RESUMO
Complex tissues contain multiple cell types that are hierarchically organized within morphologically and functionally distinct compartments. Construction of engineered tissues with optimized tissue architecture has been limited by tissue fabrication techniques, which do not enable versatile microscale organization of multiple cell types in tissues of size adequate for physiological studies and tissue therapies. Here we present an 'Intaglio-Void/Embed-Relief Topographic molding' method for microscale organization of many cell types, including induced pluripotent stem cell-derived progeny, within a variety of synthetic and natural extracellular matrices and across tissues of sizes appropriate for in vitro, pre-clinical, and clinical studies. We demonstrate that compartmental placement of non-parenchymal cells relative to primary or induced pluripotent stem cell-derived hepatocytes, compartment microstructure, and cellular composition modulate hepatic functions. Configurations found to sustain physiological function in vitro also result in survival and function in mice for at least 4 weeks, demonstrating the importance of architectural optimization before implantation.
Assuntos
Fígado/anatomia & histologia , Engenharia Tecidual/métodos , Animais , Bovinos , Compartimento Celular , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Feminino , Hepatócitos/citologia , Hepatócitos/metabolismo , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Fígado/citologia , Camundongos , Camundongos Nus , Ratos , Células Estromais/citologia , Células Estromais/metabolismoRESUMO
Success of human myocardial tissue engineering for cardiac repair has been limited by adverse effects of scaffold materials, necrosis at the tissue core, and poor survival after transplantation due to ischemic injury. Here, we report the development of scaffold-free prevascularized human heart tissue that survives in vivo transplantation and integrates with the host coronary circulation. Human embryonic stem cells (hESCs) were differentiated to cardiomyocytes by using activin A and BMP-4 and then placed into suspension on a rotating orbital shaker to create human cardiac tissue patches. Optimization of patch culture medium significantly increased cardiomyocyte viability in patch centers. These patches, composed only of enriched cardiomyocytes, did not survive to form significant grafts after implantation in vivo. To test the hypothesis that ischemic injury after transplantation would be attenuated by accelerated angiogenesis, we created "second-generation," prevascularized, and entirely human patches from cardiomyocytes, endothelial cells (both human umbilical vein and hESC-derived endothelial cells), and fibroblasts. Functionally, vascularized patches actively contracted, could be electrically paced, and exhibited passive mechanics more similar to myocardium than patches comprising only cardiomyocytes. Implantation of these patches resulted in 10-fold larger cell grafts compared with patches composed only of cardiomyocytes. Moreover, the preformed human microvessels anastomosed with the rat host coronary circulation and delivered blood to the grafts. Thus, inclusion of vascular and stromal elements enhanced the in vitro performance of engineered human myocardium and markedly improved viability after transplantation. These studies demonstrate the importance of including vascular and stromal elements when designing human tissues for regenerative therapies.
Assuntos
Miócitos Cardíacos/transplante , Transplante de Células-Tronco/métodos , Animais , Diferenciação Celular , Células-Tronco Embrionárias/citologia , Células-Tronco Embrionárias/transplante , Feminino , Humanos , Miocárdio/citologia , Miócitos Cardíacos/citologia , Ratos , Ratos Sprague-Dawley , Engenharia Tecidual/métodos , Alicerces TeciduaisRESUMO
HYPOTHESIS: The adaptation of new techniques in treatment of epidermoid carcinoma of the anal canal during the past 3 decades has improved clinical outcomes. DESIGN: Retrospective consecutive case review. SETTING: A university hospital and Veterans Affairs medical center. PATIENTS: Medical records of 76 consecutive patients treated for invasive epidermoid cancer of the anal canal between 1970 and 1999 were reviewed. Twenty-one patients were excluded because of inadequate staging information and/or follow-up of less than 12 months. MAIN OUTCOME MEASURES: Locoregional recurrence, survival, colostomy-free survival, and morbidity. RESULTS: Fifty-five patients composed the study population. Ten were treated during decade 1 (1970-1979), 16 in decade 2 (1980-1989), and 29 in decade 3 (1990-1999). Mean age and sex distributions were similar. The prevailing primary treatment modality changed during the course of the study from sequential treatment (chemotherapy then radiation therapy then radical surgery) to concurrent chemoradiation (70% and 0% of cases, respectively, in decade 1 to 7% and 76% of cases, respectively, in decade 3). Locoregional control (50%, 81%, and 93%; P =.01), crude survival (median, 28, 30, and 76 months), and colostomy-free survival (mean, 13, 90, and 80 months) improved during the 3 decades. There were no differences in major complications during the 3 decades (40%, 56%, and 41%). CONCLUSION: Primary treatment with concurrent chemoradiation has improved the local recurrence, survival, and colostomy-free survival rates in patients with invasive epidermoid carcinoma of the anal canal without increasing major morbidity.
Assuntos
Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Adulto , Idoso , Neoplasias do Ânus/patologia , Neoplasias do Ânus/cirurgia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Quimioterapia Adjuvante , Colostomia , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Complicações Pós-Operatórias/etiologia , Radioterapia Adjuvante , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
This paper addresses implications of recent tobacco legislation, policy, and tobacco use among youth in the context of health care policy and services. Tobacco use prevalence and definitions and diagnoses of nicotine addiction and dependence are described. Assessment of smoking prevalence in Texas provides a case study of the problem and potential solutions for tobacco use among youth. The case study highlights specific implications to be considered when providing health care focused on prevention and risk reduction for youth. The paper concludes with implications and critical Internet resources for health care providers engaging in youth tobacco control.
Assuntos
Indústria Farmacêutica/legislação & jurisprudência , Política de Saúde/legislação & jurisprudência , Promoção da Saúde/legislação & jurisprudência , Fumar/legislação & jurisprudência , Adolescente , Comportamento do Adolescente , Comportamentos Relacionados com a Saúde , Humanos , Internet , Prevalência , Fumar/epidemiologia , Prevenção do Hábito de Fumar , Texas/epidemiologia , TabagismoRESUMO
Research utilization approaches in nursing recently have been replaced by evidence-based practice (EBP) approaches. The heart of the new EBP paradigm is the systematic review. Systematic reviews are carefully synthesized research evidence designed to answer focused clinical questions. Systematic reviews (also known as evidence summaries and integrative reviews) implement recently developed scientific methods to summarize results from multiple research studies. Specific strategies are required for success in locating systematic reviews. Major sources of systematic reviews for use by advanced practice nurses in acute and critical care are the Online Journal of Knowledge Synthesis for Nursing, Agency for Healthcare Research and Quality, and the Cochrane Library. This discussion describes systematic reviews as the pivotal point in today's paradigm of EBP and guides the advanced practice nurse in locating and accessing systematic reviews for use in practice.
Assuntos
Medicina Baseada em Evidências/métodos , Cuidados de Enfermagem , Literatura de Revisão como Assunto , Humanos , Serviços de Informação , Terminologia como AssuntoRESUMO
OBJECTIVE: To conduct a systematic review of evidence relating to management of mild chronic hypertension during pregnancy, including associated risks, benefits, and harms of treatment with antihypertensive agents, nonpharmacologic measures, and aspirin and benefits of various monitoring strategies. DATA SOURCES: Using four broad search strategies, we searched English and non-English-language citations in 16 electronic databases from their inception to February 1999 and consulted relevant textbooks, references, and experts. STUDY SELECTION: Reviewers screened 6228 abstracts and found 215 articles that met multiple prespecified patient selection, study population, and design criteria. TABULATION, INTEGRATION, AND RESULTS: Forty-six studies consistently showed that chronic hypertension triples the risk for perinatal mortality (odds ratio [OR] 3.4; 95% confidence interval [CI] 3.0, 3.7) and doubles the risk for placental abruption (OR 2.1; 95% CI 1.1, 3.9). Thirteen small, randomized controlled trials had inadequate power to rule in or rule out moderate-to-large (20%-50%) benefits of antihypertensive treatment. Possible adverse effects were fetal renal failure when angiotensin-converting enzyme inhibitors are used in the second or third trimester and growth restriction when atenolol is used early in pregnancy. Trials showed that aspirin neither reduces nor increases perinatal and maternal morbidity, but they did not rule out possible small-to moderate beneficial or adverse effects. No studies provide guidance on benefits or consequences of various nonpharmacologic therapies or monitoring strategies. CONCLUSION: Mild chronic hypertension is associated with increased maternal and fetal risks. Beneficial treatment and monitoring regimens are not clear, but some treatments, such as angiotensin-converting enzyme inhibitors, are best avoided.
Assuntos
Hipertensão/terapia , Complicações Cardiovasculares na Gravidez/terapia , Descolamento Prematuro da Placenta/etiologia , Anti-Hipertensivos/uso terapêutico , Doença Crônica , Feminino , Humanos , Hipertensão/tratamento farmacológico , Lactente , Mortalidade Infantil , Seleção de Pacientes , Gravidez , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Medição de RiscoAssuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Complicações Cardiovasculares na Gravidez/tratamento farmacológico , Adulto , Anti-Hipertensivos/efeitos adversos , Doença Crônica , Feminino , Humanos , Hipertensão/diagnóstico , Pessoa de Meia-Idade , Monitorização Fisiológica , Gravidez , Resultado da Gravidez , Prognóstico , Medição de RiscoRESUMO
BACKGROUND: Surgical resection of tongue base cancer can leave the patient with significant functional deficits. Other therapies, such as external beam radiation followed by neck dissection and radiation implants, have shown equal tumor control with good functional outcome. METHODS: Between March 1991 and July 1999, 12 patients at Oregon Health Sciences University, the Portland Veterans Administration Medical Center and West Virginia University School of Medicine Hospital were treated with external beam radiation followed by neck dissection and Ir192 implants. Two patients had T1 disease, two had T2, five patients had T3 tumors, and three had T4 tumors. Six had N2a necks, three had N2b necks, and three had N2c. Follow-up ranged from 13 months to 8 years. RESULTS: After external beam radiation, five patients had complete response and seven had partial response in the neck without complications. One patient underwent a unilateral radical neck dissection, eight had unilateral selective neck dissections involving levels I to IV, and three had dissections involving levels I to III. One of the five patients who had a complete clinical response in the neck had pathologically positive nodes. One patient had a pulmonary embolus that was treated and had no permanent sequelae. There were three complications from brachytherapy. Two patients had soft tissue necrosis at the primary site and one patient had radionecrosis of the mandible. All healed without further therapy. One patient had persistent disease and underwent a partial glossectomy but died of local disease. Distant metastasis developed in two patients. All others show no evidence of disease and are able to eat a normal diet by mouth. CONCLUSION: This combination of therapies should be considered when treating tongue base cancer.
Assuntos
Braquiterapia , Carcinoma de Células Escamosas/terapia , Esvaziamento Cervical , Neoplasias da Língua/terapia , Idoso , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Língua/patologia , Neoplasias da Língua/radioterapia , Resultado do TratamentoRESUMO
Cranial nerve damage following head and neck radiotherapy is an unusual event. Cranial neuropathy following concurrent chemotherapy and radiotherapy is unreported. The authors report a case of a 54-year-old man treated with curative chemotherapy and radiotherapy for a stage III nasopharyngeal carcinoma who developed an unilateral hypoglossal nerve palsy five years after therapy. Follow-up examination and magnetic resonance imaging (MRI) show no evidence of recurrent disease. Hypoglossal nerve injury occurring after head and neck radiotherapy is an indirect effect due to progressive soft tissue fibrosis and loss of vascularity. This process develops over years leading to nerve entrapment and permanent damage. Cranial nerve palsies, including damage to the hypoglossal nerve, can develop years after therapy with no evidence of tumour recurrence. Chemotherapy and radiotherapy have improved progression-free and overall survival in advanced nasopharyngeal cancer. As more patients achieve long-term tumour control following chemotherapy and radiotherapy, we must be cognizant of potential late injury to cranial nerves.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Doenças do Nervo Hipoglosso/etiologia , Neoplasias Nasofaríngeas/terapia , Lesões por Radiação/etiologia , Radioterapia de Alta Energia/efeitos adversos , Terapia Combinada , Seguimentos , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Basics of evidence-based practice are presented in 2 parts. Part 1 explores the characteristics of evidence used in evidence-based practice. Part 2 presents basic terms and processes of EBP. The nature of the evidence as the basis for clinical decisions is a major distinction between the new paradigm of evidence-based practice and yesterday's approaches to research utilization. This article discusses why research evidence is the best source of clinical knowledge, and why systematic reviews, in particular, provide the most stable knowledge for clinical practice. Sources of evidence summaries, such as Agency for Healthcare Research and Quality, are also discussed.
Assuntos
Medicina Baseada em Evidências , Enfermagem , Pesquisa , Bases de Dados Factuais , Medicina Baseada em Evidências/organização & administração , Medicina Baseada em Evidências/tendências , Humanos , Guias de Prática Clínica como Assunto , Estados UnidosRESUMO
Rapid developments within the enterprise of evidence-based health care have resulted in a state of flux in the related concepts and terminology. Basic processes include original research, evidence summary, translation, implementation, and evaluation. Together with a glossary of basic terms in evidence-based practice (EBP), these provide a basis for nurses to adopt evidence-based practice into clinical decision making.
Assuntos
Benchmarking/tendências , Medicina Baseada em Evidências , Pesquisa em Enfermagem , Medicina Baseada em Evidências/métodos , Medicina Baseada em Evidências/organização & administração , Medicina Baseada em Evidências/tendências , Humanos , Terminologia como AssuntoRESUMO
The implementation of evidence-based practice in perioperative nursing holds promise of improving quality of care and client outcomes. Several factors within health care have precipitated an emphasis on evidence-based practice. The use of research results in clinical decisions is recommended as the basis of nursing practice of the future. To assist with development of evidence-based practice in nursing, basic steps of the process are presented. In addition, strategies for locating existing evidence-based practice guidelines and resources are described. Perioperative nurse researchers and practice leaders should move this issue into a top priority for the specialty.
Assuntos
Medicina Baseada em Evidências , Pesquisa em Enfermagem/organização & administração , Enfermagem Perioperatória/métodos , Enfermagem Perioperatória/normas , Previsões , Humanos , Guias de Prática Clínica como AssuntoRESUMO
PURPOSE: To evaluate (a) the displacement of the vaginal apex by a rod during radiation therapy simulation for gynecologic malignancy and (b) apical localization with implanted radiopaque markers. MATERIALS AND METHODS: Metallic markers were implanted in the cervix or vaginal cuff in nine patients with cervical or endometrial carcinoma who underwent irradiation. In all but one patient, radiographs were obtained with and then without the vaginal rod. Displacement of the markers relative to bone landmarks was measured. The total displacement was the square root of the sum of the squares of displacement in each axial direction. RESULTS: All patients showed displacement of the cervical markers by the vaginal rod (mean total displacement, 1.9 cm; range, 0.6-3.6 cm). The greatest displacement was cephalic (mean, 1.5 cm; range, 0.5-2.4 cm). Anteroposterior displacement occurred in all patients but was not as predictable as cephalic displacement. Displacement was anterior in five of the eight patients, posterior in three patients, and lateral in four patients. CONCLUSION: Displacement of the vaginal apex and/or cervix with placement of the vaginal rod during simulation was marked in all patients. Use of implanted cervical markers to localize the vaginal apex or the cervix during simulation is more accurate than use of a vaginal rod.
Assuntos
Neoplasias do Endométrio/radioterapia , Planejamento da Radioterapia Assistida por Computador/instrumentação , Neoplasias do Colo do Útero/radioterapia , Vagina/efeitos da radiação , Adulto , Idoso , Neoplasias do Endométrio/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , Monitoramento de Radiação/instrumentação , Radiografia , Dosagem Radioterapêutica , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/diagnóstico por imagem , Vagina/diagnóstico por imagemRESUMO
PURPOSE: From 1986 to 1992, "eight-drugs-in-one-day" (8-in-1) chemotherapy both before and after radiation therapy (XRT) (54 Gy tumor/36 Gy neuraxis) was compared with vincristine, lomustine (CCNU), and prednisone (VCP) after XRT in children with untreated, high-stage medulloblastoma (MB). PATIENTS AND METHODS: Two hundred three eligible patients with an institutional diagnosis of MB were stratified by local invasion and metastatic stage (Chang T/M) and randomized to therapy. Median time at risk from study entry was 7.0 years. RESULTS: Survival and progression-free survival (PFS) +/- SE at 7 years were 55%+/-5% and 54%+/-5%, respectively. VCP was superior to 8-in-1 chemotherapy, with 5-year PFS rates of 63%+/-5% versus 45%+/-5%, respectively (P = .006). Upon central neuropathology review, 188 patients were confirmed as having MB and were the subjects for analyses of prognostic factors. Children aged 1.5 to younger than 3 years had inferior 5-year estimates of PFS, compared with children 3 years old or older (P = .0014; 32%+/-10% v 58%+/-4%, respectively). For MB patients 3 years of age or older, the prognostic effect of tumor spread (MO v M1 v M2+) on PFS was powerful (P = .0006); 5-year PFS rates were 70%+/-5%, 57%+/-10%, and 40%+/-8%, respectively. PFS distributions at 5 years for patients with M0 tumors with less than 1.5 cm2 of residual tumor, versus > or = 1.5 cm2 of residual tumor by scan, were significantly different (P = .023; 78%+/-6% v 54%+/-11%, respectively). CONCLUSION: VCP plus XRT is a superior adjuvant combination compared with 8-in-1 chemotherapy plus XRT. For patients with M0 tumors, residual tumor bulk (not extent of resection) is a predictor for PFS. Patients with M0 tumors, > or = 3 years with < or = 1.5 cm2 residual tumor, had a 78%+/-6% 5-year PFS rate. Children younger than 3 years old who received a reduced XRT dosage had the lowest survival rate.
Assuntos
Neoplasias Cerebelares/patologia , Meduloblastoma/patologia , Tumores Neuroectodérmicos Primitivos/patologia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Cerebelares/tratamento farmacológico , Neoplasias Cerebelares/radioterapia , Quimioterapia Adjuvante , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Meduloblastoma/tratamento farmacológico , Meduloblastoma/radioterapia , Metástase Neoplásica , Estadiamento de Neoplasias , Tumores Neuroectodérmicos Primitivos/tratamento farmacológico , Tumores Neuroectodérmicos Primitivos/radioterapia , Prognóstico , Análise de SobrevidaRESUMO
BACKGROUND: Human papillomaviruses (HPV) have been implicated in the etiology of anogenital squamous epithelial tumors. Of the 65 HPV strains, subtypes HPV-16 and HPV-18 frequently are associated with malignant conditions and are capable of transforming keratinocytes in vitro. However, additional cellular changes are necessary to confer tumorigenicity to HPV-infected cells. Secondary events implicated in the progression to malignancy include loss of tumor suppressor genes such as p53 and/or activation of cellular oncogenes such as c-rasHa. METHODS: Polymerase chain reaction (PCR) was used to identify HPV-16 or HPV-18 genetic sequence in primary penile squamous cell carcinoma and two inguinal lymph node metastases. p53 and c-rasHa loci were analyzed by sequencing of PCR-amplified genomic DNA. RESULTS: HPV-18 but not HPV-16 infection was found in the primary carcinoma and in inguinal metastases occurring 5 and 7 years after the initial lesion. Sequence analysis did not identify any p53 mutations in the primary carcinoma or its metastases. However, although the primary lesion and the 5-year metastasis encoded wild-type c-rasHa, the 7-year metastasis had a missense mutation within c-rasHa codon 61. CONCLUSIONS: To the authors' knowledge, this is the first report of an activating c-rasHa mutation associated with squamous cell carcinoma of the penis. The presence of activated c-rasHa in the second metastasis but not in the first metastasis or the primary lesion suggests that activation of c-rasHa may be a late event in the malignant progression of HPV-18-associated penile squamous cell carcinoma. Analysis of additional samples from primary lesions and their resultant metastases is necessary to elucidate the incidence and significance of c-rasHa activation in penile squamous cell carcinoma.
Assuntos
Carcinoma de Células Escamosas/genética , Regulação Neoplásica da Expressão Gênica , Genes ras , Mutação , Papillomaviridae/isolamento & purificação , Neoplasias Penianas/genética , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/virologia , DNA Viral/análise , Genes p53 , Humanos , Queratinas/análise , Masculino , Pessoa de Meia-Idade , Papillomaviridae/genética , Neoplasias Penianas/virologiaRESUMO
OBJECT: Ependymomas in children continue to generate controversy regarding their histological diagnosis and grading. optimal management, and possible prognostic factors. To increase our knowledge of these tumors the authors addressed these issues in a cohort of children with prospectively staged ependymomas treated with radiotherapy and chemotherapy. METHODS: Children between the ages of 2 and 17.3 years harboring an intracranial ependymoma confirmed by a central review of the tumor's pathological characteristics were treated according to Children's Cancer Group Protocol 921 from 1986 to 1992. Treatment following surgery and postoperative tumor staging (including brain computerized tomography or magnetic resonance [MR] imaging, spinal MR imaging or myelography, and cerebrospinal fluid cytological investigation) included craniospinal irradiation with a local boost to the primary tumor and patient randomization to receive adjuvant chemotherapy with either 1) CCNU, vincristine, and prednisone, or 2) the eight-drugs-in-1-day regimen. Centralized review of the tumor pathological characteristics revealed 20 ependymomas and 12 anaplastic ependymomas in the 32 children included in the study. Diagnoses made at the individual institutions included anaplastic (malignant) ependymoma (15 patients), ependymoma (four patients), ependymoblastoma (nine patients), ependymoastrocytoma (one patient), and primitive neuroectodermal tumor (three patients), which were discordant with the centralized review diagnosis in 22 of 32 cases. Only three of the 32 patients had metastatic disease (two with M and one with M3 stages). At surgery, 47% of tumors were estimated to be totally resected. Among the 14 of 17 patients who suffered a relapse and were evaluated for site of relapse, 10 (71%) had an isolated local relapse, three (21%) had concurrent local and metastatic relapse, and only one (7%) had an isolated metastatic relapse. Kaplan-Meier estimates of 5-year progression-free survival (PFS) and overall survival rates were 50 +/- 10% and 64 +/- 9%, respectively. CONCLUSIONS: Predictors of PFS duration included an estimate of the extent of resection made at surgery (total compared with less than total, p = 0.0001) and the amount of residual tumor on postoperative imaging as verified by centralized radiological review (< or = 1.5 cm2 compared with > 1.5 cm2, p < 0.0001). No other factors, including centrally reviewed tumor histopathological type, location, metastasis and tumor (M and T) stages, patient age, race, gender, or chemotherapy treatment regimen significantly correlated with PFS duration. The pattern of predominantly local relapse and the important influence of residual tumor or the extent of resection on PFS duration confirms a prevailing impression that local disease control is the major factor in the prediction of outcome of ependymoma. Survival rates were comparable with those reported by other investigators who have treated patients with similar doses of radiation and no chemotherapy.