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BACKGROUND: Binding of chemokines to glycosaminoglycans (GAGs) is classically described as initiating inflammatory cell migration and creating tissue chemokine gradients that direct local leukocyte chemotaxis into damaged or transplanted tissues. While chemokine-receptor binding has been extensively studied during allograft transplantation, effects of glycosaminoglycan (GAG) interactions with chemokines on transplant longevity are less well known. Here we examine the impact of interrupting chemokine-GAG interactions and chemokine-receptor interactions, both locally and systemically, on vascular disease in allografts. METHODOLOGY/PRINCIPAL FINDINGS: Analysis of GAG or CC chemokine receptor 2 (CCR2) deficiency were coupled with the infusion of viral chemokine modulating proteins (CMPs) in mouse aortic allograft transplants (n = 239 mice). Inflammatory cell invasion and neointimal hyperplasia were significantly reduced in N-deacetylase-N-sulfotransferase-1 (Ndst1(f/f)TekCre(+)) heparan sulfate (GAG)-deficient (Ndst1(-/-), p<0.044) and CCR2-deficient (Ccr2(-/-), p<0.04) donor transplants. Donor tissue GAG or CCR2 deficiency markedly reduced inflammation and vasculopathy, whereas recipient deficiencies did not. Treatment with three CMPs was also investigated; Poxviral M-T1 blocks CC chemokine receptor binding, M-T7 blocks C, CC, and CXC GAG binding, and herpesviral M3 binds receptor and GAG binding for all classes. M-T7 reduced intimal hyperplasia in wild type (WT) (Ccr2(+/+), p< or =0.003 and Ccr2(-/-), p
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Quimiocinas/metabolismo , Glicosaminoglicanos/metabolismo , Rechazo de Injerto/inmunología , Enfermedades Vasculares/inmunología , Enfermedades Vasculares/patología , Animales , Aorta/efectos de los fármacos , Aorta/patología , Aorta/trasplante , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Quimiocinas/farmacología , Modelos Animales de Enfermedad , Rechazo de Injerto/complicaciones , Rechazo de Injerto/enzimología , Hiperplasia , Inflamación/complicaciones , Inflamación/patología , Trasplante de Riñón , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Receptores CCR2/deficiencia , Receptores CCR2/metabolismo , Sulfotransferasas/deficiencia , Sulfotransferasas/metabolismo , Análisis de Supervivencia , Donantes de Tejidos , Trasplante Homólogo , Túnica Íntima/efectos de los fármacos , Túnica Íntima/patología , Enfermedades Vasculares/complicaciones , Enfermedades Vasculares/enzimología , Proteínas Virales/farmacologíaAsunto(s)
American Recovery and Reinvestment Act , Seguridad Computacional/legislación & jurisprudencia , Registros Electrónicos de Salud/legislación & jurisprudencia , Health Insurance Portability and Accountability Act , Informática Médica/legislación & jurisprudencia , Revelación/legislación & jurisprudencia , Registros Electrónicos de Salud/economía , Humanos , Difusión de la Información/legislación & jurisprudencia , Difusión de la Información/métodos , Informática Médica/economía , Estados UnidosRESUMEN
Serine protease inhibitors (serpins) regulate coagulation and inflammation. Heparin, a glycosaminoglycan, is an important cofactor for modulation of the inhibitory function of mammalian serpins. The secreted myxoma viral serpin, Serp-1 exerts profound anti-inflammatory activity in a wide range of animal models. Serp-1 anti-inflammatory and anti-atherogenic activity is dependent upon inhibition of the uPA / uPA receptor thrombolytic complex. We demonstrate here that heparin binds to Serp-1 and enhances Serp-1 inhibition of thrombin, a human pro-thrombotic serine protease, in vitro, altering inhibitory activity to a more predominant anti-thrombotic activity. Heparin also facilitates the simultaneous thrombin-mediated cleavage of Serp-1 and prevents formation of a serpin-typical SDS-resistant complex, implying mutual neutralization of Serp-1 and thrombin. In a cell-based assay, heparin facilitates Serp-1 reversal of cellular activation by stabilizing cellular membrane fluidity in thrombin-activated monocytes. In conclusion, heparin and other GAGs serve as cofactors enhancing Serp-1 regulation of local thrombotic and inflammatory pathways.
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Nurses increasingly use telephonic assessment and counseling to manage clients with a variety of chronic illnesses. This article describes a study designed to assess a group of telephonic nurse disease managers' teaching and adherence promotion skills during actual patient interactions. Nurse care managers showed improvements after training in four main counseling skills categories, with a decrease in time spent.
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Competencia Clínica/normas , Consejo/educación , Educación Continua en Enfermería/organización & administración , Personal de Enfermería/educación , Solución de Problemas , Teléfono , Enfermedad Crónica , Conducta Cooperativa , Consejo/normas , Diabetes Mellitus/prevención & control , Diabetes Mellitus/psicología , Promoción de la Salud/normas , Humanos , Capacitación en Servicio/organización & administración , Análisis Multivariante , Rol de la Enfermera/psicología , Relaciones Enfermero-Paciente , Auditoría de Enfermería , Investigación en Educación de Enfermería , Investigación en Evaluación de Enfermería , Personal de Enfermería/psicología , Educación del Paciente como Asunto/normas , Evaluación de Programas y Proyectos de Salud , Autocuidado , Tennessee , Factores de TiempoRESUMEN
BACKGROUND: Diabetes is a common disease with self-management a key aspect of care. Large prospective trials have shown that maintaining glycated hemoglobin less than 7% greatly reduces complications but translating this level of control into everyday clinical practice can be difficult. Intensive improvement programs are successful in attaining control in patients with type 2 diabetes, however, many patients experience glycemic relapse once returned to routine care. This early relapse is, in part, due to decreased adherence in self-management behaviors. OBJECTIVE: This paper describes the design of the Glycemic Relapse Prevention study. The purpose of this study is to determine the optimal frequency of maintenance intervention needed to prevent glycemic relapse. The primary endpoint is glycemic relapse, which is defined as glycated hemoglobin greater than 8% and an increase of 1% from baseline. METHODS: The intervention consists of telephonic contact by a nurse practitioner with a referral to a dietitian if indicated. This intervention was designed to provide early identification of self-care problems, understanding the rationale behind the self-care lapse and problem solve to find a negotiated solution. A total of 164 patients were randomized to routine care (least intensive), routine care with phone contact every three months (moderate intensity) or routine care with phone contact every month (most intensive). CONCLUSION: The baseline patient characteristics are similar across the treatment arms. Intervention fidelity analysis showed excellent reproducibility. This study will provide insight into the important but poorly understood area of glycemic relapse prevention.
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PURPOSE: The purpose of this feasibility study was to examine primary care pediatricians and a diabetes specialty team sharing the care of children with type 1 diabetes in a structured network. METHODS: A diabetes specialty team and 3 pediatric practice groups participated in training and shared care of patients with type 1 diabetes. The diabetes team-consisting of 1 pediatric endocrinologist, 2 nurses in advanced practice, and 1 master's-prepared registered dietitian-initiated therapy and self-management training for families; pediatricians implemented maintenance therapy. Role definitions, specially developed records, and a communication framework guided the interaction of providers. Satisfaction of families and pediatricians was assessed by questionnaire. The A1C level was used to assess patients' metabolic control. RESULTS: Twenty-nine patients accepted pediatrician referral, 25 kept initial training sessions, and 20 completed at least 1 year in the network. All 24 invited pediatricians participated, and 17 enrolled patients. All families who completed satisfaction surveys were highly satisfied with the network. Nineteen pediatricians completed end-of-study questions and were also highly positive about sharing care with the specialty team. The mean A1C value was near target levels or better the first year, and it rose during the second year. CONCLUSIONS: The study supports the feasibility of integrating general pediatrician and diabetes specialty services for children with type 1 diabetes. Larger studies are justified to assess the efficacy and effectiveness of shared care.
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Diabetes Mellitus Tipo 1/rehabilitación , Educación del Paciente como Asunto/organización & administración , Niño , Estudios de Factibilidad , Humanos , Aprendizaje , Grupo de Atención al Paciente , Derivación y ConsultaRESUMEN
INTRODUCTION: Despite instruction, many patients do not employ diabetes-related self-management skills recommended by health professionals. One problem suggested by research is that many health professionals do not often use teaching and counseling skills widely considered to be effective. Among these are specific skills that help health professionals conduct adherence-related assessments, brainstorm workable solutions to obstacles, collaborate during long-term follow-up, and provide effective direct instruction. METHODS: "Effective Patient Teaching and Problem Solving" was developed and taught in a block of 24 hours over 3 days to groups of health professionals. Course content emphasized 13 operationally defined skills in four major categories: (A) assessment, (B) brainstorming, (C) collaboration, and (D) direct instruction skills. To evaluate participants' (n = 33) use of the various skills, a standardized patient teaching exercise was videotaped at both the beginning and end of the course. RESULTS: Total mean scores increased significantly (t = 7.7, p < .001) from 1.8 to 2.5 on a scale that ranged from 1 to 5. Skills improved in all four major categories (p < .003). The length of teaching sessions did not change, lasting 13.2 minutes before the course and 13.6 minutes after the intervention. DISCUSSION: Health professionals play a crucial role in patient education but rarely receive training in effective teaching and counseling techniques. The "Effective Patient Teaching and Problem Solving" course improved several kinds of important skills. As standards of diabetes care for improved glycemic control become more widespread, and as health providers attempt not just to teach but also to help patients overcome considerable obstacles to consistent diabetes self-management, a premium will be placed on the ability of health professionals to counsel efficiently and effectively.
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Diabetes Mellitus/terapia , Educación Continua , Educación del Paciente como Asunto , Solución de Problemas , Autocuidado , Humanos , Ontario , TennesseeRESUMEN
The deleterious pleiotropic effects of an adaptive mutation may be ameliorated by one of two modes of evolution: (1) by replacement, in which an adaptive mutation with harmful pleiotropic effects is replaced by one that confers an equal benefit but at less cost; or (2) by compensatory evolution, in which natural selection favors modifiers at other loci that compensate for the deleterious effects of the mutant allele. In this study, we have measured the potential of these two modes of evolution to ameliorate the deleterious pleiotropic effects of resistance to the antibiotic rifampicin in the soil bacterium Bacillus subtilis. One approach was to measure the fitness cost of a series of spontaneous rifampicin-resistance mutations from each of several strains. The potential for amelioration by the replacement mode was estimated by the variation in fitness cost among the mutants of a single strain. Another approach was to introduce a series of different rifampicin-resistance alleles into a diversity of strains, and to measure the fitness cost of rifampicin resistance for each allele-by-strain combination. The potential for amelioration by the replacement mode was estimated by the variation in fitness costs among rifampicin-resistance alleles; the potential for compensatory evolution was estimated by variation in the fitness cost of rifampicin resistance among strains. This study has shown that the cost of rifampicin resistance may be ameliorated by both the compensatory and replacement modes.
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We have investigated the potential for genetic exchange by transformation within a Mojave Desert population of Bacillus subtilis. Almost all strains surveyed were competent for transformation, and the strains varied over almost three orders of magnitude in their levels of competence. This high degree of variation suggests that natural selection toward an optimal level of competence is, at most, very weak in this population. Six of 24 competent strains showed sexual isolation from laboratory strain 168 (i.e., heterogamic transformation was reduced). Direct crosses between selected pairs of Mojave strains indicated sexual isolation within the Mojave population. Levels of sexual isolation observed within this population of B. subtilis were much less than those previously observed for transformation between named Bacillus species. Sexual isolation between 168 and Mojave strains, and among Mojave strains, was due to differences in restriction-modification systems and to DNA sequence divergence.