RESUMO
PURPOSE: The comprehensive complication index (CCI) is a new tool for reporting the cumulative burden of postoperative complications on a continuous scale. This study validates the CCI for urological surgery and its benefits over the Clavien-Dindo-Classification (Clavien). MATERIAL AND METHODS: Data from a prospectively maintained data base of all consecutive patients at a university care-center was analyzed. Complications after radical cystectomy (RC), radical prostatectomy (RP), and partial nephrectomy (PN) were classified using the CCI and Clavien system. Differences in complications between the CCI and the Clavien were assessed and correlation analyses performed. Sample size calculations for hypothetical clinical trials were compared between CCI and Clavien to evaluate whether the CCI would reduce the number of required patients in a clinical trial. RESULTS: 682 patients (172 RC, 297 RP, 213 PN) were analyzed. Overall, 9.4-46.6% of patients had > 1 complication cumulatively assessed with the CCI resulting in an upgrading in the Clavien classification for 2.4-32.4% of patients. Therefore, scores between the systems differed for RC: CCI (mean ± standard deviation) 26.3 ± 20.8 vs. Clavien 20.4 ± 16.7, p < 0.001; PN: CCI 8.4 ± 14.7 vs. Clavien 7.0 ± 11.8, p < 0.001 and RP: CCI 5.8 ± 11.7 vs. Clavien 5.3 ± 10.6, p = 0.102. The CCI was more accurate in predicting LOS after RC than Clavien (p < 0.001). Sample size calculations based in the CCI (for future hypothetical trials) resulted in a reduction of required patients for all procedures (- 25% RC, - 74% PN, - 80% RP). CONCLUSION: The CCI is more accurate to assess surgical complications and reduces required sample sizes that will facilitate the conduction of clinical trials.
Assuntos
Cistectomia/efeitos adversos , Nefrectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Prostatectomia/efeitos adversos , Gestão de Riscos/normas , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
PURPOSE: To systematically analyze the impact of prophylactic abdominal or retroperitoneal drain placement or omission in uro-oncologic surgery. METHODS: This systematic review follows the Cochrane recommendations and was conducted in line with the PRISMA and the AMSTAR-II criteria. A comprehensive database search including Medline, Web-of-Science, and CENTRAL was performed based on the PICO criteria. All review steps were done by two independent reviewers. Risk of bias was assessed with the Cochrane tool for randomized trials and the Newcastle-Ottawa Scale. RESULTS: The search identified 3427 studies of which eleven were eligible for qualitative and ten for quantitative analysis reporting on 3664 patients. Six studies addressed radical prostatectomy (RP), four studies partial nephrectomy (PN) and one study radical cystectomy. For RP a reduction in postoperative complications was found without drainage (odds ratio (OR)[95% confidence interval (CI)]: 0.62[0.44;0.87], p = 0.006), while there were no differences for re-intervention (OR[CI]: 0.72[0.39;1.33], p = 0.300), lymphocele OR[CI]: 0.60[0.22;1.60], p = 0.310), hematoma (OR[CI]: 0.68[0.18;2.53], p = 0.570) or urinary retention (OR[CI]: 0.57[0.26;1.29], p = 0.180). For partial nephrectomy no differences were found for overall complications (OR[CI]: 0.99[0.65;1.51], p = 0.960) or re-intervention (OR[CI]: 1.16[0.31;4.38], p = 0.820). For RC, there were no differences for all parameters. The overall-quality of evidence was assessed as low. CONCLUSION: The omission of drains can be recommended for standardized RP and PN cases. However, deviations from the standard can still mandate the placement of a drain and remains surgeon preference. For RC, there is little evidence to recommend the omission of drains and future research should focus on this issue. REVIEW REGISTRATION NUMBER (PROSPERO): CRD42019122885.
Assuntos
Cistectomia/métodos , Drenagem/métodos , Nefrectomia/métodos , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Profiláticos , Prostatectomia/métodos , Neoplasias Urológicas/cirurgia , Abdome , Humanos , Masculino , Espaço RetroperitonealRESUMO
PURPOSE: Fatty acid-binding protein 5 (FABP5), a transport protein for lipophilic molecules, has been proposed as protein marker in prostate cancer (PCa). The role of FABP5 gene expression is merely unknown. METHODS: In two cohorts of PCa patients who underwent radical prostatectomy (n = 40 and n = 57) and one cohort of patients treated with palliative transurethral resection of the prostate (pTUR-P; n = 50) FABP5 mRNA expression was analyzed with qRT-PCR. Expression was correlated with clinical parameters. BPH tissue samples served as control. To independently validate findings on FABP5 expression, three microarray and sequencing datasets were reanalyzed (MSKCC 2010 n = 216; TCGA 2015 n = 333; mCRPC, Nature Medicine 2016 n = 114). FABP5 expression was correlated with ERG-fusion status, TCGA subtypes, cancer driver mutations and the expression of druggable downstream pathway components. RESULTS: FABP5 was overexpressed in PCa compared to BPH in the cohorts analyzed by qRT-PCR (radical prostatectomy p = 0.003, p = 0.010; pTUR-P p = 0.002). FABP5 expression was independent of T stage, Gleason Score, nodal status and PSA level. FABP5 overexpression was associated with the absence of TMPRSS2:ERG fusion (p < 0.001 in TCGA and MSKCC). Correlation with TCGA subtypes revealed FABP5 overexpression to be associated with SPOP and FOXA1 mutations. FABP5 was positively correlated with potential drug targets located downstream of FABP5 in the PPAR-signaling pathway. CONCLUSION: FABP5 overexpression is frequent in PCa, but seems to be restricted to TMPRESS2:ERG fusion-negative tumors and is associated with SPOP and FOXA1 mutations. FABP5 overexpression appears to be indicative for increased activity in PPAR signaling, which is potentially druggable.
Assuntos
Carcinoma/genética , Proteínas de Ligação a Ácido Graxo/genética , Expressão Gênica , Neoplasias da Próstata/genética , RNA Mensageiro/metabolismo , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Carcinoma/secundário , Carcinoma/cirurgia , Estudos de Casos e Controles , Fator 3-alfa Nuclear de Hepatócito/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Proteínas Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Cuidados Paliativos , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Prostatectomia , Hiperplasia Prostática/genética , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Proteínas Repressoras/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Ressecção Transuretral da PróstataRESUMO
OBJECTIVES: To validate the adherence of urologists to chemotherapy recommendations given in the EAU guidelines on PeCa. The European Association of Urology (EAU) guidelines on penile cancer (PeCa) are predominantly based on retrospective studies with low level of evidence. MATERIALS AND METHODS: A 14-item-survey addressing general issues of PeCa treatment was developed and sent to 45 European hospitals. 557 urologists participated in the survey of which 43.5%, 19.3%, and 37.2% were in-training, certified, and in leading positions, respectively. Median response rate among participating departments was 85.7% (IQR 75-94%). Three of 14 questions addressed clinical decisions on neoadjuvant, adjuvant, and palliative chemotherapy. Survey results were analyzed by bootstrap-adjusted multivariate logistic-regression-analysis to identify predictors for chemotherapy recommendations consistent with the guidelines. RESULTS: Neoadjuvant, adjuvant, and palliative chemotherapy was recommended according to EAU guidelines in 21%, 26%, and 48%, respectively. For neoadjuvant chemotherapy, urologists holding leading positions or performing chemotherapy were more likely to recommend guideline-consistent treatment (OR 1.85 and 1.92 with p(bootstrap) = 0.007 and 0.003, respectively). Supporting resources (i.e., guidelines, textbooks) were used by 23% of survey participants and significantly improved consistency between treatment recommendations and Guideline recommendations in all chemotherapy settings (p(bootstrap) = 0.010-0.001). Department size and university center status were no significant predictors for all three endpoints. CONCLUSIONS: In this study, we found a very low rate of adherence to the EAU guidelines on systemic treatment for PeCa. Further investigations are needed to clarify whether this missing adherence is a consequence of limited individual knowledge level or of the low grade of guideline recommendations.
Assuntos
Antineoplásicos/administração & dosagem , Fidelidade a Diretrizes/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde , Neoplasias Penianas/tratamento farmacológico , Urologia , Europa (Continente) , Humanos , Masculino , Guias de Prática Clínica como Assunto , Sociedades MédicasRESUMO
Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) imaging for the localization of prostate cancer is increasingly available in Germany. The advances and limitations in different disease stages are reviewed. As the clinical relevance of oligometastatic disease in primary cancer detected by PSMA PET-CT imaging is not yet completely understood, it should only be used in clinical trials. In recurrent prostate cancer after therapy with curative intent, PSMA PET-CT shows encouraging potential for the planning of salvage therapy. In metastatic castration-resistant prostate cancer evidence for its use is not available.
Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias da Próstata , Alemanha , Humanos , Masculino , Recidiva Local de Neoplasia , Antígeno Prostático Específico , Neoplasias da Próstata/diagnóstico por imagemRESUMO
PURPOSE: Radical cystectomy (RC) and pelvic lymph node dissection (LND) are standard treatments for muscle-invasive urothelial carcinoma of the bladder. Lymph node staging is a prerequisite for clinical decision-making regarding adjuvant chemotherapy and follow-up regimens. Recently, the clinical and pathological nodal staging scores (cNSS and pNSS) were developed. Prior to RC, cNSS determines the minimum number of lymph nodes required to be dissected; pNSS quantifies the accuracy of negative nodal staging based on pT stage and dissected LNs. cNSS and pNSS have not been externally validated, and their relevance for prediction of cancer-specific mortality (CSM) has not been assessed. METHODS: In this retrospective study of 2,483 RC patients from eight German centers, we externally validated cNSS and pNSS and determined their prediction of CSM. All patients underwent RC and LND. Median follow-up was 44 months. cNSS and pNSS sensitivities were evaluated using the original beta-binominal models. Adjusted proportional hazards models were calculated for pN0 patients to assess the predictive value of cNSS and pNSS for CSM. RESULTS: cNSS and pNSS both pass external validation. Adjusted for other clinical parameters, cNSS can predict outcome after RC. pNSS has no independent impact on prediction of CSM. The retrospective design is the major limitation of the study. CONCLUSIONS: In the present external validation, we confirm the validity of both cNSS and pNSS. cNSS is an independent predictor of CSM, thus rendering it useful as a tool for planning the extent of LND.
Assuntos
Carcinoma de Células de Transição/patologia , Excisão de Linfonodo/métodos , Linfonodos/patologia , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/terapia , Quimioterapia Adjuvante , Estudos de Coortes , Cistectomia , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pelve , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Bexiga Urinária/terapiaRESUMO
Background: Robotic-assisted hysterectomy (RAH) is a widely accepted minimally invasive approach for uterus removal. However, as RAH is typically performed in the umbilical region, it usually results in scars in cosmetically suboptimal locations. This is the first case of RAH with cervicosacropexy performed below the bikini line, using the new Dexter robotic system™. Objectives: The aim of this article is to show the surgical steps of the first RAH with cervicosacropexy performed below the bikini line with the new Dexter robotic system™ (Distalmotion), and furthermore assess the feasibility of this approach using this robotic platform. Materials and Methods: A 43-year-old woman with uterine adenomyosis and recurrent uterine prolapse underwent a robotic-assisted subtotal hysterectomy with cervicosacropexy, performed below the bikini line, using the Dexter robotic system™, at the Clinic of Gynecology and Obstetrics at Universitätsklinikum Schleswig-Holstein (UKHS) in Kiel, Germany. Main outcome measures: Perioperative data, surgical approach specifics, objective, and subjective outcomes of this new approach. Results: The procedure was performed without intra-operative complications; estimated blood loss was 10 ml. Operative time was 150 minutes, console time 120 minutes, total docking time 6 minutes. Dexter performed as expected; no device-related issues or robotic arm collisions occurred. The patient did not require pain medication and was released on the second postoperative day. Conclusion: RAH performed below the bikini line using the Dexter robotic system™ is a feasible, safe, and adequate procedure. These initial results should be confirmed and further extensively refurbished with larger patient cohorts, and functional and psychological outcomes need further investigation.
RESUMO
Radiation-induced hemorrhagic cystitis is a late-onset complication of radiation therapy of the pelvis with an incidence rate of approximately 5-10%. The severity of hematuria can vary from mild hematuria to more severe bleeding with clot formation and urinary retention to intractable life-threatening bleeding when blood transfusions fail to keep pace with blood loss. Management of radiation-induced hemorrhagic cystitis is based on the presenting symptoms after ruling out urinary tract infection or a tumor. In cases with mild or moderate gross hematuria, hydration can be sufficient to prevent clot formation. In emergency cases, evacuation of clots and continuous bladder irrigation with isotonic saline is required, and in cases with persistent bleeding, transurethral fulguration is also required. Unfortunately, radiation-induced hemorrhagic cystitis can lead to persistent or intermittent hematuria. In these cases, intravesical instillation of astringent agents or hyperbaric oxygen therapy can alleviate symptoms. In emergency cases, transarterial embolization or surgical ligation of vesical arteries may be necessary. In rare refractory cases, urinary diversion with or without cystectomy should be performed.
Assuntos
Cistite , Lesões por Radiação , Administração Intravesical , Cistite/diagnóstico , Hematúria/etiologia , Hemorragia/etiologia , Humanos , Lesões por Radiação/diagnósticoRESUMO
PURPOSE: Comorbidities and frailty are determinants of surgical outcome. The aim of the study was to examine various measures of frailty and comorbidities in predicting postoperative outcome of partial nephrectomy (PN). METHODS: We prospectively analyzed the frailty and comorbidity status of 150 patients undergoing PN between 2015 and 2018. Primary endpoint was the occurrence of major postoperative complications (MPC) and secondary endpoints were the failure of Trifecta achievement and the need for hospital readmissions. For the transfer into clinical practice the most significant frailty parameters were summarized in a multi-dimensional test. RESULTS: Median age was 67 (33-93) years, 64.7% of the patients were male. Univariable regression analysis showed, that patients with increased frailty indices (Hopkins frailty score ≥2 (OR = 3.74, p = 0.005), Groningen frailty index ≥4 (OR = 2.85, p = 0.036)) are at higher risk to develop MPC. Furthermore, poor physical performance, such as a low handgrip strength or a Full-Tandem-Stand (FTS) < 10 s were associated with MPC (OR = 4.76, p = 0.014; OR = 4.48, p = 0.018) and Trifecta failure (OR = 3.60, p = 0.037, OR = 5.50, p = 0.010). Six measures were combined to the geriatric assessment in partial nephrectomy score (GAPN). A GAPN-score ≥3 proved to be a significant predictor for MPC (OR = 4.30, p = 0.029) and for Trifecta failure (OR = 0.20, p = 0.011) in multivariable regression analysis. CONCLUSION: The frailty status and comorbidities are important determinants of the postoperative course after PN. These parameters should be assessed preoperatively and included in the treatment planning, especially in light of available alternative therapies. In this context, the GAPN-score may be a suitable tool.
Assuntos
Fragilidade/complicações , Fragilidade/diagnóstico , Neoplasias Renais/cirurgia , Nefrectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Fragilidade/fisiopatologia , Avaliação Geriátrica/métodos , Força da Mão , Humanos , Neoplasias Renais/complicações , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente , Desempenho Físico Funcional , Medição de RiscoRESUMO
BACKGROUND: Data from interventional studies suggest that a peritoneal flap after pelvic lymph node dissection (LND) during laparoscopic, robotic-assisted radical prostatectomy (RARP) may reduce the rate of symptomatic lymphoceles in transperitoneal approach. However, most of these studies are not conducted in a randomized controlled fashion, thus limiting their scientific value. A recent prospective, randomized, controlled trial (RCT) did not show superiority of a peritoneal flap while further trials are lacking. Therefore, the aim of the presented RCT will be to show that creating a peritoneal flap decreases the rate of symptomatic lymphoceles compared to the current standard procedure without creation of a flap. METHODS/DESIGN: PELYCAN is a parallel-group, patient- and assessor-blinded, phase III, adaptive randomized controlled superiority trial. Men with histologically confirmed prostate cancer who undergo transperitoneal RARP with pelvic LND will be randomly assigned in a 1:1 ratio to two groups-either with creating a peritoneal flap (PELYCAN) or without creating a peritoneal flap (control). Sample size calculation yielded a sample size of 300 with a planned interim analysis after 120 patients, which will be performed by an independent statistician. This provides a possibility for early stopping or sample size recalculation. Patients will be stratified for contributing factors for the development of postoperative lymphoceles. The primary outcome measure will be the rate of symptomatic lymphoceles in both groups within 6 months postoperatively. Patients and assessors will be blinded for the intervention until the end of the follow-up period of 6 months. The surgeon will be informed about the randomization result after performance of vesicourethral anastomosis. Secondary outcome measures include asymptomatic lymphoceles at the time of discharge and within 6 months of follow-up, postoperative complications, mortality, re-admission rate, and quality of life assessed by the EORTC QLQ-C30 questionnaire. DISCUSSION: The PELYCAN study is designed to assess whether the application of a peritoneal flap during RARP reduces the rate of symptomatic lymphoceles, as compared with the standard operation technique. In case of superiority of the intervention, this peritoneal flap may be suggested as a new standard of care. TRIAL REGISTRATION: German Clinical Trials Register DRKS00016794 . Registered on 14 May 2019.
Assuntos
Laparoscopia , Linfocele , Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Humanos , Laparoscopia/efeitos adversos , Excisão de Linfonodo/efeitos adversos , Linfocele/diagnóstico , Linfocele/etiologia , Linfocele/prevenção & controle , Masculino , Pelve , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Procedimentos Cirúrgicos Robóticos/efeitos adversosRESUMO
Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) imaging for the localization of prostate cancer is increasingly available in Germany. The advances and limitations in different disease stages are reviewed. As the clinical relevance of oligometastatic disease in primary cancer detected by PSMA PET-CT imaging is not yet completely understood, it should only be used in clinical trials. In recurrent prostate cancer after therapy with curative intent, PSMA PET-CT shows encouraging potential for the planning of salvage therapy. In metastatic castration-resistant prostate cancer evidence for its use is not available.
Assuntos
Antígenos de Superfície/análise , Glutamato Carboxipeptidase II/análise , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Progressão da Doença , Humanos , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Neoplasias da Próstata/terapia , Neoplasias de Próstata Resistentes à Castração/diagnóstico por imagem , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/terapia , Terapia de SalvaçãoRESUMO
PURPOSE: To evaluate the possible association between bladder tumor location and the laterality of positive lymph nodes (LN) in a prospectively collected multi-institutional radical cystectomy (RC) series. METHODS: The study population included 148 node-positive bladder cancer (BC) patients undergoing RC and pelvic lymph node dissection in 2011 without neoadjuvant chemotherapy and without distant metastasis. Tumor location was classified as right, left or bilateral and compared to the laterality of positive pelvic LN. A logistic regression model was used to identify predictors of ipsilaterality of lymphatic spread. Using multivariate Cox regression analyses (median follow-up: 25 months), the effect of the laterality of positive LN on cancer-specific mortality (CSM) was estimated. RESULTS: Overall, median 18.5 LN [interquartile range (IQR), 11-27] were removed and 3 LN (IQR 1-5) were positive. There was concordance of tumor location and laterality of positive LN in 82% [95% confidence interval (CI), 76-89]. Patients with unilateral tumors (n = 78) harbored exclusively ipsilateral positive LN in 67% (95% CI 56-77). No criteria were found to predict ipsilateral positive LN in patients with unilateral tumors. CSM after 3 years in patients with ipsilateral, contralateral, and bilateral LN metastasis was 41, 67, and 100%, respectively (p = 0.042). However, no significant effect of the laterality of positive pelvic LN on CSM could be confirmed in multivariate analyses. CONCLUSIONS: Our prospective cohort showed a concordance of tumor location and laterality of LN metastasis in BC at RC without any predictive criteria and without any influence on CSM. It is debatable, whether these findings may contribute to a more individualized patient management.
Assuntos
Carcinoma de Células de Transição , Cistectomia , Excisão de Linfonodo/métodos , Vasos Linfáticos/patologia , Pelve/patologia , Neoplasias da Bexiga Urinária , Bexiga Urinária , Adulto , Idoso , Carcinoma de Células de Transição/mortalidade , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Cistectomia/efeitos adversos , Cistectomia/métodos , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Alemanha/epidemiologia , Humanos , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Avaliação de Processos e Resultados em Cuidados de Saúde , Análise de Sobrevida , Bexiga Urinária/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
1. The dipalmitoyl phosphatidylcholine/water system was employed to study the interaction of phenothiazines with model membranes. In particular the effects of the drugs upon the lipid phase transition were examined using differential scanning calorimetry and NMR spectroscopy. The studied phenothiazines have peripheral (diethazine) or central (chlorpromazine) properties. 2. Both drugs were observed to lower the phase transition temperature of dipalmitoyl phosphatidylcholine. The molar activity of chlorpromazine is somewhat higher than of diethazine. At low concentrations the drugs affect the dipalmitoyl phosphatidylcholine pretransition endotherm. 3. In the 13C NMR spectra of the drug-containing samples the signal of the trimethylammonium group of dipalmitoyl phosphatidylcholine is broadened, whereas a narrowing of the signal of the fatty-acid chain methylene groups is observed. Further, addition of the phenothiazines causes higher values of the effective chemical shift anisotropy of the 31P in the phosphate group, in comparison to the pure dipalmitoyl phosphatidylcholine sample. 4. The results obtained by three different techniques indicate a higher fluidity in the fatty-acid chain region and a mobility reduction of the polar headgroup of the dipalmitoyl phosphatidylcholine molecules in the presence of the phenothiazines. These phenomena can be well accounted for by a model for the incorporation of the phenothiazines in the dipalmitoyl phosphatidyl-choline bilayer, in which the dialkylaminoalkyl chains are located near the polar headgroups and the ring system does not penetrate far beyond the glycerol backbone into the hydrocarbon phase.
Assuntos
Fenotiazinas , Surfactantes Pulmonares , Varredura Diferencial de Calorimetria , Cinética , Espectroscopia de Ressonância Magnética , Membranas Artificiais , Conformação MolecularAssuntos
Priapismo , Diagnóstico Diferencial , Emergências , Etilefrina/administração & dosagem , Etilefrina/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Priapismo/classificação , Priapismo/diagnóstico , Priapismo/diagnóstico por imagem , Priapismo/tratamento farmacológico , Priapismo/cirurgia , Priapismo/terapia , Punções , Ultrassonografia Doppler em CoresAssuntos
Emergências , Retenção Urinária/etiologia , Doença Aguda , Idoso , Cistostomia/métodos , Humanos , Masculino , Hiperplasia Prostática/complicações , Encaminhamento e Consulta , Obstrução do Colo da Bexiga Urinária/complicações , Cateterismo Urinário/métodos , Retenção Urinária/diagnóstico , Retenção Urinária/terapiaRESUMO
Cross-sectional imaging modalities including multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) are the diagnostic standard in detection, characterization, and staging of renal masses due to their high sensitivity and specificity. Currently, most renal masses are incidentally diagnosed by imaging for other medical reasons. Recent developments have improved image acquisition with high resolution, while simultaneously reducing radiation dose. CT imaging is the most accessible cross-sectional imaging method and is, therefore, the standard technique. MRI is indicated in patients who are allergic to intravenous CT contrast medium, in patients with renal insufficiency, or in younger patients. Further characterization of renal masses is possible with functional imaging including dual energy CT, perfusion CT, or diffusion-weighted MRI. Contrast-enhanced ultrasound allows detection of even subtle enhancement in hypovascular lesions with high sensitivity and can add valuable information to CT and MRI studies.
Assuntos
Anatomia Transversal/métodos , Neoplasias Renais/diagnóstico , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada Multidetectores/métodos , Ultrassonografia/métodos , Anatomia Transversal/tendências , Técnicas de Diagnóstico Urológico/tendências , Humanos , Imageamento por Ressonância Magnética/tendências , Tomografia Computadorizada Multidetectores/tendências , Ultrassonografia/tendênciasRESUMO
3-(4-Alkylbenzoyl)acrylic acids (ABAAs) were synthesized by acylation of alkylbenzenes with maleic anhydride and then screened in vitro for inhibition of phospholipase A2 (PLA2) from snake venom and from porcine pancreas. The inhibitory potency of ABAAs increased with the length of the alkyl residues resulting in IC50 values of between 10(-7) and 10(-4) mol/L. The most potent inhibitors of the snake venom PLA2 were the 4-(n)-hexadecyl and octadecyl (OBAA) derivatives. Kinetic experiments referred to a time-dependent inhibitory reaction. Irreversibility was examined by dilution and dialysis. A molar ratio of inactivation of OBAA of nearly 20 was estimated. Double reciprocal replots of the apparent inactivation constants to the concentration of OBAA gave a (pseudo) first order rate constant of inactivation of 2.3 min-1. For the dissociation constant of the enzyme-inhibitor intermediate, a value of 6 x 10(-6) mol/L was obtained. On the other hand, the PLA2 from porcine pancreas seemed hardly to be inhibited by ABAAs. The present data are discussed in relation to the proposed model for PLA2 inactivation by manoalide. In human PMNs leukotriene B4 and 5-HETE production was essentially reduced. In human platelets the thrombin-induced TxA2 production was reduced. Since these effects disappeared after addition of arachidonic acid, these findings refer to a PLA2 inhibition. The immunologically induced bronchospasm in guinea pigs was significantly and dose-dependently inhibited by OBAA. This indicates that ABAAs might be useful in treating allergic diseases, such as asthma, eczema, allergic shock and others.
Assuntos
Acrilatos/farmacologia , Fosfolipases A/antagonistas & inibidores , Animais , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Humanos , Ácidos Hidroxieicosatetraenoicos/metabolismo , Cinética , Leucotrieno B4/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Pâncreas/enzimologia , Fosfolipases A2 , Venenos de Serpentes/enzimologia , Suínos , Tromboxano A2/metabolismoRESUMO
Ketoprofen (KP) is a potent nonsteroidal anti-inflammatory drug. However, application to the skin is problematic because the photosensitizing properties of the benzophenone moiety may cause phototoxic effects when the treated skin region is exposed to UVA light. Using capillary electrophoresis with electrochemical detection we are able to differentiate the peroxides formed during illumination of KP-containing solutions of linoleic acid. Contrary to other profens a high amount of hydrogen peroxide was found among the reaction products. For investigation of the skin damaging effect human keratinocytes were used as models. Cell viability, DNA synthesis efficiency and intracellular concentration of peroxides were determined. Viability and proliferation behavior was not altered under the influence of KP. While lower concentrations of KP (10-100 nM) led to a protection against the UVA-induced (8 J/cm2) cell proliferation damage, higher concentrations (10-100 microM) led to an amplification of the proliferation decrease. With UVB irradiation at relevant doses the effects were lower than using UVA. Furthermore, intracellular peroxide content was increased after UV irradiation and KP addition. In conclusion some efforts have to be done to avoid these side effects in the use of KP for topical or transdermal application.
Assuntos
Cetoprofeno/química , Cetoprofeno/efeitos da radiação , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/efeitos da radiação , Linhagem Celular , Humanos , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Queratinócitos/efeitos da radiação , Cetoprofeno/efeitos adversos , Fotoquímica , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/efeitos da radiação , Raios UltravioletaRESUMO
Numerous biological, chemical and photochemical processes consume molecular oxygen, thereby forming peroxides, hydroperoxides and even hydrogen peroxide. This paper describes a new system for monitoring quasi simultaneously oxygen uptake and peroxide formation. For this purpose capillary electrophoresis with electrochemical detection was connected to a new automated injector that periodically injects a sample of the reaction mixture into the capillary electrophoresis system without any contact with the atmosphere. The device was tested with some pharmacologically relevant reactions such as enzymatic oxidation of glucose catalyzed by glucose oxidase, enzymatic lipid oxidation by lipoxygenase and the photodynamic reaction of the anti-inflammatory drug ketoprofen.
Assuntos
Eletroquímica/instrumentação , Eletroforese Capilar/métodos , Oxigênio/química , Peróxidos/química , Glucose Oxidase/química , Ácido Linoleico/química , Reprodutibilidade dos TestesRESUMO
The synthesis of two types of enantiomerically pure sn-2-deoxy-2-amido-glycero-phospholipids differing in the connection of the alkyl chain at the sn-1-position is described. Both types of lipids were prepared from L-serine-methylester as the chiral starting material.