Efficacy and safety of twice-daily tramadol hydrochloride bilayer sustained-release tablets with an immediate release component for postherpetic neuralgia: Results of a Phase III, randomized, double-blind, placebo-controlled, treatment-withdrawal study.

Background: We investigated the efficacy and safety of twice-daily bilayer sustained-release tramadol hydrochloride tablets (35% immediate-release; 65% sustained-release) in patients with postherpetic neuralgia.

Methods: This was a Phase III treatment-withdrawal study with 1-4-week dose-escalation, 1-week fixed-dose, and 4-week randomized, double-blind, placebo-controlled withdrawal periods performed at 43 medical institutions in Japan. Patients aged ≥20 years, ≥3 months after the onset of herpes zoster with localized, persistent pain despite fixed-dose analgesics for ≥2 weeks before enrollment were eligible.

The safety and efficacy of clopidogrel versus ticlopidine in Japanese stroke patients: combined results of two Phase III, multicenter, randomized clinical trials.

Two Phase III studies comparing the safety and efficacy of clopidogrel with ticlopidine as antiplatelet agents for the secondary prevention of vascular events in patients with prior stroke were performed in Japan. Both studies were randomized, double-blind, double-dummy comparative trials with the primary objective of comparing the clinical safety of treatment with either clopidogrel or ticlopidine for up to 12 months. The secondary objective was to assess the incidence of a combined efficacy endpoint of cerebral infarction, myocardial infarction, and vascular death.

Antiplatelet cilostazol is beneficial in diabetic and/or hypertensive ischemic stroke patients. Subgroup analysis of the cilostazol stroke prevention study.

Background And Purpose: Although antiplatelets are known to be effective for secondary prevention of cerebral infarction, the number needed to treat is rather large and the effects in stroke patients with complications such as hypertension or diabetes are inadequately defined. This study was conducted to examine the effect of such complications on recurrence of cerebral infarction, and to assess the effect of cilostazol, an antiplatelet agent, in these high-risk subjects.

Methods: A post hoc subgroup analysis of the already reported Cilostazol Stroke Prevention Study, which was a placebo-controlled double-blind trial, has been carried out to clarify the influence of various complications on recurrence in the placebo group and the effects of cilostazol in 1,095 patients with noncardioembolic ischemic cerebrovascular disease.

Sarpogrelate-Aspirin Comparative Clinical Study for Efficacy and Safety in Secondary Prevention of Cerebral Infarction (S-ACCESS): A randomized, double-blind, aspirin-controlled trial.

Background And Purpose: The antiplatelet agent sarpogrelate is a selective inhibitor of 5-hydroxytryptamine receptors. The purpose of this study was to compare the efficacy and safety of sarpogrelate with those of aspirin in Japanese ischemic stroke patients.

Methods: In total, 1510 patients with recent cerebral infarction (1 week to 6 months after onset) were randomly assigned to receive either sarpogrelate (100 mg TID) or aspirin (81 mg/d).

A randomized, double-blind study comparing the safety and efficacy of clopidogrel versus ticlopidine in Japanese patients with noncardioembolic cerebral infarction.

Background: Patients treated with ticlopidine require careful hematologic monitoring. Clopidogrel may have greater tolerability. However, no direct comparison of these two drugs has been reported and evidence of improved safety with clopidogrel is not yet established in the Japanese population.

Effect of the Ca antagonist nilvadipine on stroke occurrence or recurrence and extension of asymptomatic cerebral infarction in hypertensive patients with or without history of stroke (PICA Study). 1. Design and results at enrollment.

Background: We examined the effect of a Ca antagonist (nilvadipine) on the occurrence or recurrence of symptomatic stroke in hypertensive patients with MRI-defined asymptomatic cerebral infarction (ACI), periventricular hyperintensity (PVH), and deep and subcortical white matter hyperintensity (DSWMH), with or without a history of stroke, and evaluated the effect of long-term treatment on the lesions.

Methods: Patients with hypertension and incidental ACI were divided into those with (group B, 235 patients) or without (group A, 181 patients) a history of symptomatic stroke, and were given nilvadipine 4-8 mg/day for 3 years. Primary evaluation points were occurrence of symptomatic ischemic stroke and development or extension of asymptomatic ischemic lesions.

[Case of consciousness disturbance following a fever with spreading lesion over the bilateral splenia of the corpus callosum on MRI].

We report a 66-year-old man with spreading lesion over the bilateral splenia of the corpus callosum shown on MRI. On admission, unknown fever and myoclonus-like involuntary movement in the left forefinger and middle finger were observed. There were no remarkably abnormal data in the serum, the cerebrospinal fluid and electroencephalogram.

[A case of cerebral putaminal hemorrhage complicating a brain abscess proved by craniotomy].

A 40-year-old man was admitted to our hospital because of consciousness disturbance, dysarthria and numbness in his right hand. Computed tomography of the head showed a cerebral hemorrhage of the left putamen. The patient was judged to have an indication of operation, and frontal craniotomy to evacuate hematoma was performed.

FK506 abrogates delayed neuronal death via suppression of nitric oxide production in rats.

Background And Purpose: The mechanism of the neuroprotective effect of FK506 in relation to nitric oxide (NO) production has not been clarified in vivo. We have investigated the effect of FK506 on ischemia-induced NO production in association with the pathogenesis of delayed neuronal death (DND) in rats.

Methods: In vivo microdialysis was performed in the hippocampus of male Sprague-Dawley rats (250-350 g).

[Genetic risk factors for ischemic cerebrovascular disease--analysis on fifteen candidate prothrombotic gene polymorphisms in the Japanese population].

Accumulating evidence suggests that several polymorphisms in factors regulating blood coagulation, platelet function, and lipid metabolism are relevant for susceptibility to ischemic cerebrovascular diseases (CVD). The present study analyzed 15 genetic polymorphisms possibly associated with atherosclerosis and thrombosis in a case-control study involving a total of 200 genetically unrelated Japanese patients with ischemic CVD (mean age 58.3 +/- 7.

[A patient with giant cell myocarditis and myositis associated with thymoma and myasthenia gravis].

We report a 62-year-old man with giant cell myocarditis and myositis associated with thymoma and myasthenia gravis (MG). He was diagnosed as having MG and invasive thymoma at the age of 45. After he had a myasthenic crisis at the age of 61, tacrolimus was indicated in order to improve his neurological symptoms, in addition to glucocorticoid.

[A young patient of acute encephalitis complicated with acyclovir encephalopathy without renal dysfunction].

A previously healthy 30-year-old woman was admitted to our hospital because of impaired consciousness after convulsion. A temporary diagnosis of herpes simplex encephalitis was made, and intravenous acyclovir (ACV) therapy (250 mg four times daily in normal saline over 2 hours) was started. Three days later, she became confused, and was having hallucinations, dysarthria and generalized painful seizures occurred without focal neurologic deficit.

Initial predictors of development of pure red cell aplasia in myasthenia gravis after thymectomy.

Pure red cell aplasia (PRCA) is well known to be concomitant with myasthenia gravis (MG), but it is difficult to predict the development of PRCA in patients with MG. Of 135 patients with MG, four (2.9%) had PRCA.

Dynamic observation of oxygenation-induced contraction of and transient fiber-network formation-disassembly in cultured human brain microvascular endothelial cells.

Oxygenation-induced contraction of nonconfluent cultured human brain microvascular endothelial cells (HBECs, n = 30) was examined by video-enhanced contrast-differential interferential contrast microscopy. After administering a continuous gentle blow of pure oxygen gas to the surface of the medium just above the flattened HBEC, the plasma membrane exhibited tensioning and wrinkling, resulting in a strong contraction of the cell body by 14 +/- 7% (P < 0.001).

Delayed phosphorylation of p38 mitogen-activated protein kinase in the AT1a knock-out mouse striatal neurons during middle cerebral artery occlusion and reperfusion.

To investigate whether the phosphorylation of p38 in cerebral ischemia occurs via angiotensin II receptor type 1a (AT1a), we examined the time course of phosphorylation of p38 and proline-rich tyrosine kinase 2 in AT1a knock-out mouse striatal neurons during middle cerebral artery occlusion (MCAO) and reperfusion. Phosphorylated-p38 was observed after 2 h and 5 h of reperfusion after 1 h of MCAO in C57/B6 mice and AT1a knock out mice, respectively. We demonstrated a delay of phosphorylation of p38 in the reperfusion model of the AT1a knock-out mouse, and detected microglia in the striatum on the ischemic side that were phosphorylated-p38-positive after 71 h of reperfusion in both animals.

Autoreactive T cells to the P3A+ isoform of AChR alpha subunit in myasthenia gravis.

In vitro T cell proliferative response to an alternative splicing variant of acetylcholine receptor alpha subunit (AChR alpha) with the P3A exon-encoded region was examined in peripheral blood samples from 28 myasthenia gravis (MG) patients and 14 healthy donors using recombinant fragments and synthetic peptides. T cells responsive to the P3A region-specific sequences were detected in five MG patients, all of whom were late-onset disease with thymoma, but in none of healthy donors. These autoreactive T cells may be involved in the pathogenic process in a subset of MG patients.

[SPECT imaging using [123I]beta-CIT and [123I]IBF in extrapyramidal diseases].

Imaging of dopaminergic function is useful in the investigation of patients with Parkinson disease (iPD) and other extrapyramidal diseases. Using agents that bind to dopamine transporters ([123I]beta-CIT) and receptors ([123I]IBF SPECT), we investigated SPECT in 9 healthy volunteers and 24 patients for dopamine transporters as well as 15 patients for dopamine receptors. In beta-CIT SPECT studies, we examined 17 iPD patients (63.

In vivo measurement of superoxide in the cerebral cortex during anoxia-reoxygenation and ischemia-reperfusion.

Abstract. The exact time profile of superoxide generation during anoxia-reoxygenation and ischemia-reperfusion was assessed in the feline cerebral cortex in vivo using a chemiluminescence technique with a probe specific for superoxide, 2-methyl-6-[p-methoxyphenyl]-3,7-dihydroimidazo[1,2-alpha]pyrazin-3-one (MCLA). MCLA solution was superfused on the cortex throughout the protocol, and MCLA chemiluminescence was measured using a newly developed photon counting system.

Subcellular localization of a promoter and an inhibitor of apoptosis (Smac/DIABLO and XIAP) during brain ischemia/reperfusion.

We explored the expression of Smac/DIABLO, a newly identified mitochondrial apoptogenic molecule, and X-linked inhibitor of apoptosis protein (XIAP) in the brain subjected to ischemia/reperfusion. Transient focal ischemia was produced for 1 hour in mice. We observed only a negligible amount of Smac/DIABLO in both mitochondria and cytosol in the normal state.

Temporal profiles of the subcellular localization of Bim, a BH3-only protein, during middle cerebral artery occlusion in mice.

BH3-only proteins are a subfamily of proapoptotic Bcl-2 proteins that act upstream of the mitochondrially mediated cell death pathway, and their association with the pathogenesis of brain ischemia remains largely unknown. The authors explored the temporal profiles of the expression levels and subcellular localization of BH3-only proteins in permanent middle cerebral artery occlusion (MCAO) by Western blot analysis. They observed an increased mitochondrial distribution of Bim at 3 to 6 hours of MCAO that appeared unrelated to transcriptional upregulation, as assessed by semiquantitative reverse transcription-polymerase chain reaction.

A novel mutation (G217D) in the Presenilin 1 gene ( PSEN1) in a Japanese family: presenile dementia and parkinsonism are associated with cotton wool plaques in the cortex and striatum.

We report a family of Japanese origin that has five individuals from two generations affected by an illness characterized by dementia, a stooped posture and an antiflexion gait with an onset in the fourth or fifth decade of life. Two siblings had a clinical phenotype characterized by dementia and Parkinsonism with stooped posture, rigidity and bradykinesia. Neuropathological alterations in both patients included numerous 'cotton wool' plaques (CWPs), senile plaques, severe amyloid angiopathy, neurofibrillary tangles, neuronal rarefaction and gliosis.