Increased homozygosity due to endogamy results in fitness consequences in a human population.

Recessive alleles have been shown to directly affect both human Mendelian disease phenotypes and complex traits. Pedigree studies also suggest that consanguinity results in increased childhood mortality and adverse health phenotypes, presumably through penetrance of recessive mutations. Here, we test whether the accumulation of homozygous, recessive alleles decreases reproductive success in a human population. We address this question among the Namibian Himba, an endogamous agro-pastoralist population, who until very recently practiced natural fertility. Using a sample of 681 individuals, we show that Himba exhibit elevated levels of "inbreeding," calculated as the fraction of the genome in runs of homozygosity (FROH). Many individuals contain multiple long segments of ROH in their genomes, indicating that their parents had high kinship coefficients. However, we do not find evidence that this is explained by first-cousin consanguinity, despite a reported social preference for cross-cousin marriages. Rather, we show that elevated haplotype sharing in the Himba is due to a bottleneck, likely in the past 60 generations. We test whether increased recessive mutation load results in observed fitness consequences by assessing the effect of FROH on completed fertility in a cohort of postreproductive women (n = 69). We find that higher FROH is significantly associated with lower fertility. Our data suggest a multilocus genetic effect on fitness driven by the expression of deleterious recessive alleles, especially those in long ROH. However, these effects are not the result of consanguinity but rather elevated background identity by descent.

Antidiabetic and antioxidant potentials of Euphorbia hirta leaves extract studied in streptozotocin-induced experimental diabetes in rats.

Euphorbia hirta, commonly known as asthma weed, is a popular folk remedy for the treatment of various ailments. Recent studies have indicated that plant has potent antioxidant properties. As part of an ongoing programme to validate the use of some reputed herbs in Indian traditional medicines, the present study was aimed to evaluate the antidiabetic and antioxidant potentials of E. hirta leaves in streptozotocin-induced experimental diabetes in rats. Oral administration of E. hirta leaves extract (300 mg/kg b.w./rat/day) for a period of 30 days indicated the antidiabetic nature of the leaves extract. Determination of the lipid peroxides, hydroperoxides, and both enzymatic and non-enzymatic antioxidants evidenced the antioxidant potential of the leaves extract. Assay of enzymes such as serum aspartate transaminase (AST), serum alanine transaminase (ALT) and serum alkaline phosphatase (ALP) revealed the non-toxic nature of E. hirta leaves. The hypoglycemic activity of the leaves extract was comparable with gliclazide, a standard reference drug.

High rate of extrapair paternity in a human population demonstrates diversity in human reproductive strategies.

Among nonhuman species, social monogamy is rarely accompanied by complete fidelity. Evolutionary theory predicts that the rate of extrapair paternity (EPP) should vary according to socioecological conditions. In humans, however, geneticists contend that EPP is negligible and relatively invariable. This conclusion is based on a limited set of studies, almost all of which describe European-descent groups. Using a novel, double-blind method designed in collaboration with a community of Himba pastoralists, we find that the rate of EPP in this population is 48%, with 70% of couples having at least one EPP child. Both men and women were very accurate at detecting cases of EPP. These data suggest that the range of variation in EPP across human populations is substantially greater than previously thought. We further show that a high rate of EPP can be accompanied by high paternity confidence, which highlights the importance of disaggregating EPP from the notion of "cuckoldry."

TATA-binding protein is limiting for both TATA-containing and TATA-lacking RNA polymerase III promoters in Drosophila cells.

We have investigated the role of the TATA-binding protein (TBP) in modulating RNA polymerase (Pol) III gene activity. Epitope-tagged TBP (e-TBP) was both transiently and stably transfected in Drosophila Schneider S-2 cells to increase the total cellular level of TBP. Analysis of the transcripts synthesized from cotransfected tRNA and U6 RNA genes revealed that both types of RNA Pol III promoters were substantially stimulated by an increase in e-TBP in a dose-dependent manner. Furthermore, a TBP-dependent increase in the levels of endogenous tRNA transcripts was produced in the stable line induced to express the e-TBP. We further determined whether the ability of increased TBP to induce RNA Pol III gene expression was due to a direct effect of increased TBP complexes on RNA Pol III gene promoters or an indirect consequence of enhanced expression of RNA Pol II genes. A TBP expression plasmid (e-TBP332), containing a mutation within the highly conserved carboxy-terminal domain, was both transiently and stably transfected into S-2 cells. e-TBP332 augmented the transcription from two RNA Pol II gene promoters indistinguishably from that observed when e-TBP was expressed. In contrast, e-TBP332 was completely defective in its ability to stimulate either the tRNA or U6 RNA gene promoters. In addition, increasing levels of a truncated TBP protein containing only the carboxy-terminal region failed to induce either the tRNA or U6 RNA gene promoter, whereas it retained its ability to stimulate an RNA Pol II promoter. Thus, the TBP-dependent increase in RNA Pol II gene activity is not sufficient for enhanced RNA Pol III gene transcription; rather, a direct effect on RNA Pol III promoters is required. Furthermore, these results provide the first direct evidence that the amino-terminal region of TBP is important for the formation or function of TBP-containing complexes utilized by TATA-less and TATA-containing RNA Pol III promoters. Together, these studies demonstrate that TBP is limiting for the expression of both classes of RNA Pol III promoters in Drosophila cells and implicate an important role for TBP in regulating RNA Pol III gene expression.

A polyherbal vaginal pessary with spermicidal and antimicrobial action: evaluation of its safety.

A polyherbal vaginal pessary (Praneem) has been formulated that has antimicrobial properties against genital pathogens in addition to spermicidal action. Thus, it has dual potential as a barrier method for contraception and for providing protection against some sexually transmitted infections. The present study reports the findings of a multicentre trial that was conducted to evaluate the safety of this product. Trials were carried out in 23 women in three centres in India: the Postgraduate Institute of Medical Education and Research, Chandigarh; Safdarjang Hospital, New Delhi; and Kamla Nehru Memorial Hospital, Allahabad. Thorough clinical and pelvic examinations were carried out as well as cervical cytology, blood biochemistry and haematology before and after use of the polyherbal pessary intravaginally once daily for 7 consecutive days. No toxicity was observed on clinical examination or by laboratory investigations. Daily intravaginal use of this pessary for 7 days had no adverse effects on cervical cytology or on metabolic and organ functions.

Abortion procedures in a tertiary care institution in India.

OBJECTIVE: To determine the complications rate of termination of pregnancy (TOP) and the risk factors for complications following TOP. METHODS: Retrospective observational study of the records of 1287 women who underwent TOP in the Department of Obstetrics and Gynaecology of the Postgraduate Institute of Medical Education and Research, Chandigarh, India, between 1997 and 2001. First-trimester abortion was performed in 1088 women (85%) and second-trimester abortion in 199 women (15%). Most women (76%) were aged between 26 and 30 years; they were educated and requested TOP primarily to limit the number of their children or to space their births. A malformed fetus was the indication for TOP in 5.9% cases, and 16% of the women had medical disorders associated with the pregnancy. Suction evacuation was the method of choice for first-trimester abortion (88%); dinoprostone gel and extra-amniotic saline solution plus oxytocin infusion were the primary methods (71%) for second-trimester abortion. RESULTS: Uterine perforation occurred in 1 patient (0.09%) after a first-trimester abortion. The total rate of complications was 3.79% after first-trimester and 4.0% after second-trimester abortions. Excessive hemorrhage and retained placenta were chief complications associated with second-trimester abortion. Incomplete abortion (1.5%) and minor infection were seen in 2.3% patients. The rate of complications was higher among parous women. Postabortion insertion of a CuT intrauterine device increased the need for a second course of antibiotics. CONCLUSION: Termination of pregnancy is safe if adequate care is taken while performing the procedure.

Vehicle interior interactions and kinematics of rear facing child restraints in frontal crashes.

The performance of rear facing child restraints in frontal crashes can be determined by controlling a) the child's kinematics and b) interactions with vehicle structures. Twelve sled tests were performed to analyze the effect of the location and structural properties of vehicle interior components. The role of restraint kinematics was studied by developing computational models which underwent idealized motions. Stiff structures originally offset from the restraint, but which contact the restraint late in the test, cause increased injury values. Attachment methods which reduce child restraint rotation and more rigidly couple the restraint to the vehicle result in the best safety performance.

Evaluating contraceptive choice through the method-mix approach. An Indian Council of Medical Research (ICMR) task force study.

The method-mix approach was used to evaluate informed contraceptive choices in the present study. A total of 8,077 potential clients were given a balanced presentation of all available contraceptive methods in the national program, ie, the CuT 200 intrauterine device (IUD), low-dose combined oral pills (OC), condom, and sterilization (female/male) along with a new method, Norplant(R).(1) The majority of women opted for spacing methods; among them, the IUD was preferred by about 60% of clients, followed by condoms (9%), OC (6%), and Norplant (5%). Sterilization, mainly female, was accepted by about 17% of the women making an informed choice. The economic status of couples did not influence the contraceptive choices, as all the methods were offered free of cost in the present study, which is the current practice in the national program. Illiterate women more often accepted sterilization (about 25%) than did literate women (15%). This is because illiterate women had more children; about 30% of illiterate women had three or more children, as opposed to 16.2% of literate women. However, literacy status did not influence the choice of any specific spacing method. The study also revealed that, by encouraging potential clients to make an informed choice, they could override the provider's bias while accepting a particular type of spacing method. This is evident from the observation that Norplant was the first choice of the provider for 35% of the women, whereas only 5% of women preferred and accepted Norplant. The present study stresses an urgent need to promote the practice of informed choices in the national program with a variety of contraceptive options-especially, spacing methods for improving contraceptive prevalence and reproductive health in the country.

Rate of metabolism of norethisterone in women from different populations.

The rate of metabolism of orally administered norethisterone was compared in fourteen centres by measuring plasma levels of the steroid by radioimmunoassay at varying times after oral administration of a 1 mg dose. The inter-centre differences were of the same order as the intra-centre differences. Variations in metabolism appeared not to be due to variations in body size.

Pharmacokinetics of ethynyloestradiol in women for different populations.

The pharmacokinetics of a dose of 50 microgram ethynyloestradiol administered orally was studied in fourteen centres. Absorption was rapid and the highest serum concentrations of total ethynyloestradiol were found in most subjects at 1 h and by 24 h concentrations were less than 250 pg/ml. Calculation of the half-lives for absorption, distribution and elimination showed wide variations between subjects, the half-life of elimination varying from 2.5 h to more than 30 h. Bioavailability as measured by the area under the serum ethynyloestradiol concentration-time curve also showed more than a ten-fold variation. Intra-centre differences in the various parameters measured were as large as the inter-centre differences.

Role of intrapartum antibiotics in prevention of vertical transmission of neonatal sepsis.

The present study evaluates the role of prophylactic intrapartum antibiotics in the prevention of neonatal sepsis. Labour and delivery characteristics of 1478 women delivering at the Nehru Hospital, PGIMER, Chandigarh were recorded. Intrapartum antibiotics (ampicillin, with or without gentamycin) were given to 69 per cent women. The neonatal sepsis rate was 1.56 per cent. This was not significantly lower in the women who received intrapartum antibiotics (1.47 vs 1.75%). Though there was a lowering of neonatal sepsis rate with intrapartum antibiotic administration when the duration of labour was more than 12 h (1.67 vs 3.09%), duration of ruptured membranes was more than 6 h (1.93 vs 3.81%) and number of pelvic examination was 3 or more (1.63 vs 4.54%), it was not statistically significant. It was concluded that intrapartum antibiotics as per the existing protocol did not prevent neonatal sepsis.

Yeast colonisation & fungaemia in preterm neonates in a tertiary care centre.

Seventy consecutive preterm neonates who stayed in the hospital for more than seven days between March and October 1996, were studied for colonisation at oral, umbilical, groin, and rectal areas and for fungaemia. Overall, 71.4 per cent of the neonates were colonised and colonisation occurred within 24 h in 38 per cent preterm neonates. Neonates weighing less than 1500 g were colonised more frequently at more than one site and had higher load of yeast. Candida albicans (19%), Pichia (Hansenula) anomala (17.5%), C. tropicalis (13.2%), C. parapsilosis (12.3%) and Trichosporon cutaneum (10.0%) were the predominant colonising yeasts. Fungaemia was detected in 22.8 per cent of preterm neonates with predominance of P. anomala fungaemia (62.5%). Prematurity, male sex, broad spectrum antibiotic therapy, intubation and higher colonising rate were identified as significant risk factors for development of fungaemia. Except one strain of C. tropicalis, all yeast strains were sensitive to commonly used systemic antifungal agents. Study highlights the importance of routine surveillance of yeast colonisation of preterm neonates with identifying possible risk factors.

Primary causes of perinatal mortality-autopsy study of 134 cases.

PIP: The methodology and results of 134 neonatal autopsies performed over a 2-year period are presented. The causes of perinatal mortality, in descending order, were: 43% by extrinsic perinatal hypoxia; 18% by infection; 12% by respiratory distress syndrome; and 10.5% by congenital abnormlities. These 4 factors accounted for 84% of the total cases. Perinatal mortality is strongly associated with obstetrical factors, respiratory distress syndrome, and prematurity. In addition, iatrogenic infections play a large contributory role in perinatal mortality. Since about 77% of the perinatal deaths occurred in low-birth-weight babies, the reduction of perinatal mortality can be promoted by reducing prematurity rates and by early detection and intervention in cases of intrauterine growth retardation. In addition, adequate and systematic antenatal care is warranted, since none of the participants in this series had received such care. In 10 cases the primary cause of death could not be determined despite complete autopsy. Briefly the methodology entailed collecting autopsy data, and then assigning primary cause of death from a previously prepared and defined list of primary causes of death, after taking into consideration clinical data in each case. Primary causes of death were, according to this methodology: extrinsic perinatal hypoxia, infection, respiratory distress syndrome, congenital anomalies, hematological disorders, idiopathic massive pulmonary hemorrhage, birth trauma, other specific causes, extreme prematurity, intrauterine growth retardation, and unexplained.^ieng

Spermicidal & contraceptive properties of Praneem polyherbal pessary.

BACKGROUND & OBJECTIVES: Though a number of barrier methods and potent spermicides are available, most of these have nonoxynol-9 (N-9) as the active ingredient which is observed to cause inflammation and genital ulceration on repeated use. The present study was undertaken to develop a safe spermicide with conjoint microbicidal properties. METHODS: A polyherbal pessary was formulated with purified ingredients from neem (Azadirachta indica) leaves, Sapindus mukerossi (pericarp of fruit) and Mentha citrata oil. Spermicidal action on human sperm was tested by Sander-Cramer slide test in vitro and by post coital tests in vivo. Contraceptive action was tested in rabbits. RESULTS: The combination of the three herbal ingredients resulted in the potentiation of the spermicidal action by 8-folds. The post coital tests confirmed the spermicidal properties of the Praneem polyherbal pessary (PPP) in women with high cervical mucous score around mid estrus. It also prevented in most women the migration of sperm into the cervical mucous. In 15 rabbits studied pregnancy was prevented by the intravaginal administration of PPP, whereas 13 of the 15 animals in the control group became pregnant. INTERPRETATION & CONCLUSION: The Praneem polyherbal pessary has potent spermicidal action on human sperm in vitro and in vivo. When applied in the vagina before mating, it prevented rabbits from becoming pregnant.

Safety of intrauterine administration of purified neem seed oil (Praneem Vilci) in women & effect of its co-administration with the heterospecies dimer birth control vaccine on antibody response to human chorionic gonadotropin.

Praneem Vilci (PV), purified neem oil was reported to exercise a reversible antifertility effect after a single intrauterine instillation in rodents and primates without any adverse effects. After toxicology, drug regulatory and ethical clearances, a phase I clinical trial was conducted on PV. Eighteen healthy tubectomised women were enrolled to evaluate the safety of a single intrauterine instillation of PV and to determine the effect of its co-administration on anti-hCG response to the heterospecies dimer (HSD) hCG vaccine. Eight women received PV alone and ten women were given the HSD-hCG vaccine in addition. Base-line and post-treatment haematological and biochemical profiles were determined as also the mid-luteal serum progesterone. Endometrial biopsies were examined to assess ovulatory status and the effect of intrauterine treatment with PV on the endometrium. Anti-hCG antibody titres were estimated in women who were concurrently immunized with the HSD vaccine. No untoward reaction was observed in any woman. Menstrual pattern and ovulatory status remained unaltered. Endometrial biopsy after PV instillation in one woman showed non-specific endometritis but she remained asymptomatic. Mild eosinophilia was seen in two women and this reverted to normal on its own. All women receiving PV and the HSD vaccine generated antibodies against hCG. Our data show that intrauterine administration of PV is safe and does not prevent the antibody response to HSD-hCG vaccine.

Preterm breech delivery in a developing country.

OBJECTIVES: To determine if cesarean section offers any advantage over vaginal delivery for a preterm breech fetus in a developing country. METHODS: A retrospective analysis from hospital records was done at a tertiary care center in North India. Two hundred and twenty-four preterm breech deliveries (28-36 completed weeks) between January 1988 and December 1991 from a total of 13,149 deliveries at the hospital during this period formed the study group. Fetal death and lethal congenital malformations diagnosed antepartum were excluded. Intrapartum and neonatal morbidity and mortality in vaginal versus cesarean deliveries were the main outcome measures. RESULTS: Although the combined intrapartum and neonatal mortality was significantly higher for vaginal delivery (35.9% vs. 17.7%), there was no significant difference when the data was correlated with birthweight or gestational age. The neonatal morbidity was also similar in both these groups. In women with a poor obstetric history, the neonatal survival was better in the cesarean group (93% vs. 43%; P = 0.0004). CONCLUSION: Even with optimum neonatal care facilities, cesarean section does not offer any advantage over vaginal delivery for a preterm breech fetus in a developing country. The present study does not advocate the routine use of cesarean section for this group of fetuses. However, it is the preferred route of delivery for women with a poor obstetric history.

Oxytocin induction of labor: a comparison of 20- and 60-min dose increment levels.

OBJECTIVES: To compare the efficacy and complications of oxytocin dose increments at 20- and 60-min intervals for induction of labor in women with low parity. METHODS: One hundred women of low parity requiring induction of labor were randomly allocated to 20- and 60-min oxytocin dose increments, 50 patients in each group. The basal oxytocin dose was 1 milliunit/min and doubling of the oxytocin dose was done at intervals of 20 and 60 min. RESULTS: The group with 60-min increments had a decreased incidence of uterine hyperstimulation, cesarean section and operative vaginal delivery. The induction-delivery interval was similar in both groups. CONCLUSION: The oxytocin infusion regimen with increments at 60-min intervals is safer than and equally effective as 20-min incremental intervals.

Recurrent leiomyoma of the vagina.

A rare case of huge vaginal leiomyoma recurrence is reported. Vaginal leiomyoma is a rare entity and recurrence after its removal is extremely rare. However, if recurrence occurs with intact ovarian function ovariectomy should also be done.

Mode of delivery in deep transverse arrest.

OBJECTIVES: To determine the trends in the mode of delivery in deep transverse arrest (DTA) over two decades and their impact on maternal morbidity and neonatal outcome. METHODS: Obstetric and neonatal records of women with DTA who delivered at Nehru Hospital, PGIMER, Chandigarh in the years 1970, 1980 and 1990 were analyzed. RESULTS: Although Kielland's forceps was used very frequently in 1970 (44.4%) it had disappeared by 1990 because of increased morbidity associated with it. Instead, use of vacuum extractor and cesarean section has increased over the years. Manual rotation forceps extraction was the most commonly used vaginal method of delivery over two decades (49.5%). Perinatal outcome was better with manual rotation forceps extraction or vacuum extraction as compared to Kielland's forceps. Cesarean section was associated with a high incidence of birth asphyxia (30%). CONCLUSIONS: Manual rotation forceps extraction and vacuum extraction are safe methods of delivery in DTA. Cesarean section as an alternative does not improve the perinatal outcome.