[Hemolytic anemia caused by fenbufen].
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Biomedical subjects
Publications and source records attributed to A Castot.
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Seven patients developed hepatitis after receiving amodiaquine for malaria prophylaxis for 4 to 15 weeks. Four patients had a minor form of hepatitis: jaundice was mild or absent, serum aminotransferase levels were moderately increased, and recovery was prompt. Three patients had a severe form: jaundice was intense, serum aminotransferase levels were markedly increased, jaundice persisted for 3 to 6 months, and liver tests were still abnormal 7 to 27 months after the onset of hepatitis. In two patients, serum aminotransferase levels increased promptly after readministration of the drug, which is consistent with an immunoallergic mechanism for amodiaquine-induced hepatitis.
The proximity of smokers exposes non-smokers to the inhalation of tobacco smoke. The existence of this absorption has been established by assays of blood nicotine concentrations or urinary thiocyanate concentrations, in volunteers: proximity with an individual who smokers approximately ten cigarettes is equivalent to smoking one cigarette. Consequences of this passive smoking are not negligible. Two studies, one Japanese and one Greek, have shown that the risk of lung cancer in wives of smokers is twice that in non-smoking women married to non-smokers, even though various American studies seem more reassuring. Another risk of cancer exists in the offspring of mothers who smoked during their pregnancy, with a rate of 14.9 x 10(5) if the mother smoked, versus 11. 4 x 10(5) if she didn't. Experimental rates of cancer in hamster fetuses confirm this risk.
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One of the most used method of medical appliances sterilization uses ethylene oxide. At high concentration, this very reactive product, causes caustic burns of skin and mucous membranes. In one case of acute pulmonary oedema, levels of ethylene oxide in the endotracheal catheter were discovered. This led us to review the toxicological data on this substance. It should be emphasized that the sterilization and the desorption according to simple and precise rules should prevent such acute accidents.
Chemical and immunological basis of hypersensitivity reactions to low molecular weight substances are recalled. Then the authors give examples of directly reactive chemicals as penicillins and some antineoplastic drugs. The possible role of reactive impurities as penicillins and aspirin is also reminded. It is emphazised that some substances induce allergic reactions through their metabolites: such reactions are mostly unforeseeable. The second part of the paper recalls the main clinical manifestations of these allergic hypersensitivity reactions to chemical residues in food. It is finally emphazised that the datas from animal experiments and epidemiological studies could allow a classification of chemical substances according to their potential risk. This would be of great importance to determine which substances may be authorized in food stuffs and/or to specify the maximum allowable concentrations.
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When a new antidepressant is put on the market, everyone is afraid of its possible cardiac effect. The control of unicellular potentials can give an hint about that effect, without being able to assess its severity; the 27 antidepressants commercialized in France have been reviewed. 180 cases of conduction delays from 10,060 overdosage in the Paris poison center were found, 7 times more often than with other drugs. In addition the 30 centers for monitoring of side effects of drugs have collected 38 cardiac side effects, as well arrhythmias or conduction disturbances.
The cost of adverse drug effects first began to be analyzed in the 1960s, with an evaluation of related admissions to hospital in the USA. The average cost per patient of adverse events requiring hospitalization in France was estimated at 6,250 F in neurology units in 1979/1980, and 14,920 F in geriatric units in 1984. Fifty per cent of these events were avoidable. A second approach is to measure the cost of certain iatrogenic manifestations, e.g. fever due to fipexide, stenosis and perforation of the small intestine due to potassium chloride, gastrointestinal bleeding due to NSAIDs, kidney damage due to aminosides, etc. Calculations of the economic impact of adverse drug effects must also take into account indirect costs such as loss of productivity. The lack of such studies should not make health care specialists forget the magnitude of the problem.
Aseptic meningitis is a very rare drug reaction involving non-steroidal antiinflammatory agents (ibuprofen and sulindac), antibiotics (cotrimoxazole, trimethoprim, ciprofloxacin) and miscellaneous drugs such as carbamazepine, human immune globulin and muromonab CD3. Meningeal symptoms occur a few hours after drug intake and resolve without sequelae within one or two days after drug withdrawal, mainly in young females with systemic lupus erythematosus or mixed connective tissue disease. Biological findings and radiological investigations are not suggestive of an infectious etiology or rheumatological/neurological disturbances. Diagnosis is simple when recurrent episodes coincide with drug ingestion.
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By November 17, 1989, the MMWR published the 154 first reports of a syndrome consisting of myalgia and eosinophilia (EMS), occurring with the consumption of L-tryptophan containing products (L-TrpCp) and which might represent a new clinical entity. To standardize reporting over the country, the CDC of Atlanta developed the following case definition: 1) a peripheral blood total eosinophil count of more than 1 x 10(9) cells per liter 2) generalized myalgia sufficiently severe to affect a patient's ability to pursue daily activities 3) the exclusion of infections or neoplastic conditions. The FDA then, announced its intention to seek a nationwide recall of all tryptophan containing products, followed by other european countries (UK, Germany, France). In France, a first decree (January 4th 1990) completed by a decree on May 11th confirms this decision for one year. This measure did not concern the medicinal products or some dietary supplements for newborn or young children. Since December 11th, 1989, 24 cases have been reported to the Regional Adverse Drug Reaction Monitoring Centres in France. These cases share the same features as the cases notified previously in the USA: overrepresentation of females, no relationship with the time and the daily intake, clinical similarities to the Shulman syndrome, and unknown prognosis. Now, more than one year after the onset of this illness, it seems that discontinuation of the ingestion of L-TrpCp can resolve or improve the symptoms in most cases, but sometimes the syndrome can persist. The causal relationship between the ingestion of L-TrpCp and this syndrome has been established. Whatever the mechanism for the development of EMS among tryptophan users remains unclear, as well as the role of eosinophilia and the factors for fibroblast proliferation. The epidemic emergence of this syndrome in July 89 raises the possibility of the contamination of tryptophan during the manufacturing process. To confirm this hypothesis, the same unusual peak in HPLC analysis was found both in case-associated L-Trp lots and in implicated-japanese manufacturer L-Trp lots in USA. But this would not explain the previous EMS reports before this contamination. Other hypotheses consist an inabnormality of tryptophan metabolism and/or an autoimmune process.
All the requests (162) from the 1st to the 31th of december 1988 (a period of one month) are analysed by the Paris Fernand-Widal ADR Monitoring Centre. The requests are classified as following: 74 pharmacological consults (39 about pregnancy, 9 for breast-feeding, 3 neonates or children, 2 about G6PD deficiency, 3 guide-lines after a therapeutic error, 3 requests for treatment of ADR, and 15 miscellaneous). 5 ADRs notified and reported to an other nearest Centre to the caller and 3 diagnosed latter as an ADR 49 ADRs registered turn to a request because of lack of information (age: 15; sex: 18; name: 1; address: 31,) or faithfullness (4) or several reasons (18). 31 general information about drugs. Usually, physicians request the Monitoring Centre but recently patients request directly the Centre; specially during pregnancy. The progressive number of the questions makes computerization necessary. A single system appears to be essential for all the Regional Centres to improve the quality of the answer and for the new ADR's alert.
One hundred and eighty six cases of amineptine abuse were reported to the Regional Centres of Pharmacovigilance or to the Laboratory Eutherapie during a ten year period, between 1978 and february 1988. The analysis was carried out on 155 cases. The principal characteristics of overconsumption are: a predominance of females; the existence of risk factors in 2 out of 3 cases; the absence of correlations between the prescribed dosage, the duration and the importance of abuse; the constant search of a psychostimulant effect; a good clinical acceptability in most cases, but the risk of acne and psychic disturbances must be emphasized; withdrawal difficulties, obtained in only 48 patients (for at least one month). Psychic symptoms on withdrawal were variable and it was not possible to identify a syndrome. The risk of abuse seems to be rare, nevertheless, one must know this occurrence and respect the recommanded dosage. In patients with certain psychiatric illnesses, and especially in patients with risks factors, drugs with stimulant properties should be prescribed with caution.
The assay by immunoenzymatic method of the blood level of digoxine in 150 old people, (m = 79 years), hospitalized during one year shows a level of more than 2 ng/ml in 31 of them, (m = 2.91 ng/ml). However, the dosage is normal or low, m = 0.206 mg/j. A renal impairment often discussed is not the mechanism: 17 patients with a blood creatinine over 135 mumol/l have a mean blood level of digoxine of 2.98 ng/ml for 2.91 in the 14 another ones without renal impairment. Physicians should be still more cautious when prescribing digoxin.
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Since 1984, the use of the official method for determining the responsibility of drugs in side-effects has been compulsory in France. This method offers, but does not define, different qualificatives for chronological and semeiological criteria. Consensus workshops have been set up to define the undesirable side-effects themselves and the different qualificatives in each of the principal fields of pathology. As regards drug-induced interstitial pneumonia, chest specialists from university hospitals, members of the national system of pharmacovigilance and representatives of the Roussel-Uclaf central department of pharmaco-vigilance have determined: the limits of time elapsed between the beginning and end of drug administration and the occurrence of the adverse reaction; how to interpret various courses of the side-effect with and without temporary discontinuation of the drug, and how to interpret a possible readministration. A list of investigations aimed at excluding the main possible causes of interstitial pneumonia has been drawn up.
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