Prothrombin time prolongation in paracetamol poisoning: a relevant marker of hepatic failure?

The association between paracetamol overdose and prolonged prothrombin time due to hepatic failure is well recognized. However, little is known of the possibility that paracetamol overdose can prolong the prothrombin time without overt hepatic failure. The few data from the literature suggest this is either due to a reduction in the functional levels of the vitamin K-dependent clotting factors by elevated doses of paracetamol, or a consequence of the administration of the antidote N-acetylcystein.

Ropivacaine combined with various anti-arrhythmic drugs results in mild alterations in myocardial contractility in pigs.

Purpose: The present study was undertaken following the observation of a marked decrease in myocardial contractility after ropivacaine in a patient on amiodarone, in order to investigate the cardiovascular effects of combining ropivacaine with anti-arrhythmic drugs (AARD).

Methods: Anesthetized domestic pigs were treated with disopyramide, flecainide, atenolol, amiodarone, diltiazem or nicardipine at a dose leading to blood levels obtained in treated patients, then received 1 mg*kg(-1) ropivacaine. Blood pressure (BP), left venticular (LV) dP/dt max, sinus heart rate, and intraventricular conduction time were measured before and following the administration of AARD, and following ropivacaine at different time points.

Effects of two pediatric vaccines on autoimmune diabetes in NOD female mice.

The induction or exacerbation of autoimmune diseases is a potential adverse effect of immunostimulating drugs. Vaccines have been suspected of such actions. Epidemiological studies, however, have so far failed to demonstrate any causal relationship between vaccination and autoimmune diseases, including insulin-dependent diabetes mellitus (IDDM).

[Preclinical evaluation of the safety of biotechnology products: specific aspects].

Biotechnology-derived products represent a class of increasingly numerous drugs. One of their major characteristics is extreme diversity, which requires specific approaches for the preclinical evaluation of their safety. The selection of relevant animal species is not easy, as most of these products are human-specific.

Tritiated thymidine incorporation does not enhance sensitivity of the popliteal lymph node assay.

The popliteal lymph node (PLN) assay has been proposed as a tool to predict drugs and chemicals with the potential to induce systemic autoimmune reactions in man. In this assay, weight and cellularity indices typically are the measured endpoints. The present study was conducted to test whether incorporation of tritiated thymidine could improve sensitivity of the PLN assay.

[Early revascularization by stent in renal pedicle trauma].

Objectives: Lesions of the renal pedicle after blunt trauma of the abdomen are rare, and the results of the various therapeutic approaches are unpredictable and usually disappointing. We therefore decided to evaluate an endovascular approach with stent placement in this indication.

Case: A 50-year-old woman, after jumping out of a window, arrived in coma with multiple organ lesions, haemorrhagic shock and initial haemodynamic instability.

From clinical to human toxicology: linking animal research and risk assessment in man.

Since the 1960s, clinical toxicologists have primarily focused on acute poisonings. This proved very successful as the prognosis markedly improved with the use of resuscitation methods, evidence-based management and new antidotes. This latter area was the first major instance linking animal research and clinical toxicology, as illustrated with N-acetyl-cysteine or specific antibodies.

NK-cell activity in immunotoxicity drug evaluation.

NK-cell activity as a tool for detection of immunotoxic effects of new human drugs has gained further attention when the recent European note for guidance CPMP/SWP/1042/99 was adopted. The inclusion of NK-cell activity plus distribution of lymphocyte subsets were suggested as an alternative to the primary antibody response to a T-cell dependent antigen. Either of the two test alternatives should be included as a routine parameter in at least one repeated dose-toxicity study, rats or mice being the species of choice.

Immunosuppressive drugs and cancer.

Among the many adverse effects induced by immunosuppressive drugs, cancers are a major cause of morbidity and mortality. This review is based on the most recent clinical data. Epidemiological studies and cancer registries have consistently shown an increased risk of malignancies in transplant patients although the calculated risk (4-500-fold increase) differs markedly between studies essentially because of differences in methodologies and selection of patients.

[Deleterious cardiac effects of serotonin in myocardial ischemia: role of naftidrofuryl].

It is now accepted that serotonin can either initiate or aggravate myocardial ischaemia through a vasoconstrictor action and platelet activation. It is therefore possible that substances likely to neutralize the effects of serotonin could be used, without any danger, in humans with ischaemic heart disease. This type of action may therefore be exerted by 5-HT2 antagonists, such as naftidrofuryl.