Prevalence of human papillomavirus infection & cervical abnormalities in HIV-positive women in eastern India.

BACKGROUND & OBJECTIVES: India has the third highest burden of HIV and highest number of cervical cancer in the world. A cross-sectional study was performed to determine the prevalence and types of human papillomavirus (HPV) infection, and the factors associated with HPV infection and abnormal cervical cytology in HIV-positive women attending the Antiretroviral Therapy (ART) Centre in a tertiary care hospital in eastern India. METHODS: We screened 216 HIV- positive women with Papanicolau smear cytology and HPV testing. HPV DNA was detected by using consensus primers followed by sequencing. RESULTS: Of the 216 HIV-positive women screened, 58 (26.85%) were HPV-positive; 56 (25.9%) were of high-risk (HR) HPV type. The most prevalent HPV type was HPV-16 (7.9%); non 16 and 18 HPV types were present in 17.6 per cent patients. Age ≤ 35 yr [(OR), 2.56 (1.26-5.19)], illiteracy [OR, 2.30 (1.19-4.46)], rural residence [OR, 3.99 (1.27-12.56)] and CD4 ≤ 350/µl [OR, 2.46 (1.26-4.83)] were associated with increased risk of acquisition of HPV. One hundred thirty nine (74.33%) patients had normal/ negative for intraepithelial lesions (NILM) cytology, three (1.60%) had atypical squamous cells of undetermined significance (ASCUS), 32 (17.11%) had low-grade squamous intraepithelial lesions (LSIL), 10 (5.35%) had high-grade squamous intraepithelial lesions (HSIL) and three (1.60%) had carcinoma cervix. WHO clinical Stage III and IV [OR, 2.83 (1.07-7.49)] and CD4 ≤ 350/µl [OR, 2.84 (1.30-6.20)] were risk factors for abnormal cytology. INTERPRETATION & CONCLUSIONS: Our study showed 26.85 per cent HPV positivity in HIV infected women in this region, with HPV-16 as the commonest genotype. Abnormal cervical cytology was seen in about 25 per cent women. Regular Pap smear screening as recommended by the National AIDS Control Organization will help in early detection of cervical abnormalities in HIV- positive women.

Comparison of Expression of Chemokine Receptor 4 in Maternal Decidua and Chorionic Villi in Women with Spontaneous Miscarriages and Women Opting for Termination of Viable Pregnancies.

BACKGROUND: Early pregnancy losses can be a distressing experience both for the parents and the treating clinician. We aim to explore the role of chemokine receptor 4 (CXCR4) in early pregnancy losses by comparing its expression among patients with spontaneous miscarriages and patients undergoing termination of viable pregnancies for unwanted pregnancies. AIM: The aim of the study was to investigate the expression of CXCR4 in early pregnancy losses and correlate the various clinical parameters with differential expression of the above receptor in the chorionic villi and maternal decidua. STUDY AND SETTING: The present study is a case-"control study done in a tertiary care center. METHODOLOGY: Fifty patients attending outdoor and antenatal clinic of the hospital aged 18-40 years with spontaneous miscarriage under 20 weeks of gestational age were included as cases and compared with fifty females of comparable age group (18-40 years) seeking medical termination of pregnancy as controls. Chorionic villi and decidua obtained from the cases and controls were analyzed for CXCR4 expression. STATISTICAL ANALYSIS: The results were analyzed using mean ± standard deviation, percentiles values, Chi-square test, and P value to determine the association of CXCR4 expression in decidua and chorionic villi of cases versus controls. RESULTS: CXCR4 expression was significantly downregulated in cases as compared to the controls with P < 0.001. The mean normalized ratio of CXCR4 expression to housekeeping gene (ß Actin) expression in the case group was 1.607 ± 1.108 and in the control group, it was 2.506 ± 1.457. There was a strong correlation between the expression of CXCR4 and maternal age. With increasing age, the expression of CXCR4 was more downregulated in both the cases and control groups (P < 0.001). The expression of CXCR4 was elevated in controls as compared to cases in <30 years age group (P = 0.009). CXCR4 expression was higher in primigravida than in multigravida (P = 0.001), and as the number of previous miscarriages increased, the expression of CXCR4 was found to be decreased (P = 0.021). CONCLUSION: CXCR4 expression is significantly reduced in women with spontaneous miscarriages in comparison with viable pregnancies. and possibly, therapies targeted at increasing the expression of CXCR4 can be used as a treatment modality for management of spontaneous miscarriages.

Hyperhomocysteinemia and low vitamin B12 are associated with the risk of early pregnancy loss: A clinical study and meta-analyses.

One-carbon metabolism is crucial for the maintenance of healthy pregnancy and alterations in this pathway have been associated with various pregnancy-related complications. Therefore, the present study was conducted to test the hypothesis that the altered folic acid, vitamin B12 and homocysteine levels are associated with the risk of early pregnancy loss (EPL). Plasma folic acid, vitamin B12 and homocysteine levels were analyzed in 83 females with EPL and 70 healthy pregnant females in their first trimester. Further, meta-analyses of folic acid, vitamin B12 and homocysteine were also performed involving various eligible studies. Results from our case-control study and meta-analysis showed that folic acid deficiency is not associated with the risk of EPL. On the other hand, low vitamin B12 and hyperhomocysteinemia were individually found to be significant risk factors for EPL in the present study (P < .01, P < .05, respectively) and meta-analysis as well (P < .001, P < .05, respectively). Vitamin B12 deficiency in combination with hyperhomocysteinemia was a more serious risk factor for EPL (Odds Ratio = 4.98, P = 0.002). Therefore, we conclude that vitamin B12 deficiency and elevated homocysteine levels are independent risk factors for EPL, and of higher risk when combined. The assessment of vitamin B12 and homocysteine levels may serve as a good screening marker for EPL risk.

High incidence of zidovudine induced anaemia in HIV infected patients in eastern India.

BACKGROUND & OBJECTIVES: Zidovudine (ZDV) is the preferred nucleoside reverse transcriptase inhibitor in the first line antiretroviral regimen in India. It is known to be associated with life threatening toxicity like anaemia. This study was aimed at determining the prevalence of ZDV induced anaemia in HIV infected patients initiated on ZDV containing antiretroviral therapy regimen and also to find out the correlates, if any, for causing ZDV induced anaemia. METHODS: This retrospective study was carried in ART Centre, Sir Sunderlal Hospital, Banaras Hindu University, Varanasi between March 2005 to December 2007. HIV infected patients registered at ART Centre were treated according to guidelines of National AIDS Control Organization (NACO). Patients (n=1256) with haemoglobin (Hb)>8 g/dl were prescribed ZDV based antiretroviral therapy regimens. Patients developing anaemia (<8 g/dl) with other causes of anaemia excluded were recorded. Correlation of baseline characteristics (age, gender, haemoglobin levels, weight, CD(4) counts and WHO clinical stage) with risk of developing anaemia was also calculated. RESULTS: Two hundred three (16.2%) patients on ZDV regimen developed anaemia (<8 g%); 7.9 per cent (n=100) of these developed severe anaemia (<6.5 g%). Females were more prone to develop anaemia (P=0.026). Age, weight, WHO clinical stage and CD4 counts had no relation to development of anaemia. INTERPRETATION & CONCLUSION: High incidence of ZDV induced anaemia seen in this study indicates regular monitoring of patients, particularly women on ZDV based antiretroviral regimens.

Altered crosstalk of estradiol and progesterone with Myeloid-derived suppressor cells and Th1/Th2 cytokines in early miscarriage is associated with early breakdown of maternal-fetal tolerance.

PROBLEM: Decline in myeloid-derived suppressor cells (MDSCs) and Th2 cytokines levels lead to early miscarriage (EM) but how the hormonal milieu of the body regulates MDSCs and Th1/Th2 cytokine balance is still a matter of investigation. METHOD OF STUDY: Peripheral blood and decidua samples were collected from 20 EM patients, and 20 healthy pregnant women opted for elective abortion. MDSCs and G-MDSCs levels were analyzed in peripheral blood mononuclear cells, and Th1/Th2 cytokines levels were determined in serum via flow cytometry. Estrogen (E2), Progesterone (P4), and Testosterone levels were measured via ELISA. Further, proliferation and apoptosis in decidual samples were checked via immunoblot/immunohistochemistry of estrogen receptor -α (ER-α), STAT-3/pSTAT-3, and caspase-3, respectively. RESULTS: Our results clearly indicate that in EM patients; decline in E2 and P4 significantly correlates with decline in MDSCs, particularly with subtype granulocytic MDSCs (G-MDSCs) and skewness of the Th1/Th2 cytokines balance toward Th1 response. Downregulation of ER- α and increased caspase-3 expression in endometrium decidua signifies poor endometrial receptivity in EM. STAT-3 activation regulates proliferation, differentiation and suppressive potency of MDSCs. In decidua of EM, significantly lower expression of pSTAT-3 indicates that these processes pertaining to MDSCs are compromised. CONCLUSION: Altogether, this unfavorable systemic milieu may drive toward early breakdown of maternal-fetal tolerance in EM. Therefore, regulated crosstalk of E2, P4 with MDSCs and balanced Th1/Th2 cytokines is prerequisite for successful pregnancy.

Spontaneous ovarian hyperstimulation syndrome in a triplet pregnancy.

Ovarian hyperstimulation syndrome (OHSS) is a potentially life-threatening complication, usually iatrogenic after ovulation induction. OHSS is a very rare event in spontaneously conceived pregnancies. Only few cases have been reported in literature to the best of our knowledge. We report a very rare case of spontaneous critical OHSS (according to classification of severity of OHSS as mentioned in Greentop guidelines no. 5, 2006) associated with triplet pregnancy in a 26-year-old woman suffering from severe abdominal pain, distension, and dyspnea. Our case highlights the importance of a strong suspicion for OHSS when a clinical presentation could not be explained by common medical conditions.