Treatment of early onset multiple sclerosis with subcutaneous interferon beta-1a

The authors studied the tolerability of subcutaneous interferon beta-1a (IFNbeta-1a) in 51 patients with early-onset multiple sclerosis. The most frequent systemic adverse effects were flu-like symptoms in 65%. Laboratory abnormalities included asymptomatic leukopenia (27%) and elevated hepatic transaminases (35%). Treatment with IFNbeta-1a was safe and well tolerated in the majority of children and adolescents.     

Occlusion of pseudoaneurysms using human or bovine thrombin using contrast-enhanced ultrasound guidance

Percutaneous thrombin occlusion of pseudoaneurysms complicating invasive coronary interventions has emerged as a useful therapeutic tool. To facilitate thrombin occlusion and make the procedure even more secure, preinjection of echo contrast medium during duplex ultrasound was tested in 132 patients. Complete and immediate occlusion of the pseudoaneurysm was achieved in 99.2% (131 of 132 patients). No complications related to the injection of thrombin were documented. Contrast-enhanced ultrasound-guided thrombin occlusion was a safe and effective therapeutic option. In aneurysms with complex morphology or multiple cavities, preinjection of contrast medium was helpful for documenting the flow pattern.     

Actin-related myopathy without any missense mutation in the ACTA1 gene

Actinopathies are defined by missense mutations in the ACTA1 gene coding for sarcomeric actin, of which some 70 families have, so far, been identified. Often, but not always, muscle fibers carry large patches of actin filaments. Many such patients also have nemaline myopathy, qualifying actinopathies as a subgroup of nemaline myopathies. This article concerns a then newborn, now 2 1/2-year-old boy, the first and single child of nonconsanguineous parents, who was born floppy, requiring immediate postnatal assisted ventilation. A quadriceps muscle biopsy revealed large patches of thin myofilaments reacting at light and electron microscopic levels with antibodies against actin but only a few sarcoplasmic rods and no intranuclear rods. DNA analysis of the patient's and both parents' blood did not reveal any missense mutation in the ACTA1 gene. Thus, this congenital myopathy can be caused by a new type of ACTA1 gene mutation, a new non-ACTA1 gene mutation, or no mutation at all, designating it as an actin-related myopathy, perhaps a new type of congenital myopathy and a new member of protein aggregate myopathies marked by aggregation of proteins within muscle fibers, among them desminopathies, alpha-beta crystallinopathies, other desmin-related myopathies (also termed myofibrillar myopathies), actinopathies and, now, actin-related myopathies.     

CSF characteristics in early-onset multiple sclerosis

The authors studied CSF characteristics in 136 patients with multiple sclerosis (MS) with a disease onset before age 16. In the initial diagnostic lumbar puncture, CSF-pleocytosis was observed in 66%, blood-CSF barrier dysfunction in 13%, and oligoclonal IgG in 92% of the early-onset MS (EOMS) patients. CSF oligoclonal IgG supports the early diagnosis of MS in childhood with a sensitivity similar to adult-onset MS.     

Effects of bone block position and orientation within the tibial tunnel for posterior cruciate ligament graft reconstructions: a cyclic loading study of bone-patellar tendon-bone allografts

BACKGROUND: Posterior laxity occurring after posterior cruciate ligament reconstruction with a tibial tunnel could be related to thinning and permanent elongation of the graft as it is cyclically loaded in vivo. HYPOTHESIS: The orientation and position of the bone block within the tibial tunnel will have a significant effect on thinning and elongation of the graft after cyclic loading. STUDY DESIGN: Controlled laboratory study. METHODS: In test series 1 (27 fresh-frozen graft pairs), all bone blocks were positioned flush with the posterior opening of the tibial tunnel; 1 graft was oriented with the bone block facing posteriorly, whereas its pair was tested with the bone block facing anteriorly. In test series 2 (20 graft pairs), all grafts were oriented with the bone block facing posteriorly; 1 graft had the bone block positioned flush with the posterior tunnel opening, whereas its pair was tested with the bone block recessed 1 cm from the posterior opening. RESULTS: In series 1, 3 of 27 grafts with posterior bone block orientations failed at the tunnel edge before 2000 cycles of testing could be completed; all specimens with anterior bone block placements survived the testing intact. In series 2, 3 of 20 grafts with recessed bone blocks failed at the tunnel edge, whereas all those with flush bone blocks survived. CONCLUSIONS: The best position for the bone block of a bone-patellar tendon-bone graft was flush with the posterior tunnel opening with the bone block facing anteriorly in the tibial tunnel.     

Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial

Context  The worldwide explosive increase in type 2 diabetes mellitus and its cardiovascular morbidity are becoming major health concerns. Objective  To evaluate the effect of decreasing postprandial hyperglycemia with acarbose, an -glucosidase inhibitor, on the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance (IGT). Design, Setting, and Participants  International, multicenter double-blind, placebo-controlled, randomized trial, undertaken in hospitals in Canada, Germany, Austria, Norway, Denmark, Sweden, Finland, Israel, and Spain from July 1998 through August 2001. A total of 1429 patients with IGT were randomized with 61 patients (4%) excluded because they did not have IGT or had no postrandomization data, leaving 1368 patients for a modified intent-to-treat analysis. Both men (49%) and women (51%) participated with a mean (SD) age of 54.5 (7.9) years and body mass index of 30.9 (4.2). These patients were followed up for a mean (SD) of 3.3 (1.2) years. Intervention  Patients with IGT were randomized to receive either placebo (n = 715) or 100 mg of acarbose 3 times a day (n = 714). Main Outcome Measures  The development of major cardiovascular events (coronary heart disease, cardiovascular death, congestive heart failure, cerebrovascular event, and peripheral vascular disease) and hypertension (=" BORDER="0">140/90 mm Hg). Results  Three hundred forty-one patients (24%) discontinued their participation prematurely, 211 in the acarbose-treated group and 130 in the placebo group; these patients were also followed up for outcome parameters. Decreasing postprandial hyperglycemia with acarbose was associated with a 49% relative risk reduction in the development of cardiovascular events (hazard ratio [HR], 0.51; 95% confidence interval [CI]; 0.28-0.95; P = .03) and a 2.5% absolute risk reduction. Among cardiovascular events, the major reduction was in the risk of myocardial infarction (HR, 0.09; 95% CI, 0.01-0.72; P = .02). Acarbose was also associated with a 34% relative risk reduction in the incidence of new cases of hypertension (HR, 0.66; 95% CI, 0.49-0.89; P = .006) and a 5.3% absolute risk reduction. Even after adjusting for major risk factors, the reduction in the risk of cardiovascular events (HR, 0.47; 95% CI, 0.24-0.90; P = .02) and hypertension (HR, 0.62; 95% CI, 0.45-0.86; P = .004) associated with acarbose treatment was still statistically significant. Conclusion  This study suggests that treating IGT patients with acarbose is associated with a significant reduction in the risk of cardiovascular disease and hypertension.      

Cytochrome c oxidase partial deficiency-associated Leigh disease presenting as an extrapyramidal syndrome

Leigh disease is a subacute neurodegenerative disorder characterized by symmetric necrotic lesions in the basal ganglia, cerebellum, thalamus, brain stem, and optical nerves and caused by altered oxidative phosphorylation. We describe the clinical, biochemical, neuroimaging, and molecular studies of a 19-year-old boy with early-onset Leigh disease manifesting as severe extrapyramidal disorder with generalized dystonia and choreoathetosis. He was born of healthy parents after an uneventful pregnancy and delivery. At the age of 2 1/2 years, after a minor respiratory infection, he developed unstable, broad-based gait and tremor of the hands. These symptoms persisted for the next several years, when ataxia became more prominent. Difficulty in swallowing, dysarthria, trunk dystonia, and marked dyskinesia of the arms and hands gradually developed. Nystagmus, transient ptosis, and strabismus also appeared. Abnormal laboratory findings included elevated plasma and cerebrospinal fluid lactate and pyruvate, with an abnormal lactate/pyruvate ratio. Cranial computed tomography and magnetic resonance imaging demonstrated signs of cerebellar atrophy, bilateral and symmetric hypodensities in the lentiform nucleus and thalamus, and transient hyperintensities of cerebral peduncles in T2-weighted sequences suggestive of Leigh disease. Muscle biopsy revealed isolated fiber atrophy, necrotic fibers undergoing phagocytosis, and no ragged-red fibers. The measured catalytic activity of cytochrome c oxidase in skeletal muscle homogenates demonstrated a partial cytochrome c oxidase deficiency No abnormalities in the mitochondrial genome and in the SURF-1 gene were found. The boy is currently receiving levodopa therapy, creatine monohydrate, and a high dosage of thiamine and lipoic acid, his condition is stabilized, and extrapyramidal symptoms are less pronounced.     

Predictive value of the index of desirable body weight for total body fat mass as measured by dilution of tritiated water--problems and limitations

The index of desirable body weight is currently used for classification of patients' weights. We examined how it is related to the degree of adiposity, and whether it can serve in the prediction of body fat to the same degree as Quetelet's index. Sixty-five women and 142 men comprising a wide range of weight indices were studied. Body fat (F) was measured by the tritium dilution technique with a precision of +/- 1.26 kg. Regressions of F/W0 on the index of desirable weight W/W0 gave a correlation coefficient of 0.969 for women and 0.939 for men. Regressions of F/H2 on Quetelet's index W/H2 had correlation coefficients of the same order, i.e. 0.971 for women and 0.936 for men. Hence both indices are equally powerful for calculation of body fat within the study population. Further progress was achieved by multiple regression of F on W and W0 which yielded correlation coefficients of 0.976 for women and 0.953 for men. The residual standard deviation reflecting the mean difference between calculated and estimated fat was 3.4 kg for women and 3.8 kg for men. Despite this self-consistency, prediction of body fat for persons outside the study population is only possible within wide limits. These are given by about twice the residual standard deviation. Therefore, prediction of body fat from weight indices can only be used for detection of larger abnormalities in body composition.     

Bis-thiolurethane aus Isocyanaten und substituierten Alkan- sowie Benzoldithiolen

Biscarbamothioates from Isocyanates and Substituted Alkane- and Benzenedithiols Substituted aliphatic and aromatic dithiols have been added to isocyanates under catalysis of triton B to yield biscarbamothioates.