RESUMO
OBJECTIVES: To investigate the symptomatic and quality of life (QoL) response to treatment with tolterodine extended release (ER) in subgroups of male patients with Overactive Bladder Syndrome (OAB) and LUTS suggestive of non-obstructive benign prostatic hyperplasia (BPH) according to age, symptom severity, diabetes mellitus status, and concomitant treatment for LUTS. METHODS: Patients treated with tolterodine ER 4 mg/day for OAB symptoms, alone or added to unsuccessful alpha-blocker treatment of > or =6 weeks duration, and presumed non-obstructive BPH (Q (max) > or = 15 ml/s) were observed for 12 weeks in a non-interventional study. Patients completed the International Prostate Symptom Score (IPSS) and Overactive Bladder Questionnaire (OAB-q) at baseline and after 12 weeks. RESULTS: 52.4% of 741 patients were aged < or =65 years; 4, 64, and 32% had mild, moderate, and severe symptoms, respectively, according to IPSS; 14% had diabetes mellitus, and in 42% tolterodine was added to alpha blockers. In the various subgroups, mean IPSS total scores improved by 2.8-11.1 points, IPSS QoL scores by 1.8-2.4 points, and all OAB-q subscores by more than 14 points. Only IPSS and OAB-q baseline scores had a relevant impact on changes during treatment, benefits were greatest in patients with more severe symptoms and bother. CONCLUSIONS: In men with symptoms of OAB and LUTS suggestive of non-obstructive BPH of all IPSS severity classes, aged < or =65 years or above, with or without concomitant diabetes or alpha-blockers, symptoms and QoL improved markedly during treatment with tolterodine ER.
Assuntos
Compostos Benzidrílicos/administração & dosagem , Cresóis/administração & dosagem , Antagonistas Muscarínicos/administração & dosagem , Fenilpropanolamina/administração & dosagem , Hiperplasia Prostática/tratamento farmacológico , Prostatismo/tratamento farmacológico , Qualidade de Vida , Bexiga Urinária Hiperativa/tratamento farmacológico , Antagonistas Adrenérgicos alfa/administração & dosagem , Fatores Etários , Idoso , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Probabilidade , Estudos Prospectivos , Hiperplasia Prostática/diagnóstico , Prostatismo/diagnóstico , Análise de Regressão , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Tartarato de Tolterodina , Resultado do Tratamento , Bexiga Urinária Hiperativa/diagnóstico , UrodinâmicaRESUMO
OBJECTIVES: Quality of work life (QWL) is an important indicator of job-related satisfaction among nurses; however, there is little information regarding the QWL of nurses in Oman. Therefore, this study aimed to explore factors affecting QWL among nurses working in governmental health institutions in Ad Dakhiliyah Governorate, Oman. METHODS: This descriptive cross-sectional study was conducted between September and November 2018 at 29 governmental health institutions in Ad Dakhiliyah Governorate. A total of 374 nurses employed at these institutions were recruited via stratified random sampling. A demographic questionnaire incorporating Brooks' Quality of Nursing Work scale was used to collect data. RESULTS: A total of 345 nurses participated in the study (response rate: 92.2%). The mean age was 33.3 ± 5.1 years and the majority were female (90.7%), married (88.7%), of Omani nationality (70.1%) and had a diploma degree (70.7%). Overall, the nurses demonstrated moderate levels of QWL (mean total score: 179.99 ± 24.17). Both job designation and nationality were found to be significant predictors of QWL (P = 0.041 and <0.001, respectively). CONCLUSION: The findings of this study represent a baseline for further research on this important topic. As with all healthcare professionals, the QWL of nurses indirectly affects quality of patient care and associated health outcomes. As such, identifying areas of poor QWL among nurses can help in the development of initiatives to improve their professional satisfaction, thereby enhancing job performance and employee retention.
Assuntos
Satisfação no Emprego , Enfermeiras e Enfermeiros , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Omã , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: This study aimed to examine the rate and factors associated with the publication of abstracts presented by residents at Oman Medical Specialty Board (OMSB) scientific meetings. METHODS: This retrospective study was performed in February 2018. Two previous national OMSB scientific meetings at which resident abstracts were presented were identified, having taken place in January 2014 and December 2016, respectively. Independent searches of the MEDLINE® (National Library of Medicine, Bethesda, Maryland, USA) and Google Scholar (Google LLC, Menlo Park, California, USA) databases were conducted to determine subsequent publication of the abstracts. RESULTS: A total of 68 resident abstracts were presented, of which most were clinical research (92.6%). Residents comprised 36.4% of the authors, of which 73.1% were senior residents. In 64 abstracts (94.1%), a resident was the first author. Overall, 15 abstracts (22.1%) resulted in articles published in 11 journals. Of these, 12 (80%) represented clinical research and 10 articles (66.7%) were published in MEDLINE®-indexed journals. Residents were the first authors of eight articles (53.3%). The median time to publication was 19 months. The presence of two or more resident authors per abstract was significantly associated with publication (odds ratio = 5.50, 95% confidence interval = 1.15-26.36; P = 0.03). CONCLUSION: The publication rate of resident abstracts presented at two OMSB research meetings was low; however, a higher number of resident authors per abstract significantly increased the likelihood of publication. These findings may influence policymakers to implement measures to support inter-resident collaboration so as to increase research productivity.
Assuntos
Internato e Residência/tendências , Editoração/estatística & dados numéricos , Pesquisa/normas , Estudos de Coortes , Educação de Pós-Graduação em Medicina/métodos , Educação de Pós-Graduação em Medicina/tendências , Humanos , Internato e Residência/estatística & dados numéricos , Modelos Logísticos , Omã , Pesquisa/estatística & dados numéricos , Estudos Retrospectivos , Faculdades de Medicina/organização & administração , Faculdades de Medicina/estatística & dados numéricos , Conselhos de Especialidade Profissional/organização & administração , Conselhos de Especialidade Profissional/tendências , Estados Unidos , Universidades/organização & administração , Universidades/estatística & dados numéricosRESUMO
INTRODUCTION: The expression of the negative cell cycle regulator p27(Kip1) is frequently found to be deregulated in various human cancer types. Whether expression of p27(Kip1) can be used as prognostically relevant biological variables for renal cell cancer patients still remains to be clarified. Therefore, in the present investigation the expression within different tissue areas obtained from renal cell carcinomas was determined. PATIENTS AND METHODS: For analysis of p27(Kip1) in 420 tumor nephrectomy specimens obtained from 420 consecutively included patients, tissue microarrays were used comprising of 1,260 tissue samples each obtained from the tumor itself, the invasive front as well as non-malignant surrounding parenchyma. A sufficient follow-up after surgical therapy was available in 251 cases. RESULTS: In univariate survival analysis, decreased expression of p27(Kip1) within tissue cores obtained from the invasion front was significantly correlated with the patients' disease-specific long-term survival (p = 0.02, log-rank test). In contrast, expression of p27(Kip1) protein within the primary tumors was not identified to reveal any prognostically important information. In Cox regression analysis, histological stage and grade (p < 0.01), the presence of regional lymph node (p < 0.01) or distant metastases at the time of surgery (p < 0.01) as well as decreased expression of p27(Kip1) (p = 0.04) within the invasion front tissue samples independently predicted the disease-specific long-term survival following surgery. CONCLUSION: Our analysis demonstrated that p27(Kip1) is heterogeneously expressed in renal cell carcinomas. Moreover, the result of the present study supports the prognostic value of p27(Kip1) protein expression for patients diagnosed with renal cell carcinoma.
Assuntos
Carcinoma de Células Renais/genética , Inibidor de Quinase Dependente de Ciclina p27/biossíntese , Neoplasias Renais/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Inibidor de Quinase Dependente de Ciclina p27/genética , Feminino , Humanos , Rim/patologia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/biossíntese , Nefrectomia , Valor Preditivo dos Testes , Prognóstico , Análise Serial de ProteínasRESUMO
The accuracy of breath alcohol measurements in intubated patients with assisted ventilation was evaluated. The breath alcohol concentration was measured in 24 patients undergoing percutaneous alcohol injection therapy for hepatocellular carcinoma with Alcotest 7410 med, from Dräger, Germany. The blood ethanol concentrations (BACs) were determined in each blood serum applying the German forensic criteria standard, namely, two alcohol dehydrogenase (ADH) and two gas chromatography (GC) measurements. The blood alcohol concentrations were between 0.07 and 1.51 per thousand in the central venous samples and 0.02-1.66 per thousand in the arterial samples. An excellent correlation between both the venous and arterial blood alcohol concentrations (r2=0.94), as well as between the breath alcohol concentrations and the venous (r2=0.84) or arterial alcohol concentration (r2=0.89), p<0.01 for both parameters was revealed. Determination of breath alcohol concentration using the Alcotest in intubated patients is reliable and reflects the blood alcohol values.
Assuntos
Intoxicação Alcoólica/diagnóstico , Testes Respiratórios , Carcinoma Hepatocelular/terapia , Depressores do Sistema Nervoso Central/sangue , Depressores do Sistema Nervoso Central/uso terapêutico , Etanol/sangue , Etanol/uso terapêutico , Neoplasias Hepáticas/terapia , Respiração Artificial , Administração Cutânea , Idoso , Depressores do Sistema Nervoso Central/administração & dosagem , Etanol/administração & dosagem , Feminino , Humanos , Instilação de Medicamentos , MasculinoRESUMO
Tissue engineering and gene therapy are currently investigated in animal studies for reconstructing penile tissue or treating erectile dysfunction. This review aims to ecamine these experimental efforts from the last years and tries to give a brief introduction to the basic methodology of these new techniques from the field of regenerative medicine.
Assuntos
Disfunção Erétil/terapia , Terapia Genética , Pênis/anormalidades , Pênis/cirurgia , Engenharia Tecidual , Animais , Anormalidades Congênitas/terapia , Humanos , MasculinoRESUMO
Whether oncogenic human papilloma viruses (HPVs) are involved in the pathogenesis of prostate cancers has been a subject of great controversy. To clarify the contradictory results of investigations, with the aim of detecting viral nucleic acids in prostate cancers, we have carried out a comparative quantitation of the HPV16-E6 sequence in 84 prostate specimens. Using single-tube quantitative competitive PCR, we characterized 47 prostate cancers and 37 control tissues of benign prostatic hyperplasia. A subgroup of the prostate tumors (10 of 47; 21%) was detected as having significantly higher copy numbers of HPV16-E6 sequences when compared to the control tissue (1 of 37; 3%), using a cutoff value of 300 copies per 12,500 diploid cells (two-sided Fisher's exact test, P = 0.02). Our results indicate that the oncogenic HPV16 might contribute to the development of a subset of prostate tumors.
Assuntos
DNA Viral/análise , Papillomaviridae/genética , Neoplasias da Próstata/virologia , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Hiperplasia Prostática/virologiaRESUMO
This article analyses three cases of death following a spontaneous rupture of the urinary bladder. One case is based on an extensive tamponade of the bladder eight days after a transurethral resection of the prostate gland. Two other cases of death by spontaneous rupture resulted from increased alcohol consumption. The paper presents an overview of pathomorphological findings such as the typical intraperitoneal rupture localisation at the posterior wall of the urinary bladder or bladder dome and the subsequent diagnosed causes of death. In addition predisposing (anamnestic) influencing factors such as chronic alcoholism are highlighted and their relevance for the clinical urologist and the forensic pathologist are discussed.
Assuntos
Patologia Legal/métodos , Doenças da Bexiga Urinária/patologia , Adulto , Idoso , Alcoolismo/complicações , Alcoolismo/patologia , Causas de Morte , Cistectomia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Prostatectomia/efeitos adversos , Ruptura Espontânea , Doenças da Bexiga Urinária/etiologia , Doenças da Bexiga Urinária/cirurgiaRESUMO
Results from experimental studies suggested a significance of the nitric oxide (NO)-cGMP- and cAMP-pathways in the control of the function of the smooth musculature of the human prostate. In addition, it has also been assumed that the vasoconstrictory peptide endothelin-1(ET-1) may play a role in the dynamic component of benign prostatic hyperplasia (BPH) and the so-called lower urinary tract symptomatology (LUTS). Nevertheless, up till now, little is known as to potential interactions between the contraction of prostatic smooth muscle mediated by ET-1 and the relaxation induced by NO and cGMP. Thus, it was the aim of the study to elucidate the effects of drugs interfering with the cGMP-pathway on the tension induced by ET-1 of isolated human prostate tissue, as well as contractile responses of isolated strip preparations to ET-1 and angiotensin-II (AT-II). Macroscopically normal human prostate tissue from the transition zone was obtained from male patients who had undergone surgery for localized cancer of the prostate or urinary bladder. Using the organ bath technique, the ability of ET-1 and AT-II to contract isolated prostate strips was evaluated. In another set-up, the effects of the NO-donor S-nitrosogluthatione (GSNO) and C-type natriuretic peptide(CNP), known as an endogenous ligand of the membrane bound guanylyl cyclase, (1 nM-1/10 microM) on the tension induced by 0.1 microM ET-1 of human prostate strips were investigated. The adenylyl cyclase stimulating agents forskolin and NO-donor natrium nitroprusside (NNP) were used as reference compounds. While AT-II failed to contract the prostate tissue, ET-1 induced stable and reproducible contractions of the tissue strips. The tension induced by 0.1 microM ET-1 was dose-dependently reversed by the drugs. The rank order of efficacy was forskolin >NNP>CNP(1 microM)>GSNO. R(max) values ranged from 55% (forskolin) to 35% (GSNO). Forskolin was the only compound which reached an EC50 value. Our results demonstrate that drugs in terfering with the cGMP- and cAMP-pathways can reverse the tension induced by ET-1. These findings are in support of the hypothesis that both cGMP and cAMP contribute to the control of the prostate smooth muscle tension and may provide new strategies for the future pharmacotherapy of LUTS und BPH.
Assuntos
AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Endotelina-1/metabolismo , Relaxamento Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/metabolismo , Doadores de Óxido Nítrico/farmacologia , Nitroprussiato/farmacologia , Próstata/efeitos dos fármacos , Próstata/metabolismo , S-Nitrosoglutationa/farmacologia , Adenilil Ciclases/metabolismo , Idoso , Angiotensina II/metabolismo , Colforsina/administração & dosagem , Colforsina/farmacologia , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Doadores de Óxido Nítrico/administração & dosagem , Nitroprussiato/administração & dosagem , S-Nitrosoglutationa/administração & dosagem , Transdução de Sinais/efeitos dos fármacosRESUMO
PURPOSE: We conducted a prospectively randomized clinical trial to compare the efficacy of three outpatient therapy regimens in 341 patients with progressive metastatic renal cell carcinoma. PATIENTS AND METHODS: Patients were stratified according to known clinical predictors and were subsequently randomly assigned. Treatment arms were: arm A (n = 132), subcutaneous interferon alfa-2a (sc-IFN-alpha-2a), subcutaneous interleukin-2 (sc-IL-2), and intravenous (IV) fluorouracil; arm B (n = 146): arm A treatment combined with per oral 13-cis-retinoic acid; and arm C (n = 63), sc-IFN-alpha-2a and IV vinblastine. RESULTS: Treatment (according to the standard 8-week Hannover Atzpodien regimen) arms A, B, and C yielded objective response rates of 31%, 26%, and 20%, respectively. Arm B, but not arm A, showed a significantly improved progression-free survival (PFS) compared with arm C (P =.0248). Both arm A (median overall survival, 25 months; P =.0440) and arm B (median overall survival, 27 months; P =.0227) led to significantly improved overall survival (OS) compared with arm C (median OS, 16 months). All three sc-IFN-alpha-2a-based therapies were moderately or well tolerated. CONCLUSION: Our results established the safety and improved long-term therapeutic efficacy of sc-IL-2 plus sc-INF-alpha-2a-based outpatient immunochemotherapies, compared with sc-INF-alpha-2a/IV vinblastine.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Imunoterapia , Neoplasias Renais/tratamento farmacológico , Adulto , Idoso , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , Injeções Subcutâneas , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interleucina-2/administração & dosagem , Isotretinoína/administração & dosagem , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes , Taxa de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagemRESUMO
This study has investigated the ability of the vasoconstrictor peptide angiotensin II to activate human peripheral blood monocytes. Activation was monitored by measuring both the release of tumor necrosis factor alpha from monocytes and their adhesion to monolayers of human endothelial cells. Angiotensin II-elicited activation of monocytes was dose-dependent (half-maximally effective concentration approximately 0.2 nM), saturable (maximally effective concentration approximately 5 nM), and sensitive to inhibition by the angiotensin type 1 receptor antagonist ZD 7155. Such direct actions imply that angiotensin II is an important candidate stimulus for the subendothelial infiltration of monocytes observed in atherogenesis and hypertension.
Assuntos
Angiotensina II/farmacologia , Monócitos/metabolismo , Sequência de Bases , Southern Blotting , Adesão Celular , Células Cultivadas , Endotélio Vascular/fisiologia , Expressão Gênica , Humanos , Lipopolissacarídeos/farmacologia , Dados de Sequência Molecular , Monócitos/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Reação em Cadeia da Polimerase , RNA/análise , RNA/metabolismo , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Cultured human neuronal (SH-SY5Y neuroblastoma) cells synthesize and secrete the potent protease inhibitor alpha 2-macroglobulin (a2M) upon stimulation with interleukin-6 (IL-6) indicating that alpha 2-macroglobulin behaves as an acute-phase protein in the human central nervous system. Exogenous addition of a2M to the cultured neuronal cells resulted in only a slight inhibition of Alzheimer beta A4-amyloid precursor protein (APP) synthesis, but markedly inhibited its secretion pointing to the possibility that a2M may affect the proteolytic APP processing. Evidence is provided that IL-6 and a2M are involved in Alzheimer's disease pathogenesis.
Assuntos
Interleucina-6/fisiologia , Neurônios/metabolismo , Inibidores de Proteases , alfa-Macroglobulinas/biossíntese , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide , Humanos , Neuroblastoma , Testes de Precipitina , Precursores de Proteínas/metabolismo , Células Tumorais CultivadasRESUMO
Microglia which are consistently associated with Alzheimer's disease (AD) senile plaques are part of the mononuclear phagocyte system. In-vitro matured human monocyte-derived macrophages feature many immunological characteristics of microglia. We found strong constitutive expression of Alzheimer's beta A4-amyloid precursor protein (APP) in human mononuclear phagocytes after terminal in-vitro maturation from monocytes to macrophages. Amyloid has previously been found to be associated with microglia in AD brains, however, it remained unclear whether the material was synthesized in or had been phagocytosed by the cells. The findings presented here support the assumption that brain microglia may contribute to APP synthesis in AD brain.
Assuntos
Peptídeos beta-Amiloides/metabolismo , Macrófagos/metabolismo , Precursores de Proteínas/metabolismo , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/imunologia , Precursor de Proteína beta-Amiloide , Anticorpos Monoclonais , Northern Blotting , Diferenciação Celular , Células Cultivadas , Expressão Gênica , Humanos , Técnicas In Vitro , Peso Molecular , Monócitos/citologia , Neuroglia/citologia , Neuroglia/metabolismo , Precursores de Proteínas/genética , Precursores de Proteínas/imunologia , RNA Mensageiro/genéticaRESUMO
In the present study, 76 specimens (T1-T4) from 76 randomly selected patients undergoing radical prostatectomy at Hannover University as well as in the Josef Hospital Regensburg (13 patients) between 1980 and 1992 for whom tissue sections for immunohistochemical investigation were available, were investigated for different biological and clinical characteristics as predictors for long-term and recurrence-free survival: age, depth of tumour infiltration, histological grade, lymph node status, as well as overexpression of the p53 protein (monoclonal antibody DO-1). After a median follow-up of 50 months, 6 of 18 patients (33%) with more than 20% of tumour cells stained positively for p53 died from tumour progression compared with 9 of 58 patients (16%) with less than 20% of tumour cells positive for p53. During univariate analysis, p53 overexpression (P = 0.011), histological grading (P = 0.009) and tumour stage (P = 0.024) were significant prognostic factors for survival, among which only p53 overexpression (P = 0.026) remained an independent significant predictor in multivariate analysis. Additionally, 18 of 66 patients (27%) with less than 40% positivity for p53 suffered tumour recurrence in contrast to 6 of 10 patients (60%) with more than 40% tumour cells exhibiting a positive staining reaction. In multivariate analysis, p53 overexpression was identified as the only prognostic parameter for recurrence-free survival (P = 0.005). Prospective studies are needed to confirm the independent prognostic potential of p53 overexpression in patients with localised prostate cancer. The availability of more refined prognostic factors should assist decision making regarding the value of radical prostatectomy versus a surveillance strategy for prognostically defined subgroups of patients.
Assuntos
Genes p53 , Proteínas de Neoplasias/metabolismo , Prostatectomia/mortalidade , Neoplasias da Próstata/cirurgia , Proteína Supressora de Tumor p53/metabolismo , Idoso , Intervalo Livre de Doença , Seguimentos , Expressão Gênica , Humanos , Imuno-Histoquímica/métodos , Excisão de Linfonodo/métodos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Prognóstico , Prostatectomia/métodos , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Análise de SobrevidaRESUMO
Overexpression of the TP53 gene protein detected by immunohistochemistry appears to identify those patients with superficial bladder cancer at risk of the development of muscle invasive or metastatic disease. However, the role of p53 overexpression in patients with advanced or metastatic bladder cancer is not yet well established. In the present study, 44 specimens from 44 patients with advanced stage bladder tumours (T2-T4) undergoing radical cystectomy were investigated for different biological and clinical characteristics as possible prognostic factors: sex, age, depth of tumour infiltration, T-stage, histological grade, lymph node status, application of adjuvant systemic chemotherapy (MVAC), proliferative activity (staining for proliferating cell nuclear antigen (PCNA) by monoclonal antibody (PC10) as well as overexpression of the p53 oncoprotein (monoclonal antibody pAb 1801)). After a median follow-up of 22 months, 16 of the 23 patients (70%) with more than 40% of tumour cells stained positively for p53 (Group B) died from tumour progression compared with 7 of the 21 patients (33%) with less than 40% of tumour cells positive for p53. During univariate analysis, p53 overexpression (P = 0.008), staining for PCNA (> or = 80% of cells positive) (P = 0.01) and tumour stage (P = 0.01) were significant prognostic factors for survival, among which p53 overexpression (P = 0.023) as well as T-stage (P = 0.012) remained independent significant predictors during multivariate analysis. Prospective studies are needed to confirm the independent prognostic potential of p53 overexpression in patients with advanced bladder cancer. The availability of more refined prognostic factors should assist decision making regarding the value of more aggressive treatment options, such as adjuvant or neoadjuvant chemotherapy, for prognostically defined subgroups of patients.
Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células de Transição/química , Proteína Supressora de Tumor p53/análise , Neoplasias da Bexiga Urinária/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Antígeno Nuclear de Célula em Proliferação/análise , Fatores de Risco , Análise de Sobrevida , Neoplasias da Bexiga Urinária/patologiaRESUMO
Since immunohistochemical studies indicated the presence of interleukin-6 in the cortices of patients with Alzheimer's disease, we were interested in the eventual biological effects of this cytokine on neuronal cells. We found that interleukin-6 and interleukin-1 induced metallothionein expression in a human neuronal (SH-SY5Y neuroblastoma) cell line. In contrast to metallothionein, amyloid precursor protein expression was unaffected by both cytokines. When searching in the same cell line for the expression of the classical 80-kDa interleukin-6 binding protein, which is part of the dimeric interleukin-6 receptor, we were unable to detect the respective mRNA. Our findings either indicate that the interleukin-6 receptor in these cells is expressed in extremely low levels or that interleukin-6 may act upon neuronal cells via a different, yet unknown neuronal receptor.
Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Interleucina-1/farmacologia , Interleucina-6/farmacologia , Metalotioneína/metabolismo , Neuroblastoma/metabolismo , Sequência de Bases , DNA/genética , Humanos , Sondas Moleculares/genética , Dados de Sequência Molecular , Neuroblastoma/patologia , Reação em Cadeia da Polimerase , Receptores de Superfície Celular/metabolismo , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Receptores de Interleucina-6 , Células Tumorais CultivadasRESUMO
Tumor-bearing human kidneys were used in an ex vivo perfusion model to screen monoclonal antibodies, recognizing renal cell carcinoma-associated antigens for diagnostic potential in vivo. Perfusion of tumor-bearing kidneys with 99mTc-labeled G250 and RC38 antibody resulted in visualization of the tumor, whereas perfusion with two other monoclonal antibodies, RC2 and RC4, did not lead to tumor visualization. Uptake of radiolabel in normal kidney tissue was low for G250 and RC38 antibody. Tumor-to-kidney tissue ratios after perfusion with G250 and RC38 antibody were 2.7 and 2.2, respectively. After rinsing for 3 hr with unlabeled perfusion fluid the tumor-to-kidney tissue ratios increased to 8.6 for G250 antibody and to 2.7 for RC38 antibody. We conclude that perfusion of tumor-bearing human kidneys with radiolabeled monoclonal antibodies is a relatively simple way to evaluate renal cell carcinoma associated monoclonal antibodies as diagnostic agents in vivo.
Assuntos
Anticorpos Monoclonais , Antígenos de Neoplasias/imunologia , Carcinoma de Células Renais/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Tecnécio , Carcinoma de Células Renais/imunologia , Humanos , Técnicas In Vitro , Neoplasias Renais/imunologia , Perfusão , CintilografiaRESUMO
Three different treatment strategies for patients with stage I non-seminomatous testicular cancer are available that will all result in long-term survival in more than 98% of the patients: a "wait and see" strategy with follow-up and chemotherapy in cases of tumour progression, retroperitoneal lymphadenectomy, with or without application of systemic chemotherapy, in cases of retroperitoneal metastases (pathological stage II disease) or primary adjuvant chemotherapy following inguinal orchiectomy. Each treatment strategy is associated with specific side-effects. In several studies histological characteristics of the primary tumour, particularly the presence of vascular invasion and of embryonal carcinoma cells, have been demonstrated to be significant prognostic factors for the risk of occult retroperitoneal metastases in patients with stage I disease. In addition, new biological prognostic factors determined by flow cytometry, cytogenetic analysis or molecular-biological DNA or RNA analysis have been investigated, among which alterations of the p53 tumour-suppressor gene may represent a promising new prognostic factor. Although alterations of p53 gene expression seem to be associated with advanced tumour stage and may predict retroperitoneal metastatic disease, the independent role of these molecular genetic alterations needs to be prospectively studied. Currently a risk-adapted treatment strategy based on the histological criteria of vascular invasion and the presence of embryonal carcinoma can be used to stratify patients into a "high-" and "low-risk" group with respect to tumour progression. While primary-nerve-sparing retroperitoneal lymphadenectomy or adjuvant chemotherapy with two cycles of platinum, etoposide and bleomycin may be appropriate for patients with a high risk (above 40%) for tumour progression, a "wait-and-see" strategy can be used for "low-risk" (less than 15% risk of progression) patients. Molecular investigations of prognostic factors may be able to improve further the stratification of patients into these different risk categories.
Assuntos
Neoplasias Testiculares/terapia , Humanos , Masculino , Estadiamento de Neoplasias , Prognóstico , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologiaRESUMO
The proto-oncogene c-kit and its ligand stem-cell factor (SCF) may play an important role in the development of normal and malignant testicular tissue. This study investigates the presence of SCF and c-kit protein in 32 orchiectomy specimens of patients with testicular cancer, in 5 specimens of normal testicular tissue and in three established non-seminomatous germ-cell cancer cell lines (H12.1, H32, 577ML) by an immunohistochemical approach. Out of 9 testicular cancer specimens classified as pure seminomas, 7 (78%) showed a strong immunohistochemical reaction for both SCF and c-kit protein on the surface of the tumour cells. Fourteen non-seminomatous germ-cell tumours composed of embryonal carcinoma were completely negative for both SCF and c-kit proteins and only faint positivity was found in 6 tumours (26%). Differentiated teratomatous structures within the specimens on non-seminomatous tumours showed a strong immunohistochemical reaction for SCF and c-kit protein in 8 of 11 (73%) cases. All three testicular cancer cell lines showed only faint staining reactions for c-kit protein and none for SCF. No secretion of SCF by the three lines in vitro was detected. The addition of high concentrations of SCF (100 ng/ml) to the testicular cancer cell lines in culture conditions without fetal calf serum resulted in a 1.4 to 3-fold growth stimulation compared to cell growth in serum-free medium alone. This effect was not detectable when the cells were cultured in serum-containing media. In the normal testicular tissue the germ-cells displayed a strong immunohistochemical reaction for c-kit protein while SCF positivity was found at the tubular membrane and on the surface of Sertoli cells. The SCF/c-kit system may possess a regulatory function in normal testicular tissue by possibly providing the microenvironment necessary for spermatogenesis. With the development of testicular cancer, this regulatory system seems to be lost, particularly in non-seminomatous germ-cell tumours. A growth-stimulatory effect of high concentrations of SCF on non-seminomatous testicular cancer cell lines can be detected only in culture conditions with serum-free media. The effects achievable by the combination of SCF with other growth factors need to be further studied, as well as the role of the c-kit/SCF regulatory system for normal spermatogenesis and its possible implications for the understanding and treatment of male infertility.
Assuntos
Germinoma/química , Proteínas Proto-Oncogênicas c-kit/análise , Fator de Células-Tronco/análise , Neoplasias Testiculares/química , Testículo/química , Humanos , Imuno-Histoquímica , Masculino , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/fisiologia , Fator de Células-Tronco/genética , Fator de Células-Tronco/fisiologia , Células Tumorais CultivadasRESUMO
Temporary electrical stimulation using anal or vaginal electrodes and an external pulse generator has been a treatment modality for urinary urge incontinence for nearly three decades. In 1981 Tanagho and Schmidt introduced chronic electrical stimulation of the sacral spinal nerves using a permanently implanted sacral foramen electrode and a battery powered pulse generator for treatment of different kinds of lower urinary tract dysfunction, refractory to conservative treatment. At our department chronic unilateral electrical stimulation of the S3 sacral spinal nerve has been used for treatment of vesi-courethral dysfunction in 43 patients with a mean postoperative follow up of 43,6 months. Lasting symptomatic improvement by more than 50 % could be achieved in 13 of 18 patients with motor urge incontinence (72,2 %) and in 18 of the 21 patients with urinary retention (85,7 %). Implants offer a sustained therapeutic effect to treatment responders, which is not achieved by temporary neuromodulation. Chronic neuromodulation should be predominantly considered in patients with urinary retention. Furthermore in patients with motor urge incontinence, refusing temporary techniques or in those requiring too much effort to achieve a sustained clinical effect. Despite high initial costs chronic sacral neuromodulation is an economically reasonable treatment option in the long run, when comparing it to the more invasive remaining therapeutic alternatives.