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排序方式: 共有2232条查询结果,搜索用时 62 毫秒
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Marlene L Hauck Susan M LaRue William P Petros Jean M Poulson Daohai Yu Ivan Spasojevic Amy F Pruitt Allison Klein Beth Case Donald E Thrall David Needham Mark W Dewhirst 《Clinical cancer research》2006,12(13):4004-4010
PURPOSE: To determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic characteristics of doxorubicin encapsulated in a low temperature sensitive liposome (LTSL) when given concurrently with local hyperthermia to canine solid tumors. EXPERIMENTAL DESIGN: Privately owned dogs with solid tumors (carcinomas or sarcomas) were treated. The tumors did not involve bone and were located at sites amenable to local hyperthermia. LTSL-doxorubicin was given (0.7-1.0 mg/kg i.v.) over 30 minutes during local tumor hyperthermia in a standard phase I dose escalation study. Three treatments, given 3 weeks apart, were scheduled. Toxicity was monitored for an additional month. Pharmacokinetics were evaluated during the first treatment cycle. RESULTS: Twenty-one patients were enrolled: 18 with sarcomas and 3 with carcinomas. Grade 4 neutropenia and acute death secondary to liver failure, possibly drug related, were the dose-limiting toxicities. The maximum tolerated dose was 0.93 mg/kg. Other toxicities, with the possible exception of renal damage, were consistent with those observed following free doxorubicin administration. Of the 20 dogs that received > or = 2 doses of LTSL-doxorubicin, 12 had stable disease, and 6 had a partial response to treatment. Pharmacokinetic variables were more similar to those of free doxorubicin than the marketed liposomal product. Tumor drug concentrations at a dose of 1.0 mg/kg averaged 9.12 +/- 6.17 ng/mg tissue. CONCLUSION: LTSL-doxorubicin offers a novel approach to improving drug delivery to solid tumors. It was well tolerated and resulted in favorable response profiles in these patients. Additional evaluation in human patients is warranted. 相似文献
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Kassiani Theodoraki Panagiota Rellia Apostolos Thanopoulos Loukas Tsourelis Dimitrios Zarkalis Petros Sfyrakis Theophani Antoniou 《Journal canadien d'anesthésie》2002,49(9):963-967
PURPOSE: Severe pulmonary hypertension (PH) is a major cause of right ventricular (RV) dysfunction. Various iv vasodilator modalities have been used with limited results because of lack of pulmonary selectivity. The aim of the present controlled study was to evaluate the efficacy of inhaled iloprost, a synthetic prostacyclin analogue, in patients with elevated pulmonary vascular resistance (PVR) immediately after separation from cardiopulmonary bypass (CPB). METHODS: Twelve patients with persistent PH after discontinuation of CPB were included in the study. In all patients standard hemodynamic monitoring was used. Inhaled iloprost was administered via nebulized aerosol at a cumulative dose of 0.2 micro g*kg(-1) for a total duration of 20 min. Complete sets of hemodynamic measurements were performed before inhalation (baseline), during and after cessation of the inhalation period. Echocardiographic monitoring of RV function was also used. RESULTS: Inhaled iloprost induced a reduction in the transpulmonary gradient at the end of the inhalation period in comparison to baseline (9.33 +/- 3.83 mmHg vs 17.09 +/- 6.41 mmHg, P < 0.05). The mean pulmonary artery pressure to systemic artery pressure ratio decreased over this period (0.28 +/- 0.08 vs 0.45 +/- 0.17, P < 0.05). A statistically significant decrease of the PVR to systemic vascular resistance ratio was also observed (0.15 +/- 0.05 vs 0.21 +/- 0.05, P < 0.05). Improved indices of RV function were observed in echocardiographic monitoring. CONCLUSION: Inhaled iloprost appears to be a selective pulmonary vasodilator and may be effective in the initial treatment of PH and the improvement of RV performance in the perioperative setting. 相似文献
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Kalpadakis Petros Rudolph Günther 《Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie》2003,241(6):522-522
Graefe's Archive for Clinical and Experimental Ophthalmology - 相似文献
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Strategies for treating pediatric malignancies have not only been successful (i.e., curative) for several disseminated childhood cancers, they have also served as paradigms for the therapy of many adult cancers. Initial strategies included combined treatment modalities (chemotherapy, surgery, radiotherapy) and combinations of different pharmacologic classes of anticancer drugs given in the appropriate schedules. Despite the currently successful therapy for some malignancies (e.g., 70% 4-year disease-free survival in acute lymphocytic leukemia), many children die without known reason. Recent advances in the clinical pharmacology of anticancer drugs have identified relationships between dose intensity and response (efficacy, toxicity). Traditional methods of measuring dose intensity (prescribed dose) have evolved to more sophisticated approaches in maximizing the intensity of treatment, with good response rates. Other methods of optimizing chemotherapy for individual patients include bone marrow support procedures and therapy with biologic response modifiers. Relatively few clinically useful new anticancer drugs have been discovered in the past several years. Fortunately, the potential to improve therapy with currently available agents has come about through enhanced knowledge of the biochemical and clinical pharmacology of anticancer drugs and biologic response modifiers, as well as improved understanding drug resistance biology. 相似文献
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The aim of the study was to identify the striated muscle forces hypothesized to assist bladder neck opening and closure in
females. Cadaveric dissection was used to identify the levator plate (LP), the anterior portion of pubococcygeus muscle (PCM),
the longitudinal muscle of the anus (LMA), and their relation to the bladder, vagina and rectum. X-ray video recordings were
made during coughing, straining, squeezing and micturition in a group of 20 incontinent patients and 4 controls, along with
surface EMG, urethral pressure and digital palpation studies. During effort, urethral closure appeared to be activated by
a forward muscle force corresponding to PCM, and bladder neck closure by backward muscle forces corresponding to LP and LMA.
During micturition the PCM force appeared to relax, allowing LP and LMA to pull open the outflow tract. The data appear to
support the hypothesis of specific directional muscle forces stretching the vagina to assist bladder neck opening and closure. 相似文献
8.
Mohand Mesbah Ilka Nemere Petros Papagerakis Jean-Raphael Nefussi Silvana Orestes-Cardoso Catherine Nessmann Ariane Berdal 《Journal of bone and mineral research》2002,17(9):1588-1596
The calciotropic hormone 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] has been established to control skeletal tissue formation and biomineralization via the regulation of gene expression. This action involves the well-characterized nuclear 1,25(OH)2D3 receptor. However, it has been recognized that several cellular responses to 1,25(OH)2D3 may not to be related to the exclusive nuclear receptor. Indeed, this secosteroid is able to generate rapid responses that have been proposed to be mediated by interactions of the ligand, which is a putative cell membrane-associated rapid-response steroid (MARRS) binding protein for 1,25(OH)2D3 [1,25D3-MARRS]. The nongenomic pathway of 1,25(OH)2D3 was studied here in detail by immunolocalization of the 1,25D3-MARRS during the specific context of human prenatal development. Western blotting with proteins extracted from 4 week- to 27-week-old embryos was performed, evidencing a 65-kDa molecular species recognized by antibody Ab 099 generated against synthetic peptides corresponding to the N terminus of the 1,25D3-MARRS from chick intestinal basolateral membranes. Based on this biochemical conservation of protein in the human species, the temporospatial expression patterns were established in the craniofacial skeleton at the same ages. Comparative analysis was performed in teeth and bones from early morphogenesis to terminal cell differentiation and extracellular biomineralization. The data show the potential implication of 1,25D3-MARRS in the heterogeneous cell population including ameloblasts, odontoblasts, osteoblasts, and osteoclasts. The epithelial-mesenchymal cascade related to odontogenesis was coincident with a sequence of up- and down-regulation of immunoreactive 1,25D3-MARRS. Biomineralization was associated with a striking up-regulation in the adjoining secretory cells in all tissues. Finally, osteoclasts appeared also to express the 1,25D3-MARRS during these early phases of bone modeling. Previously obtained data of the nuclear vitamin D receptor (VDR) expression and this study on 1,25D3-MARRS suggest the existence of cross-talk between the genomic and nongenomic pathways during human development. 相似文献
9.
Alan G. Fraser Peter T. Buser Jeroen J. Bax Willem R. Dassen Petros Nihoyannopoulos Jürg Schwitter Juhani M. Knuuti Martin Höher Frank Bengel András Szatmári 《European journal of nuclear medicine and molecular imaging》2006,33(8):955-959
Advances in medical imaging now make it possible to investigate any patient with cardiovascular disease using multiple methods which vary widely in their technical requirements, benefits, limitations and costs. The appropriate use of alternative tests requires their integration into joint clinical diagnostic services where experts in all methods collaborate. This statement summarises the principles that should guide developments in cardiovascular diagnostic services.This paper is published simultaneously in the European Heart Journal (2006;27:1750–1753) and in the European Journal of Echocardiography (2006;7:268–273). 相似文献
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