Absence of nucleotide polymorphism in a Plasmodium vivax multidrug resistance gene after failure of mefloquine prophylaxis in French Guyana.

Vivax malaria is widespread and resistance has been described for chloroquine and sulfadoxine-pyrimethamine. We report on evidence of failure of mefloquine prophylaxis in a French soldier who contracted Plasmodium vivax in French Guyana, South America. Despite regular weekly mefloquine prophylaxis (250 mg/d), the patient presented with a first episode of vivax malaria, which was treated by chloroquine alone, then experienced a second crisis in France. The reappearance of the parasites occurred one day after the end of prophylaxis, confirming parasitological and clinical resistance in a non-immune patient. Mefloquine was detected by a liquid chromatography assay in plasma at a level of 1062 ng/ml, which was higher than the expected concentration after five months of weekly prophylaxis. This isolate had no single nucleotide polymorphisms of the pvmdr1 gene at seven allele positions: pvmdr1 N91, Y189, Y976, S1071, F1076, N1079 and D1291, corresponding to codons 86, 184, 939, 1034, 1039, 1042 and 1246 in P. falciparum. This observation of failure of mefloquine prophylaxis against P. vivax, when added to previously reported chloroquine and atovaquone-proguanil failure, strengthens the case for re-evaluating drug policies for vivax malaria and the need for continuous research on molecular markers of drug resistance.

Clinical evaluation of oscillating positive expiratory pressure for enhancing expectoration in diseases other than cystic fibrosis.

The benefit of chest physiotherapy in patients with cystic fibrosis has been well documented. However, the benefit of similar rehabilitation in patients with large amounts of sputum who have diagnoses other than cystic fibrosis has not been clearly demonstrated. The aim of this study was to evaluate the acute effectiveness of a device advised for home chest physiotherapy in comparison to postural drainage combined with chest percussion in removing secretions in patients with high sputum production due to diseases other than cystic fibrosis. Fourteen in-patients, known to spontaneously produce more than 25 mL sputum.day-1, underwent two sessions each of two treatment modalities in random order. Treatment A consisted of postural drainage and manual chest percussion. Treatment B included breathing through a commercial device claimed to combine oscillating positive expiratory pressure with oscillations of the airflow. Expiratory flows and oxygen saturation were monitored and recorded throughout the study. The amount of sputum produced in the 30 min preceding, during, and in the 60 min after completing each treatment session was recorded, together with the sensation of "chest unpleasantness due to secretions" as assessed by means of a modified visual analogue scale. The mean time that the patients tolerated treatment was not different for A and B (18.7 +/- 5 and 19.3 +/- 5 min, respectively). Sputum significantly increased during both treatment periods and in the same amount for the two modalities (2.9 +/- 2.9 to 10.9 +/- 7.1 and 2.8 +/- 3.1 to 10.1 +/- 10.8 mL for A and B, respectively). Visual analogue scale score significantly decreased at the end of each treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical, cytogenetic and toxicological studies in rural workers exposed to pesticides in Botucatu, São Paulo, Brazil.

Pesticides can cause gene mutations and chromosomal aberrations in exposed individuals. We have investigated 24 workers exposed to pesticides. Clinical examinations and cytogenetic and toxicological tests were performed. Ten non-exposed individuals were used as controls. Toxicological dosages of copper, zinc and manganese (metals found in some pesticides), hepatic enzyme dosage (GOT, GPT, AR) and acetylcholinesterase activity were performed in 16 workers and 8 controls. In the exposed workers, the most relevant clinical symptoms were poor digestion with fullness sensation after meals, irritated eyes, headache and fasciculations. The exposed group showed significantly lower manganese dosage and acetylcholinesterase activity, and significantly higher levels of alkaline phosphatase. Cytogenetic studies showed significantly higher chromosomal aberrations in the exposed group compared to the control group. Although the workers used protection against the pesticide's fog, the results revealed that the workers were contaminated with the pesticides. Therefore, the cytogenetic, toxicological studies with clinical examination are necessary for monitoring workers who are exposed to pesticides in any situation.

Short term effect of intermittent negative pressure ventilation in COPD patients with respiratory failure.

Ten patients with stable chronic obstructive pulmonary disease (COPD) and hypercapnic respiratory failure were randomly submitted to intermittent negative pressure ventilation (INPV) 6 h per day for 5 consecutive days by either a cuirass or pneumo wrap ventilator. The effects were assessed by measurements of spirometry, blood gases, maximal inspiratory (MIP) and expiratory (MEP) pressures, 12 minutes walking distance test (12 mwd), sensation of dyspnoea by a visual analogue scale (VAS) and diaphragmatic electromyographic activity (Edi). Edi was recorded during INPV sessions in only 7 patients. The same measurements apart from Edi were also performed in 8 matched control patients randomly submitted to conventional physiotherapy. During INPV, Edi activity was reduced, at least temporarily down to 50% of baseline values. Comparison of baseline with post INPV values showed no changes in thoracic gas volume (TGV), forced expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC), arterial oxygen partial pressure (Pao2) and MEP; significant improvements were seen in MIP, vital capacity (VC), VAS, and 12 mwd only in patients submitted to INPV. A significant improvement in PaCO2 was observed in both groups of patients. We conclude that INPV may be effective in improving the functional reserve of the inspiratory muscles in selected COPD patients with hypercapnic respiratory failure and signs of inspiratory muscle dysfunction.