妊娠高血压综合征患者血清及尿β_2—微球蛋白测定的意义

研究目的探讨β_2—微球蛋白与妊娠高血压综合征临床意义研究设计病例对照研究研究对象 36例妊娠高血压综合征患者,孕周28～40周,年龄22～30岁;对照组为40例正常晚期妊娠孕妇。处理方法妊娠高血压综合征患者及正常孕妇血清和尿,用放射免疫分析法测定β_2—微球蛋白水平。同时测血尿素氮(BUN)以对照,测定结果进行t检验。测定结果 36例妊娠高血压综合征患者及40例正常晚期妊娠孕妇血清β_2—微球蛋白测定值分别为4.98±1.50mg/L和2.57±1.43mg/L(p<0.01,t检验)。29例妊娠高血压综合征患者及23例正常孕妇尿β_2—微球蛋白水平分别为1.03±0.91mg/L和0.55±0.40mg/L(P<0.05)。33例妊娠高血压综合征患者及25例正常孕妇,血尿素氮(BUN)测定值分别为6.16±4.17mmol/L和6.173±3.84mmol/L(P>0.05)。结论妊娠高血压综合征患者血清及尿β_2—微球蛋白水平均明显高于正常晚期妊娠孕妇,血清及尿β_2—微球蛋白测定是监测妊娠高血压综合征患者肾功能受损较敏感的方法。     

Comparative Pharmacokinetic Study of Chewable and Conventional Carbamazepine in Children

Summary: Fifteen children (7 boys and 8 girls) with generalized tonic-clonic seizures (GTCS) and partial seizures with elementary or complex symptomatology, treated with carbamazepine (CBZ) alone (n = 7) or in combination with either phenobarbital (PB, n = 6) or clobazam (CLB, n = 2) given for at least 3 months at stable individualized doses and regimens, entered an open, withinpatient, change-over study of consecutive periods, each lasting 2 weeks. During period 1, conventional CBZ was given; during period 2, a chewable CBZ formulation was substituted for conventional CBZ and given at the same total daily dosage with the same schedule as in period 1. Blood samples for measuring plasma concentration of both total CBZ and CBZ-10, 11 epoxide (CBZ-E) were taken on the last day of each period. No significant difference between the two periods was noted in the mean ±SD of C_max, Css mean, and area under the curve (AUC) of total CBZ and CBZ-E. The two different CBZ formulations, administered at the same total daily dosage, can be considered bioequivalent.     

Increasing Plasma Concentration Tolerability Study of Flunarizine in Comedicated Epileptic Patients

Twelve patients with intractable partial seizures [4 receiving carbamazepine (CBZ), 4 phenytoin (PHT), and 4 both] entered a study of the tolerability of flunarizine (FNR) at specified plasma concentrations. After an 8-week baseline period, a single-dose pharmacoki-netic study was performed for each patient to calculate a loading dose and maintenance dosage necessary to achieve a target plasma FNR concentration of 30 ng/ml. The first 8 patients received the loading dose (as divided doses) during a 1-week hospitalization and the maintenance dosage for the ensuing 8 weeks. These patients proceeded to treatment periods with target concentrations of 60 and then 120 ng/ml, using doses based on an assumed linear relation between dose and plasma concentration. The last 4 patients were studied only at the 120-ng/ml target level. Results indicated that this procedure successfully approximated target levels of 30 and 60 ng/ ml, but observed concentrations in the last period exceeded the 120-ng/ml target level and continued to increase with time, often necessitating a dosage reduction owing to intolerability. Calculated doses for a given target concentration varied by a factor of 12. The most frequently reported adverse experiences were sedation and increased fatigue; reports of dizziness, headache, and lethargy were also common. Based on this study, a target concentration of at least 60 but <120 ng/ml is recommended for a controlled clinical trial of the antiepileptic efficacy of FNR.     

皮肤末梢神经组织中的带状疱疹病毒感染

本文对2例带状疱疹患者病损皮肤末梢神经组织进行了电镜观察,首次观察到VZV存在于皮肤末梢无髓神经的雪旺细胞和束膜的纤维细胞内,以及VZV在其核内复制和成熟并通过核膜进入细胞质的过程;在神经束间及浸润其内的淋巴细胞核内见有病毒颗粒。     

Effect of single- and multiple-dose carbamazepine on the pharmacokinetics of diphenylhydantoin

Summary A three-phase trial has been done in 11 volunteers. They were given 600 mg phenytoin (Dilantin capsules) in each phase after an overnight fast. In the first study, phenytoin was given alone. In the second phase 400 mg carbamazepine (CBZ) was given at the same time as the phenytoin, and in the third part, 200 mg CBZ t. d. s. was given for one week prior to the phenytoin. Blood samples were taken for 72 h in each phase. Plasma levels of phenytoin and CBZ were determined by HPLC, and plasma protein binding was determined by equilibrium dialysis.The unbound fraction of phenytoin was 0.082, 0.085, and 0.077 in the control, single-dose CBZ, multi-dose CBZ phases, respectively. Single and multiple doses of CBZ decreased the plasma level of phenytoin. The 72-h AUC of phenytoin was 276, 237, and 176 mg h·l^–1 in the 3 phases, respectively, and the 72-h AUC of unbound phenytoin was 22.8, 20.5, 13.0 mg h·l^–1. The AUC of phenytoin (unbound and total) after multiple doses of CBZ was significantly lower than in the other two phases. The apparent volume of distribution (V_z/f) was 89.9, 110.3, and 121.3 l in the 3 phases, respectively.Through pharmacokinetic analyses, the decreased AUC and increased V_z/f were attributed to decreased bioavailability of phenytoin when CBZ was co-administered.     

Allergy to Carbamazepine: Parallel In Vivo and In Vitro Detection

Summary: Purpose: Five to 20% of patients discontinue antiepileptic drug (AED) therapy because of adverse reactions. Careful reintroduction, however, may be considered if true drug allergy can be ruled out. Definitive assessment of such immunologically mediated reactions requires demonstration of either specific antibodies or sensitized lymphocytes. Methods: We investigated whether skin patch tests (PTs) and in vitro lymphocyte proliferation assays (LPAs) were suitable for detection of allergy to carbamazepine (CBZ) and the possibly cross-reactive oxcarbazepine (OCBZ). Data of 65 patients displaying a wide range of possibly allergic side effects to CBZ were available for analysis. Data of CBZ users without any side effects and healthy volunteers served as controls. Both PTs and LPAs were done with CBZ, OCBZ and three metabolites [CBZ-10,11-epoxide (CBZ-E), 10-monohydroxy-CBZ (MHD), and 10,11-dihydroxy-CBZ (DIOL)]. Results: Positive PTs with CBZ were seen in 20% and with OCBZ in 14% of the patients. Positive LPA results with CBZ and OCBZ, respectively, were found in 40 and 19%. Both tests were positive in 14 and 7% of the patients. Cross-reactivity to OCBZ was seen in -40% of CBZ-reactive patients in both PTs and LPAs. Conclusion: These data illustrate the additional value of LPAs in the detection of CBZ allergy while showing that a major part of side effects to CBZ and OCBZ is not immunologically mediated, according to PTs and LPAs.     

Renin activity,aldosterone levels and urinary sodium and potassium excretion under tocolytic therapy with salbutamol

The effects of long-term therapy with salbutamol on renin activity, aldosterone levels and urinary sodium and potassium excretion in pregnant women are studied. Salbutamol was given intravenously in a first group of 18 patients in preterm labor, orally in a second group of 9 patients, whereas a third group of 17 patients was taken as control. No significant changes were observed in renin activity and aldosterone levels between the first and the fifth day of intravenous or oral therapy and in 24-h sodium urinary excretion. Only potassium excretion showed a significant decrease (P < 0.01) within 24 h from the start of the intravenous therapy, returning to control levels after 48 h. From these results, no replacement of potassium seems to be necessary in patients undergoing tocolytic therapy with betamimetic drugs.     

Interaction of anticonvulsant drugs with adenosine receptors in the central nervous system

The anticonvulsant carbamazepine inhibits binding of 1 nM [3H]N6-cyclohexyladenosine to rat cerebral and cerebellar A1 adenosine receptors with an IC50 value of about 50 microM. This concentration is well within that expected for therapeutic regimens. Other anticonvulsants such as phenobarbital, phenytoin, primidone, valproate sodium, and ethosuximide had little or no effect on binding, while theophylline and caffeine caused marked inhibition. Carbamazepine had no marked effect on cyclic AMP levels in guinea pig cerebral cortical or hippocampal slices, but was a weak inhibitor (IC50 about 200 microM) of 2-chloroadenosine-elicited accumulations of cyclic AMP via an A2 adenosine receptor in cortical slices. Carbamazepine is thus a somewhat selective ligand for A1 adenosine receptors in brain. The nature of its activity at those receptors is unclear, but its lack of central stimulant effects contrasts to the stimulant properties of A1 adenosine receptor antagonist such as caffeine and theophylline.     

Facilitation of opiate-and enkephalin-induced motor activity in the mouse by phenytoin sodium and carbamazepine

In the first experiment, adult male Swiss-Webster mice were systemically injected with a standard dose of morphine. Compared to the influence of vehicle, the motor activity of morphine-injected mice was increased. Neither phenytoin sodium nor carbamazepine alone facilitated motor activity, but pretreatment with both drugs further facilitated the increased motor activity produced by morphine. In a second experiment, mice were injected centrally with a long-acting analog of leu-enkephalin. It also increased motor activity in comparison with vehicle. Again, both phenytoin sodium and carbamazepine further facilitated this response. Both experiments suggest a facilitatory interaction between some aspects of these anticonvulsants and opiate-induced motor activity.