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Biomedical subjects

J Morgan

Publications and source records attributed to J Morgan.

At least 19 recordsLinked to original sources
PubMed1979

Detection, prediction, and significance of perioperative myocardial infarction following aorta-coronary bypass.

One hundred consecutive patients undergoing aorta-coronary bypass grafting (ACBG) alone, without ventricular venting, were prospectively studied to determine the incidence and consequence of perioperative myocardial infarction (PMI) and the clinical variables that were predictive of PMI. Incidence was determined by serial electrocardiography (ECG) 100 patients; serum CK, GOT, and LDH (100 patients). CK isoenzymes (qualitative 100 patients, quantitated 50 patients); vectorcardiography (VCG) (78 patients); and 99mtechnetium pyrophosphate scintigraphy (TcPyp) (52 patients). The incidence of PMI by ECG was 9%; an additional 8% of cases was diagnosed by enzymes alone. The incidence of diagnostic change by VCG was 19% and by scintigraphy, 25%. Using at least one changed variable of the remaining three as the reference standard, the relative sensitivity and relative specificity of given variables in the diagnosis of PMI were as follows: ECG 67% and 100%, respectively; VCG 85% and 94%; scintigraphy 92% and 97%; and serum enzymes 86% and 96%. By univariate analysis, unstable angina was the only significant predictor of PMI. The operative mortality rate was 2% and the mortality rate at 12 months was 5%. There was a significantly greater mortality rate in patients with PMI diagnosed by ECG (p less than 0.01), in patients with unstable angina pectoris before operation (p less than 0.05), and in women (p less than 0.05).

Analysis of Variance↗
PubMed1979

Factors influencing mouse heart creatine kinase efflux and ultrastructure.

An isolated mouse heart model has been developed to study the extracellular factors which influence the loss of myocardial enzymes. When added to a tris-HCl buffer/salt mixture at 25 degrees C, glucose, phosphate ion, increased osmolarity, oxygen exclusion and calcium reduced enzyme leakage. Of these, calcium effects on enzyme leakage and ultrastructure were assessed in detail. Concentrations less than or equal to 10(-4) M had no significant effect on enzyme efflux over a 5 hour period. At higher concentrations (10(-3) and 10(-2) M Ca2+), creatine kinase (CK) efflux was significantly altered in a time dependent fashion. In the first hour, 10(-3) and 10(-2) M Ca2+ reduced CK leakage to 33% and 25% of the control values, respectively; and to about 50% of the control values in the second and third hours. This protective effect was lost between the third and fifth hours, when an enzyme efflux 80% greater than control was observed. These studies indicated that CK leakage from mouse heart can be retarded for up to 3 hours by appropriate Ca2+ concentrations. The initial ultrastructural change, in the absence of Ca2+, was a dilatation of the transverse tubules, which gradually enlarged by coalescence. This was followed by a gradual disintegration and ultimate condensation of the myofibrils leaving altered mitochondria floating freely in an apparently intact sarcolemmal bag. These changes appeared to be delayed by Ca2+ for 3 hours, after which no protective effect was evident. Thus, CK leakage is a measure of myocardial autolysis, and numerous simple measures can retard this autolysis for several hours. This raises the possibility of prolonging the preservation of the normal heart in vitro.

Animals↗
PubMed1978

Calcium augmentation of enzyme leakage from mouse skeletal muscle and its possible site of action.

Creatine kinase efflux from isolated mouse skeletal muscle was monitored in the presence of various concentrations of Ca2+ or La3+ over a 5 hour period. Ca2+ levels between 10(-3) and 10(-2)M augmented enzyme leakage to greater than 300% above control. La3+, which is said to displace Ca2+ from sarcolemmal and t-tubule membranes, depressed enzyme efflux at concentrations between 10(-5) and 10(-3M. These data indicate that extracellular Ca2+ mediates in vitro enzyme efflux, and may be acting on the sarcolemma and its extensions. These observations may prove useful in developing new means to regulate enzyme leakage in various muscle disorders.

Animals↗
PubMed1977

Salmonella surveillance with reference to pigs--Cardiff abattoir, 1968-1975.

Between 1968 and 1975, well over 3000 samples of pig faeces and 407 samples of pig mesenteric glands were examined for salmonellas. A very wide range of serotypes was isolated. The material from this survey was used to evaluate certain aspects of salmonella isolations. The factors studied were: selective motility enrichment, size of inoculum of faeces, comparison of drain swab with animal sample and comparison of selenite F broth with Muller-Kauffmann tetrathionate broth. The conclusions drawn from these investigations allowed an efficient routine to be developed during the survey.

Abattoirs↗
PubMed1977

Adult respiratory distress syndrome (ARDS), sepsis, and extracorporeal membrane oxygenation (ECMO).

This report presents data obtained in the care of 830 patients requiring assisted ventilation. When these patients were divided into groups by the severity of their respiratory failure as defined by the duration of ventilatory assistance (greater than 48 hours, less than 48 hours) and level of positive end expiratory pressure (PEEP) required (greater than 5 cm HoH, less than 5 cm HoH), it was found that evidence of concurrent bacterial infection was present in the majority of patients with severe respiratory failure. This finding could not be explained by infection acquired after the onset of respiratory failure. In addition, this analysis demonstrated the important association of active pulmonary infection with the occurrence of barotrauma in these patients. Case analysis of patients subjected to extracorporeal membrane oxygenation has led to the suggestion that underlying sepsis in patients failing to respond to conventional ventilatory assistance similarly limits the usefulness of membrane oxygenator support.

Adolescent↗
PubMed1977

Effects of the simultaneous administration of diethylstilbestrol and prednisolone on serum enzymes in Duchenne's muscular dystrophy.

The effects of diethylstilbestrol (DES) and prednisolone (Pr), administered alone or in combination, on the serum enzyme activities in Duchenne's muscular dystrophy (DMD) have been evaluated. When DES and Pr were given simultaneously to four boys with DMD, the mean creatine phosphokinase and lactate dehydrogenase levels fell to about one half those achieved with either agent alone. No untoward or unexpected side effects were encountered. These observations, and our previous demonstration that both agents reduce enzyme efflux from skeletal muscle, give promise that a safe combination therapy may be found to approximately normalize the serum in DMD. This will permit us to test the hypothesis that lowering the serum enzymes, by reducing their loss from skeletal muscle, will slow or arrest the muscle deterioration characteristic of this disease.

Child↗
PubMed1977

Variable effects of corticosteroid treatment of serum enzyme activities in Duchenne's muscular dystrophy.

Corticosteroid administration on alternate days to five boys with Duchenne's muscular dystrophy (DMD) lowered the high serum creatine kinase and lactate dehydrogenase activities in three, caused no change in one, and increased these activities in one. These observations indicate that, as given, this therapy can partially normalize a major biochemical abnormality of this disease in some but not all patients with DMD.

Adolescent↗
PubMed1977

Penicillamine effects on enzyme efflux from skeletal and heart muscle.

We have previously shown that pretreatment of mice with diethylstilbestrol (DES) or prednisolone (Pr) lowered enzyme efflux from isolated mouse skeletal muscle. These same agents also lowered the high serum enzyme activities in boys with Duchenne's muscular dystrophy (DMD). In a continuing search for other agents with similar effects, the influence of penicillamine (Pe) on enzyme efflux from isolated muscle was assessed, because it lowered the high plasma creatine phosphokinase (CPK) and produce beneficial effects in avian muscular dystrophy. Three groups of mice received 0, 1, or 10 mg Pe daily for 14 days. All mice were given supplementary pyridoxine. The egress of CPK and lactate dehydrogenase from the isolated left gastrocnemius and heart was determined over a 5 hour period. Pe produced more modest effects than did DES or Pr. The 10 mg dose reduced enzyme efflux from the gastrocnemius by 10%. In contrast, heart enzyme efflux was augmented by 20%. Similar dose-related disparate effects on enzyme efflux from skeletal muscle and heart have been previously noted for DES and Pr. Pe is the third agent found to lower the high serum enzyme activities in muscular dystrophy and reduce gastrocnemius enzyme efflux from isolated mouse skeletal muscle. This further establishes the usefulness of the mouse assay for identifying agents that lower the high serum enzyme activities in muscular dystrophy.

Animals↗
PubMed1977

Abolition of the diethylstilbestrol reduction of enzyme leakage from muscle by a 3,3' diallyl substitution.

Diethylstilbestrol (DES) lowers enzyme efflux from isolated mouse skeletal muscle. It also lowers the high serum enzyme activities in Duchenne's muscular dystrophy. We have begun a systematic study of DES congeners, to identify those portions of the DES molecule which are critical to these effects, and to tailor a molecule which might have fewer feminizing effects. The first compound tested was the 3,3' diallyl derivative of DES (DAS). It was selected because previous reports indicated that it was as anabolic as DES, but only 1/10 to 1/30 as estrogenic. Doses of 20, 100 and 250 microgram/mouse/day were administered in 0.05 ml sesame seed oil vehicle to C57BL/6 mice. Control animals received only the vehicle. In contrast to DES which has consistently reduced muscle enzyme efflux 30-50%, DAS was inert. The substitution of the two allyl groups in the 3 and 3' positions blocks access to the neighboring ethyl groups and partially covers the two phenolic hydroxyl groups of DES. This suggests that these molecular sites have pertinence to the reduction of enzyme efflux from mouse skeletal muscle by DES, and possibly the reduction of the high serum enzyme activities in Duchenne's muscular dystrophy.

Allyl Compounds↗
PubMed1976

Diethylstilbestrol effects on serum enzymes and isozymes in muscular dystrophy.

Diethyistibestrol was administered orally to 11 boys with Duchene muscular dystrophy (DMD). Creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) activities, characteristically high in DMD, and presumably of muscle origin, were reduced significantly (P LESS THAN .05). On ther other hand, the activity of alkaline phosphatase, an enzyme not of muscle origin, increased. These enzyme changes were reversible when diethyistibestrol was discontinued. Despite appreciable alterations in totoal serum enzyme activity, no important change was found in the isozyme patterns. Piperazine estrone sulfate was administered to another patient with DMD. The effects of this physiologic hormone were, in part, similar to those of diethyistibestrol. Experimentally, diethylstilbestrol reduced the efflux of CPK and LDH from mouse skeletal muscle. This may be the manner by which diethylstilbesterol reduced the serum enzyme levels in DMD, but this has not been proved directly. These studies are the first step in an effort to identify various agents that in combinations may normalize serum enzyme levels.

Adolescent↗
PubMed1976

Disparate effects of diethylstillbestrol and prednisolone on enzyme efflux from heart and skeletal muscle.

We have previously shown that diethylstilbestrol (DES) almost always, and prednisolone (Pr) less frequently, lowered the high serum enzyme activities in Duchenne's muscular dystrophy (DMD). In experimental studies, it was shown that pretreatment of mice with each of these agents lowered enzyme efflux from isolated skeletal muscle incubated in vitro, but efflux was augmented by higher doses of Pr. This suggested that these agents may influence skeletal muscle enzyme efflux in man also, producing the effects noted in DMD. The present studies were undertaken to assess the effect on enzyme efflux from skeletal muscle and heart that these two agents would exert when given in combination. Four groups of mice (14/group) were injected with saline, 250 mug DES, 35 mug Pr, or 250 mug DES plus 35 mug Pr in saline every other day for 22 days. The left gastroecnemius and heart were isolated from animals of each group, and placed in separate tubes containing incubation medium at 25 degrees C. The efflux of creatine phosphokinase (CPK) and lactate dehydrogenase (LDH) which issued from each organ was determined over a 5 hour period. In the doses tested, it was found that: 1) DES selectively reduced enzyme efflux from skeletal muscle, but had no effect on enzyme efflux from heart; 2) a Pr dose which decreased enzyme efflux from the heart, augmented efflux from the gastrocnemius; and 3) DES prevented the enhanced enzyme efflux produced by Pr. These studies indicate that these hormones, in pharmacological doses, influence enzyme efflux from muscle. This suggests, but it is not established, that these hormones also exert a similar physiological role. Finally, this experimental model appears to be useful in assessing the effects of single agents, and agents in combination, on enzyme efflux, and should be of aid in selecting appropriate agents which may be therapeutically useful in Duchenne's muscular dystrophy.

Animals↗