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Biomedical subjects

Richard Schulz

Publications and source records attributed to Richard Schulz.

At least 19 recordsLinked to original sources

Intracellular targets of matrix metalloproteinase-2 in cardiac disease: rationale and therapeutic approaches.

A new paradigm of matrix metalloproteinase-2 (MMP-2) action in the heart undergoing oxidative stress has emerged. Although best known for its role in the proteolysis of extracellular protein targets, MMP-2 is also localized to the sarcomere within the cardiomyocyte. Oxidative stress activates full-length MMP-2 without need for proteolytic processing and inactivates an endogenous inhibitor, tissue inhibitor of metalloproteinase-4. MMP-2 proteolyzes specific targets within the cell to cause acute, reversible contractile dysfunction. Inhibitors of MMPs are discussed and their possible use for the therapy of acute heart injury caused by oxidative stress is examined.

Animals↗

Religious beliefs and practices are associated with better mental health in family caregivers of patients with dementia: findings from the REACH study.

OBJECTIVE: Providing care to a loved one with dementia and the death of that loved one are generally considered two of the most stressful human experiences. Each puts family caregivers at risk of psychologic morbidity. Although research has suggested that religious beliefs and practices are associated with better mental health, little is known about whether religion is associated with better mental health in family caregivers. Our objective, then, is to explore the relationship between religion and mental health in active and bereaved dementia caregivers. METHODS: A total of 1,229 caregivers of persons with moderate to severe dementia were recruited from six geographically diverse sites in the United States and followed prospectively for up to 18 months. Three measures of religion: 1) the frequency of attendance at religious services, meetings, and/or activities; 2) the frequency of prayer or meditation; and 3) the importance of religious faith/spirituality were collected. Mental health outcomes were caregiver depression (Center for Epidemiological Studies-Depression [CES-D] scale) and complicated grief (Inventory of Complicated Grief [ICG]). RESULTS: Religious beliefs and practices were important to the majority of caregivers. After controlling for significant covariates, the three measures of religion were associated with less depressive symptoms in current caregivers. Frequent attendance was also associated with less depression and complicated grief in the bereaved. CONCLUSIONS: Religious beliefs and practices, and religious attendance in particular, are associated with better mental health in family caregivers of persons with dementia.

Adaptation, Psychological↗

Enhancing the quality of life of dementia caregivers from different ethnic or racial groups: a randomized, controlled trial.

BACKGROUND: Caring for a family member with dementia is extremely stressful, contributes to psychiatric and physical illness among caregivers, and increases the risk for caregiver death. Finding better ways to support family caregivers is a major public health challenge. OBJECTIVE: To test the effects of a structured multicomponent intervention on quality of life and clinical depression in caregivers and on rates of institutional placement of care recipients in 3 diverse racial or ethnic groups. DESIGN: Randomized, controlled trial. SETTING: In-home caregivers in 5 U.S. cities. PARTICIPANTS: 212 Hispanic or Latino, 219 white or Caucasian, and 211 black or African-American caregivers and their care recipients with Alzheimer disease or related disorders. INTERVENTION: Caregivers within each racial or ethnic group were randomly assigned to an intervention or to a control group. The intervention addressed caregiver depression, burden, self-care, and social support and care recipient problem behaviors through 12 in-home and telephone sessions over 6 months. Caregivers in the control group received 2 brief "check-in" telephone calls during the 6-month intervention. MEASUREMENTS: The primary outcome was a quality-of-life indicator comprising measures of 6-month caregiver depression, burden, self-care, and social support and care recipient problem behaviors. Secondary outcomes were caregiver clinical depression and institutional placement of the care recipient at 6 months. RESULTS: Hispanic or Latino and white or Caucasian caregivers in the intervention group experienced significantly greater improvement in quality of life than those in the control group (P < 0.001 and P = 0.037, respectively). Black or African-American spouse caregivers also improved significantly more (P = 0.003). Prevalence of clinical depression was lower among caregivers in the intervention group (12.6% vs. 22.7%; P = 0.001). There were no statistically significant differences in institutionalization at 6 months. LIMITATIONS: The study used only a single 6-month follow-up assessment, combined heterogeneous cultures and ethnicities into a single group, and excluded some ethnic groups. CONCLUSIONS: A structured multicomponent intervention adapted to individual risk profiles can increase the quality of life of ethnically diverse dementia caregivers. ClinicalTrials.gov identifier: NCT00177489.

Aged↗

Informal caregiver burden among survivors of prolonged mechanical ventilation.

RATIONALE: Although caregiver burden is well described in chronic illness, few studies have examined burden among caregivers of survivors of critical illness. In existing studies, it is unclear whether the observed burden is a consequence of critical illness or of preexisting patient illness. OBJECTIVES: To describe 1-yr longitudinal outcomes for caregivers of patients who survived critical illness, and to compare depression risk between caregivers of patients with and without pre-intensive care unit (ICU) functional dependency. METHODS: Prospective, parallel, cohort study of survivors of prolonged (greater than 48 h) mechanical ventilation and their informal caregivers. Caregivers were divided into two cohorts on the basis of whether patients were functionally independent (n = 99, 59%), or dependent (n = 70, 41%) before admission. Functional dependency was defined as dependency in one or more activities of daily living or in three or more instrumental activities of daily living. Patient and caregiver outcomes were measured 2, 6, and 12 mo after mechanical ventilation initiation. MEASUREMENTS AND MAIN RESULTS: We studied three caregiver outcomes: depression risk, lifestyle disruption, and employment reduction. Most patients were male (59.8%), with a mean (SD) age of 56.6 (19.0) yr. Caregivers were mostly female (75.7%), with a mean (SD) age of 54.6 (14.7) yr. Prevalence of caregiver depression risk was high at all time points (33.9, 30.8, and 22.8%; p = 0.83) and did not vary by patient pre-ICU functional status. Lifestyle disruption and employment reduction were also common and persistent. CONCLUSIONS: Depression symptoms, lifestyle disruption, and employment reduction were common among informal caregivers of critical illness survivors. Depression risk was high regardless of patient pre-ICU functional status.

Caregivers↗

Differential inhibitory control of circular and longitudinal smooth muscle layers of Balb/C mouse small intestine.

We examined the inhibitory mediators acting on each of the longitudinal (LM) and circular muscle (CM) layers of mouse small intestine in the presence of atropine, prazosin and timolol. Nitric oxide (NO) and apamin-sensitive mediators exerted an inhibitory tone on pacing frequency in CM, observed as an increased frequency upon treatment with N-omega-nitro-l-arginine (LNNA) or apamin. This effect was not seen in LM. 1H-(1,2,4)oxadiazolo(4,3-A)quinazoline-1-one (ODQ) abolished the relaxation in response to electric field stimulation (EFS) in LM in a manner similar to LNNA indicating that the inhibitory mediator in this layer in NO acting via soluble guanylate cyclase. On the other hand, in CM neither LNNA nor apamin was capable of reducing the inhibition in response to EFS and their combination left a residual relaxation of 25%. ODQ reduced the EFS-evoked relaxation more effectively than LNNA at higher frequencies indicating that another ODQ-sensitive mediator was active in CM. ODQ also blocked the relaxation to exogenous vasoactive intestinal peptide in CM. In LM, the relaxation due to sodium nitroprusside was equally blocked by ODQ and apamin, while in CM, its effects were only reduced by ODQ and not apamin. These results indicate that there are differences in the inhibitory mediators and the mechanisms of action involved in LM and CM relaxation.

Animals↗

Caveolin-1 knockout alters beta-adrenoceptors function in mouse small intestine.

beta-Adrenoceptors are G protein-coupled receptors whose functions are closely associated with caveolae in the heart and cultured cell lines. In the gut, they are responsible, at least in part, for the mediation of the sympathetic stimulation that might lead to intestinal paralysis postoperatively. We examined the effect of caveolin-1 knockout on the beta-adrenoceptor response in mouse small intestine. The relaxation response to (-)-isoprenaline in carbachol-contracted small intestinal tissue segments was reduced in caveolin-1 knockout mice (cav1(-/-)) compared with their genetic controls (cav1(+/+)). Immunohistochemical staining showed that beta-adrenoceptor expression was similar in both strains in gut smooth muscle. Selective beta-adrenoceptor blockers shifted the concentration response curve (CRC) of (-)-isoprenaline to the right in cav1(+/+) intestine, but not in cav1(-/-), with greatest shift in case of the beta(3)-blocker, SR59230A. The CRC of the selective beta(3)-agonist BRL 37344 was also shifted to the right in cav1(-/-) compared with cav1(+/+). The cAMP-dependent protein kinase (PKA) inhibitor H-89 shifted the CRC of (-)-isoprenaline to the right in cav1(+/+) but not in cav1(-/-). H-89 reduced the relaxation due to forskolin and dibutyryl cAMP in cav1(+/+) but not in cav1(-/-), suggesting a reduction in PKA activity in cav1(-/-). In cav1(+/+), PKA was colocalized with caveolin-1 in the cell membrane, but PKA immunoreactivity persisted in cav1(-/-). Examination of PKA expression in the lipid raft-rich membrane fraction of the jejunum revealed reduced PKA expression in cav1(-/-) compared with cav1(+/+). The results of the present study show that the function of beta-adrenoceptors is reduced in cav1(-/-) small intestine likely owing to reduced PKA activity.

Animals↗

Isolated heart perfusion according to Langendorff---still viable in the new millennium.

The isolated perfused mammalian heart preparation was established in 1897 by Oscar Langendorff. The method was developed on the basis of the isolated perfused frog heart established by Elias Cyon at the Carl Ludwig Institute of Physiology in Leipzig, Germany in 1866. Observations made using both methods at the end of the 19th and at the beginning of the 20th century led to important discoveries, forming the basis for our understanding of heart physiology. This included the role of temperature, oxygen and calcium ions for heart contractile function, the origin of cardiac electrical activity in the atrium, the negative chronotropic effect of vagus stimulation and the chemical transmission of impulses in the vagus nerve by acetylcholine. Langendorff himself demonstrated that the heart receives its nutrients and oxygen from blood via the coronary arteries and that cardiac mechanical function is reflected by changes in the coronary circulation. The method underwent many modifications but its general principle remains the same today. Blood, or more commonly crystalloid perfusates, are delivered into the heart through a cannula inserted in the ascending aorta, either at constant pressure or constant flow. Retrograde flow in the aorta closes the leaflets of the aortic valve and as a consequence, the entire perfusate enters the coronary arteries via the ostia at the aortic root. After passing through the coronary circulation the perfusate drains into the right atrium via the coronary sinus. The simplicity of the isolated mammalian heart preparation, the broad spectrum of measurements which can be done using this method, its high reproducibility and relatively low cost make it a very useful tool in modern cardiovascular and pharmacological research, in spite of a few shortcomings. In the last decade the method has brought many important advances in many areas including ischemia-reperfusion injury, cell-based therapy and donor heart preservation for transplant.

Animals↗

Self-regulation of common age-related challenges: benefits for older adults' psychological and physical health.

This article addresses the role played by adaptive self-regulation in protecting older adults' psychological and physical health. A theoretical model is outlined illustrating how common age-related challenges (i.e., physical challenges and life regrets) can influence older adults' health. In addition, the proposed model suggests that older adults can avoid the adverse health effects of encountering these problems if they engage in adaptive self-regulation. Finally, this article reviews recent studies that examined the adaptive value of self-regulation processes for managing physical challenges and life regrets in the elderly. The findings from cross-sectional, longitudinal, and experimental studies document the importance of adaptive self-regulation for maintaining older adults' health.

Adult↗

[Obstructive sleep apnea-related cardiovascular disease].

The clinical spectrum of obstructive sleep apnea-(OSA-)related cardiovascular disease (CVD) comprises systemic arterial hypertension (prevalence: 40-60%), pulmonary hypertension (20-30%), coronary artery disease (20-30%), congestive heart failure (5-10%), and stroke (5-10%). During sleep, heart rhythm disorders such as atrioventricular blocks, sinus arrests and atrial fibrillation can be induced by OSA. OSA-related CVD mainly affects those patients with an apnea-hypopnea index > 30/h and, if left untreated, is linked to increased mortality. Epidemiologic data have clearly shown that cardiovascular risk is increased in OSA independent of confounding factors such as obesity and concomitant metabolic disease. In recent years, the pathophysiology of OSA-related CVD has been further elucidated showing that apart from the well-known sympathetic activation, increased oxidative stress and pro-inflammatory changes seem to play major roles. Furthermore, studies using high resolution ultrasonography have demonstrated endothelial dysfunction and enhanced atherosclerosis in these patients. Finally, animal models of OSA have delineated that daytime arterial hypertension is the consequence of the OSA-associated chronic intermittent hypoxia. Therapy of OSA by continuous positive airway pressure (CPAP) ventilation exerts cardioprotective effects. It has been shown to rectify the vascular micromilieu, restore endothelium-dependent vasodilation, lower 24-h blood pressure, eliminate nocturnal heart rhythm disorders, and improve left ventricular function. Furthermore, long-term CPAP therapy leads to a reduction in important clinical endpoints such as the rates of myocardial infarction and stroke.

Animals↗

The Life Engagement Test: assessing purpose in life.

This article describes a 6-item scale, the Life Engagement Test, designed to measure purpose in life, defined in terms of the extent to which a person engages in activities that are personally valued. Psychometric data are presented including information about the scale's factor structure, internal consistency, test-retest reliability, convergent validity, discriminant predictive validity, and norms. The data suggest that the Life Engagement Test is psychometrically sound across different gender, age, and ethnic groups and is appropriate for wider use. Discussion centers on the use of the Life Engagement Test in behavioral medicine and health psychology research and recent associations that have begun to emerge between the scale and health-relevant outcomes.

Adult↗

Antioxidant vitamin C improves endothelial function in obstructive sleep apnea.

RATIONALE: Obstructive sleep apnea (OSA) is associated with oxidative stress, endothelial dysfunction, and increased cardiovascular morbidity and mortality. OBJECTIVE: We tested the hypothesis that endothelial dysfunction in patients with OSA is linked to oxidative stress. METHODS: In the present study, we measured flow-mediated dilation (FMD) of the brachial artery by ultrasound in 10 otherwise healthy, untreated patients with OSA and 10 age-and sex-matched control subjects without sleep-disordered breathing before and after intravenous injection of the antioxidant vitamin C. The investigator performing the FMD measurements was blinded to the status of the patients. RESULTS: When compared with control subjects, baseline FMD was significantly reduced in the patients with OSA. After intravenous injection of 0.5 g vitamin C, vasoreactivity remained unchanged in the control subjects. In the patients with OSA, ascorbate led to an increase in FMD to a level comparable to that observed in the control group. CONCLUSION: The reduced endothelial-dependent vasodilation in untreated patients with OSA acutely improves by the free radical scavenger vitamin C. These results are in favor of oxidative stress being responsible for the endothelial dysfunction in OSA. Antioxidant strategies should be explored for the treatment of OSA-related cardiovascular disease.

Administration, Sublingual↗

Does who you marry matter for your health? Influence of patients' and spouses' personality on their partners' psychological well-being following coronary artery bypass surgery.

Research suggests that presurgical personality attributes influence postsurgical well-being in both patients and their spouses in the context of coronary artery bypass grafting (CABG) surgery. The authors hypothesized that a spouse's characteristics would influence a partner's psychological well-being, regardless of whether he or she was the patient or the caregiver. In this study, 111 male patients and their caregiver spouses completed measures of neuroticism, optimism, perceived marital satisfaction, and depression prior to elective CABG. Follow-up was conducted at 18 months. As expected, higher caregiver presurgical neuroticism predicted higher patient depressive symptoms at follow-up, with caregiver's concurrent 18-month affect controlled for. Likewise, higher patient presurgical neuroticism predicted higher caregiver depressive symptoms at follow-up. Additionally, higher patient presurgical depressive symptoms and lower presurgical optimism contributed to greater caregiving burden. Relationship satisfaction moderated these effects. These results suggest that partners' personality traits are important determinants of both patients' and their caregiving spouses' well-being.

Adult↗

Older spouses' perceptions of partners' chronic arthritis pain: implications for spousal responses, support provision, and caregiving experiences.

This study of older patients with osteoarthritis and their spouses examined concordance between patients' and spouses' reports of patients' pain severity and the association of concordance with support and caregiving outcomes. Patients and spouses independently viewed videotapes of the patient performing simulated household tasks and provided ratings of patients' pain. Spousal overestimation of patients' pain was the most common type of nonconcordance. Spouses who were accurate in their perceptions of their partner's level of pain during a log-carrying task responded less negatively and provided emotional support that was more satisfying to patients. In addition, spouses who were accurate in their perceptions of their partner's pain during the log-carrying task reported less stress from providing support and assistance. Future research that uses such observational methods may be highly useful for understanding the effects of chronic illness on older couples.

Activities of Daily Living↗

Preparing caregivers for the death of a loved one: a theoretical framework and suggestions for future research.

Caring for a terminally ill loved one and the death of that person are two of the most stressful human experiences. Recent research suggests that a substantial number of caregivers are unprepared for the death and that these caregivers may be at greater risk of psychological distress. The literature on preparedness and mental health, however, is in its infancy. The purpose of this paper, therefore, is to summarize the literature in order to stimulate discussion and research on preparedness. It is our view that preparedness for the death of a loved one is an important contributor to caregiver well-being and bereavement outcomes and that more work in this area is needed in order to improve the care provided to caregivers of seriously or terminally ill patients. We briefly review the literature on preparedness, present a theoretical model delineating the relationships between preparedness, caregiver-health care provider communication, and caregiver well-being, and provide suggestions for future research.

Caregivers↗

Caregiving at the end of life.

This paper provides a review of family caregiving for adult patients with serious, lifethreatening illness. Areas covered include the (1) epidemiology of family caregiving, (2) cross-cultural issues in caregiving, (3) impact of caregiving on families, (4) similarities and differences involved in providing care for patients with various illnesses, and (5) interventions for family caregivers. The importance of family caregiving to palliative care practice is emphasized.

Caregivers↗

Preparedness for the death of a loved one and mental health in bereaved caregivers of patients with dementia: findings from the REACH study.

BACKGROUND: Although it has been suggested that family and friends who are prepared for the death of a loved one have less distress, the relationship between preparedness and bereavement mental health is inconclusive. OBJECTIVES: To determine the relationship between preparedness for the death and mental health in bereaved caregivers of dementia patients and explore predictors of preparedness. DESIGN: A prospective study of family caregivers of persons with dementia. Standardized assessment instruments and structured questions were used to collect data at study entry and at 6, 12, and 18 months. Multiple caregiving-related variables were collected. Bereaved caregivers reported whether they were "not at all" prepared or prepared for the death of their loved one. SUBJECTS: Two hundred twenty-two bereaved caregivers RESULTS: Twenty-three percent of caregivers were not prepared for the death. These caregivers had more depression, anxiety, and complicated grief symptoms. Black caregivers, caregivers with less education, those with less income, and those with more depressive symptoms prior to the death were more likely to perceive themselves as "not at all" prepared. In contrast, the amount of pain the care recipient was in prior to death was positively associated with preparedness. CONCLUSIONS: Despite providing high-intensity care, often for years, many bereaved caregivers perceived themselves as unprepared for the death. These caregivers had more depression, anxiety, and complicated grief symptoms. Future work should be directed to confirming these findings and determining how best to intervene with high-risk caregivers.

Aged↗