Valproic acid induced encephalopathy--19 new cases in Germany from 1994 to 2003--a side effect associated to VPA-therapy not only in young children.

Valproic acid (VPA) is a broad-spectrum antiepileptic drug and is usually well-tolerated. Rare serious complications may occur in some patients, including haemorrhagic pancreatitis, bone marrow suppression, VPA-induced hepatotoxicity and VPA-induced encephalopathy. The typical signs of VPA-induced encephalopathy are impaired consciousness, sometimes marked EEG background slowing, increased seizure frequency, with or without hyperammonemia. There is still no proof of causative effect of VPA in patients with encephalopathy, but only of an association with an assumed causal relation. We report 19 patients with VPA-associated encephalopathy in Germany from the years 1994 to 2003, none of whom had been published previously.     

ADAMTS-4 activity on a proteoglycan vs. a polypeptide is controlled by the ancillary domains

Introduction In combination with the catalytic domain, the ancillary domains of the ADAMTS' are proposed to regulate activity via interactions with sulfated GAGs, the extracellular matrix (ECM) and cell surface. Interactions with both GAGs and the ECM have been attributed to the thrombospondin (TSP) type 1 motifs and spacer region ( Kuno and Matsushima 1998 ; Flannery et al. 2002 ). ADAMTS‐1, ‐4 and ‐5, all undergo cleavage within their respective spacer regions ( Flannery et al. 2002 ; Rodriguez‐Manzaneque et al. 2000 ; Georgiadis et al. 2002 ), an event which has been reported to increase activity towards the interglobular domain of aggrecan and decrease the heparin affinity of ADAMTS‐4 ( Flannery et al. 2002 ; Gao et al. 2002 ). Materials and methods V5‐ and His‐tagged recombinant human ADAMTS‐4 constructs terminating after the catalytic (?DTS), disintegrin‐like (?TS), TSP (?S) or spacer region (Full) were expressed in High‐Five cells. Proteoglycanase activities of the resultant proteins were assayed with solution digests of aggrecan and a polyacrylamide‐entrapped aggrecan particle assay. Proteolytic activity was measured using a novel, nonglycosylated, reporter substrate assay. Results All forms of ADAMTS‐4 were active to varying degrees in the reporter substrate assay. Digestion of aggrecan in solution digests was apparent in all proteins with the exception of the catalytic domain in isolation (?DTS). Activity towards aggrecan decreased with increasing truncation of the protein. Discussion Removal of the cysteine‐rich‐spacer domain and further C‐terminal truncations decrease the activity of ADAMTS‐4 towards aggrecan, whilst the proteolytic activity remains intact. Cleavages releasing the ancillary domains of ADAMTS' may therefore alter the catalytic activity of these enzymes against proteoglycans and also nonglycosylated polypeptides. More information is required about potential substrates for the processed forms of ADAMTS‐4.     

Gender differences in condom-related behaviors and attitudes among Mexican adolescents living on the U.S.-Mexico border.

Adolescents are at increasing risk for HIV infection in Mexico. Research on gender differences in risk behaviors and determinants is needed to develop effective HIV prevention interventions targeting Mexican adolescents. This study examined gender differences in the likelihood of unprotected sex and theoretical correlates among high school students in the border city of Tijuana. Three hundred seventy high-school students completed a face-to-face interview and a self-administered survey. Differences in sexual initiation, condom use, intentions to use condoms in the future, and attitudes towards condoms in this population were assessed. Although male students initiated sexual practices earlier than females, females were more likely to have unprotected sex. Females perceived themselves as more likely to avoid unprotected sex in the future and held more favorable attitudes about condoms. The results suggest that stereotypical gender roles and communication barriers place Tijuana female high school students at higher risk for HIV infection than their male peers.     

Morphometric analysis of murine skin wound healing: Standardization of experimental procedures and impact of an advanced multitissue array technique

Morphometric data based on skin wounding offer important information for the characterization of the phenotype of transgenic mouse models. The goal of this study was the comparison of technical procedures concerning wounding, processing, and evaluation of samples in different mouse strains. The multitissue array technique was used to estimate its adaptability for standardized analysis in wound healing. Skin wounds between days 1 and 14 after wounding were analyzed. The influence of mouse strain (C57BI/6 vs. FVB/N mice), sex, size of the punch biopsies, and preparation of the tissue sections was investigated on 94 mice. The parameters distance between the migration tongues (deltaMT) and surface not covered by epithelium were evaluated to describe the reepithelialization, and the distance between the adnexa was chosen to measure wound contraction. In addition, the techniques to measure the area of granulation tissue (GT) were evaluated. The data illustrate the requirement of standardized conditions for skin wound-healing experiments and demonstrate that histological preparation in serial sections is mandatory to detect slight differences in wound contraction. For the analysis of cellular composition in GT, multitissue arrays are useful tools in wound-healing studies.     

Fatigue in neuroimmunological diseases

Journal of Neurology - Fatigue is a widespread symptom in numerous neuroimmunological diseases like multiple sclerosis (MS), myasthenia gravis, morbus Behcet, neurosarcoidosis, neuroborreliosis or...     

Phenotypic variability of a distinct deletion in McLeod syndrome

The X‐linked McLeod neuroacanthocytosis syndrome strongly resembles Huntington's disease and has been reported in various countries world‐wide. Herein, we report two Chilean brothers with predominant psychiatric features at disease onset including schizophrenia‐like psychosis and obsessive compulsive disorder. Molecular genetic analysis revealed a small deletion in the XK gene (938‐942delCTCTA), which has been already described in a North American patient of Anglo‐Saxon descent and a Japanese family, presenting with seizures, muscle atrophy or chorea yet absence of psychiatric features. These findings argue against a founder effect and indicate a profound phenotypic variability associated with the 938‐942delCTCTA deletion. Our report supports the inclusion of McLeod syndrome in the differential diagnosis of Huntington's disease as well as acute psychosis in male subjects. © 2007 Movement Disorder Society     

Stem cell research and cell transplantation for myocardial regeneration.

Several human organs are not capable of functional regeneration following a tissue defect and react with scar formation. In stem cell transplantation, undifferentiated or partly differentiated precursor cells are applied to defective tissue for therapeutic regeneration. After promising preclinical investigations, the transplantation of autologous stem cells for myocardial infarction treatment is being transferred to clinical use. Mesenchymal stem cells and endothelial precursor cells derived from the bone marrow or circulating blood as well as skeletal myoblasts are employed in clinical trials. Furthermore, indications for cell transplantation and delivery routes vary considerably throughout current investigations. Initial results suggest a potential for restoration of cardiac function in stem cell-treated patients; however, the mechanisms are not fully understood. This overview will focus on objectives, recent achievements, and future perspectives of diverse stem cell transplantation approaches.     

Use of Cyclooxygenase Inhibitors and Risk of Melanoma in High-Risk Patients

Background Results from in vitro and animal studies suggest that cyclooxygenase (COX) inhibitors may reduce the risk of melanoma, but among humans, the evidence remains limited.
Objective In a pilot retrospective cohort, to determine the relationship between the use of COX inhibitors and the incidence, recurrence, and metastases of melanoma in high-risk patients.
Methods Reviewing computerized records at the Miami Veterans Affairs Medical Center, we retrospectively examined the association between COX inhibitor use and melanoma incidence, recurrence, and metastases in high-risk subjects: white subjects previously diagnosed with melanoma (1996–2003). We evaluated three potential outcomes: new melanoma diagnosis, recurrence of a previous melanoma, and melanoma metastasis.
Results Eighty-three subjects with melanoma were included. There was one metastasis among 28 subjects prescribed COX inhibitors, whereas four new melanomas (7.3%), two melanoma recurrences, and six metastases (10.9%) occurred among 55 patients not prescribed COX inhibitors. Although no individual outcomes measures reached statistical significance, combining the three measures, these were significantly lower in users of COX inhibitors compared with nonusers (1 vs 12;  p = .05  ). After adjustment for age and tumor depth of invasion, COX inhibitor users had significantly lower rates of melanoma outcome measures (odds ratio 0.08; 95% confidence interval 0.01–0.77;  p = .03  ).
Conclusion Potential exists for chemoprevention of melanoma among high-risk patients.     

When distraction is not distracting: a behavioral and ERP study on distraction in ADHD.

OBJECTIVE: Although an increased distractibility is one of the behavioral criteria of Attention Deficit Hyperactivity Disorder (ADHD), there is little empirical evidence that children with ADHD are in fact more distractible than their normal peers. METHODS: We recorded event-related potentials (ERPs) to distracting novel sounds (novels) and standard sounds, (standards) while children performed a visual two-choice reaction time task. Twenty-five children with ADHD were compared with eighteen normal controls (aged 8-12 years). RESULTS: Children with ADHD showed a larger early P3a (150-250 ms), both in response to the standard and in response to the novel. The late phase of the P3a had a larger amplitude in the ADHD group in the 250-300 ms window compared to the control group, which was only present in response to the novel. Interestingly, the novel reduced the errors of omission in the ADHD group to a greater extent than in the normal control group. CONCLUSIONS: Although children with ADHD show an increased orienting response to novels, this distracting information can enhance their performance temporarily, possibly by increasing their arousal to an optimal level, as indicated by the reduced omission rate. SIGNIFICANCE: These data indicate that distraction is not always distracting in children with ADHD and that distraction can also have beneficial effects.