Biomedical subjects

R Schulz

Publications and source records attributed to R Schulz.

At least 19 recordsLinked to original sources

PubMed1992

Opioid-controlled adenylate cyclase in the guinea-pig myenteric plexus is confined to nerve somata.

Previous studies with the electrically stimulated longitudinal muscle-myenteric plexus preparation of the guinea-pig ileum suggested that opioid control of adenylate cyclase is confined to nerve somata. No indication was found for an opioid effect on the enzyme at nerve terminals of the neuro-muscular junction. The aim of the present investigation was to directly study the effect of opioids on cAMP generation in nerve fragments associated with somata or terminals of the myenteric plexus. Employing the ultracentrifugation technique an enrichment of cell organelles in fractions relating to either somata or terminals was achieved. Opioid binding studies revealed specific mu-receptors which in both fractions were regulated by GTP. Challenge of these fractions with forskolin and prostaglandin E1, respectively, resulted in an increased production of cAMP regardless of their neuroanatomical assignment. Examining the response of neuronal material to the selective mu-opioid DAMGO ([D-Ala2, MePhe4, Gly-ol5]enkephalin) revealed an inhibitory action on cAMP synthesis in somata-enriched fractions. No effect of DAMGO was observed in material linked to nerve terminals, although the presence of mu-opioid receptors and adenylate cyclase has been demonstrated. We conclude that opioid control of adenylate cyclase in the myenteric plexus of the guinea pig is confined to nerve somata.

Adenylyl Cyclases↗

PubMed1992

Detection of methandienone (methandrostenolone) and metabolites in horse urine by gas chromatography-mass spectrometry.

The metabolic transformation of methandienone (I) in the horse was investigated. After administration of a commercial drug preparation to a female horse (0.5 mg/kg), urine samples were collected up to 96 h and processed without enzymic hydrolysis. Extraction was performed by a series of solid-liquid and liquid-liquid extractions, thus avoiding laborious purification techniques. For analysis by gas chromatography-mass spectrometry, the extracts were trimethylsilylated. Besides the parent compound I and its C-17 epimer II, three monohydroxylated metabolites were identified: 6 beta-hydroxymethandienone (III), its C-17 epimer (IV) and 16 beta-hydroxymethandienone (V). In addition, three isomers of 6 beta,16-dihydroxymethandienone (VIa-c) were discovered. Apparently, reduction of the delta 4 double bond of 16 beta-hydroxymethandienone (V) in the horse yields 16 beta,17 beta-dihydroxy-17 alpha-methyl-5 beta-androst-1-en-3-one (VII). Reduction of the isomers VIa-c results in the corresponding 6 beta,16,17-trihydroxy-17-methyl-5 beta-androst-1-en-3-ones (VIIIa-c). The data presented here suggest that screening for the isomers of VI and VIII, applying the selected-ion monitoring technique, will be the most successful way of proving methandienone administration to a horse.

Animals↗

PubMed1992

Expression of atrial natriuretic peptide in thymic macrophages after dexamethasone treatment of rats.

The rat thymus represents a site of synthesis of atrial natriuretic peptide (ANP); the immunosuppressor dexamethasone strikingly increases ANP-expression in this immune organ. The presented data suggest that this increase can be attributed to macrophages. By means of immunohistochemistry and Northern blot analysis these immune cells were found to express ANP-immunoreactivity as well as mRNA coding for ANP. In contrast, macrophages of control thymi displayed only weak ANP-immunoreactivity. Thus, ANP appears to be a constituent of rat thymic macrophages, and its synthesis in the thymus is strongly elevated by acute exposure of the animals to glucocorticoids.

Animals↗

PubMed1992

Metabolism of androstenedione and 11-ketotestosterone in the kidney of the three-spined stickleback, Gasterosteus aculeatus.

Stickleback kidneys were incubated with tritiated androstenedione (A4) or 11-ketotestosterone (OT). After the A4 incubations the following steroids were found, testosterone (T), 5 beta-androstane-3,17-dione (5 beta Ad), etiocholanolone (Et), 5 beta-dihydrotestosterone (5 beta DHT), 5 beta-androstane-3 alpha,17 beta-diol (5 beta A3 alpha 17 beta diol), androsterone, 5 alpha-androstane-3,17-dione, 5 alpha-androstane-3 alpha,17 beta-diol (5 alpha A3 alpha 17 beta diol), as well as glucuronides of T, Et, 5 beta DHT, 5 beta A3 alpha 17 beta diol, and 5 alpha A3 alpha 17 beta diol. The metabolites found in the largest amounts were usually T, 5 beta Ad, Et, and the glucuronides of T, Et, and especially of 5 beta A3 alpha 17 beta diol. These results suggest the main pathway to be A4-5 beta Ad-Et-5 beta A3 alpha 17 beta diol-5 beta A3 alpha 17 beta diol-glucuronide or Et-Et-glucuronide-5 beta A3 alpha 17 beta diol-glucuronide. The formation of 5 beta-reduced compounds was larger in postbreeding males and females than in breeding males. The opposite was the case for 5 alpha-reduced compounds. The total formation of glucuronides was lower in the breeding males than in the other groups. After the OT incubations 11-ketoandrostenedione, 17 beta-hydroxy-5 beta-androstane-3,11-dione (tentatively identified), and OT-glucuronide were found. 17 beta-Hydroxy-5 alpha-androstane-3,11-dione was not present.

Androstane-3,17-diol↗

PubMed1992

Comparison of recruitment strategies and associated disease prevalence for health promotion in rural elderly.

BACKGROUND: Although interest in health promotion for the elderly is increasing, the issues of recruitment into such programs and self-selection have not been well explored. While clinical studies require high participation levels and expensive recruitment, community efforts are satisfied with recruiting small numbers of volunteers from poorly defined populations. These small samples may not be representative of the populations at risk. METHODS: As part of the Rural Health Promotion Project, a Medicare demonstration, community-based recruitment methods were evaluated and participant characteristics were compared. A total of 3,884 individuals ages 65-79 were recruited in northwestern Pennsylvania, using four sequential recruitment strategies, varying in aggressiveness. The methods were: (A) mail only, (B) mail with phone recruitment follow-up, (C) mail with phone recruitment and scheduling, and (D) mail with aggressive phone recruitment and scheduling. RESULTS: Recruitment yields were Method A, 13.5%; B, 21.1%; and C, 31.6%. The most aggressive Method (D) yielded 37.0% participation. More aggressive methods (C and D) recruited more educated individuals. No other demographic or health status differences were noted. CONCLUSION: These data show that large numbers of the elderly can be recruited into a health promotion program using aggressive methods and professional interviewers.

Aged↗

PubMed1992

Physical illness and symptoms of depression among elderly outpatients.

Elderly outpatients were assessed to clarify relations between symptoms of depression and physical illness, disability, pain, and selected psychosocial variables. Three types of assessments were made: (a) medical evaluations by physicians, (b) self-reported symptoms of depression and physical health, and (c) demographic and psychosocial data relating to participants' life circumstances. Both objective (physician-rated illness symptoms) and subjective (self-reported health, activity restriction, and use of pain medications) indicators of health accounted for independent variance in symptoms of depression. After controlling for these factors, additional variance was explained by health-related concerns (e.g., health care expenses, service needs), social support, and "other worries" (e.g., feeling useless, becoming a burden to others).

Adaptation, Psychological↗

PubMed1992

Pain, activity restriction, and symptoms of depression among community-residing elderly adults.

Relations among physical illness, functional disability, pain, and symptoms of depression were investigated in a sample of community-residing elderly outpatients. As expected, physical illness, functional disability, and pain were correlated with depressive symptomatology. It was further hypothesized that functional disability (but not physical illness per se) would attenuate the relation between depressed affect and pain. The data supported these predictions by showing that functional disability (but not physical illness) accounted for differences in reported pain between nondepressed subjects and those at risk for developing clinical depression. Additional analyses revealed that functional disability mediated relations between pain and depressed affect and also between illness and depressed affect. These results indicate that both pain and illness are important contributors to functional disability, which in turn contributes to symptoms of depression. Secondary analyses revealed that restriction of certain activities associated with physical mobility and independence were strong individual factors in attenuating the relation between pain and depressed affect. An important implication of this research is that neither pain nor activity restriction should be treated in isolation. Maximal effects are likely to be achieved when both are targeted simultaneously.

Activities of Daily Living↗

PubMed1992

Induction and potential biological relevance of a Ca(2+)-independent nitric oxide synthase in the myocardium.

1. We have investigated whether the myocardium and isolated cardiac myocytes can express a Ca(2+)-independent NO synthase after treatment with endotoxin or cytokines. Nitric oxide synthesis was measured in cytosols from the left ventricular wall from rats treated with endotoxin, or from freshly isolated myocytes from adult rats treated in vitro with cytokines. 2. Cytosols from the ventricle of saline-treated control animals showed only Ca(2+)-dependent NO synthesis. After treatment with endotoxin, the expression of an inducible, Ca(2+)-independent NO synthase was observed. The activity of this enzyme was maximal at 6 h and returned towards control levels by 18 h; no alterations occurred in the Ca(2+)-dependent NO synthase activity. Parallel to this enzyme induction there was an increase in myocardial guanosine 3':5'-cyclic monophosphate (cyclic GMP) and plasma nitrite and nitrate (NOx-). All these changes were prevented by pretreatment of the rats with dexamethasone. 3. Myocytes possessed Ca(2+)-dependent NO synthase activity and expressed, after treatment with tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta), a Ca(2+)-independent NO synthase, the induction of which was prevented by dexamethasone and cycloheximide. 4. Since increases in cyclic GMP levels in the heart are associated with reduced myocardial contractility, it is possible that the enhanced production of NO by a Ca(2+)-independent enzyme accounts, at least in part, for the depression of myocardial contractility seen in septic shock, cardiomyopathies, allograft rejection, burn trauma, as well as during anti-tumour therapy with cytokines.

Amino Acid Oxidoreductases↗

PubMed1992

Lysoplasmenylethanolamine accumulation in ischemic/reperfused isolated fatty acid-perfused hearts.

Lysophospholipid accumulation has been implicated in the pathogenesis of irreversible injury during myocardial ischemia and reperfusion. Plasmalogens (phospholipids with a vinyl-ether bond in the sn-1 position) account for more than 50% of total myocardial sarcolemmal and sarcoplasmic reticulum phospholipids. Accumulation of plasmalogen choline and ethanolamine lysophospholipids (lysoplasmenylcholine and lysoplasmenylethanolamine) or the effects of exogenous fatty acids on lysoplasmalogen accumulation during ischemia and reperfusion have not been examined. Isolated working rat hearts perfused with buffer containing either 11 mM glucose or 11 mM glucose plus 1.2 mM palmitate were subjected to aerobic, ischemic, or ischemia/reperfusion protocols. Levels of lysoplasmenylcholine and lysoplasmenylethanolamine were quantified using a two-stage high-performance liquid chromatographic technique. In hearts perfused with glucose alone, no significant differences in levels of lysoplasmenylcholine or lysoplasmenylethanolamine were seen during ischemia or reperfusion. In fatty acid-perfused hearts, however, significant accumulation of lysoplasmenylethanolamine occurred during reperfusion but not during ischemia (723 +/- 112, 734 +/- 83, and 1,394 +/- 193 nmol/g dry wt for aerobic, ischemic, and ischemic/reperfused hearts, respectively; p less than 0.05 for ischemic/reperfused hearts versus aerobic or ischemic hearts). Lysoplasmenylcholine levels after ischemia and reperfusion did not differ significantly from aerobic values, regardless of whether fatty acids were present or absent from the perfusate. Aerobic and ischemic/reperfused rabbit hearts, in the presence of fatty acid, showed a similar profile in their lysoplasmalogen content. We conclude that differential lysoplasmenylethanolamine accumulation occurs during myocardial reperfusion when exogenous fatty acid concentrations are high. This may reflect the selective action of fatty acid intermediates on the metabolism of lysoplasmenylethanolamines.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Recruitment of an inotropic reserve in moderately ischemic myocardium at the expense of metabolic recovery. A model of short-term hibernation.

The regional, functional as well as metabolic consequences of inotropic stimulation on myocardium subjected to prolonged moderate ischemia were investigated. In 35 enflurane-anesthetized swine the left anterior descending coronary artery was cannulated and perfused at constant flow. The vein paralleling the left anterior descending coronary artery was cannulated for measurement of lactate and oxygen content. Transmural biopsies from the anterior myocardium were taken for the measurement of ATP, creatine phosphate, and glycogen. After control measurements, flow was adjusted to reduce regional contractile function (expressed as a work index, determined by sonomicrometry) by approximately 50%. After either 5, 25, 40, or 85 minutes of moderate ischemia, dobutamine was infused for 5 minutes into the ischemic region. In a separate group of five swine also subjected to 85 minutes of ischemia followed by infusion of dobutamine and 2 hours of reperfusion, triphenyltetrazolium chloride staining and light microscopy were used to identify infarcted tissue. Moderate ischemia (regional myocardial blood flow, 0.21 +/- 0.07 ml.min-1.g-1, determined by radiolabeled microspheres) was associated with a reduction of creatine phosphate after 5 minutes (from 9.35 +/- 2.54 to 6.43 +/- 1.06 mumol/g wet wt, p less than 0.05) and a further reduction after 25 minutes (3.18 +/- 0.69 mumol/g wet wt, p less than 0.05). Thereafter, creatine phosphate recovered despite continued ischemia (after 40 minutes, 4.95 +/- 1.37 mumol/g wet wt; after 85 minutes, 5.78 +/- 2.27 mumol/g wet wt). Lactate consumption during control conditions was reversed to production after 5 minutes of ischemia, which moderated during more prolonged ischemia. Without changing regional myocardial blood flow, infusion of dobutamine increased the work index significantly at any time point but also caused worsening of metabolic markers of ischemia. Nevertheless, even after 85 minutes of ischemia followed by the infusion of dobutamine and 2 hours of reperfusion, there was no evidence of necrosis. This experimental model provides a means of characterizing the mechanisms of short-term hibernation.

Animals↗

PubMed1992

[Poor reproducibility of parameters of heart rate variations].

The analysis of heart rate variability is supposed to be a marker of autonomic cardiac activity and is used for risk stratification of post-infarction patients. Analysis of heart rate variability in the frequency domain may permit a differentiation of vagal and sympathetic control; for such analyses only short time intervals characterized by a steady-state autonomic balance can be used. Yet, it is unclear whether single determinations of heart rate variability indices derived from short time intervals yield reproducible results. Therefore, the reproducibility of heart rate variability indices was studied with weekly measurements in 10 healthy volunteers under the following defined conditions: 13 min supine rest, 10 min standing, 13 min sitting, and 15 min cycle ergometry followed by a 14 min recovery period. Heart rate variability was determined in the frequency domain (fast Fourier transformation) and in the time domain. The reproducibility was estimated by the coefficient of variation (CV). Additionally, the reproducibility of heart rate, blood pressure, and the expiratory-inspiratory ratio of heart rate was determined. The reproducibility of the frequency domain indices (36.6-74.9% CV) and of the time domain indices (19.6-32.8% CV) was considerably worse than that of heart rate (5.2-8.2% CV), blood pressure (5.1-8.2% CV) and the expiratory-inspiratory ratio of heart rate (4.6% CV). The reproducibility of heart rate variability indices was not improved by orthostatic or ergometric challenge. This poor reproducibility does not permit a reliable interpretation of heart rate variability on the basis of single measurements in healthy volunteers. Given the wide range and scatter of the measured parameters, the diagnostic and prognostic value of heart rate variability indices derived from short recording periods appears questionable.

Arrhythmias, Cardiac↗

PubMed1992

Characterization of "hibernating" and "stunned" myocardium with focus on the use of calcium antagonists in "stunned" myocardium.

In the initial seconds after a sudden reduction in coronary blood flow, a temporary mismatch between myocardial energy demand and supply exists. The mechanisms underlying the rapidly ensuing reduction in contractile function in the ischemic myocardium are still unknown. In the presence of some residual blood flow, a state of "perfusion-contraction matching" develops. The metabolic status of such hypoperfused myocardium improves, since myocardial lactate production is attenuated and creatine phosphate (CP), after an initial reduction, returns toward control values. The hypoperfused myocardium responds to inotropic stimulation by dobutamine. The recruitment of an inotropic reserve implies increased energy utilization. During inotropic stimulation, after partial normalization, lactate production is again increased, and CP is decreased again. Thus, a supply-demand imbalance that had been at least partially corrected by the ischemia-induced decrease in regional contractile function is precipitated again. A situation of chronic contractile failure in viable myocardium that normalizes upon reperfusion has been termed myocardial "hibernation." Myocardial "stunning" is characterized by a reversible postischemic contractile dysfunction despite full restoration of blood flow. The details of the underlying mechanisms are not clear. An inadequate energy supply and impaired sympathetic neurotransmission have been excluded. Potential mechanisms, which are not mutually exclusive, may include (a) damage of membranes by free radicals, (b) an increase in free cytosolic calcium during ischemia and reperfusion, and (c) a decrease in the calcium sensitivity of the myofibrils. The equally pronounced increases in regional contractility in normal and "stunned" myocardium during postextrasystolic potentiation and the infusion of calcium or the calcium-sensitizing agent AR-L-57, however, suggest an unchanged calcium sensitivity of reperfused myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium↗

PubMed1992

Neuroanatomical sites mediating the central actions of beta-endorphin as mapped by changes in glucose utilization: involvement of mu opioid receptors.

Local cerebral glucose utilization, which is a correlate of neuronal activity, was measured to obtain information on the neuroanatomical sites mediating the different behaviors elicited by i.c.v. administration of the opioid peptide beta-endorphin (beta-END). The selective mu and delta opioid receptor antagonists d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) and ICI 174,864 (N,N-diallyl-Tyr-Aib-Aib-Phe-Leu-OH), respectively, were used to characterize the opioid receptor type involved in the actions of beta-END. beta-END was found to produce profound increases in glucose utilization in limbic regions such as the lateral septal nucleus, the amygdalo-hippocampal transition area, the nucleus accumbens and the hippocampal formation. The ventral hippocampus proved the most sensitive structure, displaying increases in glucose utilization of up to 200%; changes in the dorsal part amounted up to 100%. Only moderate effects were induced by beta-END in motor areas, such as the substantia nigra, pars reticulata and the nucleus ruber. This regional pattern of changes is assumed to underlie the epileptogenic-, motivational-, mood- and possibly memory-modulating actions of beta-END. The effects of beta-END on local cerebral glucose utilization were blocked by pretreatment with the mu antagonist, CTOP, whereas the selective delta opioid antagonist ICI 174,864 was less effective. An involvement of predominantly mu opioid receptors in the central actions of beta-END is, therefore, suggested.

Animals↗

PubMed1992

Description of a variably expressed and labile epitope of thyroglobulin and its occurrence in different thyroid diseases using a monoclonal antibody.

A new category of epitopes of human thyroglobulin is being described defined by a monoclonal antibody (TuTg 1). The epitope shows a very variable expression in normal individuals as well as in different thyroid diseases. According to gel filtration data the epitope is located at the intact molecule and is very sensitive to tryptic digestion. The monoclonal antibody was used in an IRMA system for plasma measurements in the follow-up of thyroid cancer patients. In individuals with high epitope expression the sensitivity to detect recurrency during T4 treatment was higher than a sensitive commercial TG IRMA.

Antibodies, Monoclonal↗

PubMed1992

Acetylsalicylic acid and blood coagulation in the horse.

Equine blood may contain salicylic acid (SA) taken up as free acid or represents the metabolite of acetylsalicylic acid (ASA). To obtain information of SA in race horses we screened blood samples of trotting-horses routinely drawn to be analyzed for doping substances. The individual values determined followed a Gaussian distribution displaying a geometric mean of 19 ng SA per ml serum. A probit analysis revealed linear relationship (r = 0.995). Additional studies examined the antithrombotic efficacy of ASA in the horse. An oral dose of 300 mg ASA considerably elevated the bleeding time for more than 2 hours with concomitant SA serum levels between 800 and 1000 ng/ml. It is concluded that salicylate levels even below 1 microgram/ml serum bring about considerable pharmacologic effects such as prolongation of bleeding time, decrease in blood viscosity and possibly dilatation of blood vessels. These effects may improve the tissue supply with blood including oxygen.

Animals↗

PubMed1992

Social discomfort and depression in a sample of adults with leg amputations.

We examined the relationship between social discomfort and depression in a sample of 89 adults with leg amputations at two outpatient clinics. It was hypothesized that individuals who reported being uncomfortable with social contacts involving acknowledgement of their amputation or prosthesis were more prone to depression than other patients. A set of questions addressing different aspects of social discomfort demonstrated internal consistency and were used as a scale. Social discomfort was significantly correlated with scores on the Center for Epidemiologic Studies-Depression Scale depression scale (r = .41). Multiple regression analysis showed that social discomfort was a significant independent predictor of depression, after holding constant the effects of age, gender, social support, time since amputation, reason for amputation, and perceived health. These data indicate that health care professionals should view the expression of social discomfort by amputee patients as a possible "marker" for depression. Further studies are planned to develop and validate an expanded social discomfort scale.

Adult↗

PubMed1992

Use of enzyme immunoassay and reverse-phase high-performance liquid chromatography to detect and confirm identity of dexamethasone in equine blood.

An enzyme immunoassay (EIA) was developed for detection of dexamethasone in equine blood. Dexamethasone 21-hemisuccinate-bovine serum albumin was used for immunization of rabbits, and prednisolone 21-hemisuccinate-horseradish peroxidase was used as enzyme conjugate. The assay had sensitivity in the low-picogram range (detection limit, 0.3 pg/well, 50% inhibition of binding at 4.5 +/- 0.7 pg/well). Apart from cortisol, which was recognized by the antiserum at concentration > 8.5 ng/ml, the dexamethasone antiserum failed to interfere with endogenous steroids, but cross-reacted with triamcinolone, flumethasone, and betamethasone. Thus, the antiserum was used to perform simultaneous screening for these synthetic glucocorticoids and to confirm their identity by combining reverse-phase high-performance liquid chromatography (RP-HPLC) and EIA. The immunoreactivity obtained by direct serum measurements was characterized by means of 2 independent RP-HPLC systems. Serum extracts were submitted to RP-HPLC systems I and II, and the fractions were tested by EIA. Immunoreactive peaks were identified by comparing their retention time with that of the standard glucocorticoids used for calibration. Coinjection of an internal standard (methylprednisolone) in RP-HPLC system II yielded reproducible relative retention times. The effectiveness of the test system was evaluated, using blood from a horse treated with commonly used veterinary preparations of dexamethasone. Administration of the free alcohol of dexamethasone and of dexamethasone 21-trioxaundecanoate, both given IV, was detected, and the identity of each was confirmed for up to 48 hours. Intramuscular administration of dexamethasone 21-isonicotinate was continued for at least 14 days after injection of a therapeutic dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Physician satisfaction in a managed care environment.

BACKGROUND: The professional literature suggests that changes toward the bureaucratization of medical practice have led to increasing job dissatisfaction, especially in primary care. To investigate this claim, we surveyed physicians in Dane County, Wisconsin, who practice in a bureaucratic setting. Dane County has experienced essentially a demise in independent practice, ie, most physicians practice in organizational settings where expenses and total patient income are pooled. About 85% of physicians have joined one of the six competing health maintenance organizations (HMOs). METHODS: In 1986 all 850 physicians in Dane County were surveyed to determine their perceptions of clinical freedom, satisfaction with income, status in their profession, autonomy, resources, and professional relations, and their overall satisfaction. RESULTS: We found that over 69% of primary care physicians were very satisfied or satisfied with their practices overall compared with 68% of physicians in all specialties. Differences between family practice and other primary care specialties were not statistically significant. Our regression analysis showed that only for satisfaction with income were responses from primary care physicians significantly different from those of physicians in surgical specialties. Perceptions of clinical autonomy and specific organizational settings were more important to predicting satisfaction. Also, age and sex contributed to differences in satisfaction with resources and status, respectively. CONCLUSIONS: We conclude that satisfaction can be fairly high for primary care physicians in bureaucratic settings similar to that of Dane County.

Group Practice↗