N.S. Murthy

Hepatitis E in pregnancy.

Objectives: To study the spectrum and the clinical and biochemical course of viral hepatitis E during pregnancy. Methods: In this prospective study, sera of 62 pregnant women having jaundice in the third trimester of pregnancy were analyzed for markers of hepatitis A, B, C and E viruses. The cord blood samples of hepatitis E virus (HEV)‐positive pregnant women at the time of delivery were tested for IgM anti‐HEV antibodies by enzyme‐linked immunosorbent assay and HEV‐RNA by reverse transcriptase polymerase chain reaction. Results: Of the 62 patients, 45.2% had HEV infection and nine developed fulminant hepatic failure (FHF). Eighty‐one percent of FHF cases and 37.25% of acute viral hepatitis cases were caused by HEV. Approximately two‐thirds of the pregnant women with HEV infection had preterm deliveries. The mortality rate among the HEV‐positive pregnant women was 26.9%. Vertical transmission was observed in 33.3% of cases. Conclusions: One‐third of the pregnant women with HEV infection had a severe form of hepatitis in the third trimester of pregnancy, i.e. FHF. Hepatitis E in pregnancy is associated with high rates of preterm labor and mortality.

Polymorphism of the p53 codon 72 arg/pro and the risk of HPV type 16/18-associated cervical and oral cancer in India

Infection of high risk human papillomaviruses (HPVs) specifically the types 16 and 18 has been strongly implicated in the development of cervical cancer. The E6 oncoproteins of these high risk HPVs are known to bind and induce degradation of p53 tumour suppressor protein through the ubiquitin pathways. This degradation is controlled by a common polymorphism of the p53 gene encoding either a proline or an arginine at its codon 72 in exon 4. Recently, it has been demonstrated that the presence of homozygous arginine at codon 72 renders p53 about seven times more susceptible to E6-mediated proteolytic degradation as well as to cervical cancer than those with proline homozygotes or proline/arginine heterozygotes. In India, prevalence of HPV as well as cancers of the uterine cervix and the oral cavity are highest in the world. We have examined this allele-specific predisposition in cervical and oral cancer which is associated with HPV as well as in a non-HPV-linked cancer of the breast. We have carried out investigation in women comprising whole spectrum of cervical lesions with 128 HPV 16/18 positive and 35 HPV negative invasive cervical carcinomas and 34 cases of HPV (16/18) positive and 16 HPV negative cervical dysplasias (mild, moderate and severe) and 104 age-group-matched healthy women as controls. Additionally, we have analysed p53Arg-Pro polymorphism in 13 high risk HPV positive and 31 HPV negative oral cancers along with 20 normal controls and 77 breast cancers with 41 age-matched healthy controls.We observed more than 2 fold higher risk for homozygous arginine (χ2 = 6.3, df = 2, p = 0.04; OR = 2.3; 95% CI: 1.08–5.16) for HPV 16/18-positive cervical carcinomas when comparison was made only between HPV positive cervical cancers and normal controls but most interestingly, no significant association either in the frequency of homozygous arginine or proline alleles or their heterozygotes could be observed when all the three groups i.e. HPV-positive, HPV-negative cervical cancers and controls were considered simultaneously. No difference was also observed for either arginine or proline polymorphism between women with precancerous lesions of the uterine cervix carrying HPV 16/18 infection and controls. Similarly, increased risk of oral or breast cancer could not be correlated with the polymorphism of arginine/proline allele.Thus the interaction between HPV oncoproteins and the p53 gene polymorphism specifically, homozygous arginine at codon 72 appears to play no role in the development of either cervical or oral cancer and also it can not serve as a biomarker for early identification of cervical, oral or breast cancer.

Increasing trend of acute hepatitis A in north India: Need for identification of high-risk population for vaccination

Background and Aims:  Hepatitis A (HAV) is endemic in India and most of the population is infected asymptomatically in early childhood with lifelong immunity. Because of altered epidemiology and decreasing endemicity, the pattern of acute HAV infection is changing from asymptomatic childhood infection to an increased incidence of symptomatic disease in the 18–40 age group. The aims of the present study were to assess whether the proportion of adults with acute HAV infection has been increasing over the years and to analyze the seroprevalence of immunoglobulin G (IgG) anti‐HAV antibodies in young adults above the age of 15 years as well as in cases of chronic liver disease.

Norfloxacin and cisapride combination decreases the incidence of spontaneous bacterial peritonitis in cirrhotic ascites

Background: Spontaneous bacterial peritonitis (SBP) is a serious complication of cirrhosis with ascites, having high recurrence despite antibiotic prophylaxis. Small bowel dysmotility and bacterial overgrowth have been documented to be related to SBP. The purpose of the present paper was (i) to study whether addition of a prokinetic agent to norfloxacin ameliorates the development of SBP in high‐risk patients; and (ii) to identify risk factors for SBP development.

CYP17 gene polymorphism and its association with high-risk north Indian breast cancer patients.

AbstractA single T > C change at the 5′ promoter region of the CYP17 gene is reported to be associated with increased risk of breast cancer. This study evaluates the influence of genetic polymorphism of CYP17 on breast cancer susceptibility. Two hundred and forty-two patients with histopathologically confirmed breast cancer and 212 age-matched controls were included in the present study. Information relating to age at onset of the disease, family history and estrogen receptor status was elicited. Investigation for CYP17 polymorphism was carried out in 106 early onset, 80 late onset and 56 familial cases. The frequencies of two CYP17 alleles were also analyzed in 116 (47.9%) cases with known estrogen receptor (ER) status confirmed immunohistochemically. A polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method was used to detect the polymorphism, and the genotypes identified were assigned as homozygous wild type (A1A1), heterozygous variant (A1A2), and homozygous variant (A2A2). Associations between the various genotypes in patients and controls were investigated with Fishers exact test. All the tests were two tailed. The results showed that the frequency of heterozygous and homozygous CYP17 genotype was higher in early onset breast cancer patients (94.3%) than in controls (80.3%), and the difference was significant (P = 0.001). A highly statistically significant increased risk in carriers of homozygous A2 allele was found in young patients (P ≤ 0.001) in comparison with patients having late onset condition (P = 0.260). However, no significant association between the genotype and breast cancer risk was observed among women with strong family history. Further, data had showed that patients (80.6%) with at least one A2 allele tended to exhibit ER-independent cell proliferation, although statistical significance could not be established (P = 0.160). The present findings suggest that CYP17 A2 allele gene polymorphism might play a significant role in breast cancer development in young Indian women.

Hepatitis C virus infection during pregnancy in North India

Hepatitis C virus (HCV) is responsible for 20% of cases of acute viral hepatitis and nearly 50% of cases of chronic viral hepatitis. Most persons acutely infected with HCV will develop a persistent infection and nearly 70% will experience chronic necroinflammation of the liver. Information concerning potential risk factors for HCV infection is provided by studies conducted on blood donors on patients with chronic liver disease and on individuals with a history of intravenous drug use. The present study aims to assess the seroprevalence of anti-HCV antibodies in healthy asymptomatic pregnant women from the Indian subcontinent. (excerpt)

SERUM LIPID PROFILE AND ITS RELATIONSHIP WITH HOST IMMUNITY IN CARCINOMAS OF THE BREAST AND UTERINE CERVIX

Carcinomas of the uterine cervix and breast, which have a different etiopathogenesis, are the most common malignancies among Indian women. Between these two cancers a comparative study was undertaken in which serum lipids were assessed along with host immunity. Thirty randomly selected cases each of breast and cervical carcinoma, and 20 matched healthy control women were studied by means of standard procedures. Significantly higher (P < 0.001) mean levels of triglycerides (x = 192.1 mg/dl, SD ± 113.5) and total cholesterol (x = 212.9 mg/dl, SD ± 49.78) were observed in breast cancer as compared to controls or cervical cancer patients. Patients with cervical cancer had low mean values of all lipid fractions. Women with the above malignancies also showed a significantly decreased CD3+ and CD4+ population (P < 0.001), while there was a significant increase in CD8+ cells (P < 0.005) compared to normal controls. Interestingly, a significant relationship (P < 0.05) was observed between CD8+cells and LDL-cholesterol among the cancer patients (r = 0.3652 and r = 0.4298 for carcinomas of breast and cervix, respectively).