Segmental absence of intestinal musculature -presentation in a 10-year-old boy with an extensive involved segment.

Segmental absence of the intestinal musculature is a rare cause of acute abdomen most likely associated with intestinal perforation and sepsis in neonates and adults. We present a case of a 10-year-old boy who developed acute abdomen and was treated with right hemicolectomy and partial resection of the ileum. The ileum showed a 20-cm-long stenotic segment showing prominent thinning of the intestinal wall. This case occurred in an older child, which appears to be rare when comparing the literature. The bowel defect was also the largest described to date, indicating the potential effect of an atonic segment leading to obstructive disease.

Intramitochondrial crystalline inclusions in nonalcoholic steatohepatitis.

UNLABELLED: Mitochondrial dysfunction is an important element in the pathogenesis of nonalcoholic steatohepatitis (NASH). Intramitochondrial crystals (IMCs) are a well-documented morphological abnormality seen on transmission electron microscopy in this disease. It has been suggested that IMCs consist of phospholipids, but their exact composition remain uncertain many years after their discovery. Micellar phase transitions of phospholipid bilayers is a well-known but little-studied phenomenon in living systems. Its presence in the mitochondria of NASH would offer significant insight into the disease with possible therapeutic implications. We postulated that intramitochondrial disturbances in NASH are sufficient to produce such transitions and that their detection in fresh biopsies would therefore be a dynamic process. To test this, we performed a blinded, prospective analysis of fresh liver biopsy samples immediately fixed under different conditions. Quantitative transmission electron microscopy morphometry, performed by systematically counting total mitochondria and IMCs within areas of uniform dimension, showed a stepwise decline in IMCs with cooler fixation temperature in each subject studied. Randomization testing (Monte Carlo resampling) confirmed that the detection of IMCs was strongly dependent on fixation temperature (P < 0.0001). CONCLUSION: These results indicate that the intramitochondrial crystals characteristic of NASH are highly dynamic and unstable structures. The findings offer the strongest support yet for their origin in micellar phase transitions. We speculate that such transitions result from microenvironmental changes within the mitochondria and carry therapeutic implications, especially in regard to dietary manipulations of mitochondrial lipid composition.

Activity of physalin F in a collagen-induced arthritis model.

The effects of physalin F (1), a steroid derivative purified from Physalis angulata, were investigated in models of collagen-induced arthritis in DBA/1 mice and allergic airway inflammation in BALB/c mice. Oral treatment with 1 or dexamethasone caused a marked decrease in paw edema and joint inflammation when compared to vehicle-treated arthritic mice. In contrast, treatment with 1 had no effect in mice with allergic airway inflammation caused by ovalbumin immunization, whereas dexamethasone significantly reduced the number of inflammatory cells and eosinophils in the broncoalveolar lavage fluid and in lung sections of challenged mice. To further demonstrate that 1 acts through a mechanism different from that of glucocorticoids, a nuclear translocation assay was performed of the glucocorticoid receptor (GR) using COS-7 cells transfected with a plasmid encoding for a yellow fluorescent protein (YFP)-GR fusion protein. Untreated or treated cells with 1 had YFP staining mainly in the cytoplasm, whereas in dexamethasone-treated cells the YFP staining was concentrated in the nuclei. It is concluded that the mechanism of the immunosuppressive activity of physalin F is distinct from that of the glucocorticoids.

Virological and histological re-evaluation of Labrea hepatitis.

BACKGROUND: a peculiar form of fulminant hepatitis known as Labrea hepatitis, probably related to hepatitis B and D, has been reported in Brazilian Amazon as early as the 1930s. METHODS: we reviewed the postmortem liver biopsies of 9 patients with Labrea Hepatitis. Immunostaining for HBV and HDV antigens were performed. RESULTS: we found several important characteristics in the liver tissues: 1) moderate hepatocellular necro-inflammation, 2) hepatocellular ballooning, 3) ballooned hepatocytes with fat droplets surrounding the nucleus (morula-like cells or spongiocytes), 4) mild to moderate necrosis and/or mild portoseptal fibrosis. Hepatitis B surface antigen (HBsAg) was identified in 7 of the 9 cases and was concentrated in the Morula-like cells. Hepatitis B core antigen (HBcAg) was present in 5 cases, mostly in the hepatocyte's nucleous. The hepatitis D virus antigen (HDV Ag) was present in 5 cases, mostly in the cytoplasm and concentrated in the Morula-like cells. CONCLUSION: labrea hepatitis is a fatal disease mostly affecting isolated communities in the Amazon. Evidence implicates HBV and HDV in the etiology of this disease, but this hypothesis needs to be confirmed with genotyping and sequencing research on HBV DNA and HDV RNA extracted from the liver and sera of these patients.

[Nonalcoholic fatty liver disease: clinical and histological characteristics in obese who underwent bariatric surgery]. / Doença hepática gordurosa não alcoólica: caractéristicas clínicas e histológicas em obesos graves submetidos à cirurgia bariátrica.

UNLABELLED: Obesity is an important risk factor of Nonalcoholic Fatty Liver Disease (NAFLD) and it has been considered a predictor of severity of this condition. However, in severe obese patients the spectrum of NAFLD is in discussion. AIM: To describe the clinical and histological characteristics of NAFLD in obese patients submitted to bariatric surgery. METHODOLOGY: The study included 141 severe obese (BMI > or = 35kg/m2) who underwent bariatric surgery from October 2004 to May 2005 had clinical and histological diagnosis of NAFLD. EXCLUSION CRITERIA: alcoholic intake more than 140 g/week, positive markers for other liver diseases. All patients were submitted to hepatic biopsy, as first procedure during the surgery. RESULTS: The mean age of the patients was of 37.3 +/- 11.1 years and 76.4% were female. BMI was greater than 40 kg/m2 in 77.7% of the cases. The frequency of metabolic syndrome was 51.9% (104). Elevated aminotransferases and hepatic steatosis on ultrasound were present in 29.5% (105) and 59.0% (105) respectively. Normal liver biopsy or unspecfic findings were found in 11.3% of the cases and NAFLD in 88.7%: isolated steatosis in 2.8%, steatohepatitis (NASH) in 85.1% (NASH and fibrosis in 76.6%) and cirrhosis in 0.7%. CONCLUSIONS: NAFLD in severe obese patients, in general, was asymptomatic and presented normal enzymes, liver function and ultrasound. However, it has a large histological spectrum and cases of steatohepatitis with fibrosis were more frequent. These results suggest that liver biopsy may be considered during the bariatric surgery to better diagnosis and prognosis of severe obese patients.

P16(INK4a) expression as a potential prognostic marker in cervical pre-neoplastic and neoplastic lesions.

An immunohistochemical analysis with monoclonal antibody p16(INK4a) was performed in formalin-fixed, paraffin-embedded samples of 60 cases. The aim was to investigate in biopsies the expression of p16(INK4a) of normal uterine cervical tissue, pre-cancerous and cancerous lesions, and their relation with human papilloma virus (HPV) and HIV status. Three parameters were evaluated: percentage of p16(INK4a) positive cells, reaction intensity, and cell staining pattern. All of these parameters were statistically different when compared among different histological groups. However, logistic regression model showed that the reaction intensity was the best indicator of the expression of p16(INK4a). This expression increases from normal to invasive squamous carcinoma. Sixty-six percent of the patients with CIN grade 1 (CIN1) expressed p16(INK4a) (all these cases were infected with high risk HPV). Our study supports the hypothesis that p16(INK4a) expression in pre-cancerous lesions and cancers can be used to identify HPV-transformed cells. Of great interest for routine diagnostic use is the fact that immunohistochemical testing for p16(INK4a) seems to be capable of identifying HPV-positive cells and potentially recognizing those lesions with an increased risk of progression to high-grade lesions.

Comparative study of the expression of cellular cycle proteins in cervical intraepithelial lesions.

Interaction of human papilloma virus oncoproteins E6 and E7 with cell cycle proteins leads to disturbances of the cell cycle mechanism and subsequent alteration in the expression of some proteins, such as p16INK4a, cyclin D1, p53 and KI67. In this study, we compared alterations in the expression of these proteins during several stages of intraepithelial cervical carcinogenesis. Accordingly, an immunohistochemical study was performed on 50 cervical biopsies, including negative cases and intraepithelial neoplasias. The expression patterns of these markers were correlated with the histopathological diagnosis and infection with HPV. The p16INK4a, followed by Ki67, showed better correlation with cancer progression than p53 and cyclin D1, which recommends their use in the evaluation of cervical carcinogenesis. These monoclonal antibodies can be applied to cervical biopsy specimens to identify lesions transformed by oncogenic HPV, separating CIN 1 (p16INK4a positive) and identifying high-grade lesions by an increase in the cellular proliferation index (Ki67). In this way, we propose immunomarkers that can be applied in clinical practice to separate patients who need a conservative therapeutic approach from those who require a more aggressive treatment.

Disruption of Splenic Lymphoid Tissue and Plasmacytosis in Canine Visceral Leishmaniasis: Changes in Homing and Survival of Plasma Cells.

Visceral leishmaniasis (VL) is a disease caused by Leishmania infantum, which is transmitted by phlebotomine sandflies. Dogs are the main urban reservoir of this parasite and the disease presents similar characteristics in both humans and dogs. In this paper, we investigated the potential pathways involved in plasma cell replacement of normal cell populations in the spleen, with respect to disease severity in dogs from an endemic area for visceral leishmaniasis. To this end, canine spleen samples were grouped into three categories: TYPE1SC- (non-infected dogs or without active infection with organized white pulp), TYPE1SC+ (infected dogs with organized white pulp) or TYPE3SC+ (infected animals with disorganized white pulp). We analyzed the distribution of different plasma cell isotypes (IgA, IgG and IgM) in the spleen. The expression of cytokines and chemokines involved in plasma cell homing and survival were assessed by real time RT-PCR. Polyclonal B cell activation and hypergammaglobulinemia were also evaluated. The proportion of animals with moderate or intense plasmacytosis was higher in the TYPE3SC+ group than in the other groups (Fisher test, P<0.05). This was mainly due to a higher density of IgG+ plasma cells in the red pulp of this group. The albumin/globulin ratio was lower in the TYPE3SC+ animals than in the TYPE1SC- or TYPE1SC+ animals, which evidences VL-associated dysproteinemia. Interestingly, TYPE3SC+ animals showed increased expression of the BAFF and APRIL cytokines, as well as chemokine CXCL12. Aberrant expression of BAFF, APRIL and CXCL12, together with amplified extrafollicular B cell activation, lead to plasma cell homing and the extended survival of these cells in the splenic red pulp compartment. These changes in the distribution of immunocompetent cells in the spleen may contribute to the progression of VL, and impair the spleen's ability to protect against blood borne pathogens.

Carcinossarcoma da glândula parótida com áreas de tumor de células gigantes / Carcinosarcoma of the parotid gland featuring foci of malignant giant cell tumor

Salivary gland carcinosarcoma is a rare neoplasm in which both stromal and epithelial components meet the microscopic criteria for malignancy. Seventy-four cases have been reported in English-language literature to date. In this study, we describe the case of an 81-year-old male patient with parotid gland carcinosarcoma featuring foci of undifferentiated carcinoma and sarcomatous components such as chondrosarcoma, high-grade undifferentiated sarcoma, and malignant giant cell tumor. We reviewed and discussed this rare occurrence of salivary gland carcinosarcoma with areas of malignant giant cell tumor, which had been reported only twice previously.

O carcinossarcoma de glândulas salivares é uma neoplasia rara na qual os componentes epitelial e estromal apresentam critérios microscópicos de malignidade. Setenta e quatro casos já foram relatados até o momento. Neste relato, descrevemos o caso de um paciente do sexo masculino, 81 anos, com carcinossarcoma da parótida, exibindo áreas de carcinoma indiferenciado e componente sarcomatoso constituído por condrossarcoma, sarcoma de alto grau e tumor de células gigantes. Revisamos e discutimos essa rara observação de carcinossarcoma de glândula salivar exibindo focos de tumor de células gigantes, descrito apenas em dois casos prévios.

Doença hepática gordurosa não alcoólica: caractéristicas clínicas e histológicas em obesos graves submetidos à cirurgia bariátrica / Enfermedad del hígado graso no alcohólico: caracteristicas clínicas e histológicas en obesos sometidos a cirugía bariática / Nonalcoholic fatty liver disease: clinical and histological characteristics in obese who underwent bariatric surgery

Obesidade é considerada um importante fator de risco da Doença Hepática Gordurosa Não Alcoólica (DHGNA), e um significante índice de gravidade da doença. Essa condição vem despertando interesse no estudo de obesos que se submetem à cirurgia bariátrica. Objetivo: Avaliar características clínicas e histológicas da DHGNA nestes indivíduos. Metodologia: O estudo incluiu 141 obesos (IMC≥ 35 kg/m2) submetidos à cirurgia bariátrica de outubro/2004 a maio/2005 tiveram diagnóstico de DHGNA. Foram excluídos os indivíduos com história de ingestão alcoólica (≥ 140g/semana) e portadores de outras doenças hepáticas. Os pacientes foram estudados através de parâmetros clínicos e histológicos. A biópsia hepática foi o primeiro procedimento na cirurgia, e a DHGNA foi graduada em esteatose isolada, esteatohepatite (esteatose com balonização ou fibrose) e cirrose. Resultados: A média de idade dos pacientes foi de 37±11 anos, sendo 76,4% eram do gênero feminino. Obesidade grau III (IMC> 40 kg/m2) esteve presente em 77,7% (141) dos casos, e síndrome metabólica foi observada em 52% (104). Elevação de aminotransferases esteve presente em 30% (31/105) dos casos, e 59% (105) apresentavam esteatose na ultra-sonografia. A biópsia mostrou fígado normal ou alterações inespecíficas em 11,3% dos casos e DHGNA em 88,7%: esteatose em 2,8%, esteato-hepatite em 85,1% (esteato-hepatite com fibrose em 76,6%), e cirrose em 0,7%. Conclusões: Em obesos graves a DHGNA é em geral assintomática e pode não apresentar alterações bioquímicas e ultrassonográficas. Entretanto, apresenta um amplo espectro histológico, com maior freqüência de casos de esteato-hepatite com fibrose. Os resultados sugerem que a biópsia hepática deve ser considerada durante cirurgia bariátrica visando uma melhor orientação destes pacientes.

La obesidad es considerada un factor importante de riesgo para la esteato-hepatitis no alcohólica (EHNA) y es un índice de la gravedad de esta enfermedad. Objetivo: evaluar características clínicas e histológicas de la EHNA en estos pacientes. Metodología: el estudio evaluó 141 obesos (IMC >/= 35 kg/m2) durante la cirugía bariátrica entre octubre de 2004 y mayo de 2005. Los pacientes fueron estudiados através de parámetros clínicos e histológicos. Fueron excluidos los pacientes con historia de ingestión de alcohol (> 140 g/semana) y portadores de otras enfermedades hepáticas. La biopsia fue el primer acto quirúrgico y la EHNA fue graduada como la esteatosis, esteatohepatitis y cirrosis. Resultados: los pacientes presentaban una media de edad de 37±11 años, siendo 76,4% mujeres. Obesidad grado III (IMC>40kg/m2) estuvo presente en 77,7% de los casos, y síndrome metabólico fue observado en 52% (54/104). Aminotransferasas elevadas fue observada en 30% (31/105) de los casos, y 59% (62/105) presentaban esteatosis en la ecografía. La biopsia mostró hígado normal o alteraciones inespecíficas en 11,3% de los casos y EHNA en 88,7%: esteatosis aislada en 2,8%, esteato-hepatitis (EHNA) en 85,1% (EHNA y fibrosis en 76,6%) y cirrosis en 0,7%. Conclusiones: en los obesos graves la EHNA es en general asintomática, puede no presentar alteraciones bioquímicas y ecográficas, pero presenta un amplio espectro histológico, con mayor frecuencia de esteatohepatitis con fibrosis. Los resultados sugieren que la biopsia hepática debe ser considerada para los obesos que fueron sometidos a cirugía bariátrica para mejor orientación clínica y pronóstica.

Obesity is an important risk factor of Nonalcoholic Fatty Liver Disease (NAFLD) and it has been considered a predictor of severity of this condition. However, in severe obese patients the spectrum of NAFLD is in discussion. Aim: To describe the clinical and histological characteristics of NAFLD in obese patients submitted to bariatric surgery. Methodology: The study included 141 severe obese (BMI≥35kg/m2) who underwent bariatric surgery from October 2004 to May 2005 had clinical and histological diagnosis of NAFLD. Exclusion criteria: alcoholic intake more than 140g/week, positive markers for other liver diseases. All patients were submitted to hepatic biopsy, as first procedure during the surgery. Results: The mean age of the patients was of 37.3±11.1 years and 76.4% were female. BMI was greater than 40kg/m2 in 77.7% of the cases. The frequency of metabolic syndrome was 51.9% (104). Elevated aminotransferases and hepatic steatosis on ultrasound were present in 29.5% (105) and 59.0% (105) respectively. Normal liver biopsy or unspecific findings were found in 11.3% of the cases and NAFLD in 88.7%: isolated steatosis in 2.8%, steatohepatitis (NASH) in 85.1% (NASH and fibrosis in 76.6%) and cirrhosis in 0.7%. Conclusions: NAFLD in severe obese patients, in general, was asymptomatic and presented normal enzymes, liver function and ultrasound. However, it has a large histological spectrum and cases of steatohepatitis with fibrosis were more frequent. These results suggest that liver biopsy may be considered during the bariatric surgery to better diagnosis and prognosis of severe obese patients

Hyperplasia of elastic tissue in hepatic schistosomal fibrosis

Elastic tissue hyperplasia, revealed by means of histological, immunocytochemical and ultrastructural methods, appeared as a prominent change in surgical liver biopsies taken from 61 patients with schistosomal periportal and septal fibrosis. Such hyperplasia was absent in ecperimental murine schistosomiasis, including mice with "pipe-stem" fibrosis. Displaced connective tissue cells in periportal areas, such as smooth muscle cells, more frequently observed in human material, could be the site of excessive elastin synthesis, and could explain the differences observed in human and experimental materials. Elastic tissue, sometimes represented by its microfibrillar components, also appeared to be more condensed in areas of matrix (collagen) degradation, suggesting a participation of this tissue in the remodelling of the extracellular matrix. By its rectratile properties elastic tissue hyperplasia in hepatic schistosomiasis can cause vascular narrowing and thus play a role in the pathogenesis of portal hypeertension