Selfotel in acute ischemic stroke : possible neurotoxic effects of an NMDA antagonist

BACKGROUND AND PURPOSE: Based on neuroprotective efficacy in animal models, we evaluated the N-methyl D-aspartate antagonist Selfotel in patients with ischemic stroke, after doses up to 1.5 mg/kg were shown to be safe in phase 1 and phase 2a studies. METHODS: Two pivotal phase 3 ischemic stroke trials tested the hypothesis, by double-blind, randomized, placebo-controlled parallel design, that a single intravenous 1.5 mg/kg dose of Selfotel, administered within 6 hours of stroke onset, would improve functional outcome at 90 days, defined as the proportion of patients achieving a Barthel Index score of >/=60. The trials were performed in patients aged 40 to 85 years with acute ischemic hemispheric stroke and a motor deficit. RESULTS: The 2 trials were suspended on advice of the independent Data Safety Monitoring Board because of an imbalance in mortality after a total enrollment of 567 patients. The groups were well matched for initial stroke severity and time from stroke onset to therapy. There was no difference in the 90-day mortality rate, with 62 deaths (22%) in the Selfotel group and 49 (17%) in the placebo-treated group (RR=1.3; 95% CI 0.92 to 1.83; P=0.15). However, early mortality was higher in the Selfotel-treated patients (day 30: 54 of 280 versus 37 of 286; P=0.05). In patients with severe stroke, mortality imbalance was significant throughout the trial (P=0.05). CONCLUSIONS: Selfotel was not an effective treatment for acute ischemic stroke. Furthermore, a trend toward increased mortality, particularly within the first 30 days and in patients with severe stroke, suggests that the drug might have a neurotoxic effect in brain ischemia.     

Frequency and Correlates of Substance Use among Preadolescents and Adolescents in a Swiss Epidemiological Study

Alcohol use and nicotine use were investigated in a representative sample of 1110 study participants aged 10 to 17 years. In addition to questions on substance use, the participants responded to questionnaires covering behavior and emotions, life events, self-related cognitions, coping capacities, perceived parental behavior, perceived school environment, and the social network. The gender gap in substance use tended to close with increasing age. Parental substance use served as a model for substance use in the participants. Substance users had more abnormal scores on almost all variables as compared to abstaining controls. Lack of acceptance and control, pressure to achieve at school, and life events significantly predicted substance use. The latter served as a moderating risk variable for delinquent behavior under stress.     

Considering structural connectivity in the triple code model of numerical cognition: differential connectivity for magnitude processing and arithmetic facts

The current study provides a generalizable account of the anatomo-functional associations as well as the connectivity of representational codes underlying numerical processing as suggested by the triple code model (TCM) of numerical cognition. By evaluating the neural networks subserving numerical cognition in two specific and substantially different numerical tasks with regard to both grey matter localizations as well as white matter tracts we (1) considered the possibility of additional memory-related cortex areas crucial for arithmetic fact retrieval (e.g., the hippocampus); (2) specified the functional involvement of prefrontal areas in number magnitude processing, and, finally; (3) identified the connections between these anatomo-functional instantiations of the representations involved in number magnitude processing and arithmetic fact retrieval employing probabilistic fiber tracking. The resulting amendments to the TCM are summarized in a schematic update, and ideas concerning the possible functional interplay between number magnitude processing and arithmetic fact retrieval are discussed.     

Performance of the integrated management of childhood illness algorithm for diagnosis of HIV-1 infection among African infants

OBJECTIVES:: Early infant HIV-1 diagnosis and treatment substantially improve survival. Where virologic HIV-1 testing is unavailable, integrated management of childhood illness (IMCI) clinical algorithms may be used for infant HIV-1 screening. We evaluated the performance of the 2008 WHO IMCI HIV algorithm in a cohort of HIV-exposed Kenyan infants. METHODS:: From 1999 to 2003, 444 infants had monthly clinical assessments and quarterly virologic HIV-1 testing. Using archived clinical data, IMCI sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated using virologic testing as a gold standard. Linear regression and survival analyses were used to determine the effect of age on IMCI performance and timing of diagnosis. RESULTS:: Overall IMCI sensitivity, specificity, PPV, and NPV value were 58, 87, 52, and 90%, respectively. Sensitivity (1.4%) and PPV (14%) were lowest at 1 month of age, when 81% of HIV infections already had occurred. Sensitivity increased with age (P?相似文献   

Diagnose und Therapie von Kopf- und Gesichtsschmerzen

The symptom headache is very frequent. Most frequently headache is the leading symptom of a primary headache syndrome such as migraine or tension-type headache. Sometimes it is caused by another disease. In everyday clinical practice it is important to diagnose and treat primary headaches properly. It is even more important not to miss a secondary headache, which is rare, but if misdiagnosed could conceal life-threatening conditions. This review provides an overview of the clinical picture, diagnostic procedures and treatment strategies of frequent headache syndromes such as migraine, tension-type headache, medication overuse headache, trigeminal autonomic cephalgias and trigeminal neuralgia. This is followed by a brief summary on symptomatic headache caused by non-neurological diseases as well as on diagnostic procedures and management of headache in the emergency situation.