The Oxford Classification predictors of chronic kidney disease in pediatric patients with IgA nephropathy / Preditores da doença renal crônica segundo a Classificação de Oxford em pacientes pediátricos com nefropatia por IgA

Abstract Objective: The Oxford Classification for Immunoglobulin A nephropathy (IgAN) identifies pathological variables that may predict the decline of renal function. This study aimed to evaluate the Oxford Classification variables as predictors of renal dysfunction in a cohort of Brazilian children and adolescents with IgAN. Methods: A total of 54 patients with IgAN biopsied from 1982 to 2010 were assessed. Biopsies were re-evaluated and classified according to the Oxford Classification. Multivariate analysis of laboratory and pathological data was performed. The primary outcomes were decline of baseline estimated glomerular filtration rate (eGFR) greater than or equal to 50%. Results: Mean follow-up was 7.6 ± 5.0 years. Mean renal survival was 13.5 ± 0.8 years and probability of decline ≥50% in baseline eGFR was 8% at five years of follow-up and 15% at ten years. Ten children (18.5%) had a decline of baseline eGFR ≥ 50% and five (9.3%) evolved to end-stage renal disease. Kaplan-Meier analysis showed that baseline proteinuria, proteinuria during follow-up, endocapillary proliferation, and tubular atrophy/interstitial fibrosis were associated with the primary outcome. Multivariate Cox analysis showed that only baseline proteinuria (HR, 1.73; 95% CI, 1.20-2.50, p = 0.003) and endocapillary hypercellularity (HR, 37.18; 95% CI, 3.85-358.94, p = 0.002) were independent predictors of renal dysfunction. No other pathological variable was associated with eGFR decline in the multivariate analysis. Conclusion: This is the first cohort study that evaluated the predictive role of the Oxford Classification in pediatric patients with IgAN from South America. Endocapillary proliferation was the unique pathological feature that independently predicted renal outcome.

Resumo Objetivo: A Classificação Oxford para a Nefropatia por Imunoglobulina A (IgAN) identificou variáveis patológicas de risco para disfunção renal. O presente estudo teve como objetivo avaliar as variáveis da Classificação de Oxford como preditores de disfunção renal em crianças brasileiras com IgAN. Métodos: Foram analisados 54 pacientes com diagnóstico de IgAN entre 1982-2010. As biópsias renais foram reavaliadas pela Classificação de Oxford. Foram feitas análises uni e multivariada das variáveis clínicas e patológicas. O desfecho primário foi queda da taxa de filtração glomerular (TFG) ≥ 50% da filtração basal. Resultados: O acompanhamento médio foi de 7,6 ± 5,0 anos. A sobrevida renal média foi de 13,5 ± 0,8 anos e a probabilidade de atingir o desfecho primário foi de 8% em cinco anos e 15% em 10 anos de seguimento. Dez crianças (18,5%) apresentaram queda na TFG basal ≥ 50% e cinco (9,3%) evoluíram para doença renal crônica terminal. A análise de Kaplan-Meier mostrou que a proteinúria basal e de seguimento, a proliferação endocapilar e a atrofia tubular/fibrose intersticial foram associadas com o desfecho primário. A análise multivariada de Cox mostrou que a proteinúria basal (HR = 1,73; IC95% 1,20-2,50, p = 0,003) e a proliferação endocapilar (HR = 37,18; IC95% 3,85-358,94, p = 0,002) foram preditores independentes de disfunção renal. Nenhuma outra variável patológica foi associada com declínio da TFG na análise multivariada. Conclusão: Este é o primeiro estudo brasileiro que avaliou a Classificação Oxford em crianças com IgAN. A proliferação endocapilar foi a única característica patológica capaz de predizer independentemente o declínio da função renal.

Interobserver agreement of Gleason score and modified Gleason score in needle biopsy and in surgical specimen of prostate cancer.

INTRODUCTION: Gleason score, which has a high interobserver variability, is used to classify prostate cancer. The most recent consensus valued the tertiary Gleason pattern and recommended its use in the final score of needle biopsies (modified Gleason score). This pattern is considered to be of high prognostic value in surgical specimens. This study emphasized the evaluation of the modified score agreement in needle biopsies and in surgical specimen, as well as the interobserver variability of this score. MATERIALS AND METHODS: Three pathologists evaluated the slides of needle biopsies and surgical specimens of 110 patients, reporting primary, secondary and tertiary Gleason patterns and after that, traditional and modified Gleason scores were calculated. Kappa test (K) assessed the interobserver agreement and the agreement between the traditional and modified scores of the biopsy and of the surgical specimen. RESULTS: Interobserver agreement in the biopsy was K = 0.36 and K = 0.35, and in the surgical specimen it was K = 0.46 and K = 0.36, for the traditional and modified scores, respectively. The tertiary Gleason grade was found in 8%, 0% and 2% of the biopsies and in 8%, 0% and 13% of the surgical specimens, according to observers 1, 2 and 3, respectively. When evaluating the agreement of the traditional and modified Gleason scores in needle biopsy with both scores of the surgical specimen, a similar agreement was found through Kappa. CONCLUSION: Contrary to what was expected, the modified Gleason score was not superior in the agreement between the biopsy score and the specimen, or in interobserver reproducibility, in this study.

Interobserver agreement of gleason score and modified gleason score in needle biopsy and in surgical specimen of prostate cancer

INTRODUCTION: Gleason score, which has a high interobserver variability, is used to classify prostate cancer. The most recent consensus valued the tertiary Gleason pattern and recommended its use in the final score of needle biopsies (modified Gleason score). This pattern is considered to be of high prognostic value in surgical specimens. This study emphasized the evaluation of the modified score agreement in needle biopsies and in surgical specimen, as well as the interobserver variability of this score MATERIALS AND METHODS: Three pathologists evaluated the slides of needle biopsies and surgical specimens of 110 patients, reporting primary, secondary and tertiary Gleason patterns and after that, traditional and modified Gleason scores were calculated. Kappa test (K) assessed the interobserver agreement and the agreement between the traditional and modified scores of the biopsy and of the surgical specimen RESULTS: Interobserver agreement in the biopsy was K = 0.36 and K = 0.35, and in the surgical specimen it was K = 0.46 and K = 0.36, for the traditional and modified scores, respectively. The tertiary Gleason grade was found in 8 percent, 0 percent and 2 percent of the biopsies and in 8 percent, 0 percent and 13 percent of the surgical specimens, according to observers 1, 2 and 3, respectively. When evaluating the agreement of the traditional and modified Gleason scores in needle biopsy with both scores of the surgical specimen, a similar agreement was found through Kappa CONCLUSION: Contrary to what was expected, the modified Gleason score was not superior in the agreement between the biopsy score and the specimen, or in interobserver reproducibility, in this study.

Predictive factors of chronic kidney disease in primary focal segmental glomerulosclerosis.

Renal histological features of focal segmental glomerulosclerosis (FSGS) are found in 75% of pediatric patients with steroid-resistant nephrotic syndrome. In order to evaluate the predictive factors of chronic kidney disease (CKD), we retrospectively reviewed the records of 110 children with biopsy-proven FSGS admitted between 1972 and 2004. Renal survival was analyzed by the Kaplan-Meier method and Cox's regression model. Two multivariate models were developed: (1) from the onset of symptoms to the occurrence of CKD and (2) from the time of renal biopsy to CKD. Mean follow-up time was 10 years [standard deviation ((SD) 5.5], and 24 patients (21.8%) progressed to CKD. At baseline, after adjustment three variables remained as independent predictors of CKD: age >6.5 years (RR=3.3, 95% CI=1.3-7.8), creatinine >1 mg/dl (RR=2.5, 95% CI=0.97-6.5), and non-response to steroids (RR=7.3, 95% CI=2.7-19.7). In a model with continuous variables only age and non-response to steroids were associated with CKD. At the time of renal biopsy, after adjustment two variables remained as independent predictors of CKD: hematuria (RR=3.0, 95% CI=1.2-7.3) and creatinine >0.8 mg/dl (RR=4.3, 95% CI=1.7-10.6). In a model with continuous variables four factors predicted CKD: age, creatinine, hematuria, and percentage of global sclerosis.

Clinical course of 110 children and adolescents with primary focal segmental glomerulosclerosis.

The purpose of this retrospective cohort study was to report the clinical course of children and adolescents with primary focal segmental glomerulosclerosis (FSGS). The records of 110 patients with biopsy-proven FSGS admitted between 1972 and 2004 were retrospectively reviewed. Demographic, clinical and laboratory data were recorded and histopathological data were reanalyzed by one pathologist who had no information about the outcome of the patients. Renal survival analysis was performed using the Kaplan-Meier method. Differences between subgroups (response to corticosteroids) were assessed by the two-sided log rank test. The median age at admission was 5 years (range: 1-15 years). Forty-two patients (38.2%) presented with hematuria at admission, and 55 (50%) presented blood pressure levels above the 95th percentile. Mean follow-up time was 10 years (SD 5.5). Twenty-four patients (21.8%) presented chronic kidney disease (CKD). It was estimated that the probability of CKD was 8% at 5 years, 17% at 10 years, and 32% at 15 years after diagnosis of nephrotic syndrome. In conclusion, on the basis of the clinical and histological characteristics observed, apparently our cohort of idiopathic FSGS is comparable with other published series. However, the long-term overall renal survival seems to be better in our cohort.

Histological evaluation of the effects of cryopreservation in bovine ovarian tissue.

The aim of this study was to show the effects of freezing and thawing in bovine ovarian tissue by histological analysis. Ten cortical slices (2-4 mm in diameter) were obtained from each ovary by tru-cut biopsy and randomly divided into two groups: five fragments were immediately processed as a fresh tissue control group, while the remaining 5 fragments were slowly frozen using DMSO plus sucrose as cryoprotectors, then stored for two weeks and quickly thawed. Histological examination of all cryopreserved ovarian fragments showed no damage in the structure of the organ. Furthermore, there was no difference in the average number of primordial and primary follicles between the two groups of ovarian tissue. These data suggest that the bovine ovary can be used as a suitable model to test new freezing and thawing procedures in search for a standard protocol of human ovary cryopreservation.

Detection of chronic endometritis by diagnostic hysteroscopy in asymptomatic infertile patients.

Chronic endometritis has been related to infertility and recurrent abortion. It is usually asymptomatic, and the diagnosis is rarely clinically suspected. We performed a prospective study to evaluate both the role of diagnostic hysteroscopy in the detection of chronic endometritis in infertile patients and Chlamydia trachomatis is a potential etiologic factor. Fifty consecutive patients who sought treatment for infertility in a tertiary academic hospital were submitted to diagnostic hysteroscopy and an endometrial biopsy for histopathological study and for diagnosis of C. trachomatis by polymerase chain reaction. The patients' mean age was 33.7 +/- (SD) 5.4 years, and the duration of the couples' infertility ranged from 1 to 18 years. The overall prevalence of chronic endometritis was 12% (6 patients). Among all patients, no cases of chlamydial infection were detected by polymerase chain reaction. In the detection of chronic endometritis, with 95% confidence intervals, the hysteroscopy sensitivity was 16.7% (range 0.9-63,5%), the specificity was 93.2% (range 80.3-98.2%), the positive predictive value was 25% (range 1.3-78.1%), and the negative predictive value was 89.1% (range 65.6-95.9%). These data suggest that hysteroscopy is not useful in the screening for chronic endometritis in asymptomatic infertile women. Further studies are needed to establish the etiology of endometritis in infertile patients.

Relato de caso: Glomerulopatiascom crescentes na infância / Crescent glomerulopathy in childhood

O objetivo é determinar, entre outras glomerulopatias estudadas no serviço e em pacientes entre 3 e 16 anos de idade, a freqüencia de glomerulopatias com crescentes (CG) e avaliar as alteraçöes morfológicas encontradas. Foi feito um estudo retrospectivo de 21 biópsias renais com quadro morfológico de glomerulopatia crescente. Tal casuística foi extraída de um total 4.324 biópsias renais de pacientes com glomerulopatias (780 biópsias realizadas em crianças), analisadas no períodos de1990 a 1998. O estudo histipatológico foi feito por meio de microscopia óptica e imunofluorescência direta. Observou-se que crianças com GC representaram 2,7 porcento do total de biópsias renais infantis, analisadas nesse período (21/780). A análise histológica mostrrou 13 casos de glomerulopatia crescêntica idipática ou associada ao lupus eritematoso sistêmico em quatro casos, à glomerulopatia difusa aguda pós-infecciosa em dois casos, à vasculite em um caso e à sindrome de Goodpasture em um caso. Mostrou-se também que näo houve diferença significativa entre a percentagem de glomérulos acometidos por crescentes e a presença de lesöes intersticiais. No presente estudo, a incidência de glomerulopatia crescente foi baixa entre as glomerulopatias analisadas nessa faixa etária.(au)

Influence of bacteria from the duodenal microbiota of patients with symptomatic giardiasis on the pathogenicity of Giardia duodenalis in gnotoxenic mice.

Recent studies have shown that the intestinal microbiota is essential for the pathogenicity but not for the multiplication of Giardia duodenalis in the intestinal lumen. The microbial components responsible for this phenomenon are not known. Twenty-eight facultative and three strictly anaerobic micro-organisms were isolated from the dominant duodenal microbiota of five patients with symptomatic giardiasis. The bacterial combinations from each patient were associated with groups (GN) of germ-free mice. Five days after the association, when their faecal populations ranged from 10(7) to 10(9) cfu/g, all groups were inoculated intragastrically with 10(5) viable trophozoites of G. duodenalis strain BT6. Two groups of germ-free (GF) and conventional (CV1) mice were also infected. Gnotobiotic animals were killed 10 days after infection and GF and CV1 animals were killed 10, 20 and 30 days after infection. More marked pathological alterations were detected in CV1 mice when compared with GF animals. Gnotobiotic animals showed intermediate pathological alterations between CV1 and GF mice. The CV1 and GF groups became infected by day 3 and faecal cyst levels were similar in both groups throughout the experiment. Total and G. duodenalis-specific IgA levels in the intestinal fluid and G. duodenalis-specific IgM and IgG levels in the serum increased during the infection and were higher in CV1 animals at all times tested when compared with GF mice. The present results confirm the stimulatory activity of the intestinal microbiota on the pathogenicity of G. duodenalis, and some combinations of microbial components of the dominant duodenal ecosystem from patients with symptomatic giardiasis can partially develop this function. However, none of these combinations was able to stimulate the protozoan pathogenicity in the same manner as the entire intestinal microbiota.

Achados ultramicroscópicos e fluoresceinográficos da obstruçäo venosa experimental pelo método da fototrombose / Ultrastructural analyses and fluorescein angiography in experimental vein oclusion by photochemically initiated thrombosis

Resumo: Objetios: Comparar a retinografia fluorescente coma microscopia óptica e com a microscopia eletrônica de transmissäo como método diagnóstico de obstruçäo/desobstruçäo venular retiana em coelhos, pelo método da fototrombose. Avaliar, pela microscopia eletrônica, a composiçäo do trombo venoso e eventuais alteraçöes na parede venular após a fototrombose. Local: Hospital Säo Geraldo da Faculdade de Medicina da Universidade Federal de Minas Gerais. Metodologia: Após a obstruçäo , 12 olhos foram submetidos a retinografia fluorescente para evidenciar a obstruçäo. Todos esses olhos foram enucleados e examinados pela microscopia óptica (4 olhos) e à microscopia eletrônica de transmissäo (8 olhos), para evidenciar histologicamente a obstruçäo e estudar suas caracteristicas microscópicas. Quatro olhos foram submetidos à retinografia fluorescente, microscopia óptica e microscopia eletrônica de transmissäo, trinta dias após a fototrombose. Resultaos: Houve complea concordância entre os resultados dos olhos submetidos à retinografia fluorescente e os do exame histológico em evidenciar a obstruçäo venular. Conclusöes: A microscopia óptica e a microscopia eletrônica de transmissäo evidenciaram o trombo venoso e os seus constituintes. A retinografia fluorescente mostrou-se semelhante ao exame anato-patológico - realizado mediante a microscopia óptica e a microscopia eletrônica de transmissäo - em evidenciar a obstruçäo/patência venular, demonstrando,assim, ser um métoo confiável para o estudo da obstruçäo venular dentro do modelo utilizado

Cutis Laxa associada à insuficiência cardíaca congestiva / Cutis laxa associated to cardiac failure

Objetivo: Chamar a atençäo para uma doença rara da infância que se apresenta como envelhecimento precoce e pode ser letal. Métodos: Os autores relatam um caso de cutis laxa, uma síndrome de envelhecimento precoce, em uma criança de oito anos de idade e discutem sobre a classificaçäo da doença, diagnóstico e prognóstico. Evoluçäo do caso: A criança apresentou sinais de envelhecimento aos quatro anos. O diagnóstico de cutis laxa foi confirmado pela biópsia de pele. Apresentou insuficiência cardíaca congestiva, uma complicaçäo sistêmica diferente das descritas em trabalhos anteriores, evoluindo para o óbito aos oito anos. Conclusöes: A importância do diagnóstico de cutis laxa reside no fato de que, além do quatro dermatológico característico, há freqüentes complicaçöes sistêmicas que podem ser alvo de uma atuaçäo preventiva, uma vez que näo existe tratamento específico para a doença. O aconselhamento genético é também importante nesta condiçäo

Paraganglioma funcionante do pescoço / Neck functioning paraganglioma

Paragangliomas funcionantes sao tumores raros, produtores de catecolaminas que se originam da crista neural. Apresentamos o caso de um paciente de 11 anos com quadro de hipertensao arterial grave e massa em regiao cervical direita. Apresentou aumento das catecolaminas e metabólitos urinários: epinefrina, 97,8 mug/24hs (Valor de Referência (VR)= 0,5 a 20); norapinefrina, 184,8 mug/24hs (VR= 15 a 80); dopamina, 513,5 mug/24hs (VR=65 a 400); metanefrina 0,08 mg/g de creatinina (VR<0,31); normetanefrina, 0,64 mg/g de creatinina (VR< 0,43); ácido vanilmandélico, 69,3 mumol/24 hs (VR= 10 a 35). A cintilografia com meta-iodobenzil-guanidina (MIBG) mostrou a presença de massa hiperfixante em regiao cervical direita, a qual foi confirmada pela ressonância magnética (RM), que mostrou também uma lesao contra-lateral, que entretanto, nao apresentou captaçao pelo MIBG. Foi realizada a exérese da lesao cervical direita, evoluindo com normalizaçao dos níveis da pressao arterial, catecolaminas e metabólitos urinários. A imuno-histoquímica identificou grânulos de secreçao para enolase neuroespecífica, neurofilamentos, cromogranina, somatostatina e serotonina, que confirmaram o diagnóstico de paraganglioma funcionante, e identificou a presença de anti-proteína S100, que é um preditor de bom prognóstico. O paciente será acompanhado com exames clínicos e laboratoriais periódicos, devido à lesao contra-lateral e para se detectar uma eventual recidiva do tumor à direita. Apesar da presença de fatores de bom prognóstico, estes tumores sao considerados potencialmente malignos.

Influence of dietary protein content on Trypanosoma cruzi infection in germfree and conventional mice

Camundongos isentos de germes (GF) e convencionais (CV) foram alimentados com racoes contendo 4,4, 13,2 ou 26,4 por cento de proteina nao ganharam peso durante quatro semanas, enquanto a racao deficiente em proteina nao afetou o crescimento dos camundongos GF. Apos quatro semanas nessas racoes, os camundongos foram inoculados com 5x10 elevado ao cubo tripomastigotos de Trypanosoma cruzi. A deficiencia em proteina afetou menos os camundongos GF do que os CV, segundo os seguintes parametros: ganho em peso, hemoglobina, niveis em proteina e albumina no plasma e conteudos em agua e proteina na carcassa. A infeccao com T. cruzi produziu um decrescimo significante nos niveis em hemoglobina, na contagem de celulas vermelhas sanguineas e nos conteudos em agua e proteina na carcaca. Este decrescimo foi mais acentuado nos camundongos GF...

Modelo experimental para produçäo de oclusäo venosa retiniana em coelhos / Experimental model for production of retinal vein occlusion in rabbits

Objetivo: descrever um método experimental de produçäo de oclusäo venosa retiniana, näo-invasivo, em coelhos, por princípio fotoquímico, utilizando-se rosa bengala intra-venosa e o laser Nd-YAG verde. Materiais e métodos: foram submetidos, à fototrombose, 74 olhos de 37 coelhos albinos, utilizando o rosa bengala como corante orgânico fotoestimulador e o laser Nd-YAG verde, de comprimento de onda 532 nm. Destes, 62 olhos foram submetidos à retinografia fluorescente para demostrar a trombose clinicamente. 12 olhos foram submetidos a estudo anatomo-patológico para evidenciar o trombo intraluminal. Resultados: a oclusäo venosa foi comprovada fluoresceinograficamente em 57 dos 62 olhos submetidos à fototrombose venosa por mecanismos fotoquímicos

Nefropatia na infância: estudo morfológico / Nefropathy in childhood: a morphological study

O presente trabalho analisou 992 biópsias de pacientes menores de 16 anos de idade no período de 1980 a 1994. As biópsias de pacientes do sexo feminino representaram 47,08% do total. As indicações clínicas para a biópsia mais frequentemente encontradas foram síndrome nefrótica, síndrome nefrítica e hematúria isolada. As glomerulopatias proliferativas representaram o diagnóstico anatomopatológico mais comum. O diagnóstico morfológico mais freqüentemente associado com a síndrome nefrótica foi a glomeruloesclerose focal e segmentar e aquele mais relacionado à hematúria isolada foi a glomerulopatia proliferativa por IgA.

In the present paper 992 renal biopsies of patients under 16 years of age were analysed in the period of 1980 though 1994. Biopsies of female patients accounted for 47,08% of all biopsies. The most freguent clinical conditions that prompted the biop- sies were nephrotic syndrome, hematuria as a sole symptom and nephritic syndrome. The proliferative glomerulopathies were found to be the most common pathologycal diagnosis. The mor- hological diagnosis most freguently associated with nephrotic syndrome was focal and segmental glomerulosclerosis and the one most often related to hematuria as a sole symptom was IgA proliferative glomerulosclerosis.

Nefropatia lúpica na infância: estudo morfológico de 18 casos / Lupic nephropathy in childhood: morphologic analysis of 18 cases

No presente estudo foram avaliados 18 casos(17 do sexo feminino e 01 do sexo masculino) de pacientes com idade média de 8,9 anos, com diagnóstico de lupus eritematoso sistêmico, que foram submetidos a biópsia renal. Ao estudo histológico observaram-se 10 casos de glomerulopatia membranoproliferativa difusa(Classe IV-OMS);4 casos de glomerulopatia proliferativa focal(Classe III-OMS);2 casos de glomerulopatia proliferativa mesangial(Classe II-OMS);e 2 casos de glomerulopatia membranosa(Classe V-OMS). concluímos que, em nossa casuística, o número de crianças com LES é pequeno, semelhante ao descrito por outros autores, apresentando-se, na sua maior parte, com padröes histológicos desfavoráveis.

Fase crônica cardíaca fibrosante da tripanossomíase cruzi experimental no cäo / Fibrosing cardiac chronic phase in experimental Chagas' disease in dogs

Os autores documentan a cardiopatia difusa fibrosante, com todos os sintomas clínicos e dados de autópsia pertinente a insuficiência cardíaca congestiva, em um dos 21 cäes infectados com a cepa Colombiana (cinco morreram na fase aguda e quatro continuam vivos) e cinco, dos 13 infectados com a cepa Berenice-78 (oito morrerm na fase aguda), num período de oito anos de observaçäo. Em vista destes resultados, os autores sugerem que o cäo possa vir a ser um modelo experimental, adequado par o estudo da história da doença de Chagas, preenchendo os requisitos estabelecidos pelo Comitê Assessor de Doença de Chagas do Programa Especial de Pesquisa e Treinamento em Doenças Tropicais da Organizaçäo Mundial de Saúde