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41.
本系统通过以Internet网为平台,将传统的医院/患者(咨询者)的遗传随访模式转为医院/Internet网/患者(咨询者)的新医疗模式,该系统会大大提高遗传随访的及时性和便利性;同时,会有利于遗传登记的开展,也有利于随访资料的保存。 相似文献
42.
S. D. ROBINSON† C. A. LUDLAM‡ N. A. BOON† D. E. NEWBY† 《Journal of thrombosis and haemostasis》2006,4(10):2262-2269
OBJECTIVES: To determine if polymorphisms of the tissue plasminogen activator (t-PA) gene influence acute endogenous t-PA release in patients with coronary heart disease (CHD). METHODS: Forearm blood flow and plasma t-PA concentrations were measured in response to intra-brachial infusion of substance P and sodium nitroprusside in 96 patients with stable CHD. Genotyping was performed using a Taqman polymerase chain reaction assay specifically designed to detect the polymorphisms of interest: (i) Alu-repeat insertion/deletion sequence; (ii) C-->T substitution in an upstream enhancer region (-7351 C/T); (iii) T-->C in exon 6 (20 099 T/C); and (iv) T-->A (27 445 T/A) in intron 10. RESULTS: Substance P and sodium nitroprusside caused dose-dependent increases in forearm blood flow in all patients (P < 0.001 for all) that were independent of the four genetic polymorphisms. Similarly, there were no differences in basal plasma t-PA antigen concentrations or net t-PA release between genotypes. Compared to non-smokers, smokers exhibited impaired substance P-induced vasodilatation (P < 0.001) and t-PA release (P = 0.05). CONCLUSIONS: Despite confirming our previous findings in cigarette smokers, we have found no effect of polymorphisms of the t-PA gene on two complementary aspects of endothelial function. We conclude that genetic variation of the t-PA locus is unlikely to have a major influence on acute t-PA release in subjects with established CHD. 相似文献
43.
维甲酸硅油的视网膜毒性实验研究 总被引:1,自引:0,他引:1
目的:了解维甲酸硅油对视网膜是否产生毒性。
方法:12只新西兰白兔的24只眼,随机分为3组,行气体压迫玻璃体手术3天后,分别向玻璃体腔内注入硅油(4只眼)、5μg/ml维甲酸硅油(10只眼)、10μg/ml维甲酸硅油(10只眼)各
0.5m1,用检眼镜、光漳和电镜检查来观察视网膜变化情况。
结果:注入硅油28天后,未发现各浓度的维甲酸硅油对视网膜产生毒性作用。结论:浓度为5、10μg/ml的维甲酸硅油注入玻璃体腔4周,对视网膜不产生毒性作用。
(中华眼底病杂志,1997,13:81-82) 相似文献
44.
The development of a unifying framework for conceptualizing the commonalities in various forms of substance abuse must encompass the data base focused upon the stimulus functions of drugs. In the first instance, for example, the research on drug self-administration has provided convincing evidence of a remarkable concordance between laboratory animals and human substance abusers in the reinforcing stimulus functions of a range of chemical agents. The recognition of these cross-species and cross-drug generalities has radically changed conceptualizations of substance abuse from a reactive to a more active process and has encouraged the kind of functional analysis of drug-seeking and drug-taking that has proven productive and useful in the study of other behavioral interactions. In this regard as well, recent refinements in the analysis of the discriminative stimulus functions of drugs have provided a more comprehensive basis for characterizing a chemical agent's spectrum of action and evaluating its abuse liability. While the correlation between the discriminative stimulus functions and the reinforcing stimulus functions is remarkably high for some drug classes, there are notable exceptions. Finally, the assessment of abuse liability requires an analysis of the eliciting stimulus functions of drugs as reflected by the physiological and behavioral changes, both acute and chronic, that follow drug administration. The methods used to evaluate both physiological dependence and behavioral toxicity in relationship to sensory and motor effects for a range of abused drugs have depended heavily upon an assessment of the eliciting stimulus functions of such compounds. 相似文献
45.
HELEN J. GILL JAMES L. MAGGS STEPHEN MADDEN MUNIR PIRMOHAMED & B. KEVIN PARK 《British journal of clinical pharmacology》1996,42(3):347-353
1 Cytochrome P450-mediated bioactivation of sulphamethoxazole to a hydroxylamine has been implicated in the hypersensitivity reactions associated with co-trimoxazole administration. Inhibiting the formation of the hydroxylamine may be one method of preventing the high frequency of toxicity which is observed in HIV-infected patients. Therefore, in this study, we have investigated the ability of fluconazole and ketoconazole, known cytochrome P450 inhibitors, to inhibit the formation of sulphamethoxazole hydroxylamine.
2 Ten healthy male volunteers were given co-trimoxazole (800 mg sulphamethoxazole and 160 mg trimethoprim) alone or 1 h after either fluconazole (150 mg) or ketoconazole (200 mg) in a randomized fashion with a washout period of at least 1 week between each phase. Urine was collected for 24 h, and sulphamethoxazole and its metabolites were quantified by electrospray LC-MS.
3 Ketoconazole had no effect on the urinary recovery of sulphamethoxazole or any of its metabolites. In contrast, fluconazole significantly ( P <0.001) inhibited the formation of sulphamethoxazole hydroxylamine by 50.0±15.1%. Fluconazole also inhibited the oxidation of sulphamethoxazole to the 5-methylhydroxy and 5-methylhydroxy acetate metabolites by 69.9±15.8% and 64.0±12.0%, respectively, but had no effect on the amount of sulphamethoxazole, N4 -acetyl sulphamethoxazole, or sulphamethoxazole N1 -glucuronide excreted in urine.
4 The potential clinical benefit of using fluconazole to prevent hypersensitivity to co-trimoxazole in patients with AIDS needs to be assessed in a prospective study using both metabolite formation and the clinical occurrence of adverse reactions as end-points. 相似文献
2 Ten healthy male volunteers were given co-trimoxazole (800 mg sulphamethoxazole and 160 mg trimethoprim) alone or 1 h after either fluconazole (150 mg) or ketoconazole (200 mg) in a randomized fashion with a washout period of at least 1 week between each phase. Urine was collected for 24 h, and sulphamethoxazole and its metabolites were quantified by electrospray LC-MS.
3 Ketoconazole had no effect on the urinary recovery of sulphamethoxazole or any of its metabolites. In contrast, fluconazole significantly ( P <0.001) inhibited the formation of sulphamethoxazole hydroxylamine by 50.0±15.1%. Fluconazole also inhibited the oxidation of sulphamethoxazole to the 5-methylhydroxy and 5-methylhydroxy acetate metabolites by 69.9±15.8% and 64.0±12.0%, respectively, but had no effect on the amount of sulphamethoxazole, N
4 The potential clinical benefit of using fluconazole to prevent hypersensitivity to co-trimoxazole in patients with AIDS needs to be assessed in a prospective study using both metabolite formation and the clinical occurrence of adverse reactions as end-points. 相似文献
46.
Brambati B.; Tului L.; Baldi M.; Guercilena S. 《Human reproduction (Oxford, England)》1995,10(4):818-825
Multiple pregnancies resulting from ovarian stimulation areat a higher risk of carrying at least one fetus affected byMendelian or chromosomal anomalies, the incidence of which isdirectly related to the order of multiples. Genetic analysisbefore fetal reduction was offered to both high-and low-riskpregnant women carrying two or more fetuses after ovulationinduction. Chorionic villus sampling (CVS) and fetal reductionwere achieved by transabdominal needling. The use of short-termculture, the polymerase chain reaction and fresh tissue enzymaticanalyses have made it possible for genetic diagnosis to be availablein a few days. A total of 100 patients had multifetal pregnancyreduction performed by a single operator; all of them completedpregnancy and none was lost at follow-up. The total fetal lossbefore 24 weeks was 7% and no statistically significant relationshipwas found with the final number of fetuses and CVS. Perinatallosses (3.9%) were only present in the series with a final numberof two fetuses. Pregnancy duration and birthweight were significantlyhigher in singletons than in twins, but were not related toCVS. The rate of chromosomal disorders was higher (7.2%) inthe study series than in singleton pregnancies not undergoingfetal reduction. Diagnostic error due to incorrect samplingwas reported in 1.5% of cases. These data support fetal reductionas a valuable strategy to improve the outcome of multiple pregnancy.The outcome of pregnancies reduced to singletons was significantlybetter than of those reduced to twins, and was not related toCVS. Therefore, prenatal genetic diagnosis should become anintegral part of counselling on multiple pregnancy, and is stronglyrecommended when reduction to singleton pregnancy is requested. 相似文献
47.
Rose-Mary Boustany 《American journal of medical genetics. Part A》1992,42(4):533-535
My experience with more than 80 cases of the late infantile and juvenile forms of the neuronal ceroid-lipofuscinoses over the last 5 years has led to the following realizations. The 2 variants are neurologically distinct entities and probably are the result of different genetic defects. Treatment includes supportive measures and anticonvulsant medication. Therapy for behavioral and psychiatric disturbances in the juvenile type proves to be particularly challenging as neuroleptic medications tend to worsen parkinsonian like symptoms. Neuropathologic and neuro radiologic explanation of clinical symptomatology correlates best with neuronal loss and not neuronal storage. There is a paucity of neuropathologic documentation of these 2 types; additional reports are encouraged. 相似文献
48.
玻璃体内注射庆大霉素致视网膜损伤的实验研究Ⅰ.组织病理学观察 总被引:1,自引:0,他引:1
为探讨庆大霉素对视网膜的毒性作用和评估玻璃体内注射庆大霉素的安全剂量,采用眼底镜观察及光镜、电镜技术对注射5种不同剂量庆大霉素的青紫蓝兔视网膜标本进行观察。结果:3000μg庆大霉素注射后眼底表现为视盘水肿,后极部视网膜大片坏死,镜下视网膜组织形态严重破坏;50~500μg剂量注射引起后极部视网膜色素改变,组织损伤早期局限在视网膜内层,晚期全层受累。提示庆大霉素对视网膜的损伤程度随注入剂量增加而加重,即使50μg的微小剂量仍可产生视网膜损伤。 相似文献
49.
Enza-Maria Valente Anjum Misbahuddin Francesco Brancati Mark R Placzek Barbara Garavaglia Sergio Salvi Andrea Nemeth Charles Shaw-Smith Nardo Nardocci Anna-Rita Bentivoglio Alfredo Berardelli Roberto Eleopra Bruno Dallapiccola Thomas T Warner 《Movement disorders》2003,18(9):1047-1051
The epsilon-sarcoglycan gene (SGCE) on human chromosome 7q21 has been reported to be a major locus for inherited myoclonus-dystonia. Linkage to the SGCE locus has been detected in the majority of families tested, and mutations in the coding region have been found recently in families with autosomal dominant myoclonus-dystonia. To evaluate the relevance of SGCE in myoclonus-dystonia, we sequenced the entire coding region of the epsilon-sarcoglycan gene in 16 patients with either sporadic or familial myoclonus-dystonia. No mutations were found. This study suggests that epsilon-sarcoglycan does not play an important role in sporadic myoclonus-dystonia and supports genetic heterogeneity in familial cases. 相似文献
50.
硝基胍的毒性研究 总被引:2,自引:1,他引:1
目的对硝基胍的毒性进行研究,为制订卫生标准提供依据.方法包括急性毒性试验、蓄积毒性试验及亚慢性毒性试验.结果硝基胍大鼠经口LD50为8 066 mg/kg,小鼠经口LD50为10 044 mg/kg,蓄积系数大于5.3.亚慢性毒性试验中,高剂量组雄性大鼠在染毒第3周和第8周,体重有明显的负增长(P<0.05);高剂量组雄性大鼠睾丸脏器系数明显高于对照组(P<0.05);红细胞免疫功能测定结果显示,中、高剂量组大鼠红细胞受体花环率分别为10.00±2.37和7.50±2.66,明显低于对照组(P<0.05,P<0.01).其余各项指标未见明显改变.结论硝基胍属于微毒级毒物,轻度蓄积,亚慢性毒性试验对动物有一定的影响. 相似文献