Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 64
Filtrar
2.
Appl Environ Microbiol ; 86(11)2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32220837

RESUMO

Most of the microbial degradation in oil reservoirs is believed to take place at the oil-water transition zone (OWTZ). However, a recent study indicates that there is microbial life enclosed in microliter-sized water droplets dispersed in heavy oil of Pitch Lake in Trinidad and Tobago. This life in oil suggests that microbial degradation of oil also takes place in water pockets in the oil-bearing rock of an oil leg independent of the OWTZ. However, it is unknown whether microbial life in water droplets dispersed in oil is a generic property of oil reservoirs rather than an exotic exception. Hence, we took samples from three heavy-oil seeps, Pitch Lake (Trinidad and Tobago), the La Brea Tar Pits (California, USA), and an oil seep on the McKittrick oil field (California, USA). All three tested oil seeps contained dispersed water droplets. Larger droplets between 1 and 10 µl revealed high cell densities of up to 109 cells ml-1 Testing for ATP content and LIVE/DEAD staining showed that these populations consist of active and viable microbial cells with an average of 60% membrane-intact cells and ATP concentrations comparable to those of other subsurface ecosystems. Microbial community analyses based on 16S rRNA gene amplicon sequencing revealed the presence of known anaerobic oil-degrading microorganisms. Surprisingly, the community analyses showed similarities between all three oil seeps, revealing common OTUs, although the sampling sites were thousands of kilometers apart. Our results indicate that small water inclusions are densely populated microhabitats in heavy oil and possibly a generic trait of degraded-oil reservoirs.IMPORTANCE Our results confirmed that small water droplets in oil are densely populated microhabitats containing active microbial communities. Since these microhabitats occurred in three tested oil seeps which are located thousands of kilometers away from each other, such populated water droplets might be a generic trait of biodegraded oil reservoirs and might be involved in the overall oil degradation process. Microbial degradation might thus also take place in water pockets in the oil-bearing oil legs of the reservoir rock rather than only at the oil-water transition zone.


Assuntos
Archaea/isolamento & purificação , Bactérias/isolamento & purificação , Microbiota , Campos de Petróleo e Gás/microbiologia , Microbiologia da Água , Archaea/classificação , Bactérias/classificação , California , Lagos , Los Angeles , RNA Arqueal/análise , RNA Bacteriano/análise , RNA Ribossômico 16S/análise , Trinidad e Tobago , Água/química
3.
Nat Med ; 26(2): 207-214, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31988462

RESUMO

Frameshift mutations in the DMD gene, encoding dystrophin, cause Duchenne muscular dystrophy (DMD), leading to terminal muscle and heart failure in patients. Somatic gene editing by sequence-specific nucleases offers new options for restoring the DMD reading frame, resulting in expression of a shortened but largely functional dystrophin protein. Here, we validated this approach in a pig model of DMD lacking exon 52 of DMD (DMDΔ52), as well as in a corresponding patient-derived induced pluripotent stem cell model. In DMDΔ52 pigs1, intramuscular injection of adeno-associated viral vectors of serotype 9 carrying an intein-split Cas9 (ref. 2) and a pair of guide RNAs targeting sequences flanking exon 51 (AAV9-Cas9-gE51) induced expression of a shortened dystrophin (DMDΔ51-52) and improved skeletal muscle function. Moreover, systemic application of AAV9-Cas9-gE51 led to widespread dystrophin expression in muscle, including diaphragm and heart, prolonging survival and reducing arrhythmogenic vulnerability. Similarly, in induced pluripotent stem cell-derived myoblasts and cardiomyocytes of a patient lacking DMDΔ52, AAV6-Cas9-g51-mediated excision of exon 51 restored dystrophin expression and amelioreate skeletal myotube formation as well as abnormal cardiomyocyte Ca2+ handling and arrhythmogenic susceptibility. The ability of Cas9-mediated exon excision to improve DMD pathology in these translational models paves the way for new treatment approaches in patients with this devastating disease.


Assuntos
Distrofina/genética , Mutação da Fase de Leitura , Edição de Genes/métodos , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , RNA Guia de Cinetoplastídeos/genética , Animais , Modelos Animais de Doenças , Éxons , Feminino , Regulação da Expressão Gênica , Terapia Genética , Genoma , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/terapia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Espectrometria de Massas , Músculo Esquelético/metabolismo , Músculos/metabolismo , Mioblastos/metabolismo , Miócitos Cardíacos/metabolismo , Proteoma , Suínos
4.
Clin Microbiol Infect ; 25(11): 1428.e7-1428.e13, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30922931

RESUMO

OBJECTIVES: Conducting manual surveillance of non-ventilator-associated hospital-acquired pneumonia (nvHAP) using ECDC (European Centre for Disease Prevention and Control) surveillance criteria is very resource intensive. We developed and validated a semi-automated surveillance system for nvHAP, and describe nvHAP incidence and aetiology at our hospital. METHODS: We applied an automated classification algorithm mirroring ECDC definition criteria to distinguish patients 'not at risk' from patients 'at risk' for suffering from nvHAP. 'At risk'-patients were manually screened for nvHAP. For validation, we applied the reference standard of full manual evaluation to three validation samples comprising 2091 patients. RESULTS: Among the 39 519 University Hospital Zurich inpatient discharges in 2017, the algorithm identified 2454 'at-risk' patients, reducing the number of medical records to be manually screened by 93.8%. From this subset, nvHAP was identified in 251 patients (0.64%, 95%CI: 0.57-0.73). Sensitivity, negative predictive value, and accuracy of semi-automated surveillance versus full manual surveillance were lowest in the validation sample consisting of patients with HAP according to the International Classification of Diseases (ICD-10) discharge diagnostic codes, with 97.5% (CI: 93.7-99.3%), 99.2% (CI: 97.9-99.8%), and 99.4% (CI: 98.4-99.8%), respectively. The overall incidence rate of nvHAP was 0.83/1000 patient days (95%CI: 0.73-0.94), with highest rates in haematology/oncology, cardiac and thoracic surgery, and internal medicine including subspecialties. CONCLUSIONS: The semi-automated surveillance demonstrated a very high sensitivity, negative predictive value, and accuracy. This approach significantly reduces manual surveillance workload, thus making continuous nvHAP surveillance feasible as a pivotal element for successful prevention efforts.


Assuntos
Automação/métodos , Monitoramento Epidemiológico , Pneumonia Associada a Assistência à Saúde/epidemiologia , Pneumonia Associada a Assistência à Saúde/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Suíça/epidemiologia , Adulto Jovem
5.
Strahlenther Onkol ; 194(9): 806-814, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29796694

RESUMO

PURPOSE: To assess the outcome of breast cancer patients with local recurrence who underwent partial external beam re-irradiation (re-RT) either as part of a second breast-conserving therapy or following mastectomy. METHODS: Between 03/2004 and 10/2016, 83 breast cancer patients with local recurrence were treated with surgery followed by re-RT. The re-RT schedules were 45 Gy (1.8 Gy per fraction) administered either to the partial breast (n = 42) or mastectomy scar (n = 41). The patients and tumor characteristics predictive of local control, distant control, and survival (overall and breast-cancer specific) were evaluated by univariate and multivariate analyses. RESULTS: The median follow-up was 35 months (range 3-143 months). The median time interval between the first irradiation and re-RT was 117 months (range 16-357 months). The prognostic factors for favorable overall survival rates were younger age (p = 0.045), lower T­category (p = 0.019), and N0 category (p = 0.005). N0 was also superior to N+ with respect to outfield recurrences (p = <0.001) and breast cancer-specific survival (p = 0.025). Acute and late skin toxicity was generally low (

Assuntos
Neoplasias da Mama/radioterapia , Fracionamento da Dose de Radiação , Recidiva Local de Neoplasia/radioterapia , Radioterapia Adjuvante , Reirradiação , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Terapia Combinada/métodos , Feminino , Seguimentos , Humanos , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Planejamento da Radioterapia Assistida por Computador , Estudos Retrospectivos , Taxa de Sobrevida
6.
Domest Anim Endocrinol ; 63: 1-9, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29172109

RESUMO

The aim of this study was to investigate the relationship between laminitis development in ponies and insulin/glucose concentrations in response to the oral glucose test (OGT) and a dietary challenge high in nonstructural carbohydrates (NSCs). After undergoing an OGT (1 g dextrose/kg BW in feed), 37 ponies with 2-h serum insulin concentrations ranging from 22 to 1,133 µIU/mL were subjected to a diet challenge period (DCP), consuming 12 g NSC/kg BW/d for up to 18 d. Insulin and glucose responses were measured on day 2 of the DCP. Clinical laminitis was diagnosed by blinded experts and confirmed radiographically. Basal ACTH levels and clinical signs were assessed to investigate concurrent putative pituitary pars intermedia dysfunction (PPID). The diet induced Obel grade 1 or 2 laminitis in 14 ponies (38%). The ponies that developed laminitis had higher maximum concentrations of blood glucose (P = 0.04) and serum insulin (P = 0.02) in response to the diet. The geometric mean (95% CI) blood glucose concentration for laminitis cases was 14.9 (12.9-17.2) mM, compared to 10.7 (9.2-12.5) mM for ponies who did not develop laminitis. Similarly, the geometric mean (95% CI) for serum insulin was 396 (301-520) µIU/mL for laminitis cases, compared to 216 (148-316) µIU/mL for ponies who did not develop laminitis. Laminitis incidence was likewise associated with insulin concentrations measured during the OGT. Laminitis occurred at frequencies of 0% (0/7) if postdextrose insulin (µIU/mL) was <50; 35% (8/23) if insulin was 50 to 195; and 86% (6/7) if insulin was >195 µIU/mL. Basal ACTH concentrations were above seasonally accepted reference ranges in 16/37 ponies, and 8 of these animals (50%) developed laminitis. This included all 5 ponies in the study that had clinical signs of PPID (100%). In contrast, hyperinsulinemia and laminitis occurred in only 3/11 ponies (27%) with elevated ACTH concentrations and no clinical signs of PPID (P = 0.009). Thus, laminitis occurrence was associated with higher glucose and insulin responses to both the OGT and challenge diet, and the frequency of laminitis can be predicted based on insulin and glucose hyperresponsiveness to these oral carbohydrate challenges.


Assuntos
Carboidratos da Dieta/efeitos adversos , Doenças do Pé/veterinária , Teste de Tolerância a Glucose , Doenças dos Cavalos/induzido quimicamente , Inflamação/veterinária , Hormônio Adrenocorticotrópico/sangue , Animais , Glicemia , Carboidratos da Dieta/administração & dosagem , Feminino , Doenças do Pé/induzido quimicamente , Casco e Garras/patologia , Cavalos , Inflamação/patologia , Insulina/sangue , Masculino , Doenças da Hipófise/veterinária
7.
Middle East Afr J Ophthalmol ; 25(3-4): 150-155, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30765953

RESUMO

AIM: The aim of the study was to assess the predictors of ocular surface squamous neoplasia (OSSN) and conjunctival squamous cell carcinoma (SCC) among Ugandan patients. MATERIALS AND METHODS: Patients presenting for removal of ocular surface lesions received human immunodeficiency virus (HIV) testing, completed questionnaires about demographic, behavioral, and historical potential risk factors for conjunctival neoplasia, and had lesions examined for interpalpebral versus other locations, rough versus smooth texture, and number of feeder vessels. Biopsies were classified pathologically using standard definitions classified OSSN and SCC. HIV rates were calculated for patients: with OSSN, SCC, and benign lesions. Potential risk factors and gross findings were tested for abilities to predict OSSN and SCC. RESULTS: One hundred and ninety-five patients presented with 212 lesions in 203 eyes. Nearly 34% of the patients were more than 60 years old, 67% were peasants, 88% spent more than 20 h/week outdoors, and only 10% wore sun protection. No potential risk factors predicted neoplasia. HIV prevalence was 17.1% among patients with OSSN compared to 11.1% among those without OSSN; 42.9% among SCC patients compared to 12.0% among those without SCC. Rough tumor surface (adjusted odds ratio [aOR] = 4.4 and 95% confidence interval [CI]: 2.2-9.1), six or more feeder vessels (aOR = 2.6, 95% CI: 1.3-5.2), and interpalpebral tumor location (aOR = 3.3, 95% CI: 1.5-7.1) predicted OSSN. Only a rough tumor surface (aOR = 34.6, 95% CI: 7.8-153.4) predicted SCC. CONCLUSION: HIV infection remained a risk factor for OSSN and particularly, SCC, but less so than in the past. Lesions' rough surface, six or more feeder vessels, and interpalpebral location increased OSSN risk. Only a rough tumor surface increased risk for SCC.


Assuntos
Carcinoma de Células Escamosas/epidemiologia , Neoplasias da Túnica Conjuntiva/epidemiologia , Neoplasias Oculares/epidemiologia , Hospitais Universitários/estatística & dados numéricos , Adolescente , Adulto , Idoso , Biópsia , Carcinoma de Células Escamosas/diagnóstico , Neoplasias da Túnica Conjuntiva/diagnóstico , Neoplasias Oculares/diagnóstico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Fatores de Risco , Adulto Jovem
8.
Acta Oncol ; 56(2): 278-287, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28068157

RESUMO

BACKGROUND: The best practice for the organization of follow-up care in oncology is under debate, due to growing numbers of cancer survivors. Understanding survivors' preferences for follow-up care is elementary for designing patient-centred care. Based on data from prostate cancer and melanoma survivors, this study aims to identify: 1) preferences for follow-up care providers, for instance the medical specialist, the oncology nurse or the general practitioner; 2) characteristics associated with these preferences and 3) the preferred care provider to discuss cancer-related problems. MATERIAL AND METHODS: Survivors diagnosed with prostate cancer (N = 535) and melanoma (N = 232) between 2007 and 2013 as registered in The Netherlands Cancer Registry returned a questionnaire (response rate was 71% and 69%, respectively). A latent class cluster model analysis was used to define preferences and a multinomial logistic regression analysis was used to identify survivor-related characteristics associated with these preferences. RESULTS: Of all survivors, 29% reported no preference, 40% reported a preference for the medical specialist, 20% reported a preference for both the medical specialist and the general practitioner and 11% reported a preference for both the medical specialist and the oncology nurse. Survivors who were older, lower/intermediate educated and women were more likely to have a preference for the medical specialist. Lower educated survivors were less likely to have a preference for both the medical specialist and the general practitioner. Overall, survivors prefer to discuss diet, physical fitness and fatigue with the general practitioner, and hereditary and recurrence with the medical specialist. Only a small minority favored to discuss cancer-related problems with the oncology nurse. CONCLUSION: Survivors reported different preferences for follow-up care providers based on age, education level, gender and satisfaction with the general practitioner, showing a need for tailored follow-up care in oncology. The results indicate an urgency to educate patients about transitions in follow-up care.


Assuntos
Assistência ao Convalescente , Melanoma/mortalidade , Neoplasias da Próstata/mortalidade , Sobreviventes , Idoso , Estudos Transversais , Feminino , Pessoal de Saúde , Humanos , Masculino , Melanoma/terapia , Pessoa de Meia-Idade , Educação de Pacientes como Assunto , Preferência do Paciente , Neoplasias da Próstata/terapia , Sistema de Registros
9.
Med Klin Intensivmed Notfmed ; 110(7): 515-20, 2015 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-26346681

RESUMO

Endoscopic hemostasis is the daily challenge that must be mastered by gastroenterologists. An emergency colonoscopy is the procedure of choice for lower gastrointestinal bleeding because of the diagnostic and therapeutic potential. Colonoscopy should be performed after oral preparation with 4-6 l polyethylene glycol solution within 12 h. In the case of massive hematochezia, colonoscopy without oral preparation employinga mechanical pump is possible and is not associated with a higher rate of complications. Many different endoscopic techniques are available (injection therapy, hemoclips, thermal coagulation, topical hemostatic substances). The suitable and most effective method must be chosen depending on the source of bleeding.


Assuntos
Doenças do Colo/etiologia , Doenças do Colo/terapia , Colonoscopia/métodos , Cuidados Críticos/métodos , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Doenças Retais/terapia , Técnicas Hemostáticas , Humanos , Polietilenoglicóis/administração & dosagem , Doenças Retais/etiologia , Irrigação Terapêutica
10.
Clin Radiol ; 70(11): 1244-51, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26231468

RESUMO

AIM: To investigate the value of advanced virtual monoenergetic image reconstruction (mono-plus) from dual-energy computed tomography (CT) for improving the contrast of CT pulmonary angiography (CTPA). MATERIALS AND METHODS: Forty consecutive patients (25 women, mean 62.5 years, range 28-87 years) underwent 192-section dual-source CTPA with dual-energy CT (90/150 SnkVp) after the administration of 60 ml contrast media (300 mg iodine/ml). Conventional virtual monochromatic images at 60 keV and 17 mono-plus image datasets from 40-190 keV (in 10 keV steps) were reconstructed. Subjective image quality (artefacts, subjective noise) was rated. Attenuation was measured in the pulmonary trunk and in the right lower lobe pulmonary artery; noise was measured in the periscapular musculature. The signal-to-noise (SNR) and contrast-to-noise ratios (CNR) were calculated for each patient and dataset. Comparisons between monochromatic images and mono-plus images were performed by repeated measures analysis of variance (ANOVA) with post-hoc Bonferroni correction. RESULTS: Interreader agreement was good to excellent for subjective image quality (ICC: 0.616-0.889). As compared to conventional 60 keV images, artefacts occurred less (p=0.001) and subjective noise was rated lower (p<0.001) in mono-plus 40 keV images. Noise was lower (p<0.001), and the SNR and CNR in the pulmonary trunk and right lower lobe pulmonary artery were higher (both, p<0.001) in mono-plus 40 keV images compared to conventional monoenergetic 60 keV images. Transient interruption of contrast (TIC) was found in 14/40 (35%) of patients, with subjective contrast being similar 8/40 (20%) or higher 32/40 (80%) in mono-plus 40 keV as compared to conventional monoenergetic 60 keV images. CONCLUSIONS: Compared to conventional virtual monoenergetic imaging, mono-plus images at 40 keV improve the contrast of dual-energy CTPA.


Assuntos
Processamento de Imagem Assistida por Computador/normas , Artéria Pulmonar/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Artefatos , Meios de Contraste , Feminino , Humanos , Processamento de Imagem Assistida por Computador/métodos , Iodo , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/normas , Estudos Retrospectivos , Razão Sinal-Ruído , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/normas
11.
Z Gastroenterol ; 53(3): 183-98, 2015 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-25775168

RESUMO

BACKGROUND: The German hospital reimbursement system (G-DRG) is incomplete for endoscopic interventions and fails to differentiate between complex and simple procedures. This is caused by outdated methods of personnel-cost allocation. METHODS: To establish an up-to-date service catalogue 50 hospitals made their anonymized expense-budget data available to the German-Society-of-Gastroenterology (DGVS). 2.499.900 patient-datasets (2011-2013) were used to classify operation-and-procedure codes (OPS) into procedure-tiers (e.g. colonoscopy with biopsy/colonoscopy with stent-insertion). An expert panel ranked these tiers according to complexity and assigned estimates of physician time. From June to November 2014 exact time tracking data for a total 38.288 individual procedures were collected in 119 hospitals to validate this service catalogue. RESULTS: In this three-step process a catalogue of 97 procedure-tiers was established that covers 99% of endoscopic interventions performed in German hospitals and assigned validated mean personnel-costs using gastroscopy as standard. Previously, diagnostic colonoscopy had a relative personnel-cost value of 1.13 (compared to gastroscopy 1.0) and rose to 2.16, whereas diagnostic ERCP increased from 1.7 to 3.62, more appropriately reflecting complexity. Complex procedures previously not catalogued were now included (e.g. gastric endoscopic submucosal dissection: 16.74). DISCUSSION: This novel service catalogue for GI-endoscopy almost completely covers all endoscopic procedures performed in German hospitals and assigns relative personnel-cost values based on actual physician time logs. It is to be included in the national coding recommendation and should replace all prior inventories for cost distribution. The catalogue will contribute to a more objective cost allocation and hospital reimbursement - at least until time tracking for endoscopy becomes mandatory.


Assuntos
Catálogos como Assunto , Grupos Diagnósticos Relacionados/economia , Endoscopia Gastrointestinal/classificação , Endoscopia Gastrointestinal/economia , Gastroenterologia/economia , Custos Hospitalares/classificação , Alocação de Custos/economia , Alocação de Custos/métodos , Tabela de Remuneração de Serviços/economia , Alemanha , Reembolso de Seguro de Saúde/economia
12.
Oncogene ; 33(30): 3927-38, 2014 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-23995784

RESUMO

The Ewing sarcoma (ES) EWS-FLI1 chimeric oncoprotein is a prototypic aberrant ETS transcription factor with activating and repressive regulatory functions. We report that EWS-FLI1-repressed promoters are enriched in forkhead box (FOX) recognition motifs, and identify FOXO1 as a EWS-FLI1-suppressed regulator orchestrating a major subset of EWS-FLI1-repressed genes. In addition to FOXO1 regulation by direct promoter binding of EWS-FLI1, its subcellular localization and activity is regulated by cyclin-dependent kinase 2- and AKT-mediated phosphorylation downstream of EWS-FLI1. Restoration of nuclear FOXO1 expression in ES cells impaired proliferation and significantly reduced clonogenicity. Gene-expression profiling revealed a significant overlap between EWS-FLI1-repressed and FOXO1-activated genes. As a proof of principle for a potential therapeutic application of our findings, the treatment of ES cell lines with methylseleninic acid (MSA) reactivated endogenous FOXO1 in the presence of EWS-FLI1 in a dose- and time-dependent manner and induced massive cell death dependent on FOXO1. In an orthotopic xenograft mouse model, MSA increased FOXO1 expression in the tumor paralleled by a significant decrease in ES tumor growth. FOXO1 reactivation by small molecules may therefore serve as a promising strategy for a future ES-specific therapy.


Assuntos
Neoplasias Ósseas/metabolismo , Fatores de Transcrição Forkhead/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Fusão Oncogênica/metabolismo , Proteína Proto-Oncogênica c-fli-1/metabolismo , Proteína EWS de Ligação a RNA/metabolismo , Sarcoma de Ewing/metabolismo , Animais , Antineoplásicos/farmacologia , Sequência de Bases , Sítios de Ligação , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Proliferação de Células , Sequência Consenso , Quinase 2 Dependente de Ciclina/metabolismo , Proteína Forkhead Box O1 , Proteína Forkhead Box O3 , Fatores de Transcrição Forkhead/genética , Inativação Gênica , Humanos , Camundongos , Proteínas de Fusão Oncogênica/genética , Compostos Organosselênicos/farmacologia , Fosforilação , Regiões Promotoras Genéticas , Processamento de Proteína Pós-Traducional , Transporte Proteico , Proteína Proto-Oncogênica c-fli-1/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteína EWS de Ligação a RNA/genética , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/genética , Transcrição Gênica , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
13.
Ann Surg Oncol ; 18(2): 514-20, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20839060

RESUMO

BACKGROUND: The status of the sentinel lymph node is an important predictor for survival in melanoma patients, but it is still unclear if early removal of micrometastases by sentinel lymph node dissection (SLND) alters survival. A large series of melanoma patients from a single center with long-term follow-up was analyzed with regard to a possible effect of SLND on the prognosis. MATERIALS AND METHODS: A total of 673 consecutive melanoma patients were assessed treated in our center either without SLND (377 patients, pre-SLN group, between January 1995 and March 2000) or with SLND (296 patients, SLN group, between April 2000 and March 2003). The median follow-up was 64.0 months in the pre-SLN and 72.5 months in the SLN group. RESULTS: The pre-SLN group and SLN group did not differ significantly with regard to characteristics of the primary melanoma thickness and ulceration, sex, and age. Kaplan-Meier analyses showed a significantly better recurrence-free survival (P < .001), distant metastases free survival (P = .006), and overall survival (P = .049) for patients of the SLN group; the 5-year melanoma-specific survival rates were 80.3% in pre-SLN patients and 84.8% in SLN patients. Initial metastases in the in-transit region and distant locations were of similar frequency in the pre-SLN and SLN groups (P = .191 and P = .959, respectively), but initial regional lymph node metastases were significantly more frequent in the pre-SLN group (P < .001). CONCLUSIONS: Our data point toward a subgroup of melanoma patients who might have a prognostic benefit from SLN.


Assuntos
Excisão de Linfonodo , Melanoma/mortalidade , Recidiva Local de Neoplasia/mortalidade , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Melanoma/patologia , Melanoma/cirurgia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Estadiamento de Neoplasias , Prognóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Taxa de Sobrevida , Adulto Jovem
14.
Histopathology ; 50(6): 764-72, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17493240

RESUMO

AIMS: The presence of micrometastases in the sentinel lymph node (SLN) is an important prognostic parameter for melanoma patients. The aim was to determine the prognostic relevance of histopathological characteristics of micrometastases in the SLN, which has not been adequately addressed thus far. METHODS AND RESULTS: In 169 melanoma patients with positive SLN, histopathological features of the SLN were correlated with overall survival (OS) and relapse-free survival (RFS). Tumour burden, expansion of melanoma cells in the periphery (infiltration of capsule) and towards the centre of the SLN [tumour penetrative depth (TPN)] were of prognostic significance for OS and RFS on univariate analysis. Multivariate analysis revealed three independent significant parameters which predict a poor prognosis: presence of infiltration of the SLN capsule, TPN > or = 2 mm and size of the largest tumour deposit > or = 30 cells. CONCLUSIONS: Histopathological analysis of SLN allows the identification of patients with a poor prognosis depending on the location of melanoma cells and tumour burden.


Assuntos
Linfonodos/patologia , Melanoma/patologia , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática/diagnóstico , Metástase Linfática/patologia , Masculino , Melanoma/diagnóstico , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/diagnóstico
15.
Tijdschr Gerontol Geriatr ; 38(1): 38-45, 2007 Mar.
Artigo em Holandês | MEDLINE | ID: mdl-17447609

RESUMO

The Telephone Interview Cognitive Status (TICS) is an instrument to screen for dementia in older persons by telephone. Although the psychometric properties of the TICS have been studied in various countries, the quality of the Dutch version of the TICS was yet unknown. This paper presents the Dutch version of the TICS and reports on its reliability and validity among 51 patients of Maastricht University Hospital, The Netherlands. The Pearson and intra-class correlations for test-retest reliability were 0.93 and 0.92, respectively. The Pearson and intra-class correlations for inter-rater reliability were 0.91 and 0.90, respectively. Sensitivity and specificity were studied in relation to the Mini Mental State Examination (MMSE, cut-off point 23/ 24) and the diagnosis of dementia as assessed according to DSM-IV criteria. When using the TICS cut-off point of 26/27, the coefficients for sensitivity and specificity were at least 0.80. The percentages ROC under the curve were 90% and 93% with the MMSE and the diagnosis dementia as criterion, respectively. We conclude that the Dutch version of the TICS is an acceptable instrument for screening for dementia in older persons, particularly when face-to-face contact is not possible.


Assuntos
Demência/diagnóstico , Entrevistas como Assunto , Psicometria/métodos , Psicometria/normas , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Humanos , Entrevista Psicológica , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Países Baixos , Curva ROC , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
16.
Cancer Gene Ther ; 14(4): 431-9, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17235352

RESUMO

In this report, the effects of a combined treatment with the proteasome inhibitor bortezomib and either a recombinant adeno-associated virus type 2 (rAAV-2)-mediated p53 gene transfer or chemotherapeutic agents, docetaxel and pemetrexed, were tested on p53 positive and p53negative non-small cell lung cancer (NSCLC) cell lines. The combination of bortezomib and rAAV-p53 led to a significant synergistic inhibition of cell growth between 62-82% depending on the p53 status of the cell line and drug concentration. Surviving cells of the combined treatment showed a significant reduced ability to form colonies. Enhanced cell toxicity was associated with a 5.3-14.4-fold increase of the apoptotic rate and intracellular p53 level up to 50.4% following vector-mediated p53 restoration and bortezomib treatment. In contrast, an antagonistic effect on tumor cell growth and colony formation was observed for the combination of bortezomib and docetaxel or pemetrexed as a reduction of cell growth between 31 and 48% was found in comparison to 50% using the single agents. Lower cytotoxic effects were associated with significantly reduced apoptosis and an increase of clonogenic growth. The observed antagonistic effects between bortezomib and docetaxel or pemetrexed might influence clinical trials using these compounds. Conversely, p53 restoration and bortezomib treatment led to enhanced, synergistic tumor cell toxicity.


Assuntos
Antineoplásicos/uso terapêutico , Ácidos Borônicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/terapia , Genes p53/genética , Terapia Genética , Neoplasias Pulmonares/terapia , Inibidores de Proteases/uso terapêutico , Pirazinas/uso terapêutico , Apoptose , Bortezomib , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Terapia Combinada , Docetaxel , Glutamatos/uso terapêutico , Guanina/análogos & derivados , Guanina/uso terapêutico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Pemetrexede , Inibidores de Proteassoma , Taxoides/uso terapêutico , Transfecção , Células Tumorais Cultivadas
17.
Sex Transm Infect ; 82(3): 229-35, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16731675

RESUMO

OBJECTIVES: Human herpesvirus 8 (HHV-8) infection is common among men who have sex with men (MSM), especially those infected with HIV, and is frequently detected in saliva. We sought to determine whether oral or anogenital contact with HIV discordant, or unknown serostatus sexual partners is associated with HHV-8 seroprevalence among HIV negative MSM. METHODS: HIV negative MSM participating in a behavioural intervention trial for the prevention of HIV infection (the EXPLORE study) were recruited from the Seattle and Denver areas for participation in this cross sectional study. Participants completed detailed questionnaires regarding sexual behaviour, focusing on activities with possible exposure to the oropharynx. Serum samples from study enrollment were tested for the presence of HHV-8 antibodies using whole virus enzyme immunoassay and immunofluorescence assay to latent and lytic proteins. RESULTS: 198/819 MSM (24.3%) were HHV-8 antibody positive. Exposure to saliva with HIV positive and HIV unknown serostatus sex partners was reported by 83% and 90% of all men, respectively. In a multivariate model, reporting more than the median number of lifetime sex partners (OR 2.2, p = 0.03) or lifetime sex partners of unknown HIV status (OR 1.7, p = 0.03), and the performance of oro-anal sex ("rimming") on partners whose HIV status is unknown (OR 2.7, p = 0.04) were independently associated with HHV-8 infection. CONCLUSIONS: The oropharynx may be an important anatomical site in HHV-8 acquisition, and contact with HIV serodiscordant or unknown sex partners is associated with higher HHV-8 seroprevalence among HIV negative MSM.


Assuntos
Soropositividade para HIV/epidemiologia , Homossexualidade Masculina/estatística & dados numéricos , Saliva/virologia , Sarcoma de Kaposi/virologia , Adulto , Idoso , Estudos de Coortes , Colorado/epidemiologia , Soronegatividade para HIV/fisiologia , Soropositividade para HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Orofaringe/virologia , Sarcoma de Kaposi/epidemiologia , Parceiros Sexuais , Washington/epidemiologia
18.
Stud Health Technol Inform ; 94: 144-50, 2003.
Artigo em Inglês | MEDLINE | ID: mdl-15455880

RESUMO

Mechanical properties of biological tissue represent important diagnostic information and are of histological relevance (hard lesions, "nodes" in organs: tumors; calcifications in vessels: arteriosclerosis). The problem is, that such information is usually obtained by digital palpation only, which is limited with respect to sensitivity. It requires intuitive assessment and does not allow quantitative documentation. A suitable sensor is required for quantitative detection of mechanical tissue properties. On the other hand, there is also some need for a realistic mechanical display of those tissue properties. Suitable actuator arrays with high spatial resolution and real-time capabilities are required operating in a haptic sensor actuator system with different applications. The sensor system uses real time ultrasonic elastography whereas the tactile actuator is based on electrorheological fluids. Due to their small size the actuator array elements have to be manufactured by micro-mechanical production methods. In order to supply the actuator elements with individual high voltages a sophisticated switching and control concept have been designed. This haptic system has the potential of inducing real time substantial forces, using a compact lightweight mechanism which can be applied to numerous areas including intraoperative navigation, telemedicine, teaching, space and telecommunication.


Assuntos
Simulação por Computador , Elasticidade , Alemanha , Humanos , Reologia , Interface Usuário-Computador
19.
Vasc Surg ; 35(2): 149-55, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11668385

RESUMO

Despite successful surgical revascularization of ischemic limbs, a local and systemic reperfusion injury may occur after normal blood reperfusion. Recent experimental and clinical application of controlled limb reperfusion in Europe has demonstrated superior results, with lower morbidity and mortality. This new surgical technique includes modification of the reperfusate (calcium, pH, substrates, osmolarity, free radical scavenger) and the circumstances of initial reperfusion (time, temperature, pressure). This report describes the first application of controlled limb reperfusion after reperfusion injury. A 16-year-old boy underwent femoral access cardiopulmonary bypass for repeat cardiac repair with an ischemic time of 245 minutes. Postoperatively, severe ischemia/reperfusion syndrome developed with muscle contracture, immobility, and anesthesia of the right leg with a second ischemic time of about 6 hours. The systemic creatine phosphokinase level was 88,000 U/L; myoglobin was 27,000 ng/mL. He underwent controlled limb reperfusion by withdrawing blood from the aorta and mixing it with a crystalloid solution (calcium-reduced, hyperosmolar, hyperglycemic, alkalotic, glutamate- and aspartate-enriched, and containing a free radical scavenger) under controlled conditions (blood:crystalloid solution 6:1, for 30 minutes, reperfusion pressure < 50 mm Hg, and normothermia) before establishing normal blood reperfusion. Metabolic data from the central and femoral vein demonstrated a significant reduction of all previous elevated enzyme levels, avoidance of hyperkalemia, normalization of acidosis, and avoidance of systemic reperfusion injury with no multiorgan failure. Limb salvage was accomplished and functional recovery almost complete. To the authors' knowledge, this is the first application of controlled limb reperfusion reported in North America. With this surgical technique we were able to prevent metabolic local and systemic reperfusion changes after prolonged ischemia and also reduced previous reperfusion changes. This report confirms former experimental data, and further clinical studies are warranted.


Assuntos
Músculo Esquelético/lesões , Traumatismo por Reperfusão , Adolescente , Extremidades/cirurgia , Humanos , Masculino , Músculo Esquelético/cirurgia , Reperfusão , Traumatismo por Reperfusão/cirurgia
20.
Fam Community Health ; 24(3): 88-103, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11563947

RESUMO

This qualitative study assessed the feasibility and comparability of findings from face-to-face versus on-line chat focus groups including 12 individuals affected by colon cancer. Discussion questions focused on issues of lifestyle (nutrition and exercise), cancer screening, and treatment. Despite demographic differences, the themes that emerged from the two types of groups were similar. On-line participants generally talked more about cancer treatment and advocacy issues and used support groups more frequently. The anonymity of on-line chat groups appeared to provide a more comfortable forum for some people to discuss sensitive personal health issues. As both methods provided similar results, researchers may wish to consider circumstances in which using chat-based focus groups may provide a feasible alternative to traditional face-to-face groups.


Assuntos
Neoplasias do Colo/psicologia , Grupos Focais/métodos , Comportamentos Relacionados com a Saúde , Internet , Relações Interpessoais , Colonoscopia , Dieta , Exercício Físico , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Estilo de Vida , Masculino , North Carolina , Defesa do Paciente , Apoio Social
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA