Fragilidade em idosos que vivem na comunidade: prevalência e fatores associados / Frailty in community-dwelling older people: prevalence and associated factors

Fundamentos: Idosos que vivem na comunidade são propensos a desenvolver fragilidade, considerada como um estado clinicamente identificável que aumenta a vulnerabilidade a resultados adversos e prediz incapacidade e mortalidade na população idosa. Objetivo: Identificar a prevalência e fatores associados à fragilidade em idosos que vivem em uma comunidade. Método: Trata-se de um inquérito domiciliar transversal e analítico, de abordagem quantitativa realizado com 854 idosos que vivem na comunidade. A fragilidade foi mensurada pela Edmonton Frail Scale (EFS). A associação entre fragilidade e variáveis sociodemográficas e de condições clínicas foi mensurada pela análise múltipla por regressão logística. Resultados: A prevalência de fragilidade encontrada neste estudo foi de 12,3% (IC95%: 10,1 a 14,5). O modelo de regressão logística mostrou que as variáveis estatisticamente associadas à fragilidade foram: queda recorrente, uso de dispositivo para auxílio à marcha, polifarmácia, autopercepção ruim de saúde, dependência nas atividades básicas e instrumentais de vida diária. Conclusão: A prevalência de fragilidade em idosos foi baixa em comparação a outros estudos nacionais que empregaram a EFS. Os resultados indicaram múltiplos fatores associados à fragilidade modificáveis. Assim, a investigação da síndrome da fragilidade bem como dos seus fatores relacionados passíveis de prevenção são ações a serem incluídas na prática clínica. (AU)

Foundations: Elderly people living in the community are prone to developing frailty, considered as a clinically identifiable state that increases vulnerability to adverse events and predicts disability and mortality in the elderly population. Objective: To identify the prevalence and factors associated with frailty in the elderly living in the community. Materials and method: This is a cross-sectional and analytical household survey with a quantitative approach conducted with 854 elderly people living in the community. Frailty was measured by Edmonton Frail Scale (EFS). The association between frailty and sociodemographic and clinical condition variables was measured by multiple analysis using logistic regression. Results: The prevalence of frailty found in this study was 12.3% (95% CI: 10.1 to 14.5). The logistic regression model showed that the variables statistically associated with frailty were: recurrent fall, use of walking aids, polypharmacy, poor self-rated health, dependence on basic and instrumental activities of daily living. Conclusion: The prevalence of frailty in the elderly was low compared to other national studies that employed the SAI. Results indicated potentially modifiable factors associated with frailty. Thus, the investigation of frailty syndrome and its related preventable factors are actions to be included in clinical practice. (AU)

Patient needs four years after first psychiatric hospitalization in a Brazilian cohort

Knowledge about the needs of psychiatric patients is essential for mental health care planning. However, research on met and unmet needs is still scarce, particularly in low- and middle-income countries. This study aimed to describe the patients' needs (met and unmet) at least four years after their first psychiatric hospitalization and to verify the role of demographic and clinical features as possible predictors of these needs. Patients who had their first psychiatric admission between January 1, 2006 and December 31, 2007 at an inpatient unit in the city of Ribeirão Preto, Brazil, were eligible to participate in the study. Patients were contacted and face-to-face interviews were conducted by psychologists using the Camberwell Assessment of Need. Data were analyzed using zero-inflated negative binomial regression model. Of 933 eligible patients, 333 were interviewed. The highest level of needs was related to welfare benefits (32.4%, unmet=25.5%), followed by household skills (30.3%, unmet=3.0%), psychotic symptoms (29.4%, unmet=9.0%), psychological distress (27.6%, unmet=8.4%), physical health (24.3%, unmet=5.4%), daytime activities (19.5%, unmet=16.5%), and money (16.8%, unmet=9.0%). Fewer years of schooling, living with relatives, and unemployment at the moment of the first admission were significantly associated with a higher number of both met and unmet needs in the follow-up. Unmet needs were also more often reported by patients living alone. In conclusion, socioeconomic indicators were the best predictors of needs. The unmet needs related to welfare benefits point to the need for specific social and health policies.

Sorotipos de Streptococcus suis identificados em suínos com meningite no estado do Paraná / Streptococcus suis serotypes identified from meningitis cases in pigs in Parana, Brazil

A total of 76 samples of Streptococcus suis isolated from meningitis cases in pigs from 2005 to 2009 were evaluated. The samples were collected from 3 to 21-week-old pigs raised in 30 farms located in Paraná state, Brazil. The samples of S. suis were obtained as part of routine procedures and were serotyped by coagglutination test using rabbit hyperimmune sera for the serotypes 1 to 9 and ½. S. suis type 2 was the most frequent, followed by serotypes 1, ½ and 3.

Análise das prevalências de doenças detectadas pelo programa nacional de triagem neonatal no município de Araraquara no ano de 2009 / Prevalence analysis of diseases detected by the National Neonatal Screening Program in Araraquara city (Brazil) in the year 2009

O Programa Nacional de Triagem Neonatal (PNTN) implantado no Brasil tem como objetivo, considerando cada fase de execução local, detectar doenças como fenilcetonúria, hipotereoidismo congênito, hemoglobinopatias e fibrose cística. O objetivo deste trabalho foi analisar, através de um estudo transversal e observacional, a prevalência das doenças detectadas pelo PNTN no município de Araraquara emitidas pela APAE de São Paulo no período compreendido entre abril e dezembro de 2009. Os resultados mostram que o município apresentou, no ano de 2009, prevalência de fenilcetonúria e hipotireoidismo congênito de 0,06% acima da média nacional, que é de 0,01% e 0,03%, respectivamente. Com relação às hemoglobinopatias, encontrou-se prevalência do traço para anemia falciforme de 2,15% abaixo da média nacional, que é de 2,6%. A prevalência do traço C no município foi de 0,57%, semelhante a valores nacionais disponíveis na literatura. FA BART´S confirmado apresentou valor de 0,13% abaixo da média de 0,38% da região do município de Araraquara. A realização do teste do pezinho e o aconselhamento aos cuidadores são fatores importantes para redução de morbidades relacionadas à evolução dessas doenças.

The National Neonatal Screening Program (NNSP) set up in all Brazil, aims, through planned phases of local implementation, to detect diseases such as phenylketonuria, congenital hypothyroidism, hemoglobinopathies and cystic fibrosis. The aim of this study was to assess, through a cross-sectional observational study, the prevalence of the diseases detected by the NNSP in the city of Araraquara, in records issued by the São Paulo APAE laboratory in the period between April and December 2009.The results show that Araraquara had a prevalence of phenylketonuria and congenital hypothyroidism 0.06% above the national averages of 0.01% and 0.03% respectively. With respect to hemoglobinopathies, the prevalence of sickle cell trait was 2.15% below the national average of 2.6%. The prevalence of Hb C in the city was 0.57%, similar to national values reported in the literature. Confirmed Hb Bart´s had a prevalence of 0.13% in Araraquara, below the average of 0.38% for the surrounding region. The neonatal screening by heel-prick test and counseling for caregivers are important factors in reducing morbidity related to the evolution of these diseases.

Advances in biliary atresia: from patient care to research

Biliary atresia, the most common cause of liver transplantation in children, remains a challenge for clinicians and investigators. The development of new therapeutic options, besides the typical hepatoportoenterostomy, depends on a greater understanding of its pathogenesis and how it relates to the clinical phenotypes at diagnosis and the rate of disease progression. In this review, we present a perspective of how recent research has advanced the understanding of the disease and has improved clinical care protocols. Molecular and morphological analyses at diagnosis point to the potential contributions of polymorphism in the CFC1 and VEGF genes to the pathogenesis of the disease, and to an association between the degree of bile duct proliferation and long-term outcome. In experimental models, cholangiocytes do not appear to have antigen-presenting properties despite a substantial innate and adaptive immune response that targets the biliary epithelium and produces duct obstruction. Initial clinical trials assessing the efficacy of corticosteroids in decreasing the inflammation and improving outcome do not show a superior effect of corticosteroids as an adjuvant treatment following hepatoportoenterostomy. The best outcome still remains linked to an early diagnosis and surgical treatment. In this regard, the Yellow Alert campaign by the Sociedade Brasileira de Pediatria and the inclusion of the Stool Color Card in the health booklet given to every neonate in Brazil have the potential to decrease the age of diagnosis, shorten the time between diagnosis and surgical treatment, and improve the long-term outcome of children with this devastating disease.

Neonatal screening for cystic fibrosis in São Paulo State, Brazil: a pilot study

Cystic fibrosis is one of the most common autosomal recessive hereditary diseases in the Caucasian population, with an incidence of 1:2000 to 1:3500 liveborns. More than 1000 mutations have been described with the most common being F508del. It has a prevalence of 23-55 percent within the Brazilian population. The lack of population-based studies evaluating the incidence of cystic fibrosis in São Paulo State, Brazil, and an analysis concerning the costs of implantation of a screening program motivated the present study. A total of 60,000 dried blood samples from Guthrie cards obtained from April 2005 to January 2006 for neonatal screening at 4 reference centers in São Paulo State were analyzed. The immunoreactive trypsinogen (IRT)/IRT protocol was used with the cut-off value being 70 ng/mL. A total of 532 children (0.9 percent) showed IRT >70 ng/mL and a 2nd sample was collected from 418 (80.3 percent) of these patients. Four affected children were detected at two centers, corresponding to an incidence of 1:8403. The average age at diagnosis was 69 days, and 3 of the children already showed severe symptoms of the disease. The rate of false-positive results was 95.2 percent and the positive predictive value for the test was 8 percent. The cost of detecting an affected subject was approximately US$8,000.00 when this cystic fibrosis program was added to an existing neonatal screening program. The present study clearly shows the difficulties involved in cystic fibrosis screening using the IRT/IRT protocol, particularly in a population with no long-term tradition of neonatal screening.

Estudo de metodologia analítica para a determinação do cetoconazol em formulações farmacêuticas / Study of analytical methodology for ketoconazole determination in pharmaceutical preparation

Cetoconazol é um antifúngico sintético, derivado imidazólico de amplo espectro de ação, efetivo no tratamento de infecções superficiais e sistêmicas. Foram estudadas diferentes metodologias para análise do cetoconazol em especialidades farmacêuticas diversas usando espectrofotometria no ultravioleta, no infravermelho e análise térmica. Os resultados mostram que a espectrofotometria ultravioleta é um método rápido, prático e econômico e apontam que outros métodos como a espectrofotometria no infravermelho e análise térmica são uma alternativa à análise do cetoconazol em diferentes especialidades farmacêuticas.

Ketoconazole is a synthetic broad-spectrum oral and topical antifungal drug derived from imidazole, effective in the treatment of superficial mycoses and systemic infections. In this study we have tested several methods to analyze ketoconazole in various pharmaceutical products containing this drug, employing techniques such as UV and IR spectrophotometry and thermal analysis. The results showed that UV spectrophotometryis a fast, practical and economical method and indicated that other methods, such as IR spectrophotometry and thermal analysis, could be good alternative methods for ketoconazole analysis in certain pharmaceutical forms.

Influencia familiar sobre la conducta alimentaria y su relación con la obesidad infantil: [revisão] / Eating behavior and childhood obesity: family influences: [review]

La conducta alimentaria es el conjunto de acciones que establecen la relación del ser humano con los alimentos. Se acepta generalmente que los comportamientos frente a la alimentación se adquieren a través de la experiencia directa con la comida, por la imitación de modelos, la disponibilidad de alimentos, el estatus social, los simbolismos afectivos y las tradiciones culturales. Además de las influencias sociales, se ha señalado que las influencias genéticas y de ambiente familiar compartido, tienen un impacto relevante sobre el patrón de ingesta, la conducta alimentaria y la obesidad infantil. Los estudios sobre ingesta de alimentos en obesidad se han centrado principalmente en determinar la cantidad y tipo de alimentos de la dieta habitual, presentando resultados controversiales. También existe un interés creciente por explorar la relación entre la obesidad y la conducta de alimentación, medida a través de herramientas psicométricas que analizan diferentes dimensiones tales como la alimentación emocional, la alimentación sin control o la restricción cognitiva. Esta revisión aborda la influencia de la familia sobre la conducta alimentaria infantil en relación con la obesidad, tanto desde la perspectiva del ambiente familiar compartido como desde la herencia genética.

Eating behavior involves all actions that define the relation between human beings and food. It is accepted that feeding habits are acquired through eating experiences and practices learned from the familiar and social context in early childhood. Besides the role of the social context, it is also assumed that familiar factors, both common family environment and genetic inheritance, have an important influence on food intake and eating behavior linked with childhood obesity. Research on food intake and childhood obesity has been traditionally focused on the amount and type of foods in the usual diet. However, it is an increasing interest to understand the link between eating behavior and obesity using questionnaires. There are several psychometric tools that have been developed specifically to deal with human eating behavior. This review summarizes the family influences, both genetic and non-genetic, on childhood feeding behavior and their relation to childhood obesity.

Swine infection by Streptococcus suis: a retrospective study / Infecção em suínos por Streptococcus suis: estudo retrospectivo

The epidemic aspects of swine infections caused by Streptococcus suis were studied, focusing mainly on the occurrence of several serotypes. A total of 323 samples of S. suis were isolated from clinically ill animals, serotyped according to the co-agglutination procedure, and analyzed. The serotyping revealed that S. suis was present in several Brazilian states. The largest number was isolated from the states of Minas Gerais (62.5 percent), São Paulo (10.8 percent), and Paraná (9.3 percent). Serotype 2 was the most frequent (61.0 percent), followed by the serotypes 1, 3, 4, 7, and 8. The largest number of isolations was obtained from the brain (60.1 percent), followed by the lungs (10.4 percent). About 9.4 percent of the cases were due to septicemia.

Estudaram-se os aspectos epidêmicos das infecções de suínos causadas por Streptococcus suis, enfocando, principalmente, a ocorrência de diferentes sorotipos. Foram analisadas 323 amostras isoladas de animais clinicamente doentes, as quais foram sorotipadas de acordo com o procedimento de co-aglutinação. Foi verificado que S. suis está presente em vários estados brasileiros e o maior número de isolados originou-se dos estados de Minas Gerais (62,5 por cento), São Paulo (10,8 por cento) e Paraná (9,3 por cento). O sorotipo 2 foi o mais freqüente (61.0 por cento), seguido pelos sorotipos 1, 3, 4, 7 e 8. Os isolamentos foram obtidos principalmente de cérebro (60,1 por cento) e pulmões (10,4 por cento). Os casos de septicemia representaram 9,4 por cento.

Toxicidade de fármacos nitrofurânicos / Toxicity of nitrofuran drugs

Durante o planejamento estrutural de novos fármacos, é possível prever a influência de grupamentos específicos na atividade farmacológica. Entre estes, encontra-se o grupo nitro, que possui potencial atividade antimicrobiana, estando presente em diversos fármacos como o metronidazol, nitrofural, furazolidona, oxamniquina, cloranfenicol, entre outros. Também, a introdução do grupo nitro na molécula pode alterar as propriedades físico-químicas e eletrônicas da substância, estando presente em fármacos de outras classes terapêuticas como anti-úlcera, ansiolítico, antiinflamatório. Entretanto, restrições têm sido apontadas para o planejamento de novos fármacos contendo este grupo, devido à toxicidade relacionada. Este estudo trata-se da revisão sobre a toxicidadede compostos nitrofurânicos, bem como os possíveis mecanismos e a utilização do método de latenciação na diminuição desta toxicidade.

Síntese e modelagem molecular do novo derivado indolinônico como candidato a antiinflamatório COX-2 seletivo / Synthesis and molecular modeling of a novel indolinone derivative as a candidate anti-inflammatory selectively inhibiting COX-2

Os fármacos antiinflamatórios são sabidamente os mais comercializados em todo o mundo, e apesar disto apresentam sérios efeitos colaterais, sobretudo no que se refere ao trato gastrintestinal. A descoberta de novos protótipos com atividade e segurança terapêutica melhoradas continua sendo uma busca constante. Com o adventoda química computacional torna-se mais fácil o estudo teórico do comportamento fisiológico de uma nova substância bem como a compreensão do possível mecanismo de ação destas novas moléculas. Assim, através de modelos matemáticos de moléculas e receptores estudou-se neste trabalho o composto I (1-(2,6- diclorofenil)indolin-2-ona) quanto à sua possibilidade deinibir seletivamente a isoforma COX-2 da enzima prostaglandina endoperóxido sintase (PGHS), e também as melhores posições para a introdução de grupamentos químicos e modificações moleculares.

Microondas doméstico na síntese de derivados ftalimídicos / Use of domestic microwave oven in the synthesis of phthalimide derivatives

Microondas são utilizadas na síntese orgânica desde 1986, e mostra-se vantajosa em diversos aspectos como possibilidade de maiores rendimentos, maior seletividade e menor decomposição térmica. A ftalimida e derivados, constituem-se em uma importante classe de compostos utilizados na química orgânica sintética, e do ponto de vista da Química Farmacêutica e Medicinal, é considerada um importante bióforo constituindo subunidade estrutural de caráter farmacofórico para uma série de compostos com diferentes atividades farmacológicas, entre elas, a anemia falciforme. O objetivo deste trabalho foi desenvolver metodologia alternativa na síntese de derivados ftalimídicos explorando a condensação de anidrido ftálico com aminas funcionalizadas sob radiação de microondas doméstico. Os resultados mostraram que os compostos ftalímidicos sintetizados podem ser obtidos em menores tempos reacionais (5-10 minutos) e maiores rendimentos(60-89%) quando comparados ao aquecimento convencional (refluxo), demonstrando o potencial da utilização do microondas na obtenção destas moléculas...

Diagnóstico da pneumonia enzoótica suína pela técnica da imunoperoxidase / Immunoperoxidase technique for diagnosis of enzootic pnemonia in swine

Avaliou-se a técnica da imunoperoxidase como método auxiliar para a detecção de Mycoplasma hyopneumoniae em suínos naturalmente infectados. Foram colhidos 80 fragmentos de pulmões de 40 animais provenientes de granjas consideradas negativas e 40 de granjas com diagnóstico positivo de pneumonia enzoótica. Com a utilização de soro policlonal específico (IgG de coelho anti- M. hyopneumoniae) observou-se correlação positiva de 77 por cento entre os diagnósticos microscópicos e imunoistoquímicos, enquanto que a correlação entre os diagnósticos macroscópico e imunoistoquímico foi de 49 por cento. Nas granjas consideradas negativas observou-se presença de discreta imunorreação em 22,5 por cento dos casos, o que poderia indicar a existência de reação cruzada com outros microrganismos. Nas granjas com diagnóstico positivo para pneumonia enzoótica a técnica da peroxidase-anti-peroxidase (PAP) revelou diferentes graus de intensidade, variando de fraca imunomarcação até espesso depósito amarronzado no epitélio ou na luz das vias aéreas, ou ainda no interior de macrófagos, com relação direta entre a intensidade das lesões e da imunorreação. A técnica imunoistoquímica possui sensibilidade de 95 por cento e especificidade de 77,5 por cento, podendo ser recomendada como ferramenta auxiliar, rápida e de baixo custo para o diagnóstico de pneumonia enzoótica suína em laboratórios de rotina em histopatologia.

Diarréia em leitões lactentes por Clostridium perfringens tipo A em granjas tecnificadas nos estados de Minas Gerais e São Paulo / Clostridium perfringens type A diarrhea in suckling piglets in industrial swine farms in the states of Minas Gerais and São Paulo

Diarrhea in suckling piglets caused by Clostridium perfringens type A was diagnosed in industrial (technified) swine farms of the states of Minas Gerais and São Paulo (Brazil), based on isolation and identification of bacterium by biochemical tests, detection of alpha toxin in animal bioassays, and PCR. This seems to be the first report of clostridial enterotoxaemia in piglets by C. perfringens type A in Brazil and allowed specific procedures to control the disease.

Anticuerpos anti-albúmina bovina (BSA) en niños diabéticos tipo 1 recién diagnosticados y su asociación con lactancia materna y exposición a leche de vaca / Bovine serum albumin (BSA) antibodies in children with recently diagnosed type 1 diabetes with breast feeding and milk exposition

BACKGROUND: Environmental and genetic factors (viruses, toxins and diet) are involved in the aetiology of type 1 diabetes. Among the dietary factors, the role of breast feeding and exposure to cow's milk proteins deserve special attention. AIM: To determine the anti-BSA-IgG levels in type 1 diabetic children and to analyse the possible association with breast feeding duration, exposure to cow's milk and beta pancreatic auto-antibodies. PATIENTS AND METHODS: Blood samples were collected from 161 diabetic children and 144 controls to measure anti-BSA-IgG level, GAD65, IA-2 and ICA autoantibodies. All children answered a questionnaire about dietary habits during infancy. RESULTS: anti-BSA-IgG was positive (using a cut off point of 25.6 ng/ml) in 98 per cent of diabetic children and 0 per cent of the control population. The length of breast feeding or early exposure to cow's milk did not influence the concentration of anti-BSA-IgG. Positive BSA titers did not increase the beta pancreatic reactivity (ICA+, GAD+, IA2+). CONCLUSIONS: Our data confirm the high frequency of anti-BSA-IgG among diabetic children. However, a specific role in the immunological process of type 1 diabetes cannot be attributed to this protein.

Incidence rate and spatio-temporal clustering of type 1 diabetes in Santiago, Chile, from 1997 to 1998

Objetibo: Estimar a taxa de incidência de diabetes tipo 1 na área urbana de Santiago, Chile, entre os dias 21 de março de 1997 e 20 de março 1998, assim como a avaliação do agrupamento espaço-temporal dos casos incidentes no período. Métodos: Foram localizados 61 casos incidentes no tempo (dia do diagnóstico) e no espaço (lugar de residência) na área do estudo. O método de Knox foi usado para avaliar o agrupamento dos casos no espaço e no tempo. Resultados: A taxa de diabetes tipo 1 foi estimada em 4,11 casos por 100.000 menores de 15 anos por ano (Intervalo de confiança 95 por cento: 3,06 ó 5,14). Essa taxa de incidência parece ter aumentado desde a última estimativa realizada na região metropolitana de Santiago, nos anos 1986-1992. Foram construídas diferentes combinações de intervalos de espaço e tempo para determinar a agregação espaço-temporal dos casos incidentes. A quase significativa agregação de casos foi detectada usando as distâncias críticas de 750 m e 60 dias (valor p não corrigido = 0,048). Conclusões: Embora o estudo só mostre resultados preliminares do agrupamento espaço-temporal dos casos de diabetes tipo 1, em Santiago, a análise dos dados sugere uma possível agregação de casos incidentes nas coordenadas de espaço e tempo

Mejoría de la función respiratoria con una técnica de apertura pulmonar (AP) / Improvement of respiratory function with a technique of open lung

Objetivo: La ventilación mecánica (VM) ha demostrado ser una terapeútica útil en pacientes con compromiso de la función respiratoria. Son múltiples las complicaciones asociadas a los modos convencionales de VM. Están en desarrollo técnicas para disminuir la incidencia de efectos adversos. El objetivo del trabajo es evaluar la técnica ventilatoria denominada APERTURA PULMONAR (AP). (Open Lung Concept. Intens Care Med. 18:319-321, 1992). Pacientes y métodos: Se incorporaron en forma prospectiva y randomizada los pacientes que requirieron VM. Se usaron Siemmens Servo 300 y 900C. Se utilizaron tres modos ventilatorios: Presión Control (PC), Volumen Control (VC), y AP (con parámetros iniciales VT 7-10 ml/kg, PEEP/Presión Inspiratoria Pico (PIP) de 5/25, e incrementos progresivos de 5 cm H20 hasta alcanzar 15/60 e inmediato descenso, posteriormente éste grupo fue ventilado en modo PC con los parámetros de PEEP/PIP de 5-10/25-30, VT 7-10 ml/kg, I:E de 1:1.3, con frec. resp. entre 10-15. La AP se repitió según criterio del equipo médico. Se usó la escala de Murray al ingreso para estratificar las muestras. Se efectuaron registros seriados de monitoreo respiratorio y gasométrico. Se compararon los valores de Pao2/Fio2 entre los diferentes modos ventilatorios. Resultados: Ingresaron 42 pacientes. Se efectuaron 505 monitoreos. En la tabla se observan las comparaciones de los valores de las Pao2/Fio2 generales entre los grupos y las Pao2/Fio2 según horas de VM y según valor de Murray. Conclusiones: el modo AP tuvo mejores índices de oxigenación, siendo más evidente con el transcurso del tiempo y en los pacientes con mayor injuria pulmonar

Histopathological diagnosis of intra-and extrahepatic neonatal cholestasis

The histopathology of the liver is fundamental for the differential diagnosis between intra- and extrahepatic causes of neonatal cholestasis. However, histopathological findings may overlap and there is disagreement among authors concerning those which could discriminate between intra- and extrahepatic cholestasis. Forty-six liver biopsies (35 wedge biopsies and 11 percutaneous biopsies) and one specimen from a postmortem examination, all from patients hospitalized for neonatal cholestasis in the Pediatrics Service of Hospital de Clínicas de Porto Alegre, were prospectively studied using a specially designed histopathological protocol. At least 4 of 5 different stains were used, and 46 hepatic histopathological variables related to the differential diagnosis of neonatal cholestasis were studied. The findings were scored for severity on a scale from 0 to 4. Sections which showed less than 3 spaces were excluded form the study. Sections were examined by a pathologist who was unaware of the final diagnosis of each case. Bile tract permeability was defined by scintigraphy of the bile ducts and operative cholangiography. The F test and discriminant analysis were used as statistical methods for the study of the hepatic histopathological variables. The chi-square method with Yates correction was used to relate the age of the patients on the date of the histopathological study to the discriminatory variables between intra- and extrahepatic cholestaasis selected by the discriminant function test. The most valuable hepatic histopathological variables for the discrimination between intra- and extrahepatic cholestasis, in decreasing order of importance, were periportal ductal proliferation, portal ductal proliferation, portal expansion, cholestasis in neoductules, foci of myeloid metaplasia, and portal-portal bridges. The only variable which pointed to the diagnosis of intrahepatic cholestasis was myeloid metaplasia. Due to the small number of patients who were younger than 60 days on the date of the histopathological study (N=6), no variable discriminated between intra- and extrahepatic cholestasis before the age of 2 months and all of them, except for the portal expansion, were discriminatory after this age. In infants with cholestasis, foci of myeloid metaplasia, whenever present in the liver biopsy, suggested intrahepatic cholstasis. Periportal ductal proliferation, portal ductal proliferation, portal expansion, cholestasis in neoductules...

A model of complete random molecular evolution by recurrent mutation

A model for random molecular evolution based on recurrent mutation is proposed. Recurrent mutation replaces completely any original base in a nucleotidic site. This occurs if more than four times the number of reproductive cycles equal to the reciprocal of the mutation rate happen; no matter the population size, the number of nucleotides a genome has, or the taxa at which it belongs. The main results are: i) the expected distribution of DNA bases in a site is an isotetranomial distribution, where Adenine (A), Guanine (G), Cytosine (C) and Thymine (T) occur with probability equal to 0.25; ii) the distribution of bases in a site is independent from the distribution of bases in other sites. Several expected consequences that can be contrasted with actual data are generated. Species or operational taxonomic units (OTUs) that evolved in big populations should present distances equal to zero and similarities equal to one. OTUs evolving in small populations should present distances equal to 3/4 and similarities equal to 1/4. Thus, random molecular evolution by recurrent mutation cannot yield a tree at all. The only possible tree is that produced by random fluctuations of distances according to their variances (stochastic tree). Some consequences of the model on the expected primary structure of proteins are also analyzed. There are sufficient generations for any DNA segment evolving apart during the last four hundred million years, to reach those expected base distributions

Detecção de isquemia miocárdica em chagásicos crônicos com precordialgia atípica pelos testes de esforço e Holter / Detection of Myocardial Ischemia in Chagas' Disease Patients with Angina-Like Symptoms by the Effort Test and Holter Monitoring

Objetivo - Investigar a freqüência e as características de alteraçöes isquêmicas miocárdicas detectadas pela eletrocardiografia de esforço e monitorizaçäo eletrocardiográfica contínua (Holter) em pacientes chagásicos com dor precordial. Métodos - Trinta e um pacientes com diagnósticos clínicos e sorológico de doença de Chagas (54,4 ñ 9,6 anos, 51// homens) foram investigados para esclarecimento causal de angina de peito intensa e preocupante a ponto de afetar o padräo de vida e exigir exploraçäo agressiva. A detecçäo de isquemia miocárdica consistiu de 1 teste de esforço máximo e 2) Holter de 24h. Todos os pacientes foram submetidos a cinecoronariografia, ocasiäo em que se executava manobra de hiperventilaçäo controlada para constataçäo de espasmo arterial coronário. Os resultados obtidos com os dois testes (esforço e Holter) foram correlacionados e confrontados com os obtidos durante a cinecoronariografia. Resultados - alteraçöes basais do eletrocardiograma (ECG) impediram a análise do segmento ST em 11 pacientes. Dos restantes, 7(35//) apresentaram angina no teste de esforço. Dois deles (10//) tiveram isquemia miocárdica concomitante, detectando-se coronariopatia orgânica/funcional em ambos (associaçäo positiva, p=0,03): lesöes de 90// na artéria circunflexa e de 50// no trajeto intramiocárdico da descendente anterior esquerda. Nesta última, após hiperventilaçäo, ocorreu espasmo que reduziu em mais de 30// o diâmetro luminal do segmento estenótico, com dor precordial e elevaçäo de ST, que reverteram com nitrato. Durante o Holter (16 pacientes com traçados aproveitáveis), 25// dos indivíduos apresentaram angina do peito, sem qualquer distúrbio arrítmico ou isquêmico concomitante. Isquemia silente ocorreu em 1 paciente (5//) durante o esforço e, em outros (18//), durante o Holter. Sua presença näo foi preditiva de alteraçöes coronárias orgânicas ou funcionais. Näo foram documentadas lesöes significativas nos 11 pacientes cujo ECG näo era passível de análise. Conclusäo - Observou-se importante limitaçäo da aplicabilidade geral dos métodos eletrocardiográficos para detecçäo de isquemia miocárdica nos pacientes chagásicos em decorrência das alteraçöes basais do ECG. Contudo, quando o ECG basal é adequado, o teste de esforço positivo (ST isquêmico, acompanhado de dor precordial) apresentou 100// de valor preditivo para doença arterial coronária orgânica/funcional. Isto ocorreu em pequena, porém näo desprezivel proporçäo desta populaçäo chagásica específica (10//). O teste de Holter näo contribuiu para elucidaçäo da origem da angina do peito em qualquer um dos doentes estudados. Ante a inconsistência dos resultados, o significado o significado clínico e fisiopatológico da isquemia silente na cardiopatia chágasica demanda investigaçäo ulterior

Purpose - To determine the incidence and characteristics of myocardial ischemia, as detected by stress electrocardiography and Holter monitoring in Chagus' patients whose main complaint was precordial pain. Methods - Thirty-one consecutive patients with Chagas' disease diagnosed on the basis of clinical and serological tests, and precordial pain severe enough to warrant cardiac catheterization were studied. Mean age was 54.4 ± 9.6 years, and 51% were males. EKG changes indicative of myocardial ischemia were sought during maximul exercise and also during 24-hour Holter monitoring. The detection of myocardial ischemia by each one of these tests was compared by Fischer exact test, and also correlated to anatomical and functional results of coronary angiography at rest and after standardized hyperventilation for detecting coronary vasospasm. Results - Baseline EKG changes mainly associated with ventricular conduction defects precluded the analysis of the ST segment in 11 patients. Among the other 20 patients, 7(35%) had angina during the exercice test, of whom only 2(10%) showed concomitant ischemic ST changes: one had 90% stenosis in the circumflex branch and the other 50% reduction of luminal diameter in a intramyocardial segment of the leit anterior descending coronary artery, undergoing further 30% constriction after hyperventilation, with pain and ST-elevation that responded to nitrate administration. Thus, a positive correlation between a positive EKG exercise test with accompanying symptoms, and organic/functional coronary artery disease was found (p = 0.03). Holter tracings of good quality were obtained in 16 patients. Angina-like symptoms occurred in 25% of these patients, without concomitant ischemic or dysrhythmic EKG changes. Conversely, silent ischemia was detected in 1 (5%) patient during exercice and in 3 (18%) patients during the Holter monitoring None of these patients had any evidence of organic or functional alterations in the coronary arteries. The absence of significant (> 50%) narrowing of the coronary arteries, t baseline and after hyperventilation, was also documented in the 11 patients in whom no valid EKG tracings were obtained for analysis. Conclusion - EKG-based methods for detecting myocardial eschemia are of limited value in the general population with Chagas' disease presenting with precordial pain, due to the high prevalence of baseline ST changes. The overall incidence of significant coronary artery disease, as detected by angiography, was low but not negligible in this population of Chagas' patients with precordial pain (4%). Nevertheless, a positive EKG test based on ST changes and accompanying pain has a 100% positive predictive accuracy for the presence of organic or functional coronary abnormalities. No additional yield was obtained with Holter monitoring, for the elucidution of the pathophysiology of the precordial pain in Chagas' patients with atypical angina. The significance of episodes of silent ischemia in some of these patients, with angiographically normal coronary arteries, remains to be determined