Multilineage mobilization of peripheral blood progenitor cells in humans following administration of PEG-rHuMGDF

The most important physiological regulator of megakaryocytopoiesis is the ligand for the c-mpl receptor (thrombopoietin/megakaryocyte growth and development factor, MGDF). We examined the effect of pegylated-recombinant human MGDF (PEG-rHuMGDF): patients received PEG-rHuMGDF at doses of 0.03, 0.1, 0.3 or 1.0 μg/kg/d or placebo for 10 d maximum in a double-blinded randomized study. There was a dose-dependent elevation in circulating platelet counts but no alteration in erythrocyte or total leucocyte counts. The number of bone marrow megakaryocytes was increased approximately 2-fold. The frequency of bone marrow progenitor cells was not altered. In contrast, both to the bone marrow results and to published pre-clinical data, there was a dose-dependent mobilization into the blood of progenitor cells of multiple cell lineages. Increased levels of Meg-CFC (maximum increase 30-fold), day 7 and day 14 GM-CFC and BFU-E were demonstrated at doses of 0.3 and 1.0 μg/kg/d PEG-rHuMGDF. At 0.1 μg/kg/d, mobilization of Meg-CFC alone occurred in two-thirds of patients. Maximum blood levels of progenitor cells occurred at day 12. Thus, administration of PEG-rHuMGDF to humans resulted in mobilization of progenitor cells of multiple lineages despite its 'lineage-specific' activity on mature cell development.     

Anti-tissue transglutaminase antibodies in the follow-up of adult coeliac disease

Background  The detection of auto antibodies directed against tissue transglutaminase (anti-tTG antibodies) has a well-established role in the diagnosis of coeliac disease, but the value of these antibodies in long-term follow-up is controversial.
Aims  To determine if serial anti-tTG antibody measurements could confirm adherence to a gluten-free diet (GFD) and identify patients at risk of disease complications.
Methods  In a 54-month cohort follow-up study, 182 adult patients were assessed. Data recorded included self-assessment of GFD adherence; anti-tTG antibody concentration and serum ferritin, vitamin B12 and folate. Where available, bone mineral density (BMD) and duodenal histology data were retrieved.
Results  Persistently elevated anti-tTG antibody levels were significantly associated with abnormal duodenal histology ( P  < 0.001), low ferritin ( P  < 0.01) and poor adherence to the GFD ( P  < 0.001). The specificity was >85% while the sensitivity was 39–60%. Anti-tTG antibody concentrations fell rapidly following successful initiation of a GFD, and maintenance of normalization identified those who continued to be adherent to the diet.
Conclusions  This study supports a strategy of using anti-tTG antibody concentrations to monitor newly diagnosed and established patients with coeliac disease, and to target dietetic intervention to reduce the risk of complication.     

Health education poster: a teaching model for clinical medical students

Summary. The teaching of health education or health promotion to medical students is often difficult because they have little experience on which to base their learning. They have limited clinical knowledge and in particular their awareness of the value of and the opportunities for health promotion in general practice is limited. The problem-oriented teaching method described here attempts to make the subject interesting and relevant by asking students, while in their practice attachments, to identify areas of need for health promotion or health education and then to prepare a poster, with supportive background and research, to satisfy that need for display in their given practice.     

Abdominal Aortic Aneurysm with Perianeurysmal Fibrosis: Demonstration of Ureteric Obstruction by Computerized Tomography

When perianeurysmal fibrosis occurs in association with an abdominal aortic aneurysm it may produce ureteric obstruction and renal function impairment. Such a case is described and the pre-operative radiological evaluation of this condition is discussed. The role of computerized tomography is emphasized in its ability to provide accurate anatomical detail regarding the aneurysm, the extent of surrounding fibrosis and ureteric involvement within it.     

Insulin receptor substrate-1 gene polymorphism and cardiovascular risk in non-insulin dependent diabetes mellitus and patients undergoing coronary angiography

Clustering of risk factors for cardiovascular disease related to insulin resistance may account for the increased incidence of vascular disease in these conditions and in non-diabetic subjects. To investigate the relationship between a coding polymorphism in the insulin receptor substrate-1 gene and the presence of cardiovascular risk factors, 209 patients with NIDDM and 452 subjects investigated for coronary artery disease (CAD) were studied. In the NIDDM subjects 22 (10.5%) were heterozygous at codon 972 for a polymorphism which codes for a glycine to arginine substitution and 187 (89.5%) were homozygous for the wild type. Patients with the mutation had lower levels of cholesterol compared with wild type (mean, 95% confidence intervals), 5.3 (4.9–5.8) vs 6.0 (5.9–6.2) mmol/l, respectively (P = 0.002), triglyceride 1.7 (1.4–2.1) vs 2.2 (2.0–2.4) mmol/l (P = 0.051), factor VII:C activity 109.5 (85.5–133.5) vs 133.5 (127–140)% (P = 0.057) and PAI-1 antigen, 16.0 (10.5–24.3) vs 22.2 (20.0–24.6) ng/ml (P = 0.054). There were no differences in body mass index, indices of glycaemic control, fasting insulin or the prevalence of hypertension. In patients with CAD, 55 (12.7%) were carriers of the mutation (including three homozygotes) (NIDDM vs CAD, NS). Although similar trends in cholesterol, factor VII, PAI-1 antigen and triglyceride existed between carriers of the mutation and the wild type, none reached statistical significance. The results indicate that the IRS-1 gene is not implicated in the pathogenesis of NIDDM or CAD.