3-甲基芬太尼衍生物构效关系及受体结合特征研究

对3-甲基芬太尼的1-苯乙基、4-N-丙酰基进行了结构改造、测定了所合成化合物的镇痛活性及部分化合物的镇痛作用持续时间、阿片受体亲和力和对阿片受体亚型的选择性。结果表明,大部分化合物均有较强的吗啡样镇痛活性,强度约为吗啡的2～180倍。所试化合物的镇痛作用持续时间比芬太尼延长6～10倍。化合物1～4的受体亲和力(IC₅₀)约为10^-7～10^-3mol。化合物13对阿片μ-受体有较高的选择性,对大鼠脑膜的λ/δ比值大于700,对小鼠脑膜的μ/δ比值为1000。     

Survivors of acute renal failure who do not recover renal function

Overall survival in 1095 with severe acute renal failure (ARF) between 1984 and 1995 was 59.5%. Of these, 107 (16.2%) remained dependent on long-term dialysis. The frequency of end-stage renal failure (ESRF) in survivors of ARF varied between 3% and 41% according to the cause of ARF, being highest in those with acute renal parenchymal disease (in whom survival was also among the highest at 84%) and lowest in ARF due to obstetrics and trauma. Patients failing to regain adequate renal function did not appear to differ on clinical grounds from survivors who became dialysis-independent. Survival in those requiring long-term dialysis was less good than for other patients with ESRF, partly due to excess mortality in those for whom vascular disease or surgery was the precipitating cause of ARF. Six patients recovered sufficient renal function to become independent of dialysis after 3-18 months on regular dialysis therapy (6-21 months after onset of ARF). ESRF resulting from ARF is more frequent than previously reported. This increase may be due to a changing case-mix, increasing age of patients (and hence reduced capacity for renal recovery), and an increase in aggressive surgery for patients with advanced vascular disease. This presents a significant and increasing problem, with implications for both clinical management and the provision of dialysis services.      

Fortgeschrittene Karzinomerkrankung und Reanimation

The decision to save or prolong the life of a patient with a definite prognosis of dying from cancer places the medical practitioner in an ethical and legal dilemma. By a timely and documented dialogue with the patient, which allows her to indicate her own preference, the practitioner can set down the patient's disposition. In addition, the practitioner must orient himself on the judicial situation, which determines the boundaries to the medical decision. In this way, attendance while dying, as well as passive, indirect and active help with dying, can be separated from one another. The intervention of the guardianship court is often the only possibility, even in the presence of the patient's disposition, to clarify the legal situation. A clear statute is therefore urgently required.     

Genetic variants of the renin-angiotensin system, diabetic nephropathy and hypertension

Summary Recent studies have suggested an association between a deletion (D) variant of the angiotensin-converting-enzyme (ACE) gene and diabetic nephropathy. However, this finding has not been confirmed by all investigators. Furthermore, an M235T variant of the angiotensinogen (AGT) gene has been associated with hypertension, an important risk factor for the development and progression of diabetic nephropathy. The objective of our study was therefore to examine the relationship between these genetic variants of the renin-angiotensin system and diabetic nephropathy and hypertension, respectively, in a large (n = 661) group of Caucasian patients with insulin-dependent (n = 360) or non-insulin-dependent (n = 301) diabetes mellitus. The study had a power of 0.8 to detect a doubling of risk of nephropathy or hypertension in patients with the ACE-DD or AGT-235TT genotype, respectively. Allelic frequencies of the ACE-D and AGT-235T alleles were similar between patients with and without nephropathy in either type of diabetes, and accordingly, there was no significant association between diabetic nephropathy and the ACE or AGT genotype. Likewise, there was no significant association between the ACE or AGT genotype and hypertension. Thus, our data, in this large and ethnically homogeneous group of patients, do not support the hypothesis that these genetic variants of the renin-angiotensin system are strongly associated with either nephropathy or hypertension in patients with insulin-dependent or non-insulin-dependent diabetes mellitus. These genetic markers are therefore unlikely to serve as clinically useful predictors of either nephropathy or hypertension in Caucasian patients with diabetes. [Diabetologia (1997) 40: 193–199] Received: 16 July 1996 and in revised form: 17 October 1996     

抗孕唑（DL－111－IT）在恒河猴体内药代动力学

恒河猴分别ｉｖ抗孕唑２０％ｃｒｅｍｏｐｈｏｒＥＬ生理盐水液２５，１２．５及６．３ｍｇ·ｋｇ－１后，用柱切换ＨＰＩ（法测定给药后２４ｈ内各时间点的血药浓度，根据各猴血药浓度－时间数据拟合曲线，均呈二房室动力学模型．其Ｙ１／２ａ分别为０．３８ｈ，０．２０ｈ及０．３６ｈ；Ｙ１／２β分别为６．６０ｈ，１０．２ｈ及１０．１ｈ；Ｖ（Ｃ）分别为５．３０，１．２６和１．４８Ｌ·ｋｇ－１．分别ｉｍ抗孕唑茶油液５０，２５和１２．５ｍｇ·ｋｇ－１３种剂量后，同上测定血药浓度，各猴血药浓度一时间数据拟合曲线，均呈－房室动力学模型。其Ｋａ分别为０．９８ｈ，１．０３ｈ及１．４５ｈ；Ｋｅ为０．４２ｈ，０．３７ｈ及０．５９ｈ；Ｔ１／２Ｋｅ为１．６６ｈ，１．９０ｈ及１．１６ｈ；Ｔ（ｐｅａｋ）为１．５２ｈ，１．５７ｈ及１．０９ｈ。     

Arterial compression of the fifth cranial nerve causing trigeminal neuralgia: angiographic findings

A common cause of trigeminal neuralgia (TN) is compression of the root of the fifth cranial nerve by a tortuous basilar artery or one of its branches. Microvascular decompression surgery has proved valuable in relieving the symptoms of these patients with nerve compression. We performed vertebral angiography on 22 patients with TN. The angiographic appearances were compared with the findings obtained from an anatomic study in which the positions of 20 trigeminal nerves in the skull were determined radiographically in 12 cadavers. By using this information, we were able to predict the presence of arterial-nerve compression in 20 of the 22 patients, and these positions were later confirmed at surgery. We describe the angiographic findings in patients with TN as well as the findings in a control group of 159 individuals with no history of TN. From these preliminary results, angiography appears to be valuable in the preoperative evaluation of patients with TN.