Search

Background and Purpose: A previous trial (the Clomethiazole Acute Stroke Study) generated the hypothesis that clomethiazole is effective in patients with a major ischemic stroke (total anterior circulation syndrome), and this was tested in the present study., Methods: A total of 1198 patients with major ischemic stroke and a combination of limb weakness, higher cortical dysfunction, and visual field deficits were randomly assigned to clomethiazole (68 mg/kg IV over 24 hours) or placebo. The study drug was initiated within 12 hours of symptom onset. Functional outcome and neurological recovery were assessed at days 7, 30, and 90, with the proportion of patients with a Barthel Index > or =60 at last follow-up as the primary outcome measure., Results: The patients were randomly assigned equally, and the two treatment groups were well matched for baseline characteristics, including stroke severity (mean National Institutes of Health Stroke Scale score 16.9+/-5.2). Ninety-six percent were classified as total anterior circulation syndrome. The proportion of patients reaching a Barthel Index score of > or =60 was 42% in the clomethiazole-treated group and 46% in the placebo-treated group (odds ratio, 0.81; 95% CI, 0.62 to 1.05; P=0.11). There was no evidence of efficacy on any secondary outcome variables (modified Rankin Score, National Institutes of Health Stroke Scale, Scandinavian Stroke Scale, and 30-day CT infarct volumes) compared with placebo. Subgroup analysis showed a similar lack of treatment effect in patients treated early (<6 hours) and in those treated later (6 to 12 hours). Somnolence was an expected pharmacological effect of clomethiazole, and this occurred during treatment as an adverse event in half of the patients randomly assigned to study drug., Conclusions: The target population was selected, and sufficient drug was given to produce the expected pharmacological effect in the brain. Clomethiazole does not improve outcome in patients with major ischemic stroke.

The adult ventricular isoform of chicken myosin heavy chain (MHC-V) is transiently expressed in all skeletal muscle primordia analyzed and is completely repressed around embryonic days 10-12, when functional innervation is established. By ribonuclease protection assay, we demonstrated that denervation of the adult anterior latissimus dorsi muscle resulted in reexpression of MHC-V mRNA. In contrast, treatment of primary cultures of fetal breast or leg muscles with embryonic brain extract or conditioned media from glial or neuroblastoma cell lines, but not from a myogenic cell line or primary muscle cell cultures, led to inhibition of MHC-V expression. This inhibitory activity was abolished by heating and increased with protein concentration. The acquisition of both brain inhibitory activity and the competence of myogenic cells to downregulate MHC-V mRNA expression were age dependent. Furthermore, either paralysis of muscle in ovo by curare or contraction arrest of cultured myotubes resulted in persistent expression of MHC-V mRNA. Thus a putative soluble factor(s) of nerve origin as well as muscle activity are involved in the developmental downregulation of MHC-V expression in muscle primordia.

Glial-cell-line-derived neutrophic factor (GDNF) promotes the survival and phenotype of central dopaminergic noradrenergic and motor neurons, as well as various subpopulations of peripheral sensory and sympathetic neurons. GDNF is structurally related to members of the transforming growth factor (TGF)-beta superfamily, several members of which have well-characterized receptor systems; however, GDNF receptors still remain undefined. Here we show that GDNF binds to, and induces tyrosine phosphorylation of, the product of the c-ret proto-oncogene, an orphan receptor tyrosine kinase, in a GDNF-responsive motor-neuron cell line. Ret protein could also bind GDNF and mediate survival and growth responses to GDNF upon transfection into naive fibroblasts. Moreover, high levels of c-ret mRNA expression were found in dopaminergic neurons of the adult substantia nigra, where exogenous GDNF protected Ret-positive neurons from 6-hydroxydopamine-induced cell death. Thus the product of the c-ret proto-oncogene encodes a functional receptor for GDNF that may mediate its neurotrophic effects on motor and dopaminergic neurons.

Using a measure of capacity for pleasurable experiences (the Pleasure Scale), the authors compared at admission and 7-month follow-up 74 psychiatric inpatients meeting DSM-III criteria for major depression. Pleasure scores were stable over 7 months despite the fact that two-thirds of the sample recovered from depression. The subgroup of subjects who were most anhedonic at admission were more likely than the remaining subjects to show clinical recovery but persisted in exhibiting a lower pleasure score (even when the comparison was limited to recovered subjects). Pleasure scores were much better predictors of clinical recovery than were neuroticism scores.

Sciatic endometriosis may cause cyclic sciatic pain and a sensorimotor mononeuropathy. Neurophysiologic tests and conventional radiologic examinations are of little value in delineating this lesion, but the pelvic CT appearance of sciatic endometriosis is distinctive. Suppression of the ovarian cycle and surgical removal of endometriosis and adhesions from in and around the sciatic nerve usually relieve the pain and stabilize neurologic function.

Fifty-five interns, representing 71% of the medicine, obstetrics-gynecology, surgery, and pediatric interns at one medical center for one year, participated in interviews involving the Schedule for Affective Disorders and Schizophrenia-Research Diagnostic Criteria (RDC) and Family History-RDC and completed symptom and attitudinal scales at 6-month intervals. Fifteen (27%) developed a depressive syndrome during the first 6 months of internship. Parental history of depression and high scores of trait neuroticism were significantly associated with onset of depression, but personal history of psychopathology, low capacity for experiencing pleasure, and workload were not.