Multi-scale analysis of lung computed tomography images

A computer-aided detection (CAD) system for the identification of lung internal nodules in low-dose multi-detector helical Computed Tomography (CT) images was developed in the framework of the MAGIC-5 project. The three modules of our lung CAD system, a segmentation algorithm for lung internal region identification, a multi-scale dot-enhancement filter for nodule candidate selection and a multi-scale neural technique for false positive finding reduction, are described. The results obtained on a dataset of low-dose and thin-slice CT scans are shown in terms of free response receiver operating characteristic (FROC) curves and discussed.Comment: 18 pages, 12 low-resolution figure

Effect of fluvoxamine on plasma risperidone concentrations in patients with schizophrenia

The effect of fluvoxamine on plasma concentrations of risperidone and its active metabolite 9-hydroxyrisperidone (9-OH-risperidone) was investigated in 11 schizophrenic patients with prevailingly negative or depressive symptoms. Additional fluvoxamine, at the dose of 100 mg/day, was administered for 4 weeks to patients stabilized on risperidone (3–6 mg/day). Mean plasma concentrations of risperidone, 9-OH-risperidone and the active moiety (sum of the concentrations of risperidone and 9-OH-risperidone) were not significantly modified following co-administration with fluvoxamine. After 4 weeks, fluvoxamine dosage was increased to 200 mg/day in five patients and then maintained until the end of week 8. At final evaluation, mean plasma levels of risperidone active moiety were not modified in the six patients who were still receiving the initial fluvoxamine dose, while concentrations increased slightly but significantly (by a mean 26% over pretreatment; P < 0.05) in the subgroup of five subjects treated with a final dose of 200 mg/day. Fluvoxamine co-administration with risperidone was well tolerated and no patient developed extrapyramidal side effects. These findings indicate that fluvoxamine at dosages up to 100 mg/day is not associated with clinically significant changes in plasma risperidone concentrations. However, higher doses of fluvoxamine may elevate plasma risperidone levels, presumably as a result of a dose-dependent inhibitory effect of fluvoxamine on CYP2D6-and/or CYP3A4-mediated 9-hydroxylation of risperidone

Short stature in chronic kidney disease: physiopathology and treatment with growth hormone

Growth failure is frequent and a clinically important issue in children with chronic kidney disease (CKD). Many factors contribute to impaired growth in these children, including abnormalities in the growth hormone (GH) - insulin-like growth factor 1 (IGF-1) axis, malnutrition, acidosis, renal bone disease and glucocorticoid associated treatment. The management of growth failure in children with CKD is complicated by the presence of other-disease related complications requiring medical intervention. Despite evidence of GH efficacy and safety in this population, this therapy is still underutilized. This review shows the impact, the causes and the treatment of growth failure in children with CKD.O atraso no crescimento é freqüente e grave em crianças com doença renal crônica (DRC). Vários fatores contribuem para o comprometimento do crescimento nestas crianças, incluindo as alterações no eixo hormônio de crescimento (GH) - insulin-like growth factor 1 (IGF-1), desnutrição, acidose, doença renal óssea e uso de corticóides. Em crianças com DRC, o tratamento do atraso no crescimento é difícil em virtude da presença de doenças associadas que necessitem de adequado tratamento médico. Apesar de as evidências a respeito da segurança e de a eficácia do GH nesta população, este tratamento ainda é pouco utilizado. Esta revisão mostra o impacto, as causas e o tratamento do atraso no crescimento em crianças com DRC.Universidade Estadual de Campinas Faculdade de Ciências Médicas Clínica MédicaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Programa de Pós-graduação do Curso de PediatriaUNIFESP-EPM Departamento de PediatriaUnicamp FCM Departamento de PediatriaUNIFESP, EPM, Programa de Pós-graduação do Curso de PediatriaUNIFESP, EPM Depto. de PediatriaSciEL

Role of exosomes released by chronic myelogenous leukemia cells in angiogenesis

The present study is designed to assess if exosomes released from Chronic Myelogenous Leukemia (CML) cells may modulate angiogenesis. We have isolated and characterized the exosomes generated from LAMA84 CML cells and demonstrated that addition of exosomes to human vascular endothelial cells (HUVEC) induces an increase of both ICAM-1 and VCAM-1 cell adhesion molecules and interleukin-8 expression. The stimulation of cell-cell adhesion molecules was paralleled by a dose-dependent increase of adhesion of CML cells to a HUVEC monolayer. We further showed that the treatment with exosomes from CML cells caused an increase in endothelial cell motility accompanied by a loss of VE-cadherin and β-catenin from the endothelial cell surface. Functional characterization of exosomes isolated from CML patients confirmed the data obtained with exosomes derived from CML cell line. CML exosomes caused reorganization into tubes of HUVEC cells cultured on Matrigel. When added to Matrigel plugs in vivo, exosomes induced ingrowth of murine endothelial cells and vascularization of the Matrigel plugs. Our results suggest for the first time that exosomes released from CML cells directly affect endothelial cells modulating the process of neovascularization

O impacto do diagnóstico citológico de atipiasi indeterminadas no sistema público de saúde

As alterações citológicas de significado indeterminado representam uma importante limitação diagnóstica nos programas de escrutíneo de lesões cérvico-vaginais. A introdução de métodos biomoleculares, como o sistema de captura híbrida para detecção de HPV de alto risco contribui para a otimização da conduta clínica dessas pacientes, indicando colposcopia com precisão. Objetivo: avaliar o significado de lesões de significado indeterminado com relação à infecção pelo HPV, com o uso do teste de DNA para HPV com o método da captura de híbridos II. Métodos: foram estudadas amostras de 236 casos consecutivos examinados no laboratório da DIGENE-BRASIL, de pacientes com diagnóstico citológico prévio de ASCUS. As amostras foram submetidas ao teste de captura híbrida para identificação de DNA-HPV de alto e baixo riscos. Resultados: dos 236 casos analisados, 183 (77,5%) foram negativos para o teste de captura híbrida, seis (2,6%) foram positivos para HPV de baixo risco e 47 (19,9%) foram positivos para HPV de alto risco. Conclusão : as amostras positivas para HPV de baixo risco representam uma pequena e não- onsiderável minoria de casos, provavelmente, transientes. Cerca de 20% dos casos foram positivos para HPV de alto risco e deverão ser encaminhados à colposcopia e biopsia, se necessário. Esses casos representam um grande potencial de progressão para lesões cervicais.In order to optimize the morphological analysis of the cases with uncertain diagnosis, we critically analyzed the cases with Atypia of Squamous Cells of Undertemined Significance (ASCUS) in cytological samples of uterine cervix collected in conventional smears (CS) and liquidbased preparations (LBC) an to correlate the findings with Hybrid Capture II (HC2) assay and biopsy. Objective: to evaluate the meanig of undetermined cytological atypia in relation to HPV infection detected by hybrid capture II test. Methods: 97 cases taken from women examined at Perola Byignton Hospital, São Paulo, Brazil, during the year of 2002. The conventional smears were taken previously than LBC. The residual sample was placed in liquid-medium and LBC preparation with DNA-Citoliq system was performed. If at least one of the paired samples were classified as ASCUS, the pair was submitted to a guided revision in order to evaluate the type of alteration taken in account to categorized ASCUS. Results: from 97 cases studied, 14 were categorized as ASCUS by the two methods simultaneously. The others had different classification under or hyper estimated. Six cases diagnosed as squamous intraepithelial lesion (SIL) by CS were ASCUS by LBC; in contrary, 19 ASCUS by CS were SIL by LBC. Eleven ASCUS by CS were diagnosed as negative by LBC, but CS categorized 47 LBC ASCUS as negative. From the morphological parameters nuclear enlargement and coarse chromatin were regarded as ASCUS. From 68 ASCUS by LBC, 36 were HC2 positive for high risk HPV (hr-HPV) : ten of them with biopsy proven lesion. From 42 CS ASCUS, 23 were hr-HPV positive, but only 7 with histological lesion. Conclusion: our results reinforced the hypothesis that ASCUS is poorly reproducible by morphological examination by CS or LBC preparations. To add HC2 as adjunct method to ASCUS cytology can improve the routine diagnosed of the uncertain atypies

Abnormal expression of p27kip1 protein in levator ani muscle of aging women with pelvic floor disorders – a relationship to the cellular differentiation and degeneration

BACKGROUND: Pelvic floor disorders affect almost 50% of aging women. An important role in the pelvic floor support belongs to the levator ani muscle. The p27/kip1 (p27) protein, multifunctional cyclin-dependent kinase inhibitor, shows changing expression in differentiating skeletal muscle cells during development, and relatively high levels of p27 RNA were detected in the normal human skeletal muscles. METHODS: Biopsy samples of levator ani muscle were obtained from 22 symptomatic patients with stress urinary incontinence, pelvic organ prolapse, and overlaps (age range 38–74), and nine asymptomatic women (age 31–49). Cryostat sections were investigated for p27 protein expression and type I (slow twitch) and type II (fast twitch) fibers. RESULTS: All fibers exhibited strong plasma membrane (and nuclear) p27 protein expression. cytoplasmic p27 expression was virtually absent in asymptomatic women. In perimenopausal symptomatic patients (ages 38–55), muscle fibers showed hypertrophy and moderate cytoplasmic p27 staining accompanied by diminution of type II fibers. Older symptomatic patients (ages 57–74) showed cytoplasmic p27 overexpression accompanied by shrinking, cytoplasmic vacuolization and fragmentation of muscle cells. The plasma membrane and cytoplasmic p27 expression was not unique to the muscle cells. Under certain circumstances, it was also detected in other cell types (epithelium of ectocervix and luteal cells). CONCLUSIONS: This is the first report on the unusual (plasma membrane and cytoplasmic) expression of p27 protein in normal and abnormal human striated muscle cells in vivo. Our data indicate that pelvic floor disorders are in perimenopausal patients associated with an appearance of moderate cytoplasmic p27 expression, accompanying hypertrophy and transition of type II into type I fibers. The patients in advanced postmenopause show shrinking and fragmentation of muscle fibers associated with strong cytoplasmic p27 expression

The association of p16INK4A and fragile histidine triad gene expression and cervical lesions

Objective. This cross-sectional study was intended to assess the association between immunohistochemical analysis of p16INK4A and fragile histidine triad (FHIT) and the presence of precancerous cervical lesions. Materials and Methods. Women seen at Pe´ rola Byington Hospital, São Paulo, Brazil, with histologically confirmed cervicitis (n = 31), cervical intraepithelial neoplasia (CIN) 1 (n = 30), CIN 2,3 (n = 30), and cervical cancer (n = 7) had also cervical material collected for liquid-based cytology, human papillomavirus Hybrid Capture 2 (HC2) test, and p16 and FHIT immunohistochemical reactions. Results. p16 and FHIT reactions were scored as the following: G1%, 1% to 5%, 95% to 25%, and 925%. Receiver operating curve analysis was used to select p16 and FHIT score cutoffs for further categorical analyses. All but one of the 37 CIN 2,3/cancer cases had a p16 score of greater than 1% to 5%. Among the 61 cervicitis/CIN 1 cases, 46 (75%) had a p16 score lower than 1% to 5%. In contrast, no association of FHIT expression and severity of cervical lesions could be demonstrated in this data set. Receiver operating curve analyses suggested the score of 1% to 5% for p16 as the cutoff that best discriminates CIN 2,3/cancer from cervicitis/CIN 1. No cutoff for FHIT scores could be suggested with data set. Conclusions. p16, but not FHIT expression, has the potential to be used as complementary diagnostic tool to investigate human papillomavirusYinduced cervical lesions, if these results are confirmed in larger studies.(undefined