Percutaneous kidney biopsies have been performed since 1944 to establish diagnoses and treatment. Risk factors based on a limited amount of data have shown age, blood pressure, kidney function and needle size as some risk factors for biopsy complications. Although the techniques of biopsy have improved over the years, it is still an invasive procedure and serious complications can occur. The overall aim of this thesis was to obtain a large series of data from biopsy procedures and to use these to bring further light on risk factors to help minimize the risk for patients and to optimize diagnostics. Specific aims were to clarify if different factors, such as gender, diagnoses, localization of biopsies, needle types and sizes, could be useful to help minimize complication risks in native kidney biopsies (Nkb) and transplant kidney biopsies (Txb). Another point to investigate was the value of the Resistive Index (RI) obtained at ultrasound before performing Txb. Materials and methods: A protocol for prospective multicentre registration of various factors and complications associated with Nkb and Txb was designed. Consecutive data were obtained from seven hospitals. All biopsies, except one computer tomography-guided Nkb, were performed using real-time ultrasound guidance and an automated spring-loaded biopsy device. For the biopsies 14- to 20- Gauge (G) needles were used. The kidney function level, i.e. estimated glomerular filtration rate (eGFR), was calculated using the Modification of Diet in Renal Disease (MDRD) formula (GFR in mL/min per 1.73m2). For statistical analyses the IBM SPSS Statistic 22 (Armonk, NY, USA) and OpenEpi (Open Source Epidemiologic Statistics for Public Health, www.OpenEpi.com) were used. Data were presented as Odds Ratio (OR), Risk Ratio (RR) and Confidence Intervals (CI). A two sided p-value of <0.05 was considered significant. In total 1299 consecutive biopsies (1039 native and 260 transplant kidneys) in 1178 patients (456 women and 722 men) were used for investigation. The median age of patients was 55 years (range 16 to 90 years). Major (require an intervention) and minor biopsy complications (no need of intervention) were registered. Results: The overall frequency of biopsy complications for Nkb was 8.8% (major 6.7%, minor 2.1%) and for Txb was 6.5% (major 3.8%, minor 2.7%); no death. Women had a higher risk for development of major (10.7% versus 4.7%, OR 2.4, CI 1.4-4.2) and overall biopsy complications (13.2% versus 6.5%, OR 2.2, CI 1.4-3.5) compared to men in Nkb. In Nkb, major complications were more common after biopsies from the right kidney in women versus men (10.8% vs 3.1%, OR 3.7, CI 1.5–9.5), in patients with lower versus higher BMI (25.5 vs 27.3, p=0.016) and for younger versus older age (44.8 vs 52.3 years, p=0.002). Lower (90 mmHg) compared to higher (98 mmHg) mean arterial pressure in Txb indicated a risk of major complications (p=0.039). Factors such as number of passes and kidney function did not influence complication rates. Biopsy needles of 16 G compared to 18 G showed more glomeruli per pass in Nkb (11 vs 8, p<0.001) and in Txb (12 vs 8, p<0.001). Sub-analysis revealed that 18 G 19 mm side-notch needles in Nkb resulted in more major (11.3% vs 3%, OR 4.1, CI 1.4-12.3) and overall complications (12.4% vs 4.8%, OR 2.8, CI 1.1-7.1) in women than in men. If the physician had performed less compared to more than four Nkb per year, minor (3.5% vs 1.4%, OR 2.6, CI 1.1-6.2) and overall complications (11.5% vs 7.4%, OR 1.6, CI 1.1-2.5) were more common. The localization of biopsy within the kidney (Nkb and Txb) was not a risk factor for complications. Patients with IgA-nephritis compared to patients with other diseases had a higher risk of major complications (11.7% vs 6.4 %, OR 1.8, CI 1.1–3.2). More major complications were found in Nkb if they had higher versus lower degree of glomerulosclerosis (31% vs 20 %, p=0.008) and in Txb if there was a higher versus lower degree of interstitial fibrosis (82% vs 33%, p<0.001). Re-biopsies (Nkb) were more common in patients with IgA-nephritis than those with other diseases (4.7% vs 1.3 %, OR 4, CI 1.5–11), in younger versus older age (42.6 vs 52.3 years, p=0.031), and in those with a higher versus lower degree of interstitial fibrosis (63% vs 34 %, p=0.046). In Txb, a RI≥0.8 compared to RI<0.8 predicted major (13.3% vs 3.2%, RR 4.2, CI 1.3-14.1) and overall biopsy complications (16.7% vs 5.3%, RR 3.2, CI 1.2-8.6). In the group <0.8, RI correlated with age (rs=0.28, p<0.001) and systolic blood pressure (rs=0.18, p=0.02). In the group ≥0.8, RI correlated with degree of interstitial fibrosis (rs=0.65, p=0.006) and systolic blood pressure (rs=0.40, p=0.03). The multiple regression analysis showed that the <0.8 RI group correlated only with age (p<0.001), whereas the ≥0.8 RI group correlated only with the degree of interstitial fibrosis (p=0.003). Conclusions: The present results motivate greater attention to be paid to the possibility of major side-effects after Nkb in women and biopsies from their right side, but as well in younger patients, and in those with lower BMI. This also applies for patients with presumptive IgA-nephritis and higher degree of glomerulosclerosis. In Txb, patients with higher degree of interstitial fibrosis had a greater risk of major complications. Moreover, the present data indicate that Nkb and Txb should be preferably taken with 16 G needles with 20 mm sample size. This results in better histological quality and there is a lower risk for major complications as compared to 18 G needles. The localization of biopsy within the kidney (Nkb and Txb) does not alter complication rates. For Nkb there were fewer complications if the physician had performed at least four biopsies per year. A RI≥0.8 in Txb indicates a greater risk for major and overall complications.

Orientador: Pedro Luiz Toledo de Arruda Lourenção / Resumo: Introdução: A constipação intestinal é uma condição debilitante que afeta mais de 27% da população, representando um problema de saúde pública, além de corresponder a 3% de todas as consultas pediátricas. Existem várias causas congênitas e adquiridas. A Doença de Hirschsprung (DH) é a principal causa congênita de constipação e envolve 90% dos casos congênitos. O diagnóstico de disganglionoses intestinais depende da análise histopatológica de biópsias retais. Nessa revisão sistemática, levantamos todas as series de casos disponíveis na literatura e desenvolvemos uma metanálise de proporções para definer a taxa de resultados conclusivos e as complicações relacionadas aos diferentes tipos de biópsia retal no diagnóstico de disganglionoses intestinais. Métodos: A partir de ampla busca na literatura em múltiplas bases de dados, foi realizada uma revisão sistemática e metanálise de proporção das séries de casos que envolviam biópsias retais em pesquisa de disganglionoses intestinais em crianças. Foram incluídas series de casos que envolvessem mais de 5 biópsias em pacientes menores de 18 anos de idade com suspeita de disganglionose intestinal, que descrevesse ao menos um tipo de biópsia retal. Os estudos deviam especificar a taxa de resultados conclusivos e a taxa de complicações das técnicas de biópsias. A análise de proporção de série de casos foi realizada e os resultados apresentados em gráficos do tipo forest plot. Resultados: Foram selecionados 151 estudos pelos critérios de ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Intestinal constipation is a debilitating condition that affects up to 27% of the population, representing an important public health problem and corresponding to 3% of all pediatric consultations. There are many different congenital and acquired conditions, but Hirschsprung’s disease (HD) is the main representative entity of congenital disease and is involved in 90% of all cases. The diagnosis of intestinal dysganglionosis depends on the histopathological analysis of rectal biopsies. Here we conducted an updated systematic review of all case series studies available in the literature and performed a pooled analysis of proportions to assess the rate of conclusive results and possible complications of different rectal biopsy techniques in the diagnosis of intestinal dysganglionosis. Methods: A broad literature search using multiple online databases. A systematic literature review and proportional meta-analysis of the available case series studies of rectal biopsies in the diagnosis of intestinal dysganglionosis in children were performed. We included case series with more than 5 rectal biopsies in children under 18 years of age suspected of intestinal dysganglionosis, that described at least one type of rectal biopsy. The studies should have specified the rate of conclusive results and the rate of complications of the biopsy procedures. Proportional meta-analysis of case series studies was performed and forest plot charts were created to summarize the data. Resul... (Complete abstract click electronic access below) / Doutor

The heterogeneity of breast cancer (disease stage and phenotype) makes it challenging to differentiate between each subtype; luminal A, luminal B, HER2, basal-like and claudin-low, on the basis of a single gene or protein. Therefore, a collection of markers is required that can serve as a signature for diagnosing different types of breast cancer. New developments in proteomics have provided the opportunity to look at phenotype-specific breast cancer cell lines and stage-specific liquid biopsies (nipple aspirate fluid [NAF], plasma samples) to identify disease and phenotype specific signature. An 8-plex iTRAQ quantification strategy was employed to compare proteomic profiles of a range of breast cancer and ‘normal-like’ cell lines with primary breast epithelial cells. From this, 2467 proteins were identified on Orbitrap Fusion and Ultraflex II, of which 1430 were common. Matched pairs of NAF samples from four patients with different stages of breast cancer, were analysed by SCX-LC-MS and a total of 1990 unique gene products were identified. More than double the number of proteins previously published data, were detected in NAF, including 300 not detected in plasma. The NAF from the diseased patients have 138 potential phenotype biomarkers that were significantly changed compared to the healthy volunteer (7 for luminal A, 9 for luminal B, 11 for HER2, 14 for basal-like and 52 for claudin-low type). The average coefficient of variation for triplicate analyses by multiple reaction monitoring mass spectrometry (MRM-MS), was 9% in cell lines, 17 % in tissue biopsies, 22% in serum samples and 24% in NAF samples. Overall, the results provide a strong paradigm to develop a clinical assay based on proteomic changes in NAF samples for the early detection of breast cancer supplementary to established mammography programmes.

A síndrome mielodisplásica primária (SMD) compreende um grupo de doenças hematopoéticas clonal de célula tronco pluripotente cacacterizada por vários graus de pancitopenia e alterações morfológica das células hematopoeticas e risco aumentado de transformação para leucemia mielóide aguda. A citogenética e a morfologia da medula óssea desempenham um papel fundamental para o diagnóstico e o prognóstico desses pacientes. Alterações cromossômicas são encontradas em aproximadamente 30-50% dos casos. Devido à importância da análise desses fatores para escolha terapêutica, torna-se necessário definir as alterações morfológicas e citogenéticas que possam contribuir para o prognóstico. Esse trabalho visa correlacionar as características morfológicas e citogenéticas da medula óssea em pacientes com SMD primária com as classificações OMS e FAB e com o IPSS. Foram estudados 32 pacientes com SMD primária diagnosticados entre 2000 e 2009 no HUPE-UERJ. As características clínicas foram analisadas através do levantamento de prontuários. A análise citogenética foi feita pela técnica de bandeamento GTG em células da medula ossea. A análise morfológica da biópsia de medula óssea e do mielograma foram realizadas através da revisão de lâminas. Vinte e três pacientes foram classificados em estágios iniciais da doença (22 AR, 1 ARSA) e 9 em estágio avançado AREB de acordo com a FAB. Alterações cromossômicas foram detectadas em 16 pacientes (50%). As mais frequentes foram: del(11)(q23) e del(17p). Dos pacientes com doença avançada, seis (66%) apresentaram aumento significativo da relação M:E (p=0,003) e sete (77%) possuíam alterações arquiteturais acentuadas (p<0,001) em comparação ao grupo de doença inicial. Pacientes classificados como intermediário 2 e alto risco pelo IPSS tiveram importante perda arquitetural (p<0,001), número significativamente maior de micromegacariócitos (p=0,017) e seis (85%) sofreram transformação leucêmica (p=0,006). ALIP foi significantemente aumentada nos pacientes de pior prognóstico (p=0,0 1) e naqueles com doença avançada (p=0,001). Nossos resultados apresentaram implicações potenciais para o diagnóstico e o prognóstico da SMD primária. As alterações morfológicas foram associadas com as classificações FAB, OMS e com os grupos de risco segundo o IPSS. / The primary myelodysplastic syndrome (MDS) comprises a heterogeneous group of clonal bone marrow disorders characterized by varying degrees of pancytopenia and morphological abnormalities of hematopoietic cells, and an increased risk of transformation into acute myeloid leukemia. The morphology and the cytogenetic of bone marrow play a key role in the diagnosis and the prognosis. Chromosomal abnormalities are found in 30-50% of cases. Due to the importance of analyzing these factors for therapeutic choice, it becomes necessary to define the morphological and the cytogenetic changes which could contribute to the prognosis.The aim of this study was to analyze the morphological and cytogenetic features of bone marrow and their correlations with FAB and WHO clasification and IPSS. We studied 32 patients with primary MDS between 2000 - 2009. The clinical data was recovered from medical records. Morphological characteristics were analyzed through a review of bone marrow biopsies and mielogram slides. Cytogenetic analysis was performed by GTG banding from bone marrow cells. The patients were classified according to FAB in initial stages: RA (22 patients) and RARS (1 patient) and nine in advanced stages - RAEB. Chromosomal abnormalities were detected in 16 patients (50%). The most frequent abnormalities were: del(11)(q23) and del(17p). Patients with advanced disease, six (66%) had significant increased M:E ratio (p=0.003) and seven patients (77%) had increased architectural changes (p<0.001). Patients classified as intermediary 2 and high risk according IPSS had important architectural loss (p<0.001), presence of micromegakaryocyte was considered significant higher (p=0.017) and six patients (85%) underwent leukemia transformation (p=0.006). ALIP was significant higher in the patients with a worse prognosis (p=0.021) and advanced stage of disease (p=0.001). Our results showed potential implications for diagnosis and prognosis of MDS. The morphological findings in this study were associated with FAB and WHO groups and prognostic risk (IPSS).

Ce travail avait pour objectif i) d'analyser les caractéristiques physiologiques et musculaires(déterminées d'après des biopsies) de rameurs poids légers entraînés, ii) de proposer une méthode de153calcul pour estimer de façon non-invasive la quantité de lactate accumulé dans l'organisme (QTLS) au cours d'un exercice épuisant sur ergomètre aviron d'après la modélisation de la cinétique lactique pendant la récupération et iii) d'explorer l'influence des caractéristiques musculaires, et de l'aptitude à échanger et à éliminer le lactate sur la capacité anaérobie des rameurs appréciée par la mesure du déficit maximal d'O2 cumulé (DMOC).Premièrement, les rameurs étudiés possédaient un rapport masse musculaire - masse corporelle élevé et leurs paramètres physiologiques et musculaires étaient caractéristiques des athlètes spécialisées en endurance.Dans un deuxième temps, nous avons démontré que QTLS était corrélé positivement à DMOC.Cette relation supporte notre hypothèse et confirme la cohérence de la méthode proposée pour calculer QTLS.Dans une dernière étude, les résultats ont démontré que DMOC était corrélée positivement à l'aptitude à éliminer le lactate. Cette dernière était également significativement corrélée à la densité capillaire et au contenu musculaire en MCT4, une protéine impliquée dans le cotransport lactate-proton à travers le sarcolemme.

Zielsetzung dieser Arbeit ist die Vorstellung des klinischen Aufbaus und des Arbeitsablaufs eines robotischen Assistenzsystems für bildgeführte Interventionen in einem konventionellen Magnetresonanztomographen (MRT), sowie die Beurteilung der Genauigkeit und der klinischen Erfahrungen bei perkutanen Biopsien in verschieden Körperregionen. Material und Methoden: Das MR- kompatible, servopneumatische robotische Assistenzsystem lässt sich mit dem Patienten in die 60- cm Gantry eines Standard- MR- Scanners fahren. Die Genauigkeit des Systems wurde anhand von Nadelpunktionen (n= 25) in einem Phantommodell ermittelt. Perkutane diagnostische Biopsien wurden bei sechs Patienten durchgeführt. Ergebnisse: Für eine Interventionstiefe zwischen 29 und 95 mm wurde eine 3-DGenauigkeit von 2,2 +/- 0,7 mm (Intervall 0,9- 3,8 mm) bestimmt. Patienten mit einem BMI bis zu ≈30 kg/m2 konnten mit dem System punktiert werden. Die klinischen Arbeitsschritte werden anhand der Fallbeispiele dargestellt. Die mittlere Interventionszeit betrug 44 Minuten (Intervall 36 – 68 Minuten). Zusammenfassung: Die Punktion verschiedener Körperregionen ist mit Hilfe des robotischen Assistenzsystems in einem geschlossenen MRT erfolgreich und sicher möglich. Die Genauigkeit des Systems ist vergleichbar mit anderen Assistenzsystemen in der Literatur und genügt den klinischen Anforderungen. Eine kürzere Interventionszeit ist mittels einer Optimierung der einzelnen Arbeitsschritte möglich.

In the present study the cross sectional areas of individual muscle fibers were investigated with focus on statistical methodology. This thesis includes data from two studies; Resistance Study and Method Study. The Resistance Study analyzes the effect of exercise by comparing muscle fiber area before and after eight weeks of resistance training. Muscle biopsies from the vastus lateralis muscle were obtained from young male participants. The purpose of the Method Study was to examine the variation between right and left leg. Contrary to previous studies, this thesis focuses on individual data rather than on group-based data, and therefore takes a different approach than the previously published articles. This is proven to be successful since information is lost when analyzing group-wise, as the increase in small muscle fibers did not show when analyzing as a group. The results of the Resistance Study is similar to the results of the Method Study. Means and standard deviations have a wide spread both between subjects and between biopsies taken from the same subject. Inference on the 10th and 90th percentiles shows a positive pattern in the Resistance Study, in the sense that both the smallest and the largest muscle fibers have grown as a result of the resistance training. If muscle fiber area is used as a proxy for training effect, the conclusion is that many people seem to have responded well to the training.

[Tuncated abstract] There has been longstanding concern over whether endobronchial biopsies adequately represent inflammation throughout the bronchial tree in diseases such as asthma, despite the endobronchial biopsy technique having been used frequently to assess airway inflammation in research settings. There has also been ongoing debate about whether endobronchial biopsies should be assessed by new, unbiased, three-dimensional (3D) stereological techniques instead of traditional, two-dimensional (2D) non-stereological techniques. Therefore, the aims of this study were: (i) to investigate whether endobronchial biopsies represent the density of mast cells in the large and small airways, in alveolar walls and in the lung as a whole (ii) to use both stereological and non-stereological methods to address this question, and where possible, to compare the results of these two approaches. '...' Mast cell density in biopsies was not related to mast cell density immediately adjacent to the biopsy site or to mast cell density in the total airway wall in the large airways, the inner airway wall in the small airways, the walls of the alveoli or the lung as a whole. In general, measurements of mean mast cell density on biopsies to a depth of 100µm below the basement membrane were poorly related to mean mast cell density in other compartments of the lung. Mean 3D and 2D mast cell densities were strongly correlated (r 0.9, p < 0.005) and where both methods were used, results were similar. The mean height and area profile of a mast cell were approximately 12µm and 68µm2 respectively. In disk-shaped IUR lung samples, percent shrinkage in height due to paraffin processing was systematically greater than percent radial shrinkage by an average of approximately 4 times. Cavalieri lung volumes were systematically smaller than displacement volumes by an average of 14%. Any given endobronchial biopsy is unlikely to represent mast cell density around the airway wall generally in the vicinity of the biopsy site. However, the average of at least 4 biopsies from different sites in the proximal airways can be used to both represent mean mast cell density in the inner airway wall of the large airways, and act as the basis for inter-subject comparisons of mean mast cell density in the total airway wall of the small airways. On biopsies, mast cell counts should be measured over the entire inner airway wall not just to a depth of 100µm or less below the basement membrane. 3D mast cell densities obtained by stereological methods are closely related to 2D mast cell densities obtained by non-stereological methods and are likely to result in similar conclusions. Lung volumes are smaller when measured by the Cavalieri method than when measured by fluid displacement. Shrinkage of isotropic uniform random samples of human lung tissue due to paraffin processing is anisotropic. The mean volume of a mast cell in the human lung is likely to be much smaller than that reported previously for monkey lungs.

No description available.

A síndrome mielodisplásica primária (SMD) compreende um grupo de doenças hematopoéticas clonal de célula tronco pluripotente cacacterizada por vários graus de pancitopenia e alterações morfológica das células hematopoeticas e risco aumentado de transformação para leucemia mielóide aguda. A citogenética e a morfologia da medula óssea desempenham um papel fundamental para o diagnóstico e o prognóstico desses pacientes. Alterações cromossômicas são encontradas em aproximadamente 30-50% dos casos. Devido à importância da análise desses fatores para escolha terapêutica, torna-se necessário definir as alterações morfológicas e citogenéticas que possam contribuir para o prognóstico. Esse trabalho visa correlacionar as características morfológicas e citogenéticas da medula óssea em pacientes com SMD primária com as classificações OMS e FAB e com o IPSS. Foram estudados 32 pacientes com SMD primária diagnosticados entre 2000 e 2009 no HUPE-UERJ. As características clínicas foram analisadas através do levantamento de prontuários. A análise citogenética foi feita pela técnica de bandeamento GTG em células da medula ossea. A análise morfológica da biópsia de medula óssea e do mielograma foram realizadas através da revisão de lâminas. Vinte e três pacientes foram classificados em estágios iniciais da doença (22 AR, 1 ARSA) e 9 em estágio avançado AREB de acordo com a FAB. Alterações cromossômicas foram detectadas em 16 pacientes (50%). As mais frequentes foram: del(11)(q23) e del(17p). Dos pacientes com doença avançada, seis (66%) apresentaram aumento significativo da relação M:E (p=0,003) e sete (77%) possuíam alterações arquiteturais acentuadas (p<0,001) em comparação ao grupo de doença inicial. Pacientes classificados como intermediário 2 e alto risco pelo IPSS tiveram importante perda arquitetural (p<0,001), número significativamente maior de micromegacariócitos (p=0,017) e seis (85%) sofreram transformação leucêmica (p=0,006). ALIP foi significantemente aumentada nos pacientes de pior prognóstico (p=0,0 1) e naqueles com doença avançada (p=0,001). Nossos resultados apresentaram implicações potenciais para o diagnóstico e o prognóstico da SMD primária. As alterações morfológicas foram associadas com as classificações FAB, OMS e com os grupos de risco segundo o IPSS. / The primary myelodysplastic syndrome (MDS) comprises a heterogeneous group of clonal bone marrow disorders characterized by varying degrees of pancytopenia and morphological abnormalities of hematopoietic cells, and an increased risk of transformation into acute myeloid leukemia. The morphology and the cytogenetic of bone marrow play a key role in the diagnosis and the prognosis. Chromosomal abnormalities are found in 30-50% of cases. Due to the importance of analyzing these factors for therapeutic choice, it becomes necessary to define the morphological and the cytogenetic changes which could contribute to the prognosis.The aim of this study was to analyze the morphological and cytogenetic features of bone marrow and their correlations with FAB and WHO clasification and IPSS. We studied 32 patients with primary MDS between 2000 - 2009. The clinical data was recovered from medical records. Morphological characteristics were analyzed through a review of bone marrow biopsies and mielogram slides. Cytogenetic analysis was performed by GTG banding from bone marrow cells. The patients were classified according to FAB in initial stages: RA (22 patients) and RARS (1 patient) and nine in advanced stages - RAEB. Chromosomal abnormalities were detected in 16 patients (50%). The most frequent abnormalities were: del(11)(q23) and del(17p). Patients with advanced disease, six (66%) had significant increased M:E ratio (p=0.003) and seven patients (77%) had increased architectural changes (p<0.001). Patients classified as intermediary 2 and high risk according IPSS had important architectural loss (p<0.001), presence of micromegakaryocyte was considered significant higher (p=0.017) and six patients (85%) underwent leukemia transformation (p=0.006). ALIP was significant higher in the patients with a worse prognosis (p=0.021) and advanced stage of disease (p=0.001). Our results showed potential implications for diagnosis and prognosis of MDS. The morphological findings in this study were associated with FAB and WHO groups and prognostic risk (IPSS).