Accuracy of echogenic periportal enlargement image in ultrasonographic exams and histopathology in differential diagnosis of biliary atresia.

OBJECTIVES: To define the sensitivity, specificity and accuracy of the ultrasound triangular cord sign and hepatic histopathology, in isolation or in combination, for diagnostic differentiation between biliary atresia and intrahepatic cholestasis. METHODS: This was a retrospective study carried out between January 1990 and December 2004. Fifty-one cases of biliary atresia and 45 of intrahepatic cholestasis were analyzed. Histopathology was performed blind by a pathologist. The triangular cord sign was identified in ultrasound reports as the only diagnostic sign of biliary atresia. Sensitivity, specificity and accuracy were calculated for the triangular cord sign and histology both in isolation and in combination. The gold standard for diagnosis of biliary atresia was the appearance of the extrahepatic biliary tree via laparotomy. RESULTS: The triangular cord sign alone had sensitivity of 49%, specificity of 100% and accuracy of 72.5%. Histopathology compatible with extrahepatic biliary obstruction alone had 90.2% sensitivity, 84.6% specificity and 87.8% accuracy. The triangular cord sign and histopathology in isolation or combination resulted in sensitivity of 93.2%, specificity of 85.7% and accuracy of 90.3%. CONCLUSIONS: Finding the triangular cord sign on ultrasound is an indication for laparotomy. If the triangular cord sign is negative, liver biopsy is indicated; if histopathology reveals signs of biliary atresia, explorative laparotomy is indicated. In cases where the triangular cord sign is absent and histopathology indicates neonatal hepatitis or other intrahepatic cholestasis, clinical treatment or observation are recommended in accordance with the diagnosis.

Development of lamellar gel phase emulsion containing marigold oil (Calendula officinalis) as a potential modern wound dressing.

Appropriate therapeutics for wound treatments can be achieved by studying the pathophysiology of tissue repair. Here we develop formulations of lamellar gel phase (LGP) emulsions containing marigold (Calendula officinalis) oil, evaluating their stability and activity on experimental wound healing in rats. LGP emulsions were developed and evaluated based on a phase ternary diagram to select the best LGP emulsion, having a good amount of anisotropic structure and stability. The selected LGP formulation was analyzed according to the intrinsic and accelerated physical stability at different temperatures. In addition, in vitro and in vivo studies were carried out on wound healing rats as a model. The LGP emulsion (15.0% marigold oil; 10.0% of blend surfactants and 75.0% of purified water [w/w/w]) demonstrated good stability and high viscosity, suggesting longer contact of the formulation with the wound. No cytotoxic activity (50-1000 µg/mL) was observed in marigold oil. In the wound healing rat model, the LGP (15 mg/mL) showed an increase in the leukocyte recruitment to the wound at least on days 2 and 7, but reduced leukocyte recruitment after 14 and 21 days, as compared to the control. Additionally, collagen production was reduced in the LGP emulsion on days 2 and 7 and further accelerated the process of re-epithelialization of the wound itself. The methodology utilized in the present study has produced a potentially useful formulation for a stable LGP emulsion-containing marigold, which was able to improve the wound healing process.

[Validation of the Williams ultrasound scoring system for the diagnosis of liver disease in cystic fibrosis]. / Validação do escore ultra-sonográfico de Williams para o diagnóstico da hepatopatia da fibrose cística.

OBJECTIVES: To describe the hepatic abnormalities revealed by ultrasound examination of cystic fibrosis (CF) patients followed at the CF Outpatient Clinic at the Federal University of Minas Gerais; to compare ultrasound data with clinical and biochemical parameters; to validate the Williams ultrasound score for the diagnosis of liver disease in CF. METHODS: Seventy cystic fibrosis patients were followed prospectively and underwent clinical, biochemical and ultrasound examinations. The ultrasound findings were compared to the results of the clinical and biochemical examinations. Clinical and biochemical criteria were used as the gold standard for the validation of the Williams ultrasound score. We calculated the sensitivity, specificity, and positive and negative predictive values for the Williams score. The patients were divided into two groups: normal (score = 3) or abnormal (score > 3) ultrasound examination. RESULTS: Ten patients met the clinical and/or biochemical criteria for liver disease (14.3%). All of them presented some abnormality on ultrasound examination of the liver. Abnormalities of the hepatic parenchyma, edge and periportal fibrosis were statistically more frequent in these patients. The Williams ultrasound score showed high specificity (91.7%; CI 80.9-96.9), but low sensitivity (50%; CI 20.1-79.9) for the diagnosis of liver disease. CONCLUSIONS: The Williams ultrasound score was not a good screening tool when compared to the clinical and biochemical examinations. Since there are currently no adequate tests that can be used to diagnose liver disease, we recommend a sequential evaluation combining clinical, biochemical and ultrasound examinations for the diagnosis of liver disease in CF.

Anti-eosinophilic effect of Lafoensia pacari in toxocariasis.

We previously reported the anti-inflammatory activity of Lafoensia pacari extract in Toxocara canis infection, a model of systemic IL-5-dependent eosinophil migration. In the present study, we describe the kinetics of the anti-inflammatory activity of L. pacari extract and compare it with dexamethasone. T. canis-infected mice were submitted to different treatment protocols and the cells present in bronchoalveolar space and peritoneal cavity were collected at the end of each treatment period. The results showed that L. pacari extract effectively inhibited eosinophil migration only when the treatment was initiated before the peak of eosinophil migration (1st to 18th; 12th to 18th and 12th to 24th day post-infection). When eosinophil migration was established, administration of L. pacari extract had no effect on it (treatment 18th to 24th day post-infection). Dexamethasone was effective in inhibiting eosinophil migration in all periods studied. We suggest that L. pacari extract can potentially be a natural alternative treatment of eosinophilic diseases.

Anti-inflammatory activity of quercetin and isoquercitrin in experimental murine allergic asthma.

OBJECTIVE: Eosinophils and cytokines are implicated in the pathogenesis of allergic diseases. In the present study, we investigate the anti-inflammatory effect of quercetin and isoquercitrin in a murine model of asthma. METHODS: BALB/c mice were immunized (ovalbumin/aluminum hydroxide, s. c.), followed by two intranasal ovalbumin challenges. From day 18 to day 22 after the first immunization, the mice received daily gavages of isoquercitrin (15 mg/kg) or quercetin (10 mg/kg). Dexamethasone (1 mg/kg, s. c.) was administered as a positive control. Leucocytes were analyzed in bronchoalveolar lavage fluid (BALF), blood and pulmonary parenchyma at 24 h after the last ovalbumin challenge. Interleukin-5 (IL-5) was analyzed in BALF and lung homogenates. RESULTS: In animals receiving isoquercitrin or quercetin, eosinophil counts were lower in the BALF, blood and lung parenchyma. Neutrophil counts in blood and IL-5 levels in lung homogenate were lower only in isoquercitrin-treated mice. No alterations in mononuclear cell numbers were observed. CONCLUSION: Quercetin and isoquercitrin are effective eosinophilic inflammation suppressors, suggesting a potential for treating allergies.

Impact of MK886 on eosinophil counts and phenotypic features in toxocariasis.

Experimental toxocariasis was used as a model of eosinophil migration. Mice inoculated with 200 Toxocara canis eggs were treated with the leukotriene inhibitor MK886 (1 mg/kg/day). Eosinophils were counted in peripheral blood (PB), peritoneal cavity (PC) and bronchoalveolar lavage fluid (BALF) samples on post-infection days 3, 6, 12, 18, 24 and 36. Eosinophil expression of Mac-1 and VLA-4 was analysed in PB and PC samples. We found that T. canis infection induced systemic eosinophilia from post-infection day 3, peaking on days 6, 12 and 24 in PB, PC and BALF samples respectively. Eosinophilia was more pronounced in PB and PC samples than in BALF samples, and MK886 downregulated eosinophilia to varying degrees in the different sample types. In PB and PC samples, T. canis infection caused early upregulation of Mac-1 with late changes in the VLA-4 profile, whereas MK886 had opposite effects. The distinct time-dependent eosinophilia peaks and differential involvement of leukotrienes in integrin expression demonstrate that, despite the systemic eosinophilia triggered by T. canis infection, inflammatory responses vary by compartment.

Lafoensia pacari extract inhibits IL-5 production in toxocariasis.

Toxocariasis is an infection induced by Toxocara canis, an intestinal parasite of dogs. In this study, an experimental murine model of toxocariasis was used to evaluate the anti-inflammatory activity of an ethanolic extract of Lafoensia pacari stem bark. Mice infected with T. canis were treated with L. pacari extract (200 mg/kg, p.o.). Subsequently, we observed a reduction in the number of eosinophils in the peritoneal cavity, bronchoalveolar fluid, blood and bone marrow. Production of interleukin (IL)-5, a major cytokine involved in eosinophilic differentiation, proliferation and activation, is also an important marker for infection. The reduced levels of IL-5 observed in serum, lung homogenates and bronchoalveolar fluid demonstrated the anti-inflammatory mechanisms of L. pacari. Larvae recovery from infected mice treated with L. pacari was comparable with that from untreated mice, suggesting that L. pacari is not toxic to the parasite. Nonetheless, our results demonstrate a potential therapeutic effect of L. pacari extract in IL-5-mediated inflammatory diseases and provide new prospects for the development of drugs to treat IL-5-dependent allergic diseases such as parasite infection and asthma.

Acurácia diagnóstica do espessamento ecogênico periportal à ultra-sonografia e da histopatologia no diagnóstico diferencial da atresia biliar / Accuracy of echogenic periportal enlargement image in ultrasonographic exams and histopathology in differential diagnosis of biliary atresia

OBJETIVOS: Definir a sensibilidade, especificidade e a acurácia do espessamento ecogênico periportal à ultra-sonografia e da histopatologia hepática, isolados ou em conjunto, na distinção diagnóstica entre atresia biliar e as colestases intra-hepáticas. MÉTODOS: Trata-se de estudo retrospectivo realizado entre janeiro de 1990 e dezembro de 2004. Foram analisados 51 casos de atresia biliar e 45 com colestase intra-hepática. A histopatologia foi realizada por uma patologista de forma cega. O espessamento ecogênico periportal foi pesquisado na ultra-sonografia como único sinal diagnóstico de atresia biliar. Foram calculados os índices de sensibilidade, especificidade e acurácia do espessamento ecogênico periportal e da histologia isoladamente ou associados. O padrão-ouro utilizado para o diagnóstico de atresia biliar foi o aspecto da via biliar extra-hepática à laparotomia. RESULTADOS: O espessamento ecogênico periportal revelou sensibilidade de 49 por cento, especificidade de 100 por cento e acurácia de 72,5 por cento. A histopatologia compatível com obstrução biliar extra-hepática conferiu sensibilidade de 90,2 por cento, especificidade de 84,6 por cento e acurácia de 87,8 por cento. O espessamento ecogênico periportal e a histopatologia isolados ou associados proporcionaram sensibilidade de 93,2 por cento, especificidade de 85,7 por cento e acurácia de 90,3 por cento. CONCLUSÕES: A evidência do espessamento ecogênico periportal na ultra-sonografia é indicação de laparotomia. Se o espessamento ecogênico periportal é negativo, está indicada a biopsia hepática; se a histopatologia revelar sinais de atresia biliar, impõe-se a laparotomia exploradora. Nos casos de espessamento ecogênico periportal negativo com histopatologia de hepatite neonatal ou de outras colestases intra-hepáticas, recomenda-se o acompanhamento ou o tratamento clínico conforme o diagnóstico.

OBJECTIVES: To define the sensitivity, specificity and accuracy of the ultrasound triangular cord sign and hepatic histopathology, in isolation or in combination, for diagnostic differentiation between biliary atresia and intrahepatic cholestasis. METHODS: This was a retrospective study carried out between January 1990 and December 2004. Fifty-one cases of biliary atresia and 45 of intrahepatic cholestasis were analyzed. Histopathology was performed blind by a pathologist. The triangular cord sign was identified in ultrasound reports as the only diagnostic sign of biliary atresia. Sensitivity, specificity and accuracy were calculated for the triangular cord sign and histology both in isolation and in combination. The gold standard for diagnosis of biliary atresia was the appearance of the extrahepatic biliary tree via laparotomy. RESULTS: The triangular cord sign alone had sensitivity of 49 percent, specificity of 100 percent and accuracy of 72.5 percent. Histopathology compatible with extrahepatic biliary obstruction alone had 90.2 percent sensitivity, 84.6 percent specificity and 87.8 percent accuracy. The triangular cord sign and histopathology in isolation or combination resulted in sensitivity of 93.2 percent, specificity of 85.7 percent and accuracy of 90.3 percent. CONCLUSIONS: Finding the triangular cord sign on ultrasound is an indication for laparotomy. If the triangular cord sign is negative, liver biopsy is indicated; if histopathology reveals signs of biliary atresia, explorative laparotomy is indicated. In cases where the triangular cord sign is absent and histopathology indicates neonatal hepatitis or other intrahepatic cholestasis, clinical treatment or observation are recommended in accordance with the diagnosis.

Validação do escore ultra-sonográfico de Williams para o diagnóstico da hepatopatia da fibrose cística / Validation of the Williams ultrasound scoring system for the diagnosis of liver disease in cystic fibrosis

OBJETIVOS: Descrever as alterações hepáticas observadas ao exame ultra-sonográfico de fibrocísticos do Ambulatório de Fibrose Cística do Hospital das Clínicas da UFMG, comparar os achados ultra-sonográficos com critérios clínicos e bioquímicos e validar o escore de Williams para o diagnóstico de hepatopatia associada à fibrose cística. MÉTODOS: Setenta fibrocísticos foram acompanhados prospectivamente e submetidos a exame clínico, bioquímico e ultra-sonográfico. Os achados ultra-sonográficos foram comparados com os resultados do exame clínico e bioquímico. Para a validação do escore ultra-sonográfico de Williams, os critérios clínicos e bioquímicos foram utilizados como padrão-ouro. Foram calculados sensibilidade, especificidade, valor preditivo positivo e valor preditivo negativo do escore de Williams. Para os cálculos, os pacientes foram divididos em dois grupos: normal ao exame ultra-sonográfico (escore = 3) ou alterado (escore > 3). RESULTADOS: Dez pacientes preencheram os critérios clínicos e/ou bioquímicos para hepatopatia (14,3 por cento). Todos os pacientes hepatopatas segundo os critérios clínicos e/ou bioquímicos apresentavam alguma alteração ao exame ultra-sonográfico. As alterações do parênquima hepático, borda hepática e fibrose periportal foram encontradas mais freqüentemente entre os hepatopatas, com diferença estatisticamente significativa. O escore de Williams apresentou alta especificidade (91,7 por cento; IC 80,9-96,9), mas baixa sensibilidade (s = 50 por cento; IC 20,1-79,9) para o diagnóstico da hepatopatia. CONCLUSÕES: O escore de Williams não constituiu um bom exame de triagem quando comparado ao exame clínico e bioquímico. Uma vez que ainda não há nenhum teste que, utilizado isoladamente, apresente sensibilidade adequada, é recomendável a utilização conjunta dos exames clínico, bioquímico e ultra-sonográfico no diagnóstico da hepatopatia associada à fibrose cística, sempre em avaliações seqüenciais.