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Biomedical subjects

R Bayer

Publications and source records attributed to R Bayer.

At least 109 records · Page 6Linked to original sources

The care of the terminally ill: morality and economics.

Are current expenditures on dying patients disproportionate, unreasonable, or unjust? Although a review of empirical data reveals that care for the terminally ill is very costly, it is not appropriate to conclude that such expenditures represent a morally troubling misallocation of societal resources. Moreover, though efforts to reduce the costs of caring for the dying are not unreasonable, they must be undertaken with great caution. At present, such efforts should concentrate on three basic goals: development of better criteria for admission to intensive- and critical-care units; promotion of patient and family autonomy with regard to decisions to stop or refuse certain kinds of treatment; and promotion of alternative forms of institutional care, such as hospice care. The most difficult moral problems will arise when patients and their physicians seek access to therapies judged only marginally useful. There may be conflict between administrators with broad institutional responsibilities and clinicians committed to particular patients.

Cost-Benefit Analysis↗

Characterization of the catalytic pathway for D-serine dehydratase. Evidence for variation of the rate-determining step with substrate structure.

Steady state kinetic parameters (kcat and Km) which were determined for the D-serine dehydratase-catalyzed decomposition of the isomers of serine and threonine at pH 5.7, 7.8, and 8.9 indicated that the enzyme exhibited considerable kinetic specificity. At pH 7.8 and 25 degrees C, the specificity constants (kcat/Km) were as follows: D-serine (3.4 X 10(5) M-1 s-1), D-threonine (2.9 X 10(4) M-1 s-1), D-allothreonine (7.5 X 10(3) M-1 s-1), and L-serine (38 M-1 s-1). Substrate C-2 deuterium atom isotope effects on the steady state kinetic parameters disclosed that the rate-determining step in the catalytic pathway varied with substrate structure and pH. Removal of the C-2 hydrogen atom of the substrate was shown to be fully rate-determining with L-serine and partially rate-determining with D-allothreonine as substrate at pH 7.8. Stopped flow measurements of absorbance and fluorescence were used to characterize intermediates in the catalytic pathway. These measurements indicated that D-serine, in addition to being the best substrate, was processed faster than the other substrates through steps in the catalytic pathway which were not rate-controlling. Kinetic evidence also was obtained which indicated that the base which accepts the proton from the C-2 carbon atom of the substrate must be aprotic. Thus, the catalytic site of D-serine dehydratase should contain a basic group in addition to the active site lysyl residue.

Escherichia coli↗

Changes in red blood cell electrolyte concentrations in digitalis intoxication.

The value of red blood cell (RBC) sodium/potassium ratio in diagnosing digitalis toxicity was studied in 60 adult patients. The normal ratio was established in 34 healthy volunteers and in 10 patients with heart disease not receiving digoxin (group I). During chronic digoxin therapy, RBC sodium/potassium (Na/K) ratio and plasma digoxin were measured in 50 nontoxic patients (group II), in 10 toxic patients (group III), and in 9 of these 10 toxic patients after resolution of digoxin toxicity. Red cell sodium and RBC Na/K ratio in nontoxic patients were significantly greater than in the control group. Red cell sodium and the RBC Na/K ratio in toxic patients were significantly greater than in nontoxic patients. Despite significant group differences in these variables, however, there was considerable overlap among the subjects studied. After resolution of toxicity, red cell sodium and the RBC Na/K ratio fell to values indistinguishable from those in the nontoxic group. Although there was a statistically significant positive correlation between RBC Na/K ratio and plasma digoxin level, the RBC Na/K ratio had weak predictive value (33%) in determining digoxin toxicity. Plasma digoxin was a better predictor of digoxin toxicity (60%). The combination of plasma digoxin concentration and of RBC Na/K ratio had a higher calculated predictive value (75%), and may be more useful as an indicator of digoxin intoxication.

Adult↗

Edited correspondence on the status of homosexuality in DSM-III.

In 1973, after a prolonged period of social agitation and professional conflict, the American Psychiatric Association deleted homosexuality from its official listing of psychiatric disorders (DSM-II). In its place a new classification for homosexuals distressed over their orientation was to be included in DSM-II. Four years later an acrimonious dispute surfaced over the status of homosexuality in the revised APA nomenclature of disorders (DSM-III). The edited correspondence of the participants in this dispute is presented here as a way of revealing the lingering conflict over homosexuality within American psychiatry.

History, 20th Century↗

The influence of aromatic substitution on the negative inotropic action of verapamil in the isolated cat papillary muscle.

The influence of ring substitution on the negative-inotropic action of the Ca-antagonist verapamil (Isoptin) by means of qualitative and quantitative analyses of the structure-activity relationships has been investigated. The relative contribution of the two aromatic rings to the negative-inotropic potency of verapamil was tested. a) Ring substituents strongly influence the negative-inotropic potency (ED50 values from 7.9 x 10(-7) mol/l to 1.3 x 10(-4) mol/l). The character of the negative-inotropic effect typical for verapamil is not altered (except by very bulky substituents).

Animals↗

The effects of diphenylhydantoin on mechanical and electrical properties of isolated cat myocardium.

The effects of diphenylhydantoin (DPH) (4 X 10(-5) to 2 X 10(-4) M) on contractile activity and electrical properties were studied in isotonically shortening cat papillary muscles exposed to DPH. 1. DPH reduces amplitudes of contraction especially at low stimulation rates (6 to 12/min). At higher, more physiological rates the negative inotropic effect is comparatively small. 2. DPH accentuates the mechanical transients usually following step changes of frequency. 3. DPH reduces the maximum rate of depolarisation (MRD) of the normal action potential (AP) and slows conduction especially at high stimulation rates. AP duration is shortened especially at low stimulation rates. 4. In Ca-mediated "slow responses" DPH reduces MRD, overshoot and AP duration and abolishes the frequency-dependent alterations of these parameters. 5. The results suggest that the antiarrhythmic potency of DPH is due to a cooperative action on both the fast and the slow membrane channels. 6. It is speculated that DPH leads to an accumulation of Ca2+ within a "limited subsarcolemmal space" thereby decreasing the driving force for the slow inward current.

Action Potentials↗

[Experimental studies on the mechanism of action of carbocromen on the isolated cat papillary muscle (author's transl)].

1. In isotonically shortening cat papillary muscle 3-(2-di-ethylaminoethyl)-4-methyl-7-(carbethoxy-methoxy)-2-oxo-1,2-chromene-hydrochloride (carbocromen; Intensain¿) (1-30 mug/ml) slightly increases contraction amplitude. 2. At low stimulation rates (6-12/min) the positive inotropic effect is more pronounced. 3. The maximal velocity of depolarization of the monophasic action potential is slightly reduced. 4. At all stimulation frequencies investigated (15-90/min) the total duration of the action potential -- especially at late repolarization level -- is strongly increased. Hence, functional refractory period is prolonged and maximal follow frequency reduced.

Action Potentials↗

Inotropic and electrophysiological actions of verapamil and D 600 in mammalian myocardium. I. Pattern of inotropic effects of the racemic compounds.

A pattern analysis of inotropic actions was carried out on isotonically chortening cat papillary muscles exposed to (+/-)-verapamil and (+/-)-D 600 and compared to other Ca-antagonistic interventions. 1. (+/-)-Verapamil (1--5mug/ml) leaves contraction amplitudes nearly unchanged at 6/min, whereas at 60/min more than 90% depression (5 mug/ml) occurs. (+/-)-D 600 is about twice as effective as (+/-)-berapamil. 2. An increase of [Ca2+]O in the presence of (+/-)-verapamil or (+/-)-D 600 does not restitute the normal amplitude-frequency relationship. There is only a shift toward higher contraction amplitudes. 3. (+/-)-Verapamil and (+/-)-D 600 lead to typical biphasic inotropic transients after step changes of the friving rhythm. First a fast and (at higher frequencies) very pronounced negative staircase occurs, followed by a rather slowly developing positive staircase. 4. These drug effects contrast to the effects of lowering [Ca2+]O or of adding Ni2+ or La3+, which all produce a rather uniform depression of contraction amplitudes at all frequencies and do not elicit staircase phenomena such as seen under the influence of (+/-)-verapamil or (+/-)-D 600. 5. In contrast to the action of Ni2+, La3+ or low [Ca2+]O, (+/-)-verapamil slows down the restitution kinetics of Ca-reavailability from internal stores as determined by the amplitude of test contractions elicited after various periods of rest. 6. Drug-induced changes in the time course of the transmembrane action potential as depending on frequency may partially but not fully explain the contractile phenomena. 7. Possible interpretations as to the sites where (+/-)-verapamil or (+/-)-D 600 interferes with cardiac excitation-contraction coupling are given by the aid of a multicompartment model. This model describes excitation-contraction coupling in terms of transmembrane and intracellular Ca-movements.

Action Potentials↗