978 resultados para Radiotherapy dosage


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La détermination directe des caractéristiques de cisaillement des bétons par des essais universels est un problème qui reste encore une préoccupation majeure des chercheurs. La plupart des études disponibles consistent à appliquer un couple de torsion à un cylindre creux ayant un rapport épaisseur/rayon le plus faible possible. Ceci pour pouvoir élaborer un critère lié au comportement du matériau et non de la structure (Fourd et al. 1982). Cependant, ces essais peuvent présenter des dispersions liées aux problèmes de fragilité à la rupture ou de non homogénéité du matériau au sein de la paroi (Gotuwka et al. 1999). Pour cela, un dispositif expérimental original a été utilisé et qui consiste en la création de deux zones de contrainte nulle par l’emplacement de corps déformables au moment du coulage de l’éprouvette. De nouvelles conditions aux frontières sont créées permettant de transformer la sollicitation de compression en cisaillement plan sur une zone bien déterminée. L’utilisation de cette technique permet la détermination de l’influence de l’inclinaison du plan de rupture sur le comportement du béton en cisaillement. Le dispositif permet d’assurer la perpendicularité NOvEMBRE 2012 5 des génératrices du cylindre ainsi que la répartition et l’homogénéité des contraintes.

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Mode of access: Internet.

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Thesis (doctoral)--

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Bibliography.

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Patient outcomes in transplantation would improve if dosing of immunosuppressive agents was individualized. The aim of this study is to develop a population pharmacokinetic model of tacrolimus in adult liver transplant recipients and test this model in individualizing therapy. Population analysis was performed on data from 68 patients. Estimates were sought for apparent clearance (CL/F) and apparent volume of distribution (V/F) using the nonlinear mixed effects model program (NONMEM). Factors screened for influence on these parameters were weight, age, sex, transplant type, biliary reconstructive procedure, postoperative day, days of therapy, liver function test results, creatinine clearance, hematocrit, corticosteroid dose, and interacting drugs. The predictive performance of the developed model was evaluated through Bayesian forecasting in an independent cohort of 36 patients. No linear correlation existed between tacrolimus dosage and trough concentration (r(2) = 0.005). Mean individual Bayesian estimates for CL/F and V/F were 26.5 8.2 (SD) L/hr and 399 +/- 185 L, respectively. CL/F was greater in patients with normal liver function. V/F increased with patient weight. CL/F decreased with increasing hematocrit. Based on the derived model, a 70-kg patient with an aspartate aminotransferase (AST) level less than 70 U/L would require a tacrolimus dose of 4.7 mg twice daily to achieve a steady-state trough concentration of 10 ng/mL. A 50-kg patient with an AST level greater than 70 U/L would require a dose of 2.6 mg. Marked interindividual variability (43% to 93%) and residual random error (3.3 ng/mL) were observed. Predictions made using the final model were reasonably nonbiased (0.56 ng/mL), but imprecise (4.8 ng/mL). Pharmacokinetic information obtained will assist in tacrolimus dosing; however, further investigation into reasons for the pharmacokinetic variability of tacrolimus is required.

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The purpose of this study was to prospectively examine the effectiveness and tolerability of a simple radiotherapy technique for the palliation of symptomatic liver metastases. Twenty-eight patients with symptomatic liver metastases were enrolled from seven centres, and received targeted (partial or whole) liver irradiation consisting of 10 Gy in two fractions over 2 days. Symptoms at baseline were hepatic pain (27 patients), abdominal distension (19), night sweats (12), nausea (18) and vomiting (eight). Twenty-two patients (76%) had failed previous treatment with chemotherapy, hormonal therapy and/or high-dose steroids. Symptoms and potential toxicities were prospectively assessed at the time of treatment, then 2, 6 and 10 weeks later. Individual symptom response rates were 53−66% at 2 weeks. Partial or complete global symptomatic responses were noted in 15 patients (54%) overall. The treatment was well tolerated with two patients (7%) experiencing grade 3 toxicity (one vomiting and one diarrhoea); however, four patients reported temporary worsening of pain shortly after treatment. This simple and well-tolerated treatment achieves useful palliation.

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Background and purpose: Despite numerous randomized trials investigating radiotherapy (RT) fractionation schedules for painful bone metastases, there are very few data on RT for bone metastases causing pain with a neuropathic component. The Trans-Tasman Radiation Oncology Group undertook a randomized trial comparing the efficacy of a single 8 Gy (8/1) with 20 Gy in 5 fractions (20/5) for this type of pain. Materials and methods: Eligible patients had radiological evidence of bone metastases from a known malignancy with no change in systemic therapy within 6 weeks before or anticipated within 4 weeks after RT, no other metastases along the distribution of the neuropathic pain and no clinical or radiological evidence of cord/cauda equina compression. All patients gave written informed consent. Primary endpoints were pain response within 2 months of commencement of RT and time to treatment failure (TTF). The hypothesis was that 8/1 is at least as effective as 20/5 and the planned sample size was 270 patients. Results: Between February 1996 and December 2002, 272 patients were randomized (8/1:20/5 = 137:135) from 15 centres (Australia 11, New Zealand 3, UK 1). The commonest primary cancers were lung (31%), prostate (29%) and breast (8%); index sites were spine (89%), rib (9%), other (2%); 72% of patients were males and the median age was 67 (range 2989). The median overall survival (95% CI) for all randomized patients was 4.8 mo (4.2-5.7 mo). The intention-to-treat overall response rates (95% Cl) for 8/1 vs 20/5 were 53% (45-62%) vs 61% (53-70%), P = 0.18. Corresponding figures for complete response were 26% (18-34%) vs 27% (19-35%), P = 0.89. The estimated median TTFs (95% CI) were 2.4 mo (2.0-3.3 mo) vs 3.7 mo (3.1-5.9 mo) respectively. The hazard ratio (95% Cl) for the comparison of TTF curves was 1.35 (0.99-1.85), log-rank P = 0.056. There were no statistically significant differences in the rates of re-treatment, cord compression or pathological fracture by arm. Conclusions: 8/1 was not shown to be as effective as 20/5, nor was it statistically significantly worse. Outcomes were generally poorer for 8/1, although the quantitative differences were relatively small. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

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Objective - To study the possible dose dependence of the foetal malformation rate after exposure to sodium valproate in pregnancy Methods - Analysis of records of all foetuses in the Australian Registry of Antiepileptic Drugs in Pregnancy exposed to valproate, to carbamazepine, lamotrigine or phenytoin in the absence of valproate, and to no antiepileptic drugs. Results - The foetal malformation rate was higher (P < 0.05) in the 110 foetuses exposed to valproate alone (17.1%), and in the 165 exposed to valproate, whether alone or together with the other antiepileptic drugs (15.2%), than in the 297 exposed to the other drugs without valproate (2.4%). It was also higher (P < 0.10) than in the 40 not exposed to antiepileptic drugs (2.5%). Unlike the situation for the other drugs, the malformation rate in those exposed to valproate increased with increasing maternal drug dosage (P < 0.05). The rate was not altered by simultaneous exposure to the other drugs. Valproate doses exceeding 1400 mg per day seemed to be associated with a more steeply increasing malformation rate than at lower doses and with a different pattern of foetal malformations. Conclusion - Foetal exposure to valproate during pregnancy is associated with particularly high, and dose-dependent risks of malformation compared with other antiepileptic drugs, and may possibly involve different teratogenetic mechanisms.