RESUMO
OBJECTIVES: As underlying heart diseases of right ventricular tachyarrhythmias, ARVC causes wall-motion abnormalities based on fibrofatty myocardial degeneration, while RVOT-VT and BrS are thought to lack phenotypic MR characteristics. To examine whether cardiac magnetic resonance (CMR) feature tracking (FT) in addition to ARVC objectively facilitates detection of myocardial functional impairments in RVOT-VT and BrS. METHODS: Cine MR datasets of four retrospectively enrolled, age-matched study groups [n = 65; 16 ARVC, 26 RVOT-VT, 9 BrS, 14 healthy volunteers (HV)] were independently assessed by two distinctly experienced investigators regarding myocardial function using CMR-FT. Global strain (%) and strainrate (s-1) in radial and longitudinal orientation were assessed at RVOT as well as for left (LV) and right (RV) ventricle at a basal, medial and apical section with the addition of a biventricular circumferential orientation. RESULTS: RV longitudinal and radial basal strain (%) in ARVC (- 12.9 ± 4.2; 11.4 ± 5.1) were significantly impaired compared to RVOT-VT (- 18.0 ± 2.5, p ≤ 0.005; 16.4 ± 5.2, p ≤ 0.05). Synergistically, RVOT endocardial radial strain (%) in ARVC (33.8 ± 22.7) was significantly lower (p ≤ 0.05) than in RVOT-VT (54.3 ± 14.5). For differentiation against BrS, RV basal and medial radial strain values (%) (13.3 ± 6.1; 11.8 ± 2.9) were significantly reduced when compared to HV (21.0 ± 6.9, p ≤ 0.05; 20.1 ± 6.6, p ≤ 0.005), even in case of a normal RV ejection fraction (EF) (> 45%; n = 6) (12.0 ± 2.7 vs. 20.1 ± 6.6, p ≤ 0.05). CONCLUSIONS: CMR-FT facilitates relevant differentiation in patients with right ventricular tachyarrhythmias: between ARVC against RVOT-VT and HV as well as between BrS with even a preserved EF against HV.
Assuntos
Displasia Arritmogênica Ventricular Direita/diagnóstico , Síndrome de Brugada/diagnóstico , Eletrocardiografia/métodos , Ventrículos do Coração/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética/métodos , Contração Miocárdica/fisiologia , Disfunção Ventricular Direita/diagnóstico , Displasia Arritmogênica Ventricular Direita/fisiopatologia , Síndrome de Brugada/fisiopatologia , Diagnóstico Diferencial , Feminino , Seguimentos , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Disfunção Ventricular Direita/fisiopatologiaRESUMO
BACKGROUND: In 2015, the German Federal Ministry of Education and Research initiated a large data integration and data sharing research initiative to improve the reuse of data from patient care and translational research. The Observational Medical Outcomes Partnership (OMOP) common data model and the Observational Health Data Sciences and Informatics (OHDSI) tools could be used as a core element in this initiative for harmonizing the terminologies used as well as facilitating the federation of research analyses across institutions. OBJECTIVE: To realize an OMOP/OHDSI-based pilot implementation within a consortium of eight German university hospitals, evaluate the applicability to support data harmonization and sharing among them, and identify potential enhancement requirements. METHODS: The vocabularies and terminological mapping required for importing the fact data were prepared, and the process for importing the data from the source files was designed. For eight German university hospitals, a virtual machine preconfigured with the OMOP database and the OHDSI tools as well as the jobs to import the data and conduct the analysis was provided. Last, a federated/distributed query to test the approach was executed. RESULTS: While the mapping of ICD-10 German Modification succeeded with a rate of 98.8% of all terms for diagnoses, the procedures could not be mapped and hence an extension to the OMOP standard terminologies had to be made.Overall, the data of 3 million inpatients with approximately 26 million conditions, 21 million procedures, and 23 million observations have been imported.A federated query to identify a cohort of colorectal cancer patients was successfully executed and yielded 16,701 patient cases visualized in a Sunburst plot. CONCLUSION: OMOP/OHDSI is a viable open source solution for data integration in a German research consortium. Once the terminology problems can be solved, researchers can build on an active community for further development.
Assuntos
Comportamento Cooperativo , Implementação de Plano de Saúde , Hospitais Universitários , Avaliação de Resultados em Cuidados de Saúde , Alemanha , Humanos , Inquéritos e Questionários , VocabulárioRESUMO
The expression patterns of the neurotrophin, brain-derived neurotrophic factor, BDNF, and the neurotrophic receptors-p75NTR and Trk receptors-in the developing human fetal inner ear between the gestational weeks (GW) 9 to 12 are examined via in situ hybridization and immunohistochemistry. BDNF mRNA expression was highest in the cochlea at GW 9 but declined in the course of development. In contrast to embryonic murine specimens, a decline in BDNF expression from the apical to the basal turn of the cochlea could not be observed. p75NTR immunostaining was most prominent in the nerve fibers that penetrate into the sensory epithelia of the cochlea, the urticule and the saccule as gestational age progresses. TrkB and TrkC expression intensified towards GW 12, at which point the BDNF mRNA localization was at its lowest. TrkA expression was limited to fiber subpopulations of the facial nerve at GW 10. In the adult human inner ear, we observed BDNF mRNA expression in the apical poles of the cochlear hair cells and supporting cells, while in the adult human utricle, the expression was localized in the vestibular hair cells. We demonstrate the highly specific staining patterns of BDNF mRNA and its putative receptors over a developmental period in which multiple hearing disorders are manifested. Our findings suggest that BDNF and neurotrophin receptors are important players during early human inner ear development. In particular, they seem to be important for the survival of the afferent sensory neurons.
Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cóclea/embriologia , Fatores de Crescimento Neural/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Receptores de Fator de Crescimento Neural/metabolismo , Animais , Sequência de Bases , Cóclea/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Glicoproteínas de Membrana/metabolismo , Camundongos , Receptor trkA/metabolismo , Receptor trkB/metabolismo , Receptor trkC/metabolismoRESUMO
AIM: Nerve-sparing surgery during laparoscopic rectal mobilization is still limited by anatomical constraints such as obesity, the narrowness of the male pelvis, an ultra low rectal cancer or all of these. The transanal approach for total mesorectal excision has overcome the shortcomings of limited access to the rectal 'no-man's land' close to the pelvic floor. The aim of this anatomical study was to define a roadmap of anatomical landmarks for the caudal to cephalic approach so as to standardize nerve-sparing rectal mobilization procedures. METHOD: Macroscopic dissections of the pelvis in a caudal to cephalic direction were performed in eight alcohol-glycerol embalmed cadavers. A roadmap of anatomical landmarks was created at different levels of section to demonstrate the sites of nerve injury. RESULTS: Extrinsic autonomic nerves to the urogenital organs and the internal sphincter muscle are closely adjacent to the lowest portion of the rectum above the pelvic diaphragm. CONCLUSION: This anatomical guide for the pelvic surgeon should facilitate a safe and nerve-sparing dissection of the mesorectal plane with a meticulous overview of the lowest autonomic nerve fibres. New anatomical insights by a 'caudal to cephalic' approach to the 'no-man's land' should help overcome anatomical constraints of a narrow, obese and male pelvis during rectal mobilization procedures.
Assuntos
Pontos de Referência Anatômicos/anatomia & histologia , Sistema Nervoso Autônomo/anatomia & histologia , Diafragma da Pelve/inervação , Reto/inervação , Cirurgia Endoscópica Transanal/métodos , Idoso , Idoso de 80 Anos ou mais , Vias Autônomas , Cadáver , Dissecação/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diafragma da Pelve/cirurgia , Reto/cirurgiaRESUMO
PURPOSE: Neurostimulation of the pudendal nerve (PN) is considered for patients who have failed sacral neuromodulation. Previous techniques for PN localization are described to be uncomplicated and promise to achieve accuracy in electrode placement. However, in clinical use, they appear challenging. We developed a puncture technique using fixed anatomical landmarks for a fast and reproducible localization of the PN. METHODS: Full-body cadavers and dissected anatomical preparations were studied for the course of the PN. Fluoroscopically controlled fixed anatomical landmarks locating the pudendal trunk were defined. Lead placement following established techniques was performed, and the topographic relationship to the PN was documented by dissection. In a pilot series of 20 patients with chronic pelvic pain, pudendal neuromodulation (PNM) was performed uni- and bilateral using the different approaches. Technical and clinical outcomes of the various techniques were compared. RESULTS: Fixed anatomical landmarks such as ischial spine, ischial tuberosity, acetabulum and anal rim resulted in a right-angled triangle with a new start and target point for puncture. Initials of the landmarks add up to the teaching acronym STAR. STAR technique including a puncture angle of 60° and a gluteal lead exit places 3-4 electrode poles at the nerve. In clinical trial, mean operation time for bilateral PNM in STAR was 85 min with mean puncture attempts of 3.5 to reach the nerve. Pain decreased statistically significant only in bilateral PNM. CONCLUSIONS: The STAR approach appears to achieve technical standardisation and optimized reproducibility in pudendal lead placement resulting into an increased feasibility of PNM.
Assuntos
Terapia por Estimulação Elétrica/métodos , Neuroestimuladores Implantáveis , Dor Pélvica/cirurgia , Nervo Pudendo/cirurgia , Cadáver , Dor Crônica , Terapia por Estimulação Elétrica/instrumentação , Humanos , Projetos Piloto , Neuralgia do Pudendo/cirurgiaRESUMO
BACKGROUND: Polo-like kinase 1 (Plk1) has an important role in mitosis. Volasertib (BI 6727), a potent and selective cell cycle kinase inhibitor, induces mitotic arrest and apoptosis by targeting Plk; this phase I study sought to determine its maximum tolerated dose (MTD) in Asian patients with advanced solid tumours. METHODS: Patients were enrolled simultaneously into two 3-week schedules of volasertib: a 2-h infusion on day 1 (schedule A) or days 1 and 8 (schedule B). Dose escalation followed a 3+3 design. The MTD was determined based on dose-limiting toxicities (DLT) in the first treatment course. RESULTS: Among 59 treated patients, the most common first course DLTs were reversible thrombocytopenia, neutropenia and febrile neutropenia; MTDs were 300 mg for schedule A and 150 mg for schedule B. Volasertib exhibited multi-exponential pharmacokinetics (PK), a long terminal half-life of â¼135 h, a large volume of distribution (>3000 l), and a moderate clearance. Partial responses were observed in two pre-treated patients (ureteral cancer; melanoma). Volasertib was generally well tolerated, with an adverse event profile consistent with its antimitotic mode of action and a favourable PK profile. CONCLUSIONS: These data support further development of volasertib and a harmonised dosing for Asian and Caucasian patients.
Assuntos
Antineoplásicos/uso terapêutico , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Neoplasias/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Pteridinas/uso terapêutico , Terapia de Salvação , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Terapia Combinada , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Meia-Vida , Doenças Hematológicas/induzido quimicamente , Humanos , Infusões Intravenosas , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/enzimologia , Neoplasias/patologia , Neoplasias/terapia , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/farmacocinética , Pteridinas/administração & dosagem , Pteridinas/efeitos adversos , Pteridinas/farmacocinética , Taiwan , Resultado do Tratamento , Quinase 1 Polo-LikeRESUMO
The pelvic floor is characterized by a complex morphology because different functional systems join here. Since a clear understanding of the pelvic floor region is crucial for female pelvic surgery and fundamental mechanisms of urogenital dysfunction and treatment, we here describe the accurate and functional anatomy of important pelvic structures and landmarks, clarify their terminology and point out possible errors or misunderstandings as to their existence.
Assuntos
Diafragma da Pelve/anatomia & histologia , Pelve/anatomia & histologia , Terminologia como Assunto , Tecido Conjuntivo/anatomia & histologia , Fáscia/anatomia & histologia , Feminino , Humanos , Ligamentos/anatomia & histologia , Sistema Urogenital/anatomia & histologiaRESUMO
This study investigated the feasibility of predicting the neutropenia-related effects of a therapy that combines the investigational drug BI 2536 (inhibitor of Polo-like kinase 1) and pemetrexed, an approved anticancer drug. Predictions were arrived at using the pharmacokinetic/pharmacodynamic (PK/PD) parameters of each of the drugs obtained from monotherapy studies and assuming that the neutropenic effect is additive when the drugs are administered as a combination therapy. Subsequently, a PK/PD model was developed to determine whether this assumption of additive effect was reasonable in relation to these two drugs. All analyses and simulations were performed using the population approach in NONMEM, version VI.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Simulação por Computador , Neoplasias Pulmonares/tratamento farmacológico , Modelos Biológicos , Neutropenia/induzido quimicamente , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/metabolismo , Ensaios Clínicos Fase I como Assunto , Estudos de Viabilidade , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Pemetrexede , Inibidores de Proteínas Quinases/administração & dosagem , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/metabolismo , Pteridinas/administração & dosagem , Resultado do Tratamento , Quinase 1 Polo-LikeRESUMO
Thrombotic complications following pancreas transplantation are still the most common cause of nonimmunologic graft loss. The aim of this study was to analyze pancreatic graft function after partial arterial graft thrombosis and the investigation of the pancreatic arterial anatomy with regard to intraparenchymal anastomoses. We retrospectively analyzed the data for 175 consecutive pancreas transplants performed between January 2002 and October 2007. Selective Y-graft angiography was performed in 10 and rubber-milk injection in 5 fresh pancreas specimens. Thrombosis of one leg of the Y-graft was diagnosed in 18 (10.3%) patients. Only one of these patients with thrombosis of the splenic artery required exogenous insulin. Sufficient graft perfusion was demonstrated in all of the remaining grafts. One graft was lost due to acute rejection. In all specimens angiography showed an excellent perfusion of the pancreaticoduodenal arcade, even after selective cannulation of the splenic artery. Arterial collaterals between the gastroduodenal, splenic artery and the superior mesenteric artery were demonstrated. Our results demonstrate that global perfusion of the pancreatic graft and sufficient graft function is sustained after the thrombotic occlusion of one branch of the Y-graft by a complex system of intraparenchymal anastomoses. These anatomical findings may have consequences for resection strategies in pancreas surgery.
Assuntos
Anastomose Cirúrgica , Sobrevivência de Enxerto , Transplante de Pâncreas , Baço/patologia , Trombose/complicações , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Modern haemorrhoidectomy techniques aim to interrupt arterial blood supply to the hypertrophied piles. The aim of this study was to investigate morphological and physiological alterations in the terminal branches of the superior rectal artery (SRA) in patients with haemorrhoidal disease treated by stapled haemorrhoidopexy (SH) using noninvasive transperineal ultrasound. METHOD: Thirty-seven consecutive patients (14 women, 23 men; median age 52, range 30-77 years) who underwent SH for treatment of grade III haemorrhoids were scanned by transperineal colour Doppler ultrasound at baseline, 4 weeks and 3 months postoperatively. Seventeen healthy volunteers served as the control group (nine women, eight men; median age 24, range 18-72 years). Calibre and arterial flow velocity (AFV) of the terminal branches of the SRA were measured. RESULTS: Baseline measurements significantly differed between patients and the control group (median calibre 2, range 0.9-3.6 mm, vs 1, range 0.6-1.2 mm, and median AFV 24, range 10-65 cm/s, vs 12, range 5-21 cm/s, P < 0.0001). Postoperative follow-up showed no significant alterations in the physiological parameters. Patients with a higher recurrence rate of haemorrhoidal disease had higher baseline AFV values. CONCLUSION: Stapled haemorrhoidopexy does not reduce arterial inflow in the feeding vessels of the anorectal vascular plexus. Preoperative ultrasound may serve as a tool for assessing vascularization status in haemorrhoidal disease and is useful in deciding whether patients should undergo SH or, for individuals with high AFV, whether conventional haemorrhoidectomy might be the better choice.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Hemorroidas/cirurgia , Reto/irrigação sanguínea , Grampeamento Cirúrgico , Adolescente , Adulto , Idoso , Feminino , Hemorroidas/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Ultrassonografia Doppler em Cores , Adulto JovemRESUMO
BACKGROUND: Posttraumatic or iatrogen compression syndromes of the common fibular nerve (CFN) are frequent. Based on previous anatomical investigations the aim of this study was to analyse the course of the CFN along the proximal portion of the leg with respect to its relationship to the anterior intermuscular septum (AIS). Further sites of constriction or fibrous fixation should be defined. MATERIAL AND METHODS: Anatomical dissection of 111 cadaveric leg specimens was performed. Twenty additional legs were used for histological examination of the respective region within the AIS of the leg. By means of medical records of three patients our current treatment strategy is demonstrated. RESULTS: A tight fixation of the most proximal motor branch of the deep fibular nerve (DFN) within the AIS at its entering point to the anterior compartment could be demonstrated. CONCLUSION: We conclude, that selective decompression not only of the CFN, but of the DFN branches which are fixed in the AIS along their course through the proximal portion of the leg, is mandatory during compression syndromes of the CFN.
Assuntos
Descompressão Cirúrgica/métodos , Microcirurgia/métodos , Síndromes de Compressão Nervosa/patologia , Síndromes de Compressão Nervosa/cirurgia , Nervo Fibular/patologia , Nervo Fibular/cirurgia , Neuropatias Fibulares/cirurgia , Adulto , Idoso de 80 Anos ou mais , Feminino , Humanos , Perna (Membro)/inervação , Masculino , Pessoa de Meia-Idade , Neuropatias Fibulares/patologiaRESUMO
PURPOSE: Vesicoureteral reflux is caused by a defective valve mechanism of the ureterovesical junction. Previous studies have revealed structural and metabolic changes in the intravesical ureter, impairing its contractile properties. Smooth musculature and nerves are replaced by collagen, while matrix degrading enzymes are over expressed. We investigated the presence of regulating cytokines and the extracellular matrix composition to elucidate further the pathophysiology of vesicoureteral reflux. MATERIALS AND METHODS: Ureteral endings were obtained from 28 children during antireflux surgery, and 14 age matched autopsy specimens served as controls. Routine histological sections were immunostained for insulin-like growth factor-1, nerve growth factor, transforming growth factor-beta1, tumor necrosis factor-alpha and vascular endothelial growth factor. Smooth muscle staining was supplemented by tenascin C, tetranectin and fibronectin detection. Staining patterns were investigated using computer assisted, high power field magnification analyses. RESULTS: Tumor necrosis factor-alpha and transforming growth factor-beta1 were significantly more abundant in vesicoureteral reflux samples, whereas insulin-like growth factor-1, nerve growth factor and vascular endothelial growth factor were more prevalent in healthy controls. Fibronectin was intensely expressed in refluxing ureters, while it was scarce in healthy children. Tenascin C was notable within the urothelium of both groups. Only vesicoureteral reflux samples displayed tenascin C in the musculature and connective tissue. Tetranectin staining was only detected in vesicoureteral reflux. CONCLUSIONS: Several cytokines are differentially expressed in primary refluxing ureters, indicating an ongoing tissue remodeling process in the ureterovesical junction region. Additionally, the smooth muscle coat is widely lacking, while extracellular matrix proteins typical for tissue shrinkage and reorganization are over expressed. These alterations are likely to contribute to the malfunctioning active ureteral valve mechanism in primary vesicoureteral reflux.
Assuntos
Citocinas/metabolismo , Matriz Extracelular/patologia , Músculo Liso/patologia , Refluxo Vesicoureteral/metabolismo , Refluxo Vesicoureteral/patologia , Biomarcadores/metabolismo , Biópsia por Agulha , Estudos de Casos e Controles , Pré-Escolar , Matriz Extracelular/metabolismo , Espaço Extracelular , Feminino , Humanos , Imuno-Histoquímica , Lactente , Junções Intercelulares/patologia , Masculino , Contração Muscular/fisiologia , Fatores de Risco , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Somatomedinas/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Ureteroscopia , Urotélio/metabolismo , Urotélio/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
The delineation of pancreatic nerve innervation during fetal life may contribute to our understanding of pancreatic pain modalities after birth. The aim of this study was to characterize the spatial and temporal distribution of nerve structures in the human pancreas throughout gestation. Computer-based image morphometry with piecewise polynomial interpolation analysis was performed to quantify nervous structures in the head, body and tail of the pancreas. Nerve structures were detected by automatic immunostaining techniques using a polyclonal antibody against two S-100 proteins that reacts strongly with human S100A and B that are detected in Schwann cells. Immunoreactivity was found in the parenchyma of head, body and tail of the pancreas with the relative density being head>body>tail. In addition to this extensive set of nerve fibers terminating in the pancreas there were large bundles of en passant nerve fibers in the dorsal region of the pancreas that were 3D reconstructed and were associated with the superior mesenteric plexus. If at first glance, the perimeter and the width of the nerve fibers seem to increase at a continuous rate up to term in all three regions of the pancreas, spatial and temporal co-analysis identified that the head of the pancreas shows a two-peak growth increase at 14 and 22 weeks of gestation with regard to the area, perimeter and width of the nerve structures, while the body and tail regions show a unique peak at 20 weeks. A developmental deceleration was found between the 22nd and the 36th week of gestation for the head region only. This is the first systematic study of nerve innervation of the human pancreas throughout gestation. The developmental dynamics of the pancreas nerve innervation corresponds approximately to the remodeling of the intrahepatic biliary system. Understanding the factors and disease states that may alter the distribution of nerve structures can be of significance for the development of therapies in pancreatic disorders of child- and adulthood.
Assuntos
Pâncreas/embriologia , Pâncreas/inervação , Feto , Humanos , Processamento de Imagem Assistida por Computador , Imageamento Tridimensional , Imuno-Histoquímica , Pâncreas/metabolismo , Proteínas S100/metabolismoRESUMO
Diagnostics and therapy of anorectal disorders are still questions of surgery. Exact knowledge of functional anatomy and precise clinical examination constitute the basis for the resulting therapeutic strategies. Three-dimensional endosonography and technical advances in flexible endoscopy using high-resolution chromoendoscopy and narrow-band imaging enable exact staging and diagnosis, even of malignancies in earliest stages. Furthermore new in-vivo staining methods combined with high-resolution imaging facilitate the discrimination of inflammatory and neoplastic lesions, which often lead to diagnostic difficulties in chronic inflammatory bowel disease. Developments in neurologic testing, including surface electromyography and sacral nerve stimulation, complement the diagnostic armamentarium.
Assuntos
Doenças do Ânus/patologia , Neoplasias do Ânus/patologia , Doenças Retais/patologia , Neoplasias Retais/patologia , Canal Anal/patologia , Canal Anal/fisiopatologia , Doenças do Ânus/diagnóstico , Doenças do Ânus/fisiopatologia , Neoplasias do Ânus/diagnóstico , Neoplasias do Ânus/fisiopatologia , Eletromiografia , Endossonografia , Potencial Evocado Motor/fisiologia , Incontinência Fecal/diagnóstico , Incontinência Fecal/fisiopatologia , Pólipos Intestinais/diagnóstico , Pólipos Intestinais/patologia , Pólipos Intestinais/fisiopatologia , Estadiamento de Neoplasias , Proctoscopia , Doenças Retais/diagnóstico , Doenças Retais/fisiopatologia , Neoplasias Retais/diagnóstico , Neoplasias Retais/fisiopatologia , Reto/patologia , Reto/fisiopatologia , Raízes Nervosas Espinhais/fisiopatologiaRESUMO
PURPOSE: Human prostate development starts in the tenth week of gestation. Initial interactions between the epithelium and mesenchyma are stimulated by androgens. The transformation of circulating testosterone to 5alpha-dihydrotestosterone by tissue linked 5alpha-reductase is a key event in androgen metabolism. The 5alpha-dihydrotestosterone mediates androgen effects in the urogenital sinus and external genitalia, leading to the formation of a male phenotype and androgen mediated prostate growth. Supposedly 5alpha-reductase 2 is the predominant isoenzyme in human accessory sex tissue, whereas the function of 5alpha-reductase 1 remains unclear. We focused on the detection, distribution and effects of the 2 isoenzymes during gestation and infancy. MATERIALS AND METHODS: Serial sections from fetuses and infants were immunostained using antibodies directed against 5alpha-reductase 1 and 2. Additionally, to detect the downstream products of androgen synthesis reverse transcriptase-polymerase chain reaction analyses were done for 17 beta-hydroxysteroid dehydrogenase types 2, 3 and 7. RESULTS: Immunohistochemistry revealed positive staining for each isoenzyme throughout fetal development. Moreover, reverse transcriptase-polymerase chain reaction for 5alpha-reductase 1 and 2 confirmed these findings on the transcription level. Additionally, the most relevant enzymatic downstream products of cellular androgen synthesis (17 beta-hydroxysteroid dehydrogenase 2, 3 and 7) were also detected by reverse transcriptase-polymerase chain reaction. CONCLUSIONS: To our knowledge this is the first study revealing the expression and distribution of each 5alpha-reductase isoenzyme as well as the potential contribution of 5alpha-reductase 1 during fetal human prostate development.
Assuntos
Colestenona 5 alfa-Redutase/genética , Isoenzimas/genética , Próstata/embriologia , 17-Hidroxiesteroide Desidrogenases/genética , Feminino , Idade Gestacional , Humanos , Técnicas Imunoenzimáticas , Recém-Nascido , Masculino , Gravidez , Próstata/crescimento & desenvolvimento , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transcrição Gênica/genéticaRESUMO
PURPOSE: Previous studies have revealed structural and metabolic changes in the distal most ureter, impairing its contractile properties, and, thus, having a role in the pathogenesis of vesicoureteral reflux. Musculature and nerves are replaced by interstitial collagen, while matrix degrading enzymes are over expressed. We investigated the microvessel architecture of the ureterovesical junction to elucidate further the pathophysiology of vesicoureteral reflux. MATERIALS AND METHODS: Ureteral endings were obtained from 28 children during antireflux surgery. Ureteral tissue from 14 age matched autopsy specimens served as control. Routine histological paraffin embedded sections were immunostained, detecting CD31 as an endothelial marker as well as vascular endothelial growth factor. Microvessel density and vascular endothelial growth factor expression were investigated based on computer assisted high power field magnification analyses. The t test and the Spearman rho test were applied for statistical evaluation. RESULTS: Overall, microvessel density was significantly reduced in cases of vesicoureteral reflux. While reflux grade and age were not correlated with microvessel density, it was particularly decreased in regions lacking smooth musculature. Vascular endothelial growth factor was observed in smooth muscle, endothelial and connective tissue cells. Additionally, cellular vascular endothelial growth factor expression was markedly abridged in cases of vesicoureteral reflux compared to healthy controls. CONCLUSIONS: Overall microperfusion is supposed to be impaired, leading to tissue ischemia due to reduction of vascular endothelial growth factor expression and subsequent microvessel density. Diminished ureteral perfusion is likely to induce and support smooth muscle dysfunction as well as subsequent extracellular matrix remodeling, including increased collagen deposition. These ongoing functional and structural alterations may further deteriorate the active valve mechanism of the ureterovesical junction, causing vesicoureteral reflux.
Assuntos
Isquemia/complicações , Ureter/irrigação sanguínea , Ureter/patologia , Refluxo Vesicoureteral/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , MasculinoRESUMO
As we suppose that the knowledge of the prenatal development within the pelvic floor is necessary to understand the subdivision of the pelvic connective tissue we studied transparent sections through the untouched pelvis of fetuses and newborn. We compared them with those of adults and included modern imaging techniques. Our results show, that the classical concept concerning the subdivision of the pelvic connective tissue needs to be revised.
Assuntos
Colo do Útero/anatomia & histologia , Colo do Útero/embriologia , Tecido Conjuntivo/anatomia & histologia , Adulto , Tecido Conjuntivo/embriologia , Feminino , Humanos , Recém-NascidoRESUMO
Experimental and clinical studies investigated whether urinary incontinence can be effectively treated with transurethral ultrasound-guided injections of autologous myoblasts and fibroblasts.This new therapy was performed in eight female pigs. It could be shown that the injected cells survived well and that new muscle tissue was formed. Next, 42 patients (29 women, 13 men) suffering from urinary stress incontinence were treated. The fibroblasts were mixed with a small amount of collagen as carrier material and injected into the urethral submucosa to treat atrophies of the mucosa. The myoblasts were directly injected into the rhabdosphincter to reconstruct the muscle and to heal morphological and functional defects. In 35 patients urinary incontinence could be completely cured. In seven patients who had undergone multiple surgical procedures and radiotherapy urinary incontinence improved. No side effects or complications were encountered postoperatively. The experimental as well as the clinical data clearly demonstrate that urinary incontinence can be treated effectively with autologous stem cells. The present data support the conclusion that this new therapeutic concept may represent a very promising treatment modality in the future.
Assuntos
Técnicas de Cultura de Células/métodos , Fibroblastos/transplante , Mioblastos/transplante , Transplante de Células-Tronco/métodos , Engenharia Tecidual/métodos , Incontinência Urinária/diagnóstico , Incontinência Urinária/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Fibroblastos/patologia , Rejeição de Enxerto/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mioblastos/patologia , Transplante de Células-Tronco/efeitos adversos , Engenharia Tecidual/efeitos adversos , Resultado do TratamentoRESUMO
Our macroanatomical studies with cadaver specimens and clinical findings in the operative treatment of tendovaginitis stenosans de Quervain confirm the high number of anatomical variations in the first dorsal compartment of the wrist. With the help of thick transparent transversal-sections in one of 14 fetal wrists manufactured by plastination histology we found the first compartment with two tendons of the abductor pollicis longus and dorsal of this compartment a connective tissue formation and a separate compartment for the extensor pollicis brevis tendon, proved as a primary anatomical disposition. Macroscopically the septation is always located distal and dorsal-ulnar to the first compartment and is evidentally more common as an intraoperative than an cadaver dissection finding and probably should be considered as a pathological condition. The secondary formation of an incomplete until complete separate septum may depend on the multiple abductor pollicis longus tendons and on chronical inflammatory reaction of the synovialis of the constricted extensor pollicis brevis tendon.
Assuntos
Tendões/anatomia & histologia , Articulação do Punho/anatomia & histologia , Feminino , Humanos , Masculino , Tendões/anormalidades , Tendões/patologia , Punho/anatomia & histologiaRESUMO
By help of thick transparent cross-sections of 10 thumbs, manufactured by plastination histology, it has been shown that the most fibres of the extensor pollicis brevis tendon insert on a special tubercle of the basis of the proximal phalanx. Our studies prove that the shape of this tubercle is configurated in the phalanx proximalis longitudinally between the first and second fifth part and in the wideness of the base, seen from radial to ulnar between the forth and fifth tenth part.