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Biomedical subjects

E Miyawaki

Publications and source records attributed to E Miyawaki.

At least 19 recordsLinked to original sources

Further evaluation of developmental toxicity of di-n-butyl phthalate following administration during late pregnancy in rats.

The objective of this study was to further evaluate the developmental toxicity of di-n-butyl phthalate (DBP) administered during the second half of pregnancy. Pregnant rats were fed a diet containing DBP at a dose of 0 (control), 0.5, 1.0 or 2.0% ad libitum on days 11-21 of pregnancy. Average daily intakes of DBP were 331, 555 and 661 mg/kg for the 0.5, 1.0 and 2.0% groups, respectively. No significant changes induced by DBP were detected in the incidence of postimplantation loss and numbers of live fetuses and of resorptions and dead fetuses. The weights of male and female fetuses at 2.0% DBP were significantly decreased. The incidences of fetuses with cleft palate and fetuses with fusion of the sternebrae at 2.0% DBP and fetuses with undescended testes at 1.0 and 2.0% DBP were significantly increased. There were significant decreases in the anogenital distance (AGD) of male fetuses in the 1.0 and 2.0% DBP groups, also. AGD of female fetuses in the DBP-treated groups was comparable to that in the control group. It was concluded that DBP administered during the second half of pregnancy produced adverse effects on the reproductive development in male fetuses.

Abnormalities, Drug-Induced

High-frequency unilateral thalamic stimulation in the treatment of essential and parkinsonian tremor.

Pharmacologic treatment for essential tremor and the tremor of Parkinson's disease is often inadequate. Stereotaxic surgery, such as thalamotomy, can effectively reduce tremors. We performed a multicenter trial of unilateral high-frequency stimulation of the ventral intermedius nucleus of the thalamus in 29 patients with essential tremor and 24 patients with Parkinson's disease, using a blinded assessment at 3 months after surgery to compare clinical rating of tremor with stimulation ON with stimulation OFF and baseline and a 1-year follow-up. Six patients were not implanted because of lack of intraoperative tremor suppression (2 patients), hemorrhage (2 patients), withdrawal of consent (1 patient), and persistent microthalamotomy effect (1 patient). A significant reduction in both essential and parkinsonian tremor occurred contralaterally with stimulation. Patients reported a significant reduction in disability. Measures of function were significantly improved in patients with essential tremor. Complications related to surgery in implanted patients were few. Stimulation was commonly associated with transient paresthesias. Other adverse effects were mild and well tolerated. Efficacy was not reduced at 1 year. Chronic high-frequency stimulation is safe and highly effective in ameliorating essential and parkinsonian tremor.

Aged

Effect of the day of administration on the developmental toxicity of tributyltin chloride in rats.

The objective of this study was to determine the susceptible day for the teratogenicity of tributyltin chloride (TBTCI) by a single administration on one of the days during organogenesis. Pregnant rats were given a single dose of TBTCI by gastric intubation at 100 mg/kg on either day 7, day 8, or day 9 and at 200 mg/kg on either day 7, day 8, day 9, day 10, day 11, day 12, day 13, day 14, or day 15 of pregnancy. The maternal body weight gain in the period immediately following administration in all TBTCI-treated groups was significantly decreased. A significant increase in the incidence of postimplantation loss was found after administration of TBTCI on day 7, day 8, and day 9 at 100 and 200 mg/kg and on day 10 and day 11 at 200 mg/kg. A significantly increased incidence of fetuses with external malformations was detected when TBTCI was given on day 8 at 100 and 200 mg/kg and on day 11, day 12, day 13, and day 14 at 200 mg/kg, and the most pronounced effect occurred after administration on day 13 of pregnancy. Cleft palate was observed exclusively after administration during late organogenesis. It could be concluded that the manifestation and susceptibility of the developmental toxicity of TBTCI vary with the developmental stages at the time of administration and that TBTCI has the biphasic sensitivity to teratogenicity on day 8 and days 11-14 of pregnancy.

Abnormalities, Drug-Induced

Developmental toxicity evaluation of phthalic acid, one of the metabolites of phthalic acid esters, in rats.

The objective of this study was to evaluate the developmental toxicity of phthalic acid (PA), which is one of the metabolites of phthalic acid esters (PAEs). Pregnant rats were given PA at a dose of 0 (control), 1.25, 2.5, or 5.0% in the diet on day 7 through day 16 of pregnancy. Average daily intakes of PA were 1021 mg/kg for the 1.25% group, 1763 mg/kg for the 2.5% group, and 2981 mg/kg for the 5.0% group. Maternal toxicity occurred in the 2.5 and 5.0% groups as can be seen by significant decreases in the maternal body weight gain and food consumption during the administration period. No significant changes in maternal parameters were found in the 1.25% group. Neither deaths nor clinical signs of toxicity were noted in any groups. No significant changes induced by PA were detected in the incidence of postimplantation loss and number and sex ratio of live fetuses. Significant decreases in the weight of male fetuses and number of ossification center of the caudal vertebrae were found in the 5.0% group. Morphological examinations of fetuses revealed no evidence of teratogenesis. Thus it appears unlikely that PA may be responsible for the production of the developmental toxicity of PAEs.

Animals

Serotonin, dopamine, and motor effects in Parkinson's disease.

We review recent reports suggesting that use of selective serotonergic agents that either inhibit synaptic reuptake or have specific serotonin receptor affinities may benefit a variety of motor disturbances in Parkinson's disease. The complex, mixed motoric effects of these agents in Parkinson's disease have not allowed for a consistent view on the interrelationship between dopamine and serotonin (5HT) in motor control but may speak to the nature of dysregulated neurotransmission in the disease.

Animals

Motor complications of chronic levodopa therapy in Parkinson's disease.

We report on motor complications of chronic levodopa therapy among 811 levodopa-responsive patients with idiopathic Parkinson's disease (PD), stratified by duration after diagnosis. Predictable "offs" were noted in 20.2% of patients in the first 5 years, in 58.3% after 15 years. Unpredictable or sudden offs and early morning dystonia were less common. Longer duration was associated with greater percentages of patients with off periods or dyskinesias (up to 70% after 15 years), although patients with 6-15 years' duration saw relatively little increase in frequency of those complications, and a minority of patients (approximately 30%) with duration into the second decade did not experience off periods or dyskinesia. Across groups, mean Hoehn and Yahr stage and daily levodopa dosage progressively increase (and mean Schwab and England disability ratings decrease), but more conservatively than in prior reports in the postlevodopa era. We note that with advancing PD duration, levodopa complications are more common, but in many cases there appear to be relatively stable periods in terms of levodopa dosage and disease severity, and a minority of patients will be relatively free of motor complications into the second decade of their disease.

Adult

High-frequency stimulation of the globus pallidus for the treatment of Parkinson's disease.

Long-term treatment of Parkinson's disease (PD) with levodopa is complicated by the development of motor fluctuations and dyskinesias. Posteroventral pallidotomy can improve tremor, bradykinesia, rigidity, and dyskinesias in PD. We performed chronic stimulation of the globus pallidus (CSGP) to duplicate the positive results of pallidotomy with reduced risk of permanent neurologic deficit in patients with advanced PD. The lead for CSGP was stereotactically implanted with the aid of microelectrode recordings in the globus pallidus pars interna. An electrical pulse generator was implanted in the subclavicular region. Stimulation settings were adjusted by computer. Five PD patients (four men, one woman) with disabling symptoms were enrolled. Three of the patients had bilateral implants. At 3 months following the last implant, four patients rated themselves as markedly improved, and one patient was moderately improved. The amount of time in the "on" state increased from 21% at baseline to 65% at 3-month follow-up (p < 0.05). There was a significant improvement in all subscales of the UPDRS (p < 0.05). One patient had an asymptomatic intracranial bleed, one patient had transient hemiparesis during surgery with stimulation, and one patient required surgical repositioning of the lead. Adverse effects caused by stimulation were minimal. CSGP is a safe and effective procedure in PD patients with motor fluctuations and dyskinesias.

Aged

Unilateral pallidal stimulation for Parkinson's disease: neurobehavioral functioning before and 3 months after electrode implantation.

Unilateral pallidotomy is thought to have a low risk for cognitive morbidity. Nonetheless, recent research suggests that some patients experience declines in memory and language and that pallidal stimulation might be a safer treatment for Parkinson's disease (PD). We investigated the neurobehavioral effects of unilateral pallidal stimulation. Nine consecutive PD patients undergoing unilateral deep brain-stimulating electrode implantation in the globus pallidus interna were evaluated with a neuropsychological test battery approximately 1 month before and 3 months after surgery. Patients reported significantly fewer symptoms of anxiety and greater vigor after surgery. There was a trend toward fewer depressive symptoms. Semantic verbal fluency and visuoconstructional test scores declined significantly after surgery. However, among five patients showing declines in semantic verbal fluency, only one patient's score declined by more than 2 SD. No patient showed significant decline or improvement in the overall level of cognitive functioning. This study supports the relative safety, in terms of cognitive function, of unilateral pallidal stimulation in PD.

Adult

[The Endotoxin Reference Standard of the National Institute of Health Sciences (the Japanese Pharmacopoeia Endotoxin Reference Standard) (Control 971)].

The third lot (Control 971) of the Endotoxin Reference Standard of the National Institute of Health Sciences (the Japanese Pharmacopoeia Endotoxin Reference Standard) was prepared. The potency of the new lot was assayed against USP Endotoxin Reference Standard (EC-6) and defined as containing 13,000 endotoxin units (EU) per vial by a collaborative study of 7 laboratories.

Endotoxins

Developmental toxicity of mono-n-benzyl phthalate, one of the major metabolites of the plasticizer n-butyl benzyl phthalate, in rats.

Mono-n-benzyl phthalate (MBeP), one of the major metabolites of the plasticizer n-butyl benzyl phthalate, was evaluated for developmental toxicity in Wistar rats. Rats were given MBeP by gastric intubation at 0, 250, 313, 375, 438 or 500 mg/kg from day 7 through day 15 of pregnancy. Significant decreases in the maternal body weight gains and food consumption during administration period were observed at 313 mg/kg and above and at 250 mg/kg and above, respectively. Significant increase in the incidence of postimplantation loss per litter was found at 438 and 500 mg/kg. The incidences of fetuses with external malformations at 438 mg/kg, of fetuses with skeletal malformations at 313 mg/kg and above and of fetuses with internal malformations at 375 mg/kg and above were higher than those in the control group. Defects in the cervical and thoracic vertebrae, ribs and kidney were frequently observed.

Abnormalities, Drug-Induced

[The Human Menopausal Gonadotrophin Reference Standard (Control 961) of the National Institute of Health Sciences].

Raw human menopausal gonadotrophin (HMG) material was examined for preparation of the "Human Menopausal Gonadotrophin Reference Standard (Control 961)". The candidate material was assayed its follicle stimulating hormone (FSH) activity and luteinizing hormone (LH) activity against the 3rd International Standard for FSH and LH, urinary (71/264) by the augmented ovarian weight gain assay and the seminal vesicle weight gain test, respectively. The potency of the new standard was defined as 56 international units of FSH activity per mg and 61 international units of LH activity per mg as the result of 13 and 5 assays, respectively, in four collaborative laboratories.

Animals

Effect of fluoxetine on anger in symptomatic volunteers with borderline personality disorder.

Clinical data and uncontrolled observations have suggested that fluoxetine is helpful in some patients with borderline personality disorder. This article describes the results of a 13-week double-blind study of volunteer subjects with mild to moderately severe borderline personality disorder. Thirteen fluoxetine recipients and nine placebo recipients received treatment. Pretreatment and posttreatment measures were obtained for global mood and functioning, anger, and depression. The most striking finding from this study was a clinically and statistically significant decrease in anger among the fluoxetine recipients. This decrease was independent of changes in depression. These data support previous observations that fluoxetine may reduce anger in patients with borderline personality disorder. The number of subjects in this study was small, the placebo responsiveness was high, and the clinical characteristics of the patients were in the mild to moderate range of severity. The data cannot be extrapolated to more severely ill borderline patients, but further study of fluoxetine and other selective serotonin reuptake inhibitors is indicated in this population.

Adult

The treatment of autonomic dysfunction.

Autonomic dysfunction is responsible for much of the morbidity associated with frequently encountered neurological disorders, such as Parkinson's disease, multiple sclerosis, cerebrovascular disease, and peripheral neuropathies, as well as with the rarer primary autonomic nervous system degenerations. We review the treatment of those aspects of autonomic dysfunction that often present to the neurologist, including orthostatic hypotension, urinary incontinence and retention, and bowel dysmotility syndromes. Pathophysiology is discussed in each instance as it relates to a rational approach to therapy. For management of orthostatic hypotension, we review the use of mineralocorticoids, direct and indirect sympathomimetic agents, other pressors, dopamine-blocking agents, vasopressin receptor agonists, and others. Treatment of urinary incontinence and retention is addressed, with attention to drugs that modulate bladder contractility and bladder outlet resistance. Therapies for bowel dysmotility syndromes (such as gastroparesis, diarrhea, and fecal incontinence) are described, including bulk agents, laxatives, prokinetic agents, and antidiarrheal drugs.

Autonomic Nervous System Diseases

Parenteral lorazepam versus parenteral haloperidol for the control of psychotic disruptive behavior.

In a double-blind, prospective study, 2 mg of intramuscular lorazepam and 5 mg of intramuscular haloperidol were equally effective in controlling aggression, agitation, and assaultive behavior. Although lorazepam and haloperidol produced an equivalent mean decrease in aggression, significantly more subjects who received lorazepam had a greater decrease in aggression ratings than haloperidol recipients; this effect was independent of sedation. Lorazepam produced significantly fewer extrapyramidal symptoms. These data support the current clinical practice of using lorazepam (alone, or in combination with a neuroleptic) for control of acute aggressive and assaultive behavior.

Acute Disease