[Importance of allergologic consultation after a ++perianesthetic complication. Report on a year of activities at the Poitiers University Hospital Center]. / Intérêt d'une consultation d'allergologie à la suite d'un accident peranesthésique. Bilan d'un an d'activité au CHU de Poitiers.

OBJECTIVE: Patients who present an accident during general anesthesia must be tested 4 to 8 weeks later in order to determine the exact cause and prevent any further acute accidents. We report the results of a prospective study based on a 1-year period of allergology consultations after peroperative accidents in the Poitiers University Hospital. PATIENTS AND METHODS: Previous history, surgical procedure, the nature and gravity, of the reaction, risk factors and tests results were recorded. All observations were transmitted to the Regional Pharmacovigilance Center. The level of causality of the administered drug was determined from these data which were integrated into the national computer bank of side effects. RESULTS: After 2,500 general anesthesia procedures, a total of 21 patients had been referred to the allergology consultation. Eighteen were positive for at least 1 test (skin tests or laboratory tests). Among the substances administered, causality was probable for 16, possible for 4 and doubtful for 1. CONCLUSION: Our findings demonstrate the importance of allergy tests and the need for close collaboration between anesthetists, allergologists and pharmacologists.

[Benzodiazepines and pregnancy]. / Benzodiazépines et grossesse.

The use of benzodiazepines is not negligible in pregnant woman and self-medication is considerable. To investigate the effects on the fetus of benzodiazepines used during pregnancy, we reviewed animal and clinical studies completed with observations of CRPV (Centres Régionaux de Pharmacovigilance). Pooled results indicate that the risk of malformations associated with first-trimester exposure to benzodiazepines remains small. However, in a fetus exposed essentially to long-acting benzodiazepines on a long-term basis, neonatal hypotonicity, failure to feed and/or withdrawal syndrom could be observed.

[Attitude of the clinican toward adverse effects of protease inhibitors]. / Attitude du clinicien face aux effets indésirables des inhibiteurs des protéases.

Since 1996, marketing of new drugs called protease inhibitors has revolutionized the treatment of patients suffering from AIDS. The side-effects of this new therapeutic family are quite well known but we wanted to evaluate the attitude of the clinician: can these adverse effects be corrected by symptomatic treatment, do they regress spontaneously or do they lead to an alternative PI therapy? We therefore carried out a retrospective survey in the Infectious Diseases Department of Poitiers Hospital consisting in research on files of patients (n = 70) treated in this department (hospitalization and consultation) for any clinical or biological abnormality attributable to the PI. For each drug we determined what sort of side-effects could be found and the position adopted by the clinician. For 30 patients the PI was stopped and for 21 of these cases because of drug toxicity (gastrointestinal, neurological, renal and metabolic effects). The biological anomalies are quite well tolerated and regress spontaneously in most cases.

Origin of extracellular dopamine increase induced by lactic acid striatal perfusion monitored by microdialysis in the awake rat.

In previous studies we showed that a striatal lactic acid perfusion-induced lactacidosis produces a diphasic increase in extracellular dopamine (DA). In the present study, different pharmacological reagents were used to determine the origin of accumulated DA. Our data show that both DA accumulations were totally suppressed by tetrodotoxin and nicardipine, indicating a relationship with membrane depolarization and a Ca(2+)-dependent effect. The first DA peak was largely reduced by a specific inhibitor of DA uptake such as GBR-12935, and the second was totally suppressed by tyramine and reserpine and lowered and delayed by GBR-12935. These results compared to data in the literature suggest that the first increase in extracellular DA resulted mainly from a release of cytosolic DA by reversal of the DA transporter, while the second was mainly due to a release of vesicular DA by exocytosis. These data indicate that lactic acid perfusion helps clarify the mechanisms involved in this process and could be useful for the study of new treatments against the hyperactive dopaminergic reaction occuring during ischemia.

Lactic acid-induced increase of extracellular dopamine measured by microdialysis in rat striatum: evidence for glutamatergic and oxidative mechanisms.

Striatal lactacidosis was induced by direct lactic acid perfusion to obtain a local pH as close as possible to that observed in ischemia. In a previous study we showed that such lactacidosis produces a diphasic increase in extracellular dopamine (DA). The present work investigated whether DA accumulation is related to a glutamatergic mechanism and/or production of reactive oxygen species (ROS) in the striatum. Concentrations of extracellular DA, glutamate and hydroxyl radicals ((.)OH) were measured in the presence or absence of an N-methyl-D-aspartate (NMDA) receptor blocker (dizocilpine, MK-801) or an antioxidant (Trolox). Measurements were performed using high-performance liquid chromatography (HPLC) with electrochemical and fluorimetric detection on samples obtained by an in vivo microdialysis perfusion technique and stored at -80 degrees C. The increase in lactic acid-induced DA was entirely suppressed by MK-801 and Trolox. Lactacidosis also induced an increase in extracellular glutamate and (.)OH concentrations at the same time as the first DA accumulation, as well as another (.)OH accumulation which preceded and accompanied the second DA concentration peak. Glutamate release was totally inhibited by MK-801 or Trolox. The first peak of (.)OH production was completely suppressed by MK-801 and Trolox, but the second one was only suppressed by Trolox. These data showed that the increase in DA induced by lactic acid was related to glutamatergic excitotoxicity and ROS production, suggested that the kinetic of events was different for the two DA accumulations.

[Prospective study on admissions for iatrogenic adverse effects in the emergency service of hospital university center in Poitiers]. / Enquête prospective sur les admissions pour iatrogénie médicamenteuse dans le service d'accueil des urgences du centre hospitalier universitaire de Poitiers.

Hospital admissions resulting from an adverse drug reaction have been studied in the emergency unit of the university hospital in Poitiers during a 27-day period. This prospective study consisted in documenting all observations considered as an ADR by the medical practitioner in charge of the patient. There were 1235 hospital admissions to the emergency unit during the study period. Thirty-one (2.5 per cent) of admissions were considered to be drug-related. Women were more often affected than men. Patients with ADR were classified taking into account the type of pathology and the drug responsible for the effect. Dermatological and gastrointestinal reactions were predominant. Antibiotic and analgesic drugs were the most common drug groups implicated in causing an ADR.

Extracellular dopamine and catabolites in rat striatum during lactic acid perfusion as determined by in vivo microdialysis.

Many experimental studies concerning hypoxia or ischemia have reported a decrease in intra/extracellular pH and massive dopamine (DA) release in the striatum. The present work investigated whether the increase in striatal extracellular DA is related to acidification or to lactate production. Striatal perfusion of lactic acid (pH 5.5) by microdialysis in conscious freely-moving rats induced an increase in extracellular concentrations of DA and catabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), as a probable result of acidification. Perfusion with sodium lactate (pH 7.4) failed to modify DA and catabolite release, whereas orthophosphoric acid produced the same effect as lactic acid. As lactic acidosis is known to induce a displacement of iron from its uptake sites, the possible role of this metal in response to acidosis was studied by perfusing ferrozine, an iron complexing agent, at the same time as lactic acid. The results showed that ferrous ions are involved in the process and suggested that oxygen free radicals play a role in the extracellular release of DA. Thus, lactic acid perfusion in rat striatum would appear to be a useful model for in vivo studies of the mechanisms responsible for increases in extracellular DA during hypoxia and ischemia.

[Propacetamol and new occupational contact dermatitis]. / Propacétamol et nouvelle allergie de contact professionnelle.

We describe the cases of three hospital nurses who presented eczematous lesions on the hands and eyelids. They worked in surgery department or in post anaesthesia recovery room, all preparing syringes of Pro-Dafalgan (propacetamol: parenteral paracetamol form). They were not sensitive to oral paracetamol or occupational products and latex. During week-end or holidays when they stopped handling Pro-Dafalgan, the eczema recovered but relapsed on working. A few cases are described in the literature so precautions begin to be preconized for healthcare workers but they are not usually in practice. Test performed with solvent, paracetamol, latex, formol and other hospital allergen tests were negative. The only allergen would be propacetamol because all tests performed with it were strongly positive. Following the official evaluation method in pharmacovigilance, based on chronologic and semiologic criterias, considering the positivity of rechallenge and specific tests, propacetamol imputability was probable in all our cases. It is preconized to declare cases to Regional Pharmacovigilance Centers to complete information about handling risks of this very usual analgesic.