Improved objective Bayesian estimator for a PLP model hierarchically represented subject to competing risks under minimal repair regime.

In this paper, we propose a hierarchical statistical model for a single repairable system subject to several failure modes (competing risks). The paper describes how complex engineered systems may be modelled hierarchically by use of Bayesian methods. It is also assumed that repairs are minimal and each failure mode has a power-law intensity. Our proposed model generalizes another one already presented in the literature and continues the study initiated by us in another published paper. Some properties of the new model are discussed. We conduct statistical inference under an objective Bayesian framework. A simulation study is carried out to investigate the efficiency of the proposed methods. Finally, our methodology is illustrated by two practical situations currently addressed in a project under development arising from a partnership between Petrobras and six research institutes.

DNA repair and recovery in Escherichia coli after psoralen and angelicin photosensitization.

The correlation between DNA repair and recovery of biological functions was studied using three wild type strains of Escherichia coli and two skinphotosensitizing furocoumarins, psoralen and angelicin, which are well known specific reagents of the pyrimidine bases of DNA. In addition to mono-adducts psoralen is able to form a high number of inter-strand cross-links, while angelicin forms only mono-adducts. Both of these damages were repaired, in a short time, in the following way: at first DNA was cut into small pieces that were then rejoined into molecules of normal size, free from cross-links, while the furocoumarin residue was split from DNA almost quantitatively. Recovery of biological functions was studied performing photosensitization experiments in such a manner that the same amounts of psoralen or of angelicin were linked to bacterial DNA. DNA synthesis, tested just after the damage, was inhibited in a similar extent by both drugs. The same bacteria, however, showed a very different colony-forming capacity; angelicin was much less effective than psoralen with a D37 dose about 2.7 times higher. A similar picture was obtained studying DNA synthesis at different times after photosensitization: in the bacteria damaged by angelicin it was restored while no recovery was observed in cells photosensitized by psoralen. These results suggest that both mono-adducts and cross-links can be chemically repaired more or less in a quantitative measure, but that repair of cross-links in much less effective on cell recovery; this behaviour is very probably connected with the different repair mechanisms of mono-adducts and of cross-links.

Role of a GenoType MTBDRplus line probe assay in early detection of multidrug-resistant tuberculosis at a Brazilian reference center.

Resistance to Mycobacterium tuberculosis is a reality worldwide, and its diagnosis continues to be difficult and time consuming. To face this challenge, the World Health Organization has recommended the use of rapid molecular tests. We evaluated the routine use (once a week) of a line probe assay (Genotype MTBDRplus) for early diagnosis of resistance and for assessment of the main related risk factors over 2 years. A total of 170 samples were tested: 15 (8.8%) were resistant, and multidrug resistance was detected in 10 (5.9%). The sensitivity profile took 3 weeks (2 weeks for culture and 1 week for rapid testing). Previous treatment for tuberculosis and the persistence of positive acid-fast smears after 4 months of supervised treatment were the major risk factors observed. The use of molecular tests enabled early diagnosis of drug-resistant bacilli and led to appropriate treatment of the disease. This information has the potential to interrupt the transmission chain of resistant M. tuberculosis.

[Cardiac performance and hemodynamic response under the effect of isoproterenol and D-isosorbitol in patients with dilated cardiomyopathy]. / Desempenho cardíaco e resposta hemodinâmica sob ação do isoproterenol e D-isosorbitol em portadores de miocardiopatia dilatada.

The authors studied cardiac performance of 36 patients with dilated cardiomiopathy through cardiac catheterization and left ventriculography in comparison with a control group. It has been verified that the end systolic volume (ESV) is more sensitive than ejection fraction (EF) as an indicator of the presence and degree of systolic dysfunction. Isoproterenol (IP) (18 patients) and D-isosorbitol (IS) (18 patients) have been used in the evaluation of hemodynamic response of DM. It has been verified equivalent responses such as: 1--decrease of ESV and end diastolic pressure (EDP); 2--increase of stroke volume and EF. The contractility indexes of left ventricle, however, showed different responses to the 2 substances: 1--with IP there was an increase of peak dp/dt and common peak isovolumetric pressure (CPIP 45 mmHg); 2--with IS there was no variation. The authors conclude that: 1--IP or similar drugs may be used during cardiac catheterization to evaluate the contractile reserve of the myocardium; 2--IS may be used in ambulatorial treatment of DM to improve ventricular function through a tendency to normalize intracardiac pressure-volume relation.

High frequency of immature dendritic cells and altered in situ production of interleukin-4 and tumor necrosis factor-alpha in lung cancer.

INTRODUCTION: Antigen-presenting cells, like dendritic cells (DCs) and macrophages, play a significant role in the induction of an immune response and an imbalance in the proportion of macrophages, immature and mature DCs within the tumor could affect significantly the immune response to cancer. DCs and macrophages can differentiate from monocytes, depending on the milieu, where cytokines, like interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) induce DC differentiation and tumor necrosis factor (TNF)-alpha induce DC maturation. Thus, the aim of this work was to analyze by immunohistochemistry the presence of DCs (S100+ or CD1a+), macrophages (CD68+), IL-4 and TNF-alpha within the microenvironment of primary lung carcinomas. RESULTS: Higher frequencies of both immature DCs and macrophages were detected in the tumor-affected lung, when compared to the non-affected lung. Also, TNF-alpha-positive cells were more frequent, while IL-4-positive cells were less frequent in neoplastic tissues. This decreased frequency of mature DCs within the tumor was further confirmed by the lower frequency of CD14-CD80+ cells in cell suspensions obtained from the same lung tissues analyzed by flow cytometry. CONCLUSION: These data are discussed and interpreted as the result of an environment that does not oppose monocyte differentiation into DCs, but that could impair DC maturation, thus affecting the induction of effective immune responses against the tumor.

Psoralen photosensitization of L 1210 leukaemia cells: an approach to a new combined therapy.

Psoralen photosensitization of L 1210 cells has a strong effect on DNA and RNA syntheses and this result appears connected with the psoralen photobinding to DNA. Protein synthesis is less sensitive and its inhibition seems due to a different photochemical interaction, very likely to the psoralen photobinding to RNA. A combined therapy using cyclophosphamide and L 1210 cells psoralen-photoinactivated was performed after the leukaemia transplant, showing a significant decrease in mortality, even in comparison with the simple treatment with the alkilating drug.

Meningomielorradiculite por Schistosoma mansoni: protocolo de investigaçäo e registro de 21 casos / Meningomyeloradiculitis by Schistosoma mansoni: research protocol and report of 21 cases

Registro de 21 casos de meningomielorradiculíte esquistossomótica (MMRE), resultado de 4 anos de investigaçäo baseada em <> aplicado em 212 pacientes. O Protocolo consistiu em submeter a investigaçäo todo o paciente que apresentasse tríade clínica inicial caracterizada por dor lombar, parentesias em membros inferiores e dificuldade a micçäo. Os critérios diagnósticos foram baseados no quadro clínico neurológico, presença de ovos de Schistosoma mansoni nas fezes ou biópsia retal positividade da reaçäo de imunofluorescência para esquistossomose no LCR, características do tipo inflamatório do LCR e diagnóstico diferencial exaustivo. Em nenhum dos casos houve estudo histopatológico. O tratamento foi realizado o mais precocemente possível e empregada a associaçäo de corticóides com oxaminiquine em todos os casos. Os pacientes säo analisados no ponto de vista do sexo, faixa etária, profissäo, quadro clínico e neurológico, nível da lesäo e forma clínica. Aspectos do exame do LCR, do tratamento e da evoluçäo clínica säo também analisadas. Acham os autores que o diagnóstico da MMRE justifica-se desde que baseado em critérios clínicos e laboratoriais rigosos, pois a MMRE é entidade nosológica bem definida do ponto de vista clínica e patológico. Os autores sugerem aos serviços de neurología planejamento e aplicaçäo de Protocolos semelhantes com o objetivo de que a MMRE seja diagnosticada e tratada precocemente. Estaräo, assim, evitando lesöes e seqüelas irreversíveis, prejudiciais aos pacientes sob o ponto de vista social