Search PubMed⌕ Search

Biomedical subjects

R C Marshall

Publications and source records attributed to R C Marshall.

At least 37 records · Page 2Linked to original sources

Identification of persons at risk for sudden cardiac death.

Before any more progress is made in reducing the incidence of sudden cardiac death, our ability to identify those at risk must be refined further. The close association with coronary artery disease necessitates that the first step must be the identification of those with underlying coronary artery disease. This is underscored by the disturbing fact that, in many, sudden death is the first sign of coronary disease. An aggressive evaluation of those with significant risk factors appears justified. The second part of the problem is the identification of those with coronary artery disease who are at especially high risk. The current diagnostic modalities available suffer from a relative lack of specificity to be applied indiscriminately in light of the expense and morbidity of effective therapies (that is, coronary artery bypass surgery, antiarrhythmic drugs, implantable defibrillators, surgical or catheter ablation). At the present time, we can identify certain subsets that warrant aggressive therapy: survivors of sudden death events or sustained ventricular tachycardia, obstructive cardiomyopathies, aortic stenosis, left main coronary artery disease, and congenital QT prolongation. Less aggressive but also less specific therapies, such as beta-blockers in myocardial infarction survivors, can be given more indiscriminately. Ultimately, of course, the greatest impact will come from prevention of coronary artery disease.

Arrhythmias, Cardiac↗

Studies of developing human hair shaft cells in vitro.

Methods for studying aspects of hair formation in vitro have been devised on the basis of isolating developing hair shaft cells. These cells were obtained using a sterile microdissection technique. Plucked anagen follicles were dissected free of surrounding tissues (inner and outer root sheaths), and presumptive hair shaft cells (including germinal epithelia) were cultured directly on mammalian fibroblasts or in media preconditioned by fibroblasts. Specimens were cultured either as dispersions or in whole tissue pieces. Trypsinized whole tissue specimens in culture were sometimes observed to form increased bulk, while dispersed cells appeared to elongate and form larger colonies. In sections of these colonies examined by transmission electron microscopy, intracellular hard keratin intermediate filaments (IFs) together with IF-matrix hard keratin complexes were observed. Radiolabelled cysteine [35S] was added to cultures (3-20 days), showing a continuing but reduced synthesis of hard keratin IF proteins (low-sulfur) over the period of study. Matrix protein (high-sulfur) production was drastically reduced after 3 days. Monoclonal antibodies directed against hair keratin IF components were used in Western transfers and immunofluorescent studies to help assess the specificity of proteins synthesized in culture. Our observations indicate that, with some refinement, the presently described methods enable preparation of hair shaft precursor cells suitable for observing certain hair-forming processes in vitro.

Cells, Cultured↗

Correlation of contractile dysfunction with oxidative energy production and tissue high energy phosphate stores during partial coronary flow disruption in rabbit heart.

The relationships between contractile function, myocardial oxygen consumption, and tissue high energy phosphate and lactate content were investigated during partial coronary flow disruption. The experimental preparation was an isolated, isovolumic retrograde blood-perfused rabbit heart. Both developed pressure (r = 0.94) and dp/dt (r = 0.95) exhibited strong linear correlations with myocardial oxygen consumption that were stable for up to 45 min after blood flow reduction. In contrast, tissue high energy phosphate content exhibited nonlinear relationships with both developed pressure and oxygen consumption such that systolic mechanical function and oxidative metabolism declined to 20 and 30% of control values, respectively, before significant abnormalities in myocardial high energy phosphate stores were observed. Similarly, developed pressure and oxygen consumption decreased to 36 and 48% of control, respectively, before abnormal tissue lactate content was detected. The results of this study indicate that: (a) mechanical function is closely related to the rate of oxidative energy production during partial coronary flow disruption, and (b) despite the development of significant contractile dysfunction, tissue high energy phosphate content remains at normal levels except under the most severely flow-deprived conditions. The preservation of tissue energy stores can be explained by the apparent coupling of contractile performance to oxidative energy production, which could function to maintain myocardial energy balance during partial coronary flow restriction.

Adenine Nucleotides↗

Response to exercise after withdrawal from chronic alcoholism.

To test for early evidence of alcoholic cardiomyopathy and to assess changes in exercise response after abstinence, 12 asymptomatic alcoholic men (group 1) underwent maximal upright bicycle exercise radionuclide ventriculography two to six days after alcohol withdrawal. Six of these patients (group 1A) had similar testing two to four weeks later. Six control subjects (group 2) had repeated exercise tests without isotope study. Group 1 left ventricular ejection fraction response (LVEF) was normal. LVEF at similar workloads did not differ in group 1A (p = NS). However, unlike group 2 results, the linear regression line relating double product to exercise stage in group 1A was higher at first exercise (p less than 0.05), probably due to the effects of alcohol withdrawal. We conclude that radionuclide left ventriculographic findings in these patients do not support the concept of a preclinical alcoholic cardiomyopathy made apparent by exercise, and exercise very early after alcohol withdrawal is associated with an increased myocardial oxygen demand at any given workload.

Adult↗

Myocardial energy production and consumption remain balanced during positive inotropic stimulation when coronary flow is restricted to basal rates in rabbit heart.

The effect on myocardial energy balance of increasing oxygen demand without altering basal myocardial perfusion rate was assessed in isolated, isovolumic, retrograde blood perfused rabbit hearts. Myocardial energy requirements were increased with paired stimulation. The capacity of rapid paired stimulation to increase mechanical energy consumption was demonstrated in the presence of increased perfusion with the rate X pressure product and oxygen consumption increasing 86 and 148%, respectively, compared with control values. In contrast, rapid paired stimulation under constant, basal flow conditions did not alter the rate X pressure product, while oxygen extraction and consumption increased only 40% relative to control. Myocardial ATP, creatine-phosphate, and lactate content were identical under control and constant flow-paired stimulation conditions. The results of this study indicate that no detectable energy imbalance was produced by rapid paired stimulation with flow held constant at basal rates. These results suggest that the myocardium does not increase mechanical energy expenditure in response to inotropic or rate stimulation in the presence of restricted flow reserve and are inconsistent with the concept of "demand-induced" or "relative" myocardial ischemia.

Adenosine Triphosphate↗

Self-monitoring behavior in a case of severe auditory agnosia with aphasia.

This case report describes an unusual combination of speech and language deficits secondary to bilateral infarctions in a 62-year-old woman. The patient was administered an extensive series of speech, language, and audiologic tests and was found to exhibit a fluent aphasia in which reading and writing were extremely well preserved in comparison to auditory comprehension and oral expression, and a severe auditory agnosia. In spite of her auditory processing deficits, the patient exhibited unexpected self-monitoring ability and the capacity to form acoustic images on visual tasks. The manner in which she corrected and attempted to correct her phonemic errors, while ignoring semantic errors, suggests that different mechanisms may underlie the monitoring of these errors.

Agnosia↗

Characterization of the proteins of human hair and nail by electrophoresis.

Low-sulfur and high-sulfur proteins from human hair and nail were characterized by two-dimensional polyacrylamide gel electrophoresis. Apparent molecular weights (estimated by SDS electrophoresis) of low-sulfur and high-sulfur proteins were in the ranges 55,500-76,000 and 26,500-43,000, respectively, but these are probably higher than the real values (12-30% for low-sulfur, 75-150% for high-sulfur) because corresponding wool proteins behave anomalously in SDS electrophoresis. Isoelectric points of the low-sulfur proteins ranged from 4.9-5.4. Six low-sulfur and 7 high-sulfur major proteins were common to hair and nail from the same individual, but each keratin contained 1 additional major low-sulfur component which was not common. Variation, presumably of genetic origin, was observed in the low-sulfur and high-sulfur proteins of hair and nail.

Chemical Phenomena↗

Identification and differentiation of resting myocardial ischemia and infarction in man with positron computed tomography, 18F-labeled fluorodeoxyglucose and N-13 ammonia.

Studies have shown that the extraction of glucose per unit flow is increased in moderately ischemic myocardium primarily due to anaerobic glucose metabolism manifested as lactate production, whereas myocardial infarction is characterized by the loss of metabolically active myocardium. To determine the feasibility of demonstrating these metabolic abnormalities reflecting both ischemia and infarction, we used positron computed tomography (PCT) to evaluate relative regional myocardial exogenous glucose utilization and perfusion in 15 patients with recent myocardial infarction. The positron-emitting tracers of glucose metabolism and perfusion, 18F-2-fluoro-2-deoxyglucose (FDG) and N-13 ammonia, respectively, were used. Fourteen of 19 documented infarctions were demonstrated by PCT to have concordantly decreased glucose utilization and perfusion. However, in an additional 11 regions, glucose utilization was disproportionately increased relative to perfusion, consistent with ischemic glucose consumption. These findings correlated with the presence of postinfarction angina, the site of ischemic electrocardiographic changes during chest pain, and the presence of regional left ventricular dysfunction and severe coronary artery disease. Because three ECG infarct zones not detected by PCT demonstrated ischemic glucose utilization, only two of 19 electrocardiographically defined infarctions had no detectable metabolic abnormality. We conclude that the changes in regional FDG and N-13 ammonia concentrations detected with PCT in patients who had had a recent myocardial infarction are consistent with regional exogenous glucose utilization and perfusion in moderately ischemic and irreversibly infarcted myocardium. This approach has the potential to identify and differentiate resting myocardial ischemia from infarction and to assess tissue viability after an ischemic event.

Adult↗

Prognosis for improved verbal communication in aphasic stroke patients.

Information for predicting to what degree a patient will recover from aphasia has not been available to the physician. This study examined the role of 10 selected prognostic variables in relation to recovery of verbal communication in a homogeneous sample of treated aphasic patients. Terminal speech performance (TSP) could be discriminated 86% of the time by 6 variables; (1) initial severity of aphasia, (2) number of months after stroke, (3) auditory comprehension ability, (4) age, (5) speech fluency, and (6) general health. The predictive value of these variables was slightly higher (91.2%) for patients with good TSP than for those with poor TSP (82.6%).

Adult↗

Assessment of the [18F]fluorodeoxyglucose kinetic model in calculations of myocardial glucose metabolism during ischemia.

The lumped constant--a term in the operational equation of the Sokoloff tracer kinetic model for deoxyglucose that accounts for the difference in transport and phosphorylation between glucose and its analog, deoxyglucose--could potentially vary from normal to ischemic conditions in the heart. To test the stability of the lumped constant during ischemia, we evaluated the ratio of the extraction fraction for (F-18)-fluorodeoxyglucose (FDG) to that for glucose (a measure of the lumped constant if there is no significant dephosphorylation of FDG-6-PO4) and the rate constant for dephosphorylation of FDG-6-PO4 (k4*) in the isolated, arterially perfused interventricular septum of the rabbit during moderate and severe demand-induced and reduced-flow ischemias. The lumped constant and k4* in each of the four ischemic experimental conditions were found not to be significantly different from the value obtained from the nonischemic controls.

Animals↗