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Tissue distribution, disposition, and metabolism of 3H-cyclosporine were studied in rats after single and repeated oral doses of 10 and 30 mg/kg and after an iv dose of 3 mg/kg. The oral doses of 10 and 30 mg/kg were dissolved in polyethylene glycol 200/ethanol or in olive oil/Labrafil/ethanol. Absorption from both formulations was slow and incomplete, with peak 3H blood levels at 3-4 hr. Approximately 30% of the radioactive dose was absorbed, which is consistent with oral bioavailability data for cyclosporine. More than 70% of the radioactivity was excreted in feces and up to 15% in urine. Elimination via the bile accounted for 10 and 60% of the oral and iv doses, respectively. Since unchanged cyclosporine predominated in both blood and tissues at early time points, the half-lives of the distribution phases (t 1/2 alpha) of parent drug and of total radioactivity were similar. In blood, kidney, liver, and lymph nodes, t 1/2 alpha of cyclosporine ranged from 6-10 hr. Elimination of radioactivity from the systemic circulation was multiphasic, with a terminal half-life of 20-30 hr. 3H-Cyclosporine was extensively distributed throughout the body, with highest concentrations in liver, kidney, endocrine glands, and adipose tissue. The concentrations of both total radioactivity and parent drug were greater in tissues than in blood, which is consistent with the high lipid solubility of cyclosporine and some of its metabolites. Skin and adipose tissue were the main storage sites for unchanged cyclosporine. Elimination half-lives were slower for most tissues than for blood and increased with multiple dosing. The amount of unchanged drug was negligible in urine and bile.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Of 15 patients operated on for achalasia in the Department of General and Abdominal Surgery at the University of Mainz between September 1985 and April 1990, 14 were followed-up. All the patients had received an extramucous myotomy combined with Dor's semifundoplication; in twelve, one or more preoperative balloon dilatations had been performed. The results are reported in this study. The average age of the patients was 55.3 years (18 to 76 years), and the average follow-up period 21 months (six to 53 months). No postoperative complications were seen in any of the case. All patients reported appreciable improvements in their symptoms, six being completely symptom-free. Occasional dysphagia was reported in six cases, one patient had occasional, another frequent, nocturnal heartburn, which however had already presented preoperatively. In all seven cases submitted to postoperative radiological examination, the diameter of the esophagogastric junction was increased, and the diameter of the middle-third of the esophagus decreased. No gastroesophageal reflux or signs of inflammation were seen in any of the cases. The low complication rate and the high success rate despite prior balloon dilatation or bougienage support the use of Heller's operation combined with Dor's semifundoplication for the surgical treatment of achalasia after failed balloon dilatation. 相似文献
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W E Berdel S de Vos J Maurer D Oberberg Z von Marschall J K Schroeder J Li W D Ludwig E D Kreuser E Thiel 《Cancer research》1992,52(12):3498-3502
The growth of a panel of eight different human glioblastoma cell lines was examined in a human tumor cloning assay in agar, a tritiated thymidine uptake assay, and by counting cell numbers, in cultures performed in the absence or presence of increasing concentrations (1 to 100 ng/ml) of recombinant human stem cell factor (SCF). Growth of 7 of 8 cell lines was not significantly and reproducibly affected by recombinant human SCF. However, growth of the CRL 1620 cell line could be stimulated up to 5-fold by the cytokine. In contrast to the other cell lines investigated, CRL 1620 expressed the c-kit protooncogene assessed on the mRNA and protein level. Furthermore, SCF-induced proliferation of CRL 1620 cells was sensitive to the tyrosine kinase inhibitor erbstatin. Our data suggest that SCF can be operative in growth modulation of malignant cells outside the hematopoietic system, and this finding should be further studied for its possible clinical implications. 相似文献
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The aim of present study was to characterize the topographical effect of thiopental on the EEG during induction of anesthesia. A multichannel (19 channels) digital EEG was recorded in 10 patients undergoing surgical treatment. The period during induction of anaesthesia before intubation was investigated in regard to peak frequency, amplitude, topography, and amplitude in conventional frequency bands. The main findings were a slowing of the EEG with a simultaneous increase of amplitude in the predominant EEG frequency (peak frequency) during induction. The topographical analysis showed a clear change of localization of the peak frequency in the occipito-frontal direction. Berger described the effect of thiopental on electrical cortical activity as early as 1933. Since then, many studies have investigated its influence on the EEG, but few have tried to characterize the effects of topographical changes in a quantitative way. 相似文献
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Transcranial Doppler Ultrasound Recording with Compression Test in Patients with Tumors Involving the Carotid Arteries 下载免费PDF全文
Transcranial Doppler ultrasound (TDU) recording is presented as a diagnostic method for the evaluation of the cerebral cross-flow in patients in whom, for therapeutic reasons, ligature or resection of the common or internal carotid artery is planned. Examinations were performed under normal conditions and while using manual compression of the ipsilateral carotid artery. Patients with various skull base and neck tumors were examined and in all patients an immediate decrease of the flow velocity in the middle cerebral artery (MCA) of 25 to 90% was registered. In 39% of these patients the flow velocity of the MCA reached 90% or more of its value under normal conditions within a short interval. In 29% of the patients the flow velocity of this vessel under manual compression of the carotid artery remained under 50% of its original value. In 68% of the cases TDU recording with manual compression of the carotid artery showed reliable results for the function of cerebral collateralization as a prognostic factor of ischemic risk due to hemodynamic changes after carotid ligature. In these cases no further examination of the cerebral cross-flow conditions was carried out. This method is convenient, harmless to the patient, inexpensive, does not require sophisticated equipment, and yields reproducible results when compared with cerebral angiography. 相似文献