RESUMEN
Myeloma is the third most common blood cancer and one of the most complex and expensive cancers to treat. Black Americans face health disparities related to myeloma incidence, age at diagnosis, access to novel treatments, and mortality. To help reduce health disparities among Black Americans through education and outreach, the Leukemia & Lymphoma Society has implemented its Myeloma Link initiative. In 2022, a formative, qualitative evaluation was conducted across the 15 U.S. cities that implemented Myeloma Link to better understand the information and communication needs and preferences of three groups: patients, community members, and primary care providers (PCPs). Data collection included interviews with eight patients, two focus groups with a total of ten community members, and interviews with six PCPs. Patients expressed wanting information about treatment experiences, including clinical trials, and emotional and peer support services, particularly from other Black American patients. Community members were largely unfamiliar with myeloma and desired outreach via trusted community organizations about disease signs and symptoms. Both groups discussed the importance of self-advocacy within the current healthcare system and wanted actionable messaging, rather than messaging leading with disparities statistics. PCPs described systemic capacity and time challenges in the context of needing to address more frequently encountered health conditions; nonetheless, PCPs welcomed information and brief trainings about myeloma diagnosis and treatment options, referrals to specialists, and how to improve care, prognosis, and caregiver support. Findings underscore the importance of outreach initiatives such as Myeloma Link to help meet these needs and reduce health disparities.
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Major histocompatibility complex class II (MHCII) is dynamically expressed on intestinal epithelial cells (IECs) throughout the intestine, but its regulation remains poorly understood. We observed that spontaneous upregulation of IEC MHCII in locally bred Rag1-/- mice correlated with serum Interleukin (IL)-18, was transferrable via co-housing to commercially bred immunodeficient mice and could be inhibited by both IL-12 and IL-18 blockade. Overproduction of intestinal IL-18 due to an activating Nlrc4 mutation upregulated IEC MHCII via classical inflammasome machinery independently of immunodeficiency or dysbiosis. Immunodeficient dysbiosis increased Il-18 transcription, which synergized with NLRC4 inflammasome activity to drive elevations in serum IL-18. This IL-18-MHCII axis was confirmed in several other models of intestinal and systemic inflammation. Elevated IL-18 reliably preceded MHCII upregulation, suggesting an indirect effect on IECs, and mice with IL-18 overproduction showed activation or expansion of type 1 lymphocytes. Interferon gamma (IFNg) was uniquely able to upregulate IEC MHCII in enteroid cultures and was required for MHCII upregulation in several in vivo systems. Thus, we have linked intestinal dysbiosis, systemic inflammation, and inflammasome activity to IEC MHCII upregulation via an intestinal IL-18-IFNg axis. Understanding this process may be crucial for determining the contribution of IEC MHCII to intestinal homeostasis, host defense, and tolerance.
Asunto(s)
Microbioma Gastrointestinal/inmunología , Antígenos de Histocompatibilidad Clase II/genética , Antígenos de Histocompatibilidad Clase II/inmunología , Interferón gamma/metabolismo , Interleucina-18/biosíntesis , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Animales , Biomarcadores , Citocinas , Disbiosis/inmunología , Enterocitos/metabolismo , Expresión Génica , Proteínas de Homeodominio/genética , Inmunidad Mucosa , Inmunofenotipificación , Inflamasomas/metabolismo , Ratones , Ratones Noqueados , Modelos Biológicos , Receptor Toll-Like 9/inmunología , Receptor Toll-Like 9/metabolismoRESUMEN
The substantial interest and investment in health partnerships in the United States is based on the assumption that collaboration is more effective in achieving health and health system goals than efforts carried out by single agents. A clear conceptualization of the mechanism that accounts for the collaborative advantage, and a way to measure it are needed to test this assumption and to strengthen the capacity of partnerships to realize the full potential of collaboration. The mechanism that gives collaboration its unique advantage is synergy. A framework for operationalizing and assessing partnership synergy, and for identifying its likely determinants, can be used to address critical policy, evaluation, and management issues related to collaboration.
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Conducta Cooperativa , Agencias de los Sistemas de Salud/organización & administración , Práctica Asociada/organización & administración , Humanos , Estados UnidosRESUMEN
There is growing interest and investment in health-related collaboration in the United States. In an environment characterized by increasingly complex health problems, substantial resource constraints, and a fragmented health system, public and private organizations as well as communities are recognizing that most objectives related to health and health care cannot be achieved by any single person or organization working alone. Partnerships that bring together diverse people and organizations have the potential for developing new and creative ways of dealing with today's turbulent environment. Despite its potential advantages, collaboration also presents daunting challenges. Further, documenting the effectiveness of partnerships in improving health and well-being has been difficult. Given the significant difficulties of collaboration and the lack of evidence of its effectiveness, questioning whether the investment in health partnerships is justified seems reasonable. In this paper we address this question by illustrating the connective power of collaboration. We describe how collaboration, by connecting individual-level services, broadening community involvement in population-based health strategies, and linking individual-level services and population-based strategies, can improve the health of communities. We then discuss activities that could assist partnerships in reaching their collaborative potential and conclude by presenting the most compelling reasons for pursuing collaboration.
RESUMEN
This study examined role restriction in 365 inner-city mothers of 5- to 8-year-old children with chronic health conditions and tested whether it could account for a previously reported relationship between children's functional limitations and maternal psychological distress. Functional limitations in the children were related to maternal role restriction with sociodemographic factors controlled. Children's functional limitations also independently predicted maternal Depression subscale scores in a regression model. Adding role restriction to this model significantly increased explained variance in Depression scores, indicating that it also is directly related to maternal distress symptoms. However, adding role restriction only slightly reduced the impact of functional limitations in the model, suggesting that it plays a small role, if any, in explaining the relationship between the other two variables. Because perceived role restriction independently predicts maternal depressive symptoms and represents a potentially modifiable risk factor, it warrants attention as a useful target for intervention.
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Protección a la Infancia , Depresión/diagnóstico , Depresión/psicología , Relaciones Madre-Hijo , Madres/psicología , Rol , Autoimagen , Niño , Preescolar , Enfermedad Crónica , Femenino , Humanos , Masculino , Conducta Materna/psicologíaRESUMEN
Major depression is a common comorbid condition in patients with coronary heart disease (CHD). Although mild emotional distress may be a normal reaction to myocardial infarction or other manifestations of CHD, major depression should not be considered a normal reaction, nor should it be ignored. Major depression is a debilitating comorbid disorder that can seriously complicate recovery and increase the risks of further cardiac morbidity and mortality. Fortunately, it is one that can be successfully treated in the majority of cases. The purpose of this review is to present the evidence for the negative prognostic effects of depression in cardiac patients and to discuss methods for assessing and treating depression in these patients.
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Enfermedad Coronaria/psicología , Trastorno Depresivo/complicaciones , Enfermedad Coronaria/complicaciones , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/tratamiento farmacológico , Humanos , PronósticoRESUMEN
We present a case of thrombolytic therapy for acute myocardial infarction with high-dose intravenous streptokinase infusion in the emergency department. Resolution of ST segment elevation and relief of chest pain occurred within one hour of the infusion, and coronary angiographic study six days later showed a significant proximal obstruction (80%) of the right coronary artery. The patient underwent coronary artery bypass surgery eight weeks after his initial hospital presentation.
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Infarto del Miocardio/tratamiento farmacológico , Estreptoquinasa/administración & dosificación , Angiografía Coronaria , Circulación Coronaria , Electrocardiografía , Servicios Médicos de Urgencia , Humanos , Infusiones Parenterales , Masculino , Persona de Mediana Edad , Infarto del Miocardio/fisiopatologíaRESUMEN
The relationship between myocardial contracture and cell calcium was studied in electrically paced, isolated perfused rabbit hearts. Isovolumic left ventricular dP/dt and end-diastolic pressure were utilized as indexes of contractility and ventricular stiffness. After 60 min of low flow (ischemia) without or with reperfusion at high flow for 10 min, calcium was measured in the mitochondrial fraction and used as an indicator of intracellular calcium. Low flow led to ventricular standstill and contracture, and reperfusion produced partial mechanical recovery with end-diastolic pressure remaining markedly elevated. Nifedipine (10(-7) M), an antagonist of myocardial calcium uptake, prevented contracture and permitted nearly complete mechanical recovery without elevation in diastolic pressure. Increases in mitochondrial calcium paralleled the severity of contracture and the lack of diastolic relaxation after reperfusion. Mitochondrial calcium did not increase in hearts protected by nifedipine. Results demonstrate a close relationship between mechanical changes induced by ischemia and accumulation of intracellular calcium.
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Calcio/metabolismo , Enfermedad Coronaria/fisiopatología , Mitocondrias Cardíacas/metabolismo , Contracción Miocárdica , Animales , Presión Sanguínea , Calcio/fisiología , Cobre/metabolismo , Metabolismo Energético , Técnicas In Vitro , Contracción Miocárdica/efectos de los fármacos , Nifedipino/farmacología , Perfusión , Proteínas/metabolismo , Conejos , Factores de TiempoRESUMEN
Production of in vivo images of the human heart, with delineation of the individual cardiac chambers and myocardial wall thickness, was accomplished by coupling a relatively simple electrocardiographic gating device to a translate-rotate type of computed body tomographic scanner. Differentiation between the myocardial wall and the intracardiac blood pool was attainable in the patient with a normal hematocrit only when intravenous iodinated contrast media was used.
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Corazón/diagnóstico por imagen , Tomografía Computarizada por Rayos X/instrumentación , Adulto , Medios de Contraste/administración & dosificación , Femenino , Humanos , Inyecciones Intravenosas , Ácido Yotalámico/administración & dosificación , Masculino , Persona de Mediana EdadAsunto(s)
Circulación Coronaria , Corazón/diagnóstico por imagen , Miocardio/metabolismo , Amoníaco , Radioisótopos de Carbono , Enfermedad Coronaria/diagnóstico por imagen , Difosfatos , Estudios de Evaluación como Asunto , Radioisótopos de Galio , Humanos , Radioisótopos de Nitrógeno , Radioisótopos de Oxígeno , Palmitatos , Radioisótopos , Cintigrafía/instrumentación , Rubidio , Tecnecio , Talio , Tomografía Computarizada por Rayos XRESUMEN
Myocardial leukocyte infiltration is one hallmark of acute myocardial infarction. In order to detect noninvasively this inflammatory response associated with acute myocardial infarction, we produced coronary occlusion in eight dogs, intravenously administered autologously labeled indium-111 (111In) leukocytes and scintigraphically monitored accumulation of radionuclide in myocardium. Seventy-two hours after coronary occlusion, 111In-labeled white cells accumulated in regions corresponding to myocardial infarcts, and positive images with 111In-labeled leukocytes correlated well with images obtained with technetium-99m pyrophosphate and computer-reconstructed tomograms obtained with nitrogen-13-labeled ammonia. In contrast, two control dogs subjected to sham operation did not exhibit positive 111In-leukocyte images. Scintigraphic results with 111In-labeled leukocytes were verified in vitro by analysis of radioactivity in normal myocardium and in infarcts. Thus, leukocytic infiltration associated with acute myocardial infarction can be detected noninvasively in vivo.
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Enfermedad Coronaria/diagnóstico , Indio , Leucocitos , Miocarditis/diagnóstico , Cintigrafía , Amoníaco , Animales , Perros , Infarto del Miocardio/diagnóstico , Radioisótopos de Nitrógeno , Radioisótopos , TecnecioRESUMEN
Ischemic myocardial injury has been detected recently in isolated perfused hearts and intact experimental animals with positron-emitting 11C-palmitate and reconstructive tomography providing cross-sectional images of the heart free from superimposed activity in overlying structures. To evaluate the applicability of positron emission transaxial tomography in detecting infarction in man, 10 normal human subjects and 12 patients who sustained documented acute myocardial infarction three to 12 months previously were studied. Tomograms were obtained after intravenous injection of 5 to 10 mCi of 11C-labeled palmitate, a physiological substrate of myocardium. Tomograms from all normal subjects exhibited homogeneous distribution of 11C-palmitate throughout each 1.5 cm thick cross section of the ventricle. Tomograms from all patients with remote anterior or inferior and posterior myocardial infarction exhibited diminished accumulation of 11C-palmitate delineating regions corresponding to the electrocardiographic locus of infarction. The distribution of 11C-palmitate detectable by positron emission transaxial tomography in a series of cross sections from apex to base in the same normal subject or patient with remote myocardial infarction was analogous to that observed in normal dogs and animals with experimentally induced myocardial infarction.
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Infarto del Miocardio/diagnóstico por imagen , Ácidos Palmíticos , Tomografía Computarizada por Rayos X , Radioisótopos de Carbono , Enfermedad Coronaria/diagnóstico por imagen , Humanos , Masculino , Tomografía Computarizada por Rayos X/métodosRESUMEN
To assess myocardial infarction quantitatively in 15 mm thick transverse sections of the canine heart in vivo we utilized a new technique, positron emission transaxial tomography (PETT) and cyclotron-produced 11C-palmitate (11C-P) injected intravenously. Results were compared to regional myocardial creatine phosphokinase (CPK) depletion, diminished 14C-palmitate accumulation in tissue extracts, and infarction estimated morphometrically 48 hours after coronary occlusion. CPK activity and 14C-P content declined in parallel in transmural biopsies (N=44) from normal and ischemic zones (r=.92) in six dogs; and infarct in 10 mm thick cross sections of the entire left ventricle estimated morphometrically (N=26) in six other animals correlated with CPK depletion in contiguous 2.5 mm thick slices (r=.92). When the percentage of infarction in 15 mm thick cross sections was assessed tomographically in six other dogs 48 hours after coronary occlusion with 11C-P injected intravenously, results correlated with infarction in corresponding cross sections from the same hearts estimated morphometrically (r=.97, N=9) and by analysis of CPK depletion (r=.93, N=9). Thus, PETT permits estimation of infarction in cross sections of the left ventricle in vivo after intravenous injection of 11C-palmitate.
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Infarto del Miocardio/diagnóstico , Palmitatos , Ácidos Palmíticos , Tomografía Computarizada por Rayos X/métodos , Animales , Creatina Quinasa/metabolismo , Perros , Ventrículos Cardíacos , Miocardio/enzimologíaRESUMEN
The relation between the accumulation of pyrophosphate and technetium-99m in myocardium with reversible and irreversible ischmic injury was studied in dogs subjected to transitory or persistent coronary arterial occlusion. Among four dogs with coronary occlusion maintained for less than 20 minutes, none had either increased MB creatine kinase (CK) (the "myocardial" CK isoenzyme) activity serum or a positive 99mTc stannous pyrophosphate image. Seven dogs with coronary occlusion maintained for 30 or more minutes had elevated serum MB CK activity, and five of the seven had positive (abnormal) images. Thus, although false negative images may occur occasionally despite myocardial damage, both increased serum MB CK and abnormal images generally accompanied prolonged coronary occlusion. In contrast, ischemia without infarction was not associated with abnormal images. Both 99mTc and 32P labeled pyrophosphate were accumulated extensively and proportionally in myocardium from zones of infarction, and uptake of both tracers was comparable although modest in isolated mitochondria. Similar results were obtained after myocardial infarction in animals with induced profound leukopenia. Thus, phagocytosis of the radiopharmaceutical agent by leukocytes migrating into the infarct is not an essential mechanism accounting for uptake. These results indicate that abnormal images reflect uptake of pyrophosphate, associated with 99mTc, by irreversibly injured myocardium rather than leukocytic infiltration involved in the inflammatory response in the heart.
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Infarto del Miocardio/diagnóstico , Cintigrafía , Animales , Embrión de Pollo , Enfermedad Coronaria/diagnóstico , Creatina Quinasa/sangre , Difosfatos , Modelos Animales de Enfermedad , Perros , Reacciones Falso Negativas , Leucocitos , Mitocondrias/análisis , Miocardio/análisis , Tecnecio , Polifosfatos de EstañoRESUMEN
Radiopharmaceuticals incorporated directly into the metabolic pathways in myocardium provide a useful means for evaluating such processes. Palmitic acid, a major physiologic substrate of myocardium, has a well-understood role in myocardial metabolism. Accordingly, 11C-palmitic acid was the substrate chosen for use in conjunction with positron emission transaxial tomography to obtain images of canine myocardium. This procedure provides high-contrast images of tranverse sections of the myocardium, with good target-to-nontarget ratios (in the image), over a period of 5 to 85 minutes. Clearance half-times for blood and myocardial tissue were found to be 4.8 and 330 min, respectively. In normal myocardium, images obtained with 11C-palmitic acid were those obtained with 13NH3 and 11CO-hemoglobin. In vivo images of hearts with myocardial infarcts showed a clear delineration of infarcts and normal tissue.
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Radioisótopos de Carbono , Infarto del Miocardio/diagnóstico , Ácidos Palmíticos , Cintigrafía , Tomografía , Amoníaco , Animales , Monóxido de Carbono , Perros , Radioisótopos de NitrógenoRESUMEN
A whole-body positron-emission transaxial tomograph (PETT III) was used to image the cross-sectional distribution of 13NH3 and 11CO-hemoglobin in the human brain and heart. Carotid and intravenous bolus injections of 13NH3 in the rhesus monkey had shown that 13NH3 is efficiently extracted by the brain and clears from it slowly (half-time, 40-50 min for carotid injections and 60-70 min for intravenous injections). The intravenous tomographic images in humans showed an excellent relationship between 13NH3 uptakes in the cortex, subcortical white matter, cerebellum, and brain stem and normal blood perfusion or flow in these structures. Cerebral lesions with high (metastasis) and low (stroke) blood flows showed correspondingly high and low uptakes of 13NH3. Large- and small-vascular structures of the brain were also clearly seen in 11CO-hemoglobin tomographic images. Normal myocardium and the ventricular chambers were well defined, and a transmural anterior myocardial infarct was clearly shown. The effective combination of positron transaxial tomography and compounds labeled with positron-emitters provides a safe new method for quantitatively imaging hemodynamic and physiologic functions of selected organs with good tomographic image quality.
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Circulación Cerebrovascular , Circulación Coronaria , Radioisótopos , Tomografía , Animales , Radioisótopos de Carbono , Trastornos Cerebrovasculares/diagnóstico , Haplorrinos , Hemoglobinas , Humanos , Macaca mulatta , Infarto del Miocardio/diagnóstico , Radioisótopos de NitrógenoRESUMEN
To characterize externally detectable changes in myocardial metabolism of free fatty acids (FFA) and glucose associated with ischemia, isovolumically beating rabbit hearts were perfused under conditions of selected flows with cyclotron-produced, short-lived (t1/2 - 20.4 minutes), 11C-labeled isotopes of glucose and FFA. Tension-time index decreased 83% and lactate production increased from 0.5 +/- 1.9 (SE) to 5.3 +/- 2.1 mumol/min per g of dry weight reflecting myocardial ischemia after flow was reduced from 20 to 5 ml/min. After 30 minutes of low flow the myocardial accumulation of 11C-octanoate, expressed as the extraction fraction, declined from 56 +/- 15% to 30 +/- 3%, reflecting metabolic suppression of FFA extraction during low flow. Effects attributable exclusively to prolonged residence time were excluded. Similar results were obtained with 11C-palmitate. The myocardial avidity for 11C-palmitate was demonstrable by rectilinear whole body scanning in dogs given 5 mCi of the agent intravenously. Diminished 11C-palmitate uptake in zones of myocardium rendered ischemic for 20 minutes prior to reflow in intact dogs was delineated by electrocardiographically gated positron-emission transaxial computer reconstruction tomography. Thus, diminished 11C-FFA extraction, externally detectable, accompanies decreased perfusion in isolated perfused hearts, and decreased 11C-FFA uptake reflecting myocardial ischemia in vivo can be evaluated noninvasively by positron-emission transaxial tomography.
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Enfermedad Coronaria/diagnóstico , Diagnóstico por Computador , Ácidos Grasos no Esterificados/metabolismo , Glucosa/metabolismo , Miocardio/metabolismo , Cintigrafía/métodos , Tomografía/métodos , Albúminas/metabolismo , Animales , Caprilatos/metabolismo , Radioisótopos de Carbono , Enfermedad Coronaria/metabolismo , Perros , Lactatos/metabolismo , Ácidos Palmíticos/metabolismo , ConejosRESUMEN
In an attempt to evaluate the possible usefulness of transmission computed tomography, CT scans of the chest of a series of dead dogs were obtained by means of an EMI body scanner. The sections thus obtained with and without the injection of contrast material reveal a great deal of cardiac morphology. Infarcts of the heart produced prior to scanning were imaged as regions of lower x-ray attenuation. The hearts of a series of live dogs following infarction were imaged by means of a positron emission transverse tomomograph (PETT) following administration of C-palmitate. The images permitted assessment of the relative size of the infarct. The relative advantages of transmission and emission tomography in cardiac visualization are discussed.
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Computadores , Corazón/diagnóstico por imagen , Animales , Medios de Contraste , Perros , Infarto del Miocardio/diagnóstico por imagen , Tomografía por Rayos XRESUMEN
Exclusion of acute myocardial infarction preoperatively, particularly in patients undergoing cardiac catheterization, is an important requirement for optimal results following coronary revascularization. Unfortunately, activity of conventionally measured serum enzymes (AST, LDH, total CPK) is frequently raised because of enzyme released from non-cardiac sources during the catheterization procedure. however, serum activity of the MB CPK isoenzyme, an isoenzyme found primarily in heart muscle, appears to be more specific. Accordingly, in the present study, total CPK and MB CPK activities were determined in serum samples from 53 patients undergoing diagnostic catheterization, immediately before study and serially for 24 hours afterwards. A comprehensive range of catheterization procedures included selective coronary arteriography in 39 patients by brachial (17) or femoral (22) artery approaches. Myocardial infarction was excluded by clinical and electrocardiographic criteria in all patients before and after the procedure. MB CPK isoenzyme activity was also measured in serum samples from 50 patients with actue myocardial infarction documented electrocardiographically, and in 20 controls admitted to hospital but without cardiovascular disease. In patients with acute myocardial infarction, both total CPK and MB CPK isoenzyme levels were significantly raised (0.78 +/- 0.087 and 0.086 +/- 0.037 IU/ml, respectively), exceeding the upper limit of normal in all cases. MB CPK activity remained within normal limits (less than 0.004 IU/ml) in all 20 subjects without cardiovascular disease. Peak total serum CPK activity exceeded control levels in all patients undergoing catheterization (0.260 +/- 0.033). However, in each case, MB CPK isoenzyme activity remained within normal limits (less than .004). Thus, in contrast to an increase of activity of conventionally used serum enzymes, increased MB CPK isoenzyme activity is a reliable indicator of myocardial infarction, even in patients undergoing cardiac catheterization.