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Koichiro Watanabe

Publications and source records attributed to Koichiro Watanabe.

31 records · Page 2Linked to original sources

[Is it valid to concurrently use multiple antipsychotics for patients with schizophrenia?].

The role of antipsychotic polypharmacy in the treatment of schizophrenia remains largely unknown, although such a mode of therapy has frequently been advocated on an empirical basis. This trend has especially been true in Japan. We briefly review current evidence in favor of and against polypharmacy in schizophrenia, then we show the data of revising antipsychotic polypharmacy to monotherapy. The study included 47 patients with chronic schizophrenia. Among the 44 patients assessable, 24 remained stable, 10 got better and 10 got worse after 24 weeks of maintenance monotherapy with the main agent. Overall, there were no significant differences in the Global Assessment of Functioning and the Global Impression of the participants. Conversion to antipsychotic monotherapy was feasible in 22 patients, while another 12 needed low dosages of low-potency agents. The chlorpromazine equivalent amount of antipsychotics was significantly reduced from 1,171 to 952 mg/day in 34 patients who were successful in switching. Although the procedure overall did not help patients much, it is suggested that many instances of antipsychotic polypharmacy are avoidable. Adding medications upon the emergence of symptoms might be an easy way to treat patients. Such an action should be validated in every case, however, and polypharmacy should be tested against prolonged, tenacious monotherapy.

Antipsychotic Agents↗

Effect of Helicobacter pylori eradication on platelet recovery in patients with chronic idiopathic thrombocytopenic purpura.

BACKGROUND: A relationship between Helicobacter pylori infection and idiopathic thrombocytopenic purpura (ITP) has previously been reported. We determined the prevalence of H pylori infection in Japanese patients with chronic ITP and the effect of its eradication on platelet count. METHODS: The study population comprised 53 Japanese adults with chronic ITP and a platelet count of less than 100 x 10(3)/ micro L. A (13)C-urea breath test was performed to determine H pylori infection status. Those patients who were H pylori positive gave written informed consent and received eradication therapy. The effect of H pylori eradication on platelet count was evaluated up to 6 months after therapy. Clinical parameters were compared between responders to the therapy (increase in platelet count) and nonresponders, as well as between H pylori-positive and -negative patients. RESULTS: Of the 53 patients with chronic ITP in the study, 39 (74%) were H pylori positive. Of the 32 infected patients who received treatment, H pylori was successfully eradicated in 27 patients (84%). In 10 (37%) of these patients, this resulted in a favorable platelet response. A partial response was seen in 5 additional patients (19%). A significant (P<.001) increase in platelet count was demonstrated in patients in whom H pylori was successfully eradicated but not in patients who were unsuccessfully treated or in untreated patients. Current corticosteroid therapy was reported more often in nonresponders than in responders. CONCLUSION: Eradication of H pylori may prove effective in increasing platelet count in H pylori-positive patients with chronic ITP.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Revising polypharmacy to a single antipsychotic regimen for patients with chronic schizophrenia.

Antipsychotic polypharmacy has been empirically used and a recent trend in favour of that mode of therapy has been suggested for the treatment of schizophrenia. The clinical efficacy, however, still remains to be clarified. In order to critically evaluate the usefulness of such kind of psychopharmacotherapy, antipsychotic combination regimen (polypharmacy) was switched to a treatment with the single main antipsychotic (monotherapy) in cross-tapered fashion, while approximately maintaining the total amount, for patients with chronic schizophrenia. Patients had been treated with an average of three antipsychotics and maintained with the same antipsychotic polypharmacy regimen for more than 6 months before the entry. They were followed up with an antipsychotic monopharmacy and evaluated at 24 wk after completion of switching. Forty-seven patients were recruited for this study. Of 44 patients for whom evaluation was possible, 24 (54.5%) remained stable, while 10 (22.7%) showed improvement and the same number of patients ended in a deleterious status. Twenty-two patients were converted to antipsychotic monotherapy, while another 12 needed minimal dosing of low-potency agents. Overall, social functioning, evaluated by the Global Assessment of Functioning and the Clinical Global Impression, remained unchanged. Eighteen of 34 successful patients showed adverse effects of the main antipsychotic medication, which necessitated a significant dose reduction. Nine out of 10 deteriorating patients had been treated with a combination of low- and high-potency antipsychotics. It is suggested that many instances of antipsychotic polypharmacy is avoidable. The result is compatible with the current treatment recommendations, which dictate the use of a single antipsychotic agent.

Adult↗

A clinical case series of switching from antipsychotic polypharmacy to monotherapy with a second-generation agent on patients with chronic schizophrenia.

Second-generation antipsychotic medications have become popular as a treatment for schizophrenia. The authors investigated 25 chronic subjects who had previously been treated with high-dose antipsychotic polypharmacy without amelioration. All patients had a history of having been treated with an antipsychotic polypharmacy regimen of the total daily chlorpromazine equivalent dose exceeding 1000 mg/day for more than 6 weeks. They were subsequently switched to a second-generation antipsychotic monotherapy. Other psychotropic medications were simplified at the same time. For successful patients whose symptoms showed at least minimal improvement, the medical chart was reviewed retrospectively. After completed switching, the patients were followed up for 12 weeks, when final evaluation was made. The Global Assessment of Functioning score improved from 32 to 47. The number of antipsychotic medications and total psychotropic medications were significantly reduced from 3.5 to 1.1 and 6.8 to 2.6, respectively. Also, the antipsychotic dose was significantly minimized from 2203 to 619 mg/day. Eleven of eighteen inpatients were discharged and the other four were better enough to be ready for discharge. By showing successful cases, the authors suggest a possibility of antipsychotic monotherapy with a second-generation agent even for those patients who had been treated with high-dose antipsychotic polypharmacy in vain.

Adult↗

Effect of sucralfate on antibiotic therapy for Helicobacter pylori infection in mice.

It has been documented that sucralfate, a basic aluminum salt, enhances the efficacies of antibiotics against Helicobacter pylori, resulting in eradication rates comparable to those associated with the use of proton pump inhibitors. However, its mechanism of action remains unclear. The aim of the present study was to investigate sucralfate's ability to complement antibiotic treatment of H. pylori infection in vivo. Four weeks following induced H. pylori infection, clarithromycin (CAM) and amoxicillin (AMPC) were administered orally to C57BL/6 mice for 5 days, both with and without sucralfate or lansoprazole. When sucralfate was concurrently given with CAM and AMPC at the maximum noninhibitory doses for the treatment of H. pylori infection, the bacterial clearance rates were comparable to those achieved by treatment with lansoprazole plus those antibiotics. The results of pharmacokinetic studies showed that lansoprazole delayed gastric clearance and accelerated the absorption of CAM, whereas sucralfate suppressed both gastric clearance and absorption. AMPC was undetectable in all samples. Scanning electron microscopy with a microscope to which a energy dispersive spectrometer was attached revealed that aluminum-containing aggregated substances coated the mucosa surrounding H. pylori in mice receiving sucralfate plus antibiotics, whereas the gastric surface and pits where H. pylori had attached were clearly visible in mice receiving lansoprazole plus antibiotics. The addition of sucralfate to the antibiotic suspension resulted in a more viscous mixture that bound to the H. pylori-infected mucosa and that inhibited the loss of CAM bioavailability in the acidic environment. Sucralfate delays gastric clearance of CAM and physically captures H. pylori through the creation of an adherent mucus, which leads to bacterial clearance.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Influence of anti-ulcer drugs used in Japan on the result of (13)C-urea breath test for the diagnosis of Helicobacter pylori infection.

BACKGROUND: The (13)C-urea breath test (UBT) is a simple breath test for the diagnosis of Helicobacter pylori infection, but several factors have been reported to affect the results of this test. In this study, the effects of the antiulcer drugs used in Japan on the results of UBT were determined. METHODS: The subjects of the study were 64 adult volunteers who tested positive for H. pylori infection by the serum antibody method. Eight classes of anti-ulcer drugs used in Japan were administered at their usual doses to these subjects: lansoprazole, a proton pump inhibitor (PPI); nizatidine, an H(2)-receptor antagonist (H(2)RA); and polaprezinc, ecabet sodium, rebamipide, teprenone, cetraxate hydrochloride, and sucralfate, all mucoprotective agents. The study drugs were randomized for administration to the subjects, and each of the drugs was administered for 14 consecutive days. The UBT was performed on days 0, 14, and 21. RESULTS: The mean Delta(13)C per thousand in the lansoprazole group was significantly decreased on day 14, to below 10 per thousand, in 4 of 16 subjects, and in 1 of the 4 subjects, the test result was negative, with the Delta(13)C per thousand falling to 1.7 per thousand. The value returned to baseline 1 week after the discontinuation of lansoprazole. The other drugs administered had no significant effect on the result of the UBT, except that the mean Delta(13)C per thousand showed a tendency to decrease after the administration of ecabet sodium and rebamipide. CONCLUSIONS: Administration of a PPI may produce a false-negative UBT result, while other anti-ulcer drugs, for the most part, have little effect on the result of the UBT when used alone. The (13)C-urea breath test (UBT) is a simple test for the diagnosis of Helicobacter pylori infection, but several factors have been reported to affect the results of this test. In this study, the effects of the anti-ulcer drugs used in Japan on the results of the UBT were determined.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Reducing the dose of antipsychotic medications for those who had been treated with high-dose antipsychotic polypharmacy: an open study of dose reduction for chronic schizophrenia.

Antipsychotic medications are often used at higher than the recommended dose and sometimes in a combination regimen to treat schizophrenia. However, in general, high-dose therapies have been abandoned in recent clinical studies. In this study, dose reduction of antipsychotic medication was implemented for patients with chronic schizophrenia, most of whom (81%) had been treated with an antipsychotic high-dose polypharmacy regimen consisting of more than 1000 mg/day in total amount. The results show that merely reducing the amount of antipsychotic led to favourable outcome in 23 out of 41 cases (56%), with another 13 cases (32%) showing no change. Dose reduction ended in failure in only five subjects (12%). Overall, the amount as well as the number of antipsychotic medications was significantly reduced from 1984 mg to 812 mg per day (reductions of 59% and from 3.6 to 2.2, respectively; both P<0.0001). The Global Assessment of Functioning scale improved from 30.6 to 37.2, which reached significance (P<0.001). Accordingly, the Severity of Illness improved from 4.7 to 4.2, and was also significant (P<0.01). Dose reduction is an encouraging strategy to consider for those patients with schizophrenia who have chronically been treated with high-dose antipsychotic polypharmacy, even if judged unavoidable in the past.

Adolescent↗

Recurrent episodes of perceptual alteration in patients treated with antipsychotic agents.

Antipsychotics have been sporadically reported to induce the brief recurrent episodes characterized by hypersensitivity of the visual perception, which is known as paroxysmal perceptual alteration (PPA) mainly in Japan. PPA is characterized by hypersensitivity of perception mainly in visual modalities, which could occur in patients treated with antipsychotics. PPA is occasionally known to be accompanied by an oculogyric crisis (OGC). In this study, we examine the prevalence and the characteristics of patients with PPA. Three hundred thirty-eight patients who were treated with antipsychotics and diagnosed with schizophrenia, mood disorders, or neurotic disorders (International Classification of Disease, or ICD-10) were interviewed. We compared the characteristics between subjects with and without PPA. The mean overall prevalence of PPA was 3.25%, which was higher among patients treated with high-potency antipsychotics (3.91%) than in subjects treated with mid-potency or low-potency drugs (1.16%). PPA occurred simultaneously with OGC at the rate of 36.4%. We also found much similarity between PPA and OGC in terms of phenomenology. We suggest that PPA could manifest itself as an undesirable effect of antipsychotics, especially those of high potency. PPA and OGC may a share common underlying mechanism.

Adolescent↗

Intraperitoneal immunization led to T cell hyporesponsiveness to Helicobacter pylori infection in mice.

During Helicobacter pylori infection, T cell response is critical in the development of active gastritis and in protective immunity against infection. We studied gastric inflammation and T cell response in H. pylori-challenged mice following an intraperitoneal immunization, using whole H. pylori lysate (HpAg) in the absence of adjuvants. H. pylori-challenged mice without immunization developed moderate to severe gastric inflammation, and splenocytes from these mice produced Th1 polarizing cytokines in response to HpAg and Con A during the acute infection. On the other hand, immunized-challenged mice (those inoculated with H. pylori following immunization) had little or no gastric inflammation despite persistent H. pylori colonization. Our immunization primed splenocytes to produce IL-2, IFN-gamma, and IL-4 in response to HpAg and Con A before infection. However, these cells became hyporesponsive to both stimulants immediately after live bacterial challenge in terms of the production of these cytokines, especially IL-2 and IFN-gamma. CTLA-4 has been documented to be a negative regulator of IL-2 production and lymphoproliferation that induces peripheral tolerance and functions 24-72 hr after the initiation of T cell activation. Compared with challenged mice, T cells from immunized-challenged mice showed higher levels of CTLA-4 expression at 72 hr after oral challenge. These data suggested that our immunization inhibited the development of H. pylori-associated gastritis and induced T cell hyporesponsiveness to H. pylori infection, which might be mediated by the early induction of CTLA-4 following challenge.

Abatacept↗

Expressed emotion and social functioning in chronic schizophrenia.

The aim of this study was to reveal the relationships between family expressed emotion (EE), family evaluations of social functioning, and the psychopathologic symptoms of patients with schizophrenia. We examined whether EE influenced the social functioning of patients with schizophrenia. Forty-four subjects with schizophrenia and 82 of their relatives participated in this study. The Five-Minute Speech Sample (FMSS) was conducted to evaluate EE, and subjects were divided into high-EE and low-EE groups. The Positive and Negative Symptom Scale (PANSS) was used to assess symptom severity. Social functioning was compared between the two groups using the Social Functioning Scale (SFS). No differences in symptom severity or social adjustment, as evaluated by a global assessment of functioning, were observed between the two groups. However, the high-EE relatives tended to evaluate the social functioning of the schizophrenia patient in their family as being rather low and showed a strong dissatisfaction with the patient's social withdrawal and level of independence (competence). Furthermore, low-EE relatives in high-EE families showed the same tendencies. The family members who were evaluated as low-EE relatives in a high-EE family were dissatisfied with the patient's social withdrawal, level of independence (competence), and also their interpersonal functioning. In the chronic stable phase of schizophrenia, the attention of the family members may be more directed towards changes in social functioning; thus, the EE may reflect a family's attitude towards improvements in the patient's social functioning.

Adolescent↗