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Biomedical subjects

R Schulz

Publications and source records attributed to R Schulz.

At least 289 records · Page 16Linked to original sources

Pessimism, age, and cancer mortality.

Cancer patients (N = 238) receiving palliative radiation treatment were followed for 8 months; 70 patients had died by the 8-month follow-up. Controlling for site of cancer and level of symptomatology at baseline, the authors studied the independent effects on mortality of pessimism, optimism, and depression. The findings show that the endorsement of a pessimistic life orientation is an important risk factor for mortality, but only among younger patients (ages 30-59). Attempts to replicate this finding with conceptually related constructs such as depression or optimism did not yield significant associations for either younger or older patients, suggesting that negative expectations about the future may contribute to mortality in unique ways. The authors conclude that attempts to link psychosocial factors to mortality should focus on specific psychological constructs instead of diffuse, global measures that cover many psychological phenomena and that the role of psychological processes in mortality may vary dramatically depending on age.

Adult↗

When primary and secondary caregivers disagree: predictors and psychosocial consequences.

The purpose of this study was to investigate primary caregiving spouses' and their lay helpers' divergent opinions about the caregiving environment. Through parallel assessments, both primary and secondary caregivers of a patient with Alzheimer's disease were asked to rate the degree of patient problem behaviors; the degree of strain the primary caregiver was experiencing; and primary care-giver efficacy, or perceived ability to cope with caregiving demands. Analyses concentrated on the general levels of disagreement in these domains, as well as on potential predictors and consequences of such disagreement. Results revealed a substantial divergence in perceptions across caregiving domains, with relatively less disagreement about patient problem behaviors and primary caregiver strain than about primary caregiver coping efficacy. Primary caregivers with relatively pessimistic secondary caregivers experienced relatively less psychosocial distress than primary caregivers with more optimistic helpers. These findings were strongest among female-female caregiving dyads. Theoretical implications and methodological limitations of the study are discussed, along with suggestions for future research.

Adaptation, Psychological↗

Spousal similarity in subjective well-being: the Cardiovascular Health Study.

This study examines the extent to which one spouse's subjective well-being predicts that of the partner (N = 1,040 spousal pairs, 65 years or older). Prior research is extended in two ways: (a) The similarity of both affective domains (depressive symptoms, feelings about life as a whole, and satisfaction with the meaning and purpose of life) and nonaffective domains (perceived health) are examined, and (b) known predictors of well-being in older adults (sociodemographic variables, self and spouse health status variables, and exposure to common environmental events) are statistically controlled. Results indicate that one spouse's assessments of well-being and depression predict the other's well-being even after controlling for known predictors of these outcomes. Given the similarity of findings for affective and nonaffective domains, multiple mechanisms, including contagion, mate selection, and common environmental influences, are speculated as likely to contribute to this phenomenon.

Activities of Daily Living↗

Human corticotropin-releasing hormone and thyrotropin-releasing hormone modulate the hypercapnic ventilatory response in humans.

Human corticotropin-releasing hormone (hCRH) and thyrotropin-releasing hormone (TRH) are known to stimulate ventilation after i.v. administration in humans. In a placebo-controlled, single-blind study we aimed to clarify if both peptides act by altering central chemosensitivity. Two subsequent CO2-rebreathing tests were performed in healthy young volunteers. During the first test 0.9% NaCl was given i.v.; during the second test 200 micrograms of hCRH (n = 12) or 400 micrograms of TRH (n = 6) was administered i.v. Nine subjects received 0.9% NaCl i.v. during both rebreathing manoeuvres. The CO2-response curves for the two tests were compared within the same subject. In the hCRH group a marked parallel shift of the CO2-response curve to the left was observed after hCRH (P < 0.01). The same effect occurred following TRH but was less striking (P = 0.05). hCRH and TRH caused a reduction in the CO2 threshold. The CO2-response curves in the control group were nearly identical. The results indicate an additive effect of both releasing hormones on the hypercapnic ventilatory response in humans, presumably independent of central chemosensitivity.

Carbon Dioxide↗

Molecular Analysis in a Patient With Waldenström's Macroglobulinemia Reveals a Rare Case of Biclonality.

Background: The immunoglobulin and T-cell receptor gene rearrangement test is used to identify monoclonal populations in B- and T-cell malignancies and has become an important adjunct to morphologic analysis and immunophenotyping by flow cytometry. Waldenström's macroglobulinemia (WM) is typically a monoclonal proliferation of B cells with morphology of plasmacytoid lymphocytes and production of monoclonal IgM. Methods and Results: We report a case of WM with biclonal gammopathy (IgM kappa and IgM lambda) involving the blood and a diffuse lymphoplasmacytic infiltrate in the bone marrow in an 83-year-old man. Immunophenotyping of the blood and bone marrow aspirate revealed B cells expressing IgM lambda surface immunoglobulins and CD5+, CD19+, and CD20+ surface markers. Gene-rearrangement analysis with the Southern blot technique revealed multiple rearranged bands in each lane of restricted patient DNA after probing with both immunoglobulin heavy (J(H))- and light (J(kappa))-chain gene probes. Conclusions: Biclonal gammopathy in WM and biclonal B-cell proliferations as determined by gene-rearrangement studies are rare entities, and few evaluations of them are reported in the literature. To our knowledge, this case is the first one of biclonal WM to have been evaluated by serum protein immunofixation, immunohistologic staining, immunophenotyping by flow cytometry, and immunoglobulin gene-rearrangement analysis.

Journal Article↗

Effects of different antigenic microenvironments on the course of CD8+ T cell responses in vivo.

The influence of microenvironment on the course of CD8 + T cell responses in vivo was investigated by injecting H-2Kb-specific T cells from donor TCR transgenic (TCR-Tg) mice into H-2kb-Tg mice. H-2Kb expression in recipients was either ubiquitous (CBK mice) or restricted to myeloid and erythroid cells (K beta mice). Donor T cells proliferated as extensively and acquired similar surface phenotypes in spleen of both recipient types. Thus, neither the restricted pattern of H-2Kb expression nor the significantly reduced level of H-2Kb expression by myeloid cells in Kbeta recipients affects the ability of the splenic microenvironment to prime T cell proliferation in vivo. However, an unsustained burst of cytolytic activity was generated rapidly in spleen of CBK recipients, whereas relatively little cytolytic activity was generated in K beta spleen. This indicates that effector T cells were not generated efficiently in spleen of Kbeta recipients even though extensive T cell proliferation was taking place in this microenvironment. Furthermore, activated donor T cells dispersed rapidly throughout primary and secondary lymphoid organs of Kbeta recipients, whereas few T cells migrated from spleen in CBK recipients. Consequently, the course of CD8+ T cell responses and the anatomical distribution of activated T cells are profoundly influenced by the nature of the antigenic microenvironment encountered in vivo. We conclude that T cells rapidly proliferate and acquire new tissue-homing characteristics but do not differentiate into cytolytic effector cells at the site of priming when they encounter myeloid cells expressing low levels of antigen in vivo.

Animals↗

Clinical outcome and echocardiographic findings of native and prosthetic valve endocarditis in the 1990's.

Prosthetic valve endocarditis is considered to be associated with a more severe prognosis than native valve endocarditis. Among other factors, inappropriate visualization of vegetations in prosthetic valve endocarditis by transthoracic echocardiography is responsible for this observation. Since the introduction of transoesophageal echocardiography into clinical practice the diagnostic sensitivity and specificity of the detection of vegetations located on prosthetic valves have been enhanced. Therefore we aimed to determine and compare the prognosis of prosthetic valve endocarditis and native valve endocarditis in the era of this improved diagnostic approach. One hundred and six episodes of infective endocarditis in 104 patients were seen at our institution between 1989 and 1993. Eighty patients (77%) had native valve endocarditis and 24 (23%) had late prosthetic valve endocarditis. In the latter group two patients had recurrent infective endocarditis. Patients with prosthetic valve endocarditis were older (mean age 64 vs 54 years in native valve endocarditis; P < 0.001) and the majority was female (62% vs 38% in native valve endocarditis; P < 0.05). In prosthetic valve endocarditis, infection of a valve in the mitral position predominated (65% vs 30% in native valve endocarditis; P < 0.01), whereas in native valve endocarditis more than half the cases had isolated aortic valve endocarditis (51% vs 27% in prosthetic valve endocarditis; P < 0.01). In prosthetic valve endocarditis more cases were caused by Staphylococcus aureus (31% vs 14% in native valve endocarditis; P = 0.08), whereas in native valve endocarditis the most frequent organisms were streptococci (29% vs 19% in prosthetic valve endocarditis; P = 0.12). Differences in the clinical features of native valve endocarditis and prosthetic valve endocarditis could not be found except for a higher rate of embolism in native valve endocarditis (40% vs 19% in prosthetic valve endocarditis; P < 0.05). Vegetations could be detected by transthoracic echocardiography more frequently in native valve endocarditis (71% vs 15% in prosthetic valve endocarditis; P < 0.0001). Transoesophageal echocardiography visualized vegetations in 95% of the episodes of native valve endocarditis and in 80% of the episodes of prosthetic valve endocarditis (P = 0.09). Thus, the diagnostic gain by transoesophageal echocardiography was greatest in prosthetic valve endocarditis. Patients with native valve endocarditis had significantly larger vegetations than patients with prosthetic valve endocarditis (P < 0.05 for length, P < 0.001 for width). The median time to diagnosis was similar in native valve endocarditis and prosthetic valve endocarditis (31 vs 28 days). Surgery was performed in 74% of patients with native valve endocarditis and in 58% of those with prosthetic valve endocarditis; the median time delay between the diagnosis of infective endocarditis and surgery tended to be shorter in prosthetic valve endocarditis than in native valve endocarditis (45 vs 60 days). The in-hospital mortality and the mortality during a follow-up of 22 +/- 10 months did not significantly differ between native valve endocarditis and prosthetic valve endocarditis (21% vs 17%; 28% vs 25%). In summary in the era of transoesophageal echocardiography, late prosthetic valve endocarditis does not seem to carry a worse prognosis than native valve endocarditis. This can be attributed in part to the improved diagnostic accuracy achieved by transoesophageal echocardiography leading to comparable diagnostic latency periods in both patient groups. Finally, better characterization of vegetations on prosthetic valves by transoesophageal echocardiography allows early lifesaving surgery in patients with prosthetic valve endocarditis.

Endocarditis, Bacterial↗

Stable expression and functional characterization of the cloned rat mu-opioid receptor in human epidermoid carcinoma (A431) cells.

Regulation of intracellular cAMP levels serves as a cellular model for chronic drug action. Since the adenylate cyclase effector system is under dual control of both stimulatory as well as inhibitory receptor systems, a permanent cell line was created in order to allow evaluation of acute and chronic opioid effects on stimulatory receptor function. For this purpose, the cloned rat mu-opioid receptor was stably expressed in human epidermoid carcinoma (A431) cells, which carries high levels of endogenous beta 2-adrenoceptors. Four out of 16 cell clones were found to express considerable amounts of [3H]diprenorphine binding sites and were further characterized. Scatchard analysis of saturation binding data revealed maximal binding capacities (Bmax) between 242.2 +/- 11 and 1,271.8 +/- 221 fmol/mg of membrane protein, whereas drug affinity was found similar among all cell clones tested (Kd = 1.4 +/- 0.2 nM). The expressed mu-receptors also mediated agonist inhibition of adenylate cyclase, indicating that these receptors are functionally coupled to intracellular signalling pathways. Long-term exposure of the cells to morphine (10 microM; 2 days) produced cellular correlates of chronic opioid action as displayed by both a decrease in the maximal degree of adenylate cyclase inhibition (tolerance) as well as an increase in overall effector activity (dependence). Thus, based on these parameters, mu-opioid receptor expressing A431 cells provide a promising tool to investigate cellular mechanisms of chronic drug action.

Adenylyl Cyclases↗

Depression and medical illness in late life: report of a symposium.

The high comorbidity of medical illnesses and late life depression poses both challenges and opportunities. Challenges in assessment techniques, diagnosis, and specific prognosis affect clinical care and research methodology alike. However, investigations that turn this vexing "confound" into research questions may prove fruitful. For clinicians working with older persons, recognizing the prognostic import of comorbid medical illnesses in late-life depression is essential to treatment planning. This comorbidity also poses difficulties in diagnosing depression inasmuch as symptoms of the medical conditions may overlap with those of an affective disorder. Symptom assessments must strike a balance between overly inclusive (e.g., mistakenly treating the psychomotor slowing of Parkinson's disease as depression) and overly exclusive (e.g., erroneously dismissing the patient's mood symptoms as "understandable"). Clinicians also should be sensitive to the broad range of symptomatic presentations with varying severities of both mood and medical disorders, as exemplified by variability across treatment settings. For researchers, similar issues are of relevance in planning investigative strategies. Consideration should be given to the following: 1. Case identification is a crucial first step; the approach to depressive symptoms potentially confounded by medical illnesses must be defined explicitly. Choice of an inclusive approach avoids premature exclusion of relevant phenomena; exploratory analyses can examine the effects of other approaches to the relationships of interest. 2. The use of similar research instruments across sample sites would greatly facilitate comparisons of results. Each subject group offers its own "leverage" for answering particular questions. Psychiatric inpatients will highlight the contributions of severe psychopathology (useful, for example, in identifying biologic markers). Medical inpatients are well suited to studies examining validity of different approaches to case identification, investigating health service utilization, or highlighting the contribution of acute, severe, life-threatening medical disorders to affective illness. Long-term care residents lend themselves to issues that benefit from compression of health processes over time. Medical outpatients have many advantages regarding generalizability and public health significance. Community samples are needed to determine the biases of all the above groups, which are each defined by service utilization. 3. Study of the relationships between depression and medical illness may further understanding of pathogenic mechanisms in late life mood disorders. Research questions might be guided by the biopsychosocial conceptual context described above. On the one hand, this context demands multidimensional study methodology to identify the routes by which medical illness influences depression in particular patient groups. Multivariate models should examine direct and indirect effects of medical illness on depression while, at the same time, considering intervening variables such as functional disability, personality, and social support. Guided multiple regressions or structural equation modeling will allow for determination of strengths of associations. 4. At the same time, and of particular importance if complex multivariate analyses are used, specific theoretic models should help direct focused investigations. The development and testing of such models is a major challenge that should be addressed by current research. Finally, from a societal perspective, the comorbidity of depression and medical illness likely has a tremendous impact on both health and health care delivery for older adults. Further study is needed to identify more specific approaches to treatment. Yet existing data clearly support a policy of routine psychiatric assessment of older people in general medical settings...

Age Factors↗

Uncoupling of contractile function from mitochondrial TCA cycle activity and MVO2 during reperfusion of ischemic hearts.

In this study we determined whether contractile function becomes uncoupled during reperfusion of ischemic hearts from mitochondrial tricarboxylic acid (TCA) cycle activity or myocardial O2 consumption (MVO2). Isolated working rat hearts perfused with buffer containing 1.2 mM palmitate and 11 mM glucose were subjected to 30 min of global ischemia followed by 60 min of aerobic reperfusion. During reperfusion, cardiac work recovered to 26.5 +/- 5.4% (n = 29) of preischemic levels, even though TCA cycle activity, fatty acid beta-oxidation, glucose oxidation, glycolysis, and MVO2 rapidly recovered. As a result, the efficiency of coupling between cardiac work and TCA cycle activity and between cardiac work and mitochondrial respiration decreased during reperfusion. In contrast, coupling of TCA cycle activity to MVO2 during reperfusion recovered to preischemic values. Addition of 1 mM dichloroacetate at reperfusion resulted in a significant increase in both cardiac work and cardiac efficiency during reperfusion. This was associated with a significant decrease in H+ production due to an improved balance between glycolysis and glucose oxidation. These data demonstrate that mitochondrial function and overall myocardial ATP production quickly recover in rat hearts after a 30-min period of global ischemia. However, mitochondrial ATP production is not efficiently translated into mechanical work during reperfusion. This may be due to an imbalance between glycolysis and glucose oxidation, resulting in an increase in H+ production and a decrease in cardiac efficiency.

Adenosine Triphosphate↗

No prevention of ischemic preconditioning by the protein kinase C inhibitor staurosporine in swine.

The delay of infarct size development by ischemic preconditioning involves the activation of protein kinase C in rats and rabbits. In dogs the role of protein kinase C in ischemic preconditioning is controversial. We investigated whether or not the activation of protein kinase C is a prerequisite for ischemic preconditioning in swine. Swine were used, since they are large mammals and since infarct development in this species, due to the lack of an innate collateral circulation, is similar to that in humans. In 20 enflurane-anesthetized swine, the proximal left anterior descending coronary artery was cannulated and perfused from an extracorporeal circuit. The impact of continuous intracoronary infusion of 10(-7) mol/L staurosporine, a potent protein kinase C inhibitor, on global and regional myocardial function (sonomicrometry), subendocardial blood flow (ENDO, microspheres), and infarct size (IS, triphenyltetrazolium chloride staining after 120 minutes of reperfusion) was analyzed. Staurosporine (10(-7) mol/L) abolished the 1.6-fold increase in coronary arterial resistance in response to 10(-6) mol/L IC 4 beta-phorbol 12-myristate 13-acetate, a potent protein kinase C activator. In the presence of staurosporine, 90 minutes of low-flow ischemia at an ENDO of 0.05 +/- 0.04 (mean +/- SD) mL.min-1.g-1 resulted in an IS of 12.5 +/- 8.6% (n = 10) of the area at risk. Also, in the presence of staurosporine, ischemic preconditioning by a cycle of 10 minutes of low-flow ischemia followed by 15 minutes reperfusion before the 90 minutes sustained ischemic period (ENDO, 0.05 +/- 0.03 mL.min-1.g-1) reduced IS to 3.3 +/- 3.4% (n = 10, P < .05). The protein kinase C inhibitor staurosporine does not prevent ischemic preconditioning in swine.

Alkaloids↗

Cardiac efficiency is improved after ischemia by altering both the source and fate of protons.

Cardiac efficiency is decreased in hearts after severe ischemia. We determined whether reducing the production of H+ from glucose metabolism or inhibiting the clearance of H+ via Na(+)-H+ exchange could increase cardiac efficiency during reperfusion. This was achieved using dichloroacetate (DCA) to stimulate glucose oxidation and 5-(N,N-dimethyl)-amiloride (DMA) to inhibit Na(+)-H+ exchange, respectively. Isolated working rat hearts were subjected to 30 minutes of global ischemia and 60 minutes of reperfusion. Glycolysis and oxidation rates of glucose, lactate, and palmitate were measured. Recovery of cardiac work, O2 consumption (MVO2), and rates of acetyl-coenzyme A and ATP production during reperfusion were determined. After ischemia, cardiac work recovered to 35 +/- 5% of preischemic values in control hearts (n = 23), although MVO2, tricarboxylic acid (TCA) cycle activity, and ATP production from glycolysis and oxidative metabolism rapidly recovered to preischemic levels. This decrease in cardiac efficiency was accompanied by a substantial production of H+ from glucose metabolism DCA caused a 2.2-fold increase in glucose oxidation, a 46 +/- 17% decrease in H+ production, a 1.6-fold increase in cardiac efficiency, and a 2.0-fold increase in cardiac work during reperfusion (n = 17). Inhibition of Na(+)-H+ exchange with DMA did not alter TCA cycle activity and ATP production rates but did result in a 1.8-fold increase in cardiac efficiency and a 1.7-fold increase in cardiac work (n = 12). These data show that cardiac efficiency and the contractile function after ischemia can be improved by either reducing the rate of H+ production from glucose metabolism during reperfusion or inhibiting the clearance of H+ via Na(+)-H+ exchange. Our data suggest that an increased requirement for ATP to restore ischemia-reperfusion-induced alterations in ion homeostasis contributes to the decrease in cardiac efficiency and contractile function after ischemia.

Acetyl Coenzyme A↗

Changes in perceived health status of depressed elderly patients treated until remission.

OBJECTIVE: The authors predicted that depressed elderly patients who responded to treatment would rate their baseline health more positively than nonresponders, that responders would again rate their health more positively once they were in remission, and that lower baseline self-ratings of health would predict lack of response to protocol treatment. METHOD: The Perception of Illness Scale was administered to 61 depressed elderly patients at baseline and again upon completion of the acute phase of a depression treatment protocol. A logistic regression was performed to ascertain whether Perception of Illness Scale scores predicted response to protocol treatment. RESULTS: Baseline Perception of Illness Scale scores were poorer among the nonresponders, accurately predicted response or lack of response in 75% of the subjects, and showed before-to after-treatment improvement among the responders. CONCLUSIONS: Patients who initially rated their health as fair to poor were less likely to recover from depression in a standardized treatment protocol. Self-ratings of health improved with resolution of depression.

Age Factors↗

Natriuretic peptide receptors on rat thymocytes: inhibition of proliferation by atrial natriuretic peptide.

Because the thymus expresses the natriuretic peptides (NP) as well as their respective receptors, an involvement of NP in the physiology of this organ has been suggested. To evaluate functional aspects of NP in the thymus, we looked for thymic cells bearing NP receptors (Npr). Furthermore, the regulation of Npr expression by activation of cells and the influence of NP on the proliferation of thymocytes was studied. Expression of receptor messenger RNAs (mRNAs) was examined by PCR and Northern blot. Existence of functional Npr was confirmed by measurement of cGMP, the second messenger of NP. Proliferation of thymocytes upon concanavalin A (Con A) stimulation was analyzed by incorporation of [3H]thymidine. We report her that thymocytes express mRNAs for the three Npr, namely Npra, Nprb, and Nprc and that activation of Npra and Nprb increases cGMP levels. Stimulation of thymocytes with Con A (1 microgram/ml, 48 h) resulted in an increase of mRNA coding for Npra, the receptor specific for atrial natriuretic peptide (ANP) and brain natriuretic peptide. Nprb and Nprc receptor expression was not altered under these conditions. In agreement with these data only ANP, but not the C-type natriuretic peptide, elicited increased cGMP response in Con A-stimulated cells. ANP inhibited also the proliferation of Con A stimulated thymocytes, whereas C-type natriuretic peptide did not show this effect. These results suggest that ANP affects the complex mechanisms of thymocyte proliferation and differentiation.

Animals↗

Interventions for caregivers of patients with Alzheimer's disease: a review and analysis of content, process, and outcomes.

Current reviews of the caregiver intervention literature have focused primarily on the outcomes of interventions for caregivers and general methodological limitations of individual studies (i.e., sampling and recruitment issues, adequacy of outcome measures, and generalization issues). Little attention has been paid to the specific factors affecting the therapeutic process, including the intensity and integrity of the interventions used. The purpose of this review is to examine closely the content and process of Alzheimer's disease (AD) caregiver interventions. We describe the types of interventions currently in use, factors affecting intervention outcomes, and we conclude with specific recommendations for the application of intervention technology and for the documentation of intervention research.

Alzheimer Disease↗

Hypotrichosis, hair structure defects, hypercysteine hair and glucosuria: a new genetic syndrome?

Structural hair changes may be the expression of a genetic disorder affecting hair growth, part of a congenital syndrome with accompanying hair malformations, or a marker for an underlying metabolic disorder. We report a 22-month-old Turkish girl and her 10-month-old brother, whose scalp hair became fragile and sparse at about 6-7 months of age. Glucosuria, without diabetes or kidney disease, was detected 3-4 months later. Clinical examination revealed normal physical and mental development, and an analysis of plucked hairs showed dysplastic and broken hair shafts. Polarizing microscopy and scanning electron microscopic studies revealed torsion, and irregularities and impressions of the hair shaft, as seen in pili torti, trichorrhexis nodosa and pseudomonilethrix. Analysis of the amino-acid composition of the hair demonstrated a significant reduction of sulphonic cysteic acid and an elevated cysteine and lanthionine content in the girl, and elevated lanthionine levels in her brother. Electrophoretic analysis of the girl's hair proteins revealed a normal composition but a high extractability of hair proteins. The triad of hypotrichosis, structural hair-shaft defects and abnormal amino-acid composition, accompanied by glucosuria without diabetes, may represent a new genetic syndrome.

Amino Acids↗