Liver and Gastrointestinal First-pass Effects of Azosemide in Rats

Since considerable first-pass effects of azosemide have been reported after oral administration of the drug to rats and man, first-pass effects of azosemide were evaluated after intravenous, intraportal and oral administration, and intraduodenal instillation of the drug, to rats. The total body clearances of azosemide after intravenous (5 mg kg^?) and intraportal (5 and 10 mg kg^?) administration of the drug to rats were considerably smaller than the cardiac output of rats suggesting that the lung or heart first-pass effect (or both) of azosemide after oral administration of the drug to rats was negligible. The total area under the plasma concentration-time curve from time zero to time infinity (AUC) after intraportal administration (5 mg kg^?) of the drug was significantly lower than that after intravenous administration (5 mg kg^?) of the drug (1000 vs 1270 μg min mL^?) suggesting that the liver first-pass effect of azosemide was approximately 20% in rats. The AUC from time 0 to 8 h (AUC_{0–8 h}) after oral administration (5 mg kg^?) of the drug was considerably smaller than that after intraportal administration (5 mg kg^?) of the drug (271 vs 1580 μg min mL^?) suggesting that there are considerable gastrointestinal first-pass effects of azosemide after oral administration of azosemide to rats. Although the AUC_{0–8 h} after oral administration (5 mg kg^?) of azosemide was approximately 15% lower than that after intraduodenal instillation (5 mg kg^?) of the drug (271 vs 320 μg min mL^?), the difference was not significant, suggesting that the gastric first-pass effect of azosemide was not considerable in rats. Azosemide was stable in human gastric juices and pH solutions ranging from 2 to 13. Almost complete absorption of azosemide from whole gastrointestinal tract was observed after oral administration of the drug to rats. The above data indicated that most of the orally administered azosemide disappeared (mainly due to metabolism) following intestinal first-pass in rats.     

关于儿童死亡焦虑的初步探讨

利用斯皮尔伯格儿童状态焦虑的图示式、死亡刺激和脸谱对三组４９名儿童进行了死亡焦虑研究。结果表明，不同年龄组死亡焦虑得分存在明显差异，且焦虑水平随被试年龄的增加而升高。不同年龄的儿童对死亡对象的焦虑程度也不同。     

SULPHASALAZINE INDUCED AUTOIMMUNE SYNDROME

A case of an unusual and severe reaction to sulphasalazine isreported. KEY WORDS: Second line agent, Systemic steroids, Sulphasalazine     

Myxoma of the kidney

A 62-year-old man had a right renal mass incidentally diagnosed by ultrasonography. Magnetic resonance imaging revealed a well-defined right renal mass with homogenous low-signal intensity on the T(1)-weighted pulse sequence and heterogeneous high-signal intensity on the T(2)-weighted pulse sequence. A right nephrectomy was performed. The histological examination showed a myxoma, which is a very uncommon neoplasm in the kidney. Eight cases have been reported previously.     

IMMUNOGENETICS OF GRAVES'' OPHTHALMOPATHY

We have performed an immunogenetic analysis of 53 patients with severe Graves' ophthalmopathy, 51 patients with Graves' disease but little or no clinically apparent eye disease, and 90 controls. The distribution of restriction fragment length polymorphisms was analysed in the three groups, using probes for the HLA-DQ alpha and DR beta regions, the T-cell receptor C alpha, V alpha, C beta and J gamma genes and the immunoglobulin gene switch regions, S alpha and S mu. There was no abnormal distribution of these polymorphisms in either group of Graves' patients, or differences between the Graves' patients with or without eye disease. It was possible to assign HLA-DR types in most patients using the polymorphisms found after probing with DQ alpha and DR beta; there was no abnormal distribution of DR types (including HLA-DR3) assigned by restriction fragment polymorphisms in the two Graves' groups. These results fail to confirm the reported associations between ophthalmopathy and HLA-DR3 and between Graves' disease and the T-cell receptor C beta polymorphism; they also argue against a strong influence of Gm allotypes in Graves' disease since these genes are in linkage disequilibrium with the S alpha polymorphisms. The association of Graves' disease with HLA-DR3, defined hitherto using serological reagents, may be less strong than previously described.     

Sodium cromoglycate delivered by pressurized aerosol in the treatment of asthma

Sodium cromoglycate (SCG) powder often clumps in the presence of high humidity, making inhalation ineffective. A pressurized aerosol containing 1 mg SCG per actuation was made; and a double-blind cross-over trial in twenty-four young patients with perennial extrinsic asthma over 8 weeks showed that 2 mg of SCG aerosol was as effective as 20 mg of the powder, and almost all patients preferred using the aerosol.