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Biomedical subjects

J M Loeb

Publications and source records attributed to J M Loeb.

At least 19 recordsLinked to original sources

Human gene therapy: a role for the primary care physician.

Human gene therapy, once thought to be the unique province of specialized clinical centers, will be diffusing rapidly into primary care medicine. More than 10 medical centers in the United States and several centers world-wide are beginning to use this potentially curative therapy. Eleven trials of protocols are under way, nine are about to begin, and more than 12 protocols are nearing completion of the approval process. The diseases being treated are not the rare disorders found only in one in 100,000 patients, but instead include various types of cancer, diseases of the cardiovascular and pulmonary systems, and inborn errors of metabolism. Combined, these diseases affect more than half of the American population.

Clinical Protocols

Technology assessment. An American Medical Association perspective.

The contemporary practice of medicine depends on the use of a wide array of technologies that did not exist 40 years ago. An exponential increase in our scientific knowledge base, and the subsequent application of this new information to clinical practice, have dramatically extended longevity, enhanced the quality of life, and improved the overall health status of the American public. Clinical medicine has become "a set of technologies for diagnosis, prevention, treatment, and rehabilitation."

American Medical Association

Human vs animal rights. In defense of animal research.

For centuries, opposition has been directed against the use of animals for the benefit of humans. For more than four centuries in Europe, and for more than a century in the United States, this opposition has targeted scientific research that involves animals. More recent movements in support of animal rights have arisen in an attempt to impede, if not prohibit, the use of animals in scientific experimentation. These movements employ various means that range from information and media campaigns to destruction of property and threats against investigators. The latter efforts have resulted in the identification of more militant animal rights bands as terrorist groups. The American Medical Association has long been a defender of humane research that employs animals, and it is very concerned about the efforts of animal rights and welfare groups to interfere with research. Recently, the Association prepared a detailed analysis of the controversy over the use of animals in research, and the consequences for research and clinical medicine if the philosophy of animal rights activists were to prevail in society. This article is a condensation of the Association's analysis.

American Medical Association

Refractory ascites due to POEMS syndrome.

A 52-yr-old woman developed exudative ascites 2 yr after the onset of peripheral neuropathy. Extensive evaluation revealed that the patient had no underlying liver disease, malignancy, infection, or cardiac or renal disease. The ascites initially responded to high-dose corticosteroid therapy. The patient had many clinical features of the recently described POEMS syndrome, including a persistent IgA lambda-paraprotein. Initially, her ascites responded to treatment with steroids. This is characteristic of the syndrome and should be considered in patients with POEMS syndrome and refractory ascites.

Ascites

Phasic influences of vagal stimulation on atrioventricular conduction.

The beat-by-beat changes in atrioventricular (AV) conduction evoked by constant frequency and phase-coupled vagal stimulation were examined both qualitatively and quantitatively in 13 anesthetized dogs. The effects of pacing cycle length and sympathetic activity on the vagally induced phasic changes in AV conduction were also characterized. When the vagal stimulus interval was nearly equal to the pacing cycle length and the vagal stimulus moved progressively through the cardiac cycle, AV interval oscillated in a rhythmic fashion. The rhythmicity of the vagally induced AV interval oscillations was altered substantially by changes in either the vagal stimulus interval or the pacing cycle length. The vagally induced AV interval oscillations were abolished during phase-coupled vagal stimulation; however, the magnitude of the resultant steady-state AV interval depended on the time relative to the phase of the cardiac cycle that the vagal stimulus was delivered. In the presence or absence of sympathetic stimulation, a vagal stimulus falling approximately 200 ms prior to atrial depolarization evoked the greatest prolongation in AV interval, regardless of the pacing cycle length. Additionally, the effects of combined sympathetic and phase-dependent vagal stimulation on the AV interval were additive. These data confirm that the influence of a vagal stimulus on AV interval can be predicted from the phase in the cardiac cycle that the vagal stimulus is delivered. Moreover, this phase dependency of vagal effects evokes marked qualitative variations in AV interval response patterns when either the vagal stimulus interval or the pacing cycle length is altered.

Animals

Integration of heart rate and sympathetic neural effects on AV conduction.

Sympathetic activation increases heart rate (HR) and reduces atrioventricular interval (AVI), whereas atrial pacing alone increases AVI. We sought to differentiate the direct effects of sympathetic activation on atrioventricular (AV) conduction time from the indirect changes associated with concurrent alterations in HR. We recorded electrocardiograms, blood pressure (BP), and intracardiac electrograms from chloralose-anesthetized autonomically decentralized dogs. Beat-by-beat HR and AVI data were collected continuously. Sympathetic stimulation (0.25-2.5 Hz; mean 0.81 Hz) resulted in a HR change of +60 beats/min after 60 s. This tachycardia was associated with a mean decrease in AVI of 22 ms. Computer-driven atrial pacing to reproduce the HR associated with control sympathetic stimulation caused a mean AVI increase of 10 ms. Propranolol (200 micrograms) was then administered via the sinoatrial node artery and sympathetic stimulation repeated. Although HR remained constant, AVI decreased by 14.8 ms. The AVIs associated with an identical HR achieved by two different mechanisms (sympathetic stimulation and atrial pacing) were significantly different. Although removal of the contribution of sympathetically induced HR changes on AV conduction might be expected to result in potentiation of neural effects at the AV node, none was evident. Thus sympathetic activity restricted to the AV node is less effective in influencing AV conduction than the response that occurs when HR changes occur concurrently. Therefore, the opposing actions of HR and sympathetic tone on AV conduction may not be predicted by a simple linear relationship.

Animals

Atrioventricular nodal accommodation: rate- and time-dependent effects.

To characterize intrinsic rate- and time-dependent properties of the atrioventricular (AV) node, we examined whether AV interval (AVI) would be comparable at identical heart rates (HR) reached using different types of stimulation paradigms. We compared changes in AVI during five consecutive 30-s, 20 beat/min increases in HR from control with AVI changes induced by 30-s single-step protocols to each of the same levels. In addition, HR was maintained at each level for 30, 60, 90, 120, and 150 s to control for the influences of time. Chloralose-anesthetized dogs (n = 16) were autonomically decentralized and instrumented to record electrocardiogram, blood pressure, and multiple intracardiac electrograms. Computer-generated HR steps were begun 20 beats/min above control, while continuously recording AVI. The beat-by-beat changes in AVI within each step were quantitated for all protocols. Differences between AVI during single- and multiple-step protocols were most pronounced during the first 15 s of atrial pacing. Accommodation in AVI (change in AV conduction time associated with an increased but constant heart rate) was evident during both protocols. The degree of accommodation during multiple-step protocols was modulated by the cumulative effects of earlier HR; however, a similar degree of accommodation occurred at higher HR irrespective of protocol used. Finally, the time to onset of loss of 1:1 AV conduction was significantly shorter when HR was increased using a multiple-step protocol. Thus the intrinsic response of the AV node to HR change is dependent on absolute level of HR, duration of rate change, and the potential cumulative effects of any earlier HR steps.

Animals