Meeting unmet need: new strategies.
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Biomedical subjects
Publications and source records attributed to J Ross.
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BACKGROUND: Hospitalization presents an opportunity for physicians to discuss advance directives with patients and to encourage completion of health care proxies. OBJECTIVE: To prospectively promote discussion and documentation of treatment-specific directives about life-sustaining interventions (cardiopulmonary resuscitation, admission to critical care units, mechanical ventilation, electrical cardioversion, and vasopressor therapy) among unselected medical inpatients in a community teaching hospital. METHODS: We conducted a time-series intervention trial from January 1, 1991, through June 30 1993, divided into three phases. During the education phase, we provided reminders, education, and feedback to attending physicians; during the intervention phase, we promoted a new documentation form for directives to be used by attending physicians; during the control phase, no interventions occurred. We studied consecutive patients (N = 1780) admitted to the hospital acute medical service in each of the following 10 periods: three in the education phase (n = 598), three in the intervention phase (n = 826), and four in the control phase (n = 356). The primary outcome measures were the frequency and content of directives documented by attending physicians in their patients' hospital charts. Secondary outcome measures included physicians' and patients' attitudes about directives, surveyed repeatedly. RESULTS: The proportion of inpatients with directives increased significantly during the intervention phase (62.5% vs 23.6% during the education phase and 25.3% during the control period, P < .001, Pearson chi 2 test). During the final intervention phase, 227 (83.2%) of 273 inpatients had directives documented in the hospital chart. Increases in clinically important ("impact") directives usually involved intensive care, not do-not-resuscitate status. Overall, 366 (86.7%) of 422 physician-attested directives agreed with the treatment preferences of interviewed patients (kappa ranges, 0.53 to 0.79). Physicians' attitudes about and interest in directives improved. CONCLUSIONS: Institutional interventions can facilitate attending physicians' documentation of treatment-specific directives about life-sustaining care for most medical inpatients. More research is needed to confirm the effect of these efforts on quality and cost of hospital care, patients' autonomy, and their eventual execution of durable directives and proxies.
The adhesion molecules intercellular adhesion molecule 1 (ICAM-1), lymphocyte function-associated antigen-1 (LFA-1) (alpha and beta chains), and very late activation antigen-4 (VLA-4) have an essential role in cell-cell interactions and the initiation of immune responses. This study used an indirect immunoperoxidase technique to investigate the expression of these molecules in the lamina propria of allografts and isografts after heterotopic rat small bowel transplantation. Normal untransplanted small bowel served as additional controls. Overall, ICAM-1 and LFA-1 alpha expression was significantly higher in allografts, although there was variable expression of these molecules in isografted animals. There were temporal differences in the expression of ICAM-1 and LFA-1 alpha in that increased ICAM-1 expression was more pronounced in the the early posttransplant period, whereas there was a progressive increase in LFA-1 alpha as rejection developed. In contrast, there was no difference between allograft and isograft expression of LFA-1 beta and VLA-4. This study has demonstrated a preferential increase in adhesion molecule expression with developing rat small bowel allograft rejection and suggests that adhesion molecules are involved in the development and progression of allograft rejection. Although the observed differences in antigen expression are not as marked as those previously reported in other organ transplants, appropriate adhesion molecules may present suitable targets for immunotherapeutic protocols after small bowel transplantation.
BACKGROUND: The wider use of written advance directives is popular but problematic. We have shown previously that acute hospitalization in the era of the Patient Self-Determination Act can facilitate directive discussions and documentation. We investigated whether a simple educational intervention following hospitalization would increase patients' execution of durable health care proxies. METHODS: We studied a consecutive series of patients (n = 162) recently discharged from the acute care medical service of a community hospital where they had been interviewed about advance directives. The intervention group was randomized to receive an educational brochure and encouragement to execute durable health care proxies. The primary outcome was the proportion of patients in each group with completed durable health care proxies on file in their primary physicians' offices. RESULTS: Overall, only 20 (12.3%) of 162 patients had documented proxies, 17 of whom (85%) were 65 years of age or older, with no difference between the intervention and control groups (11 [13.3%] of 83 vs nine [11.4%] of 79, respectively). Subgroup analysis of elderly patients also revealed no intervention effect. Univariate analysis revealed three significant predictors of patients' proxy completion: patient age, whether patients had discussed directives in hospital with their physicians, and whether patients' physicians completed proxies for themselves. Multiple logistic regression analysis showed that these three variables interact to predict the probability of patients' executing proxies. CONCLUSIONS: Simple educational interventions, like those mandated by the Patient Self-Determination Act, are unlikely to increase patients' completion of durable healthcare proxies. Multidimensional interventions that target both elderly patients and their personal physicians should be tested in the future. Discussion in hospital about advance directives can be a useful component of such efforts.
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This article briefly reviews recent experimental studies which show that beta-adrenergic receptor stimulation produces an important enhancement of the force-frequency relation on myocardial contractility. The basic property of the force-frequency effect to progressively enhance myocardial contractility as heart rate increases is augmented at each level of increasing adrenergic stimulation. This newly described intrinsic mechanism for the control of cardiac inotropic state, graded beta-adrenergic amplification of the force-frequency relation, is strongly manifested during normal exercise and infusion of a beta-adrenergic agonist at rest, and it influences both systolic and diastolic ventricular function. Significant impairment of adrenergic amplification of the force-frequency relation is observed in experimental heart failure and could contribute to impaired cardiac function during stress or exercise in this setting.
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p21ras has been implicated in the hypertrophic response of cultured cardiac myocytes to defined growth stimuli. To determine if activation of ras-dependent intracellular signaling pathways is sufficient to induce in vivo hypertrophy, transgenic mice were created that express oncogenic ras in the cardiac ventricular chamber. Mice homozygous for the transgene displayed morphological, physiological, and genetic markers of marked cardiac muscle hypertrophy. Miniaturized catheterization technology documented a selective prolongation of cardiac relaxation, similar to that seen in early human hypertrophic heart disease. An increase in left atrial mass, in the absence of transgene expression in that chamber, further supported physiologically abnormal left ventricular diastolic function. Histological analysis revealed myofibrillar disarray, indistinguishable from that in hypertrophic cardiomyopathy in man. These studies establish a ras-dependent pathway for hypertrophic heart disease and document the feasibility of mapping in vivo signaling pathways for cardiac hypertrophy and dysfunction by applying in vivo microphysiological assays to genetically manipulated mice. ras-dependent pathways may also be a rational target for developing new approaches to inhibit the genesis of hypertrophy in certain pathological settings.
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As Los Angeles County--USC Medical Center hovered on the brink of closure this summer, one of the nation's largest hospitals was far from alone in its woes. In fact, a number of public hospitals--and the communities they serve--are in trouble in an era of tightened managed care payments, Medicaid budget woes and swelling uninsured populations.
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We have recently characterized a cardiac model of ventricular chamber defects in retinoid X receptor alpha (RXR alpha) homozygous mutant (-/-) gene-targeted mice. These mice display generalized edema, ventricular chamber hypoplasia, and muscular septal defects, and they die at embryonic day 15. To substantiate our hypothesis that the embryos are dying of cardiac pump failure, we have used digital bright-field and fluorescent video microscopy and in vivo microinjection of fluorescein-labeled albumin to analyze cardiac function. The affected embryos showed depressed ventricular function (average left ventricular area ejection fraction, 14%), ventricular septal defects, and various degrees of atrioventricular block not seen in the RXR alpha wild-type (+/+) and heterozygous (+/-) littermates (average left ventricular area ejection fraction, 50%). The molecular mechanisms involved in these ventricular defects were studied by evaluating expression of cardiac-specific genes known to be developmentally regulated. By in situ hybridization, aberrant, persistent expression of the atrial isoform of myosin light chain 2 was identified in the ventricles. We hypothesize that retinoic acid provides a critical signal mediated through the RXR alpha pathway that is required to allow progression of development of the ventricular region of the heart from its early atrial-like form to the thick-walled adult ventricle. The conduction system disturbances found in the RXR alpha -/- embryos may reflect a requirement of the developing conduction system for the RXR alpha signaling pathway, or it may be secondary to the failure of septal development.
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A process has been developed for the in situ formation of the mineral phase of bone. Inorganic calcium and phosphate sources are combined to form a paste that is surgically implanted by injection. Under physiological conditions, the material hardens in minutes concurrent with the formation of dahllite. After 12 hours, dahllite formation was nearly complete, and an ultimate compressive strength of 55 megapascals was achieved. The composition and crystal morphology of the dahllite formed are similar to those of bone. Animal studies provide evidence that the material is remodeled in vivo. A novel approach to skeletal repair is being tested in human trials for various applications; in one of the trials the new biomaterial is being percutaneously placed into acute fractures. After hardening, it serves as internal fixation to maintain proper alignment while healing occurs.