RESUMEN

SETTING: As conclusive data on the performance of interferon-gamma release assays (IGRAs) in paediatric TB are lacking, many guidelines do not recommend their use for TB diagnosis in this population in Brazil. OBJECTIVE: To evaluate the performance of an IGRA by investigating its concordance with the tuberculin skin test (TST) and the role of IGRAs in clinical management and treatment outcomes in children with TB. DESIGN: A historic cohort study was used to evaluate the performance of T-SPOT®.TB (ELISpot) and other tests, such as the TST, in paediatric patients with or without immunodeficiency who were under investigation for latent tuberculous infection (LTBI) or active tuberculosis (TB). RESULTS: Of 86 paediatric patients evaluated, 41 (48%) were immunocompetent and 45 (52%) immunocompromised. All patients underwent T-SPOT.TB, while 63 underwent both ELISpot and TST; test results were concordant in 50 patients (79.4%): 22/31 (71%) in immunocompetent (κ = 0.418, P = 0.02) and 28/32 (87.5%) in immunocompromised patients (κ = 0.526, P = 0.003). TB was diagnosed on the basis of the ELISpot result in 21% (18/86) cases; the contribution of the ELISpot assay was greater in immunocompetent patients than in those who were immunocompromised (13/41, 31.7% vs. 5/45, 11.1%, χ2 P = 0.038). CONCLUSION: ELISpot and TST results were moderately concordant in both groups of patients. ELISpot contribution was higher among immunocompetent patients than among immunocompromised patients.

Asunto(s)

RESUMEN

Tuberculosis (TB) infection was evaluated in Brazilian immunocompetent children and adolescents exposed and unexposed (control group) to adults with active pulmonary TB. Both groups were analysed by clinical and radiological assessment, TST, QFT-IT and T-SPOT.TB. The three tests were repeated after 8 weeks in the TB-exposed group if results were initially negative. Individuals with latent tuberculosis infection (LTBI) were treated and tests were repeated after treatment. Fifty-nine TB-exposed and 42 controls were evaluated. Rate of infection was 69·5% and 9·5% for the exposed and control groups, respectively. The exposed group infection rate was 61% assessed by TST, 57·6% by T-SPOT.TB, and 59·3%, by QFT-IT. No active TB was diagnosed. Agreement between the three tests was 83·1% and 92·8% in the exposed and control groups, respectively. In the exposed group, T-SPOT.TB added four TB diagnoses [16%, 95% confidence interval (CI) 1·6-30·4] and QFT-IT added three TB diagnoses (12%, 95% CI 0-24·7) in 25 individuals with negative tuberculin skin test (TST). Risk factors associated to TB infection were contact with an adult with active TB [0-60 days: odds ratio (OR) 6·9; >60 days: OR 27·0] and sleeping in the same room as an adult with active TB (OR 5·2). In Brazilian immunocompetent children and adolescents, TST had a similar performance to interferon-gamma release assays and detected a high rate of LTBI.

Asunto(s)

RESUMEN

Buscando avaliar a uniformidade da dose unitária de comprimidos submetidos ao procedimento de partição, este trabalho avaliou a dureza, friabilidade, variação de peso e uniformidade de conteúdo em quatro amostras de comprimidos de furosemida de 40 mg, obtidas de diferentes fornecedores. Todas as amostras estudadas atendiam às especificações oficiais antes de serem submetidas ao procedimento de partição; porém, após serem partidas, o teor de fármaco nas metades apresentou excessiva variação, mostrando que esse procedimento pode ser terapeuticamente desaconselhável.

In order to assess the uniformity of the dose of active ingredient in the halves of tablets subjected to splitting, the hardness, friability, weight variability and uniformity of content were studied in four samples of 40 mg tablets of furosemide obtained on the Brazilian market, both whole and split into two parts. All the tablets complied with the official specifications before splitting, but, after this procedure, the drug content in the halves showed excessive variation, indicating that this procedure is inadvisable.

Asunto(s)

RESUMEN

The current drug research techniques, combinatorial synthesis and high throughput screening, enabled the obtaining and pre-evaluation of thousands of compounds in short time. In order to chose the best hits to become leads, observation of drug-likeness tries to optimize this selection. Probably, the most widely used filter is Lipinski's Rule-of-five, which proposes that molecules with poor permeation and oral absorption have molecular weight > 500, Clog P > 5, hydrogen-bond donor > 5 and hydrogen-bond acceptor > 10. In order to evaluate the Rule-of-five, the top pharmaceutical products in 2007 were analyzed. Among 60 drugs, 7 (atorvastatin, montelukast, docetaxel, telmisartan, tacrolimus, leuprolide and olmesartan) did not fit the rule, and 5 failed only one of the threshold values. It was possible to conclude that the rule is very useful to select better compounds in chemolibraries, but it must be used carefully and with criteria, to avoid a possible exclusion of promising compounds.

Asunto(s)

RESUMEN

Interação medicamentosa é o resultado de uma interferência no efeito de um medicamento por outros agentes. Dentre os fatores que resultam nas interações medicamentosas destacam-se a automedicação e a prática da polifarmácia. O objetivo deste trabalho foi realizar um levantamento de interações medicamentosas que ocorrem com fármacos que atuam no sistema nervoso central, suas possíveis consequências, bem como os motivos que propiciam tal situação. Foi realizado um estudo observacional transversal de 60 indivíduos da zona leste de São Paulo que utilizam medicamentos psicotrópicos, maiores de 21 anos e de ambos os sexos, por meio de um questionário entre junho e agosto de 2008. Os principais psicotrópicos utilizados pelos indivíduos foram benzodiazepínicos e antidepressivos (54 indivíduos), sendo que estes fármacos apresentam alto índice de interações medicamentosas. Cerca de 77% utilizam outros medicamentos em paralelo ao tratamento com psicotrópicos, sendo que destes apenas 35% o fazem com supervisão médica e 27% dos indivíduos utilizaram bebidas alcoólicas concomitantemente. As principais interações encontradas envolveram antidepressivos com benzodiazepínicos, antiulcerogênicos, anticonvulsivantes e álcool. Conclui-se que a automedicação e o uso inadequado de medicamentos são fatores que podem propiciar a ocorrência das interações medicamentosas encontradas, algumas com consequências graves.

A drug interaction is the interference in the effect of a drug by another substance. Outstanding among the factors that result in drug interactions are selfmedication and the practice of polypharmacy. The aim of this work was to conduct a survey of drug interactions that occur with drugs that act on the central nervous system, their possible consequences and the reasons for their occurrence. An observational cross-sectional study was performed on 60 subjects from East Sao Paulo who take psychotropic drugs (over 21 years old and of both genders), by means of a questionnaire applied from June to August 2008. The main drugs taken by those interviewed were benzodiazepines and antidepressants (54 subjects), which are drugs that have high rates of drug interactions. About 77% took other drugs, in parallel with the psychotropic drug treatment, of which only 35% were under medical supervision, and 27% of subjects drank alcohol while taking psychotropic drugs. The main interactions found involved antidepressants with benzodiazepines, antiulcerogenics, anticonvulsants and alcohol. We concluded that self-medication and inadequate drug usage are factors that favor the occurrence of the drug interactions found, some of them with dangerous consequences.

Asunto(s)

RESUMEN

Activated T lymphocytes often accumulate in the lower dermis of patients with systemic sclerosis (scleroderma) and may play a role in the development of dermal fibrosis. We propagated and cloned these cells directly from skin biopsies in four of eight cases of early, untreated systemic sclerosis with diffuse scleroderma. The cloning frequency estimates were f = 0.20 and f = 0.48 for T cells derived from the skin of two patients versus f = 0.68 and f = 0.96 for autologous blood T lymphocytes. All but one of 24 skin-derived scleroderma clones were CD4+. Clonal analyses performed with CD4+ clones from patients and normal controls showed that all but one skin-derived clones synthesized either interferon-gamma (60%), glycosaminoglycan-stimulatory factor (26%) or both (9%) when induced in vitro by a mitogen, concanavalin A, but not by autologous dermal fibroblasts. In contrast, blood-derived clones had a different functional phenotype. All skin-derived clones produced tumour necrosis factor-alpha. Our results demonstrate that T lymphocytes obtained from the skin of patients with systemic sclerosis synthesized cytokines which could modulate functions of human dermal fibroblasts.

Asunto(s)

RESUMEN

In comparison to normal fibroblasts cultured in parallel, scleromyxedema fibroblasts grew less well, synthesized increased amounts of glycosaminoglycans (GAG) in vitro and had ultrastructural abnormalities. Serum obtained from a patient with scleromyxedema increased in vitro fibroblast proliferation but not the GAG synthesis per cell. Serum obtained after therapy, at the time when clinical improvement was observed, continued to stimulate fibroblast proliferation. Thus the serum factor stimulating the fibroblast proliferation did not modulate their GAG synthesis and had no direct relationship to disease activity.

Asunto(s)

Asunto(s)