ABSTRACT
The prevalence of dengue antibodies was determined in the Attapeu region of South Laos with 225 blood samples collected from mostly febrile patients during the rainy season August - October 2001. An IgM capture ELISA was positive for one (0.4%) sample, while 177 (79%) samples were positive in an indirect IgG ELISA. Of the positive IgG samples, 20 (11.3%) were also positive on blood slides for Plasmodium falciparum. Dengue fever seems to be widespread in this area, but clinical dengue diagnosis remains difficult, especially in the first days of illness when physicians have to discriminate between dengue and other febrile illnesses.
Subject(s)
Antibodies, Viral/blood , Dengue Virus/immunology , Dengue/epidemiology , Immunoglobulin G/blood , Immunoglobulin M/blood , Adolescent , Adult , Child , Dengue/virology , Female , Humans , Laos/epidemiology , Male , Middle Aged , PrevalenceABSTRACT
In a retrospective study, 31 patients with Madelung deformity were reviewed. They were treated at one institution during a period of 15 years. On first presentation, the mean age was 22.5 years with a range from 10 years to 64 years. Twenty-four patients (77%) were female. The main complaints were pain, limited range of motion, and objectionable appearance. A family history of Madelung deformity was present in four patients (13%). The diagnosis of Leri-Weill syndrome could not be confirmed in any case. There was no correlation between the clinical appearance and the extent of radiologic abnormality. Five patients (16%) were operated on because of permanent pain. On postoperative examination, only one patient revealed no restricted range of mobility and no pain, whereas the other four patients improved in terms of pain but showed only limited improvement of function. The vast majority of patients, however, required no surgical therapy.
Subject(s)
Wrist Joint/abnormalities , Adolescent , Adult , Child , Female , Humans , Male , Middle Aged , Radiography , Radius/diagnostic imaging , Retrospective Studies , Ulna/diagnostic imaging , Wrist Joint/diagnostic imagingABSTRACT
Glutathione (GSH), which is known to guard Plasmodium falciparum from oxidative damage, may have an additional protective role by promoting heme catabolism. An elevation of GSH content in parasites leads to increased resistance to chloroquine (CQ), while GSH depletion in resistant P. falciparum strains is expected to restore the sensitivity to CQ. High intracellular GSH levels depend inter alia on the efficient reduction of GSSG by glutathione reductase (GR). On the basis of this hypothesis, we have developed a new strategy for overcoming glutathione-dependent 4-aminoquinoline resistance. To direct both a 4-aminoquinoline and a GR inhibitor to the parasite, double-drugs were designed and synthesized. Quinoline-based alcohols (with known antimalarial activity) were combined with a GR inhibitor via a metabolically labile ester bond to give double-headed prodrugs. The biochemically most active double-drug 7 of this series was then evaluated as a growth inhibitor against six Plasmodium falciparum strains that differed in their degree of resistance to CQ; the ED(50) values for CQ ranged from 14 to 183 nM. While the inhibitory activity of the original 4-aminoquinoline-based alcohol followed that of CQ in these tests, the double-drug exhibited similar efficiency against all strains, the ED(50) being as low as 28 nM. For the ester 7, a dose-dependent decrease in glutathione content and GR activity and an increase in glutathione-S-transferase activity were determined in treated parasites. The drug was subsequently tested for its antimalarial action in vivo using murine malaria models infected with P. berghei. A 178% excess mean survival time was determined for the animals treated with 40 mg/kg 7 for 4 days. No cytotoxicity due to this compound was observed. Work is in progress to extend and validate the strategy outlined here.
Subject(s)
Aniline Compounds/chemical synthesis , Antimalarials/chemical synthesis , Enzyme Inhibitors/chemical synthesis , Glutathione Reductase/antagonists & inhibitors , Plasmodium falciparum/enzymology , Prodrugs/chemical synthesis , Quinolines/chemical synthesis , Aniline Compounds/chemistry , Aniline Compounds/pharmacology , Aniline Compounds/toxicity , Animals , Antimalarials/chemistry , Antimalarials/pharmacology , Antimalarials/toxicity , Cell Line , Chloroquine/pharmacology , Drug Resistance , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/toxicity , Esters , Glutathione/metabolism , Glutathione Reductase/metabolism , Glutathione Transferase/metabolism , Humans , Malaria/drug therapy , Malaria/parasitology , Mice , Plasmodium berghei , Plasmodium falciparum/drug effects , Prodrugs/chemistry , Prodrugs/pharmacology , Prodrugs/toxicity , Quinolines/chemistry , Quinolines/pharmacology , Quinolines/toxicitySubject(s)
Anemia/drug therapy , Erythropoietin/therapeutic use , Uremia/drug therapy , Anemia/etiology , Erythropoietin/administration & dosage , Erythropoietin/pharmacokinetics , Humans , Recombinant Proteins/administration & dosage , Recombinant Proteins/pharmacokinetics , Recombinant Proteins/therapeutic use , Uremia/complicationsABSTRACT
In seven male haemodialysis patients, living with a constant sexual partner, sexual life (self-administered questionnaire) and sex hormones were evaluated before and 3 or 10 months after commencement of recombinant human erythropoietin (rHuEpo) therapy respectively. Haematocrit increased from 22.2 +/- 2.1% to 30.6 +/- 1% with a maintenance dose of 140 +/- 55 U/kg per week. Two patients were hypertensive before and after rHuEpo therapy; antihypertensive medication was kept constant during the study. Self-reported sexual function improved in four of seven patients, including libido and erection. This was paralleled by improved indices of wellbeing (physical fitness, mental alertness). In contrast, serum values of sexual hormones (testosterone or oestradiol) and of basal and stimulated (LHRH/TRH), prolactin and LH, and FSH were not significantly changed during rHuEpo therapy.
