Comparison of PPIs and H2-receptor antagonists plus prokinetics for dysmotility-like dyspepsia

AIM: To compare efficacy of proton pump inhibitors (PPIs) with H₂-receptor antagonists (H₂RAs) plus prokinetics (Proks) for dysmotility-like symptoms in functional dyspepsia (FD).METHODS: Subjects were randomized to receive open-label treatment with either rabeprazole 10 mg od (n = 57) or famotidine 10 mg bid plus mosapride 5 mg tid (n = 57) for 4 wk. The primary efficacy endpoint was change (%) from baseline in total dysmotility-like dyspepsia symptom score. The secondary efficacy endpoint was patient satisfaction with treatment.RESULTS: The improvement in dysmotility-like dyspepsia symptom score on day 28 was significantly greater in the rabeprazole group (22.5% ± 29.2% of baseline) than the famotidine + mosapride group (53.2% ± 58.6% of baseline, P < 0.0001). The superior benefit of rabeprazole treatment after 28 d was consistent regardless of Helicobacter pylori status. Significantly more subjects in the rabeprazole group were satisfied or very satisfied with treatment on day 28 than in the famotidine + mosapride group (87.7% vs 59.6%, P = 0.0012). Rabeprazole therapy was the only significant predictor of treatment response (P < 0.0001), defined as a total symptom score improvement ≥ 50%.CONCLUSION: PPI monotherapy improves dysmotility-like symptoms significantly better than H₂RAs plus Proks, and should be the treatment of first choice for Japanese FD.     

Restenosis after endovascular PTA/stenting for supra-aortic branches in Takayasu aortitis: report of three cases and review of the literature

Recently, endovascular management has been reported as a feasible option for Takayasu aortitis. However, few papers have focused on restenosis in the follow-up, and therefore, it is important to predict high-risk cases for restenosis after endovascular treatment. We herein report three cases with Takayasu aortitis showing repeated restenosis after endovascular percutaneous transluminal angioplasty (PTA)/stenting and discuss its clinical implications with a review of the literature. We should keep in mind that endovascular PTA/stenting for Takayasu aortitis does not always keep the patency of the affected vessels, and severity of the stenosis and/or uncontrollable systemic inflammation could be a risk factor for restenosis. Therefore, careful follow-up under strict control of inflammation is mandatory. Overall, this method is effective as an initial treatment since repeated PTA is available until collateral supply develops.     

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.     

Evaluation and structure-activity relationship of synthesized cyclohexanol derivatives on percutaneous absorption of ketoprofen using artificial neural network

The effect of 35 newly synthesized O-ethylmenthol (MET) derivatives on percutaneous absorption of ketoprofen was investigated in rats. In order to understand the relationship between the structure of compounds and promoting activity (structure-activity relationship), an artificial neural network (ANN) was employed. In the in vivo percutaneous absorption study, male Wistar rats, weighing 160-180 g, were used. The apparent penetration rate (Rp) was estimated based on a pharmacokinetic model with a constant rate of penetration through the skin after a lag time. As an index of the promoting activity of each compound, an enhancement factor (Ef), defined as follows, was used: Ef=Rp(with enhancer)/Rp(without enhancer). An irritation evoked on rat skin was microscopically judged at the end of the in vivo percutaneous absorption experiment and evaluated as a total irritation score (TIS). Ef and TIS were selected as output variables to determine the ANN structure. Calculated logP, molecular weight, steric energy (SE), van der Waals area, van der Waals volume, dipole moment, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) were used as factors to determine the structural nature of cyclohexanol derivatives. Among these parameters, logP, SE and LUMO significantly affected the prediction of Ef and TIS. The predicted values of Ef and TIS coincided well with in vivo percutaneous absorption experimental values. However, results observed with a linear regression method were poor compared with the ANN approach. The contribution index of logP was approximately 50% in the prediction of Ef, suggesting that lipophilicity among physicochemical properties contributes most of the promoting activity of these compounds.     

Clinical Variants of Tardive Dyskinesia in Japan

Abstract: Involuntary movement disorders were investigated in a psychiatric hospital in Japan. The prevalence of tardive dyskinesia was 9.9 % and four clinical variants of tardive dyskinesia could be classified. Of the 716 patients, tardive dystonia was identified in 15 cases, tardive akathisia in one, respiratory dyskinesia in two and rabbit syndrome in 17. The existence of tardive forms for acute dystonic reactions and akathisia suggests that any type of acute extrapyramidal symptoms can have a tardive form.     

Biphasic pulmonary blastoma with rapid progression

We report a rare case of biphasic pulmonary blastoma (BPB) with rapid progression in a 75-year-old man. Computed tomography (CT) of the chest revealed a well-defined tumor shadow measuring 8 × 6 cm in the right upper lobe. CT-guided lung biopsy revealed malignant cells with sarcomatous elements. Right upper lobectomy and systemic lymph node dissection with chest wall resection were performed. Histopathologically, the tumor was composed of immature embryoniclike mesenchymal and epithelial components that resembled embryonic lung tissue. The final diagnosis was BPB classified as pathological stage IIB (T3N0M0). Two months later, the tumor recurred in the right supraclavicular lymph nodes. The patient died of respiratory failure due to tumor progression 7 months after surgery.