Biomedical subjects

Mitsuru Kawai

Publications and source records attributed to Mitsuru Kawai.

7 recordsLinked to original sources

PubMed2003

D-cycloserine for the treatment of ataxia in spinocerebellar degeneration.

We studied the effects of D-cycloserine, a partial NMDA receptor allosteric agonist, on ataxia in patients with spinocerebellar degeneration. Fifteen Japanese ataxic patients enrolled in a 14-day single-blind trial of D-cycloserine (daily oral dose of 50 mg) following a 14-day single-blind placebo phase. At the end of the D-cycloserine administration, there was a significant reduction in the posture, gait and total score of the international cooperative ataxia rating scale and in the time for walking and speech tasks. D-Cycloserine was well-tolerated and no adverse effect was observed. D-Cycloserine may have therapeutic efficacy for spinocerebellar ataxia.

Adult↗

PubMed2003

Microarray analysis identifies interferon beta-regulated genes in multiple sclerosis.

The molecular mechanisms for the interferon beta (IFNbeta) treatment of multiple sclerosis (MS) remain to be characterized. Using cDNA microarray technology, we have compared the gene expression profile of T and non-T cells derived from relapsing-remitting MS before and after treatment with IFNbeta-1b. IFNbeta treatment significantly altered expression of 21 genes out of 1263 at 3 and 6 months after treatment. These genes included nine with IFN-responsive promoter elements. Whereas there was no change in Th1 or Th2 marker genes, some of the changes were unexpected but coincided with the beneficial effect of IFNbeta in MS.

Adult↗

PubMed2003

[Dichloroacetate treatment for adult patients with mitochondrial disease].

We report beneficial and adverse effects of sodium dichloroacetate (DCA) in three adult Japanese patients with mitochondrial disease: a 21-year-old male with involuntary movements, optic atrophy, hearing loss, and convulsions (patient 1), a 28-year-old man with mental deterioration, hemianopia, hearing disturbance, and convulsions (patient 2), and a 50-year-old woman with hearing disturbance, generalized muscle atrophy, and insulin dependent diabetes mellitus (patient 3). A3243G mutation was found in patient 2 and patient 3. Oral administration of DCA improved consciousness level and gait disturbances in patient 1, and ameliorated headaches, easy fatiguability, and muscle cramps in patient 2 and patient 3. DCA normalized high levels of lactate and pyruvate in blood and cerebrospinal fluids in all three patients. In patient 3, daily insulin needs decreased from 38 to 24 units, and urine C peptide increased from an undetectable level to 16 micrograms/day. In patient 1, DCA 23 mg/kg/day had been beneficial without adverse effects and he became free of convulsions for more than 32 months. However, despite of normal lactate and pyruvate, unsteady gait and lethargy developed after 50 mg/kg/day treatment for two months and one month in patient 2 and patient 3, respectively. In both patients, deep tendon reflexes disappeared and Romberg sign became positive. Nerve conduction studies confirmed sensory-dominant polyneuropathy and electroencephalogram showed diffuse slow basic activities. Cessation of DCA resulted in recovery of gait and consciousness, but sensory nerve action potentials did not recover in one month. Long term treatment of 50 mg/kg/day DCA may affect adversely the peripheral and central nervous systems in adult patients. Although effective plasma DCA concentration was previously reported as 25-160 micrograms/ml in patients under 18 years old, plasma DCA concentration of 10.2 micrograms/ml was sufficient in patient 1. We recommend lower dose of DCA in adult patients than in child patients.

Adult↗

PubMed2002

Arterial changes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) in relation to pathogenesis of diffuse myelin loss of cerebral white matter: examination of cerebral medullary arteries by reconstruction of serial sections of an autopsy case.

BACKGROUND AND PURPOSE: There is little information regarding the pathogenesis underlying diffuse myelin loss in the cerebral white matter and sparing of the U fibers in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), in which the medial smooth muscle cells of systemic arteries are characteristically involved. We sought to examine the precise extent and severity of changes in the cerebral arteries in an autopsy case of CADASIL in relation to pathogenesis of the diffuse myelin loss. METHODS: We reconstructed 1000 serial sections of the frontal cerebral medullary arteries of an autopsy subject, which was the first identified Japanese case of CADASIL, as confirmed by the presence of ultrastructural deposits of granular osmiophilic material in the media of some visceral arteries and by genetic analysis. RESULTS: We reconstructed 11 medullary arteries of the frontal lobe showing diffuse myelin loss and atrophy of the white matter with sparing of the U fibers. All of these showed complete loss of medial smooth muscle cells over their entire length and severe adventitial fibrosis. Although intimal fibrosis or hyalinosis was present, luminal occlusion was scarce. These changes were also observed in the small and large arachnoidal arteries but were relatively mild in the latter and in the cortical and subcortical medullary arteries. CONCLUSIONS: These arterial changes resulted in transformation of the cerebral arteries, in particular almost all the medullary arteries, to a so-called earthen pipe state. This supports the reported findings of a reduction in vascular reactivity to fluctuations in CO2 levels and systemic blood pressure in CADASIL.

Aged↗

PubMed2002

[Juvenile-onset multiple brain infarcts localized in the posterior circulation: a case report].

We report a 37-year-old male patient with multiple brain infarcts due to arterial lesions localized in the posterior circulation, who developed a paramedian pontine infarct on the left side. He had been treated as schizophrenia for 20 years. A cranial CT performed one year before showed old small infarcts in the territories of the bilateral thalamo-perforating and left thalamo-geniculate arteries and the right posterior inferior cerebellar artery. The vertebral and basilar arteries were small in diameter on MRI and MR angiography(MRA). Cerebral angiography revealed a narrow smooth basilar artery. In addition, the P2 segments of the bilateral posterior cerebral arteries were markedly narrow with irregular walls. Carotid arteriograms were normal and no atherosclerosis was found. The nature of these arterial lesions remains unknown in this case. Even if MRA shows vertebrobasilar artery hypoplasia, a known congenital risk factor of a posterior circulation infarct, we must rule out a possibility that some arterial pathology is going on.

Adult↗

PubMed2002

[Facioscapulohumeral muscular dystrophy with sinus dysfunction].

We report a 47-year-old man with facioscapulohumeral muscular dystrophy (FSHD) presenting with sinus dysfunction. He became unable to roll over and stand up at the age of 42, but he could still walk. Facial muscle involvement, scapular winging, asymmetrical involvement, funnel chest, and the absence of contractures were typical of FSHD. Electrocardiogram (ECG) and cardiac echogram showed the overload of both right atrium and ventricle. On Holter ECG, transient P wave inversion and P-P interval elongation (maximally 2.4 seconds) repeatedly appeared mainly during sleep. There was no bundle branch block, atrioventricular junctional rhythm, or increase of premature ventricular beats. Vital capacity was decreased (0.62 L, 16% of the predicted value). Arterial blood gas analysis showed hypercapnia and hypoxia which aggravated during sleep (PaCO2 87.3Torr, PaO2 41.5Torr). Sleep apnea was not observed. Intracardiac ECG was not performed and he died 2 weeks later. In FSHD, sinus node dysfunction may become distinct especially in the setting of respiratory failure.

Electrocardiography, Ambulatory↗

PubMed2002

[Compulsive repetition of movements in a case of progressive supranuclear palsy].

A 51-year-old right-handed man with an 8-year history of progressive supranuclear palsy developed a peculiar behavior including compulsive repetition of movements. At the age of 47, it was noted that he continuously scratched his trunk with the right hand. He also scratched his thighs until his trousers were torn. On the scalp, posterior neck and forearms, patches of skin were scraped away and the bleeding wounds were scratched over and over again. Although he perceived pain, he could not terminate the strange scratching movement. He could not stop his eating action even after the bowl became empty. He could not leave the bathroom because he continued to wipe the anus after defecation. Yet the patient was not demented. Psychometric assessments including Wechsler adult intelligence scale revised, meaningful and meaningless syllables memory test. Raven's color matrix test, Wisconsin card sorting test (Keio version), and modified Stroop test were within the normal range. When requested to write a letter or a figure, he was always successful, however, he endlessly wrote the same letter or figure until he was told to stop. Although he repeated the behavior and could not terminate the action by himself, he immediately stopped the action on verbal command. When another task was given during the repetitive action, he responded quickly and successfully. His strange behavior was compulsive because he wanted to cease it, but it was not compulsive-obsessive behavior because he did not feel anxiety or pain when his repetitive action was stopped. It was different from stereotypy because he repeated not only meaningless movements but also meaningful complex actions. Unlike perseveration, he changed his activity immediately and successfully when a new task was given. Magnetic resonance imaging findings were remarkable only for mild atrophy of the midbrain tegmentum. Single photon emission computed tomography with ethyl cysteinate dimer demonstrated hypoperfusion in the frontal lobes and the left thalamus. A thalamofrontal disconnection or dysfunction is suggested as the mechanism underlying the compulsive repetifim of moving its based on the SPECT findings in this patient.

Compulsive Behavior↗