Placebo and the Helsinki Declaration--what to do?

The Helsinki Declaration is the 'gold standard'--a directive, not a law, on how to conduct controlled studies in humans in conformity with ethical principles. In spite of many discussions about their unsuitability some articles have remained unchanged in the most recent (sixth) revision of the Declaration. The demand to use "the best treatment" excludes use of placebo in the control group and presents an obstacle to the scientific evaluation of a number of drugs and treatments in general.

Towards a core curriculum in clinical pharmacology for undergraduate medical students in Europe.

Undergraduate medical education has been under the spotlight for many years in Europe. In the United Kingdom the General Medical Council, which validates the final medical examination in all UK Medical Schools, has been trying to influence the curriculum for at least the last 50 years. Following their publication of the document "Tomorrow's Doctors" in 1993 many medical schools in the UK have completely changed their curriculum design away from didactic learning and towards an integrated problem-orientated or problem-based approach.

Conflict of interest in Croatia: doctors with dual obligations.

There is an emerging awareness of the possibility of conflicts of interest in the practice of medicine in Croatia. The paper examines areas within the medical profession where conflicts of interest can and have occurred, probably not only in Croatia. Particularly addressed are situations when a doctor may have dual obligations and how independent ethics committees can help in decreasing the influence of a conflict of interest.

How long can an escalation of dose override tolerance to the hypotensive efficacy of nitroglycerin infusion in coronary care patients.

Tolerance to nitroglycerin infusion (NG) can be overridden by dose escalation. The aim of this study was to define for how long it can be done for hypotensive efficacy of NG, in a coronary care setting. A prospective trial with an intra-individual therapeutic comparison was performed in 60 patients with acute myocardial infarction or unstable angina.

Variations in the risk of gastrointestinal hemorrhage with non-steroidal anti-inflammatory drugs and localization of lesions.

The aim of this prospective study was to determine the effect of ulcerogenic drugs in patients with bleeding peptic ulcers and erosions with respect to their age and sex, ulcer history and additional risk factors such as family medical history, alcohol use, smoking, coffee consumption and stress. Of 367 patients with bleeding gastroduodenal lesions admitted during a period of 15 months, 88 (24%) had previously received ulcerogenic drugs. The most frequently taken drugs were aspirin (44.

Problems with drugs in Croatia.

Croatia has 4.8 million inhabitants, 11,800 physicians, 2000 pharmacists, two now shareholding, pharmaceutical companies (about 6500 employees, total sales of about 350 million US dollars). There are a number of problems due to the war (GNP fell from 3800 to about 1500 US dollars), occupation of 25% of its territory, 0.

How safe are bioequivalence studies in healthy volunteers?

Between 1981 and 1994, 58 bioequivalence studies (b.s.) were performed in 885 healthy volunteers.

Access to information on drug regulation in the countries of Central and Eastern Europe.

Awareness of the importance of transparency and accountability in drug legislation is not universal and is of relatively recent origin. It is not surprising that data on the accessibility of information in the drug regulatory systems of the "Central and Eastern European countries" (CEEC) are virtually non-existent. Where drugs are concerned, these countries tend to have a number of characteristics in common, namely 1) the lack of a national drug policy, i.

Determination of bioequivalence of two furosemide preparations; the effect of high doses of furosemide on some pharmacokinetic parameters.

The bioequivalence of two oral preparations of the diuretic furosemide, namely (i) a Croatian pharmaceutical product (test preparation A) and (ii) a reference preparation B, both in a dose of 500 mg was assessed in an open, cross-over, randomized trial in 15 healthy male volunteers, in whom the HPLC method with a fluorescent detector was used to determine its concentrations. The test preparation (A) was found to achieve a considerably higher concentration (17.2 +/- 9.

Bioequivalence of two oral cyclosporine preparations.

A comparison of bioequivalence of two cyclosporine (CAS 59865-13-3) preparations was performed. Ten cyclosporine treated patients with transplanted kidneys were included. Criteria were successful transplantation and minimum period from transplantation of at least 6 months.

Pharmacokinetic changes in patients with oedema.

The pharmacokinetics of furosemide (frusemide) in patients with oedema have been relatively well studied, but in many studies it is unclear whether the disease or the oedema per se has the major effect. The rate of absorption of oral furosemide in patients with oedema was decreased, but total bioavailability was almost unchanged. The peak serum concentration (Cmax) and time taken to achieve Cmax were either decreased or unchanged.

Adverse drug reactions resulting in hospital admission.

A 14-month (1992/3) prospective study was performed in two departments of the University Hospital Centre (UHC) in Zagreb. The aim of the study was to assess the rate of drug-related hospitalizations, drugs that caused adverse drug reactions (ADRs), and all factors which could have been of importance for their appearance. One hundred and thirty (2.

Qualitative analysis of drug prescription in a geriatric population sample.

The rationality of specialist drug prescription in 154 patients older than 64 in 3 Zagreb homes for the aged was analyzed over an 11-month period. Categories analyzed were: number of prescribed drugs, justification of prescription, adequacy of the dose, route, form and therapy duration of the prescribed drugs, adequacy of the type of the prescribed drugs in the advanced age and the presence of contraindications of drugs used. The criterion of the rational drug use was the WHO's modified definition of rational drug therapy: "Application of an appropriate drug by a correct route in an adequate dose over a sufficiently long period of time".

Clinical pharmacology in Eastern European countries.

The current status of clinical pharmacology (CP) in the countries of the former Eastern block is presented. The difficulties in obtaining an accurate comparative view are pointed out. CP is unevenly developed in Eastern European countries and the number of hours devoted to basic/clinical pharmacology differs considerably 100/nil to 240/50.

Pharmacokinetics and interactions of digoxin, theophylline and furosemide in diseases with edema.

In diseases with generalized edema caused by decompensated heart and liver diseases or kidney failure digitalis preparations, diuretics and theophylline -- if lung disease accompanies one of the above states -- are often used. Literature dealing with theophylline, digoxin and furosemide pharmacokinetics in edematous diseases was analyzed as well as theophylline or digoxin interactions with furosemide. The results obtained in these investigations are very dissimilar, even contradictory.

A dynamical model for the separation of secondary resistance from tolerance to nitroglycerin infusion.

A dynamic model for the estimation of a residual hypotensive efficacy of nitroglycerin (NG) infusion was constructed to distinguish secondary resistance from tolerance to NG, as lost vs weakened efficiency. The model was tested by individual comparison in 82 of 92 patients with acute myocardial infarction or unstable angina. Ten patients were excluded from the study protocol due to complications that required therapy modification.

[A critical report on drugs in 1991].

Principal changes in the drug field in this country in 1991 were caused by the armed aggression committed against Croatia and the succession of disturbances that this aggression induced. Abroad as many as 13.6% of drugs could be ranked as category A.

Prophylactic administration of ranitidine after sclerotherapy of esophageal varices.

The present trial was carried out to determine the usefulness of H2-receptor antagonist drug therapy for the prevention of esophageal bleeding and esophageal varices in patients who underwent sclerotherapy. According to randomization, out of the 58 patients, 28 received, along with the usual standard therapy, ranitidine and 30 received placebo. Ranitidine, 50 mg, was administered intravenously over a period of 3 days every 8 hours, and then 150 mg of ranitidine was given per os in the evening for one month.

The effect of food and metoclopramide on the pharmacokinetics and side effects of bromocriptine.

The effect of food and metoclopramide on the pharmacokinetics of bromocriptine was investigated in 7 healthy subjects. Plasma concentrations of bromocriptine were measured by radioimmunoassay after a single oral dose of 7.5 mg bromocriptine.