Alcohol consumption, smoking, and subsequent risk of colorectal cancer in middle-aged and elderly Japanese men and women: Japan Public Health Center-based prospective study.

Few studies have examined the association of alcohol consumption and cigarette smoking with colorectal cancer in Asian populations whose genetic susceptibility to these factors are different from Western populations. We investigated this association and the joint effect of these factors, and estimated the population-attributable fraction to clarify the public health impact on a Japanese population, based on a prospective study. We analyzed the 10-year (cohort I) and 7-year (cohort II) follow-up data of the Japan Public Health Center-based prospective study on cancer and cardiovascular disease, derived from 90,004 (42,540 male and 47,464 female) middle-aged and elderly Japanese. We identified 716 (457 in men and 259 in women) newly diagnosed cases of colorectal cancer. Both alcohol consumption and smoking were clearly associated with colorectal cancer in men, after adjusting for age, family history of colorectal cancer, body mass index, and physical exercise. Regular heavy drinking of 150 g/week or more of ethanol showed a statistically significant increased risk compared with nondrinkers: relative risks (RRs) were 1.4 [95% confidence interval (CI), 1.1-1.9] for 150-299 g/week and 2.1 (95% CI, 1.6-2.7) for 300 g/week or more. On the contrary, regular ethanol consumption was not associated with colorectal cancer (RR, 0.7; 95% CI, 0.4-1.1) in women. In terms of smoking, the RRs were 1.4 (95% CI, 1.1-1.8) for current smokers and 1.3 (95% CI, 0.98-1.7) for ex-smokers compared with never-smokers in men. The risk of smoking in women was similar to that in men, although not statistically significant. The colorectal cancer risk with 300 g/week or more of ethanol in current smokers was estimated at 3.0 (95% CI, 1.8-5.1) compared with nondrinkers among nonsmokers in men. Colorectal cancer attributable to alcohol consumption or smoking was estimated to be 46%. In conclusion, approximately half of the colorectal cancer cases may be preventable by tobacco and alcohol controls in middle-aged and elderly Japanese men.     

Higher incidence of diabetic nephropathy in type 2 than in type 1 diabetes in early-onset diabetes in Japan

BACKGROUND: Whether the type of diabetes, race, and year and age of diagnosis affect the incidence of diabetic vascular complications is unknown. That both type 1 and type 2 diabetes occur in the young Japanese population prompted us to investigate whether the type of diabetes and the year of diagnosis are related to the incidence of nephropathy. METHODS: Of the 17,256 diabetic patients who visited the outpatient clinic at our diabetes center between 1965 and 1990, 1578 (9.1%) had early-onset diabetes (diagnosed before the age of 30); of these, 620 (39%) had type 1, and 958 (61%) had type 2 diabetes. The incidence of nephropathy was analyzed in the patients according to postpubertal duration and year of diagnosis. RESULTS: The cumulative incidence of nephropathy after 30 years of postpubertal diabetes was significantly higher (P < 0.0001) in type 2 diabetic patients (44.4%, 95% CI, 37.0 to 51.8%) than in type 1 diabetic patients (20.2%, 95% CI, 14.9 to 25.8%). The incidence of nephropathy among type 1 diabetic patients has declined during the past two decades, whereas it has not among type 2 diabetic patients. The rate ratio for type 2 diabetic patients diagnosed between 1980 and 1984 relative to type 1 diabetic patients diagnosed in the same period was 2.74 (95% CI, 1. 17 to 6.41). CONCLUSIONS: The incidence of nephropathy has declined in Japanese patients with type 1 but not in those with type 2 diabetes. In young Japanese patients, because of the higher incidence of nephropathy in type 2 diabetes and the higher prevalence of type 2 than type 1 diabetes, type 2 diabetes is likely the major cause of diabetic nephropathy.     

Expression of the long form of leptin receptor (Ob-Rb) mRNA in the brain of mouse embryos and newborn mice

The long form of the leptin receptor (Ob-Rb) has a cytoplasmic domain which activates the JAK-STAT signal transduction pathway. It is related to appetite and energy expenditure and is expressed in various parts of the brain in adults. In embryos, however, the detailed distribution of Ob-Rb expression sites and the function of the leptin-Ob-Rb system remain unclear, although leptin is detected in human cord plasma and leptin mRNA is detected in mouse embryos. In this study, we investigated the Ob-Rb mRNA expression pattern in the brains of mouse embryos and newborn mice by RT-PCR and in situ hybridization. At embryonic day 10.5 (E10.5), Ob-Rb mRNA was already detected in the brain by RT-PCR. By in situ hybridization, Ob-Rb mRNA was observed in the ventricular zone of the rhombencephalon at E11.5. At E12.5, it was also expressed in the ventricular zone of the telencephalon, mesencephalon and cerebellar primordium. From E14. 5 it was expressed in the cortical plate of the telencephalon and the ventricular zone of the thalamus. At E16.5, it was expressed in the premamillary hypothalamic nucleus, superficial gray matter of the superior colliculus, external germinal and Purkinje cell layers of the cerebellum, and facial nucleus. At E18.5, it was expressed in the arcuate nucleus and ventromedial hypothalamic nucleus. These results suggest that the leptin-Ob-Rb system is related to brain development.     

Potential role of vacuolar H-adenosine triphosphatase in neointimal formation in cultured human saphenous vein

OBJECTIVE: Vacuolar H(+)-adenosine triphosphatase plays a pivotal role in pH regulation and molecular transport across the vacuolar membranes and is involved in cell proliferation and transformation. In the present study, possible involvement of vacuolar H(+)-adenosine triphosphatase in neointimal formation was investigated in an organ culture model of human saphenous vein. Methods and results: Cultured saphenous vein segments developed neointimal formation and marked thickening of the media within 14 days. Neointimal formation and medial thickening were completely inhibited by 10 nmol/L bafilomycin A(1), a selective inhibitor of vacuolar H(+)-adenosine triphosphatase, although structurally related macrolide antibiotics FK-506 and erythromycin were without an effect. The neointimal cells were positive for alpha-smooth muscle actin and vimentin but negative for desmin, indicative of myofibroblasts. The emergence of myofibroblasts was inhibited, and endothelial cells were preserved in the saphenous vein segments treated with bafilomycin A(1). Uptake of bromodeoxyuridine, a proliferation marker, by myofibroblasts was abrogated in the saphenous vein segments treated with 10 nmol/L bafilomycin A(1). Detection of apoptotic cells by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling concomitant with identification of desmin-expressing smooth muscle cells demonstrated that neointimal myofibroblasts, but not medial smooth muscle cells, that expressed desmin underwent apoptosis by treatment with bafilomycin A(1). CONCLUSIONS: These results suggest that vacuolar H(+)-adenosine triphosphatase may be involved in myofibroblast growth that contributes to neointimal formation and medial thickening in cultured human saphenous vein. Increased sensitivity of myofibroblasts, but not endothelial cells, and differentiated smooth muscle cells to bafilomycin A(1) may have potential therapeutic implications in the treatment for vein graft disease.     

Safety Profile of Ixazomib in Patients with Relapsed/Refractory Multiple Myeloma in Japan: An All-case Post-marketing Surveillance

Objective To evaluate the safety profile of ixazomib combined with lenalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma (RRMM) in clinical practice in Japan through an all-case post-marketing surveillance. Methods This was a nationwide non-interventional observational study conducted in Japan. The study included all patients who received ixazomib from May 24 to September 24, 2017. Ixazomib was administered to RRMM patients according to the Japanese package insert. All enrolled patients were observed until the completion of the sixth treatment cycle or until ixazomib discontinuation. The patient treatment course, including adverse events (AEs), was reported. Results The safety analysis set included 741 patients; the median age was 71 (range 35-92) years old, and the median number of prior treatment lines was 3 (range 1-30). Adverse drug reactions (ADRs) occurred in 572 (77.2%) patients, most commonly being thrombocytopenia (49.9%), diarrhea (29.2%), and nausea (12.4%). Serious ADRs occurred in 193 (26.0%) patients, most commonly being thrombocytopenia (9.9%) and diarrhea (5.9%). Thrombocytopenia, severe gastrointestinal disorders, infections, skin disorders, and peripheral neuropathy were prespecified as ADRs of clinical importance; the frequency of these ADRs (grade ≥3) were 28.5%, 9.4%, 7.4%, 2.2%, and 1.3%, respectively. Treatment discontinuation was most common with thrombocytopenia and severe gastrointestinal disorders (49 and 43 patients, respectively). Eleven patients died due to ADRs (16 events). Conclusion These results suggest that ixazomib has a tolerable safety profile in clinical practice in Japan. However, close AE management for thrombocytopenia and gastrointestinal disorders should be considered.     

A Young Patient with Microscopic Polyangiitis Requiring Hemodialysis with Complications of Repeated Episodes of Posterior Reversible Encephalopathy Syndrome Probably Due to Different Etiologies

A young woman with microscopic polyangiitis (MPA) requiring hemodialysis showed repeated posterior reversible encephalopathy syndrome (PRES) with spatiotemporal multiple lesions over a period of two months. The first PRES episode with confusion and the second PRES episode with vertigo and nausea were caused by MPA, hypertension and renal failure. These symptoms were improved by the reinforcement of MPA treatment and blood pressure management. The third PRES episode with nausea, headache, seizure and visual changes was induced by rituximab infusion and hypertension. The PRES was improved with blood pressure and convulsant management. These conditions are challenging to diagnose and treat.     

Effect of thiamine on the excretion of subcutaneously injected lead in rats

The effect of thiamine on the excretion of lead in feces was investigated using rats injected subcutaneously with lead acetate and thiamine pyrophosphate. The amount of lead excreted increased with the amounts of thiamine administered, while lead concentrations in blood, liver and femur also increased. The amount of lead excreted in feces decreased, however, with administration of oxythiamine and vanadium. These results suggest that excretion of lead in feces is enhanced by thiamine and that it promotes evacuation of lead from the body.     

A case of congenital high airway obstruction syndrome managed by ex utero intrapartum treatment: case report and review of the literature

Congenital high airway obstruction syndrome (CHAOS) has been reported to be fatal. Ten cases of CHAOS that underwent ex utero intrapartum treatment (EXIT) procedure to secure the fetal airway have been reported. A 36-year-old woman (gravida 3, para 2) was referred to our hospital at 22 weeks of gestation. Sonography revealed large echogenic lungs, flattened diaphragm, and marked hydrops. Magnetic resonance imaging confirmed the diagnosis of CHAOS. Polyhydramnios and fetal skin edema were improved and the fetal ascitic fluid was regressed gradually. At 36 weeks of gestation, an EXIT procedure was undertaken. Fetal laryngoscopy and bronchoscopy showed complete laryngeal obstruction, and a tracheostomy was performed immediately. The infant was discharged from hospital at 6 weeks of age. Thereafter, he developed well both physically and mentally. A laryngoplasty was performed at 20 months of age using silicon sheet as a patent airway. The child has a tracheostomy, is able to phonate but does not speak, and is awaiting decannulation. Use of the EXIT procedure in CHAOS cases offers the potential for salvage and excellent long-term outcome of these fetuses that otherwise would not survive. However, management of the airway, particularly with regard to long-term reconstruction in children with CHAOS, remains challenging.