Effects of ursodeoxycholic acid (UDCA) on serum liver damage indices in patients with chronic active hepatitis. A double-blind controlled study.

The effects of ursodeoxycholic acid (UDCA, 450 mg daily) in patients with histologically proven chronic active hepatitis (CAH) have been evaluated in a randomized, double-blind, placebo-controlled study. Twenty-six patients with serum alanine aminotransferase (ALT) values at least twice the normal upper limit in two of three pre-treatment tests received UDCA or a placebo for twelve weeks. In all UDCA-treated patients, serum aspartate amino-transferase (AST), ALT, gamma-glutamyl transpeptidase (GGT) and alkaline phosphatase (AP) fell significantly after 4 weeks of treatment. There was a further decrease at the end of therapy, as well as a small but significant fall in total serum bilirubin. Conversely, 4 weeks after suspension of therapy, serum enzyme levels had increased, reaching values not much lower than those recorded before treatment. Total serum protein, albumin and gamma-globulin did not change after UDCA treatment. In the placebo group no significant variation in the test results were found. The results indicate that UDCA therapy in CAH, as has been observed in primary biliary cirrhosis and primary sclerosing cholangitis, is able to improve several indices of liver damage, without producing any toxic adverse effects.

Efficacy of ibopamine in the treatment of heart failure.

Loss of myocardial contractility, reflexly enhanced vasoconstriction, and neuroendocrine excitation are the pathophysiologic hallmarks of low-output heart failure. Drugs that counter both consequences afford considerable therapeutic potential in retarding and perhaps even in staying the consequences of the syndrome. Ibopamine possesses such potential through its unique ability to stimulate both dopaminergic- and beta-adrenoreceptors in the heart and circulatory system. Stimulation of dopaminergic- receptors and beta 2-adrenoreceptors results in vasodilatation in all regional vascular territories. beta 2-Adrenoreceptor agonist activity also affords mild positive inotropic activity in the heart, whereas stimulation of presynaptic dopaminergic- receptors (DA2) attenuates the increased sympathetic neural outflow. The drug also suppresses the renin-angiotensin-aldosterone system in addition to having a direct natriuretic activity. The pharmacodynamic effects of ibopamine, exerted through its metabolite epinine, are translated into measurable therapeutic benefits in patients with chronic heart failure. The increase in peripheral blood flow induced in all regional vascular territories, including the kidneys, is associated with increased cardiac output and stroke volume and reduction in left ventricular pressure work, wall stress, and myocardial oxygen consumption. Plasma norepinephrine, angiotensin, and aldosterone are also reduced, and renal sodium excretion is enhanced. These hemodynamic and neuroendocrine activities, which are not subject to tolerance during sustained administration of the drug, are accompanied by clinically significant improvement in symptoms, exercise tolerance, and the New York Heart Association classification of disability. More important, no proarrhythmic effects have been observed during sustained treatment, and the minimal side effects observed during long-term treatment enhance the safety profile of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Ibopamine does not affect insulin resistance in patients with type I diabetes.

Diabetes mellitus was assessed by investigating 8 type I diabetic patients, in good metabolic control and with congestive heart failure, who were studied after 3 weeks of placebo and ibopamine (100 mg t.i.d.) treatment. Metabolic control and daily insulin dose did not change in any patient during the study. The insulin-mediated glucose uptake during the clamp studies showed no variation after placebo or ibopamine therapy. Total cholesterol, HDL-cholesterol and triglycerides concentrations remained unchanged. This study clearly suggests that ibopamine administered at a daily dose of 300 mg for 3 weeks presents a metabolic safety in type I diabetic patients.

Safety of ibopamine in type II diabetic patients with mild chronic heart failure. A double-blind cross-over study.

Twelve outpatients with type II diabetes mellitus and mild clinical signs and history of cardiac failure were studied to assess the effects of ibopamine on glucose and lipid metabolism. For the assessment of cardiac failure a clinical score was computed, based on the evidence of dyspnea and ankle oedema. The patients were randomly allocated to ibopamine 100 mg t.i.d. or placebo in a double-blind cross-over 3 weeks design. Daily plasma glucose profile, glycaemia and plasma insulin during glucose tolerance test, serum C-peptide, lactacidemia, free fatty acids, triglycerides, urinary glucose, diuresis and clinical evaluation were the studied parameters. During the study, a clinically favourable trend for ibopamine was observed, as far as cardiac failure was concerned. No significant differences were found between ibopamine and placebo in any of the metabolic parameters. No change in diet or in the previous dosage of the antidiabetic drugs occurred during the study in any patient. We conclude that ibopamine 100 mg t.i.d. does not affect metabolic control and lipid pattern in type II diabetic patients, therefore representing a safe tool for the treatment of chronic heart failure in these patients.

Long-term therapy of chronic congestive heart failure with ibopamine: a multicenter trial.

The present multicenter open investigation was designed to provide information on the adverse reaction rate, drug interaction, and survival in a group of 544 cardiac patients treated for 1 year with ibopamine either alone or in association with digitalis, diuretics, and other drugs. Some efficacy parameters were also considered. Heart failure was due to idiopathic dilated cardiomyopathy (21%), ischemic heart disease (32%), hypertensive heart disease (31%), and others (16%). Ibopamine was given alone to 39 patients; the others were given the drug in association with digitalis, diuretics, and vasodilators. One hundred forty patients did not complete the trial (25.7%). The most common causes of discontinuation were death (12.5%), noncompliance with the protocol (5%), and adverse events (3.9%). The clinical conditions and NYHA functional class improved in most patients. The cardiothoracic ratio decreased on average. The 1-year mortality rates associated with NYHA class II, III, and IV were 4.4, 13.8, and 37.2%, respectively. Survival tended to be shorter in a small group of 22 patients with hyponatremia, thus confirming some previous reports. Adverse experiences were mainly related to cardiovascular and gastrointestinal systems; the symptoms were considered severe only in 1 of 544 patients enrolled. Ibopamine seems not to induce dangerous arrhythmias. Blood pressure and heart rate did not change over time during ibopamine treatment. Laboratory tests were not significantly affected; fluctuations observed in some tests were related to concomitant variations in the severity of the primary disease. No tolerance to ibopamine seems to be observed during this long-term therapeutic trial.

Treatment of heart failure following chronic cor pulmonale with ibopamine.

A group of 36 patients with cor pulmonale chronicum were treated for 12 months with ibopamine, a dopamine-related drug, orally active, suitable for the long-term therapy of congestive heart failure. In heart failure due to chronic pulmonary disease other drugs such as digitalis are hardly effective. The results obtained indicate that ibopamine, given alone or associated to other drugs, is clinically efficient in the treatment of cor pulmonale chronicum while very few side effects definitely related to ibopamine were reported. In particular no increase in arrhythmias or significant augmentation of anginal episodes was noted.

Inhibition of prolactin and aldosterone secretion by the dopamine derivative ibopamine.

In 7 patients with congestive heart failure acute oral administration of ibopamine, a new dopamine derivative, induced a significant decrease in serum prolactin and aldosterone without affecting serum growth hormone or cortisol. The Metoclopramide-induced secretion of prolactin and aldosterone was blunted in 6 patients pretreated with 200 mg ibopamine. The data are consistent with a dopaminergic effect of ibopamine due to a peripheral action, probably on D-2 receptors.

Pituitary hormone concentrations in cerebrospinal fluid in patients with prolactin and growth hormone-secreting tumors.

GH, PRL, LH, FSH and TSH were measured in serum and in cerebrospinal fluid (CSF) in 16 patients with chromophobe adenomas, in 8 with acromegaly and in 18 subjects with neurological diseases without endocrine troubles. Elevated mean GH and PRL levels in serum and in CSF were found in patients with chromophobe adenomas and with acromegaly. No constant correlation was observed between serum and CSF values. The highest hormonal levels in CSF were usually observed in adenomas with suprasellar extension, but this finding was inconstant. The determination of hormonal levels in CSF does not seem to supply any reliable information about the characteristics of pituitary tumors.

[Effects of somatostatin upon prolactin secretion both in normal subjects and in patients presenting pituitary adenoma (author's transl)]. / Effets de la somatostatine sur la sécrétion de prolactine. Etude chez des sujets normaux et chez des patients ayant un adénome hypophysaire.

In normal subjects somatostatin cannot modify the plasma levels of prolactin when they are in a normal range or when they are pharmacologically increased. In the case of pituitary adenoma (prolactinic or eosinophilic), the response of prolactin to somatostatin varies widely. In some patients there is a marked decrease of the prolactin levels while in others no modification is observed.

Sulpiride and extrapyramidal syndromes in chronic heroin addiction.

During the treatment of 53 young heroin addicts with intramuscular sulpiride for the prevention of withdrawal symptoms, the emergence of extrapyramidal manifestations involving the head, neck and upper trunk in about 40 percent of the patients has been observed. These symptoms occurred with sulpiride dosages in the 'antineurotic' range (not more than 400 mg daily), which practically never produce such symptoms in patients receiving the drug for other clinical indications. The symptoms appeared soon after the first few injections of sulpiride, and yielded readily to a single or repeated intravenous diazepam administration (10 mg). The possible mechanism involved in the production of extrapyramidal manifestations from sulpiride, and a tentative explanation of why such symptoms are produced by doses of this drug lower than those needed to produce the same effects in nonaddicts, are discussed.

The 24-h pattern of human prolactin in serum.

Radioimmunoassay determinations of serum prolactin every 2 hrs in twelve healthy subjects (six women and six men), aged between 22 and 34, reveal that several episodes of hormone secretion occur over a 24-h period. The two episodes displaying significant oscillations have 24-h and 8-h periods, with maxima occurring respectively at 04(30) and at 07(00), 15(00) and 23(00). Accordingly, the highest prolactin levels in serum occur during the night, but oscillations are present throughout the day. The observation schedule adopted leads us to conclude that the main secretory rhythm is synchronized with sleep. The 8-h periods seem to be rather dependent on the course of time.