Resources for Enhancing Alzheimer's Caregiver Health (REACH): overview, site-specific outcomes, and future directions.
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Adult↗
Biomedical subjects
Richard Schulz
Publications and source records attributed to Richard Schulz.
Finding the best ways to help: opportunities and challenges of intervention research on aging.
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Academic Medical Centers↗
Hospital costs in patients receiving prolonged mechanical ventilation: does age have an impact?
BACKGROUND: The aging of the population is one of the causes of the increase in healthcare costs in the past few decades. It is controversial whether chronological age alone should be used in making healthcare decisions. OBJECTIVE: To determine the association between age and hospital costs in patients receiving mechanical ventilation (MV). DESIGN: Prospective, observational study. SETTING: Intensive care units at a teaching hospital. PATIENTS: A total of 813 adults who received prolonged (> or =48 hrs) mechanical ventilation. INTERVENTION: None. MEASUREMENTS: Severity of illness, comorbidities, length of stay, hospital costs, and mortality. We evaluated the independent association of age with hospital costs using linear regression. RESULTS: Mean (+/-sd) age of patients was 60.4 +/- 18.8 yrs. Median Acute Physiology Chronic Health Evaluation III score and probability of hospital death at intensive care unit admission were 64 and 0.31, respectively. Hospital mortality was 36%. Median total hospital costs and daily costs were $ 56,056 and $2,655 US dollars, respectively. Older age was associated with lower total hospital costs after controlling for sex, intensive care unit type, severity of illness, length of stay, insurance type, resuscitation status, and survival. Hospital costs were significantly less in older patients in all cost departments examined, except for respiratory care and intensive care unit room costs. CONCLUSIONS: Daily and total hospital costs were lower in older patients. Decreased hospital resource use in older patients may be related to a preference for less aggressive care by older patients and their families or by healthcare providers.
APACHE↗
Adaptive self-regulation of unattainable goals: goal disengagement, goal reengagement, and subjective well-being.
Three studies examined associations between goal disengagement, goal reengagement, and subjective well-being. In Study 1, 115 undergraduates reported on the extent to which they were able to abandon unattainable goals and reengage their efforts in alternative goals. Study 2 examined the importance of goal disengagement and goal reengagement in groups of young adults and older adults (N = 120). In Study 3, a sample of parents of children with cancer and parents of medically healthy children was examined (N = 45). The findings confirmed that goal disengagement and goal reengagement can be associated with ratings of high subjective well-being. In addition, the results showed that goal disengagement and goal reengagement can have interactive effects on subjective well-being. The importance of the findings for effective self-regulation and successful development are discussed.
Achievement↗
Investigating moderator hypotheses in aging research: statistical, methodological, and conceptual difficulties with comparing separate regressions.
Many topics in aging research address questions about group differences in prediction. Such questions can be viewed in terms of interaction or moderator effects, and use of appropriate methods to test these hypotheses are necessary to arrive at accurate conclusions about age differences. This article discusses the conceptual, methodological, and statistical problems in one approach to investigating moderator hypotheses. The subgroup regression approach, in which separate regression analyses are conducted in two or more groups, is widely used in aging research to examine group differences in prediction, but the approach can lead to erroneous conclusions. The moderated regression approach, involving the test of a product term, is described and recommended as an a alternative approach. The question of whether social support has greater beneficial effects for younger or older adults is investigated in a study of 287 recently-bereaved adults ranging in age from 20 to 91. Using the subgroup approach, findings indicated that social support significantly predicted depressive symptoms among younger adults and did not significantly predict depressive symptoms among older adults. The moderated regression analysis, however, indicated no significant age differences in the effect of social support. These results clearly illustrate that the analysis strategy researchers choose may have important bearing on theory in aging research such as conclusions regarding the role of social support across the life span.
Adult↗
Matrix metalloproteinase inhibitors attenuate endotoxemia induced cardiac dysfunction: a potential role for MMP-9.
Enhanced cardiac generation of peroxynitrite contributes to septic cardiomyopathy. Since matrix metalloproteinases (MMPs) are activated in vitro by peroxynitrite, we hypothezised that MMPs may contribute to cardiac mechanical dysfunction in sepsis. Rats were injected (i.p.) with either lipopolysaccharide (LPS, 4 mg/kg) or vehicle. MMP inhibitors, either Ro 31-9790 (20 mg/kg), doxycycline (4 mg/kg), or vehicle were administered i.p. 30 min after LPS. At 6 h, when the symptoms of endotoxemia peak, hearts were excised and perfused as working hearts with Krebs-Henseleit buffer at 37 degrees C. Cardiac work (cardiac output x peak systolic pressure product) was measured. Perfusate and ventricle samples were analyzed by gelatin zymography to quantify MMP activity. Cardiac function was significantly depressed in LPS-treated rats compared to control rats (control: 55 +/- 4, LPS: 26 +/- 6 mmHg*mL*min(-1)). LPS also caused a loss of 72 kDa MMP-2 activity in the ventricles and the perfusate. Although MMP-9 activity was not detected in the ventricles, LPS resulted in an increase in perfusate 92 kDa MMP-9 activity. The MMP inhibitors significantly improved cardiac function of LPS-treated rats (Ro 31-9790: 38 +/- 3, doxycycline: 51 +/- 3 mmHg*mL*min(-1)), had no effect on the loss of MMP-2 activity, and significantly reduced the MMP-9 activity in the perfusate. These results demonstrate, for the first time, that LPS induced cardiac dysfunction is associated with a loss in ventricular MMP-2 activity and the release of MMP-9 from the heart. MMP inhibitors can significantly preserve cardiac mechanical function during septic shock.
Animals↗
Intracellular action of matrix metalloproteinase-2 accounts for acute myocardial ischemia and reperfusion injury.
BACKGROUND: Matrix metalloproteinases are best recognized for their ability to degrade the extracellular matrix in both physiological and pathological conditions. However, recent findings indicate that some of them are also involved in mediating acute processes such as platelet aggregation and vascular tone. The acute contractile defect of the heart after ischemia-reperfusion may involve the proteolytic degradation of the thin filament protein troponin I; however, the protease responsible for this remains obscure. METHODS AND RESULTS: Here we report that matrix metalloproteinase-2 is colocalized with troponin I within the thin myofilaments of cardiomyocytes in ischemic-reperfused hearts and that troponin I is a novel intracellular target for proteolytic cleavage by matrix metalloproteinase-2. Inhibition of matrix metalloproteinase-2 activity prevented ischemia-reperfusion-induced troponin I degradation and improved the recovery of mechanical function of the heart. CONCLUSIONS: These data reveal for the first time a novel molecular mechanism by which matrix metalloproteinase-2 causes acute myocardial dysfunction after ischemia-reperfusion-injury and that matrix metalloproteinase-2 has a biological action within the cell.
Actin Cytoskeleton↗
Preconditioning decreases ischemia/reperfusion-induced release and activation of matrix metalloproteinase-2.
Release and activation of matrix metalloproteinases (MMPs) significantly contribute to myocardial stunning injury immediately after ischemia and reperfusion, however, their role in preconditioning remains unknown. We therefore examined the effects of preconditioning and subsequent ischemia/reperfusion on MMP activity in isolated rat hearts. Hearts were subjected to a preconditioning protocol (three consecutive 5-min periods of global ischemia interspersed with 5 min of reperfusion) followed by 30 min ischemia and 5 min reperfusion. To measure MMP release, coronary effluent was collected: (a) during aerobic perfusion, (b) in reperfusion following each preconditioning ischemia, and (c) during the final reperfusion following test ischemia. MMP-2 activities could be detected by gelatin zymography in the ventricles and coronary effluent samples from the perfused hearts. The levels of MMP-2 activity in the effluent were markedly increased in effluent following test ischemia from control hearts without preconditioning. This was accompanied by a decrease in corresponding tissue MMP activities. Preconditioning significantly decreased the MMP-2 activity in the coronary effluent following test ischemia/reperfusion and preserved the MMP-2 protein content and activity in the myocardium. Our results demonstrate that classic preconditioning inhibits ischemia/reperfusion induced release and activation of MMP-2. These results suggest that preconditioning may exert part of its cardioprotective effects through the reduction of MMP-2 release.
Animals↗
Depression as a risk factor for non-suicide mortality in the elderly.
Depression can be a consequence of medical illness and disability, yet recent literature suggests it may also influence morbidity and mortality through a variety of behavioral and biological mediators. Relatively little is known about the complex temporal relations among behavior, affect, motivation, and pathophysiology to account for the association between depression and mortality. We performed a systematic review of the recent literature (1997-2001) examining the evidence linking depression to non-suicide mortality, describe possible mediators of the depression mortality effect, and identify important next steps in this area of research, including: a) the development of well-specified a-priory mediator models that articulate how depression leads to mortality; b) the conduct of longitudinal studies in which depression and behavioral and pathophyisological mediators are assessed simultaneously; c) treatment studies for depression that include assessments of associated changes in health-related quality of life, medical morbidity, and mortality; and d) treatment studies for behavioral risk factors and medical conditions that include assessment of depressive symptoms.
Aged↗
Poly(ADP-Ribose) polymerase inhibition reduces reperfusion injury after heart transplantation.
The aim of the present study was to investigate the effects of the novel poly(ADP-ribose) polymerase (PARP) inhibitor PJ34 (N-(6-oxo-5,6-dihydro-phenanthridin-2-yl)-N,N-dimethylacetamide) on myocardial and endothelial function after hypothermic ischemia and reperfusion in a heterotopic rat heart transplantation model. After a 1-hour ischemic preservation, reperfusion was started either after application of placebo or PJ34 (3 mg/kg). The assessment of left ventricular pressure-volume relations, total coronary blood flow, endothelial function, myocardial high energy phosphates, and histological analysis were performed at 1 and 24 hours of reperfusion. After 1 hour, myocardial contractility and relaxation, coronary blood flow, and endothelial function were significantly improved and myocardial high energy phosphate content was preserved in the PJ34-treated animals. Improved transplant function was also seen with treatment with another, structurally different PARP inhibitor, 5-aminoisoquinoline. The PARP inhibitors did not affect baseline cardiac function. Immunohistological staining confirmed that PJ34 prevented the activation of PARP in the transplanted hearts. The activation of P-selectin and ICAM-1 was significantly elevated in the vehicle-treated heart transplantation group. Thus, pharmacological PARP inhibition reduces reperfusion injury after heart transplantation due to prevention of energy depletion and downregulation of adhesion molecules and exerts a beneficial effect against reperfusion-induced graft coronary endothelial dysfunction.
Adenosine Diphosphate↗
Serum levels of vascular endothelial growth factor are elevated in patients with obstructive sleep apnea and severe nighttime hypoxia.
Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality; however, some patients with OSA do not develop cardiovascular disease even in the presence of severe nocturnal oxygen desaturations. Vascular endothelial growth factor (VEGF) is a hypoxia-sensitive glycoprotein stimulating neoangiogenesis. We hypothesized that VEGF production is increased in OSA because of repetitive nocturnal hypoxia. Three different groups were investigated: 10 OSA patients with severe nighttime hypoxia (Group A), 10 OSA patients with moderate hypoxia (Group B), and 10 healthy volunteers (Group C). Serum levels of VEGF were measured by ELISA from peripheral venous blood samples obtained at 7 AM. Group A had significantly (p < 0.01) increased VEGF serum levels when compared with Group B and Group C (mean +/- SEM: 410 +/- 77 pg/ml versus 224 +/- 38 pg/ml and 245 +/- 61 pg/ml). The degree of nocturnal oxygen desaturation in OSA significantly correlated with the VEGF concentrations (r = 0.67, p < 0.01). In conclusion, serum levels of VEGF are elevated in severely hypoxic patients with OSA and are related to the degree of nocturnal oxygen desaturation. This might constitute an adaptive mechanism to counterbalance the emergence of OSA-related cardiovascular disease.
Adaptation, Physiological↗
Peroxynitrite-induced myocardial injury is mediated through matrix metalloproteinase-2.
OBJECTIVES: Peroxynitrite (ONOO(-)) mediates in part both ischemia-reperfusion and pro-inflammatory cytokine-induced injury to the heart. As oxidants like ONOO(-) are known to activate matrix metalloproteinases (MMPs), we examined whether they play a role in the detrimental action of ONOO(-) in isolated perfused rat hearts. METHODS: Hearts were isolated from Sprague-Dawley rats and perfused retrogradely with Krebs-Henseleit buffer under constant flow. Peroxynitrite (30 and 80 microM) was infused into the hearts for 15 min. The release of MMPs into the coronary effluent and level of MMPs in the myocardium were measured by gelatin zymography. RESULTS: The main gelatinolytic activity in control effluent was 72-kDa corresponding to pro-MMP-2. Infusion of ONOO(-) (80 microM) for 15 min caused a vasodilatation which peaked at 5 min and then converted into vasoconstriction by 15 min. It also caused a rapid increase in the release of 72-kDa activity within 10 min and a progressive decline in cardiac mechanical function. In contrast, decomposed ONOO(-) caused no change in vascular tone, the release of 72-kDa activity or mechanical function. The MMPs inhibitor PD-166793 prevented the ONOO(-)-induced loss in myocardial mechanical function. Detoxification of ONOO(-) with glutathione prevented both the enhancement in coronary effluent 72-kDa activity and the decline in mechanical function. CONCLUSIONS: Acute cardiac toxicity induced by ONOO(-) is mediated by MMP-2.
Analysis of Variance↗
Peroxynitrite in myocardial ischemia-reperfusion injury.
Peroxynitrite is a highly reactive oxidant which is produced during reperfusion of the ischemic heart. The role that this molecule plays in reperfusion injury has been controversial. Many investigations have demonstrated toxic effects of peroxynitrite, whereas others have found it to be protective during reperfusion. This review surveys evidence supporting both sides and proposes that peroxynitrite is a dichotomous molecule with beneficial and detrimental effects on the reperfused heart. Its toxic effects are mediated by modification and activation of a variety of targets (including poly (ADP) ribose synthetase and matrix metalloproteinases) while its beneficial effects are primarily mediated through its reaction with thiols, resulting in the formation of NO donor compounds (S-nitrosothiols).
Humans↗
Health stresses and depressive symptomatology in the elderly: the importance of health engagement control strategies.
The study presents cross-sectional (N = 127) and longitudinal (n = 111) analyses examining relations between health engagement control strategies (HECSs), depressive symptoms, and health stresses in elderly individuals. HECS was measured as people's behavioral and cognitive investments toward attaining health goals. HECS was related to low levels of depressive symptoms, particularly among people experiencing acute physical symptoms. Moreover, HECS predicted reduction of depressive symptoms over time, and depressive symptomatology predicted negative change in HECS. The findings show that active investments of HECSs significantly moderate the negative affective consequences of health threats. Individuals who are characterized by low levels of HECS and high levels of depressive symptoms may be at increased risk of accelerated decline in their physical and mental health.
Activities of Daily Living↗
The association of race and socioeconomic status with cardiovascular disease indicators among older adults in the health, aging, and body composition study.
OBJECTIVES: We hypothesized that older Black adults would have a higher prevalence of cardiovascular disease (CVD) than White adults, as indicated by elevated systolic blood pressure (SBP), low ankle-arm blood pressure index (AAI), and left ventricular hypertrophy (LVH). But, accounting for a broad interpretation of socioeconomic status (SES) (i.e., education, family income, home ownership, and other assets) would reduce these differences. METHODS: Data are from the Health, Aging, and Body Composition study, a longitudinal clinical research study of 3,075 well-functioning adults aged 70-79, in which 46% of women and 33% of men are Black. Logistic regression modeled racial and SES differences in CVD indicators. RESULTS: Being Black was significantly associated with elevated SBP (men only), low AAI, and LVH, and remained significant after accounting for each SES measure. The racial association with CVD was reduced the most by income for elevated SBP in men, other assets for low AAI in women and men, and other assets for LVH in men. DISCUSSION: Contrary to the age-as-leveler theory, being Black was strongly associated with CVD indicators, and accounting for SES did not reduce this association. Whether other SES measures, such as access to care, could explain the racial association remains to be explored.
Black or African American↗
Dementia caregiver intervention research: in search of clinical significance.
PURPOSE: We reviewed intervention studies that reported dementia caregiver outcomes published since 1996, including psychosocial interventions for caregivers and environmental and pharmacological interventions for care recipients. Our goal was to focus on issues of clinical significance in caregiver intervention research in order to move the field toward a greater emphasis on achieving reliable and clinically meaningful outcomes. DESIGN AND METHODS: MEDLINE, PsycINFO, and Cumulative Index to Nursing & Allied Health databases from 1996 through 2001 were searched to identify articles and book chapters mapping to two medical subject headings: caregivers and either dementia or Alzheimer's disease. Articles were evaluated on two dimensions, outcomes in four domains thought to be important to the individual or society and the magnitude of reported effects for these outcomes in order to determine if they were large enough to be clinically meaningful. RESULTS: Although many studies have reported small to moderate statistically significant effects on a broad range of outcomes, only a small proportion of these studies achieved clinically meaningful outcomes. Nevertheless, caregiving intervention studies have increasingly shown promise of affecting important public health outcomes in areas such as service utilization, including delayed institutionalization; psychiatric symptomatology, including the successful treatment of major and minor depression; and providing services that are highly valued by caregivers. IMPLICATIONS: Assessment of clinical significance in addition to statistical significance is needed in this research area. Specific recommendations on design, measurement, and conceptual issues are made to enhance the clinical significance of future research.
Aged↗
Patients' recollections of stressful experiences while receiving prolonged mechanical ventilation in an intensive care unit.
OBJECTIVE: To describe stressful experiences of adult patients who received mechanical ventilation for > or =48 hrs in an intensive care unit. DESIGN: Prospective cohort study. SETTING: Four intensive care units within an East Coast tertiary-care university medical center. PATIENTS: Patients were 150 adult intensive care unit patients receiving mechanical ventilation for > or =48 hrs. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: As part of a study of the long-term outcomes of adult patients requiring prolonged mechanical ventilation, we used a 32-item questionnaire to collect data on patients' stressful experiences, both psychological (e.g., fearfulness, anxiety) and physical (e.g., pain, difficulty breathing), associated with the mechanical ventilation endotracheal tube and with being in an intensive care unit. Of 554 patients who met study criteria and survived prolonged mechanical ventilation, 150 consented and were oriented to person, place, and situation. Two thirds of these patients remembered the endotracheal tube and/or being in an intensive care unit. The median numbers of endotracheal tube and intensive care unit experiences remembered were 3 (of 7) and 9 (of 22), respectively. If a patient remembered an experience in the questionnaire, it was likely to be moderately to extremely bothersome. Some of the items that many patients found to be moderately to extremely bothersome were pain, fear, anxiety, lack of sleep, feeling tense, inability to speak/communicate, lack of control, nightmares, and loneliness. Stressful experiences associated with the endotracheal tube were strongly associated with subjects' experiencing spells of terror, feeling nervous when left alone, and poor sleeping patterns. CONCLUSIONS: Subjects were more likely to remember experiences that were moderately to extremely bothersome. This might be because the more bothersome experiences were easier to recall or because most of these experiences are common and significant stressors to many of these patients. In either case, these data indicate that these patients are subject to numerous stressful experiences, which many find quite bothersome. This suggests the potential for improved symptom management, which could contribute to a less stressful intensive care unit stay and improved patient outcomes.
Anxiety↗
Enhanced NO and superoxide generation in dysfunctional hearts from endotoxemic rats.
Free radicals have been implicated in the etiology of cardiac dysfunction during sepsis, but the actual species responsible remains unclear. We studied the alterations in myocardial nitric oxide (NO), superoxide, and peroxynitrite generation along with cardiac mechanical function and efficiency in hearts from lipopolysaccharide (LPS)-treated rats. Six hours after LPS (4 mg/kg ip) or saline (control) treatment, hearts were isolated and perfused for 1 h with recirculating Krebs-Henseleit buffer and paced at 300 beats/min. Cardiac work, O(2) consumption, and cardiac efficiency were markedly depressed in LPS hearts compared with controls. Plasma nitrate/nitrite level was elevated in LPS rats, and ventricular NO production was enhanced as measured by electron spin resonance spectroscopy, Ca(2+)-independent NO synthase (NOS) activity, and inducible NOS immunohistochemistry. Ventricular superoxide production was also enhanced in LPS-treated hearts as seen by lucigenin chemiluminescence and xanthine oxidase activity. Increased nitrotyrosine staining (immunohistochemistry) and higher lipid hydroperoxides levels were also detected in LPS-treated hearts, indicating oxygen radical-induced stress. Enhanced generation of both NO and superoxide, and thus peroxynitrite, occur in dysfunctional hearts from endotoxemic rats.
Animals↗