Sensitivity of effect variables in rheumatoid arthritis: A meta-analysis of 130 placebo controlled NSAID trials controlled NSAID trials

In a meta-analysis of placebo controlled NSAID trials, the sensitivity of the effect variables was calculated as the correlation coefficient and as the difference between drug and placebo, divided by the placebo group standard deviation. The patient's global evaluation was the most sensitive variable overall. Pain was more sensitive than Ritchie's index. Several variables may be omitted from clinical trials, especially if two active drugs are being compared. For example, the best maximum estimate for the difference in ESR between NSAADs and placebo was 1.0 mm/hr (95% confidence interval −1.5 to 3.4 mm/hr), and for joint size 0.44% (−1.0 to 1.9%), corresponding to a quarter of a millimeter for each of the 10 joints usually measured. It is suggested to record only the patient's global evaluation, pain, and morning stiffness.     

化疗药物外渗后局部组织损伤处理的实验研究

目的根据化疗药物外渗后局部组织损伤的特点寻找理想的处理方法。方法制作化疗药物外渗的动物坏死模型,分别采用临床常用的三种处理方法进行动物实验,进行肉眼观察及组织学观察。结果1∶5 000呋喃西林加季德胜蛇药外敷对化疗药物外渗所致的局部组织坏死疗效最佳,其次为复方利多卡因,50%硫酸镁外敷疗效甚微,对照组无效。结论临床处理化疗药物外渗应根据其局部特点选择合理有效的方法。     

Low–Density Lipoprotein Apheresis Versus Lipid Lowering Drugs in the Treatment of Severe Hypercholesterolemia: Four Years' Experience

Abstract: Elevated lipoprotein concentrations seem to be linked strongly in a dose dependent manner to an increased incidence of atherosclerosis. A total of 47 patients suffering from severe hyperlipidemia were matched to treatment with LDL apheresis (Baxter, Kaneka, Li–popak; 24 patients, aged 50.2 ±11.5 years), diet, and/or lipid–lowering drugs or with diet and lipid–lowering drugs only (23 patients, aged 48.8 ±11.8 years). After treatment periods of 49.8 ±13.4 months (apheresis group, 2,396 treatment sessions) and 38.6 ± 15.1 months (drug group), the ensuing results revealed significant differences (p <0.0001): –47.3% versus –12.1% for total cholesterol, –46.9% versus –21.8% for LDL, +8.4% versus +0.9% for HDL, –52.0% versus – 13.1% for the LDL/HDL ratio, –36.4% versus –16.2% for triglycerides, and –25.9% versus + 1.5% for lipoprotein (a). In the apheresis group, one patient died of myocardial infarction; in the drug group, there was one nonfatal myocardial infarction and the manifestation of coronary heart disease in 3 cases. There were no severe side effects in either group. All patients in the apheresis group responded to therapy. The present trial suggests that a continuing reduction in serum lipid concentrations may lower, in a dose dependent manner, the risk for development and progression of coronary heart disease. Regarding clinical and laboratory results, LDL apheresis seems to be safe, effective therapy for treatment of severe hyperlipidemia.     

Effect of Renal Impairment on the Pharmacokinetics and Tolerability of Tiagabine

Summary: Purpose: We wished to determine the effect of renal impairment on the pharmacokinetics and tolerability of the new antiepileptic drug tiagabine (TGB).
Methods: We assessed TGB pharmacokinetics and tolerability in 25 subjects with various degrees of renal function (based on creatinine clearance, n = 4–6 per group) from healthy (group I) to requiring hemodialysis (group V) in a single and multiple dose (every 12h), one-period (groups I-IV) or a single dose, two-period (group V) study (4-mg oral doses of TGB · HCl). Blood samples were collected after the first dose (both periods for group V) and after the last dose on day 5 (groups I-IV). TGB plasma concentrations and plasma protein binding were determined by high-performance liquid chromatography (HPLC) and ultrafiltration, respectively.
Results: TGB was well tolerated by all study subjects. The pharmacokinetics of TGB were similar in all subjects; no pharmacokinetic parameter (based on either total or unbound concentrations) was statistically correlated with creatinine clearance. For total TGB in plasma, single-dose mean values of the maximum plasma concentration, clearance, and half-life (t1/2) ranged from 52 to 108 ng/ml, from 7.14 to 11.02 I/h, and from 6.4 to 8.4 h, respectively.
Conclusions: TGB pharmacokinetics and tolerability were independent of renal function; therefore, dosage adjustment is unnecessary for epilepsy patients with renal impairment.     

Glycopyrrolate vs. atropine during anaesthesia for laryngoscopy and bronchoscopy

As glycopyrrolate has been reported superior to atropine with respect to reduction of salivation, stability of cardiac rate and rhythm, and recovery, a comparison of these properties of the two drugs and placebo was made in 45 patients undergoing direct laryngoscopy and 45 patients undergoing bronchoscopy, in most cases followed by mediastinoscopy. When given i.m. 30 min before anaesthesia (midazolam, alfentanil, thiopentone, and suxamethonium), the two test drugs were found to be equally potent regarding the antisialogogic effect. The same increase in heart rate after the test drugs was seen before induction, and during anaesthesia heart rate rose to the same level in the placebo group as the test groups. During anaesthesia, blood pressure was lowest in the atropine group. No differences could be demonstrated with respect to cardiac arrhythmias, possibly due to the small size of the material. The present study gives no reason for preferring either drug, and only the efficacy of both test drugs in controlling airway secretions provides an argument for using any anticholinergic drug when laryngoscopy or bronchoscopy is performed under the conditions of the present study.     

Endocrinology: Two cases of ovarian tumours in women who had undergone multiple ovarian stimulation attempts

Concerns have been raised recently about the possible associationbetween superovulation and ovarian cancer. In order to contributeto the limited literature on this important issue, two casesof ovarian tumours in women who had undergone multiple ovulationinductions are presented. In the first case, the patient hadsecondary anovulatory infertility. She was treated with humanmenopausal gonadotrophin (HMG) alone and in combination withclomiphene citrate or buserelin for six cycles. She then underwentovarian stimulation with buserelin/HMG in the long protocolfor in-vitro fertilization (IVF) and embryo transfer. In preparationfor a new IVF/embryo transfer attempt, 8 months later, the screeningultrasound revealed a cystic formation of the left ovary andan enlargement of the right. During laparotomy, both ovarieswere found to bear large tumours (approximately 6x5x4 cm) whichwere removed. Histological examination showed that they wereepithelial tumours (serous-papillary cystadenomas) of borderlinemalignancy. The patient conceived spontaneously 1.5 years afterthe operation. In the second case, the patient presented withsecondary anovulatory infertility. She underwent ovulation inductionwith clomiphene/HMG and with buserelin/HMG in the long protocol,and intra-uterine insemination with husband's spermatozoa andconceived (singleton pregnancy). She was delivered by Caesareansection, during which a cystic tumour of the left ovary wasremoved. Histological examination revealed a benign mucous cystadenomaof the ovary. In conclusion, the clinical information from thesetwo cases does not support a causal association between ovarianstimulation and ovarian tumours but does potntially supporta facilitating one.     

Selective inhibition of MAO-A,not MAO-B,results in antidepressant-like effects on DRL 72-s behavior

The effects of monoamine oxidase inhibitors (MAOIs) that selectively inhibit the MAO-A or MAO-B forms of MAO were studied in rats performing under a differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule of reinforcement. Clorgyline and CGP11305A, irreversible and reversible MAO-A inhibitors, respectively, increased the reinforcement rate, decreased the response rate, and enhanced temporal discrimination. The irreversible MAO-B inhibitor (–)-deprenyl did not produce similar effects. Pargyline did not increase the reinforcement rate at low doses that selectively inhibit MAO-B, but did increase the reinforcement rate at doses that inhibit MAO-A by more than 90%. The present results are in accord with clinical data demonstrating that MAO-A inhibitors are effective therapeutic agents in treating depression while MAO-B inhibitors are of questionable antidepressant efficacy. The present findings provide further evidence that the DRL 72-s schedule may be useful both as a screen for identifying new antidepressants and for investigating the neurochemical effects of antidepressant drugs that are responsible for their therapeutic effects.     

Dose-response curves of homovanillic acid in pre-frontal cortex and caudate following antipsychotic drugs: relation to clinical potencies

Dose-response curves for the elevation of homovanillic acid (HVA) levels, determined by high performance liquid chromatography using electrochemical detection, in the pre-frontal cortex and caudate of rats after acute treatment with 12 antipsychotic drugs are presented. The order of potency in both brain regions was: haloperidol fluphenazine > loxapine > trifluoperazine > thiothixene > molindone > clopenthixol > chlorpromazine > metoclopramide > thioridazine > clozapine > sulpiride. This ranking is roughly correlated with that based on clinical potencies. The relative elevation of the content of HVA was weaker in the pre-frontal cortex than in the caudate for all drugs tested, except clozapine at a high dose.     

肥胖相关性肾病诊疗研究进展

肥胖相关性肾病已呈流行发展趋势,已成为终末期肾病的主要原因之一。目前认为其发病机制主要与肥胖所致肾小球血流动力学改变和脂质异位沉积等相关,但其机制仍未完全阐明。减轻体重是治疗肥胖相关性肾病的重要方法,但常因环境、个人执行情况的影响而收效甚微,且有部分患者体重控制后肾病仍持续进展。综合应用有效的肥胖相关性肾病治疗方法,对控制其进展十分重要。该文综述肥胖相关性肾病的致病机制和诊疗进展,探讨中药在肥胖相关性肾病治疗中的价值,旨在为临床提供参考,提高肥胖相关性肾病一体化管理水平。