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A multicenter randomized controlled study was conducted to assess the long-term efficacy and safety of cyclosporin A therapy for psoriasis using either a continuous or an intermittent regimen. Initially, both regimens consisted of 3-5 mg/kg/day administration of CyA. Once remission was obtained, CyA dose was maintained between 0.5 and 3 mg/kg/day under the continuous regimen, while under the intermittent regimen, CyA dose was tapered off and, when necessary, topical corticosteroids were used until relapse occurred. Thirty-one patients were followed for at least 48 months (mean follow-up period: 55.9+/-4.6 months): 15 received continuous therapy, and 16 received intermittent therapy. With both regimens, the PASI (Psoriasis Area and Severity Index) score was maintained at 5-12 points throughout the follow-up period. The score was decreased by more than 70% from baseline with both regimens: the responses between them were not significantly different. However, overall control of psoriasis, as assessed from the averaged PASI score, was better in the patients receiving continuous therapy. Although the overall frequency of adverse reactions was similar for the two regimens, cancer occurred in two patients on continuous therapy (gastric cancer and hepatocellular carcinoma in one patient each). We could not, however, definitely attribute the cancers in the two patients to continuous therapy itself. There was a significantly higher incidence of renal impairment in elderly patients receiving either regimen when compared with younger patients. In conclusion, CyA administered to psoriasis patients under both regimens exhibited long-term efficacy and tolerability. Despite a lower overall efficacy, it seems proper to conclude that intermittent therapy is more useful than continuous therapy due to the occurrence of malignancies with continuous therapy. Further investigation is required to determine whether intermittent therapy is really safer than continuous therapy, and, if so, how it should be designed to minimize long-term adverse reactions and achieve overall control comparable to that of continuous CyA therapy.

BackgroundIn cardiothoracic and abdominal surgery, postoperative complications remain major clinical problems. Early mobilization has been widely practiced and is an important component in preventing complications, including orthostatic hypotension (OH) during postoperative management. We investigated cardiovascular response during early mobilization and the incidence of OH after cardiothoracic and abdominal surgery.MethodsIn this prospective observational study, we consecutively analyzed data from 495 patients who underwent elective cardiothoracic and abdominal surgery. We examined the incidence of OH, and the independent risk factors associated with OH during early mobilization after major surgery. Multivariate logistic regression was performed using various characteristics of patients to identify OH-related independent factors.ResultsOH was observed in 191 (39%) of 495 patients. The incidence of OH in cardiac, thoracic, and abdominal groups was 39 (33%) of 119, 95 (46%) of 208, and 57 (34%) of 168 patients, respectively. Male sex (OR 1.538; p = 0.03) and epidural anesthesia (OR 2.906; p < 0.001) were independently associated with OH on multivariate analysis.ConclusionsThese results demonstrate that approximately 40% patients experience OH during early mobilization after cardiothoracic and abdominal surgery. Sex was identified as an independent factor for OH during early mobilization after all three types of surgeries, while epidural anesthesia was only identified after thoracic surgery. Therefore, the frequent occurrence of OH during postoperative early mobilization should be recognized.Trial registrationUniversity hospital Medical Information Network Center (UMIN-CTR) number UMIN000018632. (Registered on 1st October, 2008).

The protective effects of some neutral amino acids against hypotonic hemolysis were examined at various pHs. At pH 5.0, 7.0 and 8.0, 50% hemolysis was induced at 200, 160 and 140 mOsM, respectively, suggesting that erythrocyte membranes became more fragile to osmotic shock with decreasing pH. All amino acids tested reduced the hypotonic hemolysis at pH 5.0, but enhanced it at pH 8.0. It is therefore likely that these amino acids controlled the osmotic fragility of the cell membranes. At pH 7.0, glycine (Gly) reduced hypotonic hemolysis with increasing concentration. Phenylalanine (Phe) also reduced hypotonic hemolysis at low concentrations, but had an incrementally opposite effect at high concentrations. It was suggested that Phe interacted with erythrocyte membranes in a similar way to amphipathic drugs. Kinetic studies demonstrated that hypotonic hemolysis occurred immediately, according to osmotic shock, and that Gly and a low concentration of Phe decreased osmotic shock. Phe at a high concentration showed fast hemolysis with a short lag-time. Gly also showed fast hemolysis after the suppression of hypotonic hemolysis. Morphological observations demonstrated that these amino acids induced exvagination, exovesiculation and then invagination. It was suggested that with exvagination, the membrane expansion decreased the osmotic fragility, but the further shape change evoked membrane hole-formation.

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[Purpose] The aim of this study was to examine the incidence and patterns of referred pain in patients with hip disease, as well as the nerve distribution in the hip and knee joints of 2 cadavers. [Subjects and Methods] A total of 113 patients with hip joint disease were included in the investigation. The incidence of regional pain and referred pain patterns were evaluated before and after arthroplasty. Two cadavers were macroscopically observed to verify the nerve innervation of the hip and knee joints. [Results] Anterior knee pain was observed preoperatively in 13.3% (in resting) and 33.6% (in motion) of the patients, which was comparable with the incidence of greater trochanter pain. In addition, the preoperative incidence rates of knee pain in resting and motion markedly decreased postoperatively. Of note is the remarkable incidence of pain radiating to the ventral lower limb. An anteromedial innervation was determined in the cadavers by the articular branches of the obturator and femoral nerve, which supply small branches to the knee joints. [Conclusion] Our results suggest that the distribution of the incidence of pain among the patients with hip disease is diverse owing to the sensory distribution of the femoral and obturator nerves.

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