Twenty-two molecular diagnostic laboratories from 14 countries participated in a consortium study to estimate the impact of Factor VIII gene inversions in severe hemophilia A. A total of 2,093 patients with severe hemophilia A were studied; of those, 740 (35%) had a type 1 (distal) factor VIII inversion, and 140 (7%) showed a type 2 (proximal) inversion. In 25 cases, the molecular analysis showed additional abnormal or polymorphic patterns. Ninety-eight percent of 532 mothers of patients with inversions were carriers of the abnormal factor VIII gene; when only mothers of nonfamilial cases were studied, 9 de novo inversions in maternal germ cells were observed among 225 cases (approximately 1 de novo maternal origin of the inversion in 25 mothers of sporadic cases). When the maternal grandparental origin was examined, the inversions occurred de novo in male germ cells in 69 cases and female germ cells in 1 case. The presence of factor VIII inversions is not a major predisposing factor for the development of factor VIII inhibitors; however, slightly more patients with severe hemophilia A and factor VIII inversions develop inhibitors (130 of 642 [20%]) than patients with severe hemophilia A without inversions (131 of 821 [16%]).

Plasma lipid peroxide concentrations were measured in 100 patients with occlusive arterial disease proved angiographically (50 patients with ischaemic heart disease, 50 with peripheral arterial disease) and compared with values in 75 control patients with no clinical evidence of atherosclerosis. Lipid peroxide concentrations were significantly higher in patients both with ischaemic heart disease (median 4-37 iimol/l (interquartile range 3-85-5-75 [tmol/l); p<0-001) and with peripheral arterial disease (median 4-37 [smoltl (3-88-5-21 [mol/l); p<0001) than in controls (median 3-65 [tmol/l (interquartile range 3-29-3-89 [mol/l)).Overall there was a significant but weak correlation between plasma lipid peroxide and plasma triglyceride concentrations (r,=0-25; p<0-001) but not between plasma lipid peroxide and plasma total cholesterol concentrations. Furthermore, hypertension, obesity, diabetes, smoking, positive family history, and intake of fi blockers and thiazide diuretics were not associated with significant differences in lipid peroxide values.This study provides clinical support to experimental data indicating that peroxidised lipids may be important in atherogenesis and its complications and also suggests that peroxidised lipids may provide an index of the severity of atherosclerosis.Thrombosis Research

The incidence of infection after needle biopsy of the prostate by different techniques was compared in 45 patients. Aerobic and anaerobic culture was made of the biopsy needle, prostate, urine and blood. In addition, endotoxin assays were determined by a new chromogenic method using Limulus lysate. All of the patients undergoing transrectal biopsy were found to have a bacteraemia; 27% were symptomatic and 87% had a post-operative urinary tract infection. A double-blind controlled trial using cefamandole with the premedication showed a significant reduction in the incidence of bacteraemia to 53% and the prevention of a urinary tract infection. Following transperineal biopsy, although the incidence of bacteraemia was 40% and urinary tract infection 27%, none of these patients was symptomatic and the organisms causing the bacteraemia were predominantly skin contaminants. The endotoxin assays showed differences between the groups with higher endotoxin values in the unprotected transrectal group.

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We investigated whether chronic fatigue syndrome (CFS) patients have physical and/or cardiovascular de-conditioning, in 273 CFS patients and 72 healthy controls. We used laboratory tests to assess haematological, biochemical, endocrinological and immunological systems. The cardiovascular system was assessed by echocardiography and carotid echography. Body composition was determined by dual energy X-ray absorptiometry (DEXA). CFS patients had smaller left ventricular end systolic (p < 0.001) and diastolic (p = 0.008) dimensions but thinner posterior walls (p = 0.02) than corresponding values in healthy controls. Left ventricular mass was also reduced in CFS patients (p = 0.006). Both maximum (p < 0.001) and minimum (p < 0.008) diameter of the carotid artery were smaller in CFS patients. The laboratory screening tests showed significant differences in serum albumin (p = 0.05), phosphate (p = 0.02), HDL-cholesterol (p = 0.03), HDL:total cholesterol ratio (p = 0.01), triglycerides (p = 0.02), neutrophils (p = 0.01) and thyroid-stimulating hormone (p = 0.04) between CFS patients and controls. Male CFS patients had an increased percentage of fat mass compared with healthy male subjects (p = 0.02). This large group of CFS patients had evidence of physical and cardiovascular de-conditioning, suggesting that in these patients a graded exercise programme could lead to physical reconditioning and could increase their ability to perform physical activities.