A drug interaction study between ticlopidine and cyclosporin in heart transplant recipients

Objectives: Previous uncontrolled studies have suggested an interaction between ticlopidine, a major antiplatelet agent, and cyclosporin in heart- and kidney-transplant recipients. The aims of this study were to examine in a randomised, double-blind fashion, the possible interaction between cyclosporin A and ticlopidine (250 mg per day) and the tolerability of this combination in heart-transplant recipients. Methods: Twenty heart-transplant recipients were randomised into either a treated or a placebo group. Blood samples were drawn for time-course evaluation of cyclosporin blood levels over a period of 12 h, following the morning intake of cyclosporin and, for platelet aggregation studies, before and after 14 days of ticlopidine administration. Twenty four-hour urine samples were collected for 6-β-hydroxycortisol measurements, before and after 14 days of ticlopidine. Results: Although given at half the recommended daily dosage, ticlopidine significantly reduced platelet aggregation. Pharmacokinetic parameters indicate that the bioavailability of cyclosporin A was not significantly modified by ticlopidine. However, one patient in the ticlopidine group was withdrawn because of a major fall in cyclosporin blood level within 3 days of treatment. Urinary excretion of 6-β-hydroxycortisol was augmented after treatment in the ticlopidine group compared with the placebo group, suggesting that induction of drug metabolism might have occurred. Data also show quite a large intra-individual variability in cyclosporin bioavailability in the placebo group, suggesting that poor absorption of the drug formulation and/or poor compliance might have contributed to the decreased cyclosporin blood levels in the patient withdrawn from this study and in previous uncontrolled studies. Conclusion: Cyclosporin bioavailability was not clearly modified by a half dosage of ticlopidine in this study. We, however, recommend closely monitoring cyclosporin blood levels when prescribing ticlopidine. Further studies will be needed with new formulations of cyclosporin or when using the full dosage of ticlopidine. Received: 20 July 1996 / Accepted in revised form: 12 February 1997     

Ocular findings in familial adenomatous polyposis

Background: Retinal pigment epithelium (RPE)lesions are predictive congenital phenotypic markersfor familial adenomatous polyposis (FAP). Thisprospective screening study aims at assessing theincidence and significance of these lesions in FAPpatients and their family members.Methods: Sixty-two members from three familiesincluding five patients with the diagnosis of FAP havebeen ophthalmologically surveyed. All RPE lesions weredocumented with fundus photography and fluoresceinangiography was performed in 13 subjects.Sigmoidoscopy and/or radiological examination wereperformed annually in 9 family members with typicalRPE lesions during 4 years to allow early diagnosis ofFAP.Results: Typical RPE lesions were present infive FAP patients and 15 family members.Telangiectatic dilatations in the retinal peripherywith small dot-like hemorrhages were detected in 6subjects from 3 families These lesions wereparticularly evident on fluorescein angiography.Annual colon analysis showed polyps in 3 out of 9subjects who were positive for RPE lesions.Conclusion: RPE lesions are valuable as aclinical marker in predicting FAP. The co-existingperipheral vascular alterations which have not beenreported before, are probably related to FAP.     

论《金匮要略》基本学术思想及辨病与辨证——从《脏腑经络先后病脉证第一》谈起

研究《金匮要略》的重点应该放在对于各种疾病的辨证论治上，而不是某些证或某些方。这里涉及到如何看待病与证以及辨病与辨证的关系。以《金匮要略》的基本学术思想立论，从四个方面阐述了在整体论思想指导下的辨证论治体系，首先注重的是病；辨证方法的确立是由在发病学上具有不同性质特点的疾病所决定的；四诊所得的各种临床信息是为了辨病然后辨证；只有正确把握病与证的关系，才有可能真正理解和掌握“治未病”的实质。     

金地鼠颊囊癌前病变的细胞增殖动力学研究

目的研究口腔上皮组织癌和癌前病变的细胞动力学变化特征。方法采用Ｓａｌｅｙ的ＤＭＢＡ涂布诱导法，建立金地鼠颊囊癌前病变模型，并用溴脱氧尿苷流式细胞动力学检测方法，对３０只叙利亚种金地鼠进行分组对照研究。结果涂药组光镜下的细胞病变程度随涂药时间延长而逐渐加重，而空白对照组无变化；ＦＣＭ检测显示涂药组与对照组在Ｓ期阳性细胞检出率存在显著差异。即使在光镜下表现为轻度不典型增生时，ＦＣＭ检测结果也有显著差别。结论金地鼠颊囊癌前病变具有细胞异常增殖的细胞动力学特征     

Direct cadiac electorphysiologic effects of sufentanil and vecuronium in isolated guinea-pig hearts

Sufentanil and vecuronium are commonly used simultaneously in anaesthesia. Bradycardia and asystole have been described immediately after the administration of these two compounds. Therefore, the purpose of the present study was to evaluate the direct cardiac effects of sufentanil and vecuronium in all parts of the cardiac pacemaker and conduction system.
The electrophysiological effects of sufentanil and vecuronium were studied in isolated spontaneously beating guinea-pig hearts perfused by the method of Langendorff. At a concentration of 0.1 μmol/1 sufentanil a significant reduction of the spontaneous sinus rate, prolongation of atrioventricular, intraventricular and His' bundle conduction could be observed. The highest concentration of 10 μmol/1 of sufentanil led to an overall slowing of conduction velocity and to an profound slowing of spontaneous sinus rate. AV nodal as well as atrial and ventricular refractoriness were markedly prolonged at this high concentration of sufentanil. In contrast, during perfusion with vecuronium at a concentration of 0.1 μmol/1 up to 10 μmol/1 no significant effects on cardiac conduction and pacemaker activity could be observed.
In conclusion, the electrophysiological effects of sufentanil are comparable to that of unspecific calcium antagonists. Therefore, especially in patients with a preexisting damage of the cardiac conduction system, the indirect effect of the combination of sufentanil and vecuronium which is predominantly responsible for bradycardia and asystole may be worsened by the direct effects of sufentanil.     

双头加压螺纹钉贴股骨距内固定治疗股骨颈骨折

在Ｘ光电视下采用双头加压螺纹钉贴股骨距内固定治疗新鲜股骨颈骨折４２例，随访平均２．５年，其中１６例随访３年以上，骨折愈合率９５．２％，骨折不愈合并股骨头缺血性坏死率４．７６％。认为加压螺纹钉贴股骨距内固定可使钉的受力由较大剪应力变为较大轴向力承受，减少骨折处的剪应力，并加压于骨折端能促进骨折愈合。具有操作简单、进钉准确、创伤小、固定牢靠、并发症少等优点。     

四氧嘧啶诱发糖尿病大鼠血管紧张素的变化

实验观察了四氧嘧啶诱发糖尿病大鼠连续饲养１１０ｄ后体内肾素一血管紧张素系统的变化。结果表明，血浆和心脏的血管紧张素Ⅱ含量无明显变化，而肾脏的ＡｎｇⅡ含量却明显低于正常对照组。另外，心脏的心钠素（ＡＮＰ）含量在糖尿病大鼠与正常对照组之间无差别，血中的糖化血红蛋白含量基本无变化。上述结果表明，糖尿病大鼠早期心脏可能无明显损伤，而肾脏的肾素一血管紧张素系统活性降低。     

In Vivo Studies of Pulsatile Implantable Impeller Assist and Total Hearts

Abstract: A pulsatile impeller assist heart and a total heart were tested as a chronic left ventricular assist device in 5 calves and an acute biventricular assist device in 4 pigs respectively, to evaluate their blood compatibility. During the left ventricular assist experiments, the indicators for hemolysis, thrombogenesis, renal dysfunction, and hepatic dysfunction were measured preoperatively, at the beginning of the pumping, 6 h postoperatively, and every following day. The results demonstrated that the impeller assist heart causes no severe blood damage nor organ dysfunction in the experiments lasting up to 11 days. In biventricular assist experiments, the number of red blood cells, white blood cells, platelets, and the he-matocrit, hemoglobin, free hemoglobin, and lactate dehy-drogenase levels were tested preoperatively at the beginning of the pumping and every 2 h postoperatively. The data remained in acceptable ranges during experiments lasting 6 h. It is confirmed that the authors' impeller assist heart and total heart have the advantages of simplicity, implantability, and pulsatility with good blood compatibility.     

Prevention of Restenosis after Coronary Angioplasty with Low-Density Lipoprotein Apheresis

Abstract: A prospective study was performed to determine whether low-density lipoprotein (LDL) apheresis, when performed only immediately before and after percutaneous transluminal coronary angioplasty (PTCA), is effective in preventing restenosis of coronary artery lesions following PTCA. Thirty-six patients with coronary heart disease (CHD) and hypercholesterolemia were divided into 2 groups. The 9 patients in the LDL group underwent LDL-apheresis 1 day before and 5 days after PTCA while the 27 patients of the control group underwent PTCA but did not undergo LDL-apheresis. Follow-up coronary angiography (CAG) was performed 4 months after PTCA. The rate of restenosis of coronary artery lesions was significantly lower in the LDL group (0%) than in the control group (30%). These findings suggest that LDL-apheresis, when performed before and after PTCA, is effective in preventing restenosis of coronary artery lesions in patients with CHD and hypercholesterolemia.     

牛骨形成蛋白在骨不连中的临床应用

应用牛骨形成蛋白（ｂｏｖｉｎｅＢｏｎｅＭｏｒｐｈｏｇｅｎｅｔｉｃＰｒｏｔｅｉｎ简称ｂ－ＢＭＰ）成功的治愈１３例骨不连病人。经过１３个月～２９个月随访观察，效果较好。本组病人术前平均已做过１．５次手术。１３例病人中，有１２例被１次治愈。１例病人再次行内固定加用牛骨形成蛋白的植入也被治愈。骨形成蛋白的应用方式，采用同锻石膏复合后植入骨不连处。平均每个病人植入１００ｍｇＢＭＰ，１３例病人平均治愈时间为４．７个月。术后没有任何并发症。