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11.
A clinical phase I study for T-2588 was carried out in 25 healthy male volunteers. Each volunteer received T-2588 in one of the following doses: 100 mg capsule or tablet as a single oral administration in fasting or non-fasting state, 200 or 400 mg capsule as a single oral administration in non-fasting state or 300 or 600 mg daily for 14 approximately 15 days as a repeated administration in non-fasting state. The results are summarized below. No subjective or objective adverse effects were noted after a single oral administration. But repeated dose of 300 mg daily for 15 days and 600 mg daily for 14 days brought about abdominal distension in 1 case and soft stool in 1 case, respectively. As an abnormal change in clinical laboratory findings, 1 case with slight increase in transaminase after a single administration and 3 cases with slight increases in transaminase after repeated doses were observed. Time to reach a maximum concentration of T-2525 in blood (Tmax) was longer in subjects at non-fasting states than subjects in fasting states. Maximum blood concentration was lower in the latter than in the former. Urinary excretion rate in 8 hours after an oral administration was 19 approximately 28% and it was higher in non-fasting subject than in fasting subject. No accumulation of T-2588 was noted after repeated doses. 相似文献
12.
H Nakagawa M Kikuhara M Sato K Sakai S Kimura 《Gan to kagaku ryoho. Cancer & chemotherapy》1987,14(9):2767-2770
A 50-year-old woman with bilateral inflammatory breast cancer (T4, N1b, M1, Stage IV) underwent right extended radical mastectomy and left modified radical mastectomy following pre-operative administration of carcinostatics (ADM, 5-FU) and irradiation. However, tumor recurrence was observed at the skin and right pleural cavity after the operation. Adriamycin-containing combination chemotherapy and radiation therapy were performed, but no significant response was obtained. CDDP was then administered intravenously at a daily dose of 62.5 mg/m2 at intervals of 60 days. The pleural effusion disappeared and the extent of skin metastasis was reduced, resulting in partial response which lasted for 90 days. The serum CEA level decreased from 13.1 ng/ml to 2.3 ng/ml. As the side effects of this therapy, slight nausea, vomiting and general fatigue were observed. This result suggested that CDDP is an effective drug for inflammatory breast cancer. 相似文献
13.
The authors investigated the effect on the brain of red blood cells that had been modified by contrast media. Rat blood was mixed with an equivolume of contrast media, and up to 200 microL of the mixture was infused to the internal carotid artery of the rat. Evans blue was administered intravenously to assess the integrity of the blood-brain barrier (BBB). Immediately after the death of the animal, or 2.5 hours after the infusion, the brain was removed for evaluation of the degree of BBB destruction and edema. Extensive destruction of the BBB, cerebral edema, and death of the animals were induced by infusion of blood mixed with an ionic contrast medium, such as diatrizoate and iothalamate, which deformed red blood cells. Microscopic observation showed atrophy and necrosis of nerve cells and decomposition of nerve fibers in the affected area of the brain. Cerebral damage was not observed in rats injected with blood mixed with a nonionic contrast medium such as iopamidol, iopromide, or metrizamide, which had less effect on red blood cells. Cerebral damage also was observed in the rats injected with blood mixed with a hyperosmotic solution of mannitol, as well as washed red blood cells mixed with an ionic contrast medium. This study's results indicate that hyperosmotic ionic contrast media affect red blood cells and cause disturbance in cerebral circulation. 相似文献
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16.
Yoshitaka Imoto Naoki Muguruma Tetsuo Kimura Masako Kaji Hiroshi Miyamoto Seisuke Okamura Susumu Ito Masahiko Nakasono Mitsuyoshi Hirokawa Toshiaki Sano 《Nihon Shokakibyo Gakkai zasshi》2007,104(3):401-406
Humoral hypercalcemia of malignancy (HHM) in neoplastic syndrome has been most commonly reported in squamous cell carcinoma. Gallbladder carcinoma with HHM is uncommon. In this report, we describe a male case of gallbladder carcinoma with marked hypercalcemia and a high level of serum parathyroid hormone-related peptide (PTHrP). An immunohistochemical examination using PTHrP was also positive. 相似文献
17.
Koichiro Ueki Yukari Hashiba Kohei Marukawa Kan Yoshida Chika Shimizu Kiyomasa Nakagawa Etsuhide Yamamoto 《Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics》2007,104(1):38-43
OBJECTIVE: To compare postoperative maxillary stability following Le Fort I osteotomy for the correction of occlusal cant as compared with conventional Le Fort I osteotomy for maxillary advancement. STUDY DESIGN: The subjects were 40 Japanese adults with jaw deformities. Of these, 20 underwent a Le Fort I osteotomy and intraoral vertical ramus osteotomy (IVRO) to correct asymmetric skeletal morphology and inclined occlusal cant. The other 20 patients underwent a Le Fort I osteotomy and sagittal split ramus osteotomy (SSRO) to advance the maxilla. Lateral and posteroanterior cephalograms were taken postoperatively and assessed statistically. Thereafter, the 2 groups were followed for time-course changes. RESULTS: There was no significant difference between the 2 groups with regard to time-course changes during the immediate postoperative period. CONCLUSION: This suggests that maxillary stability after Le Fort I osteotomy for cant correction does not differ from that after Le Fort I osteotomy for maxillary advancement. 相似文献
18.
Ung-il Chung Hiroshi Kawaguchi Tsuyoshi Takato Kozo Nakamura 《Journal of orthopaedic science》2004,9(4):410-414
Mammalian bones have three distinct origins (paraxial mesoderm, lateral plate mesoderm, and neural crest) and undergo two different modes of formation (intra-membranous and endochondral). Bones derived from the paraxial mesoderm and lateral plate mesoderm mainly form through the endochondral process. During this process, hypertrophic chondrocytes play a vital role in inducing both osteogenesis and angiogenesis. One of the essential osteogenic factors secreted from hypertrophic chondrocytes is Indian hedgehog (Ihh). In contrast, bones derived from the neural crest mainly form through the intramembranous pro-cess and do not require Ihh. Thus, depending on their origin, bones have distinct signaling properties, which need to be considered in the research and application of bone biology.Presented at the 18th Annual Research Meeting of the Japanese Orthopaedic Association, Kitakyushu, Japan, October 17, 2003 相似文献
19.
Hiroshi Morita MD Douglas P. Zipes MD Shiho T. Morita MD Jiashin Wu PhD 《Heart rhythm》2007,4(1):66-74
BACKGROUND: The Brugada syndrome is characterized by ST-segment elevation on the ECG, especially in the right precordial leads sensitive to the right ventricular outflow tract (RVOT). OBJECTIVES: The purpose of this study was to evaluate the hypothesis that right ventricular electrophysiologic heterogeneity caused arrhythmogenicity in the Brugada syndrome. METHODS: Action potentials (APs) were mapped on the epicardium of 14 RVOT preparations and on the transmural surfaces of 15 pairs of RVOT and right ventricular anteroinferior (RVAI) preparations isolated from canine hearts. Brugada ECG and arrhythmias were induced with pilsicainide (2.5-12.5 micromol/L), pinacidil (1.25-12.5 micromol/L), and terfenadine (2.0 micromol/L). RESULTS: Low doses of drugs elevated the J-ST segment and induced APs with both short and long action potential durations (APDs) in contiguous RVOT epicardial regions. In addition, APs in the RVOT had a larger phase 1 notch and longer APD than in RVAI. The longest APDs were in the epicardium in RVOT but in the endocardium in RVAI regions. High doses of drugs eliminated the phase 2 dome of the AP and abbreviated APDs in the epicardium but not in endocardium and reduced the epicardial heterogeneity of APs but increased the transmural gradient of APD in 14 (93%) of the RVOT preparations. In contrast, abbreviations of epicardial APDs occurred in only 4 (27%) of the RVAI preparations. Ventricular tachycardia occurred more frequently in the RVOT (47%) than in paired RVAI preparations (7%). Blocking the transient outward current reduced the heterogeneity of APs and eliminated arrhythmogenicity in all preparations. CONCLUSION: Compared with the RVAI region, the RVOT has greater electrophysiologic heterogeneity that contributes to arrhythmogenicity in this model of Brugada syndrome. 相似文献
20.
Tetsuya Ozeki Shuji Beppu Takuto Mizoe Yuuki Takashima Hiroshi Yuasa Hiroaki Okada 《Journal of controlled release》2005,107(3):387-394
In this study, we used a novel 4-fluid nozzle spray drier to prepare composite microparticles of a water-insoluble drug, flurbiprofen (FP), and a water-soluble drug, sodium salicylate (SS), for the purpose of improving the water solubility of FP. An ethanol solution of FP and an aqueous SS solution were simultaneously introduced through different liquid passages in the 4-fluid nozzle spray drier and then spray-dried. Quantitative elemental analysis suggested that the FP/SS ratio in each composite microparticle was nearly the same as the formulation ratio. We also found that SS and FP exist in a low crystallinity state in the composite particles. Release of FP from dissolved composite microparticles was markedly improved because of an increase in the effective surface area following rapid dissolution of SS. This study shows that it is possible to prepare FP-SS composite microparticles using a 4-fluid nozzle spray drier in single process and that this can improve the ability of FP to dissolve in water. 相似文献