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.

Childhood tuberculosis: advances in immunopathogenesis, treatment and prevention.

Tuberculosis in childhood is an important cause of mortality worldwide. The disease is difficult to diagnose and the underlying immune mechanisms are poorly understood. Advances in the application of molecular genetic tools, as illustrated by the recent completion of the genome sequence of Mycobacterium tuberculosis, provide opportunities for the development of improved diagnostic tools and vaccines for tuberculosis.

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.

Gene-targeted therapeutic strategies--Royal Pharmaceutical Society Symposium. 9-10 December 1999, London, UK.

This meeting highlighted the approaches that are currently available for gene-targeted therapeutics. The meeting focused on two strategies: antigene and anti-message. Polyamides (an example of antigene targeting) have exhibited significant antiviral activity, particularly against AIDS.

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.

Chemotactic response of Helicobacter pylori to human plasma and bile.

To clarify further the role of chemotaxis in Helicobacter pylori colonization, the in vitro bacterium response to human plasma and bile (secretions containing chemoeffector compounds that are present in the gastric mucus layer) was examined. Human plasma, after dilution to 1 % (v/v) with buffer, was found to be a chemoattractant for the motile bacillus. Human gall-bladder bile, after dilution to 2 % (v/v) with buffer, was found to be a chemorepellent, but did not cause the motility of the bacillus to be diminished after prolonged exposure.

To die or not to die: how does p53 decide?

p53 is frequently mutated in cancer and as a result is one of the most intensely studied tumour suppressors. Analysis of the primitive forms of p53 found in Caenorhabditis elegans and Drosophila, alongside studies using transgenic mouse models, indicate that the induction of apoptosis is both the most conserved function of p53 and vital for tumour suppression. p53-mediated apoptosis occurs through a combination of mechanisms which include pathways that are both dependent and independent of alterations in gene expression.

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.

Electrophysiological effects accompanying regression of left ventricular hypertrophy.

Objective: The aim of this study was to investigate changes following regression of left ventricular hypertrophy (LVH).

Methods: Electrophysiolological changes were recorded in isolated guinea-pig myocardial preparations. LVH was induced by constriction of the thoracic aorta and regression was followed after removal of the constriction.

Mutation of BCL-2 Family Proteins in Cancer.

Apoptosis is a genetically controlled cell death process that is required for normal development and tissue homeostasis. Suppression of apoptosis can confer a growth advantage to cells and contribute to cancer; many cancers are relatively resistant to apoptosis, including that induced by radiation or chemotherapeutics. Mutations which inactivate pro-apoptotic or activate anti-apoptotic proteins in cancer cells are therefore likely to be responsible for some of these differences.

Host defense function of the airway epithelium in health and disease: clinical background.

Respiratory infection is extremely common and a major cause of morbidity and mortality worldwide. The airway epithelium has an important role in host defense against infection and this is illustrated in this review by considering infection by respiratory viruses. In patients with asthma or chronic obstructive pulmonary disease, respiratory viruses are a common trigger of exacerbations.

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.

How Helicobacter pylori urease may affect external pH and influence growth and motility in the mucus environment: evidence from in-vitro studies.

Background: Survival of Helicobacter pylori is dependent upon urease in the cytoplasm and at the bacterial surface. We have sought to clarify how alkaline ammonium salts, released from urea by this enzyme, might alter mucus pH and so affect growth and motility of the bacterium in the gastric mucus environment.

Methods: Experiments were conducted in vitro to determine how the growth and motility of H.

Development of a quality-of-life assessment for the allergic child or teenager with multisystem allergic disease.

Background: Health-related quality of life (HRQOL) questionnaires currently being used to evaluate allergic disease are organ-specific. They therefore fail to take account of the systemic aspects of allergic disease.

Objective: To develop and validate a pediatric HRQOL questionnaire for allergic disease (Pediatric Allergic Disease Quality of Life Questionnaire, PADQLQ) that encapsulates problems related to the eyes, ears, nose, lungs, skin, emotions, and everyday activities.

Description of trihalomethane levels in three UK water suppliers.

Samples of drinking water are routinely analysed for four trihalomethanes (THMs), which are indicators of by-products of disinfection with chlorine, by UK water suppliers to demonstrate compliance with regulations. The THM data for 1992-1993 to 1997-1998 for three water suppliers in the north and midlands of England were made available for a UK epidemiological study of the association between disinfection by-products and adverse birth outcomes. This paper describes the THM levels in these three supply regions and discusses possible sources of variation.

Placental pathology, antiphospholipid antibodies, and pregnancy outcome in recurrent miscarriage patients.

Objective: To examine whether there are characteristic histological features in placentas from ongoing pregnancies of patients with a history of recurrent miscarriage, with and without primary antiphospholipid antibody syndrome, in relation to clinical pregnancy outcome.

Methods: Patients attending a recurrent miscarriage clinic were investigated and treated according to an established protocol. One hundred twenty-one consecutive patients achieving a potentially viable pregnancy (at least 24 completed weeks' gestation), including 60 primary antiphospholipid antibody syndrome-positive cases and 61 primary antiphospholipid antibody syndrome-negative cases were included.

Histological chorioamnionitis in relation to clinical presentation at 14-40 weeks of gestation.

This study examines the prevalence of histological inflammation of the fetal membranes according to gestational age and mode of clinical presentation in a series of 179 consecutive placentas evaluated in a single centre. The frequency of histological inflammation between clinical groups was compared and relation between the prevalence of inflammation and gestational age examined using regression analysis. One hundred and seventy-nine placentas were examined.

The epidemiological and control implications of HIV transmission probabilities within partnerships.

Background: The spread of HIV is in part determined by the probability of transmission within a sexual partnership.

Goal: The goal of the study was to examine the relationship between the per-partnership and per-act transmission probability and explore how different assumptions influence the measurement of cofactors and interventions.

Study Design: We defined the mathematical relationship between the transmission probability of HIV per sex act and per partnership for the proposed biologic mechanisms.

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.

The relationship between motion analysis and surgical technical assessments.

Background: Recent attempts to gain a more objective measure of surgical technical skill include the use of structured checklists and motion analysis of surgeons' hand movements. We aim to show whether a correlation exists between these two methods of assessment.

Methods: Fifty subjects were recruited from four experience groups in general surgery, ranging from basic surgical trainees to consultants and were assessed performing a standardized laboratory-based task.