Management of maternal obesity prior to and during pregnancy.

The prevalence of obesity is high and rising worldwide. The greatest prevalence of obesity is found in the western world and in urban developing countries. There is an increased maternal mortality associated with maternal obesity.

Obesity in pregnancy.

Overweight and obesity are common findings in women of reproductive age in the UK; as 32% of 35- to 64-year-old women are overweight and 21% obese. Obesity causes major changes in many features of maternal intermediary metabolism. Insulin resistance appears to be central to these changes and may also be involved in increased energy accumulation by the fetus.

Negative correlation between intrahepatic expression of hepatitis C antigens and apoptosis despite high-level expression of Fas and HLA antigens.

The role of virus-related apoptosis in hepatic injury in chronic HCV is unclear. It is unknown whether HCV induces apoptosis directly or whether cellular injury is immunologically mediated. We studied the relationship between infected hepatocytes, apoptosis and necroinflammation.

Transient foamy virus vector production by adenovirus vectors.

The genome of the prototype foamy virus (PFV) has been introduced into an adenoviral/PFV hybrid vector and tested for stable in vitro gene transfer. Three different adenoviruses are used to encode: (i) the PFV structural genes gag and pol (Ad-GagPolDeltaPacI); (ii) the PFV structural gene env (Ad-Env); and (iii) the PFV vector genome (Ad-MD9) encoding the transgene (the enhanced green fluorescent protein (eGFP) gene). Following cotransduction by the three adenoviruses, the target cells become transient PFV vector-producing cells, resulting in the in situ release of recombinant PFV at a titre of up to 10(3) vector particles/ml, which can then infect surrounding cells, leading to stable integration of the expression cassette.

Factor V Leiden polymorphism and the rate of fibrosis development in chronic hepatitis C virus infection.

Background: The rate of progression to cirrhosis varies among individuals chronically infected with the hepatitis C virus (HCV). Coagulation pathway activation in models of hepatic fibrosis suggests variation in coagulation pathway components may influence the rate of fibrosis. We hypothesised that polymorphisms of the coagulation factors II and V affect the rate of progression to cirrhosis in HCV infected subjects.

Intravenous salbutamol bolus compared with an aminophylline infusion in children with severe asthma: a randomised controlled trial.

Background: The relative efficacies of aminophylline and salbutamol in severe acute childhood asthma are currently unclear. A single bolus of salbutamol was compared with a continuous aminophylline infusion in children with severe asthma in a randomised double blind study.

Methods: Children aged 1-16 years with acute severe asthma were enrolled if they showed little improvement with three nebulisers (combined salbutamol and ipratropium) administered over an hour and systemic steroids.

Human foamy virus integrase fails to catalyse the integration of a circular DNA molecule containing an LTR junction sequence.

The presence of closed circular forms of the linear DNA genome of human foamy virus (HFV) has not been established. The ability of the HFV integrase (IN) to catalyse the integration of these circular forms (termed 2 long terminal repeat (LTR) circles) was investigated, with a view to producing a novel hybrid vector. To this end, a construct was made containing, in addition to the enhanced green fluorescent protein (eGFP) marker gene, the last 27 bp of the 3' U5 LTR region of HFV fused to the first 28 bp of the 5' U3 LTR, the latter representing a 2LTR circle.

New therapies and vaccines for bacterial meningitis.

Acute bacterial meningitis remains an important cause of morbidity and mortality worldwide. There have recently been major advances in the prevention of the major causes of bacterial meningitis following improvements in vaccinology. The success of immunisation against Haemophilus influenzae type b infection is being mirrored with serogroup C conjugated meningococcal vaccine and pneumococcal conjugate vaccine.

Antioxidant protection against iron in children with meningococcal sepsis.

Objective: To assess antioxidant protection against iron-catalyzed reactive oxygen species in meningococcal sepsis and to establish whether severity of illness is related to deficiencies in these antioxidant systems.

Design: Prospective, controlled study.

Setting: Pediatric intensive care unit of a postgraduate teaching hospital.

Antiphospholipid antibodies and infertility.

Antiphospholipid antibodies (aPL) are an established cause of recurrent pregnancy loss. As defective embryonic implantation is a common link between unexplained infertility and recurrent miscarriage, interest has focused on the potential relationship between aPL and implantation failure after in vitro fertilization and embryo transfer (IVF-ET). This review critically examines the published data to determine whether women undergoing IVF-ET should be routinely screened for aPL.

Treatment of chronic viral hepatitis.

Significant advances have been made in the treatment of both hepatitis B and C. Cure for the majority is becoming reality. Combination regimens are now established therapy in hepatitis C and the near future will see the adoption of a similar approach to hepatitis B.

Recurrent miscarriage and variant alleles of mannose binding lectin, tumour necrosis factor and lymphotoxin alpha genes.

Variant alleles of the mannose binding lectin (MBL) gene are associated with increased susceptibility to infection and polymorphisms of tumour necrosis factor and lymphotoxin alpha genes (TNF, LTA) are associated with increased severity of infection. Studies have associated recurrent miscarriage with low serum mannose binding lectin concentrations and premature membrane rupture and preterm delivery with elevated maternal and fetal levels of TNF and the TNF (- 308) polymorphism. In this study the frequencies of variant MBL, TNF and LTA alleles in 76 Caucasian couples with idiopathic recurrent miscarriage were compared with those in 69 Caucasian control couples with no history of miscarriage and at least one previous live birth.

Intrauterine haematomas in a recurrent miscarriage population.

Background: This study examines the effect of intrauterine haematomas (IUH) discovered during early pregnancy ultrasound scanning in patients with recurrent miscarriage. Previous studies of IUHs have reported conflicting findings, and none studied women with recurrent miscarriage.

Methods: A total of 341 women with a viable pregnancy was included.

Haemodynamics of the pressor effect of oral water in human sympathetic denervation due to autonomic failure.

Oral water ingestion increases blood pressure in normal elderly subjects and in patients suffering from autonomic failure, but the time course of the haemodynamic changes is not known. We therefore studied 14 subjects with documented sympathetic denervation due to pure autonomic failure, with continuous haemodynamic recordings obtained before and after ingestion of 500 ml of distilled water at room temperature. The time course of changes in values of systolic and diastolic beat-by-beat finger blood pressure, heart rate, stroke volume, cardiac output, ejection fraction and total peripheral resistance were analysed.

Uterine artery Doppler in predicting pregnancy outcome in women with antiphospholipid syndrome.

Objective: To assess midtrimester uterine artery Doppler in the prediction of preeclampsia and small for gestational age (SGA) infants in women with primary antiphospholipid syndrome.

Methods: One hundred seventy pregnant women with histories of recurrent miscarriage in association with antiphospholipid antibodies (32 lupus anticoagulant positive, 47 IgG anticardiolipin positive, 78 IgM anticardiolipin positive, and 13 lupus anticoagulant and anticardiolipin antibodies positive) treated with low-dose aspirin and heparin were recruited prospectively. Doppler assessment of the uterine arteries (presence or absence of notches and pulsatility index) were performed at 16-18 and 22-24 weeks.

Dysfunction of endothelial protein C activation in severe meningococcal sepsis.

Background: Impairment of the protein C anticoagulation pathway is critical to the thrombosis associated with sepsis and to the development of purpura fulminans in meningococcemia. We studied the expression of thrombomodulin and the endothelial protein C receptor in the dermal microvasculature of children with severe meningococcemia and purpuric or petechial lesions.

Methods: We assessed the integrity of the endothelium and the expression of thrombomodulin and the endothelial protein C receptor in biopsy specimens of purpuric lesions from 21 children with meningococcal sepsis (median age, 41 months), as compared with control skin-biopsy specimens.

Maternal obesity and pregnancy outcome: a study of 287,213 pregnancies in London.

Objective: To examine the maternal and foetal risks of adverse pregnancy outcome in relation to maternal obesity, expressed as body mass index (BMI, kg/m(2)) in a large unselected geographical population.

Design: Retrospective analysis of data from a validated maternity database system which includes all but one of the maternity units in the North West Thames Region. A comparison of pregnancy outcomes was made on the basis of maternal BMI at booking.

Age- and gender-related growth hormone responses to intravenous clonidine in healthy adults.

The alpha(2)-adrenoceptor agonist clonidine stimulates growth hormone (GH) release in both animals and humans. It has been used to test for GH deficiency in children, to assess central alpha(2)-adrenoceptor function in adults and to determine the pathophysiological basis and to confirm diagnosis in neurological diseases with autonomic failure. The dose and mode of administration, however, may be important, as in some studies in adults oral clonidine has minimal effects on GH.

Prevalence and features of pancreatic islet cell autoimmunity in women with gestational diabetes from different ethnic groups.

Objective: To assess the prevalence and characteristics of islet cell autoimmunity amongst women with gestational diabetes selected from South Asian and Afro-Caribbean as well as European populations.

Design: Cross-sectional retrospective survey of subject cohort.

Population: Three hundred and twenty-one women with a recent history of gestational diabetes (173 European, 86 South Asian and 62 Afro-Caribbean), a median (range) of 22 (1-150) months postpartum.

Altering ventricular activation remodels gap junction distribution in canine heart.

Introduction: Prolonged arrhythmic or paced ventricular activation causes persistent changes in myocardial conduction and repolarization that may result from altered electrotonic current flow, for which gap junctional coupling is the principal determinant. Remodeling of gap junctions and their constituent connexins modifies conduction and has been causally implicated in reentrant arrhythmogenesis. We hypothesized conversely that altering the pattern of ventricular activation causes gap junctional remodeling.

Carotid plaque echogenicity and types of silent CT-brain infarcts. Is there an association in patients with asymptomatic carotid stenosis?

Background: The aim of this study was to identify the differences in echogenicity and the degree of stenosis of asymptomatic carotid plaques associated with different types of ipsilateral silent CT-brain infarcts.

Methods: Some 273 asymptomatic carotid plaques (218 patients) causing 50 to 99% stenosis were studied with high-resolution ultrasound. B-mode images were digitised and normalised by assigning certain grey values to blood and adventitia.

Simple detection of point mutations associated with HIV-1 drug resistance.

A novel assay is described for the detection of HIV-1 drug resistance that is simple, cheap and sensitive. HIV-1 drug resistance in B and non-B HIV-1 subtypes was investigated using Mutagenically-Separated PCR (MS--PCR) --- a competitive semi-nested PCR which uses mutagenic primers. The assay was assessed for sensitivity, specificity and its ability to detect mutant virus within a mixed mutant--wild-type population.

Comparative quantification of diverse serotypes of HIV-1 in plasma from a diverse population of patients.

HIV-1 is characterised by extensive genetic variability encompassing at least 10 different phylogenetically related clades within the major group of HIV-1 subtypes. Most commercially available HIV-1 RNA plasma viral load assays have been optimised with clade B viruses and may yield misleadingly low RNA levels for nonclade B viruses that are increasingly found in Europe. In this study we compare the most recent versions of the Roche Amplicor HIV Monitor and the Chiron Quantiplex for ability to detect viraemia in a population of patients infected with a range of HIV-1 subtypes.