Attitude of patients with mood disorder toward clinical trials in Japan.
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Biomedical subjects
Publications and source records attributed to Koichiro Watanabe.
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This paper provides the results of studies on the characteristics of novel material derived from pyrolysis/melting treatment of municipal solid waste in Japan. Slag products from pyrolysis/melting plants were sampled for the purpose of detailed phase analysis and characterization of heavy metal-containing phases using optical microscopy, electron probe microanalysis (EPMA), XRF and XRD. The study revealed that the slag material contains glass (over 95%), oxide and silicate minerals (spinel, melilite, pseudowollastonite), as well as individual metallic inclusions as the major constituents. A distinct chemical diversity was discovered in the interstitial glass in terms of silica content defined as low and high silica glass end members. Elevated concentrations of Zn, Cr, Cu, Pb and Ba were recorded in the bulk composition. Cu, Pb and Ba behave as incompatible elements since they have been markedly characterized as part of polymetallic alloys and insignificantly sulfides in the form of spherical metallic inclusions associated with tracer amounts of other elements such as Sb, Sn, Ni, Zn, Al, P and Si. In contrast, an appreciable amount of Zn is retained by zinc-rich end members of spinel and partially by melilite and silica glass. Chromium exhibits similar behavior, and is considerably held by Cr-rich spinel. The intense incorporation of Zn and Cr into spinel indicates the very effective enrichment of these two elements into phases more environmentally resistant than glass. There was no evidence, however, that Cu and Pb enter into the structure of the crystalline silicates or oxides that may lead to their easier leachability upon exposure to the environment.
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There are sporadic reports of antipsychotic-induced visual hypersensitivity attack (VHA). VHA is characterized by hypersensitivity of perception mainly in the visual modality and sometimes accompanied by an oculogyric crisis. However, some researchers regard VHA as a schizophrenia symptom. To determine whether VHA is an adverse effect of antipsychotic agents, we examined the effect of dose reduction on VHA. This was an open-label 36-week study. We randomized 34 patients with VHA to a reduced-dose group and a fixed-dose group. Primary outcome measures were the frequency and duration of VHA, assessed with patients' self-reports, and the Clinical Global Impressions (CGI). Assessment also included the Drug-induced Extrapyramidal Symptoms Scale for extrapyramidal symptoms, the Positive and Negative Syndrome Scale (PANSS) for schizophrenia, and the CGI for other diagnoses. Data were collected from August 2000 to April 2005 at 4 psychiatric hospitals in Tokyo.VHA diminished in 16 patients (94.1%) in the reduced-dose group in the CGI score, the frequency (number of episodes per week), and the duration of the episodes (from 4.06 to 1.77, P < 0.001; from 2.59 to 0.82, P = 0.001; and from 1.92 to 0.66 hours, P = 0.007, respectively), but there were no changes in the fixed-dose group. There were no changes in the underlying illness as measured by the PANSS in both groups. Reducing the dose of antipsychotic agents ameliorates VHA and represents the ideal treatment option for patients with VHA.
PURPOSE: This study examined the possible relationship between peptic ulcer recurrence and the presence or absence of maintenance therapy with an H(2)-receptor antagonist performed until evaluation of Helicobacter pylori eradication. METHODS: The subjects were 483 patients with peptic ulcer (281 gastric ulcer and 202 duodenal ulcer) who were diagnosed as H. pylori positive. After receiving eradication therapy for H. pylori, patients were allocated at random to one of three different maintenance therapies: control group (no maintenance therapy), H(2)-receptor antagonist half-dose group, and H(2)-receptor antagonist full-dose group. The maintenance therapy was performed for 4 weeks until evaluation of H. pylori eradication. RESULTS: Among the 25 patients with a recurrent ulcer, 18 patients (72%) had a recurrence at the time of or before evaluation of H. pylori eradication. In the control group, the rate of ulcer recurrence occurring before evaluation of H. pylori eradication was 10.5% (14/133). This rate was significantly higher than those in the H(2)-receptor antagonist half-dose group (2.9%, 4/136) and the full-dose group (0%, 0/135). CONCLUSION: The results of this study suggest that maintenance therapy with an H(2)-receptor antagonist performed after eradication therapy until evaluation of H. pylori eradication is likely to greatly reduce the ulcer recurrence rate without affecting evaluation of H. pylori eradication.
BACKGROUND: Widespread use of eradication therapy for Helicobacter pylori has increased the prevalence of clarithromycin-resistant strains. The purpose of the present paper was to measure the in vitro antibacterial activity of minocycline against H. pylori, and study the effectiveness of minocycline-based first- and second-line eradication therapies. METHODS: For first-line therapy, 79 patients were randomly assigned to the treatment with rabeprazole, amoxicillin, and clarithromycin or with rabeprazole, amoxicillin, and minocycline. For second-line therapy, 88 patients were tested for sensitivity to metronidazole: 67 patients with metronidazole-sensitive strains received a 7-day course of rabeprazole, minocycline, and metronidazole; the remaining 21 patients were given a 7-day course of rabeprazole, minocycline, and faropenem. RESULTS: There was virtually no resistance to minocycline among the strains tested. The eradication rate of H. pylori infection in first-line therapy was significantly lower for minocycline-containing regimen (38.5%, 15/39) than for clarithromycin-containing regimen (82.5%, 33/40; P < 0.01). For second-line therapy, a high eradication rate against metronidazole-sensitive strains was obtained with rabeprazole, minocycline and metronidazole (85%, 57/67). CONCLUSIONS: A combination of rabeprazole, minocycline, and metronidazole is safe and effective for second-line therapy of H. pylori infection. Because this regimen can be administered to patients with penicillin allergy and patients who suffer adverse reactions to amoxicillin, such as diarrhea and other digestive symptoms, it should be considered useful for second- and third-line eradication therapy.
BACKGROUND: Proton pump inhibitor-amoxicillin-metronidazole is recommended as second-line Helicobacter pylori therapy in Japan. The authors assessed the efficacy and safety of second-line eradication using the H2-receptor antagonist famotidine as a substitute for proton pump inhibitor. MATERIALS AND METHODS: Sixty-one patients who failed in first-line H. pylori eradication using proton pump inhibitor-clarithromycin-amoxicillin were randomly assigned to either second-line therapy including metronidazole: a 7-day course of lansoprazole 30 mg, amoxicillin 750 mg, and metronidazole 250 mg, b.i.d. (lansoprazole group); or a 7-day course of famotidine 40 mg, amoxicillin 750 mg, and metronidazole 250 mg, b.i.d. (famotidine group). Eradication was assessed for each group at least 4 weeks after completing eradication therapy. Drug susceptibility test was performed using 57 strains in pretreatment to clarithromycin, metronidazole, and amoxicillin. RESULTS: Prior to second-line H. pylori eradication, the rate of resistance to clarithromycin was high at 84% (48/57). Similarly, resistance to metronidazole was low at 5.3% (3/57); however, no amoxicillin-resistant strains were found. The eradication rates for both lansoprazole and famotidine treatment groups were high at 97% (29/30) and 94% (29/31), respectively. CONCLUSIONS: Famotidine treatment including metronidazole-amoxicillin as second-line therapy provided a high eradication rate similar to lansoprazole therapy. Famotidine is therefore expected to serve as a useful H. pylori eradication regimen in patients with proton pump inhibitor allergy, an economic benefit in terms of reduced health-care costs is also anticipated.
Although electroconvulsive therapy (ECT) has been employed for treating depression for more than 60 years, its mechanisms of action are yet unknown. To clarify the ECT effects on brain function, we examined cerebral blood flow (CBF) using single photon emission computed tomography at 3 time points--few days before an ECT course (Pre) and approximately 5 days (Post 1) and 1 month (Post 2) after the last ECT session. Eight depressive patients completed the study. In all the patients, the depressive symptoms improved after the ECT course, and major cognitive impairment was not observed at any time point. At Pre, the regional CBF (rCBF) in the widespread areas in the frontal lobe and limbic regions including cingulate cortex and parahippocampal gyrus was lower in the patients than in the normal controls. At Post 1 and Post 2, the rCBF in the frontal and limbic regions continued to be lower in the patients than in the controls although the successive recovery of decreased rCBF in the frontal region was observed. Regarding the time course among the patients, the rCBF in the right medial frontal region significantly increased (toward normal) at Post 2, not at Post 1. These findings suggest that depressive patients have decreased CBF in the frontal and limbic regions, and the medial frontal region plays a crucial role in ECT and recovery from depression. Further, patients who have undergone ECT treatment for depression should be carefully observed because brain functions continue to change even after a successful ECT course.
In this session, the development of antipsychotics and 'atypicality' were discussed firstly. Various concepts regarding 'atypicality' had the meaning of optimal modulation of dopamine. Then, the key role of dopamine for psychotic symptoms and the question how antipsychotics should work for managing those symptoms were treated by introducing the theories by Kapur and Yagi. And from all these reasons, it came to the conclusion that megadose-polypharmacy treatment should be avoided.
Neuroleptic noncompliance is a major reason for relapse in outpatients with schizophrenia. In a 2-year follow-up study, we used the Japanese version of the Rating of Medication Influences Scale (ROMI-J) to investigate the reasons for compliance and noncompliance in outpatients with schizophrenia. Ninety outpatients who were confirmed by interview to have had good compliance for more than 3 months completed the initial interview, which included the Clinical Global Impressions Scale (CGI), the Brief Psychiatric Rating Scale (BPRS), the Global Assessment of Functioning Scale (GAF), the UKU Side Effect Rating Scale, and the ROMI-J. All the outpatients were followed up for 2 years. At the initial interview, the most frequent reason for compliance was "relapse prevention," while the most frequent reason for noncompliance was "distressed by side effects." Fifteen outpatients who proved to be noncompliant in the follow-up period had higher baseline BPRS "agitation" scores and ROMI-J "no perceived daily benefit" ratings than compliant patients. Sixty-four outpatients who maintained compliance during the follow-up had higher baseline ROMI-J ratings of "fulfillment of life goals" than their noncompliant counterparts. It is important to understand the attitudes of patients with schizophrenia toward drug therapy in order to predict better compliance and provide psychoeducation designed to forestall relapses.
RATIONALE: Taking psychotropic medications is frequently problematic from both consumers' and caregivers' perspective. Occasionally missed doses may lead to pervasive non-adherence with relapse a likely outcome. OBJECTIVE: To evaluate the simple medication regimen, all psychotropics were given at night for patients with chronic schizophrenia, who had been taking them at least twice a day for more than 12 weeks before the entry. METHODS: Switching of agents took place in two ways: converting only antipsychotic medications followed by other psychotropics, and changing all psychotropics simultaneously. Any psychotropics of little clinical significance were then cautiously minimized. Final evaluation was made 12 weeks after the competed dose consolidation. Patients finally rated their subjective impression on this intervention. RESULTS: Twenty-five patients were recruited in each treatment arm (50 in total). After switching, 11 got better, 29 remained stable whereas seven got worse, according to the Global Improvement. Three were not assessable. Overall, there were no relevant changes in clinical ratings including adverse effects. However, the chlorpromazine equivalent dose of antipsychotics and the number of total psychotropics were significantly reduced from 957 to 722 mg/day (p<0.0001) and from 4.0 to 3.2 (p<0.0001), respectively. Dose deflation of psychotropics was feasible in 35 subjects (74.5%). Twenty-six (of 40 successful) patients indicated that they favored the night-time regimen mainly because it was less complicated. Sedation in the morning was identified as an important adverse event, which should be addressed by reducing the dose. CONCLUSIONS: The procedure may be of value to counteract a recent trend of psychotropic polypharmacy in schizophrenia.
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Little is known about the long-term benefits of interventions that aim to promote early childhood development programs. The goal of this research was to determine whether an early childhood development intervention added to a nutrition intervention during preschool ages had lasting effects on the cognitive development of school-age children in communes of Thanh Hoa province in rural Vietnam. The study focused on a total of 313 children aged 6.5-8.5 y (grades 1 and 2 in primary school) in 2 communes that were exposed to nutrition intervention or nutrition and early childhood development (ECD) intervention from 1999 to 2003. Measurements of height and cognitive test scores (Raven's Progressive Matrices Test) were collected from the children; household characteristics were determined by interviews with mothers. Longitudinal analysis was performed by integrating the data with that collected from the same children in past surveys. Significant effects of the ECD intervention compared with the nutrition intervention were detected. The beneficial effect of ECD intervention on the cognitive test scores was large for the most nutritionally challenged children whose height-for-age Z-scores declined or remained in the stunted range. The findings help provide useful insights into the development of an effective integrated model of ECD and nutrition intervention for children in rural Vietnam.
Although serotonin reuptake inhibitors are recommended as first-line agents for major depressive disorder, delayed onset of action is problematic, and faster effective treatment is needed. Sulpiride, a dopamine-mediated agent, has been reported to show faster antidepressant efficacy, and we examined the efficacy of adjunctive sulpiride in combination with paroxetine (PAX), compared with PAX alone, to clarify whether the combined treatment exerts faster effect. Forty-one major depressive disorder patients were enrolled in this 12-week open-label trial and were randomly assigned to a PAX (10-40 mg/d) or a PAX (10-40 mg/d) plus sulpiride (100 mg/d) group. Assessments included the Montgomery-Asberg Depression Rating Scale, the 17-item Hamilton Rating Scale for Depression, and the Zung Self-rating Depression Scale on an intent-to-treat basis, and safety was also monitored. Thirty-three patients completed the study. Both PAX + sulpiride and PAX treatments showed a mean reduction in the total Montgomery-Asberg Depression Rating Scale score of 34.4 to 5.6 and 32.2 to 10.4, respectively (P < 0.001). The combined treatment group had a significantly superior outcome in terms of the change in the total Montgomery-Asberg Depression Rating Scale, Hamilton Rating Scale for Depression, and Zung Self-rating Depression Scale scores between week 1 and the study end point (P < 0.05). Median times to response among responders alone for the combined treatment and monotherapy were 2 and 6 weeks, respectively. Both treatments were well tolerated, with no clinically significant differences in safety measures except for an elevation of prolactin in the combined treatment group. The combination treatment may be a safe and effective strategy for accelerating antidepressant response.
BACKGROUND: Although Helicobacter pylori has been regarded as a pathogen of gastric cancer, the mechanism by which H. pylori is involved in gastric carcinogenesis remains unknown. To clarify the role of H. pylori in carcinogenesis, the expression of tumor suppressor p53 and its regulator multiple double minute 2 (MDM2) in gastric mucosa were examined before and after H. pylori eradication. METHODS: Biopsy specimens were obtained from 31 patients with H. pylori-infected gastric mucosa. Endoscopic biopsies were repeated 6 months after successful eradication. In addition, biopsy specimens from 12 patients with non-infected gastric mucosa were obtained. Immunohistochemical analysis was performed on the specimens using primary antibodies specific for p53 and MDM2. RESULTS: Six months after H. pylori eradication, labeling indices for p53 were significantly reduced in the gastric corpus (2.3-fold; P < 0.01), and in the gastric antrum (2.0-fold; P < 0.01). Similarly, labeling indices for MDM2 were significantly reduced in the corpus (1.7-fold; P < 0.01), and in the antrum (3.5-fold; P < 0.01). In the non-infected group, labeling indices for p53 and MDM2 in the gastric mucosa were significantly lower (P < 0.01) than those of the H. pylori-infected group. CONCLUSION: A significant increase is shown in p53 and MDM2 expression in H. pylori-infected gastric mucosa as compared to normal gastric mucosa; but successful eradication of H. pylori dramatically reduced the p53 and MDM2 levels. Therefore, H. pylori infection may be associated with alteration of cell proliferation and apoptosis.
Overdosing often occurs among patients with borderline personality disorder (BPD) and confronts physicians with the dilemma of whether to prescribe psychotropic agents for them or not. Prescribing psychotropic agents is often unavoidable in the real world, because psychotherapy alone is sometimes insufficient to control their labile emotions. We report two cases of BPD in which overdosing was successfully prevented by changing the dosage form from tablets to a powder and adding a bitter taste to make it difficult to swallow a large dose at one time. Prevention of overdosing by BPD patients definitely requires a comprehensive treatment approach in terms of its social, biological, psychological, and psychopathological aspects. Although no perfect method of preventing overdosing is currently available, our method provides an option when psychotropic agents are prescribed for BPD patients in clinical practice.
Persistent Helicobacter pylori infection contributes towards the development of chronic gastritis. To clarify the changes in chronic gastritis as a precursor of gastric cancer secondary to H. pylori eradication is an important issue, as it has significant implications for reducing the risk of gastric cancer. Studies published to date, however, are far from consistent with regard to the morphologic changes reported following H. pylori eradication. Of these, some papers reported improvement in gastric atrophy or intestinal metaplasia, versus others reporting no improvement, with the majority of papers published after 2000 reporting improvement in these end points. The inconsistent results concerning the impact of H. pylori eradication on gastric atrophy could be due to the inconsistency of the diagnostic criteria employed for evaluation of the morphology, confounded by the difficulties involved in evaluating atrophic changes in the gastric mucosa. While adherence to the Updated Sydney System available for evaluation of gastritis is primarily required worldwide to ensure consistency in evaluating gastritis, long-term research into the morphologic changes associated with H. pylori eradication is also required to explore strategies for the prevention of gastric cancer with H. pylori eradication.