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Hiroki Koshimichi Yoshiyuki Tsuda Toru Ishibashi Toshihiro Wajima 《Journal of pharmaceutical sciences》2019,108(5):1896-1904
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. 相似文献
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Akihiko Bo Shinichi Imura Hironori Omori Yasuhiro Okumura Masao Ando Hisatoshi Baba Patrick White Al Zarnowski 《Journal of orthopaedic science》1997,2(5):301-312
The fit and fill of the femoral canal are critical to the success of cementless femoral stems in total hip arthroplasty. It
is difficult for conventional stems to provide a good fit and fill for the femora of patients with secondary osteoarthritis.
Based on measurements of 100 femora of these patients, we designed two types of Fukui Medical School (FMS) stems with a proximal
lateral flare that differed in the medial radius. We compared the fit and fill of the FMS stems with those of four conventional
stems, using computer simulation. The mean proximal fit and total fit of the FMS stems were 46% and 53% respectively, a significant
improvement compared with the other stems examined. The mean fill of FMS stems was 82% at the lower end of the lesser trochanter
and 84% at the upper end of the isthmus, values that were significantly higher than those of the other stems. Since September
1995, we have implanted FMS stems in 15 hips with secondary osteoarthritis. Radiographic evaluations showed that the canal
fill of the FMS stems was significantly greater in the proximal femur compared with other stems previously inserted at our
department.
A summary of this paper was presented at the 9th Symposium on Computer-Assisted Radiology; June 1995, Berlin, and at the 8th
International Symposium on Technology in Arthroplasty; September 1995, Puerto Rico. 相似文献
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Xin Mei Jiang Akio Ohnishi Tatsunori Yamamoto Yoshiyuki Murai Akira Awaya Masato Ikeda 《Acta neuropathologica》1995,90(2):130-134
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. 相似文献
6.
CYP2E1 and ALDH2 Genotypes and Alcohol Dependence in Japanese 总被引:2,自引:0,他引:2
Kazuhiko Iwahashi Yoshinori Matsuo Hiroshi Suwaki Kazuhiko Nakamura Yoshiyuki Ichikawa 《Alcoholism, clinical and experimental research》1995,19(3):564-566
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). 相似文献
7.
Multicentricity of hepatocellular carcinoma (HCC) is considered, especially in patients with liver cirrhosis. This paper describes an operative case of a male patient with probable multicentric development of HCC in precirrhotic fibrosis. The main tumors inside the capsule were completely necrotic due to transarterial embolization (TAE). Histologic examination disclosed discrete tiny nodules of HCC that were not detected grossly. They showed highly differentiated trabecular arrangements: Edmondson I. A scirrhous type was noted in the center of the tumors. At the borders of the tumors the carcinoma cells exhibited replacing growth patterns and it was thought that they developed multicentrically. Partial resection must be performed as extensively as possible in a case such as the present one. 相似文献
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Definition of carcinoma of the gastric cardia 总被引:8,自引:0,他引:8
A. Misumi M.D. A. Murakami K. Harada K. Baba M. Akagi 《Langenbeck's archives of surgery / Deutsche Gesellschaft fur Chirurgie》1989,374(4):221-226
Summary This study concerns the definition of carcinoma of the gastric cardia. The topography of the esophagogastric mucosal junction (mucosal EGJ) was investigated with an endoscope in 182 patients who were free of hiatal hernias, ulcers, and neoplasms in the esophagus and stomach. The relationship between the EGJ and the cardiac gland area was then examined histologically in 56 resected specimens containing intact EGJs and cardia gland areas. Furthermore the cancerous center was determined; the shortest distance between the cancerous center and the EGJ and the amount of esophageal invasion were measured in 102 resected carcinomas located close to the junction; the carcinomas contained the EGJ and were good enough for pathohistological examination. The EGJ was located 0.5–1.0 cm proximal to the His angle (the gastric cardia) in radiological and endoscopic examinations. Histologically the cardiac gland area was found to straddle the EGJ at a range of about 1 cm proximal and 2 cm distal to the junction. Among the upper stomach carcinomas, most of the tumors (87.5%) whose center was located within 2 cm from the EGJ invaded the esophagus. In conclusion, carcinoma of the gastric cardia is defined as a lesion with its center located within 1 cm proximal and 2 cm distal to the EGJ.
Definition des Kardiacarcinoms
Zusammenfassung Diese Untersuchung befaßt sich mit der Definition von Carcinomen der Kardia. An 182 Patienten, die weder Hiatushernien, Ulcera noch Neoplasien des Oesophagus bzw. des Magens aufwiesen, wurde die Lage des Übergangs von der Oesophagus- zur Magenmucosa (esophagogastric mucosal junction, EGJ) endoskopisch untersucht. Dann wurde die Beziehung zwischen EGJ und dem Drüsengebiet der Kardia histologisch anhand von 56 Resektaten mit intaktem EGJ und Kardiadrüsenzone untersucht. Außerdem wurde an 102 resezierten Carcinomen mit Sitz in der Nähe des gastrooesophagealen Übergangs die kürzeste Ent fernung zwischen Carcinomzentrum und EGJ und das Ausmaß der Oesophagusinfiltration bestimmt; die Proben schlossen den EGJ ein und konnten pathohistologisch beurteilt werden. Bei der radiologischen und endoskopischen Untersuchung fand sind der EGJ 0,5–1,0 cm vom His-Winkel entfernt. Die histologische Untersuchung zeigte, daß die Kardiadrüsenzone sich vom EGJ etwa 1 cm nach proximal und 2 cm nach distal erstreckt. Die meisten Tumoren des oberen Magens (87,5%), deren Zentrum innerhalb von 2 cm vom EGJ entfernt lag, infiltrierten in den Oesophagus. Ein Kardiacarcinom ist demzufolge als Läsion zu definieren, deren Zentrum innerhalb von 1 cm proximal und 2 cm distal des EGJ liegt.相似文献