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1.
Res Sq ; 2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38746125

RESUMEN

Chronic Obstructive Pulmonary Disease (COPD) is a common, costly, and morbid condition. Pulmonary rehabilitation, close monitoring, and early intervention during acute exacerbations of symptoms represent a comprehensive approach to improve outcomes, but the optimal means of delivering these services is uncertain. Logistical, financial, and social barriers to providing healthcare through face-to-face encounters, paired with recent developments in technology, have stimulated interest in exploring alternative models of care. The Healthy at Home study seeks to determine the feasibility of a multimodal, digitally enhanced intervention provided to participants with COPD longitudinally over six months. This paper details the recruitment, methods, and analysis plan for the study, which is recruiting 100 participants in its pilot phase. Participants were provided with several integrated services including a smartwatch to track physiological data, a study app to track symptoms and study instruments, access to a mobile integrated health program for acute clinical needs, and a virtual comprehensive pulmonary support service. Participants shared physiologic, demographic, and symptom reports, electronic health records, and claims data with the study team, facilitating a better understanding of their symptoms and potential care needs longitudinally. The Healthy at Home study seeks to develop a comprehensive digital phenotype of COPD by tracking and responding to multiple indices of disease behavior and facilitating early and nuanced responses to changes in participants' health status. This study is registered at Clinicaltrials.gov (NCT06000696).

2.
Front Public Health ; 11: 1271162, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37915810

RESUMEN

The SARS CoV-2 (COVID-19) pandemic presented unprecedented challenges as communities attempted to respond to the administration of a novel vaccine that faced cold chain logistical requirements and vaccine hesitancy among many, as well as complicated phased rollout plans that changed frequently as availability of the vaccine waxed and waned. The COVID-19 pandemic also disproportionately affected communities of color and communities with barriers to accessing healthcare. In the setting of these difficulties, a program was created specifically to address inequity in vaccine administration with a focus on communities of color and linguistic diversity as well as those who had technological barriers to online sign-up processes common at mass vaccination sites. This effort, the Mobile Vaccine Equity Enhancement Program (MVeeP), delivered over 12,000 vaccines in 24 months through a reproducible set of practices that can inform equity-driven vaccine efforts in future pandemics.


Asunto(s)
COVID-19 , Vacunas , Humanos , Pandemias , Vacunación Masiva , Vacunación , COVID-19/prevención & control
3.
Sci Adv ; 8(7): eabj7377, 2022 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-35179956

RESUMEN

To what extent do individuals' perceptions of legitimacy affect their intrinsic motivations to comply with an authority? Answering this question has critical implications for law enforcement but is challenging because actions or institutions that affect intrinsic motivations typically also affect extrinsic, material ones. To disentangle these, we propose an experimental approach that separately identifies the effect of an authority's costly action to improve enforcement fairness on citizen behavior through both intrinsic and extrinsic channels. In experiment 1, the authority's simple attempt to institute fairer enforcement increases prosocial behavior by 10 to 12 percentage points via the intrinsic channel. A follow-up experiment demonstrates that this is not motivated by citizen attempts to "pay back" authorities. Our findings provide causally credible evidence that an authority's actions can directly shape citizens' behavior by enhancing her legitimacy and have important implications in policy domains where this conflicts with other incentives.

4.
Front Public Health ; 9: 695442, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34277553

RESUMEN

The COVID-19 pandemic caused more than 30 million infections in the United States between March 2020 and April 2021. In response to systemic disparities in SARS-CoV2 testing and COVID-19 infections, health systems, city leaders and community stakeholders in Worcester, Massachusetts created a citywide Equity Task Force with a specific goal of making low-barrier testing available to individuals throughout our community. Within months, the state of Massachusetts announced the Stop the Spread campaign, a state-funded testing venture. With this funding, and through our community-based approach, our team tested more than 48,363 individuals between August 3, 2020 and February 28, 2021. Through multiple PDSA (Plan-Do-Study-Act) cycles, we optimized our process to test close to 300 individuals per hour. Our positivity rate ranged from 1.5% with our initial testing events to a high of 13.4% on January 6, 2021. During the challenges of providing traditional inpatient and ambulatory care during the pandemic, our health system, city leadership, and community advocacy groups united to broaden the scope of care to include widespread, population-based SARS-CoV2 testing. We anticipate that the lessons learned in conducting this testing campaign can be applied to further surges of SARS-CoV2, international environments, and future respiratory disease pandemics.


Asunto(s)
COVID-19 , ARN Viral , Humanos , Massachusetts/epidemiología , Pandemias/prevención & control , SARS-CoV-2 , Estados Unidos/epidemiología
5.
J Surg Res ; 257: 203-212, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32858321

RESUMEN

BACKGROUND: Hibernating American black bears have significantly different clotting parameters than their summer active counterparts, affording them protection against venous thromboembolism during prolonged periods of immobility. We sought to evaluate if significant differences exist between the expression of microRNAs in the plasma of hibernating black bears compared with their summer active counterparts, potentially contributing to differences in hemostasis during hibernation. MATERIALS AND METHODS: MicroRNA sequencing was assessed in plasma from 21 American black bears in summer active (n = 11) and hibernating states (n = 10), and microRNA signatures during hibernating and active state were established using both bear and human genome. MicroRNA targets were predicted using messenger RNA (mRNA) transcripts from black bear kidney cells. In vitro studies were performed to confirm the relationship between identified microRNAs and mRNA expression, using artificial microRNA and human liver cells. RESULTS: Using the bear genome, we identified 15 microRNAs differentially expressed in the plasma of hibernating black bears. Of these microRNAs, three were significantly downregulated (miR-141-3p, miR-200a-3p, and miR-200c-3p), were predicted to target SERPINC1, the gene for antithrombin, and demonstrated regulatory control of the gene mRNA expression in cell studies. CONCLUSIONS: Our findings suggest that the hibernating black bears' ability to maintain hemostasis and achieve protection from venous thromboembolism during prolonged periods of immobility may be due to changes in microRNA signatures and possible upregulation of antithrombin expression.


Asunto(s)
Hemostasis/genética , Hibernación/genética , MicroARNs/metabolismo , Ursidae/genética , Tromboembolia Venosa/genética , Animales , Antitrombina III/genética , Línea Celular Tumoral , Femenino , Silenciador del Gen , Hepatocitos , Humanos , Masculino , MicroARNs/sangre , Estaciones del Año , Regulación hacia Arriba , Ursidae/sangre , Tromboembolia Venosa/prevención & control
8.
Acad Emerg Med ; 20(11): 1156-63, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-24238319

RESUMEN

OBJECTIVES: The objective was to test the generalizability, across a range of hospital sizes and demographics, of a previously developed method for predicting and aggregating, in real time, the probabilities that emergency department (ED) patients will be admitted to a hospital inpatient unit. METHODS: Logistic regression models were developed that estimate inpatient admission probabilities of each patient upon entering an ED. The models were based on retrospective development (n = 4,000 to 5,000 ED visits) and validation (n = 1,000 to 2,000 ED visits) data sets from four heterogeneous hospitals. Model performance was evaluated using retrospective test data sets (n = 1,000 to 2,000 ED visits). For one hospital the developed model also was applied prospectively to a test data set (n = 910 ED visits) coded by triage nurses in real time, to compare results to those from the retrospective single investigator-coded test data set. RESULTS: The prediction models for each hospital performed reasonably well and typically involved just a few simple-to-collect variables, which differed for each hospital. Areas under receiver operating characteristic curves (AUC) ranged from 0.80 to 0.89, R(2) correlation coefficients between predicted and actual daily admissions ranged from 0.58 to 0.90, and Hosmer-Lemeshow goodness-of-fit statistics of model accuracy had p > 0.01 with one exception. Data coded prospectively by triage nurses produced comparable results. CONCLUSIONS: The accuracy of regression models to predict ED patient admission likelihood was shown to be generalizable across hospitals of different sizes, populations, and administrative structures. Each hospital used a unique combination of predictive factors that may reflect these differences. This approach performed equally well when hospital staff coded patient data in real time versus the research team retrospectively.


Asunto(s)
Servicio de Urgencia en Hospital/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Admisión del Paciente/estadística & datos numéricos , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Triaje , Estados Unidos
9.
J Inflamm (Lond) ; 8: 4, 2011 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-21352551

RESUMEN

BACKGROUND: Bacterial endotoxin, long recognized as a potent pro-inflammatory mediator in acute infectious processes, has more recently been identified as a risk factor for atherosclerosis and other cardiovascular diseases. When endotoxin enters the bloodstream, one of the first cells activated is the circulating monocyte, which exhibits a wide range of pro-inflammatory responses. METHODS: We studied the effect of low doses of E. coli LPS on IL-8 release and superoxide formation by freshly isolated human peripheral blood mononuclear cells (PBMC). RESULTS: IL-8 release was consistently detectable at 10 pg/ml of endotoxin, reaching a maximum at 1 ng/ml, and was exclusively produced by monocytes; the lymphocytes neither produced IL-8, nor affected monocyte IL-8 release. Superoxide production was detectable at 30 pg/ml of endotoxin, reaching a maximum at 3 ng/ml. Peak respiratory burst activity was seen at 15-20 min, and superoxide levels returned to baseline by 1 h. IL-8 release was dependent on both membrane-associated CD14 (mCD14) and Toll-like receptor 4 (TLR4. Superoxide production was dependent on the presence of LBP, but was not significantly affected by a blocking antibody to TLR4. Moreover, treatment with lovastatin inhibited LPS-dependent IL-8 release and superoxide production. CONCLUSIONS: These findings suggest that IL-8 release and the respiratory burst are regulated by distinct endotoxin-dependent signaling pathways in PBMC in low level of endotoxin exposure. Selectively modulating these pathways could lead to new approaches to treat chronic inflammatory diseases, such as atherosclerosis, while preserving the capacity of monocytes to respond to acute bacterial infections.

10.
Ann Emerg Med ; 54(4): 504-10, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-19423187

RESUMEN

STUDY OBJECTIVE: We describe the effects of Lean, a process improvement strategy pioneered by Toyota, on quality of care in 4 emergency departments (EDs). METHODS: Participants in 2 academic and 2 community EDs that instituted Lean as their single process improvement strategy made observations of their behavioral changes over time. They also measured the following metrics related to patient flow, service, and growth from before and after implementation: time from ED arrival to ED departure (length of stay), patient satisfaction, percentage of patients who left without being seen by a physician (2 EDs), the time from ordering to reading radiographs (1 ED), and changes in patient volume. RESULTS: One year post-Lean, length of stay was reduced in 3 of the EDs despite an increase in patient volume in all 4. Each observed an increase of patient satisfaction lagging behind by at least a year. The narratives indicate that the closer Lean implementation was to the original Toyota principles, the better the initial outcomes. The immediate results were also greater in the EDs in which the frontline workers were actively participating in the Lean-driven process changes. A factor that considerably affected the outcomes in the second and third year postimplementation was the level of continuous leadership commitment to Lean. CONCLUSION: Lean principles adapted to the local culture of care delivery can lead to behavioral changes and sustainable improvements in quality of care metrics in the ED. These improvements are not universal and are affected by leadership and frontline workforce engagement.


Asunto(s)
Servicio de Urgencia en Hospital/organización & administración , Participación en las Decisiones , Estudios de Casos Organizacionales , Evaluación de Procesos, Atención de Salud , Hospitales Comunitarios/organización & administración , Hospitales de Enseñanza/organización & administración , Humanos , Tiempo de Internación , Innovación Organizacional , Satisfacción del Paciente , Estados Unidos
11.
Circ Res ; 104(4): 541-9, 2009 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-19122178

RESUMEN

Adipose tissue depots originate from distinct precursor cells, are functionally diverse, and modulate disease processes in a depot-specific manner. However, the functional properties of perivascular adipocytes, and their influence on disease of the blood vessel wall, remain to be determined. We show that human coronary perivascular adipocytes exhibit a reduced state of adipocytic differentiation as compared with adipocytes derived from subcutaneous and visceral (perirenal) adipose depots. Secretion of antiinflammatory adiponectin is markedly reduced, whereas that of proinflammatory cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1, is markedly increased in perivascular adipocytes. These depot-specific differences in adipocyte function are demonstrable in both freshly isolated adipose tissues and in vitro-differentiated adipocytes. Murine aortic arch perivascular adipose tissues likewise express lower levels of adipocyte-associated genes as compared with subcutaneous and visceral adipose tissues. Moreover, 2 weeks of high-fat feeding caused further reductions in adipocyte-associated gene expression, while upregulating proinflammatory gene expression, in perivascular adipose tissues. These changes were observed in the absence of macrophage recruitment to the perivascular adipose depot. We conclude that perivascular adipocytes exhibit reduced differentiation and a heightened proinflammatory state, properties that are intrinsic to the adipocytes residing in this depot. Dysfunction of perivascular adipose tissue induced by fat feeding suggests that this unique adipose depot is capable of linking metabolic signals to inflammation in the blood vessel wall.


Asunto(s)
Adipocitos/inmunología , Adipogénesis , Tejido Conectivo/inmunología , Grasas de la Dieta/efectos adversos , Mediadores de Inflamación/metabolismo , Grasa Intraabdominal/inmunología , Grasa Subcutánea/inmunología , Adipocitos/patología , Adipogénesis/genética , Adiponectina/metabolismo , Tejido Adiposo Pardo/inmunología , Animales , Aorta Torácica/inmunología , Aterosclerosis/inmunología , Proteína alfa Potenciadora de Unión a CCAAT/metabolismo , Forma de la Célula , Células Cultivadas , Quimiocina CCL2/metabolismo , Tejido Conectivo/patología , Vasos Coronarios/inmunología , Proteínas de Unión a Ácidos Grasos/metabolismo , Regulación de la Expresión Génica , Humanos , Inflamación/inmunología , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Grasa Intraabdominal/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Modelos Animales , PPAR gamma/metabolismo , Fenotipo , Grasa Subcutánea/patología , Factores de Tiempo
12.
J Emerg Med ; 37(2): 177-82, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18722732

RESUMEN

BACKGROUND: "Lean" is a set of principles and techniques that drive organizations to continually add value to the product they deliver by enhancing process steps that are necessary, relevant, and valuable while eliminating those that fail to add value. Lean has been used in manufacturing for decades and has been associated with enhanced product quality and overall corporate success. OBJECTIVES: To evaluate whether the adoption of Lean principles by an Emergency Department (ED) improves the value of emergency care delivered. METHODS: Beginning in December 2005, we implemented a variety of Lean techniques in an effort to enhance patient and staff satisfaction. The implementation followed a six-step process of Lean education, ED observation, patient flow analysis, process redesign, new process testing, and full implementation. Process redesign focused on generating improvement ideas from frontline workers across all departmental units. Value-based and operational outcome measures, including patient satisfaction, expense per patient, ED length of stay (LOS), and patient volume were compared for calendar year 2005 (pre-Lean) and periodically after 2006 (post-Lean). RESULTS: Patient visits increased by 9.23% in 2006. Despite this increase, LOS decreased slightly and patient satisfaction increased significantly without raising the inflation adjusted cost per patient. CONCLUSIONS: Lean improved the value of the care we delivered to our patients. Generating and instituting ideas from our frontline providers have been the key to the success of our Lean program. Although Lean represents a fundamental change in the way we think of delivering care, the specific process changes we employed tended to be simple, small procedure modifications specific to our unique people, process, and place. We, therefore, believe that institutions or departments aspiring to adopt Lean should focus on the core principles of Lean rather than on emulating specific process changes made at other institutions.


Asunto(s)
Eficiencia Organizacional , Evaluación de Procesos, Atención de Salud , Gestión de la Calidad Total/métodos , Centros Traumatológicos/organización & administración , Implementación de Plan de Salud , Hospitales Rurales , Humanos , Medio Oeste de Estados Unidos , Satisfacción del Paciente
13.
J Theor Biol ; 254(3): 650-4, 2008 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-18656491

RESUMEN

The expected utility theory of decision making under uncertainty, a cornerstone of modern economics, assumes that humans linearly weight "utilities" for different possible outcomes by the probabilities with which these outcomes occur. Despite the theory's intuitive appeal, both from normative and from evolutionary perspectives, many experiments demonstrate systematic, though poorly understood, patterns of deviation from EU predictions. This paper offers a novel theoretical account of such patterns of deviation by demonstrating that EU violations can emerge from evolutionary selection when individual "status" affects inclusive fitness. In humans, battles for resources and social standing involve high-stakes decision making, and assortative mating ensures that status matters for fitness outcomes. The paper therefore proposes grounding the study of decision making under uncertainty in an evolutionary game-theoretic framework.


Asunto(s)
Conducta de Elección , Toma de Decisiones , Selección Genética , Teoría del Juego , Humanos , Modelos Genéticos , Modelos Psicológicos , Medio Social
14.
Resuscitation ; 78(1): 77-84, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18406036

RESUMEN

BACKGROUND: Induced external hypothermia during ventricular fibrillation (VF) improves resuscitation outcomes. Our objectives were twofold (1) to determine if very rapid hypothermia could be achieved by intrapulmonary administration of cold perfluorocarbons (PFC), thereby using the lungs as a vehicle for targeted cardiopulmonary hypothermia, and (2) to determine if this improved resuscitation success. METHODS: Part 1: Nine female swine underwent static intrapulmonary instillation of cold perfluorocarbons (PFC) during electrically induced VF. Part 2: Thirty-three female swine in VF were immediately ventilated via total liquid ventilation (TLV) with pre-oxygenated cold PFC (-15 degrees C) or warm PFC (33 degrees C), while control swine received no ventilation during VF. All swine in both Parts 1 and 2 underwent VF arrest for 11 min, then defibrillation, ventilation and closed chest massage until resumption of spontaneous circulation (ROSC). The endpoint was continued spontaneous circulation for 1h without pharmacologic support. RESULTS: Static intrapulmonary instillation of cold PFC achieved rapid cardiopulmonary hypothermia; pulmonary artery (PA) temperature of 33.5+/-0.2 degrees C was achieved by 10 min. Nine of 9 achieved ROSC. Hypothermia was achieved faster using TLV: at 6 min VF, cold TLV temperature was 32.9+/-0.4 degrees C vs. cold static instillation temperature 34.3+/-0.2 degrees C. Nine of 11 cold TLV swine achieved ROSC for 1h vs. 3 of 11 control swine (p=0.03). Warm PFC also appeared to be beneficial, with a trend toward greater achievement of ROSC than control (ROSC; warm PFC 8 of 11 vs. control 3 of 11, p=0.09). CONCLUSION: Targeted cardiopulmonary intra-arrest moderate hypothermia was achieved rapidly by static intrapulmonary administration of cold PFC and more rapidly by total liquid ventilation with cold PFC; resumption of spontaneous circulation was facilitated. Warm PFC showed a trend toward facilitating ROSC.


Asunto(s)
Fluorocarburos/administración & dosificación , Paro Cardíaco/terapia , Hipotermia Inducida/métodos , Ventilación Liquida/métodos , Animales , Modelos Animales de Enfermedad , Estudios de Factibilidad , Femenino , Modelos Lineales , Método de Montecarlo , Estadísticas no Paramétricas , Porcinos
15.
Peptides ; 29(1): 83-92, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18082911

RESUMEN

Enkephalins are opioid peptides that are found at high levels in the brain and endocrine tissues. Studies have shown that enkephalins play an important role in behavior, pain, cardiac function, cellular growth, immunity, and ischemic tolerance. Our global hypothesis is that enkephalins are released from non-neuronal tissues in response to brief ischemia or exercise, and that this release contributes to cardioprotection. To identify tissues that could serve as potential sources of enkephalins, we used real-time PCR, Western blot analysis, ELISA, immunofluorescence microscopy, and ex vivo models of enkephalin release. We found widespread expression of preproenkephalin (pPENK) mRNA and production of the enkephalin precursor protein proenkephalin (PENK) in rat and mouse tissues, as well as in tissues and cells from humans and pigs. Immunofluorescence microscopy with anti-enkephalin antisera demonstrated immunoreactivity in rat tissues, including heart and skeletal muscle myocytes, intestinal and kidney epithelium, and intestinal smooth muscle cells. Finally, isolated tissue studies showed that heart, skeletal muscle, and intestine released enkephalins ex vivo. Together our studies indicate that multiple non-neuronal tissues produce PENK and release enkephalins. These data support the hypothesis that non-neuronal tissues could play a role in both local and systemic enkephalin-mediated effects.


Asunto(s)
Encefalinas/metabolismo , Perfilación de la Expresión Génica , Precursores de Proteínas/genética , Animales , Western Blotting , Encefalinas/biosíntesis , Encefalinas/química , Encefalinas/genética , Ensayo de Inmunoadsorción Enzimática , Epitelio/metabolismo , Corazón/fisiología , Humanos , Mucosa Intestinal/metabolismo , Intestinos/citología , Riñón/citología , Riñón/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Microscopía Confocal , Persona de Mediana Edad , Músculo Esquelético/citología , Músculo Esquelético/metabolismo , Músculo Liso/citología , Músculo Liso/metabolismo , Precursores de Proteínas/biosíntesis , Precursores de Proteínas/química , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Porcinos
16.
Am J Physiol Heart Circ Physiol ; 294(1): H402-8, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17951371

RESUMEN

Exercise increases serum opioid levels and improves cardiovascular health. Here we tested the hypothesis that opioids contribute to the acute cardioprotective effects of exercise using a rat model of exercise-induced cardioprotection. For the standard protocol, rats were randomized to 4 days of treadmill training and 1 day of vigorous exercise (day 5), or to a sham exercise control group. On day 6, animals were killed, and global myocardial ischemic tolerance was assessed on a modified Langendorff apparatus. Twenty minutes of ischemia followed by 3 h of reperfusion resulted in a mean infarct size of 42 +/- 4% in hearts from sham exercise controls and 21 +/- 3% (P < 0.001) in the exercised group. The cardioprotective effects of exercise were gone by 5 days after the final exercise period. To determine the role of opioid receptors in exercise-induced cardioprotection, rats were exercised according to the standard protocol; however, just before exercise on days 4 and 5, rats were injected subcutaneously with 10 mg/kg of the opioid receptor antagonist naltrexone. Similar injections were performed in the sham exercise control group. Naltrexone had no significant effect on baseline myocardial ischemic tolerance in controls (infarct size 43 +/- 4%). In contrast, naltrexone treatment completely blocked the cardioprotective effect of exercise (infarct size 40 +/- 5%). Exercise was also associated with an early increase in myocardial mRNA levels for several opioid system genes and with sustained changes in a number of genes that regulate inflammation and apoptosis. These findings demonstrate that the acute cardioprotective effects of exercise are mediated, at least in part, through opioid receptor-dependent mechanisms that may include changes in gene expression.


Asunto(s)
Isquemia Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/prevención & control , Miocardio/metabolismo , Péptidos Opioides/metabolismo , Esfuerzo Físico , Precursores de Proteínas/metabolismo , Receptores Opioides/metabolismo , Animales , Apoptosis/genética , Modelos Animales de Enfermedad , Expresión Génica , Inflamación/genética , Inflamación/metabolismo , Masculino , Isquemia Miocárdica/complicaciones , Isquemia Miocárdica/genética , Isquemia Miocárdica/metabolismo , Isquemia Miocárdica/patología , Daño por Reperfusión Miocárdica/etiología , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/patología , Miocardio/patología , Naltrexona/farmacología , Antagonistas de Narcóticos/farmacología , Péptidos Opioides/genética , Precursores de Proteínas/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Receptores Opioides/genética , Factores de Tiempo
17.
Microb Drug Resist ; 12(2): 126-9, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-16922629

RESUMEN

Urinary tract infections (UTIs) represent a common infection in the pediatric population. Escherichia coli is the most common uropathogen in children, and antimicrobial resistance in this species complicates the treatment of pediatric UTIs. Despite the impact of resistance on empiric antibiotic choice, there is little data on multidrug resistance in pediatric patients. In this paper, we describe characteristics of multidrug-resistant E. coli in pediatric patients using a large national database of uropathogens antimicrobial sensitivities. Antimicrobial susceptibility patterns to commonly prescribed antibiotics were performed on uropathogens isolated from children presenting to participating hospitals between 1999 and 2001. Data were analyzed separately for four pediatric age groups. Single and multidrug resistance to ampicillin, amoxicillin-clavulanate, cefazolin, ciprofloxacin, nitrofurantoin, and trimethoprim-sulfamethoxazole (TMP-SMX) were performed on all specimens. There were a total of 11,341 E. coli urine cultures from 343 infants (0-4 weeks), 1,801 toddlers (5 weeks-24 months), 6,742 preteens (2-12 years), and 2,455 teens (13-17 years). E. coli resistance to ampicillin peaked in toddlers (52.8%) but was high in preteens (52.1%), infants (50.4%), and teens (40.6%). Resistance to two or more antibiotics varied across age groups, with toddlers (27%) leading preteens (23.1%), infants (21%), and teens (15.9%). Resistance to three or more antibiotics was low in all age groups (range 3.1-5.2%). The most common co-resistance in all age groups was ampicillin/TMP-SMZ. In conclusion, less than half of all pediatric UTIs are susceptible to all commonly used antibiotics. In some age groups, there is a significant percentage of co-resistance between the two most commonly used antibiotics (ampicillin and TMP-SMZ).


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple , Escherichia coli/efectos de los fármacos , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Adolescente , Niño , Preescolar , Escherichia coli/aislamiento & purificación , Humanos , Lactante , Recién Nacido
18.
Acad Emerg Med ; 13(8): 813-9, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16766738

RESUMEN

BACKGROUND: Acute myocardial ischemia is an important cause of morbidity and mortality worldwide. The heart and other organs can be rendered more resistant to the deleterious effects of ischemia through a variety of preconditioning strategies, including treadmill exercise and brief ischemia of skeletal muscle. Some of the beneficial effects of these preconditioning strategies appear to be mediated by as-of-yet unidentified hormonal opioids. OBJECTIVES: To test the hypothesis that endogenous opioids of the enkephalin class are capable of improving ischemic tolerance and acting in a hormonal manner. METHODS: In phase one of the investigation, the authors assessed the cardioprotective potential of all four known enkephalins. This was achieved by subjecting isolated buffer-perfused rabbit hearts to a 25-minute period of test ischemia and two hours of reperfusion (protocol 1) after receiving treatment with either saline vehicle (controls) or increasing concentrations of purified enkephalins. On the basis of results from these initial studies, the authors performed additional experiments (protocol 2) to determine whether Met5-enkephalin-Arg6-Phe7 (MEAP) could be absorbed from skeletal muscle and exert a cardioprotective effect. Specifically, MEAP or vehicle (controls) was given intramuscularly 24 hours before the hearts were harvested. A similar assessment of ischemic tolerance as described in protocol 1 was then performed. Postischemic myocardial viability (infarct size) was assessed in all cases by triphenyltetrazolium chloride (TTC) staining. Hemodynamic parameters and infarct sizes for concentration-dependence studies were compared by two-way analysis of variance, and infarct sizes from protocol 2 studies were compared by using Student's t-test (significance set at p < or = 0.05). RESULTS: Mean infarct size in control hearts (+/- SEM) was 33% (+/- 4%) and 36% (+/- 6%) for protocol 1 and 2, respectively. Of the four enkephalins tested in protocol 1, only MEAP treatment showed a tendency toward cardioprotection. Interestingly, an alternative enkephalin, methionine5-enkephalin-Arg6-Gly7-Leu8, tended to exert an injurious effect. In protocol 2, MEAP treatment 24 hours before ischemia significantly reduced infarct size (14% +/- 4%) compared with controls, suggesting that it can be released from muscle and exert a distant cardioprotective effect. CONCLUSIONS: When given either directly to the heart or absorbed from a distant tissue, MEAP induces cardioprotection, supporting the hypothesis that it can act as a hormonal modulator of ischemic tolerance.


Asunto(s)
Cardiotónicos/uso terapéutico , Encefalina Metionina/análogos & derivados , Isquemia Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Encefalina Metionina/uso terapéutico , Inyecciones Intramusculares , Reperfusión Miocárdica/instrumentación , Conejos , Distribución Aleatoria , Valores de Referencia , Resultado del Tratamiento
19.
Acad Emerg Med ; 13(4): 359-64, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16531591

RESUMEN

BACKGROUND: Accumulation of acetylcholine in the central nervous system is believed to account for the rapid lethality of organophosphate pesticides and chemical nerve agents. Diazepam is known to supplement atropine therapy, but its specific mechanism of action is uncertain. OBJECTIVES: To test four centrally acting agents for early antidotal efficacy in severe dichlorvos poisoning in the murine model. METHODS: The up-and-down method was used to dose four candidate antidotes: diazepam, xylazine, morphine, and ketamine. Antidotes were administered subcutaneously to unsedated adult Sprague-Dawley rats who were pretreated with 3 mg/kg intraperitoneal glycopyrrolate. All animals received 20 mg/kg of dichlorvos subcutaneously 5 minutes later. A blinded observer adjudicated the outcomes of 10-minute mortality and survival time. RESULTS: All animals pretreated with either no antidote (8/8 deaths) or glycopyrrolate alone (8/8) died within 10 minutes of dichlorvos injection. Pretreatment with diazepam (3/9 deaths), or xylazine (3/9), decreased lethality substantially (Fisher p = 0.007; median effective doses, 0.12 mg/kg and 3.0 mg/kg, respectively). Intermediate doses of morphine (3.1 to 5.5 mg/kg) resulted in survival, but higher doses did not, presumably because of excessive respiratory depression (7/11 deaths; p = 0.09). Ketamine (7/8 deaths) was ineffective as an antidote. Survival times also were prolonged in the diazepam and xylazine groups (log-rank p < 0.001) and, to a lesser degree, the morphine group (p = 0.07). CONCLUSIONS: Doses of diazepam, xylazine, and morphine below those used for deep sedation protect against severe dichlorvos poisoning, implying that several distinct central mechanisms are each sufficient to avert lethality. These findings suggest new possibilities for prophylaxis or therapy.


Asunto(s)
Antídotos/uso terapéutico , Diazepam/uso terapéutico , Diclorvos/toxicidad , Insecticidas/toxicidad , Ketamina/uso terapéutico , Morfina/uso terapéutico , Xilazina/uso terapéutico , Animales , Relación Dosis-Respuesta a Droga , Glicopirrolato/uso terapéutico , Intoxicación/tratamiento farmacológico , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley
20.
Int J Antimicrob Agents ; 26(4): 267-71, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16154724

RESUMEN

The antimicrobial susceptibility patterns of paediatric uropathogens to six of the most common antibiotics in use for urinary tract infections were determined. The bacterial isolates came from the urine of children presenting as outpatients to participating US hospitals between April 2002 and May 2004. Strains of the six most common uropathogens were included in the analysis. Results were stratified by paediatric age group. In total, 11174 female and 1557 male positive cultures were analysed. The overall resistance rates for females and males, respectively, were as follows: ampicillin 44.3% and 44.6%; sulphamethoxazole/trimethoprim 24.5% and 36.7%; amoxicillin/clavulanic acid 12.4% and 27.5%; cefazolin 10.9% and 27.1%; ciprofloxacin 0.9% and 2.4%; and nitrofurantoin 4.4% and 11.0%. Uropathogen resistance to commonly used antibiotics in the paediatric population was high.


Asunto(s)
Antibacterianos/farmacología , Cistitis/microbiología , Resistencia a Medicamentos , Bacterias Gramnegativas/efectos de los fármacos , Staphylococcus/efectos de los fármacos , Enfermedad Aguda , Adolescente , Atención Ambulatoria , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Estados Unidos
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