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Biomedical subjects

Tetsuo Shimizu

Publications and source records attributed to Tetsuo Shimizu.

At least 55 records · Page 3Linked to original sources
PubMed2003

Relationship between clinical effects of fluvoxamine and the steady-state plasma concentrations of fluvoxamine and its major metabolite fluvoxamino acid in Japanese depressed patients.

OBJECTIVES: The relationship between clinical effects of fluvoxamine (FLV) and the steady-state plasma concentrations (Css) of FLV and its major metabolite fluvoxamino acid (FLA) was studied. METHODS: The subjects were 49 Japanese patients with major depressive disorder receiving FLV 200 mg/day for 6 weeks. Depressive symptoms and side effects were evaluated by the Montgomery Asberg Depression Rating Scale (MADRS), and the UKU Side Effect Rating Scale, respectively. The Css of FLV and FLA were measured by HPLC, and the CYP2D6 genotyping was performed by PCR methods. RESULTS: The Css of FLV and FLV+FLA showed significant negative correlations with the final MADRS score. The Css of FLV, FLA and FLV+FLA were significantly higher in the responders (final MADRS score < or =10) than in non-responders. The proportion of responders was significantly higher in the patients with the Css of FLV, FLA and FLV+FLA above 150, 55 and 180 ng/ml, respectively. In the multiple regression, the Css of FLV+FLA showed a significant negative correlation with the final MADRS score. In the logistic regression, the Css of FLA had a significant effect on the differentiation of responders from non-responders. The incidence of side effects was low, and the development of nausea, the most frequent one, was not dependent on any Css. The number of mutated CYP2D6 alleles causing absent or decreased enzyme activity was not related to the therapeutic response or development of nausea. CONCLUSIONS: The present study suggests that there is a therapeutic threshold for the Css of FLV and probably also for the Css of FLA, and the Css of FLV+FLA above 180 ng/ml best predicts a good therapeutic response.

Adult↗
PubMed2003

Heat loss, sleepiness, and impaired performance after diazepam administration in humans.

In spite of the accumulation of knowledge regarding the neuropharmacological action of benzodiazepines (Bz), the physiological process by which their sedative/hypnotic effects are induced remains poorly understood. We conducted a single-blind, crossover trial to evaluate the role of the thermoregulatory process in sleepiness and impaired psychomotor performance induced by a standard Bz, diazepam (DZP). Each of the eight healthy young male volunteers (mean age, 19.75 years; range, 18-23 years) was given a single oral dose of either 5 or 10 mg of DZP or placebo 12 h after his average sleep onset time. Changes in plasma DZP concentration, proximal body temperature (p-BT), distal body temperature (d-BT), subjective sleepiness measured by the Visual Analog Scale and Stanford Sleepiness Scale, and psychomotor performance measured by Choice Reaction Time were monitored under a modified constant routine condition in which various factors affecting thermoregulation, alertness, and psychomotor performances were strictly controlled. Orally administered DZP induced a significant transient decrease in p-BT and psychomotor performance as well as an increase in d-BT and subjective sleepiness. Distal-p-BT gradient (DPG; difference between d-BT and p-BT), which is an indicator of blood flow in distal skin regions, showed a strong positive correlation with the plasma DZP concentration, indicating that DZP in clinical doses promotes heat loss in a dose-dependent manner. The DPG also correlated positively with the magnitude of subjective sleepiness and impaired psychomotor performance. These findings indicate that the sedative/hypnotic effects of Bz could be due, at least in part, to changes in thermoregulation, especially in the process of heat loss, in humans.

Administration, Oral↗
PubMed2003

Milnacipran plasma levels and antidepressant response in Japanese major depressive patients.

The relationship between antidepressant effects and plasma levels of milnacipran was studied in 49 cases of major depression without psychotic features during 6 weeks of milnacipran treatment. The daily dose of milnacipran was 50 mg/day for the first week, and up to 100 mg/day thereafter. Depressive symptoms were evaluated by the Montgomery and Asberg depression rating scale (MADRS) before treatment and at 1, 2, 4 and 6 weeks after the beginning of this study. Thirty-four patients (69.4%) were responders (defined as a 50% or greater decrease in the baseline MADRS score). Significant differences of MADRS scores were seen from 1 week after the beginning of this study (p=0.004, unpaired t-test) between responders and nonresponders. The mean plasma milnacipran level of responders, 82.0 +/- 29.4 ng/ml, was similar to that of non-responders, 78.6+/-23.1 ng/ml; there was no significant difference between responders and nonresponders. Neither a significant linear nor a curvilinear relationship was obtained between the final MADRS score and the plasma levels of milnacipran. Although there was no significant relationship between the plasma levels of milnacipran and the antidepressant response, milnacipran should be considered an efficacious agent in the treatment of major depressive patients.

Adrenergic Uptake Inhibitors↗
PubMed2003

Quetiapine treatment of psychotic symptoms and aggressive behavior in patients with dementia with Lewy bodies: a case series.

The authors describe here the clinical outcomes of quetiapine treatment in nine patients with dementia with Lewy bodies (DLB) who manifested psychotic symptoms and aggressive behavior. Patients who had a score of 3 or higher on any of the three items of the Neuropsychiatric Inventory (NPI), agitation/aggression, hallucinations, and delusions, were given quetiapine 25-75 mg/day. Each patient's clinical status was assessed at baseline and after 4 and 8 weeks of treatment by using the NPI, Mini-Mental State Examination (MMSE), and Simpson-Angus Scale (S-A). Five of nine patients had a positive response with a decline of more than 50% in the sum of scores for three items of the NPI. The other three patients withdrew from quetiapine treatment due to somnolence or orthostatic hypotension. The remaining patient exhibited no clinically significant change in the NPI score. The S-A scale was not affected by quetiapine treatment in any patient. These findings suggest that quetiapine may be effective in treating psychotic symptoms and disruptive behavior in some patients with DLB. Further placebo-controlled, randomized, double-blind trials with this drug are needed to confirm this observation.

Aged↗
PubMed2003

Effects of the CYP 2D6 genotype and cigarette smoking on the steady-state plasma concentrations of fluvoxamine and its major metabolite fluvoxamino acid in Japanese depressed patients.

The effects of the cytochrome P450 (CYP) 2D6 genotype and cigarette smoking on the steady-state plasma concentrations (C(ss)) of fluvoxamine (FLV) and its demethylated metabolite fluvoxamino acid (FLA) were studied in 49 Japanese depressed patients receiving FLV 200 mg/d. The C(ss) of FLV and FLA were measured by HPLC, and the wild-type allele (*1) and two mutated alleles causing absent (*5) or decreased (*10) CYP 2D6 activity were identified by PCR methods. The patients were divided into three genotype groups by the number of mutated alleles: 12 cases with no (*1/*1), 27 cases with one (*1/*5 and *1/*10), and 10 cases with two (*5/*10 and *10/*10) mutated alleles. The means +/- SD of the C(ss) of FLV and FLA and the FLA/FLV ratio of all patients were 169.1 +/- 147.5 ng/mL, 83.9 +/- 52.7 ng/mL, and 0.71 +/- 0.50, respectively. The C(ss) of FLV and FLA were not significantly different among the three genotype groups. However, the FLA/FLV ratio was significantly lower in the patients with one (P < 0.05) and two (P < 0.01) mutated alleles than in those with no mutated allele. There was no significant difference between nonsmokers (n = 34) and smokers (n = 15) in these values. In the stepwise multiple regression, the C(ss) of FLA (P < 0.05) and FLA/FLV ratio (P < 0.001) showed significant negative correlations with the number of mutated alleles, and the FLA/FLV ratio was significantly (P < 0.05) lower in women than in men. The present study suggests that the CYP 2D6 genotype and cigarette smoking have no major impact on the C(ss) of FLV and FLA, though CYP 2D6 is involved in the demethylation of FLV.

Adult↗
PubMed2003

Monoamine oxidase A gene polymorphism, 5-HT 2A receptor gene polymorphism and incidence of nausea induced by fluvoxamine.

Selective serotonin reuptake inhibitors cause a side effect of nausea with high frequency, but there have been no accurate methods to predict its incidence. The authors first investigated whether a functional polymorphism in the monoamine oxidase A (MAOA-VNTR) and a -1438G/A polymorphism in the promoter region of the 5-HT(2A) gene were associated with the incidence of nausea induced by fluvoxamine. Fluvoxamine was administered for 6 weeks with a specific dosage plan (50-200 mg/day) in 66 Japanese major depressive patients. The frequency of MAOA-VNTR allele 1 was significantly higher in the patients without nausea than in ones with nausea in the statistical analysis including the patients whose plasma levels were below the average and who were considered to be pharmacodynamically more sensitive to nausea. This study showed that the genetic polymorphism of MAOA-VNTR might affect the incidence of nausea induced by SSRIs. If this finding is replicated in other studies with more subjects, MAOA-VNTR polymorphism would be of great clinical use to predict the incidence of nausea induced by SSRIs.

Adult↗
PubMed2003

Effectiveness of switching to quetiapine for neuroleptic-induced amenorrhea.

This study investigated the effectiveness and tolerability of a switching strategy using quetiapine in 16 women with schizophrenia who were suffering from haloperidol- or risperidone-induced amenorrhea. Findings revealed that 10 patients (71.6%) resumed menstruation, without worsening of psychotic symptoms.

Adult↗
PubMed2003

Stability of sleep timing against the melatonin secretion rhythm with advancing age: clinical implications.

Aging is often associated with decreased ability of sleep maintenance. It has been hypothesized that the elderly experience a delayed timing of sleep period relative to the circadian phase of various sleep-promoting physiological functions, possibly causing decreased sleep propensity in the latter part of their nocturnal sleep. We evaluated the relationship between the sleep timing and circadian phase of melatonin secretion, which is known as a possible human sleep modulator as well as a stable marker of biological clock phase (BCP). Actigraph sleep recordings were performed, followed by the evaluation of melatonin phase under dim light in 42 healthy elderly volunteers (mean age, 68.8 yr; male/female ratio, 16/26) and 27 healthy young male volunteers (22.5 yr). Elderly subjects showed remarkable clock time advances in both the midpoint of BCP and sleep timing, with a significant decrease in sleep maintenance ability. However, they showed no significant age-related changes in the sleep timing against the midpoint of BCP, suggesting that early morning awakening in the elderly appeared in a BCP for which sleep propensity remained sufficient to sustain sleep. The present findings do not support the hitherto known hypothesis that age-related delay in the sleep timing against the BCP induces the deterioration in sleep maintenance in the elderly.

Aged↗
PubMed2003

Pharmacological mechanism in slip-down behavior of mice.

Slip-down from a raised platform was previously found in mice treated with morphine, and this behavior was also recognized in mice treated with a monoamine releaser methamphetamine. Pharmacological examination on the slip-down indicated that the behavior was induced by receptor stimulations by D2 agonist PPHT and 5HT-2 agonist DOI. In mice treated with PPHT, antagonists of D1, alpha2, 5HT-2 and opioid mu and kappa suppressed the behavior. In mice treated with DOI, antagonists of D1, alpha2, 5HT-1A, 5HT-3 and opioid mu and delta suppressed the behavior. These present findings suggest that the slip-down was mainly induced by opioid mu receptor activity regulated with monoamine activities. When the slip-down is considered as an anxious behavior, it may be also suggested that the anxiety induced by 5-HT activities furthermore stimulated the behavior via the other opioid receptor activities.

Animals↗
PubMed2003

High-performance liquid chromatographic determination of fluvoxamine and fluvoxamino acid in human plasma.

A high-performance liquid chromatographic (HPLC) method has been developed for the simultaneous determination of fluvoxamine and its major metabolite fluvoxamino acid in plasma. Fluvoxamine and fluvoxamino acid in plasma were extracted using a C18 bonded-solid phase cartridge, followed by C4 reversed-phase HPLC separation.Fluvoxamine, fluvoxamino acid and moperone as an internal standard were detected by ultraviolet absorbance at 254 nm. It was possible to determine both fluvoxamine and fluvoxamino acid in the concentration range of 25.0-200.0 ng/mL, respectively. The detection limits of both fluvoxamine and fluvoxamino acid were 10.0 ng/mL, respectively. The mean recoveries of fluvoxamine and fluvoxamino acid added to plasma were more than 94.0% and 96.5%, with a coefficient of variation of less than 7.6% and 8.2%, respectively. This method has been used for the simultaneous determination of steady-state plasma concentration (Css) of fluvoxamine and fluvoxamino acid in depressive patients treated with 200 mg of oral fluvoxamine dosed as 100 mg twice-daily. The Css values of fluvoxamine and fluvoxamino acid in twelve Japanese patients were showed individual variations, which were in the range of 48.3-532.9 ng/ml and 35.6-307.1 ng/ml, respectively.

Amino Acids↗
PubMed2003

Hypersomnia and low CSF hypocretin-1 (orexin-A) concentration in a patient with multiple sclerosis showing bilateral hypothalamic lesions.

A 45-year-old Japanese woman with multiple sclerosis (MS) manifested hypersomnia in a relapse of MS. Magnetic resonance imaging revealed new bilateral hypothalamic lesions, and the hypocretin-1 level in the cerebrospinal fluid (CSF) was significantly low. Methylprednisolone pulse treatment successfully resolved the hypersomnia and the left hypothalamic lesion, and it normalized the hypocretin-1 level in the CSF. These findings suggest that the hypothalamic hypocretin (orexin) system may be crucial to maintaining the arousal level and that lesions in the system can cause hypersomnia in MS.

Anti-Inflammatory Agents↗
PubMed2003

[An adult case of tuberculous meningitis].

A 36-year-old man was referred to our hospital with complaints of high fever and headache. A diagnosis of miliary tuberculosis with tuberculous meningitis was made. He was treated with isoniazid (400 mg/day), rifampicin (300 mg/day), ethambutol (750 mg/day), pyrazinamide (1.0 g/day) and prednisolone (60 mg/day). However, he lost consciousness because of hydrocephalus on the second day of hospitalization. Emergency cerebrospinal fluid drainage improved his neurological symptoms. After two months, he again complained of headache with nausea and double vision. Numerous tuberculomas were found not only in the cerebrum but also in the liver, the spleen and the retina. Recurrent hydrocephalus was treated with a V-P shunt, and combination therapy with four antituberculous agents was maintained for 18 months. He was discharged in a healthy condition, although a mild left facial palsy remained. In addition, we examined the inflammatory cytokine levels in both the CSF and the serum over the period of the patient's hospitalization. We concluded that the cytokine levels in the CSF may be associated with the progress and the prognosis of tuberculous meningitis.

Adult↗
PubMed2003

[Two cases of pulmonary Mycobacterium xenopi infection].

We report on two patients diagnosed as having Mycobacterium xenopi infections. Case 1 occurred in a 40-year-old man. His chest radiograph revealed a cavitary lesion with a granular shadow in the right upper lung field. His sputum and bronchial lavage were negative for acid-fast bacilli and malignant cells. For a definitive diagnosis, lung resection was performed by video-assisted thoracoscopy. Case 2 was in a 45-year-old man. His chest radiograph showed a cavitary lesion with infiltration in the right upper lung field. Acid-fast bacilli were seen in his sputum specimens and M. xenopi was identified by culture. Despite medication with isoniazide, rifampicin and ethambutol, the infiltrative shadow in his radiograph increased in size. In this case, right upper lobectomy was performed. In recent years, 8 cases of pulmonary Mycobacterium xenopi infection have been reported in Japan. In the future, the number of such case reports may increase as a result of diagnosis by molecular biological methods. It is necessary to consider carefully whether surgical resection is required when chemotherapy is refused by the patient or is likely to be unsuccessful.

Adult↗
PubMed2003

[A case of pulmonary cryptococcosis with multiple nodular shadows under treatment of bronchiolitis obliterans with organizing pneumonia (BOOP)].

A 66 year-old man was introduced to our hospital because of multiple infiltrative pulmonary shadows on February, 2001. We diagnosed bronchiolitis obliterans with organizing pneumonia (BOOP) from the clinical and bronchoalveolar lavage fluid (BALF) findings, and initiated oral steroid therapy. Since the abnormal chest shadows disappeared, the dose of steroid was decreased and maintained at 10 mg/day. In August 2001, multiple infiltrative shadows returned, and we therefore increased the steroid dose to 30 mg/day. The expanding infiltrative shadows were then joined by new multiple nodular shadows. The bronchioalveolar lavage fluid revealed small bodies of cryptococcus species. A positive result for anti-cryptococcus antigen was also obtained from the serum. We then diagnosed pulmonary cryptococcosis without meningitis. Therapy was started with anti-mycotic agents including amphotericin-B, flucytosine and fluconazole, which proved successful. This case of opportunistic cryptococcus infection in an immunocompromized patient, which responded to anti-mycotic therapy, is reported.

Aged↗
PubMed2002

Tardive dystonia and genetic polymorphisms of cytochrome P4502D6 and dopamine D2 and D3 receptors: a preliminary finding.

Tardive dystonia is an uncommon but intractable and distressing complication of neuroleptic treatment. It is suggested that individual predisposing vulnerability plays a major role in the development of the side effect. This study aimed to investigate relationship tardive dystonia and several genetic factors such as polymorphism of cytochrome P4502D6, and receptor polymorphisms of dopamine D(2) (TaqI A and -141C Ins/Del polymorphisms) and D(3) (Ser(9)Gly polymorphism). Nine patients with tardive dystonia were genotyped for these genetic polymorphisms. No specific genotypes or alleles were overpresented in the patients. This study suggests that these polymorphisms are not related to the development of tardive dystonia.

Adult↗