CINRG randomized controlled trial of creatine and glutamine in Duchenne muscular dystrophy

We tested the efficacy and safety of glutamine (0.6 gm/kg/day) and creatine (5 gm/day) in 50 ambulant boys with Duchenne muscular dystrophy in a 6-month, double-blind, placebo-controlled clinical trial. Drug efficacy was tested by measuring muscle strength manually (34 muscle groups) and quantitatively (10 muscle groups). Timed functional tests, functional parameters, and pulmonary function tests were secondary outcome measures. Although there was no statistically significant effect of either therapy based on manual and quantitative measurements of muscle strength, a disease-modifying effect of creatine in older Duchenne muscular dystrophy and creatine and glutamine in younger Duchenne muscular dystrophy cannot be excluded. Creatine and glutamine were well tolerated.     

Synaptic dynamics mediate sensitivity to motion independent of stimulus details

Humans and other animals generally perceive motion independently of the cues that define the moving object. To understand the underlying mechanisms of this generalization of stimulus attributes, we have examined the cellular properties of avian wide-field tectal neurons that are sensitive to a variety of moving stimuli but not to static stationary stimuli. This in vitro study showed phasic signal transfer at the retinotectal synapse and binary dendritic responses to synaptic inputs that interact in a mutually exclusive manner in the postsynaptic tectal neuron. A model of the tectal circuitry predicts that these two cellular properties mediate sensitivity to a wide range of dynamic spatiotemporal stimuli, including moving stimuli, but not to static stationary stimuli in a tectal neuron. The computation that is independent of stimulus detail is initiated by tectal neurons and is completed by rotundal neurons that integrate outputs from multiple tectal neurons in a directionally selective manner.     

Relationship of physical fitness vs body mass index with coronary artery disease and cardiovascular events in women

Context  Individual contributions of obesity and physical fitness (physical activity and functional capacity) to risk of coronary heart disease in women remain unclear. Objective  To investigate the relationships of measures of obesity (body mass index [BMI], waist circumference, waist-hip ratio, and waist-height ratio) and physical fitness (self-reported Duke Activity Status Index [DASI] and Postmenopausal Estrogen-Progestin Intervention questionnaire [PEPI-Q] scores) with coronary artery disease (CAD) risk factors, angiographic CAD, and adverse cardiovascular (CV) events in women evaluated for suspected myocardial ischemia. Design, Setting, and Participants  The National Heart, Lung, and Blood Institute–sponsored Women's Ischemia Syndrome Evaluation (WISE) is a multicenter prospective cohort study. From 1996-2000, 936 women were enrolled at 4 US academic medical centers at the time of clinically indicated coronary angiography and then assessed (mean follow-up, 3.9 [SD, 1.8] years) for adverse outcomes. Main Outcome Measures  Prevalence of obstructive CAD (any angiographic stenosis 50%) and incidence of adverse CV events (all-cause death or hospitalization for nonfatal myocardial infarction, stroke, congestive heart failure, unstable angina, or other vascular events) during follow-up. Results  Of 906 women (mean age, 58 [SD, 12] years) with complete data, 19% were of nonwhite race, 76% were overweight (BMI 25), 70% had low functional capacity (DASI scores <25, equivalent to 7 metabolic equivalents [METs]), and 39% had obstructive CAD. During follow-up, 337 (38%) women had a first adverse event, 118 (13%) had a major adverse event, and 68 (8%) died. Overweight women were more likely than normal weight women to have CAD risk factors, but neither BMI nor abdominal obesity measures were significantly associated with obstructive CAD or adverse CV events after adjusting for other risk factors (P = .05 to .88). Conversely, women with lower DASI scores were significantly more likely to have CAD risk factors and obstructive CAD (44% vs 26%, P<.001) at baseline, and each 1-MET increase in DASI score was independently associated with an 8% (hazard ratio, 0.92; 95% confidence interval, 0.85-0.99; P = .02) decrease in risk of major adverse CV events during follow-up. Conclusions  Among women undergoing coronary angiography for suspected ischemia, higher self-reported physical fitness scores were independently associated with fewer CAD risk factors, less angiographic CAD, and lower risk for adverse CV events. Measures of obesity were not independently associated with these outcomes.      

Abstammungsbegutachtung mit der RFLP- und STR-Analyse

The combination of restriction fragment length polymorphism (RFLP) and short tandem repeat (STR) analyses for paternity analysis is presented. The two methods were compared by investigating 113 paternity cases. RFLP analysis was done using the single locus probes YNH24, MS31 and MS43A and for STR investigations the Identifiler Plus kit was employed. The lowest paternity probability obtained via RFLP analysis was 98.936% compared to 99.99844% when using STR analysis and the highest values were 99.9996 (RFLP) and >99.999999% (STR). Using 3 single locus DNA probes the paternity probability was <99.9% in 45.5% of the cases, while STR analysis always led to at least 99.9%. In 36 cases the father was excluded. Using STR analysis between 4 and 12 exclusions out of 15 investigated loci per case were observed. In 14 cases (39%) RFLP analysis alone did not yield the 3 exclusions necessary for exclusion of paternity. In summary it could be shown that in all cases both STR analysis alone and the combination of STR and RFLP investigations led to results which conformed to the requirements of the German guidelines.     

Human small cell lung cancer NYH cells selected for resistance to the bisdioxopiperazine topoisomerase II catalytic inhibitor ICRF-187 demonstrate a functional R162Q mutation in the Walker A consensus ATP binding domain of the alpha isoform.

Bisdioxopiperazine drugs such as ICRF-187 are catalytic inhibitors of DNA topoisomerase II, with at least two effects on the enzyme: namely, locking it in a closed-clamp form and inhibiting its ATPase activity. This is in contrast to topoisomerase II poisons as etoposide and amsacrine (m-AMSA), which act by stabilizing enzyme-DNA-drug complexes at a stage in which the DNA gate strand is cleaved and the protein is covalently attached to DNA. Human small cell lung cancer NYH cells selected for resistance to ICRF-187 (NYH/187) showed a 25% increase in topoisomerase IIalpha level and no change in expression of the beta isoform. Sequencing of the entire topoisomerase IIalpha cDNA from NYH/187 cells demonstrated a homozygous G-->A point mutation at nucleotide 485, leading to a R162Q conversion in the Walker A consensus ATP binding site (residues 161-165 in the alpha isoform), this being the first drug-selected mutation described at this site. Western blotting after incubation with ICRF-187 showed no depletion of the alpha isoform in NYH/187 cells in contrast to wild-type (wt) cells, whereas equal depletion of the beta isoform was observed in the two sublines. Alkaline elution assay demonstrated a lack of inhibition of etoposide-induced DNA single-stranded breaks in NYH/187 cells, whereas this inhibition was readily apparent in NYH cells. Site-directed mutagenesis in human topoisomerase IIalpha introduced into a yeast Saccharomyces cerevisiae strain with a temperature-conditional yeast TOP2 mutant demonstrated that R162Q conferred resistance to the bisdioxopiperazines ICRF-187 and -193 but not to etoposide or m-AMSA. Both etoposide and m-AMSA induced more DNA cleavage with purified R162Q enzyme than with the wt. The R162Q enzyme has a 20-25% decreased catalytic capacity compared to the wt and was almost inactive at <0.25 mM ATP compared to the wt. Kinetoplast DNA decatenation by the R162Q enzyme at 1 mM ATP was not resistant to ICRF-187 compared to wt, whereas it was clearly less sensitive than wt to ICRF-187 at low ATP concentrations. This suggests that it is a shift in the equilibrium to an open-clamp state in the enzyme's catalytic cycle caused by a decreased ATP binding by the mutated enzyme that is responsible for bisdioxopiperazine resistance.     

Recurrent urinary tract infection in girls. Group with lower tract findings and a benign course

A group of girls is described with recurrent urinary tract infections characterized by predominantly lower tract symptoms. Clinical, laboratory, and radiography findings during the period of follow-up are presented. Infection persisted in most patients over several years. Response to medical and surgical treatment was unsatisfactory. The mean interval between the initial and most recent radiological study was 6 1/2 years. No case of renal parenchymal scarring was seen.     

Schmerzkonzept einer kinderchirurgischen Klinik

The principle of an anxiety and pain-free treatment necessitates, particularly in childhood, a standardized age-related pain management. The oral, rectal or i.v. administration of a sedative/analgesic in pediatric surgery is mostly accompanied by a great deal of stress for all involved and the alternative of general anesthesia is often not readily available or even not available at all. The high analgesic, anxiolytic and sedative potency of nitrous oxide has been known worldwide for a long time but the inhalative administration is not in general use as the approval as a ready to use pharmaceutical was only granted in Germany in 2008. Nitrous oxide is absorbed and eliminated through the lungs and because metabolism does not take place in the body fasting is unnecessary. Side effects can occur but are completely reversible at the end of the application.