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AIMS--To examine the advantage of systematic plasma iodine assays in establishing the thyroid function of patients with thyroid disorders. METHODS--Iodine was determined by inductively coupled plasma mass spectrometry (ICPMS) in the plasma of 799 patients consulting for possible thyroid disorders, indicated by FT4 and TSH assays. RESULTS--Plasma iodine was below 40 micrograms/l in 57 (7%) patients, most of whom had hypothyroidism; 40-80 micrograms/l in 439 (55%) patients, most of whom had normal thyroid hormone function; 80-250 micrograms/l in 240 (30%) patients, most of whom had hyperthyroidism; and above 250 micrograms/l in 63 (8%) patients, almost all of whom had iodine overload caused by iodinated drugs, particularly amiodarone, resulting in euthyroidism (24%), hyperthyroidism (36%), and hypothyroidism (16%). Sixty five (7%) had been treated with amiodarone and 27 (3%) with other iodinated drugs. More than 10% of patients with thyroid disorders therefore had an iodine overload. CONCLUSIONS--The determination of total plasma iodine using the simple, accurate ICPMS technique, should be carried out in patients consulting for thyroid disorders, particularly for the detection of an iodine overload. [ABSTRACT FROM PUBLISHER]

Introduction: Methotrexate (MTX) is a known teratogenic drug used off-label in the treatment of ectopic pregnancies (EP). As MTX polyglutamated derivatives remains into the cells during several weeks, it is recommended to avoid conception during 3 to 6 months following MTX therapy. We report the follow-up of pregnancies after preconceptional exposure to MTX for EP., Material/methods: Prospective cases of pregnancy occurring within 3 months after MTX injection for an EP recorded in the Terappel database were analyzed., Results: Data were obtained on 52 pregnant women. The median age of patients was 28 (18-38), and the median gestational age at inclusion was 7 weeks after last menstrual period (3-22). The time between the last MTX injection and conception ranged from 12 days to 13 weeks and the total MTX dose was between 40 to 210mg. Out of 45 pregnancies with known outcome, there were 39 live births (87%), 3 spontaneous abortions (6.7%) occurring 63 to 94 days after MTX administration, 2 elective terminations, and 1 medical termination after premature rupture of membranes, oligohydramnios and arthrogryposis (48mg of MTX 9 and 8 weeks before conception). Two additional cases of major malformations were observed among 40 examinable babies or fetuses: tetralogy of Fallot (MTX 6 weeks before conception), and cerebral ventriculomegaly with normal karyotype (50mg of MTX 9 to 13 weeks before conception). The resulting rate of major malformations was 7.5% (95% CI: 1.6-20.4)., Discussion/conclusion: Although this prospective study shows a major malformation rate higher than expected in the general population, the observed malformations are not consistent with the typical pattern of methotrexate embryopathy. However, the case of tetralogy of Fallot is reminiscent of previously published cases with MTX exposure during early pregnancy. Owing to the small sample size, more powerful studies are needed to confirm or refute these findings., (Copyright © 2016 Société française de pharmacologie et de thérapeutique. Published by Elsevier Masson SAS. All rights reserved.)

Non-pharmaceutical forms of Artemisia annua (a Chinese plant containing artemisinin) are used by some travellers who believe these products are safer than anti-malarial drugs. We report two cases of severe Plasmodium falciparum malaria requiring hospitalization in an Intensive Care Unit following prophylaxis with non-pharmaceutical A. annua in French travellers., (© International Society of Travel Medicine, 2016. All rights reserved. Published by Oxford University Press. For permissions, please e-mail: journals.permissions@oup.com.)

Methotrexate is a folic acid analog, which is a thymidylate synthetase and dihydrofolate reductase inhibitor. It is used in oncology, dermatology and rheumatology and off labelling in the treatment of ectopic pregnancies. This paper is a review of methotrexate pharmacology with focus on data concerning ectopic pregnancies., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

Purpose: To analyse the conditions of use of the drug combination in outpatients., Methodology: The first section consisted of a population-based analysis using computerized records from the French national health insurance system. The study population consisted of adult patients, receiving long-term treatment with spironolactone (SPIR) and angiotensin-converting enzyme inhibitor (ACEI). For each patient, the reimbursement of serum potassium and creatinine determinations was searched for in the database during the 6-month period preceding the date of the last dispensation. The second section comprised a written questionnaire on use practises, sent to practitioners who prescribed the drug combination to randomly selected patients. Analysis of the answers to the questionnaire made it necessary to develop a reference system. In the third section, procedure one was repeated at a later stage, following an information campaign, in order to measure its impact., Results: The exhaustive population under procedure 1 consisted of 3620 patients (71 +/- 11 years). During the 6 months prior to the index date, 51% of patients underwent at least one determination of both serum potassium and serum creatinine. The randomised population under procedure two consisted of 441 patients (70 +/- 13 years) and their 375 practitioners. When compared with the reference system, SPIR-ACEI was used for the recommended indications, at the appropriate SPIR-ACEI dosages, and under minimal monitoring of biological parameters in only 65 patients (15%). After the information campaign, results were disappointing because only 55% of patients underwent the minimal laboratory monitoring., Conclusion: The use of the drug combination in general practice was mainly inappropriate., (Copyright 2007 John Wiley & Sons, Ltd.)

Objective: To study the incidence and risk factors of drug-induced hyperkalemia in adult, hospitalized patients., Methodology: A three months prospective observational study was used including all hospitalized, non dialyzed, patients older than 17 years who presented with a hyperkalemia egal or over 6 mmol/L. The studied variables were demographic, clinical, biological and therapeutic., Results: Forty patients, among 112 included, had a hyperkalemia promoted by drug(s) (3.5 cases for 1000 hospitalized patients). They were 73 +/- 15 years old and 72.5% had a past medical history of chronic renal failure. The hyperkalemia (6.42 +/- 0.48 mmol/L) was associated with an increase in creatininemia in 67.5% of patients. The most frequent treatment observed were renin angiotensin system drugs in 62.5% of patients, spironolactone in 37.5% or both drugs in 25%., Conclusion: A better use of these drugs would be able to prevent some cases of hyperkalemia.

Introduction: Generic drugs are copies of original drugs, hence their low cost. In France, expansion of the use of generic drugs is not significant and the support of practitioners is essential in increasing this., Aim: The purpose of this study was to survey the opinion and practical experience of physicians regarding generic drugs, in order to develop a proposal for the safer use of these drugs., Methods: A form was sent to the 1235 general and specialist practitioners in the Maine-et-Loire "département" with assistance from the regional health insurance, in March 2002. The main topics studied were prescribing practices, risks associated with generic drugs and pharmacist substitutions. The chi2 test and Fisher's exact test were used in the data analysis., Results: Four hundred and twenty-nine forms were returned (34.7%). Only 55% of practitioners considered generic drugs to be as safe and effective as original drugs. Fifty-nine percent prescribe generics rarely or never. The prescribing depends on many factors, linked to the practitioner, the patient or the drug. Many practitioners reported adverse events with generic medicines. With regard to the switch by the pharmacist, it was reported that 45% of prescribers would refuse it in some instances. Among the proposals, cooperation between practitioners and pharmacists in the choice of the generic drugs was approved by 57% of physicians., Discussion: The main perception is that the vastness of the generic world and the fear of adverse events are somewhat bewildering for both patients and health professionals. Among the proposals made by practitioners, a decrease in the number of generics for a same molecule and the institution of a standard price are widely approved., Conclusion: Practitioners do not refuse to use generic drugs but are very concerned about the risks of adverse effects for their patients. They regard it as important that a patient receiving chronic treatment be given the same generic drug each time.

Cases of adverse drug reactions which occurred in the elderly, and were notified to the Regional Centre of Pharmacovigilance of Angers between 1995 and 1998, were analysed in two subgroups: from 75- to 84-years-old and older than 84 years. Among the 263 cases recorded in the elderly, there was no significant difference between the 75- to 84-year-old patients (180 cases) and the patients older than 84 years (83 cases) concerning past medical history, severity of effects or medication. Side-effects in patients over 74 were mainly cutaneous, haematological and neuropsychiatric, involving in decreasing order of frequency cardiovascular, neuropsychiatric, antibiotic, analgesic and anti-inflammatory drugs. In comparison with patients under 75, adverse drug reactions are more frequent and more serious, notably overdose and drug interactions, in elderly people. The occurrence of some avoidable side-effects justifies the strengthening of information about therapeutic safety in the elderly.

The aim of this study was to investigate possible discrepancies between the drug prescribed and that recorded in the patient's file. A prospective open blind study was conducted with 178 patients included consecutively. We analysed 1011 prescriptions (the median (range) number of drugs per patient was 5 (1-37)) and identified 49 discrepancies (5 per cent of cases). In 18 cases, the drug given to the patient by a nurse was not the drug initially prescribed but the drug recorded in the patient's file was the drug actually given to the patient. In another 31 cases, the drug given to the patient was not the drug initially prescribed, but the drug recorded was that prescribed. This inquiry shows that there may be a discrepancy between the drug initially prescribed and that actually administrated and suggests that poor traceability may affect pharmacological surveillance surveys.

The aim of this study was to investigate the interaction between drugs chosen for their clinical neurotoxicity or chemical structure and vitamin B6 metabolism. After a preliminary screening of drugs to determine their potential inhibitory effect on erythrocyte nonpurified pyridoxal kinase (PLK) (EC 2.7.1.35), additional investigations, including kinetic studies and detection of chemical reactivity between the inhibiting drugs and pyridoxal (PL) or pyridoxal-5'-phosphate (PLP), using UV-visible spectrophotometry and mass analysis, were carried out to specify the mechanism of PLK inhibition. Depending on the results, the inhibiting drugs were divided into three groups. The first group included theophylline and progabide and inhibited PLK using either PL or pyridoxamine (PM) as substrate and thereby were true inhibitors. Moreover, they did not form covalent complexes with PL or PLP. The second group, which included cycloserine, dopamine, isoniazid, and thiamphenicol glycinate, inhibited PLK using PL, but not PM, as substrate. They were able to react with PL or PLP to form covalent complexes, and kinetic studies suggested that the observed PLK inhibition was due to these formed complexes. A third group, which consisted of levodopa, D-penicillamine, and muzolimine, inhibited PLK using PL, but not PM, as substrate. They formed, with PL or PLP, chemical derivatives that probably had no inhibitory effect on PLK. These results and the clinical consequences of such interactions are discussed and compared with results of previous studies.

Kinetic studies were conducted to examine the effects of K+, Na+ and Li+ on human erythrocyte pyridoxal kinase (PK) activity. A dialyzed hemolysate served as the PK source. The substrates used were pyridoxal (PL) and ATP. Determination of the enzymatic activity was based on HPLC separation and fluorimetric detection of PL and pyridoxal 5'-phosphate as semicarbazone derivatives. In comparison to the poor activity of PK assayed without monovalent cation, all tested cations are activators. Among them, K+ is the most effective, improving both PK affinity for the substrates and maximal velocity. Na+ increases maximal velocity and PK affinity for ATP but decreases it for PL. Li+ is a poor activator which seems to modify the enzymatic mechanism from a random to an ordered sequential pattern with ATP bound before PL. Results suggest that K+ and Na+ bind to PK on the same site while Li+ binds on another site. This hypothesis and the mechanism of monovalent cation-PK interaction are compared to other well-known K(+)-activated enzymes.

Objective: Our purpose was to study pregnancies and birth outcomes in a population of women treated for epilepsy., Study Design: A retrospective uncontrolled study of 75 pregnancies in 55 epileptic women under treatment was conducted in the nursery of CHU Angers. The course of pregnancies and deliveries, the frequency of congenital malformations and the clinical state of the neonates during the first 6 days of life were recorded., Results: There was a high rate of prematurity (15%) especially in patients treated by phenobarbital, a 10.5% rate of intra-utero growth retardation, a 11% rate of major congenital malformations and a 9% rate of isolated minor congenital malformations. Congenital malformations were mainly facial dysmorphia, cardiopahties, urogenital tract abnormalities. The neonatal symptomatology was associated with a high level of antiepileptic drugs in neonates or to a withdrawal syndrome or to hypovitaminosis., Conclusion: Overall results justify implementing prevention and detection measures.