In silico models for predicting vector control chemicals targeting Aedes aegypti.

Human arboviral diseases have emerged or re-emerged in numerous countries worldwide due to a number of factors including the lack of progress in vaccine development, lack of drugs, insecticide resistance in mosquitoes, climate changes, societal behaviours, and economical constraints. Thus, Aedes aegypti is the main vector of the yellow fever and dengue fever flaviviruses and is also responsible for several recent outbreaks of the chikungunya alphavirus. As for the other mosquito species, the A. aegypti control relies heavily on the use of insecticides. However, because of increasing resistance to the different families of insecticides, reduction of Aedes populations is becoming increasingly difficult. Despite the unquestionable utility of insecticides in fighting mosquito populations, there are very few new insecticides developed and commercialized for vector control. This is because the high cost of the discovery of an insecticide is not counterbalanced by the 'low profitability' of the vector control market. Fortunately, the use of quantitative structure-activity relationship (QSAR) modelling allows the reduction of time and cost in the discovery of new chemical structures potentially active against mosquitoes. In this context, the goal of the present study was to review all the existing QSAR models on A. aegypti. The homology and pharmacophore models were also reviewed. Specific attention was paid to show the variety of targets investigated in Aedes in relation to the physiology and ecology of the mosquito as well as the diversity of the chemical structures which have been proposed, encompassing man-made and natural substances.

Synthesis and evaluation of new lipomonosaccharide-imprinted polymers as MISPE supports.

Molecular imprinted polymers (MIP) were prepared by the copolymerization of styrene (S) or methyl methacrylate (MMA) and methacrylic acid (MAA) using ethylene glycol dimethacrylate (EGDMA) as the crosslinker with molar ratios of [monomer]/[crosslinker] and [MAA]/[template] of 3:7 (to obtain a rigid structure) and 1:6 (to optimise hydrogen interactions), respectively. The polymerizations occurred in presence of the template molecule (MIP) - GlcNcouma - an amphiphilic monosaccharide. The same materials, non-imprinted polymers (NIP), were also prepared in absence of the template. These MIPs were characterized and used as SPE supports for selective enrichment. The results showed the correlation between retention efficiency and the porogen character of the polymerization solvent.

Epidemiology of poisoning in children: a 7-year survey in a paediatric emergency care unit.

Acute poisoning in children is still a major public health problem, and represents a frequent cause of admission in emergency departments. We carried out an epidemiological study of poisonings leading to admission to a paediatric emergency care unit (PECU). We analysed data from 2988 children who were admitted to the PECU of Bordeaux, France with acute poisoning from 1989 through 1995. During the 7-year period, the poison exposure numbers decreased slightly from 490 to 382 (6% vs. 3% of total medical emergencies). This represented a mean annual incidence of 1.4 poison exposures per 1000 children younger than 18 years of age and living in Bordeaux and its surroundings. Characteristics of the study population, circumstances of poisoning and substances involved were similar to those previously described. Eighty per cent of children were younger than 5 years of age, presented with a benign course. Forty per cent were not treated and 75% were discharged home either immediately or within 24 hours of admission. Only 1.5% of cases, mainly adolescent girls who attempted suicide, were admitted to a paediatric intensive care unit. Overall mortality rate was 0.33/1000. In children, most cases of acute poisoning are accidental, benign, and mainly attributed to the ingestion of a non-toxic substance. This points to the need for better information of the population on availability of poison control centre calling facilities, in order to decrease the number of admissions to the PECU. Patients suspected of having ingested a potentially dangerous substance can be managed in short-stay observation units, thus avoiding unnecessarily prolonged hospitalization. Acute poisoning in children remains a frequent problem, highlighting the need to develop an education programme on primary prevention in our region.

Guillain-Barré syndrome occurring in two women after ketoacidosic comatose state disclosing an insulin-dependent diabetes mellitus.

We report two women who presented with a Guillain-Barré syndrome just after a ketoacidosic comatose state disclosing an insulin-dependent diabetes mellitus. One had characteristic clinical signs and the other had major motor involvement. At neurophysiologic investigations, one had typical demyelinating neuropathy whereas the second had mainly axonal degeneration. At ultrastructural examination of a peripheral nerve biopsy, features of macrophage-associated demyelination were present in both nerve specimens, thus confirming the diagnosis of acute inflammatory demyelinating polyneuropathy, i.e., Guillain-Barré syndrome. Prominent axonal involvement was also present in the motor nerves of the second patient. Insulin therapy had to be permanently continued and these two cases are quite different from the transient diabetes sometimes observed in certain cases of Guillain-Barré syndrome. Both the latter and insulin-dependent diabetes mellitus probably have auto-immune mechanisms. It is likely that in our two patients both auto-immune diseases were triggered by a common event. Such cases of Guillain-Barré syndrome have to be distinguished from other acute diabetic neuropathies.

[Acute adrenal insufficiency due to bilateral adrenal hematoma following severe thrombopenia induced by low-molecular-weight heparin]. / Insuffisance surrénalienne aiguë par hématome surrénalien bilatéral au décours d'une thrombopénie sévère induite par une héparine de bas poids moléculaire.

BACKGROUND: Bilateral adrenal hematoma is an uncommon cause of acute adrenal insufficiency. An association with thrombopenia induced by low-molecular-weight heparin even more so. Diagnosis is difficult as the clinical manifestations mimic septic shock. CASE REPORT: A 63-year-old woman developed acute adrenal insufficiency due to bilateral adrenal hematoma following severe thrombopenia induced by low-molecular-weight heparin prescribed after an orthopedic operation. Outcome was favorable. CONCLUSION: Acute adrenal insufficiency must be entertained as a possible diagnosis in patients with heparin-induced thrombopenia.

Non-fatal clozapine (LEPONEX) intoxication with toxicokinetic evaluation.

A 29-y-old male attempted suicide with 3000 mg clozapine, 150 mg zopiclone, alprazolam and unknown quantities of alcohol. He was admitted in a deep hypotonic coma with respiratory depression, inhalation pneumonia and vascular collapse. Symptomatic treatment involved mechanical ventilation, vascular filling and antibiotics. The patient was discharged from the Intensive Care Unit 72 h after the suicide attempt with no sequelae. To detect and quantify clozapine in plasma, high-pressure liquid chromatography showed a 4 h absorption phase and a peak serum concentration of 5200 ng/ml. Three successive elimination t1/2 values of 38, 24 and 13 h were calculated.

[Severity of ingestion of caustic substance in children]. / Gravité des ingestions de produits caustiques chez l'enfant.

BACKGROUND: Caustic ingestion is frequent in children, sometimes leading to esophageal stricture. PATIENTS AND METHODS: Between 1988 and 1994, esogastroscopy was performed in 65 children after caustic ingestion. The children were classified in three groups: no lesion (group A), minimal lesions (group B) and severe lesions (group C). Nature of the caustic substance, clinical signs and evolution were compared in the three groups. RESULTS: Median age was 2 years for the 65 children (24 girls, 41 boys). Ingestion occurred at home (94%) during meal periods. Substances were dishwater detergents (n = 14), oven cleaner (n = 10), bleach (n = 9), washing powder (n = 4), others (n = 20), more often in a liquid form (n = 37) than solid (n = 28). Children had no symptoms (57%), presented emesis (n = 20) or abdominal pain (n = 10) not correlated to endoscopic findings, and hematemesis (n = 3) or respiratory distress (n = 4), both symptoms seen only in group C. Buccal lesions (41%) were not correlated to endoscopic findings. After endoscopy, 28 children (43%) were classified into group A and 20 children (31%) in group B. Among the 17 children (26%) of the group C, eight developed an esophageal stricture: seven long strictures requiring replacement of the esophagus, one short stricture requiring repeated dilations. CONCLUSION: Esophageal stricture is still a severe complication after caustic ingestion. These data stress the interest of controlled studies to confirm the preventive role of high dose corticosteroids, and the importance of the prevention of accidental caustic ingestions in children.

Glyphosate herbicide poisoning: use of a routine aminoacid analyzer appears to be a rapid method for determining glyphosate and its metabolite in biological fluids.

Glyphosate containing herbicides are an alternative to paraquat and are widely used throughout the world. Despite animal studies showing a low mammalian toxicity, human fatalities are reported after suicidal ingestions of glyphosate. Among the numerous analytical methods proposed, the reference method is the HPLC Monsanto procedure which is available in very few laboratories. The Monsanto procedure consists of a pre-column derivatization with detection of the resulting chromophore by HPLC with a variable wavelength UV/VIS detector. We propose a simple and rapid method for the diagnosis and monitoring of glyphosate poisoning. This method uses an aminoacid analyzer (Beckman 6300) with the program for biological fluids. With this procedure the glyphosate and amino methyl phosphoric acid retention times are respectively 1.75 and 3.54 min. This method gives a rapid result. The time between collecting the sample and completing the result is 45 min. This method may be useful for the diagnosis and monitoring of glyphosate poisoning and is easy to perform with an apparatus usually available in every laboratory involved in aminoacid analysis.

New in vitro assay based on glucose consumption for determining intraconazole and amphotericin B activities against Aspergillus fumigatus.

We developed a new in vitro method of evaluating antifungal molecules. Fungal growth was determined by measuring glucose consumption, the only carbon source in a synthetic medium. First, the growth of 12 Aspergillus fumigatus strains was studied. Glucose consumption was an excellent indicator of fungal growth. Second, the partial inhibition of growth was calculated in terms of the 90% or 50% inhibitory concentration for the 12 strains after treatment with itraconazole and amphotericin B. With a 3-day incubation time, the calculated 90% and 50% inhibitory concentrations agreed with those obtained by a macromethod and with those reported in previous publications. In each case the high degrees of efficacy of itraconazole and amphotericin B against A. fumigatus were confirmed. Partial inhibition induced by low concentrations of antifungal agents was quantifiable by this new method.

[Ventricular arrhythmia and halofantrine intake. Probable deleterious effect. Apropos of 3 cases]. / Arythmies ventriculaires et prise d'halofantrine. Effet délétère probable. A propos de 3 observations.

Incidence and malignant forms of imported Plasmodium falciparum malaria are increasing, and chemoprevention is more and more replaced by stand-by treatment and radical cure in preventing access on return from malaria areas. Halofantrine is recommended for this radical cure: it's an habitually well-tolerated amino-alcohol with very few side-effects. We report three cases of long QT-interval due to halofantine: three different young women coming back from Africa took halofantrine (500 mg (2 tablets) six hourly for three doses on the first and the seventh day) and all presented with syncopal episodes. Serum electrolyte concentrations and echocardiograms were normal. In one case only, a diagnosis of Plasmodium falciparum malaria was made, without severe manifestations, and in the two other cases, treatment was a radical cure. In two cases, several bursts of torsades de pointes ventricular tachycardia due to halofantrine were proven and electrophysiological cardiac tests concluded that they had a congenital long QT-interval/Romano-Ward syndrome). So far halofantrine cardiac toxicity was unknown with single dose of 24 mg/kg/d. This phenomenon can be very severe in case of preexisting cardiopathy. In spite of the rarity on the congenital Romano-Ward syndrome, systematic electrocardiogram is necessary before giving halofantrine.

[Ceftriaxone and severe infections in medical resuscitation]. / Ceftriaxone et infections graves en réanimation médicale.

Ceftriaxone was used in 24 medical intensive care patients to treat 8 pulmonary infections, 12 septicaemias, 3 urinary tract infections, 1 meningitis. It was administered at a single intravenous dose of 2 g every 24 h. The therapy was successful, clinically and bacteriologically in 16 patients. The reasons of the failures are analysed. Plasma concentrations were obtained: they demonstrate that ceftriaxone is effective when given once a day in most cases.

[Therapeutical study in patients admitted to an emergency unit (author's transl)]. / Essai thérapeutique dans un centre d'admissions et de tri d'urgences (CATU).

In an emergency Unit tiaprid has been used in: acute alcoholism and delirium or pre-delirium states. Good results have been obtained with 200 mg (IV) possibly repeated every twenty minutes.