Incidental sonographic finding of an extracranial internal carotid artery aneurysm confirmed by CT angiography.

We report a rare case of an extracranial internal carotid artery aneurysm (EICAA) discovered incidentally by color Doppler sonography (CDUS) and confirmed by CT angiography with three-dimensional reconstructions. As both brain MRI and cerebral angiography were normal and the patient remained asymptomatic, he was neither operated on nor stented but was discharged with appropriate antiplatelet therapy. The volume of his EICAA is checked regularly by CDUS.

[Clinical data on COX-1 and COX-2 inhibitors: what possible alerts in pharmacovigilance?]. / Les inhibiteurs de COX-1 et COX-2, données cliniques: quelles alertes possibles en pharmacovigilance?

Adverse effects of NSAIDs are serious, mainly related to gastrointestinal bleeding, and throughout the world cause about 260,000 hospitalizations and 26,000 deaths a year, but each day at least thirty million patients take NSAIDs. Selective COX-2 inhibitors (i.e. celecoxib, rofecoxib) have demonstrated in clinical trials better gastrointestinal tolerability but their safety in patients with active ulcer, cardiovascular or renal disease has still to be further investigated. When their long-term safety has been established by pharmacovigilance studies they could be prescribed in the at-risk population or for other indications, including pre-term labour, colorectal cancer and Alzheimer's disease, provided they have shown efficacy and safety in controlled trials.

[Use of the CD-ROM "Tox-Didact" for teaching of toxicology and pharmacology]. / Application du CD-ROM 'Tox-Didact' à l'enseignement de la toxicologie et de la pharmacologie.

Tox-Didact is a multimedia teaching software package for initial training, continuing training and self-learning of toxicology and pharmacology. This software covers a large part of toxicology in its acute and chronic pathology using several approaches: drugs (salicylics, paracetamol, lithium ...); toxins (lead, methanol, carbon monoxide ...); drug addiction and doping (cocaine, heroin, LSD, amphetamines ...); systemic targets (kidneys, skin, liver ...). Tox-Didact is currently composed of 39 modules in validation, each tackling the diagnosis, biological surveillance, treatment, prevention and documentation of a real clinical case. Each module is organized around four types of questions, requiring a choice either (drug, symptom, formula ...) or an open response. Each validated answer is analysed by software which then comments on or corrects it. The essential points which characterize this software are: its multidisciplinarity (toxicology, pharmacology, semiology ...), its reliability (validated by experts), its simplicity of use. It is modular and offers an interactive teaching approach. The objective is to create a portable multimedia tool operational with all computer systems (IBM PC, Macintosh). This program is sustained by the Région des Pays de la Loire and by the Multimedia Resource Office of the French Ministry of National Education.

Warning! One buflomedil may hide another one!

A 75-year-old woman experienced fever and convulsions. She was treated for diabetes mellitus, angina pectoris and also for arteritis with Buflomedil Merck (3 tab/d). Further investigations failed to find any aetiology. Buflomedil dosage was elevated to 6.3 mg/l (N = 4-4.5 mg/l). The drug was discontinued and there was no recurrence of symptoms. There was no evidence of error in dosage or interaction. A failure of the generic product was suspected. Only a pharmacist solved the problem. Fonzylane (buflomedil) had recently been switched to Buflomedil Merck. The patient misunderstood the change and took both drugs! Our purpose is not to report a known effect but to emphasize the importance of extending the information given to the patient and the risk of misuse of the generic product.

[Cutaneous side effects of ketoprofen gels: results of a study based on 337 cases]. / Kétoprofène gel et effets secondaires cutanés: bilan d'une enquête sur 337 notifications.

Ketoprofen gels, since their introduction on the French market (1989), have been responsible for various cutaneous side-effects (essentially photosensitization and contact eczemas). A study conducted by the French drug surveillance system detected 337 cases. Analysis showed that the frequency of cutaneous adverse events was from 0.008/1000 to 0.023/1000 according to the commercial gel. The sex ratio was well distributed, and the population was young (30-40 years) and athletic. Treatment lasted about 7 days, and the appearance of the side-effect was sometimes quite delayed relative to discontinuance of treatment. Reactions were severe in 40 per cent of cases. The factors favourable to side-effects were essentially exposure to the sun (one-third of cases) and occlusive dressing. No particular predisposing conditions were noted, although 2.6 per cent and 8.5 per cent of cases respectively involved earlier sensitization by a topical NSAID. The side-effect lasted about 16 days. The course was usually favourable but hospitalization was required in about 10 per cent of cases. Photoallergological testing indicated photosensitization to ketoprofen. These results led the National Commission of the French drug surveillance system to request a modification in the indications for the prescription of the ketoprofen gels.

Quantitation of amphotericin B in plasma by second-derivative spectrophotometry.

A method is described for determining amphotericin B in plasma using second-derivative spectrophotometry after deproteinization. The assay was based on the absorbance at 407.5 nm. The second-derivative spectrum recorded between 350 and 450 nm allowed identification of the analyte and showed absence of drug interference. Only bilirubin interfered at high concentration (> or = 50 mumol l-1. The linear concentration ranges were 0.05 -5.0 mg l-1 (r = 0.999, slope = 2.731, intercept = 0.008). Between-day CV < or = 9.7%, within-day CV < or = 5.5%, analytical recovery close to 100% were suitable for clinical investigations. This method provides better specificity than direct absorbance, is simpler and faster than a high performance liquid chromatography assay and can be used routinely by any laboratory possessing a spectrophotometer with a derivative accessory.

[French system of drug surveillance]. / Le système francais de pharmacovigilance.

The French drug surveillance system is characterized by: a network of thirty one regional drug surveillance centres, located to provide convenient proximity to health care professionals; a causality assessment method, compulsory for all persons involved in drug surveillance, to assess the causal relationship between an adverse effect and one or more drugs; if necessary, an additional evaluation of the causal relationship will be performed using pharmaco-epidemiology methods; a Technical committee and a National Commission of Drug Surveillance which centralize and assess all the data in order to provide a consensual advice to the relevant authorities on necessary measures, to prevent, or reduce a drug related adverse effect; in the case of an inquiry, the drug surveillance department of the pharmaceutical company and the network of regional drug surveillance centers will pool their data with the aim to exchange information and ideas.

A pilot study of 220 mg/m2 melphalan followed by autologous stem cell transplantation in patients with advanced haematological malignancies: pharmacokinetics and toxicity.

We studied the pharmacokinetics and toxicity of 220 mg/m2 melphalan (HDM 220) followed by autologous stem cell transplantation in 16 patients with advanced haematological malignancies. Pharmacokinetic parameters (mean values of steady-state volume of distribution 14.6 l/m2, total body clearance 313 ml/min/m2, elimination half-life 46 min) were the same as those of 140 or 200 mg/m2 melphalan in previous reports. HDM 220 was feasible. Extramedullary toxicity was mainly W.H.O. grade 4 mucositis (13/16 patients). The median duration of 41 d (10, not reached) of thrombocytopenia < 25 x 10(9)/l was long. In multiple myeloma the response rate was 89% in heavily pretreated patients, suggesting that HDM 220 could be considered earlier in the course of the disease as an alternative consolidation therapy.

A 2-year evaluation of questions concerning "Drugs--Pregnancy" at the CRPV in Nantes March 1992--March 1994. / Bilan de 2 années du suivi des questions "Médicaments--Grossesse" au CRPV de Nantes entre Mars 1992 et Mars 1994.

Since 1990, the 'Centre Regional de Pharmacovigilance' of Nantes has systematically monitored pregnant women exposed to drugs. To increase physicians' participation in this study (34 per cent), the protocol was modified in 1992. Phoned answers are confirmed by mail. At the supposed time of the delivery, the physician receives a questionnaire about the outcome of pregnancy. A second letter and phone call are planned. With this method, 89 per cent of the pregnancies were fully documented between March 92 and March 94. Answers are classified according to the type of the practice. Pregnancy outcome is studied according to the drugs and the moment of exposure during pregnancy. Quality of the information, motivation of the physicians, and the benefits and difficulties of this method are discussed.

Pharmacokinetics of high-dose melphalan in adults: influence of renal function.

BACKGROUND: The pharmacokinetics of melphalan were studied in 20 patients with multiple myeloma, primary amyloidosis or lymphoma after IV dose of 140 mg/m2 infused over 30 minutes (two patients were treated with a higher dose). MATERIALS AND METHODS: Six patients received melphalan alone, 8 received melphalan combined with total body irradiation, 2 received busulphan plus melphalan and 4 received the BEAM association (BCNU + etoposide + high dose aracytine + high dose melphalan). Creatinine clearance was measured immediately before the infusion of melphalan, and 9 blood samples were taken to monitor elimination kinetics. RESULTS: Pharmacokinetic parameters (CIT, Vdss, t1/2) and areas under the curve (AUC) were comparable to those obtained by Ardiet et al after rapid IV injection. For all patients, AUC, CIT, Vdss, t1/2 beta and MRT were significantly correlated with creatinine clearance; the different pharmacokinetic parameters calculated showed great interindividual variations. CONCLUSIONS: Renal insufficiency did not lead to a large decrease in melphalan clearance compared to interindividual variations in systemic clearance.

[Determination of plasma retinol and alpha-tocopherol by HPLC]. / Dosage du rétinol et de l'alpha-tocophérol plasmatique par CLHP.

Retinol (vit A) and alpha-tocopherol (vit E), the active compounds of vitamins A and E, were assayed by reversed-phase high performance liquid chromatography (HPLC) (C18) with UV absorbance detection at 280 nm. Plasma was deproteinized and liquid-liquid extraction performed with hexane. After evaporation, the residue was dissolved in organic solvents (ether:methanol 25:75, V/V). Standard curves were prepared by adding known amounts of standards to plasma. The use of acetonitrile in the mobile phase (acetonitrile:methanol:water 64.5:33:2.5, V/V) avoided interference peaks, giving a total run time of 8 min. Analyte stability required that samples be treated in the dark. Analytical performance was good: recovery around 100%, detection limits 0.015 mg/l for vit A and 0.030 mg/l for vit E, linear range 2 mg/l for vit A and 20 mg/l for vit E, no recorded interference, and between-run and within-run precision with coefficients of variation < 11%. Analytes were stable at room temperature for 24 h (vit A) and 48 h (vit E) in plasma stored in the dark for one month at -20 degrees C. The standard solution containing both vit A and vit E increased vit A stability. Plasma concentrations (mg/l) for vit A and E were respectively: 0.63 +/- 0.17 and 9.61 +/- 3.1 in adults (n = 29), 0.39 +/- 0.17 et 7.10 +/- 2.41 in children 0 to 15 years (n = 21). This method allows regular monitoring of patients with cystic fibrosis to check for retinol and alpha-tocopherol deficiencies. The usefulness and results of the method are discussed in terms of previous studies.

[Neutropenia caused by acenocoumarol associated with hairy cell leukemia]. / Neutropénie à l'acénocoumarol associée à une leucémie à tricholeucocytes.

We report the case of a woman splenectomized to treat her hairy cell leukemia (at the moment in remission) 11 years before the detection of neutropenia. The neutropenia began just after the treatment of pulmonary embolism by acenocoumarol. The neutropenia disappeared quickly after substitution of acenocoumarol by fluindione. We discuss the attribution of the neutropenia to acenocoumarol and the part played by hairy cell leukemia.