The Amount of Residual Incretin Regulates the Pancreatic β-cell Function and Glucose Homeostasis

The gastrointestinal tract is considered an important endocrine organ for controlling glucose homeostasis via the production of incretins. A 21-year-old man emergently underwent total colectomy due to severe ulcerative colitis, and overt diabetes became evident. Weekly administration of a glucagon-like peptide (GLP)-1 receptor agonist (RA) dramatically improved his glucose control. Levels of GLP-1 or gastric inhibitory polypeptide (GIP) were low at the baseline in the duodenum and serum of the patient. After 11 months of GLP-1RA treatment, his HbA1c worsened again, and intensive insulin therapy was necessary to control his glucose levels. Our report may explain the significance of residual incretin for maintaining the pancreatic β-cell function.     

Perforin defects of primary haemophagocytic lymphohistiocytosis in Japan

The perforin gene was analysed in 15 Japanese patients with primary haemophagocytic lymphohistiocytosis (HLH). Perforin gene defects were found in two out of eight patients with familial HLH (FHL), and one out of seven without affected siblings. Four novel mutations were identified. Compound heterozygous mutations (one FHL and one sporadic HLH) and only one allele mutation (one FHL) were defined. Flow cytometry revealed no perforin expression in CD8+ or CD56+ cells from a surviving patient with a mutation. The frequency of mutation was at least 20% of FHL in Japan. Flow cytometry for intracellular perforin may be useful for the screening of FHL2.     

Risk stratification and survival in post myocardial infarction patients: a large prospective and multicenter study in Japan

BACKGROUND: Recent clinical trials suggest that the mortality in high-risk patients with ischemic heart disease can be significantly reduced with the use of implantable cardioverter-defibrillator (ICD). Given the high cost and invasiveness of the procedure, it is important to apply it to the patients after myocardial infarction (MI) highly susceptible to sudden arrhythmic death. OBJECTIVE: The purpose of this study was to assess clinical predictors of mortality in post-MI patients in Japan. METHODS AND RESULTS: In 495 consecutive MI survivors, 350 (71%) received acute-reperfusion therapy, whereas 145 (29%) did not. Nonsustained ventricular tachycardia (NSVT) was present in 136 patients (28%) in 24-h ambulatory ECGs at 7+/-6 in-hospital days. Left ventricular dysfunction (LVEF< or =35%) was present in 20/347 patients (5.7%) at 13+/-8 days. Forty-eight patients (9.7%) died during the follow-up period (48+/-13 months); 23 from cardiac and 25 from noncardiac causes. Kaplan-Meier survival analyses showed that mortality rates were higher among patients who were > or =70 years old (log-rank test, P<0.0001); had heart failure at admission (Killip scale> or =2, P=0.001); did not receive acute-reperfusion (P=0.004); and had left ventricular dysfunction with LVEF< or =35% (P=0.02). The presence of NSVT was a significant predictor of death (P=0.036) only in the patients who did not receive acute-reperfusion. Multivariate Cox regression analysis revealed that an independent predictor of total mortality was an age> or =70 (odds ratio, 1.06; 95% confidence interval, 1.01-1.11; P<0.00001). CONCLUSIONS: High-risk patients after acute MI can be identified on the basis of age, ventricular dysfunction, heart failure and acute-reperfusion therapy. The presence of NSVT before discharge has a prognostic value only in the patients without acute-reperfusion.     

p53 point mutations in primary human gastric carcinomas

Summary p53 point mutations in primary gastric carcinomas were analyzed by performing cDNA deoxynucleotide sequencing of the gene. Out of 16,9 (56.3%) primary gastric carcinoma cases, including early cancer, showed one or more p53 point mutations in their open-reading frame, and 4 out of 9 cases had a p53 point mutation within highly conserved domains. The characteristics of the p53 mutation spectrum observed in primary tumors were (a) frequent mutation at an A:T pair (50%, 7 out of 14 mutations), (b) high transversion incidence (29%, 4 out of 14 mutations), (c) no transition at CpG, and (d) no G:C to T:A transversion. Our results suggest that p53 mutation is a common event in gastric carcinoma occurring from the early stage of progression with its specific mutation spectrum.Abbreviation PCR-SSCP polymerase chain reaction single-strand conformation polymorphism     

Ticlopidine alone versus ticlopidine plus aspirin for preventing recurrent stroke

OBJECTIVE: To compare the efficacy and safety of two antiplatelet regimens, ticlopidine alone (200 mg daily) and ticlopidine (100 mg daily) plus aspirin (81 mg daily), in patients with ischemic stroke from the Tokai district of Japan. METHODS: A randomized comparative study was performed from April 1992 until December 1995, with follow-up for an average of 1.59 years (maximum: 3 years). Statistical analysis was done on 270 eligible patients (138 treated with ticlopidine alone and 132 treated with ticlopidine plus aspirin). PATIENTS: A total of 276 patients who had cerebral infarction within the previous 1 to 6 months, or one or more transient ischemic attacks within the previous 3 months. RESULTS: The incidence of ischemic and hemorrhagic stroke, myocardial infarction, and other vascular events was 10.1% (n = 14) in the ticlopidine group and 9.8% (n = 13) in the ticlopidine plus aspirin group, showing no significant difference (p = 0.933). There was also no significant difference in the event-free rate between the two groups (p = 0.5003, Kaplan-Meier analysis and log-rank test). Regarding serious adverse reactions, neutropenia occurred in one patient from the ticlopidine group, while gastric ulcer and thrombocytopenia occurred in one patient each from the ticlopidine plus aspirin group. CONCLUSION: We conclude that both antiplatelet regimens are comparable in efficacy and safety for preventing the recurrence of ischemic stroke.     

MPO-ANCA-positive slowly progressive glomerulonephritis with focal tuft necrosis and crescents

A 37-year-old woman had been found to have proteinuria in October 1996. About 8 months later, the first renal biopsy was performed, revealing focal segmental necrotizing and crescentic glomerulonephritis. At that time, serum creatinine was 1.0 mg/dl and urinary protein 3+. In October 1999, laboratory tests revealed positivity for MPO-ANCA and a serum creatinine level of 1.42 mg/dl, anemia and proteinuria of 2+. A second renal biopsy showed almost the same histological findings. Accordingly, a diagnosis of MPO-ANCA positive glomerulonephritis was made. This patient was thought to be a rare case of MPO-ANCA-positive slowly progressive glomerulonephritis presenting focal segmental tuft necrosis and crescents.     

Quantitative Monitoring of Circulating Epstein-Barr Virus DNA for Predicting the Development of Posttransplantation Lymphoproliferative Disease

Epstein-Barr virus (EBV)-DNA was quantitatively measured to assess posttransplantation virus reactivation by real-time polymerase chain reaction (PCR). In the first retrospective analysis of a 7-year-old boy with lymphoproliferative disease (LPD) after an unrelated cord blood transplantation, serum EBV-DNA progressively increased to 4 x 10(5) copies/mL. EBV load was then prospectively monitored in peripheral blood from posttransplantation patients. The second case was an 8 year-old boy with aplastic anemia who received a CD34+ cell transplantation. This patient died of LPD with the progression of pulmonary nodules. EBV-DNA increased to 4 x 10(4) copies/mL after the control of cytomegalovirus reactivation. On the other hand, EBV-DNA was undetectable (<200 copies/mL) in the series of all 58 samples from 10 patients who did not develop LPD after hematopoietic stem cell transplantation. Sequential monitoring of circulating EBV-DNA by quantitative PCR may be a useful indicator for predicting the development of posttransplantation LPD.     

Stabilization of postural sway on a sideward slope using cuboid support insoles

[Purpose] The purpose of this study was to elucidate whether insoles alter postural sway on a sideward slope rather than on level ground. [Participants and Methods] This study involved 20 flat-footed individuals and 20 normal-footed individuals. The postural sway was determined based on the total length of the locus and the body sway area, which were measured using the Zebris system. The participants were divided into three groups: the BMZ insoles, Superfeet insoles, and no insole groups. These insoles were worn by the participants with their normal shoes worn daily. [Results] The total length of the locus of the BMZ group was significantly lower than those of the Superfeet and no-insole groups. The body sway area did not significantly differ based on the insole condition. [Conclusion] BMZ insoles improve postural sway in both normal-footed and flat-footed individuals on a sideward slope.