Social, behavioral, and metabolic determinants of plasma viscosity in the Whitehall II Study.

Purpose: To examine the social, biological, and metabolic associations of plasma viscosity in a large epidemiological study.

Methods: Plasma viscosity was measured from 4548 men and 1837 women that took part in the fifth phase of the Whitehall II Study (1997-1999). Employment grade was used as a measure of social position.

Flow cytometric characterisation of cells of differing densities isolated from human term placentae and enrichment of villous trophoblast cells.

Cells were isolated from human term placentae by trypsinisation of fragments of chorionic villi and fractionation of cells on a Percoll density gradient into six layers. A panel of 10 monoclonal antibodies to antigens on or in trophoblast cells (placental alkaline phosphatase (PLAP), cytokeratin-7, beta-human chorionic gonadotrophin (beta-hCG), human leucocyte antigen-G (HLA-G)), leucocytes (CD45), monocytes, macrophages, dendritic cells, B cells (HLA class II), mesenchyme cells (vimentin), fibroblasts (fibroblast antigen) and nucleated cells excluding villous trophoblast (HLA class I, CD9) was used to characterise the cells by flow cytometry. For staining intracellular antigens (cytokeratin, vimentin, beta-hCG) the cells were first fixed and permeabilised.

The molecular basis of familial hypercholesterolaemia in Turkish patients.

Familial hypercholesterolaemia (FH) is an autosomal dominant disorder of lipoprotein metabolism. In the majority of patients FH is caused by mutations in the gene for the low-density lipoprotein receptor (LDLR), and to date more than 700 mutations have been reported worldwide. In this study, 36 paediatric patients with a clinical diagnosis of FH (20 homozygous and 16 heterozygotes) were screened for mutations in the LDLR gene.

Pediatric lung disease: from proteinases to pulmonary fibrosis.

One distinctive outcome of interstitial lung diseases in childhood is the abnormal accumulation of pulmonary extracellular matrix. The clinical consequence of such excessive connective tissue accumulation is known as pulmonary fibrosis. While numerous aspects of its pathogenesis have become familiar, many key events involved in its inception and progression still remain unclear.

Clinical grand round: a rapidly progressive pyramidal and extrapyramidal syndrome with a supranuclear gaze palsy.

The case history of a patient with a rapidly progressive spastic tetraparesis, pseudobulbar palsy, supranuclear gaze palsy, and extrapyramidal signs is presented. The patient died 17 months after symptom onset, and the differential diagnosis and pathological findings are reviewed.

Genetic linkage analysis supports the presence of two susceptibility loci for alcoholism and heavy drinking on chromosome 1p22.1-11.2 and 1q21.3-24.2.

Background: In order to confirm a previous finding of linkage to alcoholism on chromosome 1 we have carried out a genetic linkage study.

Methods: DNA from eighteen families, densely affected by alcoholism, was used to genotype a set of polymorphic microsatellite markers at loci approximately 10 centimorgans apart spanning the short arm and part of the long arm of chromosome 1. Linkage analyses were performed using the classical lod score and a model-free method.

Health risk appraisal for older people in general practice using an expert system: a pilot study.

The prevention of disability in later life is a major challenge facing industrialised societies. Primary care practitioners are well positioned to maintain and promote health in older people, but the British experience of population-wide preventive interventions has been disappointing. Health risk appraisal (HRA), an emergent information-technology-based approach from the USA, has the potential for fulfilling some of the objectives of the National Service Framework for Older People.

Pathophysiology of histological changes in early pregnancy loss.

An early pregnancy loss (EPL) or first-trimester miscarriage is the most common complication of human reproduction, with an incidence ranging between 50 and 70% of all conceptions. Two-thirds of EPL cases present with a thinner and fragmented trophoblastic shell, and reduced cytotrophoblast invasion of the tips of the spiral arteries. This leads to incomplete plugging during early pregnancy, and premature onset of the maternal circulation throughout the placenta.

Factor Xa stimulates fibroblast procollagen production, proliferation, and calcium signaling via PAR1 activation.

Fibroblast proliferation and procollagen production are central features of tissue repair and fibrosis. In addition to its role in blood clotting, the coagulation cascade proteinase thrombin can contribute to tissue repair by stimulating fibroblasts via proteolytic activation of proteinase-activated receptor-1 (PAR1). During hemostasis, the coagulation cascade proteinase factor X is converted into factor Xa.

PI3-kinase/Akt is constitutively active in primary acute myeloid leukaemia cells and regulates survival and chemoresistance via NF-kappaB, Mapkinase and p53 pathways.

The phosphoinositide 3-kinase (PI3-kinase) signalling pathway plays a key role in the regulation of cell survival and proliferation. We show that the PI3-kinase/Akt pathway is constitutively active in primary acute myeloid leukaemia (AML) cells and that blockade by the selective inhibitor LY294002 reduces survival of the total blast population (mean 52%). The ERK/MAPK module is also constitutively active and treatment with the MAPKK inhibitor U0126 reduces cell survival by 22%.

Comparison of image analysis software packages in the assessment of adhesion of microorganisms to mucosal epithelium using confocal laser scanning microscopy.

We have compared current image analysis software packages in order to find the most useful one for assessing microbial adhesion and inhibition of adhesion to tissue sections. We have used organisms of different sizes, the bacterium Helicobacter pylori and the yeast Candida albicans. Adhesion of FITC-labelled H.

The D allele of the ACE I/D common gene variant is associated with Type 2 diabetes mellitus in Caucasian subjects.

The deletion D allele of the angiotensin-I converting enzyme (ACE) I/D gene variant is associated with higher ACE activity in Caucasians and previous studies in non-Caucasian samples have suggested an association between the D allele and type 2 diabetes (Type 2DM). The aim of this study was to compare the genotype distribution between Caucasian subjects with Type 2DM and non-diabetic Caucasian men. Genotype distribution was compared between 574 Caucasian subjects with Type 2DM, recruited from the UCL Diabetes and Cardiovascular Disease Study and 2413 non-diabetic Caucasian men, recruited from the second Northwick Park Heart Study.

Risk factors for cardiac autonomic neuropathy in type 1 diabetes mellitus.

Aims/hypothesis: Cardiac autonomic neuropathy (CAN) is associated with increased morbidity and mortality in type 1 diabetes. Apart from glycaemic control, risk factors for CAN have not been extensively studied.

Methods: As part of the EURODIAB Prospective Complications Study, CAN--defined as either a loss of heart rate variability or postural hypotension on standing--was assessed at baseline and follow-up (7.

Bilateral peripheral T-cell lymphoma of the fallopian tubes.

Background: Lymphoma of the female genital tract is rare, and usually involves the ovaries or the uterus. Most cases of fallopian tube lymphoma reflect disease arising in the ovaries. All previously reported cases of primary lymphoma of the fallopian tube were of B cell lineage.

Asthma exacerbations in children immediately following stressful life events: a Cox's hierarchical regression.

Background: A recent prospective study of children with asthma employing a within subject, over time analysis using dynamic logistic regression showed that severely negative life events significantly increased the risk of an acute exacerbation during the subsequent 6 week period. The timing of the maximum risk depended on the degree of chronic psychosocial stress also present. A hierarchical Cox regression analysis was undertaken to examine whether there were any immediate effects of negative life events in children without a background of high chronic stress.

Polyol concentrations in the fluid compartments of the human conceptus during the first trimester of pregnancy: maintenance of redox potential in a low oxygen environment.

Polyols are sugar alcohols formed by the reduction of aldoses and ketoses. Production is favored under conditions of low oxygenation, when it may provide an alternative means to production of lactate for regulating the oxidation-reduction balance of pyridine nucleotides. Polyols also act as important organic osmolytes and as precursors of cell membrane components.

Effect of Interleukin-6 promoter polymorphisms in survivors of myocardial infarction and matched controls in the North and South of Europe. The HIFMECH Study.

Elevated plasma IL-6 levels have been implicated in the pathogenesis of coronary heart disease. We have investigated the association of two polymorphisms in the promoter of IL-6 (-572G>C and -174G>C) with levels of inflammatory markers and risk of myocardial infarction (MI) in a European study of MI survivors and age-matched controls from two high-risk centres in the North of Europe, and two low risk centres in the South. IL-6 and CRP levels were similar in controls in both regions, but were higher in cases.

A combination of two common thrombomodulin gene variants (-1208-1209TTdelTT and A455V) influence risk of coronary heart disease: a prospective study in men.

In a previous case control study of myocardial infarction (MI), we identified risk associated with the combination of two variants in the thrombomodulin (TM) gene (-1208-1209TTdelTT and A455V) and an interaction with increased body mass index (BMI). The rare alleles at these two common variant sites in the TM gene occur in most individuals on the same allele (V/delTT) and are in strong linkage disequilibrium (Delta=0.67, P <0.

Cytomegalovirus following stem cell transplantation: from pharmacologic to immunologic therapy.

Human cytomegalovirus is a large DNA virus that is well-equipped to evade both innate and adaptive host immune responses and to establish lifelong latency. It is a major opportunistic pathogen in immunocompromised hosts. Following allogeneic transplantation, immune responses are often inadequate to inhibit viral reactivation, resulting in progressive tissue damage, manifesting as overt human cytomegalovirus disease that usually presents as pneumonitis, colitis or hepatitis.

Outcome of HIV-associated tuberculosis in the era of highly active antiretroviral therapy.

Background: The benefit of highly active antiretroviral therapy (HAART) in the treatment of patients coinfected with tuberculosis (TB) and human immunodeficiency virus (HIV) is unclear because of concerns about treatment-related complications.

Methods: We compared outcomes in patients starting TB treatment during the pre-HAART era (before 1996; n=36) with those in patients starting treatment during the HAART era (during or after 1996; n=60).

Results: During a median of 3.

Pathogenesis of intracranial hypertension in acute liver failure: inflammation, ammonia and cerebral blood flow.

Background/aims: The study aims were to determine the role of inflammation in the pathogenesis of increased intracranial pressure (ICP) in patients with acute liver failure (ALF) and its interplay with cerebral blood flow (CBF) and ammonia.

Methods: Twenty-one patients with ALF were studied from the time they were ventilated for grade 4 encephalopathy until receiving specific treatment for increased ICP. Depending upon the ICP, the patients were divided into two groups; those that required specific treatment (ICP>20 mmHg, group 1: n=8, ICP: 32 (28-54) mmHg); and those that did not (ICP< or =20 mmHg, group 2: n=13, ICP: 15 (10-20) mmHg).

Analysis of glenoid fixation for a reversed anatomy fixed-fulcrum shoulder replacement.

The restoration of pain-free stable function in gleno-humeral arthritic cases in various situations such as rotator cuff deficiency, old trauma and failed total shoulder arthroplasty is a challenging clinical dilemma. The Bayley-Walker shoulder has been designed specifically for very difficult cases where surface replacement devices do not provide sufficient stability. This device is a fixed-fulcrum reverse anatomy implant where the centre of rotation is placed medially and distally with respect to the normal shoulder, to increase the lever arm of the abductor muscles.

Photodynamic therapy for pancreatic carcinoma: experimental and clinical studies.

Pancreatic carcinoma is the sixth leading cause of cancer-related mortality in the United Kingdom, with an overall 5-year survival of less than 5%. Attempted curative surgery is possible in less than 20% of cases and is associated with a 5-year survival of just 10-20%. Palliative radio-chemotherapy improves symptoms of pancreatic cancer but rarely extends median survival beyond 12 months.