[Risk of deep venous thrombosis during an air flight: prevention and counselling at the counter]. / Le risque de thrombose veineuse profonde lors d'un voyage en avion : prévention et conseil à l'officine.

Worldwide air traffic reaches about 2.3 billion passengers per year. The increasing number of persons at thrombo-embolic risk, together with potentially severe or fatal complications of deep venous thrombosis, suggests community pharmacists can give basic preventive advice to persons identified as at risk.

[Acute myocarditis and eosinophilic pneumonia: good outcome after medical treatment and long-term follow-up]. / Myocardite aiguë et pneumopathie à éosinophiles: évolution favorable après traitement médical et suivi à long terme. A propos d'un cas.

The authors report a case of acute eosinophilic myocarditis (AEM) with acute left ventricular failure preceded by an acute hypoxaemic eosinophilic pneumonia. The diagnosis of myocarditis was confirmed histologically. That of the eosinophilic pneumonia was base on the abundance of eosinophilic polynuclear cells in the bronchoalveolar lavage and appearances on computerised tomography. The pulmonary lesions rapidly and definitely regressed and complete recovery of left ventricular function was obtained by long-term steroid therapy. This favourable outcome has been sustained after 11 years of follow-up despite the presence of chronic mild hypereosinophilia. In the absence of specific clinical and paraclinical data, the diagnosis of AEM was based on the demonstration of an inflammatory infiltrate rich in polynuclear eosinophils and necrotic myocardial lesions. This histological signature may be obtained in vivo by endomyocardial biopsy, the indication of which must be rapidly recognised. Only the instauration of early and intensive steroid therapy seems to influence the outcome which is frequently poor. The synthesis of the anatomo-clinical and experimental data suggests a myocardial aggression by cytotoxic effects of granular protein components released during activation of polynuclear eosinophils. The role of AEM is discussed in the different aspects of cardiac hypereosinophilia.

[Chronic tropical pancreatitis: a case report]. / La pancréatite chronique tropicale: à propos d'un cas.

The purpose of this report is to describe a case of tropical calcific pancreatitis (TCP). This disease is specific to tropical regions and constitutes the main cause of chronic pancreatitis in children worldwide. It can also be observed in young adults (2nd and 3rd decade). Shortage of dietary lipids during childhood has been implicated in the development of TCP and mutation of the SPINK1 gene has been cited as a predisposing genetic factor. The underlying pathophysiology of TCP is the same as chronic calcific pancreatitis (CCP) due to alcohol abuse. The main features are a sex ratio of 1, absence of alcohol consumption, occurrence of childhood diabetes in one third of cases, low incidence of acidoketosis, and presence of macro-calcifications especially in ducts. In 10% of cases TCP is complicated by pancreatic carcinoma occurring at an early age, located mainly in the body and tail of the pancreas, and having a less favorable prognosis than primary cancer. Treatment of patients with TCP is the same as for patients with CCP due to alcohol abuse. Prevention depends on improvement of nutritional status of the population.

The effects of antimalarial drugs on ventricular repolarization.

Cardiotoxicity has become a major concern during treatment with antimalarial drugs. Lengthening of the QTc and severe cardiac arrhythmia have been observed, particularly after treatment with halofantrine for chloroquine-resistant Plasmodium falciparum malaria. The purpose of this prospective study was to evaluate whether antimalarial agents alter dispersion of the QTc and ventricular repolarization dynamicity. Sixty patients with uncomplicated falciparum malaria were randomly allocated in four groups of 15 patients and treated with quinine, mefloquine, artemether, or halofantrine at recommended doses. Patients in treatment groups were compared with a group including 15 healthy controls with no history of malaria and/or febrile illness within the last month. QTc dispersion was measured on surface electrocardiograms. Repolarization dynamicity was analyzed from Holter recordings, which allow automatic beat-to-beat measurement of QT and RR intervals. Plasma drug concentration was determined by reversed-phase high-performance liquid chromatography. No change in QTc dispersion was observed after treatment with quinine, mefloquine, or artemether. Treatment with halofantrine was followed by a significant increase in QTc dispersion at 9 hours (P < 0.0001) and 24 hours (P < 0.01). Assessment of QT heart rate variability by QT/RR nychtohemeral regression slope demonstrated no significant difference between the artemether (mean +/- SEM = 0.170 +/- 0.048), mefloquine (0.145 +/- 0.044), and the control groups (0.172 +/- 0.039). A significant decrease in the Q-eT/RR slope was observed in the quinine group compared with the control and artemether groups (0.135 +/- 0.057; P < 0.04). With halofantrine, a significant increase in the QT/RR regression slope (0.289 +/- 0.118) was observed (P < 0.0002). QTc interval, QT dispersion, and QT regression slope were significantly correlated with halofantrine and quinine plasma concentration. Mefloquine and artemether did not alter ventricular repolarization. Quinine induced a significant decrease in QT/RR slope of the same order of magnitude as those previously observed with quinidine. Both QTc dispersion and QT/RR slope were significantly modified by halofantrine. These repolarization changes were related to a class-III antiarrhythmic drug effect and may explain the occurrence of ventricular arrhythmia and/or sudden deaths reported after halofantrine intake.

[Mechanism of action of antimalarials. Value of combined atovaquone/proguanil]. / Les modes d'action des antipaludiques. Interet de l'association atovaquone-proguanil.

Determining the mode of action of different antimalarial drugs at the cellular level is essential to optimizing their use and to understanding the mechanisms underlying plasmodial resistance. The main targets for antimalarial drugs in Plasmodium falciparum have been the food vacuole and mitochondrial system. A new target is recently discovered organelle named the apicoplast. The apicoplast is the site of a number of metabolic pathways crucial to the survival of the parasite. It may also be involved in DNA replication and transcription. Antimalarial drugs are classified into three groups according to site of action, i.e., drugs that act on the food vacuole, drugs that block metabolic synthesis and oxidative processes, and drugs that interfere with membrane processes. Knowledge of these sites of action has enabled identification of new drugs with the most promising potential for development. Current antimalarial strategies prioritize combination therapies such as atovaquone/proguanil or artemether/lumefantrine and prolonged treatments to limit the risk of inducing drug resistant Plasmodium.

Malaria prophylaxis in the French armed forces: evolution of concepts.

Malaria is still a serious public health problem in the world and control remains a major priority for the approximately 25.000 French troops deployed, mostly on permanent assignment, in malaria transmission regions. Epidemiological surveillance of malaria provides data necessary to assess morbidity, monitor changing patterns of Plasmodium falciparum drug-sensitivity, and evaluate the efficacy of malaria control measures. About 540 cases were observed in 1999 for an incidence of 4.1 p. 100 men. year. Since 1991, strong emphasis has been placed on prophylaxis. In addition to vector control measures and individual protection against mosquito bites (impregnated bednets, protective clothing, application of repellents, and indoor insecticide spraying), drug prophylaxis has been recommended using a combination of 100 mg of chloroquine and 200 mg of proguanil chlorhydrate (CQ + PG) in a single capsule manufactured by the French Health Army Service. Initially this policy led to a significant decrease in malaria cases among French soldiers. However the incidence of malaria rose in 1995 and 1996. This recrudescence was attributed to poor compliance with chemoprophylaxis and to the declining efficacy of the CQ + PG combination. In response to these problems, a new policy was implemented especially in countries where cycloguanil-resistant Plasmodium falciparum incidence rate is increasing. The new chemoprophylactic regimen calls for a personal prescription of mefloquine. Doxycycline monohydrate is used in case of mefloquine contra-indication or intolerance. Combination of CQ + PG delivered in a single capsule remains a suitable chemoprophylactic regimen in Sahel countries as well as Horn of Africa.

[Buerger's disease and coronary disease]. / Maladie de Buerger et atteinte coronaire.

The authors report the case of a 33 year old man with distal occlusive arterial disease diagnosed as Buerger's disease, with two previous transient ischaemic attacks and coronary disease resulting in myocardial infarction. Coronary angiography showed narrowing of the second segment of the left anterior descending artery, occluded distally and not suitable for revascularisation. The observation of coronary artery disease is very rare in Buerger's disease and data of coronary angiography are very sparse in this context. The occurrence of myocardial infarction and the angiographic appearances of the left anterior descending artery raise the question of coronary involvement of Buerger's disease.

[Salmonella aortic valve endocarditis presenting with rupture of a femoral artery mycotic aneurysm]. / Anévrisme mycotique fémoral rompu, révélateur d'une endocardite aortique à salmonelle.

The incidence of Salmonella enteritidis infections has greatly increased over the last few years. Cardiovascular are amongst the most severe extra-digestive complications. The authors report a case of Salmonella enteritidis presenting with rupture of a femoral artery mycotic aneurysm in a chronic alcoholic patient. Salmonella enteritidis was isolated from blood cultures and the operation specimen after the obligatory limb amputation. The outcome was finally favourable after appropriate antibiotic therapy with a residual, stable grade 3 aortic regurgitation. This rare condition is generally observed in immuno-compromised subjects and carries a high mortality (40 to 70% of cases). The initial infectious signs may be masked, and, in these cases, rupture of an aneurysm is often the mode of presentation. Rapid treatment is essential with, ideally, resection of the aneurysm with reestablishment of arterial continuity and adapted, prolonged antibiotic therapy.

The comparative efficacy and tolerability of CGP 56697 (artemether + lumefantrine) versus halofantrine in the treatment of uncomplicated falciparum malaria in travellers returning from the Tropics to The Netherlands and France.

CGP 56697 (Riamet) is a new oral anti-malarial drug composed of artemether and lumefantrine (benflumetol) which combines the fast, short-acting artemether for rapid parasite clearance with the prolonged action of lumefantrine for intended radical cure. In this double-blind, comparative trial, the efficacy and tolerability of CGP 56697, given as a course of 4 x 4 tablets over 48 h, was compared to halofantrine, given as 3 x 2 tablets over 12 h with a second course 1 week later. Patients (mostly non-immune) with acute, uncomplicated Plasmodium falciparum infection were randomly assigned to either CGP 56697 (n = 51) or halofantrine (n = 52). CGP 56697 proved superior with respect to parasite clearance time (median 32 vs. 48 h, P < 0.001) and parasite reduction at 24 h (median 99.7 vs. 89.6%, P < 0.001) with a non-significant difference in resolution of fever (median 24 vs. 32 h, P = 0.835). However, a 28-day cure rate of 82% was observed for CGP 56697 and 100% for halofantrine. Significant QTc prolongations (> 30 ms) were seen 6-12 h after halofantrine intake but not after CGP 56697 intake. CGP 56697 is an effective, well-tolerated treatment for uncomplicated falciparum malaria but for this dosing regimen the recrudescence rate is unacceptablyhigh (18%). For travellers contracting malaria abroad, we propose a six-dose regimen of CGP 56697 over 3 days.

[Simple malaria attack]. / Accès palustre simple.

The clinical presentation of malaria is, in most of cases, a malaria attack. It occurs in 90% of imported cases in France within 30 days after return of endemic area. Characteristic malaria paroxism have three stages: chills, high fever (> 39 degrees C) and sweating stage. In this typical form, parasitaemia is easily disclosed. With the increasing spread of chemoresistance P. falciparum strains, many patients experience non specific symptoms before the onset of paroxysm, often complaining of malaise, headaches, myalgias and anorexia. In some cases temperature did not exceed 38 degrees C and physical examination revealed sometimes liver or splenic enlargement. These atypical presentations can masquerade other diseases such as a viral illness. In those patients blood smears were often negative and malaria diagnosis is carried out only by QBC or parasight test. Treatment of malaria attack needs antimalarial drugs effective against chemoresistant P. falciparum strains. Mefloquine of halofantrine can be delivered with the respect of guidelines prescription, given major side effects observed with these drugs (neuropsychiatric disorders with mefloquine and cardiac arrhythmias with halofantrine). Oral quinine sulfate can be used when the above drugs are not allowed.

[Aorto-coronary dysplasia and pseudoxanthoma elastica]. / Dysplasie aorto-coronaire et pseudoxanthome élastique. A propos d'un cas.

The authors report the case of a 50 year old man with pseudowanthoma elastica with a history of myocardial infarction and severe aortic regurgitation. Angiography showed multiple coronary artery aneurysms and aneurysmal dilatation of the aortic annulus. The outcome after triple coronary bypass surgery with aortic valve replacement in a valved Bentall conduit was favourable. Pseudoxanthoma elastica is a rare condition in which the prognosis depends on the degree of vascular involvement. In this context, coronary artery aneurysms and aneurysmal dilatation of the aorta are rare complications.

[Heart rate variability and vagal syncope in the young adult]. / Variabilité sinusale et syncope vagale chez l'adulte jeune.

Heart rate variability is a sign of sympathetic activity. The authors compared two study populations of young males aged 19 to 30 years: population T comprised 15 healthy volunteers who had two negative tilt tests, one under basal conditions and the other after a bolus of isoproterenol; population S comprised 12 patients without cardiac or other disease, who were followed up for malaise and in whom the basal tilt test was positive, confirming the vagal origin of syncope. Temporal and spectral (total power, low frequency 0.04-0.15 Hz, hight frequency 0.16-0.40 Hz) data was obtained concerning heart rate variability from 24 hour Holter monitoring. The main difference between the two study populations was in the temporal data over 24 hours especially with respect to the heart rate (T = 73.5 +/- 6.9; S = 65.4 +/- 6.2/min; p = 0.004) and the percentage of successive R-R intervals varying by more than 50 ms (PNN 50) (T = 20.2 +/- 8.3%; S = 30.7 +/- 10.2%; p = 0.024). At night, the lowest SDANN/5 (standard deviation of RR intervals over periods of 5 minutes) were observed in group S (67.2 +/- 16.7 ms vs 87.3 +/- 24.4 ms; p = 0.026). No statistically significant differences between the two groups was observed in the spectral data. The temporal data of heart rate variability on Holter ECG monitoring over 24 hours could therefore have a good predictive value of the vagal origin of syncope in young adults.

Tilt table testing of young adult patients: improved speed and sensitivity using an isoproterenol bolus and a continuous 60 degrees tilt.

The tilt table is a diagnostic device used to induce vagal syncope and determine etiology. Sensitivity enhancing techniques, such as the administration of isoproterenol, can be applied to children and young adults to compensate for the otherwise low sensitivity (20%-30%) observed in that population. This study describes an improved test that offers a simplified approach while decreasing the amount of time involved by up to 50%, without compromising sensitivity. This 45-minute procedure relies on sensitization with isoproterenol administered as a 2- to 80 micrograms bolus instead of a continuous infusion. The isoproterenol is injected at the 30th minute of a 45-minute 60 degrees tilt test without returning the patient to the supine position. In this study, the isoproterenol bolus tilt test was found to be "positive" in 24 of 30 patients reporting unexplained syncope: 10 cases before the 30th minute (11.2 +/- 8.4 min) and 14 cases after administration of 5.1 +/- 1.9 micrograms of isoproterenol.

[The heart and the eosinophil]. / Le coeur et l'eosinophile.

The beneficial effects of polynuclear eosinophils (PE) are well known. However, under certain circumstances, PE can be harmful. The heart is a prime target for PE toxicity which is due to release of basic proteins by eosinophils including major basic protein, cationic protein, and peroxidase. The most common manifestation of PE toxicity is chronic parietal endocarditis (CPE) which regroups two entities: Loeffler's fibroplastic endocarditis and Davies' endomyocardial fibrosis. Loeffler's fibroplastic endocarditis occurs mainly in temperate climates. Patients present high, persistent eosinophil levels similar to those observed in essential hypereosinophilic syndrome (EHS) or Chusid syndrome. Davies' endomyocardial fibrosis occurs in tropical countries where eosinophilic helminthiasis are endemic. The incidence of eosinophilic myocarditis (EM) is low but probably underestimated. EM can be observed in any case involving PE and has been described in many cases of drug-induced atopy, in Churg and Strauss syndrome, and in EHS. The most common cause of death is short-term occurrence of cardiogenic shock or dilated hypokinetic cardiomyopathy. Some patients have been successfully treated by early, intensive corticosteroid therapy and/or heart transplantation. The nosological classification of EM and CPE remains controversial. The two disorders may form a continuum with CPE as the second phase. Other authors have suggested that EM and CPE result from the action of PE on two distinct targets, i.e. endothelial cells for EM and myocytes for CPE. In the future, it may be possible to identify subjects with a predisposition to PE-induced heart disease by studying of genes coding for interleukins (IL-5, IL-4, IL-3) and GM-CSF in the 5q31-q33 region of chromosome 5.

[Acute eosinophilic myocarditis: a diagnostic and therapeutic emergency]. / La myocardite aigue a eosinophiles: une urgence diagnostique et therapeutique.

This report describes three histologically documented cases of acute eosinophilic myocarditis. These three cases illustrate the different clinical and therapeutic outcomes of this disease which can range from full recovery under prolonged corticosteroid treatment to requirement for emergency heart transplantation or death due to intractable cardiac insufficiency. In absence of specific clinical or laboratory data, diagnosis must be established in vivo by endomyocardial biopsy demonstrating eosinophil-rich inflammatory infiltration and necrotic lesions. Rapid decision-making is necessary to allow early initiation of intensive corticosteroid treatment without which the most likely outcome is death. Clinicopathological and experimental evidence suggests that acute eosinophilic myocarditis is caused by the cytotoxic effects of granule components (mainly major basic protein) released by activated polynuclear eosinophils.

[Diagnostic and treatment of hypereosinophilia upon return from the tropics: 102 patients]. / Diagnostic et traitement des hypereosinophilies sanguines au retour des tropiques: a propos de 102 patients.

Management of blood eosinophilia in travelers returning from the tropics is controversial. In this prospective study, 102 asymptomatic tropical travelers underwent investigation and treatment for hypereosinophilia. In contrast with direct tests for parasitic infection which were positive in only 15% of cases, immunological tests were suggestive of helminthic infection is 77%. The most common diagnoses were toxocarosis (49%), strongyloidiasis (30%), and filariasis (19%). Anti-parasite treatment was undertaken based on laboratory findings (12 cases) or on presumptive diagnosis using two-agent therapy (ivermectin and praziquantel) in 13 cases or three-agent therapy (ivermectin, praziquantel, flubendazole) in 77 cases. As a result of treatment, eosinophil count returned to normal in 61% of cases and decreased in 30%. These findings suggest that presumptive treatment of blood eosinophilia can be undertaken in tropical travelers using three anti-parasitic drugs: ivermectin (1 x 0.4 mg/kg), flubendazole (2 x 100 mg per day for 3 days), and praziquantel (1 x 40 mg). As a precaution before using ivermectin, tests should be performed to detect loiasis which can lead to adverse reactions.