Transcriptional activation of the non-muscle, full-length dystrophin isoforms in Duchenne muscular dystrophy skeletal muscle.

Despite promoter tissue specificity, up-regulation of the brain and Purkinje cell type dystrophin isoforms was described in skeletal muscle of X-linked dilated cardiomyopathy (XLDCM) and BMD affected individuals. An extended population of 11 Duchenne muscular dystrophy (DMD) and 11 Becker muscular dystrophy (BMD) patients was investigated to determine whether ectopic muscle expression of the two full-length non-muscular isoforms is a common event in dystrophinopathies and if it has functional significance. Up-regulation of the two non-muscle-specific isoforms was detected in four DMD patients but in none of the BMD affected individuals or non-dystrophic controls. This is the first report of an expression of these two isoforms in DMD skeletal muscle. Ectopic expression is not confined to regenerating or revertant fibers and does not correlate with age at biopsy, clinical phenotype, cardiac involvement, deletion size or location.We consider that muscle ectopic expression of the brain and Purkinje cell-type isoforms has no favorable prognostic significance in DMD and BMD patients.     

Methods and resources for physics education in radiology residency programs: survey results

Over the past 2 years, ongoing efforts have been made to reevaluate and restructure the way physics education is provided to radiology residents. Program directors and faculty from North American radiology residency programs were surveyed about how physics is being taught and what resources are currently being used for their residents. Substantial needs were identified for additional educational resources in physics, better integration of physics into clinical training, and a standardized physics curriculum closely linked to the initial certification examination of the American Board of Radiology.     

Neurocognitive profiles in Duchenne muscular dystrophy and gene mutation site

The presence of nonprogressive cognitive impairment is recognized as a common feature in a substantial proportion of patients with Duchenne muscular dystrophy. To investigate the possible role of mutations along the dystrophin gene affecting different brain dystrophin isoforms and specific cognitive profiles, 42 school-age children affected with Duchenne muscular dystrophy, subdivided according to sites of mutations along the dystrophin gene, underwent a battery of tests tapping a wide range of intellectual, linguistic, and neuropsychologic functions. Full-scale intelligence quotient was approximately 1 S.D. below the population average in the whole group of dystrophic children. Patients with Duchenne muscular dystrophy and mutations located in the distal portion of the dystrophin gene (involving the 140-kDa brain protein isoform, called Dp140) were generally more severely affected and expressed different patterns of strengths and impairments, compared with patients with Duchenne muscular dystrophy and mutations located in the proximal portion of the dystrophin gene (not involving Dp140). Patients with Duchenne muscular dystrophy and distal mutations demonstrated specific impairments in visuospatial functions and visual memory (which seemed intact in proximally mutated patients) and greater impairment in syntactic processing.     

Sporadic distal myopathy with early adult onset: study of muscle biopsies and muscle cell cultures

A 28-year-old man with negative family history for neuromuscular diseases showed a distal myopathy. Creatine kinase was slightly increased. Two muscle biopsies were performed. The first showed myopathic features, rimmed vacuoles in a limited area and increase of free glycogen; the second showed only nonspecific pathological findings, demonstrating the patchy nature of vacuolar alterations. Biochemical investigation of the glycogenolytic and glycolytic pathways in muscle homogenates ruled out enzyme deficiencies. Muscle cell cultures developed normally.     

Clinical experience with topiramate dosing and serum levels in patients with epilepsy.

OBJECTIVE: To investigate the relevance of serum topiramate (TPM) levels (SL) monitoring in the clinical management of epileptic patients. METHODS: Twenty-seven patients with different epileptic syndromes on TPM therapy were studied. TPM was used as add-on in 26 patients, only in one as monotherapy de novo; one case changed from TPM as add-on to TPM monotherapy. The mean follow-up time was 11 months. TPM SL were measured by fluorescence polarization immunoassay. RESULTS: We analyzed the TPM SL in 43 samples from 27 patients. Mean TPM dose was 3.9mg/kg, mean TPM SL 13.43mumol/l. The mean level to dose ratio (LDR) was 3.63mumol/l/mg/kg. Four patients became seizure-free, all with TPM dosages lower than the mean. Eleven patients had at least 50% seizure reduction. The comedication with enzyme-inducing AED significantly reduced TPM SL and LDR. On the other hand, the influence of valproic acid (VPA) on TPM LDR was not univocal. Indeed, patients younger than 15 years showed SL values lower than the adults did, although not significant. CONCLUSION: We could not detect a direct relationship between high TPM SL and efficacy neither between high TPM SL and tolerability. However, the data we collected seem to favour the hypothesis that high TPM dosage and SL might be associated to a greater probability to reduce seizure severity.     

The effect of alcoholism on membrane lithium transport

Red cell lithium efflux rates in major affective disorder and alcoholic patient groups were studied. Current alcoholism was associated with significant elevation of lithium transport in white but not black subjects. This effect of alcoholism on the characteristics of membrane ion transport was independent of the blood pressure elevating effects of alcoholism and the diagnosis of major affective disorder. A model to explain the mechanism of this race-specific membrane effect of alcoholism is proposed and discussed.     

Poems syndrome: role of two angiogenic factors, VEGF and EPO.

Objective: The proliferation of medical knowledge (including media attention for health) and this emergence of chronic disease laid fertile ground for the self‐care movement and revision of the doctor‐patient relationship. The growing emphasis on self‐care has led to increasing needs for accurate patient information on alternative approaches to clinical problems. Carpal tunnel syndrome (CTS) is the most frequent focal neuropathy. Postures are relevant for development worsening or improvement of CTS. Hence, CTS exemplifies a pathology in which patients can be instructed by the use of a video, avoiding wrong positions that can worsen the pathology. Materials and Methods: We developed an instructional video for CTS patients to educate themselves on how to avoid postures that could worse the median nerve entrapment. Furthermore, we performed the first steps of validation. Results: The first steps of validation showed that the video is able to transfer the arguments we believe are relevant to avoid negative posture. To complete the validation, a randomised controlled trial is ongoing to evaluate the efficacy of the video. Discussion: We can imagine self‐care as a low‐cost program for promoting health self‐management, improving elements of health status while reducing care costs in populations with diverse chronic diseases. CTS is an ideal model to evaluate the efficacy of the self‐care approach. The developed video was able to instruct patients about the importance of posture on this disease and how to avoid/modify daily activities negative for the entrapment syndrome. Note that the use of the video was explicitly intended to augment the usual doctor‐patient interaction, not to substitute it.