Changes of cancer diagnosis disclosure to children in Japan in the last 20 years

International Journal of Clinical Oncology - The practice of cancer diagnosis disclosure to children has been changed with the times. The regulations of clinical trials in the 2000s might change...     

Infective Endocarditis Due to Treponema pallidum: A Case Diagnosed Using Polymerase Chain Reaction Analysis of Aortic Valve

Syphilis is a sexually transmitted disease caused by Treponema pallidum. Syphilitic aortitis might coexist in a dysfunctional aortic valve, but the etiology remains unclear, because microbiological diagnosis is difficult. A 62-year-old man with low-grade fever was diagnosed with aortitis and infective endocarditis, due to Treponema pallidum infection, using polymerase chain reaction analysis. This case suggests that syphilis might cause infective endocarditis.     

Population Pharmacokinetic and Exposure-Response Analyses of Baloxavir Marboxil in Adults and Adolescents Including Patients With Influenza

Baloxavir marboxil, a prodrug that is metabolized to baloxavir acid, suppresses viral replication by inhibiting cap-dependent endonuclease. Our aim is to characterize its pharmacokinetics and exposure-response relationships. Population pharmacokinetic analysis of the baloxavir acid was performed using 8310 plasma concentration data points from 1109 subjects. Exposure-response analyses were performed regarding the time to alleviation of symptoms and the reduction in the influenza virus titer. A 2-compartment model with first-order absorption and lag time well described the plasma concentration data for baloxavir acid, and body weight and race were found to be the most important factors influencing the clearance and distribution volume. A dose regimen based on the body weight (40 mg for patients weighing <80 kg and 80 mg for patients weighing ≥80 kg) could provide sufficient exposures for expecting efficacy irrespective of body weight or race; however, the exposures were dependent on the body weight and race. Exposure-response analyses suggested that the reduction in the influenza virus titer was greater in any exposure-based groups in baloxavir marboxil treatment than in the oseltamivir phosphate treatment and placebo groups. In conclusion, the population pharmacokinetic model and exposure-response relationships would be useful for understanding the pharmacokinetic and pharmacodynamic characteristics of baloxavir acid.     

Easier node dissection after chemoradiotherapy for lung cancer with collagen insertion at mediastinoscopy

Objective: Induction chemoradiotherapy followed by anatomical resection is a current therapeutic strategy for non-small-cell lung cancer with mediastinal node involvement. Dense peritracheal fibrosis and sclerosis after chemoradiotherapy cause difficult mediastinal node dissection. We evaluated a novel technique to make the mediastinal node dissection easier after induction therapy. Methods: At the end of mediastinoscopic node biopsy for staging of lung cancer, cotton-type collagen was inserted anterior and lateral to the trachea in patients with pathologically confirmed mediastinal node involve-ment (n=45). The induction therapy consisted of concurrent use of platinum-based chemotherapy and hyperfractionated radiotherapy. After the chemoradiotherapy all patients underwent a pulmonary resection with complete mediastinal node dissection 7–12 weeks after the collagen insertion. Surgical findings of the mediastinum and the time for node dissection were compared with those without collagen insertion at mediastinoscopy after chemoradiotherapy (n=5). Results: All five patients without collagen insertion showed sclerotic and fibrotic change of mediastinal nodes with severe adhesion to the trachea. In 42 of 45 patients with collagen insertion (93.3%) the collagen remained unabsorbed and separated the mediastinal nodes from the trachea. Mediastinal node dissection was easily accomplished by removing mediastinal tissues lateral and anterior to the collagen. The rate of mediastinal node separation was significantly higher with collagen insertion than without (p< 0.0001). The times for node dissection in patients with and without collagen insertion showed no significant difference. Conclusion: Cotton-type collagen insertion at staging mediastinoscopy for lung cancer separates the mediastinal nodes from the trachea and makes the node dissection easier after induction chemoradiotherapy.     

Effects of anthocyanidin derivative (HK-008) on relaxation in rat perfused mesenterial bed.

Anthocyanins, which are responsible for a variety of bright colors (including red, blue, and purple) in fruits, vegetables, and flowers, are consumed as dietary polyphenols. Anthocyanin-containing fruits are thought to decrease coronary heart disease and are used in anti-diabetic preparations. Diabetes is associated with a variety of cardiovascular complications that may be mediated by endothelial dysfunction, and so this study was designed mainly to characterize the influence of a synthesized anthocyanidin derivative (HK-008) over acetylcholine (ACh)-induced relaxation in mesenteric arterial beds isolated from rats. In a glucose-tolerance test in intact rats, HK-008 (30 mg/kg) reduced the glucose level as effectively as the same dose of glibenclamide. The aortic relaxation induced by pinacidil (an ATP-sensitive potassium channel opener) was greatly inhibited by glibenclamide (10 microM), and also significantly inhibited by HK-008 (10 microM). Interestingly, the ACh-induced relaxation in the perfused, preconstricted mesenteric arterial bed was significantly enhanced by HK-008 (10 microM), and this enhancement was significantly attenuated by indomethacin (10 microM). The ACh-induced mesenteric relaxation was impaired by an increase in oxidative stress, viz. superoxide-generating treatment [xanthine oxidase (XO; 0.1 U/ml) plus hypoxanthine (HX; 10 microM)]. However, this impairment was strongly suppressed by HK-008 (10 microM). These results suggest that HK-008 increases endothelium-induced relaxation by suppressing oxidative stress or modulating prostanoids signaling. This compound may therefore be useful against certain cardiovascular disorders.     

The effect of MS-818, a pyrimidine compound,on the regeneration of peripheral nerve fibers of mice after a crush injury

One of the pyrimidine compounds, 2-piperadino-6-methyl-5-oxo-5,6-dihydro(7H)pyrrolo[3,4-d]pyrimidine (MS-818), has neurotropic effects in vitro. Therefore, we studied the effect of MS-818 on the regeneration of the peroneal nerve in C57BL/6J mice after a crush injury. Two test groups, which received a daily intraperitoneal injection of 5 mg/kg or 10 mg/kg MS-818, respectively, were compared with controls, which received daily intraperitoneal injections of physiological saline, over a 14-day period. The maximum foot-width ratio (crushed side/uncrushed side) was obtained on days 1, 8 and 14 after the crush injury, and the various morphometric parameters were evaluated at both 5 and 10 mm distal to the proximal portion of the crush site. The significant effects of MS-818 included a larger maximum foot width (P<0.04) and a greater number of unmyelinated axons per nerve at both levels (P<0.003) in both test groups than in controls. MS-818 had no significant effects on body weight, the increase of total transverse fascicular area after the crush injury, the total number of myelinated fibers with their size distributions, or the number of nuclei of Schwann cells and macrophages. Therefore, we conclude that MS-818 promotes axonal sprouting and elongation after a crush injury in mice.     

CYP2E1 and ALDH2 Genotypes and Alcohol Dependence in Japanese

The genotypes of the CYP2E1 and ALDH2 loci of alcoholic (alcohol dependence) and nonalcoholic (healthy) Japanese were investigated to examine the relationship between the polymorphism of CYP2E1 (C₁/C₂) and ALDH2 ( ALDH2*1/ALDH2*2 ), and the susceptibility to alcoholism. There was no significant difference in C₂ gene frequency between alcoholics (0.19) and nonalcoholics (controls) (0.20), whereas there was a significant difference in ALDH2 allele frequency, suggesting that, in Japanese, the C₂ genotype of CYP2E1 may have nothing to do with the risk of developing alcohol dependence. However, the ALDH2*1 allele may influence drinking behavior and the development of alcohol dependence. Furthermore, racial interethnic differences in the frequency of the mutated allele of the CYP2E1 gene (CJ were found, like the ALDH2 gene. Japanese healthy controls showed a significantly higher frequency of the C₂ allele than did Swedish healthy controls (0.05; reported by Persson et al., FEBS Lett. 319:207-211,1993).