Rapid genotyping of loci involved in antifolate drug resistance in Plasmodium falciparum by primer extension

Current methods used to genotype point mutations in Plasmodium falciparum genes involved in resistance to antifolate drugs include restriction digestion of PCR products, allele-specific amplification or sequencing. Here we demonstrate that known point mutations in dihydrofolate reductase and dihydropteroate synthase can be scored quickly and accurately by single-nucleotide primer extension and detection of florescent products on a capillary sequencer. We use this method to genotype parasites in natural infections from the Thai-Myanmar border. This approach could greatly simplify large-scale screening of resistance mutations of the type required for evaluating and updating antimalarial drug treatment policies. The method can be easily adapted to other P. falciparum genes and will greatly simplify scoring of point mutations in this and other parasitic organisms. © 2002 Australian Society for Parasitology Inc. Published by Elsevier Science Ltd. All rights reserved.

Drug resistance in the sexually transmitted protozoan Trichomonas vaginalis

Trichomoniasis is the most common, sexually transmitted infection. It is caused by the flagellated protozoan parasite Trichomonas vaginalis. Symptoms include vaginitis and infections have been associated with preterm delivery, low birth weight and increased infant mortality, as well as predisposing to HIV/AIDS and cervical cancer. Trichomoniasis has the highest prevalence and incidence of any sexually transmitted infection. The 5-nitroimidazole drugs, of which metronidazole is the most prescribed, are the only approved, effective drugs to treat trichomoniasis. Resistance against metronidazole is frequently reported and cross-resistance among the family of 5-nitroimidazole drugs is common, leaving no alternative for treatment, with some cases remaining unresolved. The mechanism of metronidazole resistance in T. vaginalis from treatment failures is not well understood, unlike resistance which is developed in the laboratory under increasing metronidazole pressure. In the latter situation, hydrogenosomal function which is involved in activation of the prodrug, metronidazole, is down-regulated. Reversion to sensitivity is incomplete after removal of drug pressure in the highly resistant parasites while clinically resistant strains, so far analysed, maintain their resistance levels in the absence of drug pressure. Although anaerobic resistance has been regarded as a laboratory induced phenomenon, it clearly has been demonstrated in clinical isolates. Pursuit of both approaches will allow dissection of the underlying mechanisms. Many alternative drugs and treatments have been tested in vivo in cases of refractory trichomoniasis, as well as in vitro with some successes including the broad spectrum anti-parasitic drug nitazoxanide. Drug resistance incidence in T. vaginalis appears to be on the increase and improved surveillance of treatment failures is urged.

Key issues in determining the ethics of research subject payment: the special case of drug abuse epidemiology

The authors identify key issues that researchers, funding bodies, ethics committees and ethicists might consider in contemplating research subject payment ethics. They argue that what is missing from the broader debate is due consideration of ethics committee decision processes; research subject reasons for participation; and current research practices. The authors explore these issues and how they relate to existing guidelines on voluntary consent, and arguments that have been proposed for and against research subject payments. (non- author abstract)

Alcohol and other drug use disorders among older-aged people

In Australia people aged 65 years or older currently comprise 12.1% of the population. This has been estimated to rise to 24.2% by 2051. Until recently there has been relatively little research on alcohol and other drug use disorders among these individuals but, given the ageing population, this issue is likely to become of increasing importance and prominence. Epidemiological research shows a strong age-related decline in the prevalence of alcohol and other drug use disorders with age. Possible reasons for this include: age-related declines in the use and misuse of alcohol and other drugs; increased mortality among those with a lifetime history of alcohol and other drug use disorders; historical differences in exposure to and use of alcohol and other drugs. Despite the age-related decline in the prevalence of these disorders, they do still occur among those aged 65 years or older and, given historical changes in exposure to and use of illicit drugs, it likely that the prevalence of these disorders among older-aged individuals will rise. Specific issues faced by older-aged individuals with alcohol and other drug use problems are discussed. These include: interactions with prescribed medications, under-recognition and treatment of alcohol and drug problems, unintentional injury and social isolation. Finally, a brief discussion of treatment issues is provided.

S-nitrosocaptopril: acute in-vivo pulmonary vasodepressor effects in pulmonary hypertensive rats

The effects of S-nitrosocaptopril (SNOcap), administered either intravenously or by oral gavage, on pulmonary artery pressure (PAP) were examined in anaesthetised normotensive rats and rats with hypoxic pulmonary hypertension (10% oxygen for 1 week). Mean PAP (MPAP) values in hypoxic and normoxic rats were (mmHg) 26 +/- 1.7 and 15 +/- 1.1, respectively. When given intravenously, 1 mg kg(-1) SNOcap reduced MPAP by 28 and 32% in hypoxic and normoxic rats, respectively. The effects of 2 mg kg(-1) were no greater than those of 1 mg kg(-1). Pulmonary vasoclepressor responses reached equilibrium in 1.7 +/- 0.18 min following intravenous administration. When given orally 30 min before the measurement of PAP, 30 mg kg(-1), but not 10 mg kg(-1), significantly reduced MPAP in hypoxic rats to 17 +/- 1.5 mmHg. These in-vivo data are consistent with previous in-vitro data showing that SNOcap has direct pulmonary vasorelaxant properties in both large and small pulmonary arteries and also show that SNOcap causes pulmonary vasodepression in the setting of pulmonary hypertension. Since SNOcap also inhibits pulmonary vascular angiotensin converting enzyme (ACE) in pulmonary blood vessels (previous study), it would be an interesting drug with which to assess the benefits of direct pulmonary vasodilatation combined with ACE inhibition (which attentuates pulmonary vascular remodelling) in a long-term study in pulmonary hypertension.

Antibiotic desensitization in adults with cystic fibrosis

Objective: Allergic reactions to antibiotics occur in up to 30% of patients with cystic fibrosis (CF). Repeated antibiotic exposure and immune hyper-responsiveness increase the risk of allergic reactions and may limit antibiotic choice. Desensitization may allow the successful administration of an antibiotic despite previous allergy. We aimed to determine the success of antibiotic desensitization in patients with CF in an adult CF unit over a 7-year period. Methodology: A retrospective medical record review was performed on the 19 patients who had undergone antibiotic desensitization procedures. Data collected included drug allergy and intolerance profiles, nature of allergies, and the outcome of desensitization procedures. Desensitization procedures were performed in a ward setting according to published methods. Results: Nineteen patients (13 females) reported 62 drug allergies with a mean of 3.3 per patient. Of the 71 desensitization procedures undergone by this group, 54 (76%) were successful. Fifteen of the 19 patients were allergic to two or more beta-lactam antibiotics. Over half of the patients were desensitized to more than one antibiotic. Nine different antibiotics were used in 31 different patient/drug combinations. A successful outcome was achieved in 18/31 (58%) combinations, with three requiring treatment for mild allergic reactions. Allergic reactions caused drug cessation in a total of 19 patient/drug combinations (three after initial successful desensitization and full courses of antibiotics). Over 50% of these reactions occurred on day 1. Desensitization failures were more common in patients with well-documented allergic reactions to a specific drug. Conclusion: This study demonstrates that multiple antibiotic allergies are common in adults with CE Cross-reactivity between beta-lactam antibiotics may limit antibiotic choice for the treatment of pulmonary exacerbations. Antibiotic desensitization allows safe and successful treatment in the ward setting of many patients with previous allergies to an antibiotic. In many patients symptoms of allergy still occur and result in cessation of the antibiotics. Use of corticosteroids and antihistamines may improve the success rate of desensitization procedures.

A política antidrogas brasileira : velhos dilemas

O debate atual sobre drogas tem sido organizado em torno de discursos científicos que tendem a configurar a questão ora como problema de segurança pública (relacionado ao tráfico e à repressão), ora como problema de saúde pública (relacionado à repressão da demanda por um lado e à redução de danos por outro). O presente texto traz uma reflexão que busca configurar como a política de enfrentamento às drogas no Brasil enseja em suas proposições uma luta entre as lógicas de segurança pública e de saúde pública expressas no embate entre as duas políticas instituídas pelo governo brasileiro no enfrentamento à questão – a política nacional antidrogas regulamentada em 2003 pela Secretaria Nacional Antidrogas (estrutura criada no governo Fernando Henrique Cardoso – FHC - por meio da medida provisória nº 1669, de 1998, e modificada no governo Lula para "Política Pública Sobre Drogas") e a Política de Atenção Integral ao Usuário de Álcool e Drogas do Ministério da Saúde (também formulada no governo FHC)

Efeitos subjetivos do processo de trabalho vivenciados por profissionais em um Centro de Atenção Psicossocial Álcool e Drogas

Esta tese apresenta os resultados da pesquisa que teve como objetivo analisar como os trabalhadores vivenciam os efeitos subjetivos produzidos pelo processo de trabalho de um Centro de Atenção Psicossocial Álcool e Drogas (CAPSad). A pesquisa foi realizada sob uma abordagem qualitativa, em um CAPSad do município de Vila Velha, Espírito Santo. A coleta de dados se deu por meio de cinco etapas: 1. Análise documental das políticas vigentes sobre uso de drogas; 2. Análise de prontuários; 3. Entrevista coletiva com dez trabalhadores; 4. Oitenta horas de observação do cotidiano de trabalho; 5. Entrevista em profundidade com treze trabalhadores. Para análise de dados foi utilizada a técnica da Análise Temática. Constatamos que no plano das políticas sobre o assunto,há prevalência de ideias relacionadas à repressão dos usuários, apesar da tentativa do Ministério da Saúde (MS) em abordar a redução de danos como uma estratégia que valoriza o sujeito e sua singularidade. A análise ainda apontou as dificuldades que os profissionais enfrentam neste município para atuar segundo as diretrizes do MS, uma vez que as ações municipais dão ênfase à repressão, à religiosidade e ao amedrontamento como estratégia de prevenção, com apoio da justiça e da polícia. Enfatizamos que tais ambiguidades repercutem no trabalho e para o trabalhador. Apontamos ainda outros aspectos que geram efeitos para os trabalhadores: condições de trabalho precárias (devido à estrutura do serviço, baixos salários e rede de atenção inexistente), falta de reconhecimento (devido à omissão da gerência e à ausência de normas) e sobrecarga (devido à falta de profissionais e aos conflitos nas divisões de tarefas). Essas situações levam a efeitos subjetivos como: desgaste, adoecimento, medo, incapacidade de agir, apatia, desvalorização, desmotivação e no aprisionamento do trabalhador. Notamos que estes efeitos são todos negativos e que os profissionais os vivenciam por meio do distanciamento afetivo no processo de trabalho, o que repercute negativamente na possibilidade de produção de um cuidado efetivo. Sugerimos que haja investimentos na formação de todos os trabalhadores que atuam nesse local, com foco na educação permanente, uma vez que por meio desta há o incentivo da aprendizagem e o enfrentamento criativo dos efeitos vivenciados no cotidiano.É preciso que haja diálogo, seja entre os trabalhadores e a gestão, entre os próprios trabalhadores e entre trabalhadores e usuários.

Towards Emotional Interaction: Using Movies to Automatically Learn Users' Emotional States

The HCI community is actively seeking novel methodologies to gain insight into the user’s experience during interaction with both the application and the content. We propose an emotional recognition engine capable of automatically recognizing a set of human emotional states using psychophysiological measures of the autonomous nervous system, including galvanic skin response, respiration, and heart rate. A novel pattern recognition system, based on discriminant analysis and support vector machine classifiers is trained using movies’ scenes selected to induce emotions ranging from the positive to the negative valence dimension, including happiness, anger, disgust, sadness, and fear. In this paper we introduce an emotion recognition system and evaluate its accuracy by presenting the results of an experiment conducted with three physiologic sensors.