The effect of amiloride on amphotericin B-induced hypokalaemia.

Amiloride was administered to 19 oncology patients exhibiting marked amphotericin B-induced electrolyte wasting. Mean serum potassium concentrations increased in the 5 days preceding and following administration (3.4 +/- 0.5 versus 3.9 +/- 0.8 mmol/L, P = 0.002). A trend towards decreased potassium supplementation was also observed (48.0 +/- 66.5 versus 29.4 +/- 43.2 mmol/day, P = 0.12). Amiloride is a therapeutic option to decrease potassium wasting in patients being treated with amphotericin B.     

Unusual causes of hypokalaemia and paralysis

We demonstrate how the application of physiological principles may help to identify unusual causes of a very low plasma potassium (K+) concentration (P(K)) and paralysis. In the two patients described, the short time course of the illness suggested that there was an acute shift of K+ into cells. The combination of a low rate of excretion of K+, the absence of a metabolic acid-base disorder, and the fact that the clinical findings occurred very soon after a large intake of carbohydrate supported this impression. Surprisingly, the P(K) remained low for many hours after these stimuli to shift K+ into cells had abated. The missing link in this story was eventually provided by the attending medical team with the help of their mentor, Professor McCance.     

湖南地区乙型肝炎病毒相关性肾炎临床病理特征

目的研究 38例乙型肝炎病毒相关性肾炎 (HBG )的临床及病理学特征。方法对 38例HBG患者肾穿刺组织进行光镜、电镜和免疫组化染色观察 ;按年龄分成少儿组和青壮年组 ,对其临床资料及病理学特征进行分析。结果少儿组 :均有浮肿病史 ,三大阳者 10 0 % ,合并肾病综合征者 79.2 % ,好发于男孩( 91.6 % ) ;青壮年组 :大部分有浮肿病史( 74.1% ) ,三大阳者 6 4.2 % ,合并肾病综合征者 42 .8% ,多见于男性 ( 71.4% )。结论HBG临床上以儿童多见 ,表现为肾病综合征 ,血清HBV标志物阳性。病理特征以膜性肾病为主 ,HBsAg、HBcAg免疫组化标记是诊断HBG的重要指标     

Moderate alcohol consumption lowers the risk of type 2 diabetes: a meta-analysis of prospective observational studies

OBJECTIVE: This meta-analysis was undertaken to obtain insight regarding the shape and strength of the relationship between alcohol consumption and the risk of type 2 diabetes, the effects of adjustment for confounders, and the effect of modification by type 2 diabetes definition, sex, and BMI. RESEARCH DESIGN AND METHODS: The 15 original prospective cohort studies that were included comprise 11,959 incident cases of type 2 diabetes in 369,862 individuals who, on average, were followed for 12 years. RESULTS: After pooling the data, a U-shaped relationship was found. Compared with nonconsumers, the relative risk (RR) for type 2 diabetes in those who consumed /=48 g/day) was equal to that in nonconsumers (1.04 [0.84-1.29]). In general, nonsignificant trends for larger RR reduction associated with moderate alcohol consumption were observed for women compared with men, for crude compared with multivariate-adjusted analyses, and for studies that used self-reports instead of testing for type 2 diabetes definition. No differences in RR reductions were found between individuals with low or high BMI. CONCLUSIONS: The present evidence from observational studies suggests an approximately 30% reduced risk of type 2 diabetes in moderate alcohol consumers, whereas no risk reduction is observed in consumers of >/=48 g/day.     

Dangerous interaction between amitriptyline and pimozide in the presence of hypokalaemia

A 23 year old woman on pimozide 4mg mane and amitriptyline 50mg mane and 100mg nocte developed ventricular tachycardia following ingestion of twice her usual evening dose of amitriptyline. Serum K⁺ was 3.0mmol/L. There were no other obvious contributory factors. Pimozide has previously been linked with sudden death and a variety of ECG changes. This report raises the possibility that interaction between pimozide and amitriptyline may cause ventricular tachycardia, particularly in the presence of hypokalaemia.     

Detection of Bence Jones Proteinuria

The heat test is the most important screening test for demonstrating Bence Jones protein, and should be done under the optimal conditions described in this paper. However, because it is difficult to standardize the heat test between laboratories, paper electrophoresis of concentrated urine is considered the most reliable method of detecting Bence Jones protein.     

An approach to the patient with severe hypokalaemia: the potassium quiz

The objective of this teaching session with Professor McCance is to develop an approach to the management of patients with a very low plasma potassium (K(+)) concentration (P(K)). The session begins with a quiz based on six recent medical consultations for a P(K) < 2 mmol/l. Professor McCance outlined how he would proceed with his diagnosis and therapy, using the synopsis that described each patient. This approach was then applied to a new patient, a 69-year-old woman who had a large volume of dependent oedema and developed a severe degree of weakness and hypokalaemia during more aggressive diuretic therapy that included a K(+)-sparing diuretic. The initial challenge for Professor McCance was to deduce why the K(+)-sparing diuretic was not effective in this patient. He also needed to explain why the P(K) was so low on admission.     

Plasma protein binding of amphotericin B and pharmacokinetics of bound versus unbound amphotericin B after administration of intravenous liposomal amphotericin B (AmBisome) and amphotericin B deoxycholate

Unilamellar liposomal amphotericin B (AmBisome) (liposomal AMB) reduces the toxicity of this antifungal drug. The unique composition of liposomal AMB stabilizes the liposomes, producing higher sustained drug levels in plasma and reducing renal and hepatic excretion. When liposomes release their drug payload, unbound, protein-bound, and liposomal drug pools may exist simultaneously in the body. To determine the amounts of drug in these pools, we developed a procedure to measure unbound AMB in human plasma by ultrafiltration and then used it to characterize AMB binding in vitro and to assess the pharmacokinetics of nonliposomal pools of AMB in a phase IV study of liposomal AMB and AMB deoxycholate in healthy subjects. We confirmed that AMB is highly bound (>95%) in human plasma and showed that both human serum albumin and alpha(1)-acid glycoprotein contribute to this binding. AMB binding exhibited an unusual concentration dependence in plasma: the percentage of bound drug increased as the AMB concentration increased. This was attributed to the low solubility of AMB in plasma, which limits the unbound drug concentration to <1 microg/ml. Subjects given 2 mg of liposomal AMB/kg of body weight had lower exposures (as measured by the maximum concentration of drug in serum and the area under the concentration-time curve) to both unbound and nonliposomal drug than those receiving 0.6 mg of AMB deoxycholate/kg. Most of the AMB in plasma remained liposome associated (97% at 4 h, 55% at 168 h) after liposomal AMB administration, so that unbound drug concentrations remained at <25 ng/ml in all liposomal AMB-treated subjects. Although liposomal AMB markedly reduces the total urinary and fecal recoveries of AMB, urinary and fecal clearances based on unbound AMB were similar (94 to 121 ml h(-1) kg(-1)) for both formulations. Unbound drug urinary clearances were equal to the glomerular filtration rate, and tubular transit rates were <16% of the urinary excretion rate, suggesting that net filtration of unbound drug, with little secretion or reabsorption, is the mechanism of renal clearance for both conventional and liposomal AMB in humans. Unbound drug fecal clearances were also similar for the two formulations. Thus, liposomal AMB increases total AMB concentrations while decreasing unbound AMB concentrations in plasma as a result of sequestration of the drug in long-circulating liposomes.     

In vitro antifungal activities of amphotericin B and liposome-encapsulated amphotericin B.

The in vitro activities of liposome-encapsulated amphotericin B and free amphotericin B against Candida albicans 336 were comparable. Amphotericin B concentrations 12-fold and greater than 50-fold higher were required to kill the same organism when cholesterol and ergosterol were incorporated into the liposomes. The addition of cholesterol to liposomes caused a significant increase in the minimal fungicidal concentration of amphotericin B in 7 of 19 other yeast strains tested, whereas ergosterol caused an increase in 18 of the 19 strains.     

血清白蛋白和球蛋白对乙型肝炎相关肝硬化的诊断意义

目的:评价血清白蛋白(albumin,ALB)、球蛋白(globulin,GLB)水平和白蛋白/球蛋白(A/G)比值诊断肝硬化的价值。方法:慢性乙型肝炎患者172例,其中病理诊断为肝硬化的患者28例,非肝硬化的患者144例。1s肝穿刺法行肝组织活检,用光学显微镜多视野观察进行组织学分级和分期。肝穿刺前后1周内早晨空腹采血,分离血清后用Roche Modular-P全自动生化分析仪测定血清ALB、GLB。结果:血清ALB水平和A/G比值诊断非肝硬化的ROC曲线下面积分别为0.221(95%CI:0.138～0.304)和0.229(95%CI:0.133～0.326),血清GLB水平诊断肝硬化的ROC曲线下面积为0.720(95%CI:0.617～0.824)。血清ALB和GLB水平和A/G比值诊断肝硬化的最佳截断值分别为40.35g/L、34.70g/L和0.98,其诊断肝硬化的灵敏度、特异度、阳性预测值、阴性预测值、准确度、Youden指数分别为0.821和0.607和0.571、0.646和0.771和0.868、0.311和0.340和0.457、0.949和0.910和0.912、0.674和0.74...     

Comparative in vitro and in vivo evaluation of N-D-ornithyl amphotericin B methyl ester, amphotericin B methyl ester, and amphotericin B.

N-D-Ornithyl amphotericin B methyl ester (O-AME), a semisynthetic derivative of amphotericin B methyl ester (AME), was compared with amphotericin B (AMB) and AME. In vitro, O-AME was more active than the other two against Candida spp. and other fungi and was only slightly affected by inoculum size, addition of serum, or changes in pH. In vivo, the dose of O-AME required to produce a 10,000-fold reduction of Candida albicans in a mouse kidney infection was similar to that of AMB and 1/10 that of AME. After intravenous treatment of infected mice and rats and subcutaneous treatment of mice, average 50% protective doses for O-AME and AMB were similar. Acute intravenous 50% lethal doses in mice indicated that O-AME was one-ninth as toxic as AMB but twice as toxic as AME. Acute renal function tests in rats indicated that Sch 28191 was less than 1/10 as toxic as AMB and slightly more toxic than AME. On this basis, the calculated advantage relative to AMB (with AMB equal to 1) was 8 for O-AME and 1.5 for AME.