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Churg-Strauss syndrome (CSS) is a disorder characterised by hypereosinophilia and systemic vasculitis complicating a preexisting asthma. Twenty cases have been studied. Mean duration of asthma before CSS was 8 years, the peripheral-blood eosinophilia, always > 1,700/microL, went above 5,000/microL in 17 cases. The clinical manifestations were the following: 20 impairements of general state with fever, 13 peripheral neuropathies, 15 cutaneous injuries, 10 pericardial or myocardial attacks, 10 digestive impairements, 9 muscular and articular diseases, 7 renal diseases--all of them linked with the vasculitis--and 9 upper respiratory tract involvements. Pleuropulmonary or cardiac anomalies have been discovered at the chest X-ray in 14 cases. The diagnosis has been histologicaly confirmed in 15 cases. No clinical or biological or evolutive distinction was noticed between the 15 positive biopsy patients and the 5 negative ones. During 8.4 (+/- 7.9 years) the evolution was caracterised by relapses which have always been announced by increasing eosinophilia. Eighteen patients have been successfully treated with corticoids alone or associated with cyclophosphamid in 9. Survival at 5 years was 85%. Five deaths occured because of CSS (2 because of an unadapted treatment). We have to focus the need for an emergency treatment of CSS. The diagnosis can be done by clinical investigation only, before any anatomopathologic results.

Background: Even in patients with Behçet's disease, disease, the development of severe aphthosis should suggest the possibility of a drug reaction., Case Report: We observed a case of giant lingual aphthosis that developed four months after adding microrandil to the regimen of a patient with Behçet's disease who had been treated with colchicine for 16 years. The aphthosis healed after withdrawal of nicorandil., Discussion: There have been 21 cases of nicorandil-induced buccal aphthosis reported in the literature. All healed at drug withdrawal. He delay between initiation of treatment of the stomatitis in most patients, the development of the aphthosis after increasing he nicorandil dose in two patients, its regression after reducing the dose in one and pathology date from biopsied cases suggest a dose-dependent toxic mechanism rather than an immunoallergic process is involved. To our knowledge, our case is the first reported with Behçet's disease. In our opinion, nicorandil should not be given to patients with Behçet's disease.

We report three personal cases of hydrocarbide aspiration pneumonia. High-viscosity non-volatile hydrocarbides (paraffin oil, for instance) cause often pseudotumoral exogenous fat-aspiration lung disease. Low-viscosity volatile hydrocarbides (petroleum, gasoline, white spirit, for instance) cause acute pseudo-infectious lung disease with dyspnea and fever which usually resolves within a few weeks but which may also be life-threatening. Purely symptomatic treatment has greatly progressed with advances in intensive ventilatory assistance. Gastric emptying with emetic agents or lavage procedures is dangerous and must be avoided except for exceptional cases. When required, the airways must be protected with tracheal intubation. Volatile hydrocarbides should be stored in protected areas in containers with safety stoppers which children cannot open.

Withdrawal syndrome after discontinuing serotonin re-uptake inhibitors, especially paroxetine, is largely unknown to most physicians. Variable incidence has been reported. Our aim was to stress the main clinical features of this syndrome. Serotonin re-uptake inhibitor withdrawal syndrome generally begins within 24 to 48 hours after discontinuing the drug. Signs reach their maximum on day 5 and usually resolve within 2 to 3 weeks. Withdrawal syndrome is more common with short half-life drugs (paroxetine, fluvoxamine). The intensity of the clinical signs depends on the daily dose and how long the drug has been given. The main signs are dizziness, vertigo, headache, nausea, and flu-like symptoms as well as anxiety, confusion, irritability, excessive dreaming and insomnia. Risk factors usually stressed are poor treatment compliance, previous withdrawal syndrome with another drug, concomitant medication and alcohol consumption. The syndrome can be prevented by tapering off the dose and patient education. When a withdrawal syndrome is present, it is advisable to reintroduce the drug then withdraw gradually.

Drugs are a very common cause of gynecomastia and should always be entertained as the possible causal agent of such a condition. This drug side-effect is due to an impaired balance in the serum estrogen/serum androgen ratio, whatever the mechanism, or a rise in prolactin level. Sex hormones, antiandrogens, are frequently involved as well as spironolactone, cimetidine, verapamil and cancer chemotherapy (especially alkylating agents). Diazepam, tricyclic antidepressants, neuroleptics, calcium channel blockers, captopril, digitalis glycosides, omeprazole, some antibiotics and growth hormone are all possibly, but less often, the responsible agent. Criteria of the French method for determining drug causality are discussed.

The effect of hyperthyroidism on the short-term memory variability of blood pressure and heart rate was evaluated in 12 untreated hyperthyroid patients during thyrotoxicosis and after a 6 1/2 month treatment designed to achieve a stable euthyroid state. Beat-by-beat finger blood pressure was measured with a Finapres device. The pulse interval, from which pulse rate was derived, was obtained from the blood pressure signal. Due to the significant change in heart rhythm associated with thyrotoxicosis, both pulse interval (taken as a surrogate of heart period) and pulse rate (taken as a surrogate of heart rate) were computed. Power spectral analysis showed a reduction in the overall heart period variability in the supine position in the hyperthyroid compared to the euthyroid state. This effect was observed in the low-frequency (0.005-0.068 Hz), mid-frequency (0.068-0.127 Hz) and high-frequency (respiratory) domains as well, with a significant reduction of the modulus of these bands of 31%, 35% and 47%, respectively. The heart rate spectral modulus also exhibited a reduction of the high-frequency component (31%) in the supine position in the hyperthyroid subjects. These changes in heart rhythmicity corroborate a vagal deficit in hyperthyroidism. In addition, blood pressure spectral power exhibited a significant deficit in the orthostatism-induced mid-frequency systolic blood pressure rise in the hyperthyroid state (64%) compared with the euthyroid state. This observation may reflect a reduced vascular sympathetic activation with standing. The resulting vasodilatation could well contribute to normalize blood pressure in thyrotoxicosis in which cardiac output is increased.

The combination of lysine acetylsalicylate and metoclopramide is effective in the treatment of migraine attacks. It was unknown whether repeated doses could improve efficacy. The aim of this open trial was to evaluate the effects of a second, and eventually a third dose of lysine acetylsalicylate and metoclopramide when a first dose of the treatment was ineffective. Patients were asked to take a second dose 2 hours after a first dose when they thought that the first dose was ineffective. They were allowed to take a third dose or their rescue medication 2 hours after the second dose when they judged that the treatment remained ineffective. Two hundred ninety-two patients were included in the study; 262 of the 292 patients treated 517 attacks. Headache relief (reduction in headache severity from grade 3 or 2 to grade 1 or 0) was observed in 54.8% of attacks after one dose, in 48.1% of attacks after a second dose, and in 40.3% of attacks after a third dose. Complete headache relief without recurrence and without use of a rescue medication was reported in 37% of the total attacks. The patients judged their treatment as good or excellent in 78% of attacks treated with one dose, in 41% of those treated with two doses, and in 19% of those treated with three doses. Tolerance, as judged by the patients, was considered good in 92% of treated attacks. Minor side effects occurred in 6% of attacks after a first dose, in 4.5% of attacks after a second dose, in 1.5% of attacks after a third dose, in 2% after unspecified delay, and in 14% overall. In conclusion, the efficacy of lysine acetylsalicylate and metoclopramide in the treatment of migraine attacks can be improved by repeated doses. It is well tolerated.

There have been recently a prescription error and a dispensing error in our department due to drug names which look or sound alike. Errors of this type have frequently been quoted in the Anglo-Saxon literature. The method of choosing a drug trade name is recalled, and a table of French drug names which can involve errors of prescription and dispensing errors is provided.

Elderly people are particularly at risk for drug interactions, for several reasons. They are the part of the population who consume the most drugs: over 75 years the mean number of drugs on a prescription is 5.6. As they suffer from various associated diseases, they see several medical specialists, each of them adding a new prescription to the others. Self-prescriptions complicate the problem because they are rarely mentioned. Changes in pharmacokinetics in the elderly tend to increase blood concentrations of drugs. Elderly people suffer from altered homeostatic mechanisms to compensate for adverse drug effects. As a whole, such individuals are more exposed to the side effects of drugs. The drugs most often involved in these interactions are diuretics, non-steroidal anti-inflammatory drugs, benzodiazepines, antiarrhythmics, cardiac glycosides, antihypertensive drugs, oral antidiabetics and antalgics. The clinical accidents most often occurring with these drug interactions are: malaise, orthostatic hypotension, loss of conciousness, amnesia, confusion, renal insufficiency, digestive problems. Since elderly people are less likely to recover easily, this problem of drug interaction should be looked for systematically.

The evaluation of the rate of gastroduodenal toxicity of anti inflammatory drugs is a difficult problem. We tried to analyse that question by studying the general endoscopic registers of the Gastro-Enterologic department of the hospital. This retrospective study concerns 2,945 endoscopies performed during the year 1988 and 1992 randomly chosen among the last 5 years. 992 results show injuries suggestive of non steroidal anti inflammatory drugs (NSAID) toxicity, however only in 65 cases the potential role of an anti inflammatory drug is mentioned: 36 men and 29 women, mean age: 50.6 +/- 19.6 years. Concerning the drugs, only the pharmacological classes they belong to are mentioned except for Aspirin. Acetyl salicylate acid 7 cases, NSAIDS 36 and Steroids 22. In the drug group 63% of injuries are located to the stomach (ulcers 13%, gastritis 50%), 37% to the duodenum (19% ulcers, 18% duodenitis). Compared to the groups with the same kind of injuries, but without any mention of drugs, there are no statistical difference in the proportion of ulcers. Aging and sex are not influent in our results on the genesis of drug induced ulcers. These results must be discussed because a lot of datas are missing in the registers and so the number of patients taking drugs is probably underestimated. This means that unless a prospective study is held with someone enquiring for all the risk factors, the study of the general endoscopic registers is not a good way to estimate gastrointestinal damages due to drugs.

We report four cases of deep venous thrombosis of the upper extremity, which occurred in two women and two men (mean age 79 years) in whom a pacemaker electrode had been inserted 4 years on averages previously. In three of these four cases phlebitis developed after immobilization of the limb containing the electrode. Deep venous thrombosis of the upper extremity is rare, but 28% of catheterizations are responsible for phlebitis. One to 3% of patients fitted with a pacemaker have symptomatic phlebitis, but these figures rise to 28-65% when phlebography is systematically performed in subjects wearing a pacemaker. The clinical signs are the same as those of the classical forms, and the diagnosis is made by doppler-ultrasonography and by phlebography which informs on the collateral circulation. Cure is obtained with efficient anticoagulant therapy. These cases prompt us to prescribe a preventive subcutaneous heparin therapy in those pacemaker-fitted subjects whose arm is immobilized. The heparin dosage remains to be determined precisely.

A study of 200 patients hospitalized in the Internal Medicine ward for malaise enabled us to specify several clinical features and to estimate the cost of this disorder. Clinical data from our investigation showed that the mean age of patients was 60 +/- 1.7 years, the women were older than the men, and age is an important parameter for orienting examinations which affects the length of hospitalization and increases with it. Among the etiological diagnoses of malaise, the systematic search for orthostatic hypotension is extremely important: it was responsible for 22 of the malaises of which only half were diagnosed in the emergency room. In addition, 12% of our series of malaises were medication-associated. The 200 patients represent 1,300 hospital-days at a total cost of 2,273,000 FF (congruent to US$454,600), and an average cost of 11,660 FF (congruent to US$2330) per malaise, of which 730 FF (congruent to US$145) was paid for complementary examinations. Thus it appears that the "hotel accommodations" part of the bill is the major element. All the complementary examinations ordered during the etiological search do not provide the same information and cost-benefit analysis showed that several simple tests, i.e., ECG, blood-sugar level, blood electropherogram and dosage of toxic substances, led to approximately 75% of the diagnoses; more sophisticated tests, e.g., cerebral computed-tomography scanning, Holter ECG or echocardiography, did not concern more than 25% of the malaises studied.(ABSTRACT TRUNCATED AT 250 WORDS)

Therapeutic drugs are the main cause of postural hypotension, notably in elderly people. This syndrome is harmful as it reduces patients' compliance with treatment and is responsible for severe accidents. Drugs which lower cardiac output by acting on heart rate and cardiac muscle contractility, and drugs which decrease blood volume may produce postural hypotension; diuretics are often responsible for hypovolemia and hypokalaemia. The principal mechanisms involved are interferences of drugs with vegetative blood pressure regulation. They include vasomotor centre depressors (morphine-like compounds, antihypertensive agents, neurosedatives, neuroleptics, antiparkinsonians); ganglioplegics; inhibitors of noradrenaline production (methyldopa, disulfiram) or re-uptake (antidepressants); catecholamine depressors (guanethidine); drugs acting on chromaffin granules (monoamine oxidase inhibitors) and those which inhibit post-synaptic receptors (alpha- and beta-blockers). Drugs which act on vascular smooth muscle tone (nitrites, calcium channel antagonists, angiotensin-converting enzyme inhibitors) occasionally cause postural hypotension. To the actions of these drugs must be added endogenous and exogenous factors and notably physiological ageing of the baroceptor reflex; these factors must be taken into account whenever therapeutic drugs are prescribed.

Beta-blocker eyedrops used on asthmatic patients are known to enhance asthma which is, as chronic bronchitis, an obstructive disease of the lung, and an authentic bronchoconstriction is always possible. A single blind parallel trial in 3 groups of 10 patients with grade II and III chronic bronchitis, was conducted to evaluate the cardiovascular and bronchial tolerance of 3 beta-blocker eyedrops: timolol, betaxolol and carteolol compared to placebo. The following parameters were measured during a 90 minutes period: heart rate, systolic and diastolic blood pressure, forced expiratory volume in one second, vital capacity. It appeared that only heart rate lowers significantly under the influence of the beta-blocker eyedrop, the other parameters did not change and no difference was noticed between the three eyedrops. However, comparison of individual values showed a significant decrease of forced expiratory volume in one second in certain subjects and this, although betaxolol is a beta 1 selective beta-blocker. Caution should be taken each time beta-blocker eyedrops are prescribed for glaucoma to patients with chronic bronchitis.

Changes in heart rate induced by inclining an orthostatic table to 30 degrees and 60 degrees and by standing was studied in 200/healthy volunteers of either sex. Study subjects were divided in eight ten-year age groups, from 16 to 97 years. The 56-65 year age group was the youngest group to develop systolic orthostatic hypotension. This response occurred in 4% of subjects aged 56-65 years and became increasingly prevalent from one age group to the next (25%, 36% and 44%). In some patient, the fall in systolic BP reached 70 mmHg. Systolic hypotension occurred in some patients at 30 degrees but in most cases developed only at 60 degrees. No significant difference was found between the falls in SBP seen at 60 degrees and during active standing (90 degrees), indicating that muscular activity does not play a major role in BP regulation. Diastolic hypotension was less common and was mainly seen in patients above 75 (20%) who also had systolic hypotension. Orthostatism was responsible for tachycardia but this response became increasingly less common beyond 55 years of age (60, 60, 52 and 36% in the four age groups above 55). This reflects increasing loss of sensitivity of the baroreflex with advancing age. These date are useful for comparing the age-specific effects of disease states (e.g. diabetes mellius, alcohol abuse) or treatments (psychoactive drugs, antihypertensive agents).

The pharmacokinetics of a single i.v. dose of dl-bisoprolol 0.16 mg.kg-1 ideal body weight has been studied in 8 obese women (mean weight 91 kg; 161% of ideal body weight) and 8 non-obese women (51 kg; 94% of ideal body weight). Compared to the controls, the obese subjects showed an increase in the total apparent volume of distribution (Vz) (182 vs 1351) and a decrease in Vz per kg body weight (2 vs 2.71.kg-1). There was a negative correlation between Vz l.kg-1 and the percentage of ideal body weight (r = -0.672). Total body clearance was increased, but t1/2 and renal clearance was unchanged. It is concluded that tissue diffusion of bisoprolol in obese subjects is limited, despite its lipophilicity, possibly because of alteration in the blood flow to adipose tissue produced by bisoprolol.

Authors report results of an investigation led in 2 separate departments concerning 200 subjects: --blood donors: they are by definition healthy subjects who regularly are in touch with a medical structure; --patients with acute traumatic pathology leading to bone surgery consultation. The aim of this investigation was to analyse the different parameters involved in self-medication and to compare their distribution. Self-medication has an overall incidence of 87.5% in these studied groups and has generally been lasting from 2 to 9 years. The main reason for it is the lack of gravity to go and see a physician; although 52% of the patients tested take the advise of another person. The clinical signs leading to self-medication are looked for; 468 different drugs are listed essentially antalogics and drugs for ear, nose and throat as well as respiratory tract diseases. Self prescribed drugs usually come from the familial stock. Blood donors have some specific characteristics. In this population self-medication is more frequent and has been lasting longer. They more often feel able to take themselves in charge, but in contrast ask for the chemist's or the doctor's advise more frequently.

Six obese subjects (mean +/- s.d. : 145.1 +/- 16.7% of ideal body weight) were randomly assigned to a single i.v. dose either of (+/-)-propranolol base (0.108 mg kg-1 of ideal body weight) or of (+/-)-sotalol base (1.06 mg kg-1 of ideal body weight). Each subject received the other drug 7 days later. Pharmacokinetic parameters were compared with those obtained previously in non-obese control subjects. In obese subjects, the pharmacokinetic data calculated for sotalol were comparable with those measured in controls (total body clearance = 9.4 +/- 2.9 L h-1; volume of distribution during the terminal phase = 79.8 +/- 19.8 L or 0.9 +/- 0.2 L kg-1; terminal half-life = 6.2 +/- 1.6 h). For propranolol, total clearance (44.3 +/- 15.9 L h-1) and volume of distribution (230.5 +/- 48.2 L or 2.7 +/- 0.7 L kg-1) were significantly less than control values. The terminal half-life (3.9 +/- 1.1 h), was not significantly increased. These results could be explained by altered tissue blood flow and a decreased metabolic capacity of the liver in obese subjects.

The beta 1- and beta 2-adrenoreceptor blockade by means of the systemic diffusion of three beta-blocker eyedrops--timolol, carteolol, and betaxolol--was evaluated in a randomized, single-blind, three-way crossover study in 18 volunteers. The blockade was evaluated by analyzing the variations of the beta 1- and beta 2-blockade effects of isoproterenol before and after instillation of one drop in each eye. The beta 1-blockade effect was judged on the variation of heart rate, and the beta 2-blockade effect was judged on the change in peripheral blood flow measured by veno-occlusive plethysmography. Comparison of the blockade by these drops showed that carteolol and timolol totally inhibited the beta 1 and beta 2 effects of a dose of isoproterenol able to increase heart rate by 50% (placebo eyedrops were used as a control). Betaxolol differ significantly because it allowed the same effects with the same dose of isoproterenol. Intensity of the blockade was measured by comparison of the effective doses of isoproterenol. Carteolol and timolol were shown to be four times more inhibitory.