877 resultados para JWH-018
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OBJECTIVE. The purpose of our study was to evaluate hepatic, gastrointestinal, and cardiac toxicity after PRECISION transarterial chemoembolization (TACE) with drug-eluting beads (DEB) versus conventional TACE with doxorubicin in the treatment of intermediate-stage hepatocellular carcinoma (HCC).SUBJECTS AND METHODS. Two hundred twelve patients (185 men and 27 women; mean age, 67 years) were randomized to TACE with DEB or conventional TACE. The majority of patients (67% in both groups) presented in a more advanced stage. Safety was measured by rate of adverse events (Southwest Oncology Group criteria) and changes in laboratory parameters. Cardiotoxicity was assessed with left ventricular ejection fraction (LVEF) mainly on MRI or echocardiography.RESULTS. The mean maximum postchemoembolization alanine transaminase increase in the DEB group was 50% less than in the conventional TACE group (p < 0.001) and 41% less in respect to aspartate transaminase (p < 0.001). End-of-study values returned to approximately baseline levels but with greater variability in conventional TACE patients. Treatment-emergent adverse events in the hepatobiliary system organ class occurred in 16.1% of DEB group patients compared with 25% of conventional TACE patients. There were fewer liver toxicity events in the DEB group. There was a small but statistically significant difference in mean change from baseline in LVEF between the two groups of 4 percentage points for the conventional TACE group (95% CI, 0.71-7.3; p = 0.018).CONCLUSION. PRECISION TACE with DEB loaded with doxorubicin offers a safe therapy option for intermediate-stage HCC, even in patients with more advanced liver disease.
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Aging adults represent the fastest growing population segment in many countries. Physiological and metabolic changes in the aging process may alter how aging adults biologically respond to pollutants. In a controlled human toxicokinetic study (exposure chamber; 12 m³), aging volunteers (n=10; >58 years) were exposed to propylene glycol monomethyl ether (PGME, CAS no. 107-98-2) at 50 ppm for 6 h. The dose-dependent renal excretion of oxidative metabolites, conjugated and free PGME could potentially be altered by age. AIMS: (1) Compare PGME toxicokinetic profiles between aging and young volunteers (20-25 years) and gender; (2) test the predictive power of a compartmental toxicokinetic (TK) model developed for aging persons against urinary PGME concentrations found in this study. METHODS: Urine samples were collected before, during, and after the exposure. Urinary PGME was quantified by capillary GC/FID. RESULTS: Differences in urinary PGME profiles were not noted between genders but between age groups. Metabolic parameters had to be changed to fit the age adjusted TK model to the experimental results, implying a slower enzymatic pathway in the aging volunteers. For an appropriate exposure assessment, urinary total PGME should be quantified. CONCLUSION: Age is a factor that should be considered when biological limit values are developed.
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Based on data available in the Information System for Notifiable Diseases, predictive factors of favorable results were identified in the treatment of pulmonary tuberculosis, diagnosed between 2001 and 2004 and living in Recife-PE, Brazil. Uni- and multivariate logistic regression methods were used. In multivariate analysis, the following factors remained: Age (years), 0 to 9 (OR=4.27; p=0.001) and 10 to 19 (OR=1.78; p=0.011), greater chance of cure than over 60; Education (years), 8 to 11 (OR=1.52; p=0.049), greater chance of cure than no education; Type of entry, new cases (OR=3.31; p<0.001) and relapse (OR=3.32; p<0.001), greater chances of cure than restart after abandonment; Time (months) 2, 5-|6 (OR=9.15; p<0.001); 6-|9 (OR=27.28; p<0.001) and More than 9 (OR=24.78; p<0.001), greater chances of cure than less than 5; Health Unit District, DS I (OR=1.60; p=0.018) and DS IV (OR=2.87; p<0.001), greater chances of cure than DS VI.
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OBJECTIVES: The aim of our study was to evaluate the role of cell-membrane expressed TLRs and the signaling molecule MyD88 in a murine model of OA induced by knee menisectomy (surgical partial removal of the medial meniscus [MNX]). METHODS: OA was induced in 8-10weeks old C57Bl/6 wild-type (WT) female (n=7) mice and in knockout (KO) TLR-1 (n=7), -2 (n=8), -4 (n=9) -6 (n=5), MyD88 (n=8) mice by medial menisectomy, using the sham-operated contralateral knee as a control. Cartilage destruction and synovial inflammation were evaluated by knee joint histology using the OARSI scoring method. Apoptotic chondrocytes and cartilage metabolism (collagen II synthesis and MMP-mediated aggrecan degradation) were analyzed using immunohistochemistry. RESULTS: Operated knees exhibited OA features at 8weeks post-surgery compared to sham-operated ones. In menisectomized TLR-1, -2, -4, and -6 deficient mice, cartilage lesions, synovial inflammation and cartilage metabolism were similar to that in operated WT mice. Accordingly, using the same approach, we found no significant protection in MyD88-deficient mice in terms of OA progression as compared to WT littermates. CONCLUSIONS: Deficiency of TLRs or their signalling molecule MyD88 did not impact on the severity of experimental OA. Our results demonstrate that MyD88-dependent TLRs are not involved in this murine OA model. Moreover, the dispensable role of MyD88, which is also an adaptor for IL-1 receptor signaling, suggests that IL-1 is not a key mediator in the development of OA. This latter hypothesis is strengthened by the lack of efficiency of IL-1β antagonist in the treatment of OA.
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Background. This study is an evaluation of the vacuum-assisted closure (VAC) therapy for the treatment of severe intrathoracic infections complicating lung resection, esophageal surgery, viscera perforation, or necrotizing pleuropulmonary infections.Methods. We reviewed the medical records of all patients treated by intrathoracic VAC therapy between January 2005 and December 2008. All patients underwent surgical debridement-decortication and control of the underlying cause of infection such as treatment of bronchus stump insufficiency, resection of necrotic lung, or closure of esophageal or intestinal leaks. Surgery was followed by intrathoracic VAC therapy until the infection was controlled. The VAC dressings were changed under general anesthesia and the chest wall was temporarily closed after each dressing change. All patients received systemic antibiotic therapy.Results. Twenty-seven patients (15 male, median age 64 years) underwent intrathoracic VAC dressings for the management of postresectional empyema (n = 8) with and without bronchopleural fistula, necrotizing infections (n = 7), and intrathoracic gastrointestinal leaks (n = 12). The median length of VAC therapy was 22 days (range 5 to 66) and the median number of VAC changes per patient was 6 (range 2 to 16). In-hospital mortality was 19% (n = 5) and was not related to VAC therapy or intrathoracic infection. Control of intrathoracic infection and closure of the chest cavity was achieved in all surviving patients.Conclusions. Vacuum-assisted closure therapy is an efficient and safe adjunct to treat severe intrathoracic infections and may be a good alternative to the open window thoracostomy in selected patients. Long time intervals in between VAC changes and short course of therapy result in good patient acceptance. (Ann Thorac Surg 2011;91:1582-90) (C) 2011 by The Society of Thoracic Surgeons
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OBJECTIVES: To preliminarily evaluate prospectively the accuracy and reliability of a specific ad hoc reduction-compression forceps in intraoral open reduction of transverse and displaced mandibular angle fractures. STUDY DESIGN: We analyzed the clinical and radiologic data of 7 patients with 7 single transverse and displaced angle fractures. An intraoral approach was performed in all of the patients without using perioperative intermaxillary fixation. A single Arbeitsgemeinschaft Osteosynthese (AO) unilock reconstruction plate was fixed to each stable fragment with 3 locking screws (2.0 mm in 5 patients and 2.4 mm in 2 patients) at the basilar border of the mandible, according to AO/American Society of Internal Fixation (ASIF) principles. Follow-up was at 1, 3, 6, and 12 months, and we noted the status of healing and complications, if any. RESULTS: All of the patients had satisfactory fracture reduction as well as a successful treatment outcome without complications. CONCLUSION: This preliminary study demonstrated that the intraoral reduction of transverse and displaced angle fractures using a specific ad hoc reduction-forceps results in a high rate of success.
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RESUMO Objetivo Identificar e analisar os coeficientes de incidência de úlceras por pressão (UP) e os fatores de risco para o seu desenvolvimento em pacientes críticos com doenças cardiopneumológicas. Método Estudo de coorte, prospectivo realizado na Unidade de Terapia Intensiva (UTI) Cardiopneumológica de um hospital de grande porte na cidade de São Paulo, durante os meses de novembro de 2013 a fevereiro de 2014. Participaram do estudo 370 pacientes maiores de 18 anos, que não apresentavam UP na admissão e que estavam na UTI há menos de 24 horas. Os dados foram analisados por meio de análises univariadas e multivariada (Classification And Regression Tree - CART). Resultados Os coeficientes de incidência de UP foram: 11,0% para o total, distribuindo-se em 8,0% entre os homens e 3,0% para as mulheres (p=0,018); 10,0% na raça branca e 6,5% em pessoas com idade igual e superior a 60 anos. Os principais fatores de risco encontrados foram tempo de permanência na UTI igual ou superior a 9,5 dias, idade igual ou superior a 42,5 anos e raça branca. Conclusão O estudo contribui para os conhecimentos relacionados à epidemiologia das UP em pacientes críticos com doenças cardiopneumológicas, favorecendo o planejamento de cuidados preventivos específicos para essa clientela.
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To determine the role of Chlamydia trachomatis in miscarriage, we prospectively collected serum, cervicovaginal swab specimens, and placental samples from 386 women with and without miscarriage. Prevalence of immunoglobulin G against C. trachomatis was higher in the miscarriage group than in the control group (15.2% vs. 7.3%; p = 0.018). Association between C. trachomatis-positive serologic results and miscarriage remained significant after adjustment for age, origin, education, and number of sex partners (odds ratio 2.3, 95% confidence interval 1.1-4.9). C. trachomatis DNA was more frequently amplified from products of conception or placenta from women who had a miscarriage (4%) than from controls (0.7%; p = 0.026). Immunohistochemical analysis confirmed C. trachomatis in placenta from 5 of 7 patients with positive PCR results, whereas results of immunohistochemical analysis were negative in placenta samples from all 8 negative controls tested. Associations between miscarriage and serologic/molecular evidence of C. trachomatis infection support its role in miscarriage.
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BACKGROUND: Survival after pancreatic head adenocarcinoma surgery is determined by tumor characteristics, resection margins, and adjuvant chemotherapy. Few studies have analyzed the long-term impact of postoperative morbidity. The aim of the present study was to assess the impact of postoperative complications on long-term survival after pancreaticoduodenectomy for cancer. METHODS: Of 294 consecutive pancreatectomies performed between January 2000 and July 2011, a total of 101 pancreatic head resections for pancreatic ductal adenocarcinoma were retrospectively analyzed. Postoperative complications were classified on a five-grade validated scale and were correlated with long-term survival. Grade IIIb to IVb complications were defined as severe. RESULTS: Postoperative mortality and morbidity were 5 and 57 %, respectively. Severe postoperative complications occurred in 16 patients (16 %). Median overall survival was 1.4 years. Significant prognostic factors of survival were the N-stage of the tumor (median survival 3.4 years for N0 vs. 1.3 years for N1, p = 0.018) and R status of the resection (median survival 1.6 years for R0 vs. 1.2 years for R1, p = 0.038). Median survival after severe postoperative complications was decreased from 1.9 to 1.2 years (p = 0.06). Median survival for N0 or N1 tumor or after R0 resection was not influenced by the occurrence and severity of complications, but patients with a R1 resection and severe complications showed a worsened median survival of 0.6 vs. 2.0 years without severe complications (p = 0.0005). CONCLUSIONS: Postoperative severe morbidity per se had no impact on long-term survival except in patients with R1 tumor resection. These results suggest that severe complications after R1 resection predict poor outcome.
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Retinitis pigmentosa (RP) is a degenerative disease of the retina leading to progressive loss of vision and, in many instances, to legal blindness at the end stage. The RP28 locus was assigned in 1999 to the short arm of chromosome 2 by homozygosity mapping in a large Indian family segregating autosomal-recessive RP (arRP). Following a combined approach of chromatin immunoprecipitation and parallel sequencing of genomic DNA, we identified a gene, FAM161A, which was shown to carry a homozygous nonsense mutation (p.Arg229X) in patients from the original RP28 pedigree. Another homozygous FAM161A stop mutation (p.Arg437X) was detected in three subjects from a cohort of 118 apparently unrelated German RP patients. Age at disease onset in these patients was in the second to third decade, with severe visual handicap in the fifth decade and legal blindness in the sixth to seventh decades. FAM161A is a phylogenetically conserved gene, expressed in the retina at relatively high levels and encoding a putative 76 kDa protein of unknown function. In the mouse retina, Fam161a mRNA is developmentally regulated and controlled by the transcription factor Crx, as demonstrated by chromatin immunoprecipitation and organotypic reporter assays on explanted retinas. Fam161a protein localizes to photoreceptor cells during development, and in adult animals it is present in the inner segment as well as the outer plexiform layer of the retina, the synaptic interface between photoreceptors and their efferent neurons. Taken together, our data indicate that null mutations in FAM161A are responsible for the RP28-associated arRP.
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BACKGROUND: Higher nighttime blood pressure (BP) and the loss of nocturnal dipping of BP are associated with an increased risk for cardiovascular events. However, the determinants of the loss of nocturnal BP dipping are only beginning to be understood. We investigated whether different indicators of physical activity were associated with the loss of nocturnal dipping of BP. METHODS: We conducted a cross-sectional study of 103 patients referred for 24-hour ambulatory monitoring of BP. We measured these patients' step count (SC), active energy expenditure (AEE), and total energy expenditure simultaneously, using actigraphs. RESULTS: In our study population of 103 patients, most of whom were hypertensive, SC and AEE were associated with nighttime systolic BP in univariate (SC, r = -0.28, P < 0.01; AEE, r = -0.20, P = 0.046) and multivariate linear regression analyses (SC, coefficient beta = -5.37, P < 0.001; AEE, coefficient beta = -0.24, P < 0.01). Step count was associated with both systolic (r = 0.23, P = 0.018) and diastolic (r = 0.20, P = 0.045) BP dipping. Nighttime systolic BP decreased progressively across the categories of sedentary, moderately active, and active participants (125mm Hg, 116mm Hg, 112mm Hg, respectively; P = 0.002). The degree of BP dipping of BP increased progressively across the same three categories of activity (respectively 8.9%, 14.6%, and 18.6%, P = 0.002, for systolic BP and respectively 12.8%, 18.1%, and 22.2%, P = 0.006, for diastolic BP). CONCLUSIONS: Step count is continuously associated with nighttime systolic BP and with the degree of BP dipping independently of 24-hour mean BP. The combined use of an actigraph for measuring indicators of physical activity and a device for 24-hour measurement of ambulatory BP may help identify patients at increased risk for cardiovascular events in whom increased physical activity toward higher target levels may be recommended.
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Background: Interventional catheterization is being increasingly used for relief of residual lesions in congenital heart disease. Exact anatomical imaging is crucial in the planning of an intervention. This can be provided non-invasively and without radiation by contrast-enhanced MR angiography (CEMRA). Aim: To evaluate the accuracy of the measurements of the vessels obtained by CEMRA in comparison to those obtained by conventional X-ray angiography (CXA). Methods: Retrospective blinded measurement of the diameters of aorta and pulmonary arteries on the CEMRA and CXA images, in the same locations. Comparison of the results by Pearson correlation and by calculating the limits of agreement. Results: Twenty-one children with congenital heart disease, mean age 5.6 +- 5.2 years, weight 21.1 +- 18.4 kg, underwent CEMRA and catheterization for assessment or treatment of a residual lesion. The time interval between the CEMRA and the CXA examination was 2.6 +- 2.3 months. A total of 98 measurements, 37 of the aorta and 61 of the pulmonary arteries were performed on the images obtained by each technique. The correlation between CEMRA and CXA measurements was excellent, r = 0.97, p < 0.0001. The mean difference between the two techniques was 0.018 +- 1.1mm; the limits of agreement were -2.14 and +2.18mm. Similar agreement was found for measures of the aorta (r +- 0.97, mean difference 0.20 = 1.08 mm) and of the pulmonary arteries (r +- 0.97, mean difference 0.048 = 0.89 mm). Conclusions: CEMRA provide accurate quantitative anatomical information, which highly agrees with CXA data, and can therefore be used for planning interventional catheterization.
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OBJECTIVE: Assess outcome of patients with descending thoracic aortic aneurysms complicated by aortobronchial and aortoesophageal fistulae in comparison to patients undergoing repair of aortic aneurysms without fistulae. METHODS: In a consecutive series of 145 patients (age 60 +/- 12 years) with repair of descending thoracic and thoracoabdominal aortic aneurysms, 11 patients (8%; age 63 +/- 9; NS) primarily presented for hematemesis and/or hemoptysis. In 8/11 patients (73%) an aortobronchial fistula was identified, and 3/11 patients (27%) suffered from an aortoesophageal fistula. Five of 11 patients (45%) had undergone previous aortic surgery in the same region. RESULTS: Extent of aortic segments (range 1-8) replaced was 3.1 +/- 1.4 for all versus 2.6 +/- 0.9 for fistulae (NS). Aortic cross clamp time was 38 +/- 22 min for all versus 45 +/- 15 min for fistulae (NS). Mortality at 30 days was 18/145 (12%) for all versus 16/134 (12%) without fistulae versus 2/11 (18%) with fistulae (NS). Paraparesis and or paraplegia was observed in 11/145 (8%) for all versus 10/134 (7%) without fistulae versus 1/11 (9%) for cases with fistulae (NS). Nine additional patients died after hospital discharge, seven without fistulae and two with fistulae (days 80, and 120) bringing the 1-year mortality up to 23/134 (17%) without fistulae versus 4/11 (36%) with fistulae (NS). Further analysis shows that the 1-year mortality accounts for 1/8 patients (13%) with aorto-bronchial fistulae versus to 3/3 patients (100%) with aorto-esophageal fistulae (esophageal versus bronchial fistula: P = 0.018; esophageal versus no fistula: P = 0.006). CONCLUSIONS: Outcome of patients suffering from descending thoracic aortic aneurysms complicated by aorto-bronchial fistulae can be similar to that without fistulae, whereas for cases complicated by aorto-esophageal fistulae the prognosis seems to remain poor even after successful hospital discharge.
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PURPOSE: The Gastro-Intestinal Working Party of the EORTC Radiation Oncology Group (GIWP-ROG) developed guidelines for target volume definition in neoadjuvant radiation of adenocarcinomas of the gastroesophageal junction (GEJ) and the stomach. METHODS AND MATERIALS: Guidelines about the definition of the clinical target volume (CTV) are based on a systematic literature review of the location and frequency of local recurrences and lymph node involvement in adenocarcinomas of the GEJ and the stomach. Therefore, MEDLINE was searched up to August 2008. Guidelines concerning prescription, planning and treatment delivery are based on a consensus between the members of the GIWP-ROG. RESULTS: In order to support a curative resection of GEJ and gastric cancer, an individualized preoperative treatment volume based on tumour location has to include the primary tumour and the draining regional lymph nodes area. Therefore we recommend to use the 2nd English Edition of the Japanese Classification of Gastric Carcinoma of the Japanese Gastric Cancer Association which developed the concept of assigning tumours of the GEJ and the stomach to anatomically defined sub-sites corresponding respectively to a distinct lymphatic spread pattern. CONCLUSION: The GIWP-ROG defined guidelines for preoperative irradiation of adenocarcinomas of the GEJ and the stomach to reduce variability in the framework of future clinical trials.