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1.
Spine J ; 17(6): 759-767, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-26239762

RESUMO

BACKGROUND: With recent advances in oncologic treatments, there has been an increase in patient survival rates and concurrently an increase in the number of incidence of symptomatic spinal metastases. Because elderly patients are a substantial part of the oncology population, their types of treatment as well as the possible impact their treatment will have on healthcare resources need to be further examined. PURPOSE: We studied whether age has a significant influence on quality of life and survival in surgical interventions for spinal metastases. STUDY DESIGN: We used data from a multicenter prospective study by the Global Spine Tumor Study Group (GSTSG). This GSTSG study involved 1,266 patients who were admitted for surgical treatments of symptomatic spinal metastases at 22 spinal centers from different countries and followed up for 2 years after surgery. PATIENT SAMPLE: There were 1,266 patients recruited between March 2001 and October 2014. OUTCOME MEASURES: Patient demographics were collected along with outcome measures, including European Quality of Life-5 Dimensions (EQ-5D), neurologic functions, complications, and survival rates. METHODS: We realized a multicenter prospective study of 1,266 patients admitted for surgical treatment of symptomatic spinal metastases. They were divided and studied into three different age groups: <70, 70-80, and >80 years. RESULTS: Despite a lack of statistical difference in American Society of Anesthesiologists (ASA) score, Frankel neurologic score, or Karnofsky functional score at presentation, patients >80 years were more likely to undergo emergency surgery and palliative procedures compared with younger patients. Postoperative complications were more common in the oldest age group (33.3% in the >80, 23.9% in the 70-80, and 17.9% for patients <70 years, p=.004). EQ-5D improved in all groups, but survival expectancy was significantly longer in patients <70 years old (p=.02). Furthermore, neurologic recovery after surgery was lower in patients >80 years old. CONCLUSIONS: Surgeons should not be biased against operating elderly patients. Although survival rates and neurologic improvements in the elderly patients are lower than for younger patients, operating the elderly is compounded by the fact that they undergo more emergency and palliative procedures, despite good ASA scores and functional status. Age in itself should not be a determinant of whether to operate or not, and operations should not be avoided in the elderly when indicated.


Assuntos
Procedimentos Neurocirúrgicos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Neoplasias da Coluna Vertebral/cirurgia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Contraindicações de Procedimentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/estatística & dados numéricos , Qualidade de Vida , Neoplasias da Coluna Vertebral/secundário
3.
Cancer Epidemiol Biomarkers Prev ; 21(10): 1620-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23045536

RESUMO

BACKGROUND: Patient navigation (PN) has been suggested as a way to reduce cancer health disparities; however, many models of PN exist and most have not been carefully evaluated. The goal of this study was to test the Ohio American Cancer Society model of PN as it relates to reducing time to diagnostic resolution among persons with abnormal breast, cervical, or colorectal cancer screening tests or symptoms. METHODS: A total of 862 patients from 18 clinics participated in this group-randomized trial. Chart review documented the date of the abnormality and the date of resolution. The primary analysis used shared frailty models to test for the effect of PN on time to resolution. Crude HR were reported as there was no evidence of confounding. RESULTS: HRs became significant at 6 months; conditional on the random clinic effect, the resolution rate at 15 months was 65% higher in the PN arm (P = 0.012 for difference in resolution rate across arms; P = 0.009 for an increase in the HR over time). CONCLUSIONS: Participants with abnormal cancer screening tests or symptoms resolved faster if assigned to PN compared with those not assigned to PN. The effect of PN became apparent beginning six months after detection of the abnormality. IMPACT: PN may help address health disparities by reducing time to resolution after an abnormal cancer screening test.


Assuntos
Detecção Precoce de Câncer , Navegação de Pacientes , Adulto , Idoso , Idoso de 80 Anos ou mais , American Cancer Society , Neoplasias da Mama/diagnóstico , Neoplasias Colorretais/diagnóstico , Feminino , Disparidades em Assistência à Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Ohio , Apoio Social , Fatores de Tempo , Neoplasias do Colo do Útero/diagnóstico
4.
J Clin Oncol ; 30(30): 3726-33, 2012 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-23008299

RESUMO

PURPOSE Cancer-related lymphedema (LE) is an incurable condition associated with lymph-involved cancer treatments and is an increasing health, quality of life (QOL), and cost burden on a growing cancer survivor population. This review examines the evidence for causes, risk, prevention, diagnosis, treatment, and impact of this largely unexamined survivorship concern. METHODS PubMed and Medline were searched for cancer-related LE literature published since 1990 in English. The resulting references (N = 726) were evaluated for strength of design, methods, sample size, and recent publication and sorted into categories (ie, causes/prevention, diagnosis, treatment, and QOL). Sixty studies were included. Results Exercise and physical activity and sentinel lymph node biopsy reduce risk, and overweight and obesity increase risk. Evidence that physiotherapy reduces risk and that lymph node status and number of malignant nodes increase risk is less strong. Perometry and bioimpedence emerged as attractive diagnostic technologies, replacing the use of water displacement in clinical practice. Swelling can also be assessed by measuring arm circumference and relying on self-report. Symptoms can be managed, not cured, with complex physical therapy, low-level laser therapy, pharmacotherapy, and surgery. Sequelae of LE negatively affect physical and mental QOL and range in severity. However, the majority of reviewed studies involved patients with breast cancer; therefore, results may not be applicable to all cancers. CONCLUSION Research into causes, prevention, and effect on QOL of LE and information on LE in cancers other than breast is needed. Consensus on definitions and measurement, increased patient and provider awareness of signs and symptoms, and proper and prompt treatment/access, including psychosocial support, are needed to better understand, prevent, and treat LE.


Assuntos
Linfedema/etiologia , Neoplasias/terapia , Exercício Físico , Humanos , Linfedema/diagnóstico , Linfedema/terapia , Neoplasias/complicações , Sobrepeso , Fatores de Risco , Biópsia de Linfonodo Sentinela , Sobreviventes
5.
J Neurosurg Sci ; 56(3): 203-7, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22854588

RESUMO

Use of biologic graft extenders in spinal fusions is increasing. Multiple allograft alternatives exist to the "gold-standard" autologous bone grafting. The ideal graft extender is osteoconductive, osteoinductive and has osteogenic potential. While the ideal graft extender has yet to be found, available bone graft extenders have varying degrees of predominantly osteoconductive and osteoinductive properties. This review will provide an update on available graft extenders including bone morphogenetic proteins, mesenchymal stem cells, and demineralized bone matrix. The goal is to provide a review of the current use in spinal fusions and future directions in biologics for spinal fusion.


Assuntos
Proteínas Morfogenéticas Ósseas/uso terapêutico , Substitutos Ósseos/uso terapêutico , Transplante Ósseo/tendências , Transplante de Células-Tronco Mesenquimais/tendências , Doenças da Coluna Vertebral/cirurgia , Fusão Vertebral/métodos , Humanos
6.
J Cancer Educ ; 27(2 Suppl): S157-64, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22362356

RESUMO

A gap exists between cancer prevention research and its translation into community practice. Two strategies to reduce this gap are community-based participatory research (CBPR) and dissemination research. CBPR offers an avenue to engage academic and community partners, thereby providing mechanisms for joint learning and application of knowledge. Dissemination research examines the movement of evidence-based public health and clinical innovations to practice settings. While applying these approaches may reduce the gap between research and practice, the cancer prevention workforce may be inadequate in size, insufficiently trained, lack resources and incentives, or face structural barriers to effectively participate in CBPR and disseminate evidence-based research findings into practice. Information on translating cancer prevention information to communities and workforce implications was obtained from a panel of experts and through a review of the literature on CBPR and dissemination research. The expert panel and literature review identified major barriers to successfully conducting CBPR and dissemination research in community settings. Barriers included inadequate policies; insufficient networking and communication infrastructures; unsupportive research cultures, climates, and mindsets; inadequate researcher and practitioner education; and limited CBPR and dissemination research with adequate study designs. No specific estimates of the cancer prevention workforce were found; however, indirect evidence for a shortfall were identified. We recommend expanding CBPR training for academic and community partners; increasing funding for dissemination research and practice; supporting proven partnerships; and providing strategic coordination for government agencies, research institutions, nongovernmental organizations, and the private sector to foster better dissemination of information and integration of community-based cancer prevention and control programs and practices. Specific challenges and needs that must be addressed to improve the translation of cancer prevention research into community settings were identified.


Assuntos
Pesquisa Participativa Baseada na Comunidade/organização & administração , Atenção à Saúde , Oncologia , Neoplasias/prevenção & controle , Guias de Prática Clínica como Assunto , Competência Profissional , Pesquisa Translacional Biomédica/organização & administração , Humanos , Oncologia/educação , Neoplasias/diagnóstico , Recursos Humanos
7.
Patient Educ Couns ; 86(1): 120-6, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21458195

RESUMO

OBJECTIVE: To explore Appalachian women's perceptions of trust and distrust of healthcare providers and the medical care system as they relate to views about cervical cancer and screening. METHODS: Thirty-six Ohio Appalachia female residents participated in community focus groups conducted by trained facilitators. Discussion topics included factors related to cervical cancer, and the issues of trust and distrust in medical care. The tape-recorded focus groups were transcribed and analyzed to identify salient themes. RESULTS: Five themes emerged related to trust in healthcare. Patient-centered communication and encouragement from a healthcare provider led women to trust their physicians and the medical care system. In contrast, lack of patient-centered communication by providers and perceptions of poor quality of care led to distrust. Physician gender concordance also contributed to trust as women reported trust of female physicians and distrust of male physicians; trust in male physicians was reported to be increased by the presence of a female nurse. CONCLUSIONS: Important factors associated with trust and distrust of providers and the medical care system may impact health-seeking behaviors among underserved women. PRACTICE IMPLICATIONS: Opportunities to improve patient-centered communication around the issues of prevention and cervical cancer screening (such as providing patient-focused information about access to appropriate screening tests) could be used to improve patient care and build patients' trust.


Assuntos
Detecção Precoce de Câncer/psicologia , Satisfação do Paciente , Relações Médico-Paciente , Confiança/psicologia , Neoplasias do Colo do Útero/diagnóstico , Saúde da Mulher , Adulto , Idoso , Idoso de 80 Anos ou mais , Região dos Apalaches , Comunicação , Medo , Feminino , Grupos Focais , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Pessoa de Meia-Idade , Ohio , Assistência Centrada no Paciente/métodos , Pesquisa Qualitativa , Fatores Sexuais , Gravação em Fita , Neoplasias do Colo do Útero/psicologia , Adulto Jovem
8.
Cancer Epidemiol Biomarkers Prev ; 20(10): 2042-7, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21980012

RESUMO

The number of cancer survivors and the amount of cancer survivorship research have grown substantially during the past three decades. This article provides a review of interventional and observational cancer survivorship research efforts as well as a summary of current cancer survivorship research projects being conducted by National Cancer Institute-designated cancer centers in an effort to identify areas that need further attention.


Assuntos
Neoplasias/mortalidade , Neoplasias/terapia , Pesquisa Biomédica , Humanos , National Cancer Institute (U.S.) , National Institutes of Health (U.S.) , Literatura de Revisão como Assunto , Taxa de Sobrevida , Estados Unidos
9.
CA Cancer J Clin ; 61(4): 237-49, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21659419

RESUMO

Although patient navigation was introduced 2 decades ago, there remains a lack of consensus regarding its definition, the necessary qualifications of patient navigators, and its impact on the continuum of cancer care. This review provides an update to the 2008 review by Wells et al on patient navigation. Since then, there has been a significant increase in the number of published studies dealing with cancer patient navigation. The authors of the current review conducted a search by using the keywords "navigation" or "navigator" and "cancer." Thirty-three articles published from November 2007 through July 2010 met the search criteria. Consistent with the prior review, there is building evidence of some degree of efficacy of patient navigation in terms of increasing cancer screening rates. However, there is less recent evidence concerning the benefit of patient navigation with regard to diagnostic follow-up and in the treatment setting, and a paucity of research focusing on patient navigation in cancer survivorship remains. Methodological limitations were noted in many studies, including small sample sizes and a lack of control groups. As patient navigation programs continue to develop across North America and beyond, further research will be required to determine the efficacy of cancer patient navigation across all aspects of the cancer care continuum.


Assuntos
Atenção à Saúde , Neoplasias/epidemiologia , Continuidade da Assistência ao Paciente , Detecção Precoce de Câncer , Acessibilidade aos Serviços de Saúde , Disparidades nos Níveis de Saúde , Humanos , Neoplasias/diagnóstico , Neoplasias/terapia , Fatores Socioeconômicos , Estados Unidos
10.
QJM ; 103(12): 929-40, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20739355

RESUMO

OBJECTIVES: NHS North West aimed to fully implement the European Working Time Directive (EWTD) 1 year ahead of the August 2009 national deadline. Significant debate has taken place concerning the implications of the EWTD for patient safety. This study aims to directly address this issue by comparing parameters of patient safety in NHS North West to those nationally prior to EWTD implementation, and during 'North West-only' EWTD implementation. DESIGN: Hospital standardised mortality ratio (HSMR), average length of stay (ALOS) and standardised readmission rate (SRR) in acute trusts across all specialties were calculated retrospectively throughout NHS North West for the three financial years from 2006/2007 to 2008/2009. These figures were compared to national data for the same parameters. RESULTS: The analysis of HSMR, ALOS and SRR reveal no significant difference in trend across three financial years when NHS North West is compared to England. HSMR and SRR within NHS North West continued to improve at a similar rate to the England average after August 2008. The ALOS analysis shows that NHS North West performed better than the national average for the majority of the study period, with no significant change in this pattern in the period following August 2008. When the HSMRs for NHS North West and England are compared against a fixed benchmark year (2005), the data shows a continuing decrease. The NHS North West figures follow the national trend closely at all times. CONCLUSION: The data presented in this study quantitatively demonstrates, for the first time, that implementation of the EWTD in NHS North West in August 2008 had no obvious adverse impact on key outcomes associated with patient safety and quality of care. Continued efforts will be required to address the challenge posed nationally by the restricted working hour's schedule.


Assuntos
Tempo de Internação/tendências , Programas Nacionais de Saúde/organização & administração , Assistência ao Paciente/normas , Readmissão do Paciente/tendências , Admissão e Escalonamento de Pessoal/organização & administração , Qualidade da Assistência à Saúde/normas , Inglaterra , Humanos , Assistência ao Paciente/mortalidade , Qualidade da Assistência à Saúde/organização & administração
11.
Cancer ; 116(20): 4727-34, 2010 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-20597135

RESUMO

BACKGROUND: Despite evidence of the importance of cervical cancer screening, screening rates in the United States remain below national prevention goals. Women in the Appalachia Ohio region have higher cervical cancer incidence and mortality rates along with lower cancer screening rates. This study explored the expectations of Appalachian Ohio women with regard to Papanicolaou (Pap) test cost and perceptions of cost as a barrier to screening. METHODS: Face-to-face interviews were conducted with 571 women who were part of a multilevel, observational community-based research program in Appalachia Ohio. Eligible women were identified through 14 participating health clinics and asked questions regarding Pap test cost and perceptions of cost as a barrier to screening. Estimates of medical costs were compared with actual costs reported by clinics. RESULTS: When asked about how much a Pap test would cost, 80% of the women reported they did not know. Among women who reportedly believed they knew the cost, 40% overestimated test cost. Women who noted cost as a barrier were twice as likely to not receive a test within screening guidelines as those who did not perceive a cost barrier. Furthermore, uninsured women were more than 8.5 times as likely to note cost as a barrier than women with private insurance. CONCLUSIONS: Although underserved women in need of cancer screening commonly report cost as a barrier, the findings of the current study suggest that women may have a very limited and often inaccurate understanding concerning Pap test cost. Providing women with this information may help reduce the impact of this barrier to screening.


Assuntos
Teste de Papanicolaou , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal/economia , Adolescente , Adulto , Região dos Apalaches , Detecção Precoce de Câncer , Feminino , Humanos , Seguro Saúde , Pessoa de Meia-Idade , Ohio , Percepção , Neoplasias do Colo do Útero/economia , Esfregaço Vaginal/estatística & dados numéricos
12.
J Bone Joint Surg Am ; 91(11): 2568-76, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19884429

RESUMO

BACKGROUND: The increased risk for venous thromboembolic events following spinal trauma is well established. The purpose of the present study was to examine the literature in order to determine the optimum thromboprophylaxis regimen for patients with acute spinal injuries with or without spinal cord injury. METHODS: EMBASE, MEDLINE, and Cochrane databases were searched from the earliest available date to April 2008 for clinical trials comparing different methods of thromboprophylaxis in adult patients following acute spinal injuries (with or without spinal cord injury). Outcome measures included the prevalences of deep-vein thrombosis and pulmonary embolism and treatment-related adverse events. RESULTS: The search yielded 489 studies, but only twenty-one of them fulfilled the inclusion criteria. The prevalence of deep-vein thrombosis was significantly lower in patients without spinal cord injury as compared with patients with spinal cord injury (odds ratio = 6.0; 95% confidence interval = 2.9 to 12.7). Patients with an acute spinal cord injury who were receiving oral anticoagulants had significantly fewer episodes of pulmonary embolism (odds ratio = 0.1; 95% confidence interval = 0.01 to 0.63) than those who were not receiving oral anticoagulants (either untreated controls or patients managed with low-molecular-weight heparin). The start of thromboprophylaxis within the first two weeks after the injury resulted in significantly fewer deep-vein-thrombosis events than delayed initiation did (odds ratio = 0.2; 95% confidence interval = 0.1 to 0.4). With regard to heparin-based pharmacoprophylaxis in patients with spinal trauma, low-molecular-weight heparin significantly reduced the rates of deep-vein thrombosis and bleeding episodes in comparison with the findings in patients who received unfractionated heparin, with odds ratios of 2.6 (95% confidence interval = 1.2 to 5.6) and 7.5 (95% confidence interval = 1.0 to 58.4) for deep-vein thrombosis and bleeding, respectively. CONCLUSIONS: The prevalence of deep-vein thrombosis following a spine injury is higher among patients who have a spinal cord injury than among those who do not have a spinal cord injury. Therefore, thromboprophylaxis in these patients should start as early as possible once it is deemed safe in terms of potential bleeding complications. Within this population, low-molecular-weight heparin is more effective for the prevention of deep-vein thrombosis, with fewer bleeding complications, than unfractionated heparin is. The use of vitamin K antagonists appeared to be effective for the prevention of pulmonary embolism.


Assuntos
Traumatismos da Medula Espinal/complicações , Traumatismos da Coluna Vertebral/complicações , Tromboembolia Venosa/prevenção & controle , Doença Aguda , Medicina Baseada em Evidências , Humanos
13.
J Clin Neurosci ; 15(10): 1176-9, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18710810

RESUMO

Intramedullary spinal cord neoplasms are relatively uncommon. The most common intramedullary tumors are astrocytomas and ependymomas. Meningiomas can occur as an intradural tumor; however, they are typically in the extramedullary compartment. A 42-year-old male presented with progressive sensory loss in the upper extremities and lower extremity weakness. Pre-operative imaging suggested an intramedullary cervical lesion. To treat the progressive neurological abnormality, surgical resection was planned. At surgery, it was noted that the tumor originated in the cervical spinal cord and extended into the extramedullary region. Histology confirmed the lesion to be a meningioma. This meningioma variant has not previously been described. Spinal meningiomas may occur in locations other than intradural, extramedullary locations, and should be included in the differential diagnosis of intramedullary lesions. Intramedullary meningiomas can be successfully treated with surgery.


Assuntos
Meningioma/patologia , Compressão da Medula Espinal/etiologia , Neoplasias da Medula Espinal/patologia , Adulto , Vértebras Cervicais , Descompressão Cirúrgica , Humanos , Masculino , Meningioma/complicações , Meningioma/cirurgia , Compressão da Medula Espinal/patologia , Compressão da Medula Espinal/cirurgia , Neoplasias da Medula Espinal/complicações , Neoplasias da Medula Espinal/cirurgia , Vértebras Torácicas , Resultado do Tratamento
14.
Clin Exp Allergy ; 37(4): 526-35, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17430349

RESUMO

BACKGROUND: There are few published studies on geographical variation in prevalence of eczema in adults or its association with recognised risk factors for allergic disease. OBJECTIVE: To describe the geographical variation in prevalence of eczema in adults, assess the associations with sociodemographic risk factors, serum-specific IgE and IgG, and exposure to allergen. METHODS: A community-based sample of 8206 adults aged 27-56 years, in 25 European centres and Portland, USA, provided questionnaire information on symptoms of eczema. Serum-specific IgE to house dust mite (HDM), cat, grass and Cladosporium, and IgG and IgG4 to HDM and cat were measured. Mattress levels of mite and cat allergen were assessed. RESULTS: Overall prevalence of eczema was 7.1% (range between countries of 2.2-17.6%). Eczema was associated with female gender [odds ratio (OR) 1.25; 95% confidence interval (CI) (1.01-1.55)], family history of atopic disease (OR 1.43; 95% CI 1.18-1.74), IgE sensitization to at least one allergen (OR 1.50; 95% CI 1.19-1.90), particularly Cladosporium (OR 3.65; 95% CI 1.81-7.37), and total IgE. Eczema was negatively associated with age and no clear associations were observed with sibship size, mattress mite and cat allergen levels or with cat and HDM-specific IgG or IgG4. CONCLUSIONS: There is geographical variation in the prevalence of eczema in adults both within and between countries. Although the disease is associated with IgE sensitization, in this study it was not related to mattress mite or cat allergen levels.


Assuntos
Alérgenos/administração & dosagem , Dermatite Atópica/epidemiologia , Eczema/epidemiologia , Adulto , Alérgenos/efeitos adversos , Alérgenos/imunologia , Antígenos de Dermatophagoides/imunologia , Proteínas de Artrópodes , Cisteína Endopeptidases , Dermatite Atópica/etiologia , Dermatite Atópica/imunologia , Eczema/etiologia , Eczema/imunologia , Exposição Ambiental/efeitos adversos , Europa (Continente)/epidemiologia , Feminino , Glicoproteínas/imunologia , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Prevalência
15.
Neurosurgery ; 49(4): 814-20; discussion 820-2, 2001 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11564241

RESUMO

OBJECTIVE: Carotid angioplasty with stent placement is becoming an established treatment modality for patients with high-risk carotid stenosis. Unlike carotid endarterectomy, angioplasty causes direct mechanical dilation of the stenotic carotid artery and bulb. Stimulation of the sinus baroreceptors induces a reflexive response that consists of increased parasympathetic discharge and inhibition of sympathetic tone, which results in bradycardia and subsequent cardiogenic hypotension. METHODS: At a single institution, the experience with 43 patients treated from November 1994 to January 2000 with 47 angioplasty and stent procedures for occlusive carotid artery disease was retrospectively reviewed. Prophylactic temporary venous pacemakers were used to prevent hypotension from possible angioplasty-induced bradycardia. Pacemakers were set to capture a heart rate decrease below 60 beats per minute. Variables analyzed included demographics, etiology of disease, side of the lesion, the presence of symptoms, history of coronary artery disease, percent stenosis, type of stent used, number of dilations, pressure of dilation, and angioplasty balloon diameter. RESULTS: Ten patients were excluded because pacemakers were not used during their angioplasty procedures, and these included three emergencies and a lesion that was unrelated anatomically to the carotid sinus (petrous carotid). The remaining 37 procedures were performed in 33 patients with a mean age of 67 years, and consisted of 17 men, 16 women, 20 right and 17 left-sided lesions. The pacemakers maintained a cardiac rhythm in 23 (62%) of the 37 procedures and in no case did the pacemaker fail to respond when activated. Recurrent (56%; 10 of 18), radiation-induced (78%; 7 of 9), and medically refractory carotid stenosis (67%; 6 of 9) required intraprocedural pacing. Two patients with recurrent stenosis became hypotensive despite the aid of the pacing device but were not symptomatic. Seventy-nine percent (15 of 19) of symptomatic lesions and 57% (8 of 14) of nonsymptomatic lesions required pacing, which was statistically significant (P = 0.049). No patient experienced an operative morbidity or mortality as a consequence of the temporary pacing devices. CONCLUSION: Angioplasty-induced bradycardia is a common condition, and it is more prevalent in radiation-induced stenosis and with symptomatic lesions. Temporary venous demand pacing is a safe procedure and may prevent life-threatening, baroreceptor-induced hypotension.


Assuntos
Angioplastia com Balão , Bradicardia/prevenção & controle , Estenose das Carótidas/terapia , Hipotensão/prevenção & controle , Marca-Passo Artificial , Idoso , Idoso de 80 Anos ou mais , Bradicardia/etiologia , Cateterismo Cardíaco , Feminino , Humanos , Hipotensão/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Stents
16.
J Immunol ; 165(8): 4397-404, 2000 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-11035077

RESUMO

The TNF receptor (TNFR) family plays a central role in the development of the immune response. Here we describe the reciprocal regulation of the recently identified TNFR superfamily member herpes virus entry mediator (HVEM) (TR2) and its ligand LIGHT (TL4) on T cells following activation and the mechanism of this process. T cell activation resulted in down-regulation of HVEM and up-regulation of LIGHT, which were both more pronounced in CD8(+) than CD4(+) T lymphocytes. The analysis of HVEM and LIGHT mRNA showed an increase in the steady state level of both mRNAs following stimulation. LIGHT, which was present in cytoplasm of resting T cells, was induced both in cytoplasm and at the cell surface. For HVEM, activation resulted in cellular redistribution, with its disappearance from cell surface. HVEM down-regulation did not rely on de novo protein synthesis, in contrast to the partial dependence of LIGHT induction. Matrix metalloproteinase inhibitors did not modify HVEM expression, but did enhance LIGHT accumulation at the cell surface. However, HVEM down-regulation was partially blocked by a neutralizing mAb to LIGHT or an HVEM-Fc fusion protein during activation. As a model, we propose that following stimulation, membrane or secreted LIGHT binds to HVEM and induces receptor down-regulation. Degradation or release of LIGHT by matrix metalloproteinases then contributes to the return to baseline levels for both LIGHT and HVEM. These results reveal a self-regulating ligand/receptor system that contributes to T cell activation through the interaction of T cells with each other and probably with other cells of the immune system.


Assuntos
Regulação para Baixo/imunologia , Ativação Linfocitária , Proteínas de Membrana/biossíntese , Receptores do Fator de Necrose Tumoral/antagonistas & inibidores , Receptores do Fator de Necrose Tumoral/biossíntese , Receptores Virais/antagonistas & inibidores , Receptores Virais/biossíntese , Simplexvirus/imunologia , Subpopulações de Linfócitos T/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/virologia , Separação Celular , Células Cultivadas , Cicloeximida/farmacologia , Inibidores Enzimáticos/farmacologia , Humanos , Ligantes , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas de Membrana/fisiologia , Metaloendopeptidases/antagonistas & inibidores , Metaloendopeptidases/fisiologia , Microscopia Confocal , Inibidores da Síntese de Proteínas/farmacologia , RNA Mensageiro/metabolismo , Receptores do Fator de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/metabolismo , Membro 14 de Receptores do Fator de Necrose Tumoral , Receptores Virais/genética , Receptores Virais/metabolismo , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/virologia , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/fisiologia , Regulação para Cima/imunologia
17.
J Biomol Screen ; 4(4): 205-214, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10838440

RESUMO

The herpes virus entry mediator (HVEM) receptor and its ligand, HVEM-L, are involved in both herpes simplex virus type-1 (HSV-1) herpes simplex virus type-2 (HSV-2) infection, and in T-cell activation such that antagonists of this interaction are expected to have utility in viral and inflammatory diseases. In this report we describe the configuration of a homogeneous 384-well assay based on time-resolved energy transfer from a europium chelate on the HVEM receptor to an allophycocyanin (APC) acceptor on the ligand. Specific time resolved emission from the acceptor is observed on receptor:ligand complex formation. The results of various direct and indirect labeling strategies are described. Several assay optimization experiments were necessary to obtain an assay that was robust to automation and file compound interference while sensitive to the effect of potential inhibitors. The signal was stable for more than 24 h at room temperature using the Eu(3+) chelates, suggesting no dissociation of the lanthanide ion. The 384-well assay was readily automated and was able to identify more than 99.5% of known positive controls in the validation studies successfully. Screening identified both a series of known potent inhibitors and several structural classes of hits that readily deconvoluted to yield single compound inhibitors with the desired functional activity in secondary biological assays. The equivalence of the data in 384- and 1536-well formats indicates that routine implementation of 1536-well chelate-based energy transfer screening appears to be primarily limited by liquid handling rather than detection issues.

18.
J Biol Chem ; 273(42): 27548-56, 1998 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-9765287

RESUMO

Herpesvirus entry mediator (HVEM), a member of the tumor necrosis factor (TNF) receptor family, mediates herpesvirus entry into cells during infection. Upon overexpression, HVEM activates NF-kappaB and AP-1 through a TNF receptor-associated factor (TRAF)-mediated mechanism. Using an HVEM-Fc fusion protein, we screened soluble forms of novel TNF-related proteins derived from an expressed sequence tag data base. One of these, which we designated HVEM-L, specifically bound to HVEM-Fc with an affinity of 44 nM. This association was confirmed with soluble and membrane forms of both receptor and ligand. HVEM-L mRNA is expressed in spleen, lymph nodes, macrophages, and T cells and encodes a 240-amino acid protein. A soluble, secreted form of the protein stimulates proliferation of T lymphocytes during allogeneic responses, inhibits HT-29 cell growth, and weakly stimulates NF-kappaB-dependent transcription.


Assuntos
Antineoplásicos/metabolismo , Substâncias de Crescimento/metabolismo , Proteínas de Membrana/metabolismo , Receptores do Fator de Necrose Tumoral/metabolismo , Receptores Virais/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Sequência de Aminoácidos , Antineoplásicos/farmacologia , Proteínas de Bactérias/metabolismo , Regulação da Expressão Gênica , Inibidores do Crescimento/metabolismo , Inibidores do Crescimento/farmacologia , Substâncias de Crescimento/farmacologia , Células HT29/efeitos dos fármacos , Humanos , Ligantes , Teste de Cultura Mista de Linfócitos , Proteínas de Membrana/genética , Proteínas de Membrana/farmacologia , Dados de Sequência Molecular , NF-kappa B/metabolismo , Ligação Proteica , Membro 14 de Receptores do Fator de Necrose Tumoral , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Homologia de Sequência de Aminoácidos , Linfócitos T/efeitos dos fármacos , Distribuição Tecidual , Fator de Transcrição AP-1/metabolismo , Membro 14 da Superfamília de Ligantes de Fatores de Necrose Tumoral , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/farmacologia
19.
J Immunol ; 161(4): 1786-94, 1998 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-9712045

RESUMO

TR2 (TNFR-related 2) is a recently identified member of the TNFR family with homology to TNFRII. We have demonstrated previously that TR2 mRNA is expressed in resting and activated human T cells and that TR2-Ig partially inhibits an allogeneic mixed leukocyte proliferation response. We now characterize TR2 further by the use of specific mAbs. Flow-cytometry analysis using TR2 mAbs confirmed that resting PBL express high levels of cell surface TR2, and that TR2 is widely expressed on all freshly isolated lymphocyte subpopulations. However, stimulation of purified T cells with either PHA or PHA plus PMA resulted in decreased surface expression within 48 h of activation before returning to resting levels at 72 h. TR2 mAbs inhibited CD4+ T cell proliferation in response to stimulation by immobilized CD3 or CD3 plus CD28 mAbs. Assay of culture supernatants by ELISA showed inhibition of TNF-alpha, IFN-gamma, IL-2, and IL-4 production, which, for IL-2 and TNF-alpha was also confirmed by intracellular cytokine staining. Furthermore, expression of activation markers on CD4+ T cells, including CD25, CD30, CD69, CD71, and OX40 (CD134), was inhibited. TR2 mAbs inhibited proliferation in a three-way MLR, and a response to soluble recall Ag, tetanus toxoid. In conclusion, these results suggest that TR2 is involved in the activation cascade of T cell responses and TR2 mAbs prevent optimal T cell proliferation, cytokine production, and expression of activation markers.


Assuntos
Anticorpos Bloqueadores/farmacologia , Anticorpos Monoclonais/farmacologia , Antígenos de Diferenciação de Linfócitos T/biossíntese , Citocinas/antagonistas & inibidores , Ativação Linfocitária/imunologia , Receptores do Fator de Necrose Tumoral/imunologia , Receptores Virais/imunologia , Linfócitos T/imunologia , Animais , Anticorpos Bloqueadores/metabolismo , Anticorpos Monoclonais/metabolismo , Afinidade de Anticorpos , Antígenos de Diferenciação de Linfócitos T/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linhagem Celular , Citocinas/biossíntese , Epitopos de Linfócito T/imunologia , Inibidores do Crescimento/farmacologia , Humanos , Imunossupressores/farmacologia , Teste de Cultura Mista de Linfócitos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Receptores de Antígenos de Linfócitos T/antagonistas & inibidores , Receptores de Antígenos de Linfócitos T/biossíntese , Receptores do Fator de Necrose Tumoral/biossíntese , Membro 14 de Receptores do Fator de Necrose Tumoral , Simplexvirus/imunologia , Solubilidade , Linfócitos T/citologia , Linfócitos T/metabolismo , Células Tumorais Cultivadas
20.
Neurosurg Focus ; 5(4): e14, 1998 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-17112213

RESUMO

Carotid endarterectomy for atherosclerotic occlusive disease has become the standard of care for the treatment of symptomatic and asymptomatic occlusive disease of the carotid bifurcation, based on the results of the North American Symptomatic Carotid Endarterectomy Trial, as well as the Asymptomatic Carotid Atherosclerosis Study. For surgical treatment to be of benefit, the perioperative complication rate for neurological events should be 6% or less in the symptomatic population and 3% or less in the asymptomatic group. The performance of carotid endarterectomy for recurrent stenosis and radiation-induced stenosis has reported neurological events ranging from 4 to 10%. It is in this particular population that carotid angioplasty and stent placement may play a role. The authors performed a retrospective analysis of 11 patients who underwent carotid angioplasty and stent placement for recurrent or radiation-induced stenosis. One patient in whom endarterectomy was performed by the vascular surgery service had a critical stenosis distal to the endarterectomy site and awoke with a neurological deficit. This patient underwent reexploration and placement of a stent in the artery distal to the arteriotomy site. The follow-up period ranged from 7 to 12 months. Patient age ranged from 65 to 77 years (mean 75 years). Five of eight patients underwent angioplasty and stent placement for recurrent atherosclerotic disease. Two patients had radiation-induced stenosis, and one patient had a stent placed intraoperatively. All patients, with the exception of the one who underwent intraoperative stent placement, had posttreatment stenoses of less than 15%. The surgical patient had a 30% residual stenosis distally. There were no intra- or postoperative transient ischemic attacks, major or minor strokes, or deaths. Patients who have recurrent or radiation-induced stenosis are potential candidates for angioplasty and stent placement. Before this can be recommended as an alternative to surgical correction, a longer follow-up period is required.

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