Validation of physician certified verbal autopsy using conventional autopsy: a large study of adult non-external causes of death in a metropolitan area in Brazil.

BACKGROUND: Reliable mortality data are essential for the development of public health policies. In Brazil, although there is a well-consolidated universal system for mortality data, the quality of information on causes of death (CoD) is not even among Brazilian regions, with a high proportion of ill-defined CoD. Verbal autopsy (VA) is an alternative to improve mortality data. This study aimed to evaluate the performance of an adapted and reduced version of VA in identifying the underlying causes of non-forensic deaths, in São Paulo, Brazil. This is the first time that a version of the questionnaire has been validated considering the autopsy as the gold standard. METHODS: The performance of a physician-certified verbal autopsy (PCVA) was evaluated considering conventional autopsy (macroscopy plus microscopy) as gold standard, based on a sample of 2060 decedents that were sent to the Post-Mortem Verification Service (SVOC-USP). All CoD, from the underlying to the immediate, were listed by both parties, and ICD-10 attributed by a senior coder. For each cause, sensitivity and chance corrected concordance (CCC) were computed considering first the underlying causes attributed by the pathologist and PCVA, and then any CoD listed in the death certificate given by PCVA. Cause specific mortality fraction accuracy (CSMF-accuracy) and chance corrected CSMF-accuracy were computed to evaluate the PCVA performance at the populational level. RESULTS: There was substantial variability of the sensitivities and CCC across the causes. Well-known chronic diseases with accurate diagnoses that had been informed by physicians to family members, such as various cancers, had sensitivities above 40% or 50%. However, PCVA was not effective in attributing Pneumonia, Cardiomyopathy and Leukemia/Lymphoma as underlying CoD. At populational level, the PCVA estimated cause specific mortality fractions (CSMF) may be considered close to the fractions pointed by the gold standard. The CSMF-accuracy was 0.81 and the chance corrected CSMF-accuracy was 0.49. CONCLUSIONS: The PCVA was efficient in attributing some causes individually and proved effective in estimating the CSMF, which indicates that the method is useful to establish public health priorities.

Validation of SmartVA using conventional autopsy: A study of adult deaths in Brazil.

Background: Accurate cause of death data are essential to guide health policy. However, mortality surveillance is limited in many low-income countries. In such settings, verbal autopsy (VA) is increasingly used to provide population-level cause of death data. VAs are now widely interpreted using the automated algorithms SmartVA and InterVA. Here we use conventional autopsy as the gold standard to validate SmartVA methodology. Methods: This study included adult deaths from natural causes in São Paulo and Recife for which conventional autopsy was indicated. VA was conducted with a relative of the deceased using an amended version of the SmartVA instrument to suit the local context. Causes of death from VA were produced using the SmartVA-Analyze program. Physician coded verbal autopsy (PCVA), conducted on the same questionnaires, and Global Burden of Disease Study data were used as additional comparators. Cause of death data were grouped into 10 broad causes for the validation due to the real-world utility of VA lying in identifying broad population cause of death patterns. Findings: The study included 2,060 deaths in São Paulo and 1,079 in Recife. The cause specific mortality fractions (CSMFs) estimated using SmartVA were broadly similar to conventional autopsy for: cardiovascular diseases (46.8% vs 54.0%, respectively), cancers (10.6% vs 11.4%), infections (7.0% vs 10.4%) and chronic respiratory disease (4.1% vs 3.7%), causes accounting for 76.1% of the autopsy dataset. The SmartVA CSMF estimates were lower than autopsy for "Other NCDs" (7.8% vs 14.6%) and higher for diabetes (13.0% vs 6.6%). CSMF accuracy of SmartVA compared to autopsy was 84.5%. CSMF accuracy for PCVA was 93.0%. Interpretation: The results suggest that SmartVA can, with reasonable accuracy, predict the broad cause of death groups important to assess a population's epidemiological transition. VA remains a useful tool for understanding causes of death where medical certification is not possible.

Profile of deaths from unspecified stroke after investigation of garbage codes in 60 cities in Brazil, 2017. / Perfil dos óbitos por acidente vascular cerebral não especificado após investigação de códigos garbage em 60 cidades do Brasil, 2017.

INTRODUCTION: Unspecified stroke (UnST) is of great importance in mortality statistics, as it is the fourth leading cause of death in Brazil. The objective of this study was to identify the profile of reclassified causes of death after investigation of deaths caused by UnST in Brazil. METHODS: All deaths registered as UnST in 2017 in the Mortality Information System (SIM) were considered as garbage codes. The specific causes, detected after investigation in 60 selected cities, were analyzed by age and sex. RESULTS: Of the total deaths due to UnST identified in these 60 cities (n = 11,289), 25.8% were investigated. Of these, 56.3% were reclassified to ischemic stroke, 12.7% to hemorrhagic stroke, and 23.3% to other specific causes, such as diabetes and chronic kidney disease, in both sexes. DISCUSSION: The higher proportion of deaths due to ischemic stroke in comparison to hemorrhagic stroke was expected. However, the detection of other specific causes outside the stroke group indicates possible quality problems in the filling of death certificate (DC). CONCLUSION: The investigations allowed the identification of subgroups of deaths due to stroke. In addition to the research, however, it is important to conduct physician training in the adequate filling in of the DC, in order to improve estimates of specific stroke mortality, and to enable appropriate targeting of health actions and services.

INTRODUÇÃO: O acidente vascular cerebral não especificado (AVC-NE) é de grande relevância nas estatísticas de mortalidade, sendo a quarta maior causa de morte no Brasil. O objetivo deste estudo foi identificar o perfil de causas reclassificadas após investigação de óbitos por AVC-NE no Brasil. MÉTODOS: Foram selecionados todos os óbitos registrados em 2017 no Sistema de Informação sobre Mortalidade (SIM) como AVC-NE, considerados códigos garbage. As causas específicas, detectadas após investigação em 60 cidades selecionadas, foram analisadas segundo idade e sexo. RESULTADOS: Do total de óbitos por AVC-NE das 60 cidades (n = 11.289), foram investigados 25,8%, dos quais 56,3% foram reclassificados para AVC isquêmico, 12,7% para AVC hemorrágico, e 23,3% migraram para outras causas específicas, como diabetes e doença renal crônica, em ambos os sexos. DISCUSSÃO: A maior proporção de reclassificação dos óbitos por AVC-NE para AVC isquêmico em relação ao hemorrágico era esperada. No entanto, a detecção de outras causas específicas fora do grupo de AVC indica possíveis problemas de qualidade do preenchimento das causas na declaração de óbito (DO). CONCLUSÃO: As investigações realizadas permitiram identificação de subgrupos de AVC. Além da investigação, entretanto, é importante realizar capacitação com médicos para o preenchimento adequado da DO, a fim de melhorar as estimativas da mortalidade por AVC específico e possibilitar direcionamento adequado das ações e dos serviços de saúde.

Perfil dos óbitos por acidente vascular cerebral não especificado após investigação de códigos garbage em 60 cidades do Brasil, 2017 / Profile of deaths from unspecified stroke after investigation of garbage codes in 60 cities in Brazil, 2017

RESUMO Introdução: O acidente vascular cerebral não especificado (AVC-NE) é de grande relevância nas estatísticas de mortalidade, sendo a quarta maior causa de morte no Brasil. O objetivo deste estudo foi identificar o perfil de causas reclassificadas após investigação de óbitos por AVC-NE no Brasil. Métodos: Foram selecionados todos os óbitos registrados em 2017 no Sistema de Informação sobre Mortalidade (SIM) como AVC-NE, considerados códigos garbage. As causas específicas, detectadas após investigação em 60 cidades selecionadas, foram analisadas segundo idade e sexo. Resultados: Do total de óbitos por AVC-NE das 60 cidades (n = 11.289), foram investigados 25,8%, dos quais 56,3% foram reclassificados para AVC isquêmico, 12,7% para AVC hemorrágico, e 23,3% migraram para outras causas específicas, como diabetes e doença renal crônica, em ambos os sexos. Discussão: A maior proporção de reclassificação dos óbitos por AVC-NE para AVC isquêmico em relação ao hemorrágico era esperada. No entanto, a detecção de outras causas específicas fora do grupo de AVC indica possíveis problemas de qualidade do preenchimento das causas na declaração de óbito (DO). Conclusão: As investigações realizadas permitiram identificação de subgrupos de AVC. Além da investigação, entretanto, é importante realizar capacitação com médicos para o preenchimento adequado da DO, a fim de melhorar as estimativas da mortalidade por AVC específico e possibilitar direcionamento adequado das ações e dos serviços de saúde.

ABSTRACT Introduction: Unspecified stroke (UnST) is of great importance in mortality statistics, as it is the fourth leading cause of death in Brazil. The objective of this study was to identify the profile of reclassified causes of death after investigation of deaths caused by UnST in Brazil. Methods: All deaths registered as UnST in 2017 in the Mortality Information System (SIM) were considered as garbage codes. The specific causes, detected after investigation in 60 selected cities, were analyzed by age and sex. Results: Of the total deaths due to UnST identified in these 60 cities (n = 11,289), 25.8% were investigated. Of these, 56.3% were reclassified to ischemic stroke, 12.7% to hemorrhagic stroke, and 23.3% to other specific causes, such as diabetes and chronic kidney disease, in both sexes. Discussion: The higher proportion of deaths due to ischemic stroke in comparison to hemorrhagic stroke was expected. However, the detection of other specific causes outside the stroke group indicates possible quality problems in the filling of death certificate (DC). Conclusion: The investigations allowed the identification of subgroups of deaths due to stroke. In addition to the research, however, it is important to conduct physician training in the adequate filling in of the DC, in order to improve estimates of specific stroke mortality, and to enable appropriate targeting of health actions and services.

Notes from the Field: Evidence of Zika Virus Infection in Brain and Placental Tissues from Two Congenitally Infected Newborns and Two Fetal Losses--Brazil, 2015.

Zika virus is a mosquito-borne flavivirus that is related to dengue virus and transmitted primarily by Aedes aegypti mosquitoes, with humans acting as the principal amplifying host during outbreaks. Zika virus was first reported in Brazil in May 2015 (1). By February 9, 2016, local transmission of infection had been reported in 26 countries or territories in the Americas.* Infection is usually asymptomatic, and, when symptoms are present, typically results in mild and self-limited illness with symptoms including fever, rash, arthralgia, and conjunctivitis. However, a surge in the number of children born with microcephaly was noted in regions of Brazil with a high prevalence of suspected Zika virus disease cases. More than 4,700 suspected cases of microcephaly were reported from mid-2015 through January 2016, although additional investigations might eventually result in a revised lower number (2). In response, the Brazil Ministry of Health established a task force to further investigate possible connections between the virus and brain anomalies in infants (3).

Comparative study of Low-level laser therapy and microcurrent on the healing of skin burns in rats / Estudo comparativo da laserterapia de baixa intensidade e microcorrente no reparo tecidual de queimaduras em ratos

This study investigated and compared the effects of low-level laser therapy (LLLT) and microcurrent in the burn healing process in Wistar rats. We conducted a randomized controlled study with 30 rats divided into 3 groups (n = 10); control group (CG), laser group (LG) and microcurrent group (MG). After thermal damage, 10 applications of 660 nm diode laser were performed in GL and 10 applications of 60 Hz microcurrent (160 µA) in MG. The semi-quantitative histological analysis was done using scores (0­3), in sections stained by hematoxylin and eosin and Masson's trichrome. The results indicated a significant improvement in the fibroblasts proliferation, collagen fibers deposition, neoangiogenesis, and cutaneous appendages regeneration in MG and LG. When microcurrent and LLLT were compared, no difference was detected, except the regeneration and formation of new cutaneous appendages, observed in MG. Despite the similar effects, GM showed faster tissue repair with the formation of skin appendages.

Este trabalho teve por objetivo investigar e comparar os efeitos da laserterapia de baixa intensidade (LTBI) e microcorrente no processo de reparo de queimadura em ratos Wistar. Foi realizado um estudo randomizado controlado com 30 ratos divididos em 3 grupos (n = 10); grupo controle (GC), grupo laser (GL) e grupo microcorrente (GM). Após lesão térmica, 10 aplicações de laser InGaAlP de 660 nm foram submetidas ao GL e 10 aplicações de microcorrente de 60 Hz (160 µA) ao GM. Foi realizada análise semi-quantificativa dos dados histológicos através de escores (0-3), em cortes corados por hematoxilina e eosina e tricrômico de Masson. Os resultados indicaram que houve melhora significativa na proliferação de fibroblastos, deposição de fibras colágenas, neoangiogênese e regeneração de apêndices cutâneos no GM e GL. Quando a microcorrente e a LTBI foram comparados, não houve diferença, exceto na regeneração e formação de apêndices cutâneos, observada no GM. O laser e a microcorrente produziram melhora no reparo tecidual de queimaduras em ratos. Embora possua efeitos semelhantes, o GM apresentou reparação tecidual mais rápida com o aparecimento de apêndices cutâneos.

Laserterapia e microcorrente na cicatrização de queimadura em ratos. Terapias associadas ou isoladas? / Low-level laser therapy and micro current in burn wound healing in rats. Associated or isolated therapy? / Laserterapia y microcorriente en la cicatrización de quemaduras en ratas. ¿Terapias asociadas o aisladas?

Este estudo teve o objetivo de investigar se há diferenças entre as terapias associadas e isoladas do laser e microcorrentes no reparo de lesão por queimadura em ratos. Um total de 40 animais foi dividido aleatoriamente em quatro grupos: grupo controle (GC); grupo microcorrente (GM), grupo laser (GL) e grupo laser/microcorrente (GLM), tratados com laser associado a microcorrentes. Após lesões térmicas induzidas no dorso do animal, foi realizado um total de dez dias de tratamento. Amostras do tecido foram coletadas para estudo histopatológico semiquantitativo com Hematoxilina Eosina e Tricrômico de Masson. Foram utilizados os testes de Kruskal-Wallis e post-hoc de Dunn. Houve diferença significativa entre os grupos para a produção de fibroblastos (p=0,0003), colágeno (p=0,0153), neoangiogênese (p=0,0031) e anexos cutâneos (p=0,0004). Na análise histológica semiquantitativa, o GLM apresentou valores menores nos parâmetros histológicos de presença de colágeno, número de fibroblastos e anexos cutâneos (p<0,05) em relação às terapias isoladas, exceto para a neoangiogênese, cujos valores da terapia associada foram semelhantes aos grupos de terapia com modalidade única. Apesar do laser e da microcorrente separadamente terem efeitos benéficos para a cicatrização tecidual, a associação das modalidades parece ter diminuído a ação de reparo. No entanto, sugere-se que a associação destes recursos parece diminuir os efeitos do tratamento quando se comparam os grupos de modalidade única.

This study aimed to investigate if there are differences between the associated and isolated therapies from the laser and micro current on healing of burn wound healing in rats. A total of 40 male rats were randomly allocated into four groups: control group (CG), micro current group (MG), laser group (LG) and laser/micro current group (LMG), treated with associated laser and micro current. Thermal damage was done on the back of the animal and a total of ten days therapy was performed. After treatment samples were taken from the lesions to perform semi quantitative histopathological study using Hematoxylin Eosin and Masson Trichrome. The Kruskal-Wallis and Dunn's Test were used for statistical analyses. We observed a significant difference between groups for production of fibroblasts (p=0.0003), collagen (p=0.0153), neoangiogenesis (p=0.0031) and skin annexes (p=0.0004). In semi-quantitative histological analysis, the LMG showed lower values in presence of collagen, fibroblasts and number of skin appendages, only for neoangiogenesis, the associated therapy showed similar values to single modality therapy groups. Laser and microcurrent have beneficial effects on tissue healing. However, it is suggested that the association of these two therapies reduces the effectiveness of the treatment when compared to single mode treatment.

Este estudio tiene el objetivo de investigar si hay diferencias entre las terapias asociadas y aisladas del láser y microcorrientes en la reparación de lesión por quemadura en ratas. Un total de 40 animales fueron divididos aleatoriamente en cuatro grupos: grupo control (GC), grupo microcorriente (GM), grupo láser (GL) y grupo láser/microcorriente (GLM), tratados con láser asociado a microcorrientes. Después de inducidas las lesiones térmicas en el dorso del animal, fueron realizados en total diez días de tratamiento. Las muestras de tejido fueron recolectadas para el estudio histopatológico semicuantitativo usando Hematoxilina Eosina y Tricómico de Masson. Fueron utilizados los tests de Kruskal-Wallis y post-hoc de Dunn's. Hubo diferencia significativa entre los grupos para la producción de fibroblastos (p=0,0003), colágeno (p=0,0153), neoangiogénesis (p=0,0031) y anexos cutáneos (p=0,0004). En el análisis histológico semicuantitativo, el GLM presentó valores menores en los parámetros histológicos de presencia de colágeno, número de fibroblastos y anexos cutáneos (p<0,05) en relación a las terapias aisladas, excepto para la neoangiogénesis, cuyos valores de la terapia asociada fueron semejantes a los grupos de terapia con modalidad única. A pesar de que el láser y la microcorriente de forma aislada tienen efectos benéficos para la cicatrización del tejido, la asociación de las modalidades parece haber disminuido la acción de la reparación. El láser y las microcorrientes son efectivos en acelerar el proceso de reparación del tejido. Sin embargo, se sugiere que la asociación de estos recursos parece disminuir los efectos del tratamiento cuando son comparados con los grupos de modalidad única.

Relationship between oxidative stress and diabetic osteopenia in premenopausal rats / Relação entre o estresse oxidativo ea osteopenia diabética em ratos pré-menopausa

The relationship between lipid peroxidation, antioxidant defense and diabetic osteopenia remains unclear. This study evaluated the relationship among lipid peroxidation index, antioxidant defense parameters and bone metabolism in a premenopausal diabetic model using measures including thiobarbituric acid-reactive substances concentration (TBARS) and reduced glutathione (GSH) content in brain homogenates, histomorphometric analysis, biomechanical testing and bone mineral density (BMD). Female Wistar rats with regular estrous cycle were divided into two groups: Group 1: control rats (n = 15) and Group 2: diabetic rats (n = 15). Diabetes was induced by alloxan and confirmed by glycemia >250 mg/dL. The lipid peroxidation index, measured by TBARS concentration, showed a significant increase (p<0.05) in diabetic animals in comparison to control animals. However, the antioxidant parameter measured by GSH content, was significantly lower (p<0.05) in diabetic animals. Histomorphometric analysis showed a significant increase (p<0.05) in femoral trabecular separation together with a significant decrease (p<0.05) in trabecular thickness, and reduced trabecular bone volume in diabetic rats. Moreover, biomechanical testing and BMD values were significantly lower (p<0.05) in the diabetic group. Thus, our results demonstrated that increased lipid peroxidation and altered antioxidant defense could be related to the development of oxidative stress and diabetic osteopenia in premenopausal rats.

A relação entre peroxidação lipídica, defesa antioxidante e osteopenia diabética permanece obscura. Este estudo avaliou a associação entre índice de peroxidação lipídica, parâmetro de defesa antioxidante e metabolismo ósseo em um modelo diabético pré-menopausa através de medidas como a concentração de substâncias reativas ao ácido tiobarbitúrico (SRAT) e conteúdo de glutationa reduzida (GSH) no homogenato cerebral, análises histomorfométricas, teste biomecânico e densidade mineral óssea (DMO). Ratos Wistar fêmeas com ciclo estral regular foram distribuídos em dois grupos: Grupo 1 - ratas controle (n = 15) e Grupo 2 - ratas diabéticas (n = 15). O diabetes foi induzido pela aloxana e confirmado pela glicemia >250 mg/dL. O índice de peroxidação lipídica, medido pela concentração de SRAT, demonstrou um aumento significativo (p<0.05) nos animais diabéticos, em relação aos animais controle. Entretanto, o parâmetro de defesa antioxidante, mensurado pelo conteúdo de GSH, foi reduzido significativamente (p<0.05) nos animais diabéticos. As análises histomorfométricas mostraram um aumento significativo (p<0.05) da separação trabecular do fêmur, associado à diminuição significativa da espessura trabecular (p<0.05) e volume ósseo trabecular reduzido nas ratas diabéticas. Além disso, o teste biomecânico, medido pela força máxima, e valores de DMO foram reduzidos significativamente (p<0.05) no grupo diabético. Dessa maneira, nossos resultados demonstraram que a peroxidação lipídica aumentada e defesa antioxidante modificada podem estar relacionadas ao desenvolvimento do estresse oxidativo e osteopenia diabética em ratas pré-menopausadas.

Cytokine expression in the duodenal mucosa of patients with visceral leishmaniasis.

INTRODUCTION: Visceral leishmaniasis (VL) is a neglected tropical disease with a complex immune response in different organs. This pattern of organ-specific immune response has never been evaluated in the gastrointestinal tract. The aim of this study was to determine the in situ immune response in duodenal biopsies on patients with VL. METHODS: A case-control study was conducted on 13 patients with VL in comparison with nine controls. The immune response was evaluated using immunohistochemistry, for CD4, CD8, CD68, IL-4, IFN-gamma, TNF-alpha and IL-10. Histological findings from the villi, crypts and inflammatory process were analyzed. RESULTS: All the cases of VL presented Leishmania antigens. No antigen was detected in the control group. The villus size was greater in the VL patients (p < 0.05). CD68 (macrophages) and CD4 levels were higher in the VL patients (p < 0.05). No differences in the expression of CD8, TNF-alpha, IL-10 or IL-4 were demonstrated. The number of cells expressing IFN-gamma was lower in the VL patients (p < 0.05). CONCLUSIONS: Low levels of cytokines were found in the gastrointestinal tract of patients with VL. This pattern was not found in other organs affected by the disease. Immunotolerance of this tissue against Leishmania could explain these findings, as occurs with intestinal bacteria.

Cytokine expression in the duodenal mucosa of patients with visceral leishmaniasis / Expressão de citocinas na mucosa duodenal de pacientes com leishmaniose visceral

INTRODUCTION: Visceral leishmaniasis (VL) is a neglected tropical disease with a complex immune response in different organs. This pattern of organ-specific immune response has never been evaluated in the gastrointestinal tract. The aim of this study was to determine the in situ immune response in duodenal biopsies on patients with VL. METHODS: A case-control study was conducted on 13 patients with VL in comparison with nine controls. The immune response was evaluated using immunohistochemistry, for CD4, CD8, CD68, IL-4, IFN-γ, TNF-α and IL-10. Histological findings from the villi, crypts and inflammatory process were analyzed. RESULTS: All the cases of VL presented Leishmania antigens. No antigen was detected in the control group. The villus size was greater in the VL patients (p < 0.05). CD68 (macrophages) and CD4 levels were higher in the VL patients (p < 0.05). No differences in the expression of CD8, TNF-α, IL-10 or IL-4 were demonstrated. The number of cells expressing IFN-γ was lower in the VL patients (p < 0.05). CONCLUSIONS: Low levels of cytokines were found in the gastrointestinal tract of patients with VL. This pattern was not found in other organs affected by the disease. Immunotolerance of this tissue against Leishmania could explain these findings, as occurs with intestinal bacteria.

INTRODUÇÃO: Leishmaniose visceral (LV) é uma doença tropical negligenciada com uma resposta imune complexa em diferentes órgãos. Este padrão de resposta imune órgão-específica nunca foi avaliada no trato gastrointestinal. O objetivo deste estudo foi determinar a resposta imune in situ em biópsias duodenais de pacientes com LV. MÉTODOS: Um estudo de caso controle com 13 pacientes com LV foi comparado com 9 controles. A resposta imune foi avaliada por imunohistoquímica para CD4, CD8, CD68, IL-4, IFN-γ, TNF-α e IL-10. Achados histológicos nos vilos, criptas e processo inflamatório foram analisados. RESULTADOS: Todos os casos de LV apresentaram antígenos de Leishmania. Nenhum antígeno foi encontrado no grupo controle. O tamanho do vilo foi maior em pacientes com LV (p < 0,05). CD68 (macrófagos) e CD4 estavam aumentados em pacientes com LV (p < 0,05). Nenhuma diferença foi demonstrada na expressão de CD8, TNF-α, IL-10 e IL-4. O número de células expressando IFN-γ foi mais baixo que no grupo controle (p < 0,05). CONCLUSÕES: Baixos níveis de citocinas foram encontrados no trato gastrointestinal de pacientes com LV. Este padrão não foi encontrado em outros órgãos acometidos pela doença. Uma imunotolerância do tecido contra Leishmania poderia explicar estes achados, como ocorre com as bactérias entéricas.

Comparison of prophylactic and therapeutic use of short-chain fatty acid enemas in diversion colitis: a study in Wistar rats.

OBJECTIVES: To study the effect of short-chain fatty-acids on atrophy and inflammation of excluded colonic segments before and after the development of diversion colitis. INTRODUCTION: Diversion colitis is a chronic inflammatory process affecting the dysfunctional colon, possibly evolving with mucous and blood discharge. The most favored hypotheses to explain its development is short-chain fatty-acid deficiency in the colon lumen. METHODS: Wistar rats were submitted to colostomy with distal colon exclusion. Two control groups (A1 and B1) received rectally administered physiological saline, whereas two experimental groups (A2 and B2) received rectally administered short-chain fatty-acids. The A groups were prophylactically treated (5th to 40th days postoperatively), whereas the B groups were therapeutically treated (after post-operative day 40). The mucosal thickness of the excluded colon was measured histologically. The inflammatory reaction of the mucosal lamina propria and the lymphoid tissue response were quantified through established scores. RESULTS: There was a significant thickness recovery of the colonic mucosa in group B2 animals (p = 0.0001), which also exhibited a significant reduction in the number of eosinophilic polymorphonuclear cells in the lamina propria (p = 0.0126) and in the intestinal lumen (p = 0.0256). Group A2 showed no mucosal thickness recovery and significant increases in the numbers of lymphocytes (p = 0.0006) and eosinophilic polymorphonuclear cells in the lamina propria of the mucosa (p = 0.0022). CONCLUSION: Therapeutic use of short-chain fatty-acids significantly reduced eosinophilic polymorphonuclear cell numbers in the intestinal wall and in the colonic lumen; it also reversed the atrophy of the colonic mucosa. Prophylactic use did not impede the development of mucosal atrophy.

Hepatic stellate cell activation and hepatic fibrosis in children with type 1 autoimmune hepatitis: an immunohistochemical study of paired liver biopsies before treatment and after clinical remission.

OBJECTIVES: The activation of hepatic stellate cells (HSC) is considered the most important event in hepatic fibrogenesis. The precise mechanism of this process is unknown in autoimmune hepatitis (AIH), and more evidence is needed on the evolution of fibrosis. The aim of this study was to assess these aspects in children with type 1 AIH. METHODS: We analyzed 16 liver biopsy samples from eight patients, paired before treatment and after clinical remission, performed an immunohistochemical study with anti-alpha actin smooth muscle antibody and graded fibrosis and inflammation on a scale of 0-4 (Batts and Ludwig scoring system). RESULTS: There was no significant reduction in fibrosis scores after 24+/-18 months (2.5+/-0.93 vs. 2.0+/-0.53, P=0.2012). There was an important decrease in inflammation: portal (2.6+/-0.74 vs. 1.3+/-0.89, P=0.0277), periportal/periseptal (3.0+/-0.76 vs. 1.4+/-1.06, P=0.0277), and lobular (2.8+/-1.04 vs. 0.9+/-0.99, P=0.0179). Anti-alpha actin smooth muscle antibodies were expressed in the HSC of the initial biopsies (3491.93+/-2051.48 mum), showing a significant reduction after remission (377.91+/-439.47 microm) (P=0.0117). CONCLUSION: HSC activation was demonstrated in the AIH of children. The reduction of this activation after clinical remission, which may precede a decrease in fibrosis, opens important perspectives in the follow-up of AIH.

Comparison of prophylactic and therapeutic use of short-chain fatty acid enemas in diversion colitis: a study in Wistar rats

OBJECTIVES: To study the effect of short-chain fatty-acids on atrophy and inflammation of excluded colonic segments before and after the development of diversion colitis. INTRODUCTION: Diversion colitis is a chronic inflammatory process affecting the dysfunctional colon, possibly evolving with mucous and blood discharge. The most favored hypotheses to explain its development is short-chain fatty-acid deficiency in the colon lumen. METHODS: Wistar rats were submitted to colostomy with distal colon exclusion. Two control groups (A1 and B1) received rectally administered physiological saline, whereas two experimental groups (A2 and B2) received rectally administered short-chain fatty-acids. The A groups were prophylactically treated (5th to 40th days postoperatively), whereas the B groups were therapeutically treated (after post-operative day 40). The mucosal thickness of the excluded colon was measured histologically. The inflammatory reaction of the mucosal lamina propria and the lymphoid tissue response were quantified through established scores. RESULTS: There was a significant thickness recovery of the colonic mucosa in group B2 animals (p = 0.0001), which also exhibited a significant reduction in the number of eosinophilic polymorphonuclear cells in the lamina propria (p = 0.0126) and in the intestinal lumen (p = 0.0256). Group A2 showed no mucosal thickness recovery and significant increases in the numbers of lymphocytes (p = 0.0006) and eosinophilic polymorphonuclear cells in the lamina propria of the mucosa (p = 0.0022). CONCLUSION: Therapeutic use of short-chain fatty-acids significantly reduced eosinophilic polymorphonuclear cell numbers in the intestinal wall and in the colonic lumen; it also reversed the atrophy of the colonic mucosa. Prophylactic use did not impede the development of mucosal atrophy.

Absence of peritumoral fibrosis or inflammatory infiltrate may be related to clinical progression of papillary thyroid microcarcinoma.

Rio Grande do Norte (RN) shows the highest relative incidence of papillary carcinomas in Brazil. To analyze histological features that might be associated with this incidence, the authors compared thyroid glands from 463 autopsies performed in RN with 427 surgical and autopsy glands previously studied in Sao Paulo (SP). The authors found 41 papillary thyroid microcarcinomas (PTMs) in 35 glands (8.1%), an incidence similar to the one reported in SP (7.8%). However, PTMs were predominantly nonencapsulated nonsclerosing at microscopy (44.0%), in contrast with SP where these types of lesion represented only 4 out of 32 PTMs (12.5%; P = .0046). The authors suggest that these nonencapsulated lesions with no sign of inflammation may represent an early stage that may evolve to clinical cancers, contributing to the high incidence of clinically differentiated thyroid carcinomas observed in RN.

Primary diffuse leptomeningeal sarcoma with rhabdomyoblastic differentiation. A case report and immunohistochemical study.

Primary meningeal neoplasias are rare, and their diffuse growth within the subarachnoid space may simulate inflammatory processes or metastatic neoplastic dissemination. We report here the case of a boy with an 18-day history of fever and progressive neurological deterioration. While in the hospital, the patient showed neurological deterioration and did not respond to antituberculosis treatment. His cerebrospinal fluid (CSF) cytology disclosed an elevated white blood cell count accompanied by a mildly elevated protein level and a slightly decreased glucose level. The child died, and pathology revealed that his meningeal process was a sarcoma. The immunophenotype of the neoplastic cells showed expression of a sarcomeric actin marker, characterizing rhabdomyoblastic differentiation of the cells that occupied the subarachnoid space and invaded superficially the encephalon. Rhabdomyoblastic differentiation in leptomeningeal diffuse primary sarcoma (LDPS) is an aspect rarely observed in this malignant meningeal neoplasia, with few reported cases. The present case is the first reported in the Portuguese literature and the fifth reported in the English literature.

[Olfactory groove schwannoma: case report]. / Schwannoma da goteira olfatória: relato de caso.

Intracranial schwannoma not related to cranial nerves are unusual and rarely found in the subfrontal region. We report a case of olfactory groove schwannoma in a 27-year-old male, who presented with anosmia and headache initiated one year ago. At admission, bilateral papilledema was noted with absense of motor deficits or cranial nerves abnormalities. Cranial computed tomography (CT) revealed a bifrontal multicystic isodense enhancing mass lesion causing a frontal ventricular horn compression. Radiological features resembled that of a cystic olfactory groove meningioma. Decompressive bifrontal craniotomy was done. One month later, CT demonstrated a homogeneously contrast-enhancing mass in the olfactory groove region who extended into the left nasal cavity. Magnetic resonance imaging did not add more informations. A second surgical procedure was done through a nasoethmoidal approach with incomplete resection of the lesion. The complete tumor resection was only possible in a third surgery through another bifrontal approach. The hystopathological diagnosis of schwannoma was performed by conventional methods and confirmed by immunohistoquemical staining for S-100 protein. The rarity of this tumor and his clinical, radiological and histological aspects justify this publication.

Schwannoma da goteira olfatória. Relato de caso / Olfactory groove schwannoma: case report

Schwannomas intracranianos näo associados a nervos cranianos säo incomuns e raramente encontrados na regiäo subfrontal. Apresentamos raro caso de schwannoma da goteira olfatória, acometendo paciente de 27 anos, masculino, com quadro iniciado há 1 ano com perda da olfaçäo e cefaléia. Ao exame de admissäo, apresentava papiledema bilateral e anosmia. Tomografia computadorizada de Cranio (TC) revelou processo expansivo bifrontal hipodenso ao parênquima, com aspecto multicístico, sem captaçäo do contraste iodado, promovendo compressäo dos cornos ventriculares frontais. Os achados radiológicos sugeriam meningeoma cístico da goteira olfatória. Foi submetido a craniotomia frontal para descompressäo. Um mês após, TC de controle revelou processo expansivo da regiäo da goteira olfatória homogeneamente captante do contraste iodado, que se estendia para o interior da cavidade nasal esquerda. RM näo adicionou novas informações. Foi realizado segundo procedimento cirúrgico por via naso-etmoidal, com ressecçäo incompleta da lesäo. A ressecçäo completa foi possível através de re-operaçäo por craniotomia bifrontobasal. O diagnóstico histopatológico de schwannoma foi realizado através de microscopia óptica convencional e confirmado por técnica de imuno-histoquímica, utilizando o anticorpo para proteína S-100. A raridade deste tumor, seus aspectos clínicos, radiológicos e histológicos justificam esta publicaçäo

Artrite experimental induzida por zymosan: caracterizaçäo citológica, histopatológica e imuno-histoquímica da sinóvia e estudos histoquímico e bioquímico dos glicoconjugados da matriz condróide / The zymosan induced arthritis: cytological. histopatological and immunohistochemistry characteristc of sinovia and hystochemical and biochemical study of glycoconjugados of condroide matrix

A artrite crônica induzida por injeção intra-articular de Zy, em ratos Wistar, caracteriza-se, na fase aguda, por exsudação de PMNs no líquido articular e na membrana sinovial, associada a erosão da sinóvia, depósitos de material fibrinóide e hiperplasia de sinoviócitos de revestimento, com presença de linfócitos B, sugerindo participação transitória de linfócitos T CD4+ Th2. Os sinoviócitos mostram imuno-ativação, às 72 horas, com gradativa substituição dos PMNs por linfócitos e macrófagos, além de indução de significativa proliferação vascular, com posterior formação do pannus (l4 dias). Linfócitos expressando IL-2 podem ser vistos, desde o 71 dia, o que implica na participação de células T CD4+ Th1, no processo. Linfócitos T CD8 , situados em torno de aglomerados de macrófagos, são também observados e há formação de granulomas epitelíóides, não necróticos, com presença de células gigantes tipo Langhans e progressiva deposição de fibras colágenas. Concomitante, há agressão à cartilagem articular, com formação de fendas intersticiais e fragmentação estrutural, degradação do AH e redução do conteúdo de CS. AZy é, portanto, um modelo decorrente de resposta imunológica celular dependente de linfócitos T CD4+ Th1, com algumas alterações citológicas, histológicas, imunológicas e bioquímicas que se assemelham à AR e cujos parâmetros foram cronologicamente caracterizados. Este modelo poderá ser ampliado e melhor dissecado visando o estudo do dano tissular mediado imunologicamente e ser usado para análise da atividade de linfócitos T Thl/Th2. Também permite dissecar algumas fases da reação inflamatória intra-articular crônica e se presta para testes de efeitos profiláticos de drogas, uma vez que se pode determinar, precisamente, o seu início e monitorizar sua evolução. Pode ainda ser usado em investigações futuras sobre o papel da angiogênese no processo inflamatório e na formação do pannus

Repercussões histopatológicas da colostomia no coto colônico distal desfuncionalizado: estudo experimental em ratos / Histopathological consequences of colostomy in the defunctional intestinal segment: an experimental study in rats

O objetivo deste trabalho foi evidenciar as repercussões histopatológicas da colostomia no segmento desfuncionalizado e, dessa forma, criar um modelo experimental da colite de derivação fecal (CD). Foram utilizados 65 ratos, adultos, da raça Wistar, com peso variando de 220 a 300g. Os animais foram divididos em 13 grupos, contendo cinco ratos. Do grupo 1 ao grupo 12, os animais foram submetidos a laparotomia mediana, sendo realizada uma colostomia terminal tipo boca única, e observados, por períodos variados de tempo, com o máximo de cem dias. Os animais, após serem mortos, foram necropsiados e retirado o segmento colônico desfuncionalizado para a avaliação histopatológica. Essa avaliação consistia de uma análise quantitativa, através da medida da espessura da mucosa colônica, e de uma análise qualitativa, mediante avaliação subjetiva: da presença de infiltrado inflamatório agudo ou crônico na lâmina própria; das alterações na arquitetura das criptas colônicas; da presença de hiperplasia folicular linfóide e de linfócitos na luz dos vasos da submucosa; e da presença de eosinófilos na luz intestinal. No grupo 12, após o 100 dia de pós-operatório (DPO), foi realizada a reconstrução do trânsito intestinal, e, após trinta dias, o cólon descendente foi retirado para a análise histopatológica. O método de Tukey e o teste "t" de Student foram utilizados como parte da análise dos resultados. Verificou-se uma redução estatisticamente significante da espessura da mucosa colônica a partir do 40 DPO. Concluiu-se que a colostomia desfuncionalizante realizada em ratos reproduziu alterações histopatológicas compatíveis com a colite de derivação, e que estas mostraram-se reversíveis após a reconstrução do trânsito intestinal