutive, treatment-naïve, genotype 1 and 4 chronic HCV patients were included in the study. The patients were randomized into two groups: Vitamin D supplemented group received pegylated (PEG)-interferon ?-2a 180 ?g per week plus ribavirin (RBV) (1000-1200 mg/d) together with vitamin D3 (2000 IU/d) and control group received identical therapy without vitamin D (32 patients). Results: There were no significant differences between the two groups in terms of age, sex, body mass index and baseline laboratory values. Lower vitamin D levels were associated with higher grades of fibrosis in liver histology (vitamin D >20 ng/ml - 70% vs vitamin D <20 ng/ml - 37%, P<0.05). Vitamin D supplemented group had similar rapid viral response (40 vs 28%, P=0.36), complete early viral response (53.2 vs 40%, P=0.34), end of treatment response (64 vs 46%, P=0.17) and sustained virological response (SVR) (60 vs 44%, P=0.19) as compared to control group. Interleukin 28B polymorphism [odds ratio (OR)-15.37, 95% confidence interval (CI)-2.32-101.76, P=0.04] and baseline serum vitamin D levels (OR-6.36, 95% CI-1.36-29.61 P=0.02) were independent predictors of SVR in genotype 1/4 CHC. Vitamin D supplementation was not found to be predictor of response in genotype 1/4 CHC on multivariate analysis (OR-2.79, 95% CI- 0.63-12.34, P=0.74). Interpretation & conclusions: The present study showed that addition of vitamin D to PEG/RBV combination therapy in treatment-naïve patients who were infected with HCV genotype 1/4 had no effect on the rates of rapid, early and sustained viral responses.

Cervical mediastinoscopy: Re-evaluation of an old technique in era of new imaging technology.

Context. With the advent of modern anatomical and functional imaging technologies, application of cervical mediastinoscopy has decreased in diagnosis and staging of mediastinal diseases. Aim. To evaluate the usefulness of cervical mediastinoscopy in assessing the mediastinal disease when imaging modalities are non-diagnostic. Settings and Design. Retrospective analysis of records of a tertiary care hospital. Patients and Methods. Thirty-nine patients with mediastinal pathology of varied aetiologies underwent cervical mediastinoscopy. Pre- and post-operative diagnosis was compared. Results. In 34 out of 39 cases (87.5%), cervical mediastinoscopy provided a confirmatory final diagnosis. One case had a major complication in the form of recurrent laryngeal nerve palsy. Conclusion. Cervical mediastinoscopy is useful, minimally invasive modality in a scenario where anatomical and functional imaging tools are non-diagnostic.

Immunohistochemical localization and correlation of p53 and PCNA expression in breast carcinoma.

The object of the present study is to detect the p53 tumour suppressor gene and proliferation cell nuclear antigen (PCNA) expression in breast carcinoma by immunohistochemistry and correlate them with the prognostic parameters. Total 35 cases of primary breast carcinoma were studied and classified histologically. Paraffin sections were stained by using monoclonal antibody D07 for p53 protein and PC-10 for PCNA. Out of 35 cases, 16 (45.7%) were p53 positive and 25 (71.4%) were PCNA positive. The mean PCNA labelling index (PCNA LI +/- SD) was 58.97 +/- 22.72 in tumors positive for both p53+ and PCNA+ while cases negative for p53- and positive for PCNA+ has higher PCNA LI +/- SD (59.24 +/- 18.97). The difference in the two groups was not significant. Most cases were positive for both p53+ and PCNA+ in the age group < 30 with higher mean PCNA LI +/- SD (62.20 +/- 27.13) than in the group > 30 (57.88 +/- 18.47). In the pre-menopausal group 57.1% cases were positive for p53+ with higher PCNA LI +/- SD (59.94 +/- 24.22). Maximum p53 and PCNA positivity was observed in grade III tumors (63.2% and 84.2%). The mean PCNA LI +/- SD was also highest in grade III carcinomas (66.83 +/- 13.97). No significant correlation was found between p53 and PCNA status with morphological type and tumour size except that logistic regression showed a positive correlation with tumour grade. Therefore the present study suggests that both p53 expression and PCNA are markers of poor differentiation in breast cancer.

Isolation and identification of yolk proteins in Indian major carp, Labeo rohita.

Two yolk proteins (YP1 and YP2) from the ovaries of Indian major carp, Labeo rohita were isolated by gel filtration and partially characterized by the use of hydroxyapatite ultrogel column in conjunction with native PAGE. On native PAGE YP1 gave a single protein band, whereas YP2 of gel filtration revealed the contamination of YP1, which was removed by adsorption chromatography on hydroxyapatite ultrogel and then the YP2 was the purified one as judged by electrophoresis. Both YP1 and YP2 also stained for lipid and contained alkali-labile phosphorus. Therefore, both yolk proteins were lipophosphoprotein. The molecular weights of YP1 and YP2 were 620 kDa and 225 kDa respectively as determined by gel filtration on Sepharose 4B. When YP1 and YP2 were compared in relation to some physicochemical characteristics with yolk proteins of other oviparous vertebrates including fish, they were lipovitellin like. Antiserum to YP2 crossreacted with YP2 and vitellogenin suggesting that YP2 was the cleaved product of vitellogenin. Anti-YP2 antiserum was not crossreacted with native YP1, whereas reduced and/or denatured YP1 was crossreacted indicating the presence of antigenic determinants in the inner core region of YP1 polypeptide.

Wilms' tumour : a clinicopathologic study with special reference to its morphologic variants.

Twenty five cases of Wilms' tumour were studied with special reference to their morphological variations. Wilms' tumour constituted 7.6% of all the malignant tumours of childhood and 50% of renal malignancies. Male/female ratio was 4:1; the mean age being 3.5 years. Left side was commonly involved (60.9%) center dot bilateral involvement in one case (4.3%). Morphologic study revealed triphasic pattern in 60% cases, biphasic (epithelial + stromal) in 12% and monophasic pattern in 28%. Other features observed were myxomatous degeneration, rhabdomyoblasts, calcification and squamous epithelial pearls seen in 20%, 12%, 8% and 4% respectively.

Tumours of the male urogenital tract: a clinicopathologic study.

The present communication deals with the study of 388 tumours of the male urogenital tract diagnosed histopathologically during the period of 1984 to 1990. Of these 12 (3.09%) were benign and the rest 376 (96.91%) malignant. The incidence of malignant growths of male urogenital tract was 8.71% of all the malignancies or 14.19% of all cancers in males. Renal tumours constituted 10.64% of all the malignant tumours of male urogenital tract or 1.51% of all the male cancers. Morphological variants were renal cell carcinoma (37.5%), Wilms' tumour (47.5%), transitional cell carcinoma (7.5%), papillary cystic adenocarcinoma (3.5%), leiomyosarcoma (2.5%), metastatic from thyroid (2.5%). The mean age of the cases for renal cell carcinoma was 50.3 years and for Wilms' tumour 3.5 years. Urinary bladder cancer comprised 29.52% of all the malignancies of male urogenital tract or 4.19% of all malignant growths in males. The average age of the patients was 53.9 years. Transitional cell carcinoma was the commonest type of tumour (91.9%). Primary malignant tumours of the testis constituted 0.95% of all the malignancies, 1.55% of all male cancers, 10.9% of all malignancies of male urogenital tract or 18.3% of all the malignant growths of male genital tract. The mean age of the patients was 40.6 years. Seminoma was the commonest -46.34% of all the testicular tumours. The incidence of prostatic cancer was 1.81% of all cancers, 2.95% of all malignancies in males or 20.74% of all malignancies of male urogenital tract or 34.82% of malignancies of male genital tract.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlative study of histopathology and bacteriology in patients of tubercular lymphadenitis.

Histopathology as well as bacteriology of lymph node specimen are useful diagnostic tools for tuberculous lymphadenitis. In the present study, a total of 71 cases of lymphadenitis were selected for histopathological and bacteriological studies. Only 46 patients had caseating type and 4 had non-caseating type of tuberculous lymphadenitis while 21 patients revealed non-specific chronic lymphadenitis on histopathological examination. Only 6 lymph node smears were positive for acid fast bacilli (AFB), 19 cases were positive for mycobacterial culture growth. Thus, it is not necessary that the cases which are histopathologically positive will be positive for culture as well. Therefore, both bacteriology and histopathology are complimentary diagnostic tools for tuberculous lymphadenitis.

Mitochondrial ATP synthase genes may be implicated in cytoplasmic male sterility in Sorghum bicolor.

Incompatible nuclear-cytoplasmic interactions are responsible for the phenomenon of cytoplasmic male sterility in plants. We have analysed male sterile (2077A, 296A), maintainer fertile (2077B, 296B) and fertility restored (2077R, 296R) lines of sorghum for the restriction fragment locations of various mitochondrial genes and their transcripts. We report here a polymorphism in genes related to the ATP synthase complex between two different cytoplasms from the A and Β set of lines of 2077 and 296. There is also a difference in the transcript size of the atpA gene between the A and Β cytoplasms. We propose that incompatibility in nuclear cytoplasmic interactions may be explained in terms of incompatible subunits being synthesized by the mitochondria and nucleus for a multisubunit complex of the mitochondrial membrane such as ATPase.

A histomorphologic and ultrastructural study of the malignant tumours of the renal pelvis.

The study was carried at two different centres. Only 9 cases of primary malignant tumours of the renal pelvis could be collected during the period of 7 years (1984-1990). Renal pelvis malignancies constituted 0.21% of all the malignancies and 12.16% of all the malignant growths of the kidney (9 out of 74 cases). The age of these patients ranged from 24 to 70 years; the mean being 41.7 years. Male/female ratio was 8:1. Common triad of complaints (pain, haematuria and lump) was noticed in 22.2% of patients. Individually they were noticed in 77.8%, 66.7% and 44.4% of patients respectively. Transitional cell carcinoma was the commonest, seen in 7 patients (77.8%) whereas squamous cell carcinoma and adenocarcinoma were noticed in one patient (11.1%) each. Hydronephrosis, chronic pyelonephritis and nephrolithiasis were noticed in 66.7%, 44.4% and 22.2% of patients respectively. Ultrastructural study of urothelial tumours revealed tumour cells in various stages of differentiation with loss of intercellular junctions and dense collection of rough endopasmic reticulum fibrils around the nucleus.

Demonstration of two forms of vitellogenin in serum of estradiol-17 beta-treated Indian major carp, Labeo rohita.

Vitellogenin (Vg) synthesis was induced in the male and non-vitellogenic female Rohu, the Indian major carp, by estradiol-17 beta(E2) where effect was more in female. A crude preparation of Vg was isolated in the second peak after gel filtration on Ultrogel AcA 34 from the sera of vitellogenic female Rohu and E2-treated male and female Rohu. Estimation of alkali-labile phosphorus was shown to be used as an index of Vg. Native-PAGE analysis has revealed the presence of two forms of Vg (Vg1: 430,000 dalton and Vg2:240,000 dalton) in Vg fraction obtained after gel filtration as well as in the sera of E2-treated male and female Rohu. Immunological cross-reaction studies between antiserum to yolk protein and Vg fractions as well as the sera from E2-treated male and female Rohu further indicates the presence of two precipitin lines (not clearly visible as the two lines fused to form a thick line) suggesting the occurrence of two forms of Vg in the Rohu.

Ultrastructural reappraisal of endometrial glandular changes in women wearing Cu-T200 device for longer duration.

The present communication deals with the effects of Copper-T200 Sq mm intrauterine device on the endometrial glands in the women using it for a longer duration i.e. up 8 years. The ultrastructural changes in the lining endometrial glands were studied during both non-ovulatory and ovulatory phases of the menstrual cycle. The ultrastructural studies demonstrated significant progressive changes in the lining endothelial cells of endometrial glands. The findings showed marked accumulation of glycogen in the cells in secretory phase of the endometrial cycle. Ultrastructural changes in glandular lining cells were more pronounced in women using Cu-IUCD for 4-8 years having distorted morphology with disrupted cell organelles, swollen mitochondria, irregular pattern of microvilli, deposition of electron dense material on cell surface and narrowing of glandular lumen.

Ultrastructural changes in parietal cells in iron deficiency anemia.

Eighteen patients with iron deficiency anemia (IDA) and 14 age and sex matched control subjects were studied with regard to ultrastructural changes in parietal cells. The control subjects had normal hemoglobin and serum iron levels and endoscopic examination of the upper gastrointestinal tract. Thirteen cases of iron deficiency anemia had chronic superficial gastritis on light microscopy. Ultrastructural abnormalities in the parietal cells, such as indented or pyknotic nucleus with irregular outline, grossly distorted canalicular system, abnormal large empty spaces in the cytoplasm and paucity of mitochondria, were demonstrated in all IDA patients but not in controls. The presence of superficial gastritis and ultrastructural changes were not related either to hemoglobin or serum iron levels in the IDA group.