Sleep disorders in pregnancy and their association with pregnancy outcomes: a prospective observational study.

PURPOSE: Sleep disturbances such as insomnia, nocturnal awakenings, restless legs syndrome, habitual snoring, and excessive daytime sleepiness are frequent during pregnancy, and these have been linked to adverse maternal and fetal outcomes. METHODS: A prospective observational study was performed in high-risk Indian pregnant women. We used modified Berlin questionnaire (MBQ), Pittsburgh sleep quality index (PSQI), International Restless Legs Syndrome Study Group 2011 criteria, and Epworth sleepiness scale to diagnose various sleep disorders, such as symptomatic OSA, poor sleep quality and insomnia, RLS, and excessive daytime sleepiness, respectively, in successive trimesters of pregnancy. Outcome variables of interest were development of gestational hypertension (GH), gestational diabetes mellitus (GDM), and cesarean delivery (CS); the Apgar scores; and low birth weight (LBW). The relationship between sleep disorders and outcomes was explored using logistic regression analysis. RESULTS: Outcome data were obtained in 209 deliveries. As compared to nonsnorers, women who reported snoring once, twice, and thrice or more had odds ratios for developing GH-4.0 (95 % CI 1.3-11.9), 1.5 (95 % CI 0.5-4.5), and 2.9 (95 % CI 1.0-8.2) and for undergoing CS-5.3 (95 % CI 1.7-16.3), 4.9 (95 % CI 1.8-13.1), and 5.1 (95 % CI 1.9-14.9), respectively. Pregnant women who were persistently positive on MBQ had increased odds for GH and CS. CONCLUSIONS: Snoring and high-risk MBQ in pregnant women are strong risk factors for GH and CS. In view of the significant morbidity and health care costs, simple screening of pregnant women with questionnaires such as MBQ may have clinical utility.

Decreased expression of DNA repair genes (XRCC1, ERCC1, ERCC2, and ERCC4) in squamous intraepithelial lesion and invasive squamous cell carcinoma of the cervix.

Reduced DNA repair might affect the risk of progression from infection with carcinogenic human papillomavirus (HPV), the etiologic agent for cervical cancer (CC), to persistent HPV infection, and hence to cervical pre-cancer and cancer. We assessed the variation in baseline expression of base excision repair gene XRCC1 and three nucleotide excision repair genes ERCC1, ERCC2, and ERCC4 and the risk of developing cervical cancer. A hospital-based case-control study was designed with 50 invasive cervical cancer patients, 40 squamous intraepithelial lesions (SIL) patients and 85 controls subjects. RT-qPCR and Western blotting was used to quantitate in vitro the mRNA and protein levels in fresh CC, SIL and normal cervix tissue. The levels of XRCC1, ERCC2, ERCC4, and ERCC1 transcripts and their respective proteins were lower in cervical cancer and SILs as compared to controls (p ≤ 0.001, 0.001, 0.001, and 0.025, respectively). In multivariate logistic regression analysis (adjusting for parity, age at first child birth, use of oral contraceptives, smoking status), low expression of XRCC1, ERCC2, ERCC4, and ERCC1 was associated with a significant increased risk for CC and SIL. Our results suggest that individuals whose expression of XRCC1, ERCC4, ERCC2, and ERCC1 are reduced may be at a higher risk of developing SIL which eventually leads to invasive cervical carcinoma. Moreover, independently also the reduced expression of these genes can directly lead to cervical cancer progression.

Increased complication rates in vaginal hysterectomy in genital tuberculosis.

PURPOSE: To evaluate the complication rate in women with genital tuberculosis undergoing vaginal hysterectomy. METHODS: A retrospective study of seven women who underwent vaginal hysterectomy and anterior and posterior colpoperineorraphy for uterovaginal prolapse and found to have genital tuberculosis and 63 women who underwent vaginal hysterectomy during the same period without genital TB. RESULTS: The mean age was 52.7 in the study group as compared to 47.4 years in the control group. Indications for surgery were genital prolapse in 7 (100%) women in group I, 43 (68.25%) in group II, AUB in 0 and 6 (9.5%), CIN III in 0 and 5 (7.9%), fibroid up to 10 weeks in 0 and 9 (14.31%) in group I and II, respectively. Surgery performed in group I was vaginal hysterectomy and pelvic floor repair in 7 (100%) and 43 (68.25%) in group II, while it was nondescent vaginal hysterectomy in 0 and 20 (31.7%) cases respectively. There was very high rate of complications in vaginal hysterectomy done in genital tuberculosis as compared to controls like excessive bleeding in 2 (28.56%) versus 3 (4.76%); need for relaparotomy in 1 (14.28%) case versus 0 in control; postoperative peritonitis and flare-up in 4 (57.14%) cases versus 0 in groups I and II respectively. CONCLUSION: Vaginal hysterectomy is associated with higher complication rate in women with genital tuberculosis.

Abdomino-peritoneal tuberculosis masquerading as ovarian cancer: a retrospective study of 26 cases.

PURPOSE: Evaluation of clinical, laboratory, and operative findings in women of abdomino-pelvic tuberculosis undergoing laparotomy for suspected ovarian cancer. METHODS: A retrospective analysis of 26 women who underwent laparotomy for ovarian cancer and found to have abdomino-pelvic tuberculosis in three hospitals of Delhi. RESULTS: The mean age was 34.65 years. Symptoms were menstrual dysfunction in 12 (46.2%), abdominal distension (8 women, 30.7%), abdominal pain (26 women, 100%), abdominal mass (5 women, 19.2%). Mean and standard deviation (SD) of Ca-125 levels were 594.22 ± 770.07. The mean ± SD of right and left tubovarian mass being 5.82 ± 3.94 cm and 5.81 ± 3.21 cm, respectively. Abdominal hysterectomy was done in 4 (15.4%) cases, right ovariotomy in 5 (19.2%), left Ovariotomy in 6 (23.1%), biopsies from right ovary 11 (42.3%), left ovary 7 (26.9%), omentum 10 (38.5%), peritoneum in 15 (57.7%). Tuberculous granuloma and AFB stain on histopathology were observed in all cases. CONCLUSION: Peritoneal tuberculosis with abdomino-pelvic masses was difficult to differentiate from ovarian cancer. Antitubercular drugs are the treatment of choice and complete surgery being difficult and hazardous should be avoided.

Single nucleotide polymorphisms in the DNA repair genes in HPV-positive cervical cancer.

Genetic variation in DNA repair genes can modulate DNA repair capacity and may be related to the risk of cancer. The human papillomavirus is considered to be a necessary but not sufficient cause for cervical cancer and, therefore, other factors contribute to the carcinogenesis. A hereditary component for this neoplasia has been reported. Evaluation of the association of six polymorphisms was carried out in the following DNA repair genes: XRCC1 (Arg194Trp, Arg280His, and Arg399Gln), ERCC1 (Asp118Asp), ERCC2 (Lys751Gln), and ERCC4 (Arg415Gln). The cases (n=110) included 65 squamous cell carcinomas (SCCs) and 45 squamous intraepithelial lesions (SIL). Controls (n=68) were recruited from among women without cervical abnormalities. Genotypes were determined by PCR-restriction fragment length polymorphism and DNA sequencing. A positive association was observed between the polymorphisms of XRCC1 genes, that is, in codons 194 [P=0.001, odds ratio (OR)=20.1, 95% confidence interval (CI)=5.9-68.8], 280 (P=0.001, OR=5.4, 95% CI=2.3-12.6), and 399 (P=0.008, OR=4.2, 95% CI=1.5-12.1) and cervical cancer. SIL patients also showed a significant association with codon 194 (P=0.012, OR=3.8, 95% CI=1.3-10.6), but not with 280 (P=0.35) and 399 (P=0.81). A positive correlation was also found in ERCC4 Gln415Gln in both SCCs and SILs (P=0.001, OR=21.3, 95% CI=7.1-64.0 and P=0.001, OR=7.8, 95% CI=2.9-20.9, respectively). For ERCC2 Gln751Gln, the association was significant for both SCCs (P=0.001, OR=10.1, 95% CI=2.6-37.9) and SILs (P=0.001, OR=8.9, 95% CI=2.8-28.3). However, the risk of SCC did not appear to differ significantly among individuals with the ERCC1 Asp118Asp genotype (P=0.404). For SILs, it appeared to be a protective genotype (95% CI=0.1-0.7). This study indicates that variant types of DNA repair genes play an important role in modifying individual susceptibility to SCC.

Prospective evaluation of qualitative and quantitative ¹8F-FDG PET-CT parameters for predicting survival in recurrent carcinoma of the cervix.

OBJECTIVE: The aim of this study was to evaluate the prognostic significance of qualitative and quantitative F-fluorodeoxyglucose (F-FDG) PET-computed tomography (PET-CT) parameters in patients with recurrent cervical carcinoma. METHODS: Twenty-six patients (age: 44 ± 10.1 years) with histologically proven recurrent carcinoma of the cervix (squamous, 21; adenocarcinoma, five) were prospectively enrolled and they underwent F-FDG PET-CT before salvage therapy. The qualitative parameters included for analysis were vaginal involvement, regional nodal metastasis, and distant metastasis on PET-CT. The quantitative PET-CT parameters included were standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Cutoff values were determined using receiver operating characteristic curve analysis. A Kaplan-Meier analysis was carried out to compare survival among groups. Impact of PET-CT parameters on progression-free survival (PFS) and overall survival (OS) was evaluated using Cox proportional hazard regression. RESULTS: On PET-CT, vaginal involvement was seen in 16 patients, regional nodal metastasis in 12 patients, and distant metastasis (node and lung) in 11 patients. The mean SUVmax was 6.8 ± 4, MTV was 8.2 ± 12.8 ml, and TLG was 49.6 ± 108.4 ml. On multivariate analysis, SUVmax of up to 4.9 [hazard ratio (HR): 0.026, confidence interval (CI): 0.002-0.268, P=0.002] and distant metastasis (HR: 18.88, CI: 2.14-166.24, P=0.008) were independent predictors of PFS. On multivariate analysis, SUVmax greater than 9 (HR: 19.25, CI: 2.15-172.17, P=0.008) and distant metastasis (HR: 33.88, CI: 2.17-526.61, P=0.012) were also independent predictors of OS. MTV, TLG, and regional node involvement evaluated using PET-CT were found to be significant on univariate analysis but not on multivariate analysis. CONCLUSION: SUVmax and the presence of distant metastasis on F-FDG PET-CT are independent predictors of PFS and OS in patients with recurrent cervical carcinoma.

Increased complication rates associated with laparoscopic surgery among patients with genital tuberculosis.

OBJECTIVE: To compare the complications and surgical difficulties encountered during laparoscopy between women diagnosed with and without genital tuberculosis (TB). METHODS: Retrospective review of the records of women diagnosed with and without genital TB who underwent laparoscopy primarily for infertility and chronic pelvic pain from January 2006 through July 2009. Genital TB was diagnosed by laboratory studies and endoscopic findings. RESULTS: A total of 313 women were included in the study: 87 (27.8%) with genital TB and 226 (72.2%) without. Laparoscopy was performed in 48 (55.2%) patients with genital TB and 19 (8.4%) without; laparoscopy with hysteroscopy was performed in 39 (44.8%) with the disease and 132 (58.4%) without. Although individual complication rates were all higher in the genital TB group, significant differences were seen for inability to see the pelvis (10.3% vs 1.3%, P=0.027), excessive bleeding requiring transfusion (2.3% vs 0%, P=0.045), and peritonitis (8.0% vs 1.8%, P=0.037). Other complications encountered were inability to create pneumoperitoneum, bladder injury, trocar site discharge, and need for laparotomy. CONCLUSION: Laparoscopic surgery may be associated with increased complication rates in patients with genital TB compared with those without the disease.

An antiprogestin steroid and PGE2 for an early pregnancy termination.

A non-surgical, preferably self-administered, procedure would be an attractive alternative to vacuum for the termination of early pregnancy. 20 patients with 49 days of amenorrhea and confirmation of pregnancy by ultrasound, urine testing and human chorionic gonadotrophin (beta-hCG) analysis, were administered RU 486, 25 mg twice daily for 4 days, (Group I). A further 20 patients received the same dose of RU 486 for 3 days (Group II). All patients received an intramuscular injection of the prostaglandin derivative sulprostone, 0.25 mg, on the last day of RU 486 treatment. Outcome of therapy was assessed on the second follow up visit (day 15) on the basis of clinical courses, ultrasound findings and hCG levels. In Group I, all patients had a complete abortion with a success rate of 100%. In Group II, a success rate of 95% was achieved. Side effects were minimal and did not require any medication. A dramatic fall was observed in the plasma beta-hCG and progesterone levels on days 8 and 14, correlating with the clinical course of abortion. Plasma cortisol levels remained within the normal range. It is concluded that sequential therapy with RU 486 and prostaglandin is a highly safe, simple and effective non-surgical method for termination of early pregnancy.

Telomerase--a potential molecular marker of lung and cervical cancer.

Telomerase, a ribonucleoprotein enzyme that adds hexameric TTAGGG nucleotide repeats onto telomeres is reactivated in most malignancies. Lung cancer is a common malignant disease worldwide as well as in India. Most patients present in advanced stages. As noninvasive diagnostic techniques are preferred, we assayed the telomerase activity in pre-bronchoscopy sputum and compared it with that of bronchial washings and bronchoscopic biopsies by telomeric repeat amplification protocol (TRAP) in 53 cases of lung cancer. These were corroborated with cytopathological/histopathological examinations. Telomerase activity was detected in 58.5% of sputum samples, 70% of bronchial washings and 74% of bronchoscopic biopsies thereby making it a good noninvasive diagnostic marker of lung cancer. Cervical cancer is the 7th most common cancer worldwide, with 100,000 new cases being reported annually in India. It is routinely screened by Papanicolaou's (Pap) smear. Human papilloma virus (HPV) is one of its etiological agents. We have assayed telomerase activity in relation to HPV-16/18 in cervical samples from 93 subjects ranging from normal to precancerous to frank cancers in tissue biopsies and cervical scrapings. HPV infection was detected by polymerase chain reaction (PCR) in 81% of tumor samples, in 6% of control hysterectomy samples and in 2% of cervical scrapings of normal healthy controls with HPV-16 being the predominant type. Telomerase activity was detected in 96.5% of cervical tumor samples, in 68.7% of premalignant cervical scrapings but was not detected in control hysterectomy samples, or in cervical scrapings of normal healthy controls. There was 71% correlation between telomerase activity and HPV-16/18 infection.