Sunesh Kumar

Network of cytokines, integrins and hormones in human trophoblast cells

Trophoblast cells of the developing embryo are unique not only for transporting oxygen and nutrients from the mother to the fetus but also for their array of other functions throughout the pregnancy beginning from the attachment of the blastocyst to the endometrium during the process of implantation, its well regulated invasion in the uterine tissue, proliferation, differentiation and immuno-endocrine functions which subsequently maintain the pregnancy. Using human trophoblast cells in culture, we have tried to understand the molecular mechanisms which regulate such a variety of functions for trophoblast cells. Our RT-PCR studies show that trophoblast cells express the laminin and collagen receptors: integrins alpha1 and alpha2, which are both stimulated by IL-1 and IL-6. These two cytokines, also synthesised by the trophoblast cells themselves, act in an autocrine/paracrine manner to induce their own expression. In addition, IL-1 expression seems to be modulated by a large variety of cytokines and growth factors usually present in the uterine milieu whereas IL-6 expression appears to be significantly stimulated by growth factors like EGF and bFGF only. Hormones like estrogen, progesterone and hCG exhibit a general negative modulation in the expression of IL-1 and IL-6. Since, both IL-1 and IL-6 are known to be involved in the proliferation, invasion and differentiation of trophoblast cells, they might be the key factors involved in trophoblast functions.

Early Clinical Outcomes and Toxicity of Intensity Modulated Versus Conventional Pelvic Radiation Therapy for Locally Advanced Cervix Carcinoma: A Prospective Randomized Study

PURPOSE To evaluate the toxicity and clinical outcome in patients with locally advanced cervical cancer (LACC) treated with whole pelvic conventional radiation therapy (WP-CRT) versus intensity modulated radiation therapy (WP-IMRT). METHODS AND MATERIALS Between January 2010 and January 2012, 44 patients with International Federation of Gynecology and Obstetrics (FIGO 2009) stage IIB-IIIB squamous cell carcinoma of the cervix were randomized to receive 50.4 Gy in 28 fractions delivered via either WP-CRT or WP-IMRT with concurrent weekly cisplatin 40 mg/m(2). Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events, version 3.0, and late toxicity was graded according to the Radiation Therapy Oncology Group system. The primary and secondary endpoints were acute gastrointestinal toxicity and disease-free survival, respectively. RESULTS Of 44 patients, 22 patients received WP-CRT and 22 received WP-IMRT. In the WP-CRT arm, 13 patients had stage IIB disease and 9 had stage IIIB disease; in the IMRT arm, 12 patients had stage IIB disease and 10 had stage IIIB disease. The median follow-up time in the WP-CRT arm was 21.7 months (range, 10.7-37.4 months), and in the WP-IMRT arm it was 21.6 months (range, 7.7-34.4 months). At 27 months, disease-free survival was 79.4% in the WP-CRT group versus 60% in the WP-IMRT group (P=.651), and overall survival was 76% in the WP-CRT group versus 85.7% in the WP-IMRT group (P=.645). Patients in the WP-IMRT arm experienced significantly fewer grade ≥2 acute gastrointestinal toxicities (31.8% vs 63.6%, P=.034) and grade ≥3 gastrointestinal toxicities (4.5% vs 27.3%, P=.047) than did patients receiving WP-CRT and had less chronic gastrointestinal toxicity (13.6% vs 50%, P=.011). CONCLUSION WP-IMRT is associated with significantly less toxicity compared with WP-CRT and has a comparable clinical outcome. Further studies with larger sample sizes and longer follow-up times are warranted to justify its use in routine clinical practice.

Prediction of perinatal asphyxia with nucleated red blood cells in cord blood of newborns.

Objective: To determine normal level of nucleated red blood cells (NRBC) per 100 white blood cells (WBC) in cord blood of term non‐asphyxiated newborns and to investigate variations in NRBC counts in perinatal asphyxia. Methods: A total of 75 cases were studied. Levels of NRBC per 100 WBC in umbilical venous blood were compared between 26 asphyxiated newborns (group I) and 49 non‐asphyxiated newborns (group II). Correlation with neonatal outcome was also evaluated. Results: The mean (±S.D.) NRBC per 100 WBC level in umbilical blood of newborns in group I was 16.5±6.4, range 3–25; whereas that in group II was 8.6±7.01, range 1–26. This difference was statistically significant (P<0.001). A statistically significant negative correlation existed between NRBC level and markers of acute intrapartum asphyxia, Apgar score and umbilical arterial pH (r=−0.50, P<0.001 and r=−0.48, P<0.001, respectively). Positive correlation was demonstrated with evidence of chronic antepartum asphyxia, presence of pregnancy induced hypertension and intrauterine growth restriction (r=2.66, P=0.02). A high NRBC count in umbilical blood correlated with poor early neonatal outcome. Conclusions: The level of NRBC per 100 WBC correlates both with acute as well as chronic antepartum asphyxia. Further, it can be used as a reliable index of early neonatal outcome.

Phase I clinical trials with three formulations of anti-human chorionic gonadotropin vaccine

Comparative phase I clinical trials were carried out in 5 centres with three formulations of beta-hCG-based vaccines inducing antibodies against human chorionic gonadotropin. The objectives of these trials were to determine their relative immunogenicity, duration, reversibility and safety. A total of 116 tubal ligated women volunteers were enrolled in the study and 101 subjects were followed-up for one year or more until the antibody titres declined to near zero levels. Every woman receiving the vaccine produced anti-hCG and anti-tetanus antibodies. Clinical examination carried out at intervals of 4-6 weeks revealed no abnormality. No serious side effects or adverse reactions were reported with any of the formulations during primary immunization with three monthly injections of the vaccine. Eleven women, however, demonstrated hypersensitivity to test dose at the time of the booster injection. The reaction was to tetanus toxoid; gonadotropin subunits conjugated to another carrier did not evoke any such reaction. Progesterone in bleeds taken at midluteal phase, as well as complete progesterone and estradiol done in two immunized women, indicated normal ovulatory cycles. Immunization with these formulations had no significant effect on haematological, clinical chemistry and other metabolic parameters. In summary, the results indicate that none of the three beta-hCG-based contraceptive vaccines had any adverse effects clinically, on endocrine status and metabolic parameters. Formulations A and B induced comparatively higher anti-hCG titres than M. Thus, further work can be undertaken to study the efficacy of these vaccines in humans for preventing pregnancy.

Sublingual misoprostol versus oxytocin infusion to reduce blood loss at cesarean section

Objective: To compare the effectiveness of sublingual misoprostol administered immediately after delivery of the neonate at cesarean section, with intravenous oxytocin infusion in prevention of uterine atony and thereby reducing blood loss at cesarean section. Methods: One hundred women with singleton term pregnancy undergoing elective or emergency lower segment cesarean section under spinal anesthesia were included in this study. They were randomly allocated to receive either misoprostol 400 μg sublingually or intravenous infusion of 20 units of oxytocin soon after delivery of the neonate. The main outcome measures were blood loss at cesarean section, change in hemoglobin levels, need for additional oxytocics and drug related side effects. Results: The mean blood loss estimated was significantly lower in misoprostol group compared to oxytocin group (819 ml versus 974 ml; p = 0.004). The number of women who had blood loss exceeding 500 ml and the change in hemoglobin, however, was comparable between the two groups. There was a need for additional oxytocic therapy in 16% and 18% after use of misoprostol and oxytocin respectively (p = 0.673). The incidence of side effects such as pyrexia, shivering and metallic taste was significantly higher in misoprostol group compared to oxytocin group. Conclusion: Sublingual misoprostol appears to be as effective as intravenous infusion of oxytocin in reducing blood loss at cesarean section. However, occurrence of transient side effects such as shivering and pyrexia were noted more frequently with the use of misoprostol.

Analysis of menstrual records of women immunized with anti-hcg vaccines inducing antibodies partially cross-reactive with hLH

Menstrual data of 13 control subjects and 88 subjects immunized with three beta-hCG-based vaccine formulations were analysed. Immunization did not change the menstrual regularity; bleeding days were normal (3-7 days) and 89% of the menstrual cycles were within the normal range of 22-35 days. Irregular (short or long) cycles were observed in both immunized and control groups. These were, however, unrelated to prevailing anti-hCG antibody titres or to cross-reactivity of antibodies with hLH.

Sublingual misoprostol versus methylergometrine for active management of the third stage of labor

Objective: To compare the efficacy and side effects of sublingual misoprostol and intravenous methylergometrine for active management of third stage of labor. Method: One hundred twenty low risk pregnant women at term with spontaneous onset of labor were included in the study. The women were randomized to receive either two tablets of misoprostol (200 μg/tablet) sublingually or 1 ml of methylergometrine (200 μg) intravenous injection, after the delivery of the anterior shoulder of the baby. The main outcome measures were: need for additional oxytocic drugs, blood loss ≥500 ml, change in hemoglobin levels and side effects. Results: Postpartum hemorrhage as defined by hemorrhage ≥500 ml occurred in 3.1% of the women in the sublingual misoprostol group but none of the women in the methylergometrine group (P>0.05). There was a need for additional oxytocic drugs in 5.0% and 8.3% after methylergometrine and misoprostol, respectively (P>0.05). The change in hemoglobin levels at 24 h postpartum were 0.8 and 0.7 gm% in methylergometrine and misoprostol group, respectively(P>0.05). In the misoprostol group, 6.6% women developed fever ≥38 °C and 21.6% had shivering while in methylergometrine group none experienced these side effects. However, the incidence of other side effects like nausea, vomiting, headache and giddiness were similar in both groups. Conclusion: Sublingual misoprostol appears to be as effective as intravenous methylergometrine in the prevention of postpartum hemorrhage. However, larger randomized studies are needed to advocate its routine use.

Prevalence of urinary incontinence and other urological problems during pregnancy: a questionnaire based study

ObjectiveTo find out the prevalence of various urological symptoms in pregnant women, the status before pregnancy, and their perceived impact.MethodsA questionnaire incorporating various urological problems was prepared and used over 240 pregnant women to know their prevalence in different trimesters of pregnancy and compare them with prevalence before pregnancy.ResultsIncreased urinary frequency (>10/day) (40.8 vs. 3.8%), nocturia (72.9 vs. 50.6%), burning micturition (21.3 vs. 3.8%), UTI (4.6 vs. 1.6%), urinary hesitancy (14.6 vs. 1.6%), urinary incontinence (25.8 vs. 8.2%) and botheration (22.1 vs. 2.7%) were seen during and before pregnancy, respectively. These also show an increment with advancement of gestation. Urinary incontinence was seen more often with advancing age and parity.ConclusionThere is a very high prevalence of urological symptoms during pregnancy as compared to before pregnancy.

Maternal antenatal profile and immediate neonatal outcome in VLBW and ELBW babies

ObjectiveTo evaluate the antenatal profile of the mother and the immediate neonatal morbidity and mortality till discharge.MethodsThe study was a retrospective analysis of 92 patients of preterm labour who delivered babies weighing <1500 gms at 26 weeks to 34 weeks of gestation. The maternal demographic profile, causes of preterm labour, treatment profile and delivery outcome were recorded. Similarly the immediate neonatal morbidity and mortality were recorded in our case file. Both these data of maternal and neonatal profile were pooled and analysed.ResultsA total of 92 mothers in preterm labour at 26 to 34 weeks were admitted and subsequently delivered 70 VLBW babies (<1500 gms) and 36 ELBW babies (<1000 gms) including 8 pairs of twins and 3 triplets pregnancies. Majority of the patients (93.4%) were booked. Amongst the various high risk factors for preterm labour, anaemia, during pregnancy (32.6%), bacterial vaginosis (26%), gestational hypertension (18.4%) and pervious history of preterm labour (18.4%) were common associations. Calcium channel blocker (Depin) tocolysis was effective in postponing labour, from 48 hours to more than 2 weeks. The cesarean section rate was very high (67.3%) in our study. The commoner neonatal complications in both VLBW and ELBW babies were RDS, neonatal jaundice and sepsis. Features of IUGR were seen in both the groups (22.8% in VLBW and 22.2% in ELBW babies). The neonatal mortality rate till discharge was 15.7% in VLBW group and 33.3% in ELBW group. The morality rate was highest in 26 to 30 weeks gestation babies and in babies weighing <800 gms.ConclusionAntenatal profile of preterm labour in our series showed a number of high risk factors. The identification of common high risk factors is important for appropriate prenatal care. A better neonatal survival rate was possible due to timely intervention, appropriate management and NICU care facility available in our tertiary care centre.

Metformin therapy in women with polycystic ovary syndrome.

To determine the clinical, biochemical, hormonal, and ultrasonographic effects of 6 months of metformin therapy in women with polycystic ovary syndrome (PCOS) and compare with pretherapy parameters.