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Background: Eclampsia is a major killer of pregnant women in the developed world and Tanzania has one of the highest rates of maternal mortality worldwide. Early recognition and treatment of pre-eclampsia may help prevent maternal mortality and morbidity. Aim: To characterise the presentation of eclampsia in rural Tanzania. Methods: A prospective study of all women presenting with eclampsia at Muheza District Designated Hospital, in rural north-east Tanzania, between May 2007 and April 2008. Results: 47 women presented with eclampsia during the study period. Three women died and there were eight perinatal deaths. 89% of women were booked and had received antenatal care. Maternal demographics are shown in Table 1. 53% of seizures occurred antepartum, 13% intrapartum and 34% postpartum (up to 13 days post delivery). Only six percent of patients were diagnosed with severe pre-eclampsia prior to seizure and 63% percent of seizures occurred out of hospital. 20% were asymptomatic prior to seizure. Prodromal symptoms present included headache (78%), visual disturbance (44%), epigastric pain (20%), and nausea and vomiting (2%). 62% of patients received treatment with magnesium sulphate, 35% received concurrent diazepam and 33% received only diazepam. Hypertension was treated with hydralazine in 74% of cases.

Background: Alternative splicing of fms –like tyrosine kinase 1 (Flt-1) produces a soluble protein (sFlt v1), which is markedly increased in the blood of pre-eclamptic women. It is believed that this angiogenic factor plays an important role in the pathogenesis of pre-eclampsia. A novel splice variant (sFlt_v2) has recently been discovered and may be elevated in pre-eclampsia. Preliminary reports suggest that, like pre-eclampsia, the novel variant may be specific to human and primate placentae. It has not as yet been characterised in severe early onset pre-eclampsia. Aims: To determine expression of the sFlt_v2 in the placenta in severe early onset pre-eclampsia Methods: Placenta was collected at delivery from 16 pre-eclamptic women (gestational age range 22-34 weeks), six pre-eclamptics complicated by HELLP syndrome (range 24 – 36 weeks), 15 normotensive women with spontaneous preterm labour (range 28-36 weeks) and 30 term normotensive controls (range 38-42 weeks). RNA was isolated from the placental tissue and transcribed into cDNA. Real-Time qPCR was performed for Flt1, sFlt_v1 and sFlt_v2 and expression levels were normalized to the housekeeping gene. Results: The expression of sFlt_v1 and sFlt_v2, and Flt1, were increased in placentae in severe pre-eclampsia compared to normotensive controls. sFlt_v2 was the predominant variant expressed in the placenta in severe early onset pre-eclampsia. Conclusions: The recently discovered sFlt variant (sFlt_v2) is the predominant splice variant expressed in the placenta in severe early onset pre-eclampsia. This discovery may have important implications on improving our understanding of pre-eclampsia, its diagnosis and in the development of potential therapeutics.

Ectopic pregnancies are serious gynaecological emergencies that can cause fatal haemorrhage. Most are treated surgically. Given the placenta is heavily reliant on Epidermal Growth Factor Receptor (EGFR) signaling, we set out to develop a medication-based treatment of ectopics using combination gefitinib (EGFR inhibitor) and methotrexate (folate antagonist). Both drugs are well tolerated and available in tablet form. We used in vitro and in vivo approaches to test the ability of gefitinib and methotrexate to regress placental tissue, and to explore molecular mechanisms. In vitro assays included immunohistochemistry (EGFR staining) western blot (EGFR phosphorylation), cell viability assays (Cell-Titre Blue, LDH cytotoxicity assay, xCELLigence system), apoptosis assays (PCR, FACS of M30 antibody) and The Bioplex Platform (phosphorylation of the EGFR pathway). JEG-3 xenografts were used to assess regression of placental tissue in vivo, where serum hCG was also measured (ELISA). EGFR was highly expressed in placentae from ectopic pregnancies. Combination treatment was supra-additive in inducing cell death of placental tissue in vitro, with >70% cell death by 48 hours (Syncytialised BeWos, JEG-3 and 1st trimester trophoblast). This supra-additive effect was demonstrated in both end point assays (cell viability) and regular monitoring using The xCELLigence system. Gefitinib potently blocks EGFR phosphorylation in placental tissues in vitro (Western blot). Both drugs may be converging to inhibit Akt phosphorylation (Bioplex analysis). Combination treatment increases apoptosis (FACS of M30 antibody). In vivo, Gefitinib or MTX as single agents induced significant decrease in xenograft tumour volume in a dose dependent manner (n ≤ 5 mice per treatment). However, combining these drugs was supra-additive in decreasing xenograph tumour volume and weight. Serum hCG in mice was lowest with combination treatment. Combination gefitinib and methotrexate potently regresses placental tissue. It may be a novel therapeutic approach to cure ectopic pregnancies, potentially replacing surgery with tablets.

OBJECTIVE: To investigate whether persistently absent umbilical artery end-diastolic flow in the intrauterine growth-restricted fetus after betamethasone administration is associated with altered perinatal outcomes. METHODS: This is a retrospective cohort study of 92 pregnancies complicated by intrauterine growth restriction (IUGR) and absent end-diastolic flow in which antenatal betamethasone was given. Predefined maternal outcomes (maternal age, gestational age at diagnosis of absent end-diastolic flow, gestational age at delivery, preexisting medical conditions) and neonatal outcomes (including birth weight; perinatal mortality; duration of neonatal intensive care unit admission; requirement for intubation, assisted ventilation, inotropic support; duration of supplemental oxygen, assisted ventilation; respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage) were analyzed. RESULTS: Betamethasone administration was associated with a transient return of end-diastolic umbilical artery flow in 58 pregnancies (63%) and persistent absent end-diastolic flow in 34 (37%). Persistent absent end-diastolic flow was seen more frequently in women with prepregnancy medical disorders (59% compared with 24%, P

RNA interference (RNAi) is a new therapeutic approach, silencing genes to disrupt diseases. However, short interfering siRNAs (molecule used in RNAi) can have off-target effects, activating the immune system through RNA sensing toll-like receptors (TLR) 3, 7 and 8. We have previously proposed that in some diseases (cancers, ectopic pregnancies) it may be useful to enhance the immune response. A novel class of immunostimulatory siRNAs could be developed, silencing genes important to disease and recruiting the immune system to further aid disease clearance. We set out to develop a rational design strategy that enhances immunostimulatory properties to any siRNA sequence but maintains effective gene silencing. We screened a set of siRNAs targeting lamin. All were of the same sequence, except for different immunostimulatory motifs on the 3′ end of the sense strand. We also investigated a different design where we added a small micro-RNA like poly-uridine bulge (potentially immunostimulatory) on the sense strand. We used human peripheral blood mononuclear cells (PBMCs) to test for immunostimulation, and HEK 293-T-cells to test for lamin gene knockdown.Of all strategies tested, the poly-uridine bulge was best. It silenced the lamin gene as effectively as control, but caused a 2–3 fold increase of IFN-α and TNF-α. We verified this approach by adding the poly-uridine bulge onto an siRNA of low immunostimulatory potential targeting GFP. The bulge markedly enhanced immunostimulation in a dose response manner, and did not compromise gene knockdown. The addition of a poly-uridine bulge to siRNAs can increase immunostimulation without affecting gene silencing efficacy. Immunostimulatory siRNAs might be particularly efficacious to treat ectopic pregnancies where there are abundant immune cells, and functional TLR 7/8 in the trophoblast (unpublished observations). We now plan to test this immunostimulatory siRNA approach in an in vivo ectopic pregnancy model using JEG-3 cells xenographted in NOD-SCID mice.

It has been suggested that losses of twin conceptuses in very early pregnancy are high, and that for every liveborn twin pair there are a further 10–12 twin pregnancies that end up as a singleton birth1. Here we show that in a group of women who had double-ovulated and conceived, the probability of the second egg also becoming fertilized and developing is 20–30% — which is comparable to the probability of conception and survival of a single conceptus2. We conclude that the presence of one embryo does not affect the development of its twin.

Fifty-nine elements, poly chlorinated biphenyls, volatile N-nitrosamines and gamma emission were determined in 30 sewage sludges from 23 American cities using several analytical methods. Relatively high concentrations of toxic metals were found in sludges from specific municipal plants. The pH and levels of calcium and iron in certain of the sludges appeared to reflect the addition of lime, ferric chloride and/or spent pickle liquor during sewage treatment. Of 15 sludges analyzed, the carcinogen, N-nitrosodimethylamine was detected in 14 and various other N-nitrosamines in 12 of them. Based on present federal guidelines, only 7 of the 30 municipal sludges analyzed would be considered suitable for land application owing to their elevated content of one or more heavy metals.

Some of the man-made objects (beads, pieces of bangles/rings, and slag fragments) dating as far back as about 700 B.C., and recovered in the Nevasa excavations (west-central India) have been analyzed using an electron microprobe analyzer. The exposed surfaces showed almost total absence of alkalis, indicating leaching effect. A surface layer, roughly 230 μm thick, showing differential etching, was observed. The interiors (after limited sectioning) showed presence of Na2O and K2O (generally 12–21 wt%), SiO2, relatively low CaO, somewhat high Al2O3, and a wide use of colorants such as Fe3O4, and MnO. Chloride concentrations as high as 1.5 % were detected. The low CaO contents generally fit Brill's criteria for glasses of Indian origin. However, many of the glasses did have quite low Al2O3 content in contrast with Brill's findings.

Many novel solutions to the nationwide problem of solid waste disposal have been proposed. A recent one which has been studied is the feeding of paper products to farm animais such as dairy cattle as a source of cellulose (MERTENS et ai. 1971a). Cattle will consume rations containing up to 20 weight % paper and assimilate up to 90% of the dry matter of certain of them such as brown cardboard (MERTENS et ai. 1971b). Office paper has also been advantageously incorporated in sheep rations (NISHIMUTA et,ai. 1969). It is known that compounds such as the polychlorinated biphenyls (PCB's) are used as dye carriers in specialt'y printing inks. High concentrations of PCB's have been reported as present in carbonless copying paper (MASUDA et al. 1972). It is possible that these compounds may survive when specialty paper products are regenerated for use in other paper products such as cardboard. Paperboard has been reported to contain PCB-type compounds (ANONYMOUS 1972). These compounds could be transferred to cows' milk or meat as residues. Contamination of food by contact is possible if the paper material becomes part of a food container. Electron capturing peaks in extracts of cereal grains have been traced to the presence of corresponding compounds in cloth bags (LEVl and NOWICKI 1972). Certain metals may also be present in paper as constituents of the ink or as a result of the printing process. Furthermore deep rooted trees may absorb unusual elem~Its from lower soil horizons (ROBINSON et ai. 1958) which may then be present in paper. In the work reported a survey of about i00 papers and paper products has been made for the presence of chlorinated organic compounds using gas chromatography with electron affinity and electrolytic conductivity detectors and the combination gas chromatography-mass spectrometry. Metals and other elements in paper were also determined by spark source mass spectrometry. Experimental

Current ultrasound techniques can accurately determine the chorionicity of twins, but not zygosity. We previously proposed that the zygosity of spontaneously conceived twins can be determined at early ultrasound, where 2 corpora lutea infers dizygosity, and 1 implies monozygosity. Here we did a case series, comparing zygosity predicted using this method with definitive DNA genotyping of twins after birth. We retrospectively identified 14 ultrasound reports of spontaneous twin pregnancies at 6(+0 days) to 13+6 weeks' gestation, where both ovaries were seen and the number of corpora lutea documented. We visited all twin pairs, obtained buccal smears, and determined zygosity by genotyping 9 independent microsatellite markers. All 8 cases where 2 corpora lutea were seen were dizygotic pregnancies. One further case where 3 corpora lutea were seen was also dizygotic. All 3 sets of monozygotic twins had 1 corpus luteum. There were 2 cases incorrectly assigned, where 1 corpus luteum was seen in dizygotic pregnancies. We conclude if 2 corpora lutea are seen at a first trimester ultrasound of spontaneously conceived dichorionic twins, they appear to be almost certainly dizygotic. However, if 1 corpus luteum is seen in dichorionic twins, zygosity cannot be determined with certainty since it is either monozygotic, or dizygotic where a second corpus luteum has been missed.

Background There is a debate about the cost-efficiency of methotrexate for the management of ectopic pregnancy (EP), especially for patients presenting with serum human chorionic gonadotrophin levels of >1500 IU/L. We hypothesised that further experience with methotrexate, and increased use of guideline-based protocols, has reduced the direct costs of management with methotrexate. Methods We conducted a retrospective cost analysis on women treated for EP in a large UK teaching hospital to (1) investigate whether the cost of medical management is less expensive than surgical management for those patients eligible for both treatments and (2) to compare the cost of medical management for women with hCG concentrations 1500–3000 IU/L against those with similar hCG concentrations that elected for surgery. Three distinct treatment groups were identified: (1) those who had initial medical management with methotrexate, (2) those who were eligible for initial medical management but chose surgery (‘elected’ surgery) and (3) those who initially ‘required’ surgery and did not meet the eligibility criteria for methotrexate. We calculated the costs from the point of view of the National Health Service (NHS) in the UK. We summarised the cost per study group using the mean, standard deviation, median and range and, to account for the skewed nature of the data, we calculated 95% confidence intervals for differential costs using the nonparametric bootstrap method. Results Methotrexate was £1179 (CI 819–1550) per patient cheaper than surgery but there were no significant savings with methotrexate in women with hCG >1500 IU/L due to treatment failures. Conclusions Our data support an ongoing unmet economic need for better medical treatments for EP with hCG >1500 IU/L.

The literature suggests that up to 19% of umbilical cord blood samples are invalid. Accordingly, it has been proposed that blood should be universally collected from both vessels. We prospectively collected paired arterial and venous blood to examine whether our centre, where staff were experienced in single vessel collection, was more accurate. Of 289 paired samples, 53 (18.3%) were considered invalid. Despite this significant error rate, we propose that routinely, only arterial sampling is needed and that an additional venous sample need only be taken to validate samples in cases of pH < 7.15, a difficult delivery or a non-vigorous baby.