Avaliação a longo prazo do tratamento etiológico da doença de Chagas com benznidazol

O objetivo deste artigo é verificar o resultado da terapêutica específica com o benznidazol na doença de Chagas aguda e crônica, após prazo longo de seguimento dos pacientes, tomando como base do critério de cura a reversão pós-terapêutica definitiva à negatividade das reações sorológicas convencionais quantitativas. Foram avaliados 21 pacientes agudos e 113 crônicos, em uma ou outra das diferentes formas clínicas, selecionados por terem sido tratados somente com o benznidazol e acompanhados por longo tempo, de 13 a 21 anos os agudos e de seis a 18 anos os crônicos. Expôs-se o esquema terapêutico, dando ênfase à estreita correlação entre os efeitos colaterais e a dose total de 18 g, aproximadamente, limite obrigatório porque com essa dose surge a polineurite, se já não estiver presente. Foram relacionadas algumas precauções para a segurança do tratamento. Anotou-se a duração da doença, tanto aguda como crônica, circunstância que influi no resultado do tratamento. As reações sorológicas usadas foram a de fixação do complemento, a de imunofluorescência indireta, a de hemaglutinação indireta, e, ocasionalmente, a da ELISA. Verificou-se a cura em 76 por cento dos pacientes agudos e de apenas 8 por cento dos crônicos. Tendo em mente esses resultados, discutiram-se pontos duvidosos da terapêutica etiológica da doença de Chagas, como critério de cura, o papel da imunossupressão para o conhecimento da patogenia da doença e as reações adversas ao medicamento. A hipótese do autor é que na doença crônica de longa duração o T. cruzi persiste nos tecidos, após o tratamento, na grande maioria dos doentes tratados, escapando à ação do medicamento e mantendo positivos os testes sorológicos. Relacionam-se razões que justificam o tratamento na doença crônica. Com relação ao ciclo vital do Trypanosoma cruzi no hospedeiro vertebrado, há ainda pontos obscuros e controvertidos. Embora não haja prova da existência de formas resistentes ou latentes, a descoberta, ao longo dos últimos 15 anos, de que a imunossupressão desencadeia a doença aguda nos pacientes crônicos de longa duração, justifica revisão do assunto.The aim of this article is to present an investigation of cure rate, after long follow up, of specific chemotherapy with benznidazole in patients with both acute and chronic Chagas disease, applying quantitative conventional serological tests as the base of the criterion of cure. Twenty one patients with the acute form and 113 with one or other of the various chronic clinical forms of the disease were evaluated, after a follow up period of 13 to 21 years, for the acute, and 6 to 18 years, for the chronic patients. The duration of the acute as well as the chronic disease, a condition which influences the results of the treatment, was determined. The therapeutic schedule was presented, with emphasis on the correlation between adverse reactions and the total dose of 18 grams, approximately, as well as taking into consideration precautions to assure the safety of the treatment. Quantitative serological reactions consisting of complement fixation, indirect immunofluorescence, indirect hemagglutination, and, occasionally, ELISA, were used. Cure was found in 76 per cent of the acute patients but only in 8 per cent of those with chronic forms of the disease. In the light of such contrasting results, fundamentals of the etiological therapy of Chagas disease were discussed, like the criterion of cure, the pathogenesis and the role of immunosuppression showing tissue parasitism in long standing chronic disease, in support of the concept that post-therapeutic consistently positive serological reactions mean the presence of the parasite in the patient's tissues. In relation to the life-cycle of T. cruzi in vertebrate host, there are still some obscure and controversial points, though there is no proof of the existence of resistant or latent forms. However, the finding over the last 15 years, that immunosuppression brings about the reappearance of acute disease in long stand chronic patients justifies a revision of the matter. Facts were quoted in favor of the treatment of chronic patients

Raman-scattering study of the phonon dispersion in twisted bi-layer graphene

Bi-layer graphene with a twist angle \theta\ between the layers generates a superlattice structure known as Moir\'{e} pattern. This superlattice provides a \theta-dependent q wavevector that activates phonons in the interior of the Brillouin zone. Here we show that this superlattice-induced Raman scattering can be used to probe the phonon dispersion in twisted bi-layer graphene (tBLG). The effect reported here is different from the broadly studied double-resonance in graphene-related materials in many aspects, and despite the absence of stacking order in tBLG, layer breathing vibrations (namely ZO' phonons) are observed.Comment: 18 pages, 4 figures, research articl

Group theory for structural analysis and lattice vibrations in phosphorene systems

Group theory analysis for two-dimensional elemental systems related to phosphorene is presented, including (i) graphene, silicene, germanene and stanene, (ii) dependence on the number of layers and (iii) two stacking arrangements. Departing from the most symmetric $D_{6h}^{1}$ graphene space group, the structures are found to have a group-subgroup relation, and analysis of the irreducible representations of their lattice vibrations makes it possible to distinguish between the different allotropes. The analysis can be used to study the effect of strain, to understand structural phase transitions, to characterize the number of layers, crystallographic orientation and nonlinear phenomena.Comment: 24 pages, 3 figure

Two decades of ART: improving on success through further research

Since the introduction of the Atraumatic Restorative Treatment (ART) approach over twenty years ago, more than 190 research publications have appeared. The last research agenda defining research priorities for ART was published in 1999. The objective of the present work was to review existing research in the context of future research priorities for ART. MATERIAL AND METHODS: An internet survey was conducted amongst those who had published on ART or were known to be working on the ART approach, to solicit their views as to areas of future ART research. Three broad categories were defined, namely: 1. Basic and laboratory research; 2. Clinical research, and, 3. Community, Public Health, Health Services Research. RESULTS: A 31% response rate was achieved. The study identified a number of new areas of research as well as areas where additional research is required. These are expressed as recommendations for future ART research. CONCLUSIONS: The ART approach is based on a robust, reliable and ever-growing evidence base concerning its clinical applications which indicates that it is a reliable and quality treatment approach. In common with all other oral health care procedures, targeted applied research is required to improve the oral health care offered

Group Theory analysis of phonons in two-dimensional Transition Metal Dichalcogenides

Transition metal dichalcogenides (TMDCs) have emerged as a new two dimensional materials field since the monolayer and few-layer limits show different properties when compared to each other and to their respective bulk materials. For example, in some cases when the bulk material is exfoliated down to a monolayer, an indirect-to-direct band gap in the visible range is observed. The number of layers $N$ ($N$ even or odd) drives changes in space group symmetry that are reflected in the optical properties. The understanding of the space group symmetry as a function of the number of layers is therefore important for the correct interpretation of the experimental data. Here we present a thorough group theory study of the symmetry aspects relevant to optical and spectroscopic analysis, for the most common polytypes of TMDCs, i.e. $2Ha$, $2Hc$ and $1T$, as a function of the number of layers. Real space symmetries, the group of the wave vectors, the relevance of inversion symmetry, irreducible representations of the vibrational modes, optical selection rules and Raman tensors are discussed.Comment: 32 pages, 4 figure

Therapeutical evaluation of different dose regimens of praziquantel in schistosomiasis mansoni, based on the quantitative oogram technique

A clinical trial involving 80 patients of both sexes, from ages 15 to 55, with chronic intestinal or hepatointestinal schistosomiasis mansoni, was carried out to evaluate the therapeutical efficacy of different dose regimens of praziquantel. The patients were randomly allocated into four groups with an equal number of cases and were then treated with one of the following dosages: 60 mg/kg for 1 day; 60 mg/kg daily for 2 days; 60 mg/kg daily for 3 days; and 30 mg/kg daily for 6 days. The assessment of parasitological cure was based on the quantitative oogram technique through rectal mucosa biopsies which were undertaken prior to, as well as, 1,2,4 and 6 months post-treatment. Concurrently, stool examinations according to the qualitative Hoffman, Pons & Janer (HPJ) and the quantitative Kato-Katz (K-K) methods were also performed. The best tolerability was observed with 30 mg/kg daily for 6 days whereas the highest incidence of side-effects (mainly dizziness and nausea) was found with 60 mg/kg daily for 3 days. No serious adverse drug reaction has occurred. The achieved cure rates were: 25% with 60 mg/kg for 1 day; 60% with 60 mg/kg daily for 2 days; 89.5% with 60 mg/kg daily for 3 days; and 90% with 30 mg/kg daily for 6 days. At the same time there has been a downfall of 64%, 73%, 87% and 84% respectively, in the median number of viable S. mansoni ova per gram of tissue. Thus, a very clear direct correlation between dose and effect could be seen. The corresponding cure rates according to stool examinations by HPJ were 39%, 80%, 100% and 95%; by K-K 89%, 100%, 100% and 100%. This discrepancy in results amongst the three parasitological methods is certainly due to their unequal accuracy. In fact, when the number of viable eggs per gram of tissue fell below 5,000 the difference in the percentage of false negative findings between HPJ (28%) and K-K (80%) became significative. When this number dropped to less than 2,000 the percentage of false negative results obtained with HPJ (49%) turned significant in relation to the oogram as well. In conclusion, it has been proven that praziquantel is a highly efficacious agent against S. mansoni infections. If administered at a total dose of 180 mg/kg divided into either 3 or 6 days, it yields a 90% cure rate. Possibly, one could reach 100% by increasing the total dose to 240 mg/kg. Furthermore, it was confirmed that the quantitative oogram technique is the most reliable parasitological method when evaluating the efficacy of new drugs in schistosomiasis mansoni.Uma pesquisa clínica compreendendo 80 pacientes de ambos os sexos, de 15 a 55 anos de idade, portadores de esquistossomose mansônica crônica, formas intestinal ou hepatintestinal, foi efetivada para avaliar a eficácia do praziquantel em diferentes esquemas posológicos. Os pacientes foram distribuídos aleatoriamente em quatro grupos, com igual número de casos, sendo tratados com uma das seguintes dosagens: 60 mg/kg em um dia, 60 mg/kg diários por dois dias, 60 mg/kg diários por três dias e 30 mg/kg diários por seis dias. A avaliação da cura parasitológica baseou-se na técnica do oograma quantitativo mediante biópsias da mucosa retal, realizadas antes, bem como um, dois, quatro e seis meses após o tratamento. Concomitantemente, efetuaram se exames de fezes segundo os métodos qualitativo de Hoffman, Pons & Janer e quantitativo de Kato-Katz. A melhor tolerabilidade foi verificada com 30 mg/kg diários durante seis dias, enquanto a maior incidência de efeitos colaterais, em especial tontura e náusea, ocorreu com 60 mg/kg diários durante três dias. Nenhuma reação adversa grave foi observada com o medicamento. Alcançaram se os seguintes índices de cura: 25% com 60 mg/kg em um dia; 60% com 60 mg/kg diários por dois dias; 89,5% com 60 mg/kg diários por três dias e 90% com 30 mg/kg diários por seis dias. Paralelamente houve uma queda de, respectivamente, 64%, 73%, 87% e84% no número mediano de ovos viáveis de S. mansoni por grama de tecido. Assim, constatou se uma correlação direta entre dose e efeito. Os correspondentes índices de cura, segundo os exames de fezes, foram 39%, 80%, 100% e 95% com o método de Hoffman, Pons & Janer e com o de Kato-Katz 89%, 100%, 100% e 100%. A discrepância encontrada nos resultados entre os três métodos parasitológicos decorre da desigualdade na precisão dos mesmos. Quando o número de ovos viáveis por grama de tecido caiu abaixo de 5000, a diferença no percentual de achados falso-negativos entre Hoffmann, Pons & Janer (28%) e Kato-Katz (80%) tornou-se significativa. Quando esse número baixou para menos de 2000, a percentagem de resultados falso-negativos encontrada com Hoffman, Pons & Janer (49%) também passou a ser significativa em relação ao oograma. Em conclusão, ficou provado que o praziquantel é altamente eficaz na infecção pelo S. mansoni. Administrado na dose total de 180 mg/kg, dividida em três ou seis dias, o praziquantel proporcionou 90% de cura. Provavelmente, poderia atingir 100% se a dose total fosse aumentada para 240 mg/kg. Ademais, confirmou-se que o oograma quantitativo consiste no método mais fidedigno para avaliar a eficácia terapêutica de novas drogas na esquistossomose mansônica

Avaliação das necessidades energéticas no doente crítico

Introdução: Os doentes críticos são um grupo de do- entes francamente hipermetabólicos que necessitam de um suporte nutricional adequado às suas necessidades. Objectivos: Verificar o melhor método para determinar as neces- sidades energéticas de doentes críticos. Material e métodos: Estudo transversal analítico no qual foram recolhidos dados demográficos, determinado o consumo energético quer por calorimetria indirecta, quer pela fórmula de Harris-Benedict e além disso calculado o fator de stress de pacientes internados entre 2004 e 2009. Resultados: Incluíram- se neste estudo 139 doentes (33% feminino, 67% masculino). Foram efetuadas 298 medidas pela calorimetria indireta, com tempo útil médio de 9 horas, que foram compa- radas às necessidades energéticas calculadas a partir da equação de Harris-Benedict. Encontraram-se diferenças significativas entre os resultados obtidos. O consumo energético mensurado foi 27,9 Kcal/kg (mediana), e quando comparado à equação de Harris-Benedict, evidenciou-se um valor subestimado em 25% (7 Kcal/kg). A mediana do fator de stress encontrado para a correção da fórmula de Harris- Benedict foi de 1,31. Discussão e conclusão: Embora exista uma variabilidade do consumo energético nesses doentes, a fórmula de Harris-Benedict, quando associada a um fator stress entre 1,25 – 1,35, poderá ser um método eficaz na avaliação das necessidades nutricionais. Por outro lado, pode-se optar também por uma abordagem mais simplificada, utilizando valores energéticos entre 25 a 30 Kcal por quilograma de peso. Obviamente, a calorimetria indireta continua a ser o “gold standard’’ da avaliação do consumo energético, já que nos permite adequar as necessidades energéticas em função do consumo energético in- dividual de acordo com o gasto real de cada doente