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Biomedical subjects

C Schulz

Publications and source records attributed to C Schulz.

At least 109 records · Page 6Linked to original sources

Na(+)-channel activators increase cardiac glycoside sensitivity in failing human myocardium.

Na(+)-channel activators increase intracellular Na+ and thereby enhance the transport rate of sarcolemmal Na+,K(+)-ATPase. We investigated the interaction of the new Na(+)-channel activator BDF 9148 (BDF) with the cardiac glycoside ouabain (OUA) in human myocardium. The influence of OUA (0.01-0.1 microM) and of OUA after prestimulation with BDF (0.1 microM, 1 microM; BDF+OUA) on isometric force of contraction (FOC, force of contraction; +T/-T, peak rate of tension increase/decay) of electrically driven (1 Hz, 37 degrees C) papillary muscle strips from terminally failing [New York Heart Association classification IV (NYHA IV) heart transplants, n = 19] human myocardium was studied. We also examined the effects of BDF and OUA on nonfailing human myocardium (brain death resulting from traumatic injury, n = 5). 0.01 microM OUA enhanced FOC only after prestimulation with BDF (NYHA IV+2.9 +/- 0.4 mN; p less than 0.01). The time until maximal (Tmax: BDF+OUA 117 min, OUA 166 min), half-maximal (T1/2max: BDF+OUA 47 min, OUA 85 min) inotropic effects and time until toxic signs (contracture, extrasystoles) occurred were significantly shorter with BDF+OUA as compared with OUA alone. BDF influenced Tmax, T1/2max, and time until toxic side effects occurred (Ttox) of the OUA-mediated inotropism in a concentration-dependent manner. Both OUA and BDF enhanced +T and -T. The effectiveness of OUA and BDF in increasing FOC was similar to that of Ca2+ (1.8-15 mM) but significantly (p less than 0.01) higher as compared with the beta-adrenoceptor-agonist isoprenaline in NYHA IV. In myocardial membranes, [3H]ouabain binding (Bmax, Kd) was not affected by BDF.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Positive inotropic effects due to partial agonistic activity of the beta-adrenoceptor antagonist celiprolol following amplification of cAMP formation in failing human myocardium.

The present study investigated the effects of celiprolol a novel beta 1-antagonist with partial beta 2-agonist activity on the human failing heart. Experiments were performed on isolated electrically driven atrial and ventricular cardiac preparations and in membrane preparations from the left ventricles of nine patients (four with dilated cardiomyopathy; five with ischemic cardiomyopathy) undergoing cardiac transplantation for terminal heart failure. Celiprolol produced a negative inotropic effect in atrial and ventricular heart muscle. However, in the presence of forskolin--which activates the catalyst of the adenylate cyclase-or the cAMP phosphodiesterase inhibitor milrinone, celiprolol produced concentration-dependent positive inotropic effects and positive lusitropic effects. Experiments with the beta 1-and beta 2-selective antagonists CGP 207.12A and ICI 118.551, respectively, suggest that the positive inotropic response is mediated by beta 2-adrenoceptors. In radioligand binding experiments, a selectivity of 15.7 [-Gpp(NH)p] or 23.9 [+Gpp(NH)p] as judged from the Ki values--of binding to beta 2-adrenoceptors was measured in the failing human ventricular myocardium. Competition curves with celiprolol alone and in the presence of the guanine nucleotide Gpp(NH)p revealed no evidence for agonist activity at beta 1- or beta 2-adrenoceptors. It is concluded that amplification of the cAMP response is able to unmask partial agonist activity of celiprolol in the failing human heart at beta 2-adrenoceptors. The inotropic measurements are a more sensitive approach than radioligand binding studies. Whether the pharmacological profile of celiprolol will be useful in conditions like heart failure is questionable with respect to the potential downregulation of beta 2-adrenoceptors by its partial agonist activity.

Adrenergic beta-Agonists↗

Organ donation: the role of hospitals.

Three models of cooperation between hospitals and transplant centres are: (1) performance of brain death diagnosis, organ removal and preservation at the peripheral hospital; (2) performance of brain death diagnosis at the peripheral hospital and transportation of the dead body under ICU modalities to the transplant centre; (3) transport of a potential organ donor to the transplant centre. The key issues for success in cooperation between peripheral hospitals and transplant centres are: positive attitudes of hospital representatives; motivation and acceptance of ICU staff, supported by the whole community; and availability of adequate facilities to perform organ recovery in practice.

Attitude of Health Personnel↗

[Frequency of hypoxic episodes during general anesthesia in children].

We measured the frequency and extent of arterial hypoxemia during pediatric general anesthesia under routine clinical conditions. The subjects were 91 children (13 newborns, 27 infants, 37 children under 6 years, 14 children under 14 years) with normal heart and lungs scheduled for extrathoracic surgery. Mask anesthesia (spontaneous/assisted ventilation) was performed in 30 cases, endotracheal anesthesia (controlled ventilation) in 61 cases. Arterial oxygen saturation (SaO2) was determined by pulse oximetry at entry into the operating room and recorded continuously from induction of anesthesia to emergence. Hypoxic episodes (minimum duration: 30 s) were classified as slight (SaO2 less than or equal to 95%), minor (SaO2 less than or equal to 90%) and major (SaO2 less than or equal to 85%). The data were analyzed with the Fisher's test. 52% of all children experienced at least one hypoxic episode. Frequency and extent of hypoxic episodes decreased as age and weight of the children increased. Major hypoxic episodes occurred in 54% of the newborns, 26% of the infants, 8% of the children under 6 and 7% of the children under 14. A body weight of 10 kg appeared to constitute a threshold: in children below this weight arterial oxygen desaturation occurred significantly more frequently (p less than 0.001), and the incidence of major episodes was significantly higher (p less than 0.005). Major episodes were almost evenly distributed between induction and awakening from anesthesia, only one episode occurred during maintenance. Desaturation was more likely to occur in intubated children than in those with a mask (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Effect of epidermal growth factor in severe experimental alkali burns.

Ten rabbits with the right eye burnt by 1 N NaOH were treated 5 times daily with epidermal growth factor (EGF) eyedrops or placebo. The epithelium seemed to heal better under EGF treatment than with placebo. Also, ulceration and secondary calcification of the cornea were reduced in the EGF-treated group. The vascularisation was slightly diminished by EGF. The lactate dehydrogenase and N-acetylglucose aminidase activities and the lactate and glucose levels in the corneae were not different between the EGF and the placebo groups. The results showed that there was a beneficial effect of EGF in these experiments with most severe eye burn disease. But the improved regeneration of the epithelium seemed to be counteracted and partly abolished by the severe inflammatory reaction in these eyes.

Animals↗

Management practices, physician autonomy, and satisfaction. Evidence from mental health institutions in the Federal Republic of Germany.

Physicians are moving into organized settings where their autonomy is more constrained and where management has more responsibility for physician satisfaction. The relationship of management practices to physician autonomy and satisfaction was explored in a survey of 185 psychiatrists in the State of Hessen in the Federal Republic of Germany (FRG). Analysis revealed that controlling for physician and institutional characteristics, management practices in relationship to participative activities, supportive communication, and peer review activities were the most important predictors both of perceived clinical autonomy and of work satisfaction. Gender was also a factor in that male physicians experienced greater perceived autonomy. Perceived clinical autonomy was an important factor in explaining satisfaction, whereas a few other physician and institutional characteristics were significant in predicting satisfaction. Unexpectedly, there was more perceived clinical autonomy among psychiatrists in larger, less well funded, more managerially constrained, state institutions than in smaller, community general hospitals and private organizations. Implications for further research are discussed.

Cross-Sectional Studies↗

Hydraulic conductivity of venous endothelium as measured with a volume clamp method.

Hydraulic conductivity (Lp) of cava vein endothelium was obtained with a new method that measures fluid flow at constant volume. Dogs were anesthetized with pentobarbital sodium. A vessel segment was removed, cannulated, and hung free from a force transducer calibrated to measure weight. Hydraulic pressure difference drove fluid across the vessel wall. This fluid was washed out from the vessel surface by external perfusion, causing a weight loss that was transmitted to a Grass polygraph through the force transducer. Shifting the polygraph balance caused a voltage output which was used to activate a controller operating a microsyringe pump. By injecting fluid into the vessel lumen, this servomechanism counteracted weight changes and kept volume and pressure at a fixed level. Recording the volume injected allowed continuous monitoring of fluid flow. This avoided the problems caused by frequent pressure and volume resetting in previous methods. Fluid flow was a linear function of the applied pressure (r = 0.87). Lp was 0.91 +/- 0.05 (SD) X 10-7 cm X s-1 X cmH2O-1. This value was very similar to those in continuous capillaries and arterial endothelium.

Animals↗

Organ procurement in Munich: financial and organizational aspects.

The Transplantation Center at the University of Munich is like all other German centers financially supported by the Insurance Companies via a non-profit organization (Kuratorium für Heimdialyse e.V.). The financial modalities are based on the arrangement that the Insurance Companies pay a certain amount for each transplantation to the non-profit organization. This institution, in cooperation with the University, uses this money to cover all extra expenses arising in the field of organ procurement as well as clinical transplantation (providing additional staff, equipment, etc). This model of a transplant center (ie, cooperation between University and non-University institutions) proved to be successful in the past 9 years. There was a steady increase of donor nephrectomies (200 donor kidneys in 1984) as well as kidney transplantations (171 transplantations in 1984).

Cadaver↗

Neuropsychological function following mild exposure to pentaborane.

Neuropsychological tests and self-report personality inventories were administered to 14 workers and rescue squad personnel approximately 2 months following mild exposure to pentaborane, a highly toxic volatile liquid boron hydride. Performance decrements were evident on 5 of 11 neuropsychological tests, including Block Design and measures of sustained attention and recent memory. Neuropsychological deficits were not related to emotional changes reported on the Hopkins Symptom Checklist nor to the presence of CT scan abnormality. These results indicate mild residual brain dysfunction following pentaborane intoxication, including possible dysfunction in subcortical regions mediating memory processes and in cortical areas mediating visuo-spatial abilities.

Adolescent↗

Violent automatism in a partial complex seizure. Report of a case.

We describe a patient who had a violent automatism that occurred during a partial complex seizure. The initial spike wave activity was recorded from nasopharyngeal leads that were lost as the patient began his vigorous, violent activity. This activity included nondirected, automatic, stereotyped behavior with physical assaults on objects in his path.

Adult↗

Cytochrome P450cam and its complexes. Mössbauer parameters of the heme iron.

Mössbauer spectroscopy has been used to study the heme iron in various states of cytochrome P450cam from the camphor-hydroxylating system of the bacterium Pseudomonas putida. Native, camphor-free P450cam contains low-spin ferric iron, part of which (approx. 50-70%) is converted to the high-spin ferric state upon addition of camphor. The Mössbauer spectra of the camphor-free enzyme (S equals 1/2) and of the high-spin component (S equals 5/2) of the camphor complex have been successfully simulated using a model based on crystal-field theory and simple convalency considerations. The native low-spin ferric state of P450cam forms a complex with 2-phenylimidazole, with small changes in the g values and Mössbauer spectra. These changes can be accounted for consistently in the crystal-field model referred to above. The addition of putidaredoxin to the camphor-complexed, oxidized P450cam decreases the intensity of the high-spin component and changes its quadrupole splitting. The reduced form of P450cam contrins high-spin ferrous iron, both in the presence and absence of camphor. The complex of reduced P450cam with molecular oxygen is diamagnetic and has a combination of quadrupole splitting and isomer shift that is unusual for a ferrous complex, but strongly resembles that of oxyhemoglobin. These results are compatible with the bound superoxide, Fe3+-O-2, model proposed for oxyhemoglobin (Weiss, J. J. (1964) Nature 202, 83-84). Reduced P450cam and its complexes, oxyP450cam-CO, are all found to be analogous in some respects to the corresponding hemoglobin complexes.

Binding Sites↗