[Imaging features of iatrogenic drug disorders]. / Imagerie de la pathologie iatrogène médicamenteuse.

Iatrogenic drug disorders should be considered when presented with a number of imaging findings mainly involving the nervous, musculoskeletal, gastrointestinal or genitourinary system. Care should be used when differentiating between imaging findings related to the underlying pathology and imaging findings related to drug-related complications: examples include the impact of steroid therapy on bones and the impact of triple-drug anti-HIV therapy and its impact of fatty tissue. Knowledge of the necessary imaging surveillance protocol is implied.

Incidence of Reye's syndrome in France: a hospital-based survey.

At the time of the study no information was available in France about the incidence of Reye's Syndrome (RS) and no warnings about RS and aspirin. The objective was to evaluate the incidence of RS in France by a hospital-based study. For a period of 1 year from November 1995 to November 1996, all French paediatric departments were required to report any child under 15 years with unexplained noninflammatory encephalopathy (i.e., CDC consciousness level stage I or deeper with normal CSF) and a threefold (or greater) increase in serum aminotransferase and/or ammonia. All suspected cases were classified by a panel of experts as probable RS or excluded RS. In 10% of randomly selected paediatric departments we checked that every suspected case had been reported. Forty-six suspected cases were reported during the year of the survey, of which 14 were classified as RS. Five of these 14 cases had a metabolic disorder. Nine children were definitively diagnosed as having RS (i.e., an estimated incidence of RS of 0.79/1,000,000 children, i.e., below 15/year). Eight children had been exposed to aspirin, four to aspirin alone and four to aspirin and acetaminophen. On the basis of these results the incidence of RS in France in 1996-1997 was not substantially different from that of countries where warning labels were already in use, but it was higher than in the US after 1994. This was probably due to the reduction in aspirin prescription in France because of warnings in Europe and the US and also because many cases of RS are now identified as metabolic disease. On the basis of these results and because the relationship between aspirin and RS has already been proved, public and professional warnings concerning RS on aspirin-containing products in cases of varicella and viral febrile illness have been adopted by the French Drugs Agency.

[Antiretroviral agents and pregnancy: mitochondrial dysfunction and nucleoside analogs]. / Antirétroviraux et grossesse: cytopathie mitochondriale et analogues nucléosidiques.

An alert was published during 1999 by the French Perinatal Cohort: eight cases of mitochondrial dysfunction were reported among 1754 infants exposed to nucleoside analogues in utero and during the neonatal period. These eight infants were not infected by HIV. Mitochondrial toxicity of nucleoside analogues is clearly described in adult HIV patients receiving NRTI. Zidovudine (the only and the first NRTI studied) induced mitochondrial DNA dysfunction in animals (monkeys) and neurobehavourial effects in mice at a dose similar to the human dose. Practitioners have been informed. Retrospective and prospective studies are in progress. The recommendations for prevention of maternofoetal transmission of HIV are not reassessed. Pregnant women in rich countries are receiving combination antiretroviral therapy. Information of women has to be undertaken and therapeutic strategies for maternal indication have to be discussed case by case. Careful long term follow up of children exposed to antiretroviral agents is a priority.

[Mucolytic agents for acute respiratory tract infections in infants: a pharmacoepidemiologic problem?]. / Fluidifiants bronchiques dans les infections respiratoires aiguës du nourrisson: un problème pharmacoépidémiologique?

OBJECTIVE: To study the use of mucolytics agents, i.e. acetylcystein and carbocystein, in infants. To evaluate their efficacy and safety for their main indications. METHODS: A prospective one-day survey of prescriptions among 95 office-based pediatricians. A systematic review of the literature. RESULTS: Among 1327 prescriptions regarding infants, 4.3% were mucolytics agents. Main indications were rhinopharyngitis, isolated cough, and acute bronchitis. Our review did not identify any study of rigorous methodological quality that supported the efficacy or safety of mucolytics agents in infants for their in-label (isolated cough, acute bronchitis) and off-label (rhinopharyngitis) indications. Six cases of infants, aged less than eight months, presenting paradoxical bronchial congestion during a treatment with mucolytics agents, have been reported to the French pharmacovigilance system. No causal relationship was established from these cases because of a possible protopathic bias. DISCUSSION: Our results concerning mucolytics agents use are similar to those reported by the French Health Care Funds. In addition to the lack of studies on efficacy, no studies on the dose-response relationship were available, leading to suggested dose regimens in the French license of acetylcystein ranging from 44.4 to 16.4 mg kg-1 j-1 between one to 24 months. These dose regimens could predispose to overdosing in the youngest infants as it seems observed in the six reported cases. CONCLUSION: In infants, mucolytics agents efficacy has never been demonstrated and some elements suggest poor safety (paradoxical bronchial congestion).

[Cancer and pregnancy: risks of exposure to cancer chemotherapy during pregnancy]. / Risques des médicaments.

Animal studies reveal that almost all antineoplastic agents are teratogenic. But extrapolation to human beings is not simple because of species differences. Few human data are available, most are sporadic case reports. Other toxic effects for the fetus and neonate (intrauterine exposure during second and third trimester) must be taken in consideration when prescribing chemotherapy for pregnant women. Adverse effects observed in adult and children are helpful if data during fetal life are lacking. Long-term studies are needed to evaluate the transplacental effects of chemotherapy during pregnancy; these studies should assess the child's mental and physical development, infertility and the occurrence of second malignancies.

[Growth retardation and amino acids. Analysis of maternal plasma and amniotic fluid]. / Hypotrophie et acides aminés. Analyse du plasma maternel et du liquide amniotique.

We have carried out an analysis of the amino acids in the mother's plasma and in the liquor amnii of 26 pregnant women who delivered either normal premature babies or those with intra-uterine growth failure. The levels found at delivery showed no difference in cases of prematurity in the composition of the substances in the plasma, but the liquor is poor in glycocol (GLY), Tyrosine (TYR), Phenylalanine (PHE). In the case of growth failure a significant drop in the concentration of Threonine (THR), Alanine (ALA), Valine (VAL), Methionine (MET) and Arginine (ARG) was found in the plasma. The liquor amnii however had shown no change in composition.

[Fetal toxicity of non-steroidal anti-inflammatory agents]. / Toxicité foetale des anti-inflammatoires non stéroïdiens.

All non-steroidal anti-inflammatory drugs (NSAIDs) are prostaglandin inhibitors, which explains their foetal toxicity. So far, no epidemiological study of their cardiopulmonary and renal effects has been carried out, but case-reports have been published. The cardiopulmonary effects of NSAIDs include closure of the ductus arteriosus, pulmonary hypertension cardiopathy and tricuspid valve insufficiency. They were responsible for 31 neonatal accidents, 8 of which were fatal (for 22 pregnant women, 7 bearing twins, 1 bearing triplets). The renal effects of NSAIDs consisted of acute renal failure with oedema, oliguria, hyponatraemia and marked hyperkalaemia. They affected 23 neonates, 8 of whom died (for 17 pregnant women, 4 bearing twins, 1 bearing triplets). A few epidemiological studies have reported foetal haemorrhages when aspirin was used by the mother as anti-inflammatory agent. In comparative trials of indomethacin as short treatment of premature labour and polyhydramnios the drug proved to be effective. In obstetrical tocolysis NSAIDs can be given in the absence of alternative therapy with beta-adrenergic agents, and their risk can be minimized by ultrasonographic examination and monitoring of foetal cardiac function and diuresis. In the field of rheumatology, corticosteroids would be a good alternative to NSAIDs for rheumatic diseases, but using NSAIDs for low back pain, sciatica, haemorrhoids, toothaches, sinusitis, etc., would not be justified in pregnant women. Self medication must be discouraged.

[Are mydriatic eyedrops dangerous for pre-term infants?]. / Les collyres mydriatiques sont-ils dangereux chez le nouveau-né prématuré ?

The funduscopic examination is essential in neonatology to screen for retinopathy in the pre-term infant. Mydriatic eyedrops, which are used for this examination, are known to induce digestive side effects. We present a case of necrotizing enterocolitis developing in a pre-term infant as a complication of mydriatics. This infant was a girl born at 28 weeks gestation and 5 days, with Down's syndrome, who died on the 44th day of life, due to necrotizing enterocolitis, after instillation of 1 drop of atropine 0.3% in each eye. The chronology of events, the application method, and the clinical symptoms of atropine impregnation argue in favor of a causal relationship between atropine and necrotizing enterocolitis. The review of the literature made on the basis of this observation shows that side effects of mydriatic eyedrops are frequent in pre-term infants and raise the question of atropine hypersensitivity in pre-term infants with Down's syndrome.