Baseline tumour necrosis factor alpha levels predict the necessity for dose escalation of infliximab therapy in patients with rheumatoid arthritis

Objectives: To investigate the possible role of baseline plasma tumour necrosis factor alpha levels (baseline-TNF) on the clinical response to infliximab in patients with rheumatoid arthritis (RA). Methods: Patients with RA refractory to methotrexate received 3, 6, or 10 mg/kg of infliximab every 8 weeks, in a randomised, double-blind manner: the RISING study. Clinical response (disease activity score in 28 joints based on C-reactive protein or American College of Rheumatology core set) at week 54 and serum infliximab levels were compared in three patient groups with low, intermediate, or high baseline-TNF (TNF-low, TNF-int, or TNF-high). Results: In TNF-low patients, the clinical response to different doses of infliximab was comparable, whereas TNF-int patients exhibited a dose-dependent trend. In contrast, TNF-high patients (approximately 13% of the total patients) had a clinical response to 10 mg/kg significantly better than the response to 3 and 6 mg/kg of infliximab. In TNF-high patients, the median trough serum levels of infliximab were below the detection limit (<0.1 μg/ml) at 3 and 6 mg/kg but were greater than 2 μg/ml at 10 mg/kg, whereas the levels were approximately 1 μg/ml for each dosage group in TNF-low patients. Conclusion: In patients with RA, baseline-TNF is significantly associated with the clinical response to infliximab in patients with a high baseline-TNF. A higher dose of infliximab may be necessary in these patients, whereas lower doses of infliximab are sufficient for those with a low baseline-TNF. Baseline-TNF may be a useful measure for personalising the treatment of RA using infliximab

High-Pressure Crystal Structure Prediction Using Evolutionary Algorithm Simulation

We implemented a high-pressure crystal structure prediction using evolutionary algo-rithm method, one of successful method to deal with this kind of problems. This method employs three evolution operators to generate a new o spring from its parents; heredity operator, permu-tation operator, and mutation operator. We run two simulation tests to this method and found results having a good agreement with experimental results. We also found some metastable struc-tures produced by this method

Anti-hepatitis C virus activity of geranylgeranylacetone treatment in hepatitis C-infected patients

Background. Geranylgeranylacetone (GGA), which is an isoprenoid compound, has been used orally as an antiulcer drug inJapan. GGA induces antiviral gene expression by stimulating the formation of interferon-stimulated gene factor 3 in humanhepatoma cells. This study verified the anti-hepatitis C virus (HCV) activity of GGA in chronic hepatitis C-infected patients.Methods. The present prospective study included 20 consecutive anti-HCV antibody-positive, HCV-genotype 1b, and chronicgastritis patients who visited Nagasaki University Hospital between January 1999 and December 1999. GGA (150 mg per day,which is the dose generally used for chronic gastritis) was taken orally for four weeks. We evaluated HCV-RNA titers and otherclinical parameters at pretreatment, posttreatment, and at the endpoint of the study. Pretreatment was the beginning point ofGGA treatment. Posttreatment was the termination point of GGA treatment. The endpoint was the point four weeks after theposttreatment point.Results. All patients completed four weeks of GGA treatment and four weeks of observation. HCV-RNA titers at postpointwere not significantly diminished compared to those at pretreatment. However, HCV-RNA titers were significantly diminishedat endtreatment compared to pretreatment. Unfortunately, we did not observe a case with no titer of HCV-RNA. Alanineaminotransferase values and other parameters were not affected by GGA treatment.Conclusion. GGA has anti-HCV activities in chronic hepatitis C-infected patients. In the future, it will be necessary to examinethe clinical effectiveness of the combination of treatment with both GGA and interferon in HCV patients

Development of a novel automatic ascites filtration and concentration equipment with multi‐ring‐type roller pump units for cell‐free and concentrated ascites reinfusion therapy

Cell‐free and concentrated ascites reinfusion therapy (CART) is an effective therapy for refractory ascites. However, CART is difficult to perform as ascites filtration and concentration is a complicated procedure. Moreover, the procedure requires the constant assistance of a clinical engineer or/and the use of an expensive equipment for the multi‐purpose blood processing. Therefore, we developed a CART specialized equipment (mobility CART [M‐CART]) that could be used safely with various safety measures and automatic functions such as automatic washing of clogged filtration filter and self‐regulation of the concentration ratio. Downsizing, lightning of the weight, and automatic processing in M‐CART required the use of newly developed multi‐ring‐type roller pump units. This equipment was approved under Japanese regulations in 2018. In performing 41 sessions of CART (for malignant ascites, 22 sessions; and hepatic ascites, 19 sessions) using this equipment in 17 patients, no serious adverse event occurred. An average of 4494 g of ascites was collected and the total amount of ascites was processed in all the sessions without any trouble. The mean weight of the processed ascites was 560 g and the mean concentration ratio was 8.0. The ascites were processed at a flow rate of 50 mL/min. The mean ascites processing time was 112.5 minutes and a 106.5‐minutes (95.2%) ascites processing was performed automatically. The operator responded to alarms or support information 3.2 times on average (3.1 minutes, 2.1% of ascites processing time). Human errors related to ascites processing were detected by M‐CART at 0.4 times per session on average and were appropriately addressed by the operator. The frequencies of automatic washing of clogged filtration filter and self‐regulation of the concentration ratio were 31.7% and 53.7%, respectively. The mean recovery rates (recovery dose) of protein, albumin, and immunoglobulin G were 72.9%, 72.9%, and 71.2% (65.9 g, 34.9 g, and 13.2 g), respectively. Steroids were administered in 92.7% of the sessions to prevent fever and the mean increase in body temperature was 0.53°C. M‐CART is a compact and lightweight automatic CART specialized equipment that can safely and easily process a large quantity of ascites without the constant assistance of an operator

The linkage between medical student readiness for interprofessional learning and interest in community medicine

Objectives: The purpose of this study is to investigate the relationship between medical student readiness for interprofessional learning and interest in community medicine prior to incorporating community-oriented interprofessional education into the curriculum. Methods: A questionnaire was administered to students at Nagasaki University School of Medicine in Japan during each of three consecutive years (N=2244). The Readiness for Interprofessional Learning Scale (RIPLS) was administered in addition to a questionnaire to evaluate interest in community medicine. The Kruskal-Wallis and Steel-Dwass tests were used to determine differencesbetween school years. Correlation between the RIPLS score and interest in community medicine was evaluated with Spearman\u27s rank correlation coefficient. Relationships between RIPLS score and demographic parameters, and interest in community medicine were evaluated with multiple linear regression analysis. Results: Eighty-four percent (1891/2244) of students responded. The RIPLS score was highest in school year 1, followed by year 6, year 5,year 3, and years 4 and 2. Interest in community medicine correlated with the RIPLS score (rs = 0.332, p < 0.001),but less in year 1 (rs = 0.125, p = 0.002) than in other years. RIPLS score was significantly associated with gender, age, school year, interest in community medicine, but not the year that the survey was conducted. Conclusions: Community-oriented interprofessional education has the potential to improve attitudes towards interprofessional learning. When introducing this promising education into the curriculum from year 1, attracting students\u27 interest in community medicine should be considered