Cervical squamous intra-epithelial changes and human papillomavirus infection in women infected with human immunodeficiency virus in Pune, India

In view of the dual burden of HIV infection and cervical cancers in India, this study was undertaken to estimate the prevalence of Pap smear abnormalities and human papillomavirus infection among HIV-infected women. Consecutive HIV-infected women attending voluntary counseling testing clinics were enrolled. Written informed consent, demographic information, Pap smears, cervical swabs for HPV typing and a blood sample for CD4+ cell count were collected. Treatment for opportunistic and sexually transmitted infections and reproductive tract infections was provided. Women with Pap smear abnormality were referred for further intervention. Between January 2003 and May 2004, 287 HIV-infected women were enrolled. Pap smear abnormalities were seen in 6.3% women and were more common among women aged 30 and above (P=0.042) and those who had suffered from opportunistic infections (P=0.004). In multivariate analysis, Pap smear abnormalities were associated independently with opportunistic infections (P=0.02, AOR 3.8, 95% CI 1.2--11.5). Of the 100 random cervical specimens screened for HPV 16 and 18 genotypes, 33% (95 CI 23.9--43.1) were positive for HPV 16/18. Of the 122 patients who returned for a follow-up visit, 5 patients (4.1%) who did not have Pap smear abnormality at baseline, had developed Pap smear abnormality. The incidence of Pap smear abnormalities was 5.5 per 100 person year of follow-up. In order to prevent thousands of deaths due to cervical cancer in India, there is a need for strengthening the Pap smear screening program and HPV vaccine development.     

Thyroid stimulating hormone inhibits rat granulosa cell steroidogenesis in primary culture

It is not known why hypothyroidism predisposes the ovary to develop cystic follicles in hCG-treated rats. This study examined the effect of TSH on steroidogenesis in cultured granulosa cells. Granulosa cells were isolated from the ovaries of hCG-treated Long-Evans rats. Cells were cultured in medium with either 0 or 100NM: testosterone or 25(OH)cholesterol and treated with 0, 2.5, 10 or 20 ng/ml of TSH. TSH reduced 3β-HSDI activity in these cells to 12% of control. Progesterone secretion decreased by 72% and estradiol secretion was non-detectable during the second day of treatment with 20 ng/ml of TSH. We conclude that TSH is capable of regulating the secretion of progesterone and estradiol by cultured granulosa cells.     

Tissue repair plays pivotal role in final outcome of liver injury following chloroform and allyl alcohol binary mixture.

The objective of this study was to evaluate the interaction profile of chloroform (CHCl(3))+allyl alcohol (AA) binary mixture (BM)-induced acute hepatotoxic response. Plasma alanine aminotransferase (ALT) was measured to assess liver injury, and 3H-thymidine (3H-T) incorporation into hepatonuclear DNA was measured as an index of liver regeneration over a time course of 0-72 h. Male Sprague-Dawley (S-D) rats received single ip injection of 5-fold dose range of CHCl(3) (74, 185 and 370 mg/kg) in corn oil (maximum 0.5 ml/kg) and 7-fold dose range of AA (5, 20 and 35 mg/kg) in distilled water simultaneously. The doses for BM were selected from individual toxicity studies of CHCl(3) alone [Int. J. Toxicol. 22 (2003) 25], and AA alone [Reg. Pharmacol. Toxicol. 19 (1999) 165]. Since the highest dose of each treatment (CHCl(3)- 740 and AA- 50 mg/kg) yielded mortality due to the suppressed tissue repair followed by liver failure, this dose was omitted for BM. The levels of CHCl(3) (30-360 min) and AA (5-60 min) were quantified in blood and liver by gas chromatography (GC). The liver injury was more than additive after BM compared to CHCl(3) alone or AA alone at highest dose combination (370+35 mg/kg), which peaked at 24 h. The augmented liver injury observed with BM was consistent with the quantitation data. Though the liver injury was higher, the greater stimulation of tissue repair kept injury from progressing, and rescued the rats from hepatic failure and death. At lower dose combinations, the liver injury was no more than additive. Results of the present study suggest that liver tissue repair, in which liver tissue lost to injury is promptly replaced, plays a pivotal role in the final outcome of liver injury after exposure to BM of CHCl(3) and AA.     

Type 1 diabetic mice are protected from acetaminophen hepatotoxicity.

Streptozotocin (STZ)-induced diabetic (DB) mice challenged with single ordinarily lethal doses of acetaminophen (APAP), carbon tetrachloride (CCl4), or bromobenzene (BB) were resistant to all three hepatotoxicants. Mechanisms of protection against APAP hepatotoxicity were investigated. Plasma alanine aminotransferase, aspartate aminotransferase, and liver histopathology revealed significantly lower hepatic injury in DB mice after APAP administration. HPLC analysis of plasma and urine revealed lower plasma t1/2, increased volume of distribution (Vd), and increased plasma clearance (CLp) of APAP in the DB mice and no difference in APAP-glucuronide, a major metabolite in mice. Interestingly, covalent binding of 14C-labeled APAP to liver target proteins; arylation of APAP to 58, 56, and 44 kDa acetaminophen binding proteins (ABPs); and glutathione (GSH) depletion in the liver did not differ between nondiabetic (non-DB) and DB mice in spite of downregulated hepatic microsomal CYP2E1 and 1A2 proteins in the DB mice, known to be involved in bioactivation of APAP. Compensatory cell division measured via 3H-thymidine pulse labeling and immunohistochemical staining for proliferating cell nuclear antigen (PCNA) indicated earlier onset of S-phase in the DB mice after exposure to APAP. Antimitotic intervention of liver cell division by colchicine (CLC) after administration of APAP led to significantly higher mortality in the DB mice suggesting a pivotal role of liver cell division and tissue repair in the protection afforded by diabetes. In conclusion, the resistance of DB mice against hepatotoxic and lethal effects of APAP appears to be mediated by a combination of enhanced APAP clearance and robust compensatory tissue repair.     

Respiratory syncytial virus genotypes and disease severity among children in hospital

OBJECTIVES: To determine the spectrum of N and G genotypes of respiratory syncytial virus (RSV) causing respiratory tract infection and whether particular genotypes are associated with severity of infection. PATIENTS AND METHODS: Nasopharyngeal aspirates (NPAs) were obtained from 114 infants with acute respiratory tract infection due to RSV over two seasons. Viral mRNA was extracted from NPAs or cultured virus, reverse transcribed, and the cDNA amplified by the polymerase chain reaction using primers directed to parts of the N and G gene respectively. Amplicons were separately digested with four different restriction endonucleases for each gene. The fragments were separated by agarose gel, electrophoresis, and the electrophoretic patterns used to assign the various genotypes. Disease severity was assessed as very mild (upper respiratory tract signs only), mild (coryza and signs of lower respiratory tract infection), moderate (requiring nasogastric or intravenous fluids), and severe (requiring oxygen or ventilation). RESULTS: Five of the six known N genotypes were detected, but NP4 and NP2 were found most frequently. There was no association between N genotype and disease severity. Six G (SHL) genotypes were detected. Significantly (p = 0.04) more of the infants infected with the SHL2 genotype had severe or moderate disease. CONCLUSIONS: During the seasonal peaks of RSV respiratory tract infection at least 10 different RSV genotypes cocirculated. While there is no association between N genotypes and disease severity, infection with the SHL2 G genotype appears to result in moderate to severe disease.     

Comparison of first trimester transvaginal anatomy scan to the second trimester structural survey in normal weight and obese populations: a pilot study

Purpose: To compare visualization of first trimester fetal anatomic transvaginal ultrasound (TVUS) to the second trimester transabdominal anatomic ultrasound (TAU) in normal weight and obese patients.

Materials and methods: In a prospective cross-sectional study design, 25 women underwent a TVUS between 12 and 14 weeks, and a TAU at 18–22 weeks. For each anatomic structure, the percentage of patients achieving optimal visualization was recorded. Risk ratios for visualizing a structure in the second trimester versus the first were calculated.

Results: Twenty-five patients underwent a TVUS and 24 completed the TAU. The average BMI in the obese and nonobese groups was 34?kg/m² and 23?kg/m², respectively. All structures were more consistently visualized during the TAU for the both groups. The cardiac views, hands and feet were more difficult to visualize in all the patients at both scan times but were more frequently visualized in the TAU. For the obese patients, hands, feet, cardiac and spine views were less frequently visualized in both the scans. The posterior fossa and profile views were more difficult to obtain in the TVUS.

Conclusions: The first trimester TVUS detects many of the structures assessed during an anatomic survey; however, it is not superior to the second trimester TAU in normal weight and obese patients.