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51.
Luc Rochette Anne-Marie Bralet Jean Bralet 《Naunyn-Schmiedeberg's archives of pharmacology》1982,319(1):40-42
Summary The turnover of noradrenaline (NA) and dopamine (DA) was estimated in various rat brain regions by measuring the depletion of the amines after inhibition of their biosynthesis by -methyltyrosine. Acute treatment with clonidine (0.1 mg/kg) reduced NA turnover in the brain stem, hypothalamus and rest of the brain but had no effect on DA turnover in the corpus striatum and rest of the brain. After chronic clonidine treatment (0.1 mg/kg, twice daily for 15 days), NA turnover was not affected by an additional injection of clonidine in the brain stem or in the hypothalamus but was still markedly reduced in the rest of the brain. In addition, DA turnover was reduced in the corpus striatum and rest of the brain, an effect which was also observed after a single injection of a high dose of clonidine (1 mg/kg). These findings suggest that a chronic administration of clonidine may cause regionally differential changes in the sensitivity of central NA receptors. 相似文献
52.
Werner B?r Marco Schwarz Markus Alber Luc J Bos Ben J Mijnheer Coen Rasch Christoph Schneider Fridtjof Nüsslin Eugene M F Damen 《Radiotherapy and oncology》2003,69(3):251-258
BACKGROUND AND PURPOSE: To compare intensity-modulated treatment plans of patients with head and neck cancer generated by forward and inverse planning. MATERIALS AND METHODS: Ten intensity-modulated treatment plans, planned and treated with a step&shoot technique using a forward planning approach, were retrospectively re-planned with an inverse planning algorithm. For this purpose, two strategies were applied. First, inverse planning was performed with the same beam directions as forward planning. In addition, nine equidistant, coplanar incidences were used. The main objective of the optimisation process was the sparing of the parotid glands beside an adequate treatment of the planning target volume (PTV). Inverse planning was performed both with pencil beam and Monte Carlo dose computation to investigate the influence of dose computation on the result of the optimisation. RESULTS: In most cases, both inverse planning strategies managed to improve the treatment plans distinctly due to a better target coverage, a better sparing of the parotid glands or both. A reduction of the mean dose by 3-11Gy for at least one of the parotid glands could be achieved for most of the patients. For three patients, inverse planning allowed to spare a parotid gland that had to be sacrificed by forward planning. Inverse planning increased the number of segments compared to forward planning by a factor of about 3; from 9-15 to 27-46. No significant differences for PTV and parotid glands between both inverse planning approaches were found. Also, the use of Monte Carlo instead of pencil beam dose computation did not influence the results significantly. CONCLUSION: The results demonstrate the potential of inverse planning to improve intensity-modulated treatment plans for head and neck cases compared to forward planning while retaining clinical utility in terms of treatment time and quality assurance. 相似文献
53.
Vialettes B Reynier P Atlan-Gepner C Mekki N Lesluyes-Mazzochi L Luc G Lairon D Malthiery Y 《The British journal of nutrition》2000,83(6):615-622
This present case report describes two siblings with severe type V hyperlipoproteinaemia, diagnosed very early in life and due to the combination of the common apolipoprotein (Apo) E2 allele and rare mutant variant of ApoE, ApoE3 (Arg 136-->Ser). Phenotyping of ApoE falsely identified E2/E2 phenotype. The presence of mutated ApoE was suspected on an unusual restriction polymorphism of a Hha 1 restriction site and confirmed by sequence analysis of the cloned polymerase chain reaction fragment of exon 4 and familial segregation study. The severity of the hypertriacylglycerolaemia was modulated by the lipid content of the diet. A low-fat diet enriched in medium-chain triacylglycerol (TAG) decreased but did not normalize plasma TAG levels in both affected patients of the pedigree. A standardized lipid-enriched test meal showed a marked impairment of TAG-rich lipoprotein (TRL) clearance, especially the exogeneous TRL bearing ApoB-48 which still represented 79% of total TRL 7 h after the fat load. Finally, differences between the male and female siblings with the existence of a consanguine relationship in their parents suggested the involvement of other genetic factors in modulating the severity of phenotypic expression. This observation reinforces the usefulness of genotyping of ApoE for the characterization of genetic hypertriacylglycerolaemia and selection of the appropriate diet and treatment. 相似文献
54.
Ines Lessa Maria Jenny Araújo Lucélia Magalh?es Naomar de Almeida Filho Estela Aquino Maria Cecília R Costa 《Pan American journal of public health》2004,16(2):131-137
OBJECTIVE: To estimate the frequency of modifiable cardiovascular risk factors, with and without inclusion of arterial hypertension, occurring simultaneously in a racially-mixed population. METHOD: A cross-sectional study was carried out with 1,298 adults aged > or = 20 years in the city of Salvador, Brazil, in 2000. Eight modifiable cardiovascular risk factors were assessed, in any combination: total cholesterol > or = 240 mg/dL; high density-lipoprotein cholesterol (HDL-c) < 40 mg/dL; triglycerides > or = 200 mg/dL; glycemia > or = 126 mg/dL + well-controlled diabetes; body mass index > or = 25 kg/m2, waist > or = 102 cm for males and > or = 88 cm for females, smoking and alcoholism. The results were stratified according to the number of simultaneous risk factors (zero to five or more and two or more risk factors). The data were analyzed in terms of estimated proportions and 95% confidence intervals (95%CI), with and without the inclusion of arterial hypertension (VI Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure [JNC-VI], United States of America), ratio of proportions and chi-square for proportions as a measure of association. RESULTS: Among men (41.4% of participants), 7.5% (95%CI: 2.5 to 9.7) did not present risk factors; 68.8% (95%CI: 65.0 to 72.8) presented two or more risk factors, not including hypertension. After inclusion of hypertension, 73.4% (95%CI: 69.7 to 77.1) presented two or more risk factors. Among women, 11.6% did not present risk factors. The presence of two or more risk factors, not including hypertension, was observed in 67.7% (95%CI: 64.8 to 71.4). After inclusion of hypertension, 71.7% (95%CI: 68.5 to 74.9) of the women presented two or more risk factors. Significant differences were observed for the presence of two or more risk factors in men with not more than 4 years of schooling vs. 5 to less than 11 years of schooling (P < 0.05); in women with not more than 4 years of schooling vs. 5 to less than 11 years of schooling; in women with not more than 4 years of schooling vs. 11 or more years of schooling (P < 0.01); and in black vs. white women (P < 0.01). CONCLUSIONS: The high proportion of clustering cardiovascular risk factors in Salvador, with or without hypertension, especially in the population with little schooling and in black individuals, suggests the need for broad social strategies to reduce social inequality, promote health, and facilitate the treatment of cardiovascular risk factors. 相似文献
55.
Dorotheé Bouron-Dal Soglio Isabelle Harvey Salam Yazbeck Fran?oise Rypens Luc L Oligny Jean-Christophe Fournet 《Pediatric and developmental pathology》2006,9(1):61-64
The association of pleuropulmonary blastoma and cystic nephroma is an uncommon entity, with only 4 cases of such an association in the same patient described in English literature. We report a 5th histologically documented case in a 32-month-old boy. The boy underwent a pulmonary biopsy that showed a pleuropulmonary blastoma and a nephrectomy that showed a cystic nephroma. The pleuropulmonary mass showed an important regression with postbiopsy chemotherapy, allowing subsequent tumorectomy. To date very little is known about this rare entity, and a genetic link between these 2 tumors is hypothesized. 相似文献
56.
Maria Carmen Iglesias-Osma Sandy Bour Maria Jose Garcia-Barrado Virgile Visentin Maria Francisca Pastor Xavier Testar Luc Marti Gemma Enrique-Tarancon Philippe Valet Julio Moratinos Christian Carpn 《Pharmacological research》2005,52(6):21-484
It has been reported that benzylamine reduces blood glucose in rabbits, stimulates hexose uptake, and inhibits lipolysis in mouse, rabbit, and human adipocytes. In the presence of vanadate, benzylamine is also able to improve glucose disposal in normoglycaemic and diabetic rats. Such insulin-mimicking properties are the consequence of hydrogen peroxide production during benzylamine oxidation by semicarbazide-sensitive amine oxidase (SSAO). The aim of the study was to determine whether other SSAO-substrates could share such potential antidiabetic properties. Thus, mafenide, a synthetic antimicrobial sulfonamide structurally related to benzylamine, and which has been recently reported to interact with SSAO, was tested in the above mentioned models, in parallel with methylamine, a proposed endogenous SSAO-substrate. All tested amines stimulated glucose uptake and inhibited lipolysis in rat and mouse fat cells. Methylamine and benzylamine, but not mafenide, reduced the hyperglycaemic response during a glucose tolerance test in rabbits while the three amines tested were devoid of insulin-releasing activity under both in vivo and in vitro conditions. In human adipocytes, mafenide did not stimulate glucose transport since it was not a high-affinity substrate for SSAO and generated less hydrogen peroxide than benzylamine or methylamine. Therefore, mafenide could not be considered as an antidiabetic drug despite being oxidized and exhibiting insulin-mimicking effects in rat and mouse adipocytes. By contrast, the endogenous substrate methylamine improved glucose utilization in all in vitro and in vivo models, leading to consider novel SSAO substrates as drugs with potential anti-hyperglycaemic properties. 相似文献
57.
Risk management strategies in the postmarketing period : safety experience with the US and European bosentan surveillance programmes. 总被引:1,自引:0,他引:1
Eleanor S Segal Cecile Valette Laurence Oster Luc Bouley Catarina Edfjall Peter Herrmann Massimo Raineri Mary Kempff Saundra Beacham Cinda van Lierop 《Drug safety》2005,28(11):971-980
In view of the shortcomings of the current system for postmarketing drug surveillance that is based on voluntary spontaneous adverse drug reaction (ADR) reporting, new approaches are needed.We describe an approach involving a combination of limited distribution, patient and physician education, as well as a novel pharmaco-vigilance system that is capable of promoting the safe and adequate use of a new drug. Importantly, it provides the possibility of calculating true ADR occurrence rates, as the exposed population (denominator) and the number of patients with events (numerator) are known. These measures were taken for the oral dual endothelin ET(A)/ET(B) antagonist bosentan (Tracleer). In recent guidelines issued by the European Society of Cardiology, American College of Chest Physicians and the WHO, this drug is considered as first-line oral treatment for the treatment of pulmonary arterial hypertension, a devastating orphan disease associated with a poor prognosis. Bosentan was approved in 2001/2 on the basis of two pivotal studies that showed improved exercise capacity and haemodynamic parameters while delaying time to clinical worsening. Elevations in serum liver aminotransferase levels of >3 times the upper limit of normal were noted in 10.2% of patients (placebo-subtracted incidence). Therefore, liver function tests have to be performed on a regular basis. In addition, bosentan has potential as a teratogen.In the US, a controlled distribution network for bosentan (Tracleer) Access Program [T.A.P.]) and the development of a patient database to follow patients was set up. Accompanied by comprehensive physician and patient education programmes, T.A.P. was developed to provide a mechanism to assist with the primary risk management goals for bosentan therapy, namely pregnancy prevention and liver enzyme monitoring and prevention of hepatic injury.In Europe, the Tracleer) Excellence (TRAX PMS) database is a novel European non-interventional, prospective, internet-based surveillance system initiated by the manufacturer in cooperation with the European Medicines Agency. It collected potential safety signals associated with bosentan use including adverse events, elevations of liver aminotransferase levels, other abnormal laboratory values, death and hospitalisation. TRAX PMS has accrued 79% of all known patients in the EU and the data provide supportive 'real-life' evidence on the long-term safety of bosentan.The two different systems had similar goals and outcomes. The data received concerning thousands of patient-years of use have confirmed the clinical trial results regarding product safety and the favourable benefit/risk ratio of bosentan, especially with regard to known type A adverse events. The clinical monitoring algorithm has also been confirmed. In addition, no rare type B events were uncovered despite the increased reporting rate. These systems might serve as templates for future pharmaco-vigilance efforts regarding drugs that require particular safety attention. 相似文献
58.
Tumor lymphangiogenesis in inflammatory breast carcinoma: a histomorphometric study. 总被引:11,自引:0,他引:11
Ilse Van der Auwera Gert G Van den Eynden Cecile G Colpaert Steven J Van Laere Peter van Dam Eric A Van Marck Luc Y Dirix Peter B Vermeulen 《Clinical cancer research》2005,11(21):7637-7642
PURPOSE: At the time of diagnosis, metastatic dissemination of tumor cells via the lymphatic system has occurred in nearly all patients with inflammatory breast cancer (IBC). The objective of this study was twofold: (a) to determine which is the most suitable marker of lymph vessels in primary breast tumors and (b) to compare histomorphometric lymph vessel variables in IBC and non-IBC. EXPERIMENTAL DESIGN: Serial sections of 10 IBCs and 10 non-IBCs were immunostained for D2-40, LYVE-1, podoplanin, and PROX-1. Relative lymph vessel area, lymph vessel perimeters, and counts and lymphatic endothelial cell proliferation (LECP) were then measured in D2-40/Ki-67 double-immunostained sections of 10 normal breast tissues, 29 IBCs, and 56 non-IBCs. RESULTS: D2-40 was the most suitable antibody for staining peritumoral and intratumoral lymph vessels. D2-40-stained intratumoral lymph vessels were present in 80% of non-IBCs and 82.8% of IBCs (P = 0.76). In non-IBC, lymph vessels located in the tumor parenchyma were smaller and less numerous than those at the tumor periphery (P < 0.0001) whereas in IBC, intratumoral and peritumoral variables were not significantly different. The mean relative tumor area occupied by lymph vessels was larger in IBC than in non-IBC (P = 0.01). LECP at the tumor periphery was higher in IBC than in non-IBC: median LECP was 5.74% in IBC versus 1.83% in non-IBC (P = 0.005). CONCLUSIONS: The high LECP in IBC suggests that lymphangiogenesis contributes to the extensive lymphatic spread of IBC. 相似文献
59.
60.
Weidong He Luc Van Puyvelde Norbert De Kimpe Luc Verbruggen Kristel Anthonissen Mark Van der Flaas Jan Bosselaers Simon G Mathenge Francis P Mudida 《Phytotherapy research : PTR》2002,16(1):66-70
Bioassay-guided fractionation of the dichloromethane extracts of the roots and the bark of Zanthoxylum usambarense led to the isolation of two physiologically active compounds, i.e. canthin-6-one 1 (fungicide) and pellitorine 4 (insecticide). Together with oxychelerythrine 2, norchelerythrine 3, (+)-sesamin 5 and (+)-piperitol-3,3-dimethylallyl ether 6, they were isolated for the first time from this plant. 相似文献