Do infectious diseases drive MHC diversity?

The primary function of the major histocompatibility complex (MHC) is to allow the immune system to identify infectious pathogens and eliminate them. Infectious diseases are now thought to be the main selection force that drives and maintains the extraordinary diversity of the MHC.

Recurrent miscarriage--an aspirin a day?

Recurrent miscarriage and later pregnancy complications are in some cases associated with placental thrombosis and infarction. The aim of this study was to assess the value of low dose aspirin (75 mg daily) in improving the subsequent livebirth rate amongst women with either unexplained recurrent early miscarriage (<13 weeks gestation; n = 805) or unexplained late pregnancy loss (n = 250). Amongst women with recurrent early miscarriages, there was no significant difference in the livebirth rate between those who took aspirin (251/367; 68.

Reproducibility of computer-quantified carotid plaque echogenicity: can we overcome the subjectivity?

Background And Purpose: We sought to assess the reproducibility, interobserver variability, and application to clinical studies of a new method for the quantitative assessment of carotid plaque echogenicity.

Methods: Carotid plaques were scanned with the use of ultrasound, and their images were stored in a computer. They were normalized by assigning certain gray values to blood and adventitia, and the gray scale median (GSM) was used to quantify their echogenicity.

Obstetric management of antiphospholipid syndrome.

The obstetric management of women with antiphospholipid (aPL) syndrome remains controversial. Despite recent advances, the controversies have been fueled by our limited understanding of the multi-factorial causes of aPL-associated pregnancy loss and the lack of data from randomized studies. We have escaped from the narrow confines of the concept of aPL pregnancy loss being purely thrombotic in aetiology and attention is now focused on the adverse effects of aPL on embryonic implantation and trophoblast invasion.

Increased excretion of urinary glycosaminoglycans in meningococcal septicemia and their relationship to proteinuria.

Objectives: Meningococcal septic shock is a devastating illness associated with an increase in vascular permeability leading to hypovolemia and accumulation of plasma proteins and fluid in tissues. The capillary leak syndrome is often associated with widespread thrombosis in the skin, limbs, and digits. We postulated that the increase in vascular permeability and the intravascular thrombosis might be caused by an inflammation-induced loss of endothelial and basement membrane glycosaminoglycans (GAGs), which play a role in the permeability and thromboresistant properties of the microvasculature.

A myocardial cytotoxic process is involved in the cardiac dysfunction of meningococcal septic shock.

Objective: Myocardial dysfunction is a characteristic component of meningococcal septic shock and contributes to the persisting high mortality from the disease. Specific treatment of the myocardial failure has been hampered by the lack of understanding of its pathophysiology. We were interested to determine whether myocardial cell death was occurring in the presence of meningococcal septicemia and whether it correlated with the degree of left ventricular dysfunction and disease severity.

Species-barrier-independent prion replication in apparently resistant species.

Transmission of prions between mammalian species is thought to be limited by a "species barrier," which depends on differences in the primary structure of prion proteins in the infecting inoculum and the host. Here we demonstrate that a strain of hamster prions thought to be nonpathogenic for conventional mice leads to prion replication to high levels in such mice but without causing clinical disease. Prions pathogenic in both mice and hamsters are produced.

Quantification and characterisation of arteries in retinal images.

A computerised system is presented for the automatic quantification of blood vessel topography in retinal images. This system utilises digital image processing techniques to provide more reliable and comprehensive information for the retinal vascular network. It applies strategies and algorithms for measuring vascular trees and includes methods for locating the centre of a bifurcation, detecting vessel branches, estimating vessel diameter, and calculating angular geometry at a bifurcation.

Disseminated intravascular coagulation and purpura fulminans secondary to infection.

Infection is one of the commonest causes of disseminated intravascular coagulation (DIC). DIC is a complex disorder that results from an imbalance of the pro- and anticoagulant regulatory pathways. This chapter will explain the cellular and molecular basis of the disorder and consider the rationale behind current and experimental treatment strategies.

Examination of the human prion protein-like gene doppel for genetic susceptibility to sporadic and variant Creutzfeldt-Jakob disease.

A novel human gene named Doppel (DPL) that has homology to the prion protein gene (PRNP) has recently been identified on chromosome 20p. By automated sequencing we have found a common (M174T, 48%) and an uncommon coding polymorphism. The polymorphic frequency of the M174T allele was examined in cases of variant and sporadic Creutzfeldt-Jakob Disease and compared with the frequency in the normal UK population.

Prevalence of hepatitis C among pregnant women attending an inner London obstetric department: uptake and acceptability of named antenatal testing.

Objective: To examine the value of universal antenatal screening for hepatitis C virus (HCV) infection among an inner London population, with regard to prevalence, uptake, and acceptability of testing, and identification of new cases.

Design: Serum analysis for antibodies against HCV in pregnant women following informed consent ("opt out" policy). Samples positive for HCV antibodies were tested for the presence of HCV RNA by polymerase chain reaction.

Hepatitis C virus infection: co-infection with HIV and HBV.

Hepatitis C shares common routes of infection with hepatitis B (HBV) and the human immunodeficiency virus (HIV). It is, therefore, not surprising to find that some patients with HCV are co-infected with either HIV and/or HBV. Until recently, the effects of HIV on HCV infection have not been investigated--sadly patients with HIV died long before their liver disease became problematic.

Therapeutic options for HCV--management of the infected individual.

Patients with chronic hepatitis C infection should be assessed by liver biopsy prior to consideration of anti-viral therapy. Patients with histologically mild disease should be observed at regular intervals and assessed with a repeat liver biopsy after an interval of 3-4 years. Those with severe disease should receive early treatment with interferon-alpha and ribavirin.

Single cell analysis of cytokine expression kinetics by human CD4+ T-cell clones during activation or tolerance induction.

Exposure to optimal peptide antigen concentrations induces human CD4+ T-cell clones to proliferate and secrete various cytokines. Higher (> 10-fold optimal) antigen concentrations cause long-term proliferative unresponsiveness, which can be reversed by exogenous interleukin-2 (IL-2). We call this condition 'tolerance'.

Ethnic and gender differences in electrocardiographic QT length and QT dispersion in hypertensive subjects.

Background: Prolonged QT intervals and/or increased QT dispersion (QTd) are associated with various pathological conditions and predict death in healthy individuals. Among hypertensives, QTd correlates with blood pressure (BP) and left ventricular mass index (LVMI) and QT intervals are prolonged in those with left ventricular hypertrophy (LVH). In normotensives, heart-rate corrected QT length (QTc) is longer in females than males, but QTd is greater in males than females.

Prospective pregnancy outcome in untreated recurrent miscarriers with thyroid autoantibodies.

The purpose of this study was to determine the prevalence of thyroid antibodies in women with recurrent miscarriage and to observe whether their presence was predictive of future pregnancy outcome. A total of 870 consecutive, non-pregnant women with a history of three or more pregnancy losses and normal parental karyotypes were investigated for the presence of thyroglobulin antibodies (TgAb) and for thyroid microsomal antibodies (TmAb). Thyroid antibodies were found in 162 (19%) women.

Superficial endometrial vascular fragility in Norplant users and in women with ovulatory dysfunctional uterine bleeding.

The aim of this study was to develop an objective test for superficial endometrial vascular fragility at hysteroscopy, and to apply this test to women using Norplant((R)) for contraception and to women with ovulatory dysfunctional uterine bleeding (DUB). A prospective observational study was carried out in 34 Norplant users and 20 women with menorrhagia due to ovulatory DUB. Superficial endometrial vascular fragility was assessed at hysteroscopy by observing the source and extent of frank and subepithelial bleeding during controlled collapse and redistension of the uterine cavity.

Efficacy of chest CT in a pediatric ICU: a prospective study.

Study Objectives: (1) To determine whether chest CT provides additional information compared with chest radiography regarding the nature of intrathoracic disease in critically ill children, (2) to determine whether such information alters clinical management, (3) to assess the role of a low-dose high-resolution CT (HRCT) protocol in pediatric ICU (PICU) patients.

Design: Prospective study.

Setting: Specialized PICU in a teaching hospital serving London and the south of England.