The effect of anti-lymphocyte serum on subpopulations of blood and tissue leucocytes: possible supplementary mechanisms for suppression of rejection and the development of opportunistic infections.

Xenogeneic anti-lymphocyte serum (ALS) remains a major reagent for immunosuppression in clinical practice, but mechanisms of action and risks of opportunistic infection have not been considered in the context of innate immunity and its role in immune responsiveness. Rabbit anti rat ALS was administered intraperitoneally. Blood was taken for flow cytometry to establish absolute counts of leucocyte subsets.

Mutation, selection, and evolution of the Crohn disease susceptibility gene CARD15.

Three common mutations in the CARD15 (NOD2) gene are known to be associated with susceptibility to Crohn disease (CD), and genetic data suggest a gene dosage model with an increased risk of 2-4-fold in heterozygotes and 20-40-fold in homozygotes. However, the discovery of numerous rare variants of CARD15 indicates that some heterozygotes for the common mutations have a rare mutation on the other CARD15 allele, which would support a recessive model for CD. We addressed this issue by screening CARD15 for mutations in 100 CD patients who were heterozygous for one of the three common mutations.

Assessment of venous thromboembolism risk and the benefits of thromboprophylaxis in medical patients.

Hospitalized patients with acute medical conditions are at significant risk of venous thromboembolism (VTE): approximately 10-30% of general medical patients may develop deep-vein thrombosis or pulmonary embolism, and the latter is a leading contributor to deaths in hospital. Despite consensus-group recommendations that at-risk medical patients should receive thromboprophylaxis, there is currently no consensus as to which patients are at risk, and many patients may not receive appropriate thromboprophylaxis. This paper reviews evidence for the risk of VTE associated with different medical conditions and risk factors, and presents a risk-assessment model for risk stratification in medical patients.

SNP selection for association studies: maximizing power across SNP choice and study size.

Selection of single nucleotide polymorphisms (SNPs) is a problem of primary importance in association studies and several approaches have been proposed. However, none provides a satisfying answer to the problem of how many SNPs should be selected, and how this should depend on the pattern of linkage disequilibrium (LD) in the region under consideration. Moreover, SNP selection is usually considered as independent from deciding the sample size of the study.

Effects of high-dose growth hormone on glucose and glycerol metabolism at rest and during exercise in endurance-trained athletes.

Context: Recombinant human-GH (r-hGH), in supraphysiological doses, is self-administered by athletes in the belief that it is performance enhancing.

Objective: The objective of this study was to determine whether r-hGH alters whole-body glucose and glycerol metabolism in endurance-trained athletes at rest and during and after exercise.

Design: This was a 4-wk double-blind placebo-controlled trial.

Single pulse electrical stimulation for identification of structural abnormalities and prediction of seizure outcome after epilepsy surgery: a prospective study.

Background: Abnormal late responses to single pulse electrical stimulation (SPES) in patients with intracranial recordings can identify epileptogenic cortex. We aimed to investigate the presence of neuropathological abnormalities in abnormal SPES areas and to establish if removal of these areas improved postsurgical seizure control.

Methods: We studied abnormal responses to SPES during chronic intracranial recordings in 40 consecutive patients who were thereafter operated on because of refractory epilepsy and had a follow-up period of at least 12 months.

Transient bullous dermolysis of the newborn in three generations.

Transient bullous dermolysis of the newborn (TBDN) is a rare form of dystrophic epidermolysis bullosa (DEB) that presents with neonatal skin blistering but which usually improves markedly during early life or even remits completely. Skin biopsies reveal abnormal intraepidermal accumulation of type VII collagen which results in poorly constructed anchoring fibrils and a sublamina densa plane of blister formation. The reason for the spontaneous clinical improvement is not known, but there is a gradual recovery in type VII collagen secretion from basal keratinocytes to the dermal-epidermal junction, with subsequent improvement or correction of anchoring fibril morphology.

Reference ranges for 51Cr-EDTA measurements of glomerular filtration rate in children.

Background: 51Cr-Ethylenediaminetetraacetic acid (51Cr-EDTA) is widely used to measure the glomerular filtration rate (GFR) in children and adults.

Aim: To produce paediatric reference data for use with the British Nuclear Medicine Society (BNMS) GFR guidelines.

Methods: This was a retrospective study of children and adolescents, aged 0-17 years, undergoing combined 99mTc-dimercaptosuccinic acid (99mTc-DMSA) scintigraphy and GFR examination.

Assessment of subtle changes in glucocorticoid negative feedback using prednisolone: comparison of salivary free cortisol and urinary cortisol metabolites as endpoints.

Background: Prednisolone is better than dexamethasone to probe subtle changes in HPA axis sensitivity but cortisol assay as an endpoint risks cross-reaction with prednisolone. We compared capillary gas chromatography, which distinguishes urinary cortisol and prednisolone metabolites, and salivary cortisol immunoassay.

Methods: Twenty adult volunteers (10 m) collected urine for consecutive 3 h periods and saliva at 3 h intervals from 2100 for 24 h, took prednisolone (5 mg) at midnight and continued collecting until 2100.

Characterization of matrix metalloproteinases in denervated muscle.

In a nerve crush model of denervation, we examined muscle matrix metalloproteinase (MMP) expression, localization and activity. In normal muscle, MMP mRNA levels were low, and immunohistochemically MMPs were distributed around the muscle fibre with MMPs-3, -7 and -9 also staining at the neuromuscular junction. Seven days after nerve crush, muscle MMP immunoreactivity, especially MMP-12 and MMP-14, became irregularly distributed.

Differential changes in brain glucose metabolism during hypoglycaemia accompany loss of hypoglycaemia awareness in men with type 1 diabetes mellitus. An [11C]-3-O-methyl-D-glucose PET study.

Aims/hypothesis: Hypoglycaemia unawareness in type 1 diabetes increases the risk of severe hypoglycaemia and impairs quality of life for people with diabetes. To explore the central mechanisms of hypoglycaemia awareness, we used [11C]-3-O-methyl-D-glucose (CMG) positron emission tomography (PET) to measure changes in global and regional brain glucose metabolism between euglycaemia and hypoglycaemia in aware and unaware diabetic subjects.

Materials And Methods: Twelve men with type 1 diabetes, of whom six were characterised as aware and six as unaware of hypoglycaemia, underwent two CMG-PET brain scans while plasma glucose was controlled by insulin and glucose infusion either at euglycaemia (5 mmol/l) or at hypoglycaemia (2.

Non-invasive assessment of respiratory muscle strength in patients with previous poliomyelitis.

Unlabelled: In patients with poliomyelitis, respiratory failure requiring ventilatory support may occur during the acute illness. Some patients continue to require long-term nocturnal ventilatory support; others are weaned but subsequently require support because of a late deterioration in ventilatory function.

Objectives: To assess the sensitivity of sniff nasal inspiratory pressure (SNIP) to post-poliomyelitis respiratory muscle weakness and to assess the relationship between the respiratory muscle strength and the need for ventilatory support in patients with previous poliomyelitis (post-polio patients).

Humoral detection of leukaemia-associated antigens in presentation acute myeloid leukaemia.

The serological analysis of recombinant cDNA expression libraries (SEREX) technique was used to immunoscreen a testes cDNA expression library with sera from newly diagnosed acute myeloid leukaemia (AML) patients. We used a testis cDNA library to aid our identification of cancer-testis (CT) antigens. We identified 44 antigens which we further immunoscreened with sera from AML, chronic myeloid leukaemia (CML), and normal donors.

Development of a real-time probe-based PCR assay for the diagnosis of Pneumocystis pneumonia.

This paper describes the development of a rapid probe-based real-time polymerase chain reaction assay (PCR) for the diagnosis of Pneumocystis pneumonia. To develop the PCR, primers and fluorescent resonance energy transfer probes were designed after sequencing products obtained using previously published primers. This gave results that were concordant with conventional cytological staining techniques, but were available within 2 h instead of greater than 24 h.

Cognitive behaviour therapy in addition to antispasmodic treatment for irritable bowel syndrome in primary care: randomised controlled trial.

Objective: To assess the efficacy of cognitive behaviour therapy delivered in primary care for treating irritable bowel syndrome.

Design: Randomised controlled trial.

Setting: 10 general practices in London.

Single-pulse electrical stimulation identifies epileptogenic frontal cortex in the human brain.

Objective: To assess the value of single-pulse electrical stimulation (SPES) to identify frontal epileptogenic cortex during presurgical assessment.

Methods: SPES (1-millisecond pulses, 4 to 8 mA, 0.1 Hz) has been used during chronic recordings in 30 patients with intracranial electrodes in the frontal lobes.

New antithrombotics in the prevention of thromboembolic disease.

New anticoagulants are under development to improve on current ones that, although effective, have limitations in efficacy, safety and convenience. We have reviewed the use of these agents as thromboprophylactic drugs. These new agents have more specific modes of action and can be divided into three groups.

A 13-year follow-up of patients with breast cancer presenting to a District General Hospital breast unit in southeast England.

The purpose of this clinical cohort study was to examine long-term survival in groups of screen-detected and symptomatic breast cancer patients attending a specialist breast unit, and to determine the factors affecting this survival. A total of 3239 breast cancer cases (1252 screen-detected and 1987 symptomatic) diagnosed between 1989 and 2002 were followed up until the end of 2002, and breast cancer-specific survival was examined in the screened and symptomatic groups, in relation to patient age, tumour size, nodal status and histological grade. Long-term survival in this clinical cohort was high.

Systematic review of specialist palliative day-care for adults with cancer.

Goal Of Work: To inform future practice, research and policy in specialist palliative day-care by systematically reviewing the evidence for how the structure and process of this form of care relate to outcomes for adults with cancer.

Patients And Methods: Medical, nursing and social science computerized databases were searched up until December 2003 for studies of palliative day-care reporting information on service structure, care processes or outcomes including symptom control, quality of life, social and psychological support, and patient and relative satisfaction with care. Qualitative and quantitative studies were assessed for methodological quality and graded, and the findings synthesized into the review.

Exploration of peptide motifs for potent non-viral gene delivery highly selective for dividing cells.

Background: The immunogenicity of viral DNA vectors is an important problem for gene therapy. The use of peptide motifs for gene delivery would largely overcome this problem, and provide a simple, safe and powerful approach for non-viral gene therapy.

Methods: We explored the functional properties of two motifs: the (Lys)(16) motif (for binding and condensing DNA, and probably also nuclear translocation of plasmids) and the fusogenic peptide motif of influenza virus (for acid-dependent endocytic escape of peptide/DNA particles).

GPs' attitudes to discussing prognosis in severe COPD: an Auckland (NZ) to London (UK) comparison.

Background: A palliative care approach, as used routinely in cancer, is also valid for incurable chronic illnesses such as chronic obstructive airways disease (COPD). However, a London study recently reported that general practitioners (GPs), who provide most end-stage care for COPD patients, do not routinely discuss prognosis with these patients.

Objective: To compare the views of GPs in Auckland, New Zealand (NZ) and London, United Kingdom (UK) on discussions of prognosis in severe COPD.

Fracture prediction by bone density measurements at sites other than the fracture site: the contribution of BMD correlation.

It is widely believed that the most reliable BMD measurement for predicting fracture risk at any given skeletal site is one made at the fracture site itself. This study examines the hypothesis that the ability of BMD measurements at other distant sites in the skeleton remote from the fracture site to predict fracture risk is due to their correlation with the BMD measurements at the fracture site. We refer to this assumption as the correlation hypothesis.