Caregiving for children and adults with chronic conditions: introduction to the special issue.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
R Schulz
Publications and source records attributed to R Schulz.
Adenylyl cyclase supersensitivity in opioid-withdrawn NG108-15 hybrid cells requires Gs but is not mediated by the Gsalpha subunit.
On the cellular level, opioid dependence is characterized by a significant elevation of adenylyl cyclase (AC) activity after drug withdrawal, a regulatory phenomenon termed "AC supersensitivity" or "cAMP overshoot." The present study examines the role of the stimulatory G protein (Gs) in the expression of naloxone precipitated opioid withdrawal in chronically morphine (10 microM; 3 days) treated neuroblastoma X glioma (NG108-15) hybrid cells. Determination of high-affinity [3H]forskolin binding to intact cells, which provides a direct parameter for the binding of the activated alpha-subunit of Gs (Gsalpha) to AC, revealed that the enhancement of AC activity after opioid withdrawal is not caused by an increased stimulation of effector activity by Gsalpha. Although not a direct function of Gs, the expression of AC supersensitivity required Gsalpha-mediated stimulation of AC, because 1) the enhancement of AC activity after opioid withdrawal was observed only in the presence of low, but not of high concentrations of forskolin, and 2) chemical inactivation of Gsalpha by low pH pretreatment abolished the induction of AC supersensitivity. Moreover, the regulatory mechanism underlying AC supersensitivity not only required the presence of activated Gsalpha per se, but functional intact stimulatory signal transduction pathways. Indeed, blockade of prostaglandin E1 receptor/Gs interaction in situ with a site-specific anti-Gsalpha antibody, as well as uncoupling of prostaglandin E1 receptor signaling by cholera toxin-catalyzed ADP-ribosylation of Gsalpha, prevented the expression of AC supersensitivity in membranes from opioid-withdrawn cells. These results suggest that the enhancement of AC activity in opioid-dependent cells, triggered by drug withdrawal, is not a direct Gsalpha effect, but involves a secondary regulatory event that requires costimulation of AC by acutely receptor-activated Gsalpha.
Adenylyl Cyclases↗
Features of short-term myocardial hibernation.
When severe ischemia, such as that resulting from a sudden and complete coronary artery occlusion, is prolonged for more than 20-40 min, myocardial infarction develops, and there is irreversible loss of contractile function. When myocardial ischemia is less severe but nevertheless prolonged, the myocardium is dysfunctional but can remain viable. In such ischemic and dysfunctional myocardium, contractile function is reduced in proportion to the reduction in regional myocardial blood flow; i.e. a state of 'perfusion-contraction matching' exists. The metabolic status of such myocardium improves over the first few hours, as myocardial lactate production is attenuated and creatine phosphate, after an initial reduction, returns towards control values. Ischemic myocardium, characterized by perfusion-contraction matching, metabolic recovery and lack of necrosis, has been termed 'short-term hibernating myocardium'. Short-term hibernating myocardium can respond to inotropic stimulation with increased contractile function, although at the expense of renewed worsening of the metabolic status. This occurrence of increased regional contractile function at the expense of metabolic recovery during inotropic stimulation can be used to identify short-term hibernating myocardium. When inotropic stimulation is prolonged, short-term hibernation is impaired and myocardial infarction develops. The mechanisms responsible for the development of short-term myocardial hibernation remain unclear at present. Significant involvement of adenosine and activation of ATP-dependent potassium channels have been excluded. The role of triggering events and acidosis is controversial. Short-term hibernating myocardium is, however, characterized by reduced calcium responsiveness.
Acidosis↗
Endogenous protective mechanisms in myocardial ischemia: hibernation and ischemic preconditioning.
Myocardial ischemia, even if it persists for a prolonged period of time, does not inevitably induce irreversible damage. Recent studies have identified 2 phenomena that are characterized by endogenous cardioprotective features, i.e., myocardial hibernation and ischemic preconditioning. Myocardial hibernation is characterized by chronic contractile dysfunction during persistent ischemia. The myocardium remains viable, and function is restored upon reperfusion. Ischemic preconditioning is characterized by delayed development of infarct size when prolonged and severe myocardial ischemia is preceded > or = 1 short-lasting episodes of ischemia and reperfusion. While ischemic preconditioning involves the activation of the adenosine A1 receptor, the bradykinin receptor, and activation of adenosine triphosphate (ATP)-dependent potassium channels, the mechanisms underlying myocardial hibernation are still unclear.
Adaptation, Physiological↗
Regulation of stimulatory adenylyl cyclase signaling during forskolin-induced differentiation of mouse neuroblastoma x rat glioma (NG108-15) cells.
Chronic exposure of neuroblastoma x glioma (NG108-15) cells to substances that elevate intracellular cAMP levels results in morphological differentiation into a more neuronal-like phenotype. Here we report that forskolin-induced differentiation is accompanied by a biphasic regulation of stimulatory adenylyl cyclase (AC) signaling. While 1 day of forskolin exposure produces an initial increase in basal, [AIF4](-)-, and prostaglandin E1 (PGE1)-stimulated AC activities, stimulatory signal transduction is substantially reduced after complete differentiation of the cells (6 days). Western blot analysis revealed that these functional changes correlate well with changes in the quantity of G(s)alpha, the stimulatory component of AC. Additional forskolin-induced adaptations were found for PGE1 receptors, inhibitory G proteins and AC. These data demonstrate that neuronal differentiation of NG108-15 cells is associated with complex regulatory changes within the stimulatory PGE1 receptor system.
Adenylyl Cyclases↗
Influence of age on symptoms at presentation in patients with community-acquired pneumonia.
BACKGROUND: Advanced age has become a well-recognized risk factor for death in patients with pneumonia. It may also be associated with reduced symptom reporting, raising the possibility that diagnosis and treatment may be delayed in older patients. OBJECTIVE: To evaluate the association between age and the presenting symptoms in patients with community-acquired pneumonia. METHODS: This study was conducted at inpatient and outpatient facilities at 3 university hospitals, 1 community hospital, and 1 staff-model health maintenance organization. Patients included adults (age > or = 18 years) with clinical and radiographic evidence of pneumonia, who were able to complete a baseline interview. The presence of 5 respiratory symptoms and 13 nonrespiratory symptoms were recorded during a baseline patient interview. A summary symptom score was computed as the total number of symptoms at presentation. RESULTS: The 1812 eligible study patients were categorized into 4 age groups: 18 through 44 years (43%), 45 through 64 years (25%), 65 through 74 years (17%), and 75 years or older (15%). For 17 of the 18 symptoms, there were significant decreases in reported prevalence with increasing age (P < .01). In a linear regression analysis, controlling for patient demographics, comorbidity, and severity of illness at presentation, older age remained associated with lower symptom scores (P < .001). CONCLUSIONS: Respiratory and nonrespiratory symptoms are less commonly reported by older patients with pneumonia, even after controlling for the increased comorbidity and illness severity in these older patients. Recognition of this phenomenon by clinicians and patients is essential given the increased mortality in elderly patients with pneumonia.
Adult↗
Medical outcomes and antimicrobial costs with the use of the American Thoracic Society guidelines for outpatients with community-acquired pneumonia.
CONTEXT: The American Thoracic Society (ATS) published guidelines based on expert opinion and published data--but not clinically derived or validated--for treating adult outpatients with community-acquired pneumonia. OBJECTIVE: To compare medical outcomes and antimicrobial costs for patients whose antimicrobial therapy was consistent or inconsistent with ATS guidelines. DESIGN: Multicenter, prospective cohort study. SETTING: Emergency departments, medical clinics, and practitioner offices affiliated with 3 university hospitals, 1 community teaching hospital, and 1 health maintenance organization. PARTICIPANTS: A total of 864 immunocompetent, adult outpatients with community-acquired pneumonia: 546 aged 60 years or younger with no comorbidity and 318 older than 60 years or with 1 comorbidity or more. MAIN OUTCOME MEASURES: Patients' antimicrobial therapy was classified as being consistent or inconsistent with the ATS guidelines. Mortality, subsequent hospitalization, medical complications, symptom resolution, return to work and usual activities, health-related quality of life, and antimicrobial costs were compared among those treated consistently or inconsistently with the guidelines. RESULTS: Outpatients aged 60 years or younger with no comorbidity who were prescribed therapy consistent with ATS guidelines (ie, erythromycin with some exceptions) had 3-fold lower antimicrobial costs ($5.43 vs $18.51; P<.001) and no significant differences in medical outcomes. Outpatients older than 60 years or with 1 comorbidity or more who were prescribed therapy consistent with ATS guidelines (ie, second-generation cephalosporin, sulfamethoxazole-trimethoprim, or beta-lactam and beta-lactamase inhibitor with or without a macrolide) had 10-fold higher antimicrobial costs ($73.50 vs $7.50; P<.001); despite trends toward higher mortality and subsequent hospitalization, no significant differences in medical outcomes were observed. CONCLUSION: Our findings support the use of erythromycin as recommended by the ATS guidelines for outpatients aged 60 years or younger with no comorbidity. Although the antimicrobial therapy recommended in outpatients older than 60 years or with 1 comorbidity or more is more costly, this observational study provides no evidence of improved medical outcomes in the small subgroup who received ATS guideline-recommended therapy.
Adult↗
[Geriatric orthopedic treatment of Jehovah's Witnesses?].
The proceedings in elective surgery on "Jehova's Witnesses" differ from customary operations. Intensive physical therapy, high complaint, internal and anesthesiologic examination, exact information about the risks and facilities as "cell-saving" etc. and postoperative planing are necessarily required ahead of the indication to operate. Additional complications may be possible. The higher costs are balanced by avoiding, respectively getting rid of disability, immobilisation and the needing of care. A religious dogma leads to a special point of view towards life, death, health and expectations towards' the life and its quality as well as social support. It is a difficult undertaking in elective surgery to bring this dogma and our ethic and moral values into accord. It is not medicine vs. religion, but to point out a way and the limits by respecting the individual ideology, abstract conceptions and philosophy of life.
Aged↗
Effects of atrial natriuretic peptide on phagocytosis and respiratory burst in murine macrophages.
Atrial natriuretic peptide (ANP) is known to affect cardiovascular physiology displaying both hormone- and neurotransmitter characteristics. However, there is increasing evidence that ANP possesses additional biological activities referring to the immune system. To further strengthen this hypothesis the effect of ANP on two major functions of macrophages, i.e., phagocytosis and respiratory burst was tested. Both parameters were analyzed by flow cytometry employing bone marrow derived macrophages and the murine macrophage cell line J774. In both cell types preincubation with ANP dose dependently (10(-10)-10(-7) M) increases ingestion of opsonized fluorescent latex particles. The respiratory burst activity was monitored by oxidation of dihydrorhodamine-123 in cells stimulated either with phorbol-myristate (PMA, 10 ng/ml) or formyl-Met-Leu-Phe (fMLP, 1 microM). In both cases preexposure of cells to ANP (10(-8)-10(-6) M) for 2 h enhances reactive oxygen production. The data demonstrate an influence of ANP on important defense mechanisms of macrophages and thus extend the knowledge regarding the pharmacological profile of this natriuretic peptide.
Animals↗
Distinct efficacies for two endogenous ligands on a single cognate gonadoliberin receptor.
A cDNA encoding a putative gonadoliberin receptor was cloned from the pituitary of the African catfish. Conceptual translation predicts a protein of 379 amino acids which shows typical characteristics of GTP-binding-protein-coupled receptors. The isolated cDNA was stable expressed in human embryonic kidney (HEK) 293 cells which were used for studies on gonadoliberin-activated second messenger systems (inositol phosphate production; increase in cAMP and/or intracellular Ca2+). The isolated cDNA encoded a functional receptor, designated catfish gonadoliberin receptor (cfGnRH-R), which had an amino acid sequence similarity of 38% with mammalian gonadoliberin receptors. In contrast to its mammalian counterparts which lack an intracellular carboxy-terminal domain, the cfGnRH-R contains an additional 49 amino acid residues. From the two endogenous gonadoliberins in African catfish, chicken gonadoliberin-II had a several hundredfold higher potency than catfish gonadoliberin to activate cfGnRH-R-associated second messenger systems in transfected HEK 293 cells. This is in line with the previously determined higher gonadotropin-release capacity of chicken gonadoliberin-II in catfish. Stimulation of second messenger systems with chicken gonadoliberin-II, but not with catfish gonadoliberin, resulted in a biphasic effect and chicken gonadoliberin-II led to a higher maximum stimulation than catfish gonadoliberin. Challenging cfGnRH-R simultaneously with chicken gonadoliberin-II and catfish gonadoliberin did not lead to additive effects. In contrast, two types of mutual inhibitory effects were recorded. These data indicate that a single cognate cfGnRH-R couples with distinct efficacies to signal transduction systems upon stimulation by the two endogenous gonadoliberins which, in addition, may interact negatively.
Amino Acid Sequence↗
Health effects of caregiving: the caregiver health effects study: an ancillary study of the Cardiovascular Health Study.
We propose that two related sources of variability in studies of caregiving health effects contribute to an inconsistent pattern of findings: the sampling strategy used and the definition of what constitutes caregiving. Samples are often recruited through self-referral and are typically comprised of caregivers experiencing considerable distress. In this study, we examine the health effects of caregiving in large population-based samples of spousal caregivers and controls using a wide array of objective and self-report physical and mental health outcome measures. By applying different definitions of caregiving, we show that the magnitude of health effects attributable to caregiving can vary substantially, with the largest negative health effects observed among caregivers who characterize themselves as being strained. From an epidemiological perspective, our data show that approximately 80% of persons living with a spouse with a disability provide care to their spouse, but only half of care providers report mental or physical strain associated with caregiving.
Activities of Daily Living↗
Research on physiological and physical concomitants of caregiving: where do we go from here?
This article discusses the current state of research on the physiological and physical concomitants of caregiving. We offer recommendations about theoretical, empirical, and treatment issues that researchers should consider in future investigations. Important theoretical issues include specifying acute and chronic stress in caregiving research. Empirical issues include sample selection, home versus clinic assessments, the use of experimental probes, moderating and mediating variables, and measurement issues (problems with self-report of health, medical records, physical exams, and lab assessments). Finally, we note that investigators should use this newfound knowledge to target interventions to specific subsets of vulnerable caregivers. In this way, basic research into caregiving, as a model of chronic human stress, can provide more focused approaches to benefit both caregivers and patients.
Arousal↗
[Embolic complications in bacterial endocarditis].
Embolic complications are a major prognostic determinant in the clinical course of infective endocarditis (IE) with an incidence of about 30-50%. In order to analyze risk factors leading to embolism in native (NVE) and prosthetic valve endocarditis (PVE), we reviewed 177 consecutive patients; 43% were female, 57% male, PVE occurred in 24% of all patients all left-sided, among the NVE were 11% right-sided IE. Major embolic complications occurred in 40% of all patients. In NVE, a higher rate of embolic events (45% vs. 26%; p < 0.05), and a larger vegetation size compared to PVE was observed (14 +/- 6 mm vs. 11 +/- 5 mm; p < 0.05). The most important risk factor for embolic complications in NVE was Staphylococcus aureus (odds ratio 6.4). Furthermore, double valve endocarditis, fever, and mitral valve endocarditis were associated with the risk for embolism. In case of severe regurgitation the rate of embolic complications was reduced (54% vs. 77%; p < 0.05). In PVE, fever was a risk factor for embolic events. Staphylococcus aureus was also a frequent microorganism in embolism (45% vs. 22%). The in-hospital mortality was significantly increased in case of embolism (NVE 40% vs. 11%; p < 0.001; PVE 36% vs. 9% p < 0.05). About 50% of all embolic events occurred before admission. In NVE, due to high in-hospital mortality, the rate of patients with embolism undergoing surgery was lower (57% vs. 72%; p < 0.05); whereas in PVE no significant difference was observed. In patients with NVE, aspirin therapy because of coronary artery disease appeared to reduce the rate of embolic complications (11% vs. 47%). However, the low number of patients on aspirin (9%) does not allow recommendations regarding a potential benefit. In conclusion, identification of risk factors leading to embolism in IE may be useful in considering early surgical therapy. However, the high rate of embolic complications before hospital admission indicates a need for improving the diagnostic delay in the prehospital phase.
Adult↗
Generation of peroxynitrite contributes to ischemia-reperfusion injury in isolated rat hearts.
OBJECTIVE: The acute release of radicals upon reperfusion following myocardial ischemia may include both nitric oxide (NO) and superoxide anion (O2-.). The generation of peroxynitrite (ONOO-) from these radicals may contribute to ischemia-reperfusion injury. Our objective was to measure the generation of ONOO- during reperfusion of isolated hearts subjected to ischemia and to determine the effects of inhibition of NO synthase with NG-monomethyl-L-arginine (L-NMMA), or supplementation of NO with S-nitroso-N-acetyl-D,L-penicillamine (SNAP), on ONOO- generation and on the recovery of mechanical function. METHODS AND RESULTS: Isolated rat hearts were perfused at constant pressure with Krebs' buffer containing L-tyrosine, which reacts with ONOO- to form dityrosine, a fluorescent product. Dityrosine was detected in the coronary effluent of hearts infused with synthetic ONOO-. In hearts subjected to 20 min of global, no-flow ischemia there was a marked rise in endogenous ONOO- formation which peaked at 30 s of reperfusion. Formation of ONOO- was dependent upon synthesis of both NO and O2-., as dityrosine release was abolished by L-NMMA or superoxide dismutase, respectively. L-NMMA caused a concentration-dependent improvement in the recovery of mechanical function during reperfusion. Infusion of SNAP also abolished dityrosine release at reperfusion and improved the recovery of post-ischemic function. CONCLUSIONS: Our results show for the first time that reperfusion of the ischemic heart causes the acute production of ONOO-. Inhibiting the biosynthesis of ONOO- with L-NMMA or antagonizing its oxidant actions with SNAP are possible strategies to protect the heart from ischemia-reperfusion injury.
Animals↗
'Myocardial hibernation'--questions and controversies.
Explore the source record for details and available documents.
Animals↗
Nitric oxide and platelet function: implications for neonatology.
Nitric oxide (NO) is a mediator that modulates vessel wall tone and hemostatic-thrombotic balance. Platelet function is regulated by NO generated from platelets, endothelial cells and leukocytes. Nitric oxide has been shown to inhibit platelet adhesion, aggregation, and stimulate disaggregation of preformed platelet aggregates. Many of the effects of NO are mediated by its stimulation of guanylate cyclase and the formation of cyclic GMP and its subsequent transduction mechanism. In vivo, NO is likely to interact with prostacyclin, metabolites of ecto-nucleotidase, and lipoxygenase to modulate platelet function in a synergistic manner. An imbalance of NO production (deficiency or overproduction) has been implicated in the pathogenesis of various vascular disorders including thrombosis, atherosclerosis, septicemia, and ischemia-reperfusion injury. It is likely that some of detrimental effects of NO are mediated through its reaction with superoxide anion to form the potent oxidant, peroxynitrite. Nitric oxide gas and NO donors are used for the pharmacological treatment of various vascular disorders. Because inhaled NO has been documented to improve systemic oxygenation and reduce the need for extracorporeal membrane oxygenation, it has been widely used in neonates with severe hypoxemia. An inhibition of platelet function, resulting in a prolonged bleeding time, has been shown in adults receiving inhaled NO. Because bleeding complications may occur in high-risk infants, it is important to evaluate the effect of inhaled NO on platelet function and its correlation with clinical consequences such as intracranial hemorrhage. For these reasons, hemostasis should be carefully monitored during the administration of inhaled NO to critically ill neonates.
Blood Platelets↗
Little Evidence for Lethal Reperfusion Injury to Cardiomyocytes.
Explore the source record for details and available documents.
Journal Article↗
Assessment of depression in patients with brain pathology: the case of stroke.
The assessment of depression in patients with brain pathologies--a topic of considerable clinical and research interest--is complicated by a variety of factors. Among the most problematic are cognitive consequences of brain injury that can diminish the reliability and validity of information used to diagnose depression, determine its severity, ascertain its predictors, and evaluate its impact. In this article, the authors examine the challenges to depression assessment in patients who have had a stroke, the neurologically impaired population in which it has been most frequently studied. Focusing on poststroke depression research, they describe methodological limitations that may contribute to conflicting outcomes and conclusions and offer suggestions for improving the specificity, consistency, validity, and reliability of assessment methods and procedures when investigating depression in patients with brain pathologies.
Brain Damage, Chronic↗