Simulation Evaluation for Methods Used to Determine Muscular Internal Force Based on Joint Stiffness Using Muscular Internal Force Feedforward Controller for Musculoskeletal System.

This study proposes two novel methods for determining the muscular internal force (MIF) based on joint stiffness, using an MIF feedforward controller for the musculoskeletal system. The controller was developed in a previous study, where we found that it could be applied to achieve any desired end-point position without the use of sensors, by providing the MIF as a feedforward input to individual muscles. However, achieving motion with good response and low stiffness using the system, posed a challenge. Furthermore, the controller was subject to an ill-posed problem, where the input could not be uniquely determined. We propose two methods to improve the control performance of this controller. The first method involves determining a MIF that can independently control the response and stiffness at a desired position, and the second method involves the definition of an arbitrary vector that describes the stiffnesses at the initial and desired positions to uniquely determine the MIF balance at each position. The numerical simulation results reported in this study demonstrate the effectiveness of both proposed methods.

Sorafenib and hepatic arterial infusion chemotherapy for unresectable advanced hepatocellular carcinoma: A comparative study.

Sorafenib is a kinase-targeted drug that has high efficacy for advanced hepatocellular carcinoma (HCC). The aim of the present study was to determine whether sorafenib is more effective than hepatic arterial infusion chemotherapy (HAIC) for HCC. Twenty patients treated with sorafenib (sorafenib group) initiated at 800 mg/day and 45 patients treated with HAIC (HAIC group) for unresectable Child-Pugh A advanced HCC were investigated retrospectively. The treatment effect was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST). As a result, the overall response rate was significantly lower in the sorafenib group than in the HAIC group (P=0.03), while the disease control and survival rates did not differ between the two groups. In the sorafenib group, treatment was discontinued in 19 patients, including 12 due to side effects. In subgroups of patients treated with sorafenib, the survival rate was significantly lower in patients (n=11) administered sorafenib for <60 days compared to those (n=9) treated for ≥60 days. A shorter treatment period (<60 days) was an independent risk factor for unfavorable survival [hazard ratio (HR), 3.34; 95% confidence interval (CI), 1.45-7.66 vs. HAIC], while survival in patients treated with sorafenib for ≥60 days did not differ from those treated with HAIC (HR, 0.79; 95% CI, 0.27-2.34). In conclusion, the disease control and survival rates of patients treated with sorafenib for advanced HCC were comparable to such rates in patients treated with HAIC. However, the prognosis was poor when long-term sorafenib treatment was not possible due to side effects, demonstrating the importance of patient selection for sorafenib treatment.

[Evaluation of transhepatic artery chemotherapy for highly advanced hepatocellular carcinoma].

We conducted transhepatic arterial infusion chemotherapy (TAI) was on 62 patients with highly advanced hepatocellular carcinoma without distant metastases and therapeutic outcome was compared with 18 who were untreated. TAI significantly prolonged the survival of the patients, and was the most important prognostic factor on multivariate analysis. The following 3 regimens for trans-arterial injection were compared: A, a combination of a bolus hepatic artery injection of 3 agents (cisplatin, mitomycin-C and epirubicin)+low dose 5-fluorouracil+cisplatin (FP); B, low-dose FP alone; and C, bolus intrahepatic artery injection of the above 3 agents combined without FP. Regimen A yielded in the most effective survival rate, with an efficacy rate of 41.6% and a CR of about 20%. These results indicate that TAI is an effective therapeutic modality, and the dose FP combined with a bolus intrahepatic arterial infusion may improve outcomes in advanced liver cancer.

Peginterferon-alpha-2b plus ribavirin therapy in patients with chronic hepatitis C as assessed by a multi-institutional questionnaire in Japan.

BACKGROUND AND AIM: There has so far been no questionnaire report on patients who were treated with peginterferon plus ribavirin (PEG IFN+RBV) therapy. The purpose of this study was to investigate the problems of this therapy by a questionnaire survey. PATIENTS AND METHODS: A survey of 681 patients with chronic hepatitis C who received treatment with PEG IFN+RBV was conducted in the Kyushu region of Japan. Using an original questionnaire, the survey was conducted prior to the treatment, during the third month of treatment, at the completion of treatment or the discontinuation of treatment, and at 6 months after the completion of treatment. RESULTS: It was indicated that the patients had a high level of comprehension and understanding of chronic hepatitis C and PEG IFN+RBV treatment. However, the results also indicated that patients had a high level of anxiety. Side effects were adequately dealt with by physicians. However, dermatological symptoms were not adequately explained to the patients, although they were the second most severe side-effect. It was also revealed that side-effects were most distressing during the first and second months after the start of treatment. CONCLUSION: The questionnaire survey provided new information that has never been reported. It is believed that understanding this information is important for future treatment.

Association between changes in body composition and the increasing prevalence of fatty liver in Japanese men.

AIM: Prevalence of fatty liver is increasing. In this study, to elucidate the factor that contributes most to recent increases in prevalence of fatty liver, we determined the independent predictors for the onset of fatty liver and compared these predictors between 2000 and 2005. METHODS: Japanese persons, aged 30-74 years, who participated in regular health checks at Kagoshima Kouseiren Medical Health Care Center (10 336 persons in 2000 and 11 011 persons in 2005) were enrolled in the study. Diagnosis of fatty liver was performed by ultrasonography. Body fat percentage (BFP) was determined using a bipedal bioimpedance instrument. RESULTS: The prevalence of fatty liver has increased between 2000 and 2005 in men (33.3 vs 38.5% in 2000 vs 2005, respectively, P < 0.0001), but not in women (21.3 vs 21.0%, P = 0.8101). Logistic regression analysis revealed that both body mass index (BMI) and BFP are independent predictors of fatty liver in both men and women. BMI did not change in either men (23.4 +/- 2.9 vs 23.8 +/- 3.0 kg/m(2), P = 0.0528) or women (22.8 +/- 3.1 vs 22.8 +/- 3.3 kg/m(2), P = 0.9862) during the survey period. In contrast, BFP increased in men (20.6 +/- 4.7 vs 22.3 +/- 5.0 kg/m(2), P = 0.0003), but not in women (27.4 +/- 5.5 vs 28.4 +/- 5.9 kg/m(2), P = 0.3993). There was no significant change in triglycerides and glucose levels. CONCLUSION: These results suggest that altered body composition, particularly increased BFP without an increase in BMI, has developed in men and is strongly associated with the increasing prevalence of fatty live amongst Japanese men.

Novel genetic variants of Anaplasma phagocytophilum, Anaplasma bovis, Anaplasma centrale, and a novel Ehrlichia sp. in wild deer and ticks on two major islands in Japan.

Wild deer are one of the important natural reservoir hosts of several species of Ehrlichia and Anaplasma that cause human ehrlichiosis or anaplasmosis in the United States and Europe. The primary aim of the present study was to determine whether and what species of Ehrlichia and Anaplasma naturally infect deer in Japan. Blood samples obtained from wild deer on two major Japanese islands, Hokkaido and Honshu, were tested for the presence of Ehrlichia and Anaplasma by PCR assays and sequencing of the 16S rRNA genes, major outer membrane protein p44 genes, and groESL. DNA representing four species and two genera of Ehrlichia and Anaplasma was identified in 33 of 126 wild deer (26%). DNA sequence analysis revealed novel strains of Anaplasma phagocytophilum, a novel Ehrlichia sp., Anaplasma centrale, and Anaplasma bovis in the blood samples from deer. None of these have been found previously in deer. The new Ehrlichia sp., A. bovis, and A. centrale were also detected in Hemaphysalis longicornis ticks from Honshu Island. These results suggest that enzootic cycles of Ehrlichia and Anaplasma species distinct from those found in the United States or Europe have been established in wild deer and ticks in Japan.

Orally administered Kampo medicine, Juzen-taiho-to, ameliorates anemia during interferon plus ribavirin therapy in patients with chronic hepatitis C.

BACKGROUND: Interferon plus ribavirin (IFN/Rib) therapy is currently standard treatment for chronic hepatitis C. Hemolytic anemia, however, is a serious side effect of this treatment, requiring reductions in or complete withdrawal of ribavirin. METHODS: We retrospectively investigated the effect of the Kampo medicine Juzen-taiho-to (TJ-48), which contains bone marrow-stimulating compounds, on anemia in 67 patients with chronic hepatitis C, who received IFN/Rib therapy. RESULTS: The reduction in hemoglobin levels was significantly ameliorated in TJ-48-treated patients (P<0.05). Consequently, only 13% (4/32) of TJ-48-treated patients received altered doses of ribavirin, while the ribavirin dose had to be reduced or withdrawn in 43% (15/35) of patients in the absence of TJ-48 administration (P<0.001). CONCLUSIONS: These results indicate the possibility that oral administration of TJ-48 supports IFN/Rib therapy without necessitating ribavirin reduction or withdrawal.

Branched-chain amino acids supplements in the late evening decrease the frequency of muscle cramps with advanced hepatic cirrhosis.

Eight outpatients with advanced hepatic cirrhosis were tested over 3 months for branched-chain amino acids (BCAA) supplements in the late evening. Serum albumin level (2.8+/-0.3 vs. 3.1+/-0.2 g/dl, P<0.002), serum cholin esterase activity (54+/-13 vs. 67+/-17 IU/l, P<0.02), and plasma Fischer's ratio (1.3+/-0.9 vs. 1.4+/-0.9, P<0.005) increased over the 3 months. The frequency of muscle cramps decreased (7.4+/-2.0 vs. 0.3+/-0.5 times/week, P<0.0001) dramatically. These data suggest that BCAA supplements in the late evening are of benefit to malnourished patients with hepatic cirrhosis. Relief of muscle cramping is an important outcome of BCAA supplements in the late evening.

Effectiveness of carbohydrate-restricted diet and arginine granules therapy for adult-onset type II citrullinemia: a case report of siblings showing homozygous SLC25A13 mutation with and without the disease.

Case 1 is a 37-year-old Japanese man who was admitted to this hospital with a disturbance of consciousness. A diagnosis of adult-onset type II citrullinemia was made by DNA analysis of SLC25A13 (851del4/851del4) and measurement of hepatic ASS activity (2% of control value). After regaining consciousness, Case 1 was started on a dietary therapy, revealing that hypertriglyceridemia and ketogenesis impairment deteriorated on a low-protein diet and ameliorated on a carbohydrate-restricted (high-protein) diet. Case 1 could tolerate 70 g/day of protein while using arginine granules and developed hyperammonemia only after discontinuation of the administration. Case 2 (an elder brother of Case 1) is also homozygote for the same SLC25A13 mutation. The hepatic activity of argininosuccinate synthetase was about 20% of the control value. However, Case 2 exhibited neither hyperammonemia nor lipid metabolism abnormalities. These results suggest that, although adult-onset type II citrullinemia is caused by a deficiency of citrin, which plays key roles in carbohydrates, amino acids and even lipid metabolism, some other environmental or genetic factors are required for the onset of the disease, and from the authors' clinical experience, a carbohydrate-restricted (relatively high-protein) diet is advocated as a benefit to the patients, and that arginine granules are indispensable to this new dietary therapy.

[A patient with hepatocellular carcinoma with intraperitonial lymph node metastases in whom oral UFT treatment was markedly effective].

We report a patient with hepatocellular carcinoma (HCC) with intraperitoneal lymph node metastases in whom UFT (uracil + tegafur) was markedly effective. The patient was a 70-year-old woman with chronic hepatitis C, who developed HCC mainly infiltrating the medial segment of the liver. Arterial infusion chemotherapy and embolization were performed, and radiofrequency ablation was also conducted. Despite these interventions, the serum alpha-fetoprotein level continued to increase, and reached a level as high as 208,000 ng/ml by the second month of treatment. Abdominal computed tomography (CT) revealed no recurrence in the liver, but multiple metastases to intraperitoneal lymph nodes were identified. UFT-E treatment was initiated at the dose of 400 mg/day. A subsequent abdominal CT revealed complete disappearance of the intraperitoneal lymph node metastases 2 months after the start of UFT treatment. The serum alpha-fetoprotein level returned to normal 4 months after the start of UFT treatment. We consider that the patient described here is a good example to illustrate the remarkable effectiveness of UFT in the treatment of metastatic HCC.