The influence of liver dysfunction on cyclosporine pharmacokinetics —A comparison between 70 per cent hepatectomy and complete bile duct ligation in dogs—

The influence of experimentally induced hepatic dysfunction on the pharmacokinetics of Cyclosporine A (CsA) was determined in dogs. The pharmacokinetics of oral (PO) and intravenous (IV) CsA were studied before and after 70 per cent hepatectomy or complete bile duct ligation (CBDL). Changes in liver function were monitored by serial measurements of serum bilirubin, and by the maximum removal rate (Rmax) and plasma disappearance rate (ICG-K) of indocyanine green (ICG). Concentrations of CsA in whole blood were measured by HPLC. Seventy per cent hepatectomy caused significant liver dysfunction: the ICG-Rmax decreased by 47.7±7.1 per cent (mean±SD) and the ICG-K decreased by 61.3±9.7 per cent during the first week after hepatectomy. At the same time, the systemic clearance (CLs) of IV-CsA decreased by 43.9±8.2 per cent, the area under the concentration curve (AUC) of IV-CsA increased by 35.4±20.8 per cent and the bioavailability of CsA decreased by 26.4±14.8 per cent. CBDL also induced significant liver dysfunction: the ICG-Rmax decreased by 39.1±12.8 per cent and the ICG-K decreased by 65.6±3.6 per cent in the second week after the operation. During the same period, the AUC of PO-CsA decreased by 69.9±10.7 per cent and the bioavailability of CsA also decreased markedly by 73.9±15.6 per cent. These data indicate that hepatic impairment significantly influences the pharmacokinetics of CsA, not only by the changes in intestinal absorption, but also by those in hepatic, metabolism. Dose adjustment is therefore necessary in the presence of hepatic dysfunction in order to maintain an adequate blood concentration of CsA without causing side effects. This research was performed in the Department of Surgery, University of Pittsburgh Health Center, University of Pittsburgh, USA     

Poor oxygenation in the lungs of patients with hyperosmolar hyperglycemic non-ketotic diabetic coma after cardiac surgery

The ratio of PaO₂ to FiO₂ was often low (300 or less) in four patients with complications of hyperosmolar hyperglycemic non-ketotic diabetic coma (HHNKDC) following open heart surgery. Four of our patients had poor oxygenation and subsequent spontaneous recovery from in the immediate post-operative period, although HHNKDC occurred only in one during this period. In the 3 others, poor oxygenation without accompanying HHNKDC lasted for 1–6 days and HHNKDC developed about 2 weeks after open heart surgery at time when poor oxygenation reoccurred. If a working diagnosis of congestive heart failure was made only on the basis of the most common probability, and the fluid supply was restricted, HHNKDC would readily occur or be aggravated by the dehydration iatrogenically produced. It is thus concluded that HHNKDC should be included in diagnoses for pulmonary dysfunction.     

Adherence to recommendations and improvement over time in men with erectile dysfunction

Men with erectile problems seen for a comprehensive urology-department-based medical and psychological evaluation were sent questionnaires 2 to 3 years later. A representative sample of 99 (52%) responded. The majority (51%) has taken no action and reported that their sexual function was no better. Patients were more likely to comply with a recommendation for sex therapy than with one for a penile prosthesis. This was related to their attitude towards mental health professionals. These findings suggest the need for more knowledge of patient psychology and expectations.These data were presented in preliminary form at the Tenth Meeting of the International Academy of Sex Research, Cambridge, England, September 1984.     

1型糖尿病患者勃起功能障碍的患病情况及相关因素分析

目的探讨1型糖尿病（T1DM）患者勃起功能障碍（ED）的患病情况及相关影响因素。方法收集182例已婚男性T1DM患者，用无记名问卷形式根据国际勃起功能指数问卷进行自我评分。并对年龄、病程、糖化血红蛋白（HbA1c）、睾酮、尿微量白蛋白排泄量、肾功能、血压、吸烟史、饮酒史、应用药物等因素进行调查，分析其与ED的关系。结果T1DM患者ED患病率为37．36％（68／182）。Logistic逐步回归分析结果显示，病程、年龄、HbA1c、收缩压、尿微量白蛋白排泄量与T1DM患者ED发生独立相关，病程增加5年、年龄增加10岁、HbA1c增加2％、收缩压增加4kPa及尿微量白蛋白排泄量的OR值分别为1．6275、1．1613、2．4211、2．3715、1．5234，P均〈0．01。结论加强对T1DM患者ED高危因素的关注和定期检测，有助于早期发现ED。     

MODS患儿血清磷酯酶A2的变化及意义

目的：探讨磷酯酶A2（PLA2）在多脏器功能障碍综合征（MODS）患儿中的作用及意义。方法：结合危重病例评分，采用ELISA法检测26例MODS患儿血清PLA2含量，并与健康体检儿童20例对照。结果：多脏器功能障碍综合征患儿血清PLA2含量明显高于正常对照组，P＜0．01，并与危重病例评分成正相关。结论：PLA2参与MODS的病理生理过程，与危重病的病情有关，并可作为早期预警多脏器功能障碍综合征的实验参数。     

Prophylaxis and treatment of bladder dysfunction after Wertheim-Meigs operation: the positive effect of early postoperative detrusor stimulation using the cholinergic drug betanecholchloride

The efficacy of betanecholchloride in the postoperative treatment of bladder dysfunction is controversial. We therefore performed a comparative study on the effect of this therapy for the prophylaxis of detrusor hypotonia after Wertheim-Meigs operation. Forty patients with cervical cancer FIGO stage Ib/IIa were divided into two study groups. The control group (24 patients) only received betanecholchloride if the residual urine persisted above 50 ml after the 10th postoperative day. The study group (16 patients) received 50 mg betanecholchloride three times a day from the 3rd postoperative day onward. In this group postoperative catheter treatment, and consequently hospital stay, were significantly shorter (9.6 versus 13.3 days and 15.5 versus 18.6 days). The residual urinary volume normalized faster (8.0 versus 13.0 days) and the rate of cystitis was lower (18.8 versus 25%). According to our study, a prophylactic application of the parasympathomimetic drug betanecholchloride diminishes postoperative complications associated with bladder dysfunction after Wertheim-Meigs operation. EDITORIAL COMMENT: Bladder dysfunction plays an important role after radical hysterectomy. The authors present data indicating improved and quicker resumption of bladder function following radical hysterectomy with early administration of betanecholchloride, versus use of the medication only when indicated by elevated postvoid residual. Although the study is not a double-blinded placebo-controlled trial, the patients who received beta-necholchloride from postoperative day 3 had significantly decreased postoperative catheter treatment, earlier resumption of adequate bladder emptying defined as a postvoid residual of less than 50 ml, decreased incidence of bladder infection and shorter hospital stay. This information is encouraging for this subset of patients, who characteristically are at high risk for long-term bladder dysfunction. Further studies in this area are needed to clarify therapeutic options to improve patients’ quality of life, specifically in regard to bladder function following treatment of their cancer.     

DTPA renal scan assessment of renal allograft dysfunction in rats

The precise cause of allograft dysfunction after renal transplantation often cannot be established by non-invasive means. In clinical practice, radionuclide scans form an integral part of the clinician's armamentarium in the assessment of these patients [1, 2]. Unfortunately, in the clinical setting more than one pathological process may be responsible for the impaired function, making it difficult to correlate the scan appearances with the pathology. In this study in rats we compared the renal DTPA scan appearances of the various pathological processes which may cause renal allograft dysfunction in the immediate post-transplant period.     

Normothermic cardiopulmonary bypass: effect on the incidence of persistent postoperative neurological dysfunction following coronary artery bypass graft surgery

We retrospectively reviewed the records of 250 consecutive patients undergoing coronary artery bypass graft surgery (CABG) from January 1994 through January 1996 to determine the incidence of persistent postoperative neurological dysfunction after CABG and to compare normothermic and moderate hypothermic cardiopulmonary bypass (CPB). Normothermic CPB was used in 128 patients (36°–37°C) and hypothermic CPB (27°–28°C) in 122 patients. Postoperative neurological dysfunction included focal motor deficits, delayed recovery of consciousness (>24h) after surgery, and seizures within 1 week postoperatively. Persistent neurological dysfunction was diagnosed if complete resolution had not occurred within 10 days of surgery. The incidence of persistent postoperative neurological dysfunction was 4.1% in the hypothermic CPB group and 2.3% in the normothermic CPB group. There were no statistically significant differences between the two groups (P=NS). These results suggest that normothermic CPB did not increase the incidence of persistent postoperative neurological dysfunction compared to hypothermic CPB.     

Olfactory Absorption of Insulin to the Brain

A vast number of potent neuropharmaceuticals, many of which are peptides, are excluded from entry into the brain because of the highly selective blood-brain barrier. The fact that a number of drugs have been shown to be transported directly to the central nervous system following application to the olfactory region of the nose is therefore of major interest. In the present study, the feasibility of delivering peptides to the brain via the olfactory route was assessed using insulin as a model peptide. Systemic hyperinsulinemia induced by subcutaneous injection did not significantly reduce the amount of ¹²⁵I-insulin transported from the nose to the brain in vivo, which suggests that the impact of systemic absorption on drug transport is minimal. A linear relationship was seen between insulin accumulation in the brain and the dose applied, without any relevant saturation. Contrary to what was expected, both systemic and olfactory absorption of insulin was enhanced when the pH of the medium was near the isoelectric point. The amount absorbed to the brain was found to be linearly related to the net charge of the molecule (r = -0.61; n = 20). It was concluded that insulin gains access to the central nervous system from the olfactory region of the nose by a nonspecific pathway. The olfactory route may therefore become an important means to deliver peptides to the brain.     

糖尿病血管内皮损害标志物的检测及其与尿白蛋白的关系

目的　对比观察2型糖尿病(DM)及糖尿病肾病(DN)患者血管内皮损害标志物,分析其与白蛋白尿相关性。方法　6 8例2型糖尿病患者根据尿白蛋白排泄率分为正常白蛋白尿组(Ⅰ组)和微量白蛋白尿组(Ⅱ组) ,同时以健康成人作为对照组(Ⅲ组) ,分别检测其循环内皮细胞(CEC)、vonWillebrand因子(vWF)、内皮素- 1 (ET - 1 )的变化,并分析其相关性。结果　DM患者CEC、vWF和ET - 1明显增高,尤其是DN组(P <0 .0 5 ) ,各指标间以及与尿白蛋白排泄呈正相关。结论　2型DM患者在出现白蛋白尿前已存在血管内皮功能异常,其白蛋白排泄与血管内皮功能障碍程度有一定相关性。