The Development of a Series of Cast Metal Sculpture Using the Lost Wax Process

The purpose of this problem is twofold. First, I feel impelled to make a personal statement regarding my philosophies about form, and secondly to explore the possibility of relating negative and positive form as a sculptural unity in bronze casting

Ionic transfer in cardiac muscle. An explanation of cardiac electrical activity

The evidence has been reviewed which suggests that the upstroke of the action potential in heart muscle is due to the entry of sodium ions. This conclusion is based on the failure of the upstroke to occur if 90 per cent of the sodium is replaced by sucrose, and the demonstration of a reduction in amplitude of the rising phase of the action potential with each decrement in extracellular sodium concentration or an increase in amplitude with increasing extracellular sodium concentration. In addition, the demonstration of a change in membrane resistance of one-hundred-fold at the time of the rising phase suggests increased permeability of the membrane at this time.The voltage-clamp studies in the squid giant axon clearly show an inward movement of current during the rising phase, which disappears when choline replaces sodium in the perfusing bath.The resting membrane potential resembles the model of a potassium and chloride concentration cell, since calculations based on measured concentrations across the membrane agree fairly closely with measured potentials. Furthermore, the membrane resting potential is altered in a predictable manner by changed extracellular potassium and chloride concentration, but is not appreciably affected by changing sodium concentration. Since the skeletal muscle membrane appears to be freely permeable to chloride, and only sparingly so to potassium, and since potassium permeability is selectively altered during the electrical cycle, the chloride ionic concentration gradient is probably dependent on the transmembrane potential, and, therefore, is passive. The current carried by the chloride ion in cardiac fibers is small.Little is known of the factors which alter membrane permeability or affect the transfer rates during recovery, but it is apparent that sodium is removed from the cell after the rising phase and is replaced by potassium to restore membrane resting potential.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32171/1/0000226.pd

Mitral valve prolapse syndrome: The effect of adrenergic stimulation

Previous studies demonstrating increased adrenergic tone in symptomatic patients with mitral valve prolapse prompted a study of the response of symptomatic patients with mitral valve prolapse to adrenergic stimulation. Sixteen such patients had plasma catecholamines and 24 hour urinary epinephrine plus norepinephrine values that were greater than those of control subjects (473.3 ± 92.8 pg/ml versus 292 ± 15 and 44.7 ± 2.3 μg/g creatinine versus 29.8 ± 2.3; p < 0.01 and < 0.001, respectively). Twenty-four hour urinary sodium was lower in the patient group than in the control group (75 ± 7.4 versus 141 ±11 mEq; p < 0.01), with an inverse relation between urinary sodium and norephinephrine in the patient group (r = - 0.78) but not in the control group.Isoproterenol infusions, 0.5, 1.0 and 2.0 μg/min for 6 minutes, produced a dose-related, greater increase in heart rate in the mitral valve prolapse group than in the control group (16.1 ± 2.3 versus 10 ± 2; 31.8 ± 3.5 versus 19.6 ± 3; 48 ± 4.1 versus 27 ± 3; p< 0.01 with 0.5, 1.0 and 2.0 μg, respectively). The greater increase in heart rate resulted in a significantly shorter diastolic time in the patient group than in the control group (26.4 ± 2 s/min versus 30.6 ± 2; 27 ± 1.5 versus 30.6 ± 2; 26.6 ± 2 versus 30.9 ± 2; p < 0.01 with 0.5, 1.0 and 2.0 μg, respectively). The QT interval was 25 ms shorter than electromechanical systole (QS2) in the normal group and 26.5 ms shorter than QS2in the mitral valve prolapse group at rest; during isoproterenol infusion QT-QS2values were different in the mitral valve prolapse and control groups (3.3 ± 3 versus -7.0 ± 3; 31.9 ± 2.8 versus 10 ± 4; 52 ± 9.2 versus 29 ± 8; p < 0.01 with 0.5, 1.0 and 2.0 μg/min, respectively). Isoproterenol infusion also reproduced symptoms on a dose-related basis in 14 patients with mitral valve prolapse but not in control subjects (excluding palpitation).Symptomatic patients with mitral valve prolapse and high rest values of catecholamines were hypersensitive to isoproterenol infusion, suggesting that some of the symptoms are catecholamine-related or mediated

The use of potassium in the treatment of heart disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32003/1/0000045.pd

An experimental study of the electromotive forces of the heart

Propagated wavefronts were produced by mechanical stimulation at points located deeply within the myocardium, and the external field so produced was measured by electrodes located within a radius of 10 mm. from the centrally stimulated point. In 104 experiments in 10 dogs the external field so produced was negligible until propagation reached either the epicardial or endocardial surfaces. If it is assumed that propagated intramural activity is temporarily a closed electromotive surface, then the data presented suggest that there is a uniform difference in potential across this surface. Since there is no fundamental difference in the wavefront characteristics of closed electromotive surfaces and those which present boundaries on the epicardial or endocardial surfaces, these data strongly suggest that there is a uniform difference in potential across all propagated wavefronts in normal ventricular muscle.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32059/1/0000103.pd

Clinical evaluation of glucagon by continuous infusion in the treatment of low cardiac output states

A continuous infusion of glucagon in an average dose of 4 mg. per hour over several days produced distinct improvement in the clinical state of 12 of 16 patients. Improvement was noted by an increase in blood pressure and urinary output and decrease in dyspnea, pulmonary rales, diaphoresis, and peripheral edema when present. Serum potassium must be carefully monitored. The rise in blood glucose has not been a clinical problem. No cardiac arrhythmias were induced by glucagon, and as cardiac function improved, the heart rate usually decreased. Nausea was the most frequent side effect, but no toxic effects or tachyphylaxis were observed. Long-term therapy with glucagon infusion is both safe and highly efficacious in selected patients with severe cardiovascular disease states and is the treatment of choice in cardiac decompensation secondary to beta-blocking agents.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32778/1/0000151.pd

A clinical trial of antazoline in the treatment of arrhythmias

Antazoline is a comparatively safe and effective antiarrhythmic drug in many situations, for both the conversion and prevention of arrhythmias. It appeared to be most effective in the abolition of ventricular tachycardia, possibly helpful in 2 cases of cardiac arrest due to ventricular fibrillation and beneficial in the prevention of atrial and ventricular premature beats. It was useful and deserves further trial in the prevention of paroxysmal ventricular tachycardia. It was almost ineffective in the conversion and prophylaxis of atrial flutter and atrial fibrillation but appeared to be of value in the prevention of paroxysmal atrial tachycardia.There was a high incidence of mild side effects, mostly of the gastrointestinal type, some of which were prevented by taking the drug with meals or with an antacid preparation. No irreversible or serious side actions were encountered, but diarrhea, central nervous system symptoms and chills and fever necessitated stopping the drug in a small percentage of patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/32096/1/0000146.pd

Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis