High-performance liquid chromatographic determination of ursodeoxycholic acid after solid phase extraction of blood serum and detection-oriented derivatization.

Ursodeoxycholic acid (3 alpha,7 beta-dihydroxy-5 beta-cholanoic acid, UDCA) is a therapeutically applicable bile acid widely used for the dissolution of cholesterol-rich gallstones and in the treatment of chronic liver diseases associated with cholestasis. UDCA is more hydrophilic and less toxic than another therapeutically valuable bile acid, chenodeoxycholic acid (CDCA), the 7 alpha-epimer of UDCA. Procedures for sample preparation and HPLC determination of UDCA in blood serum were developed and validated. A higher homologue of UDCA containing an additional methylene group in the side chain was synthetized and used as an internal standard (IS). Serum samples with IS were diluted with a buffer (pH=7). The bile acids and IS were captured using solid phase extraction (C18 cartridges). The carboxylic group of the analytes was derivatized using 2-bromo-2'-acetonaphthone (a detection-oriented derivatization), and reaction mixtures were analyzed (HPLC with UV 245 nm detection; a 125--4 mm column containing Lichrospher 100 C18, 5 microm; mobile phase: acetonitrile--water, 6:4 (v/v)). Following validation, this method was used for pharmacokinetic studies of UDCA in humans.

[Thyrotoxicosis due to long-term therapy with interferon alpha in the patient with mixed chronic active hepatitis B and C]. / Tyreotoxikóza vzniklá pri dlouhodobé lécbe Interferonem alfa u nemocné se smísenou chronickou aktivní virovou hepatitidou typu B a C.

The authors describe a case report of 48-year-old woman treated with Interferon alpha for the chronic active hepatitis B and C. During this therapy thyrotoxicosis occurred. It disappeared after the withdrawal of Interferon alpha and administration of strumigens. Immediately after stopping of the administration of Interferon alpha and three month later antibodies against the thyroid epithelium were found.

[Comparison of the effects and safety of atenolol and nifedipine in the treatment of angina pectoris]. / Srovnání úcinku a bezpecnosti atenololu a nifedipinu v lécbe anginy pectoris.

The effects of atenolol (100 mg/day) and nifedipine (60 mg/day) on angina symptoms and exercise tolerance were compared in an open, randomized study. Twelve-week treatment period was compared with two weeks of placebo treatment in 51 patients with chronic stable angina pectoris. Mean frequency of angina attacks decreased significantly from 8.3 to 1.6 attacks per week after atenolol treatment (p < or = 0.05). Both drugs increased exercise tolerance to development of signs of ischemia on electrocardiogram (p < or = 0.05) and increased maximal exercise tolerance as well (p < or = 0.05). Mean ST segment depressions at peak exercise were significantly decreased after treatment with atenolol and nifedipine (p < or = 0.05). Both drugs also increased total exercise capacity in comparison with placebo period, stated as 100%:192% after atenolol and to 191% after nifedipine. No significant changes of heart rate and blood pressure were noted during treatment period. Twelve patients did not finished study, two of them suffered myocardial infarction with death in one of them (atenolol group, other one nifedipine group). Thus, atenolol in one daily dose is as effective as nifedipine in chronic stable angina patients when administered as single therapy.

[Drug therapy of chronic congestive heart failure: the why and how]. / Medikamentózní lécba chronického mestnavého srdecního selhávání: proc a jak.

As the prevalence of congestive heart failure is steadily increasing correct treatment becomes more and more important. In pathophysiology, clinical signs once believed to express the effort of the body to "compensate" for the failure (hypervolaemia, tachycardia, sympathetic stimulation) have been recognized as sort of a physiological error: to a primary signal which still remains not fully understood, the body responds in a similar way as to dehydration. As late as the mid-sixties, "function curves" represented a framework for our conceptual thinking and digitalis the essential treatment. Since then, we had to realize that the function of the failing ventricle is not determined just by filling and contractility-the way it is in the healthy ventricle is-but also by aortic impedance. Vasodilators have become the cornerstone of therapy. At present, diuretics are the most important drugs for congestive heart failure treatment. Thiazides, given together with loop diuretics, ameliorate extracellular fluid volume in all treated patients, but their effect is accompanied by potassium losses due to increased aldosterone levels. Angiotensin converting enzyme (ACE) inhibitors are unique in not only decreasing ventricular afterload and improving haemodynamics but, also, in decreasing circulating norepinephrine levels, protecting kidneys from inappropriate efferent arteriolo-constriction and suppression of aldosterone secretion. In other words, ACE inhibitors change the essential physiological set-up: they turn a high-perfusion-pressure body into a low-perfusion-pressure one. Furthermore, they convincingly improve life expectancy. Combination of diuretics and ACE inhibitors is the best we can do for our patients today. Although useful in some patients, the definite value of digitalis, and particularly its effect on longevity, remains an unresolved question.

[Suicidal ingestion of thioridazine as a cause of severe impairment of heart rhythm--polymorphic ventricular tachycardia]. / Sebevrazedné pozití thioridazinu jako prícina závazné poruchy srdecního rytmu--polymorfní komorové tachykardie.

A 35-year-old female alcohol addicted ingested with suicidal intentions a single dose of 500 mg thioridazine. The course of intoxication was complicated by the development of polymorphous ventricular tachycardia of the torsade de pointes type, about six hours after ingestion. The dysrhythmia was immediately suppressed by stimulation from the right atrium. After 36 hours the stimulation could be abolished. Because of delirium tremens the patient with a normal ECG tracing was returned to the psychiatric clinic.

[Severe antihistamine poisoning complicated by ventricular tachycardia]. / Závazná intoxikace antihistaminiky komplikovaná komorovou tachykardií.

A 26-year-old female clerk without previous heart disease ingested with suicidal intensions antihistaminic drugs--H1 blockers, astemizole (a total of 700 mg) and terfenadine (a total of 900-1200 mg). The main sign of intoxication was repeated polymorphous ventricular tachycardia type torsade de pointes, which at the onset of hospitalization changed into ventricular fibrillation. Therapeutically the impaired rhythm was controlled by electric cardioversion and atrial stimulation with a frequency of 120/min. On the third day it was possible to discontinue atrial stimulation and later the patient was discharged without any permanent sequelae.