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Biomedical subjects

J Karliner

Publications and source records attributed to J Karliner.

At least 19 recordsLinked to original sources

United Nations Development Program solicits funds from corporations.

The Global Sustainable Development Facility (GSDF) project, a collaboration between the U.N. Development Program and a variety of global corporate sponsors, some with poor human rights, labor, and environmental records, has come under criticism from prestigious nongovernmental organizations around the world. A letter to James Gustave Speth, Administrator of the U.N. Development Program, expresses concern about the threat posed by the GSDF project to the independence and credibility of the U.N. Development Program.

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Dual trophic effects of the alpha 1-adrenergic receptor in cultured neonatal rat heart muscle cells.

The molecular signals regulating myocardial hypertrophy are unknown. We used a new model system to study this problem. Muscle cells from the neonatal rat ventricle were cultured in serum-free medium. Control cells did not change in size over time and did not show spontaneous contractile activity. Incubation with norepinephrine or epinephrine had two major trophic effects that developed over 1-2 days. The first was stimulation of muscle cell hypertrophy or increase in size. The second was induction of spontaneous contractile activity. The hypertrophic response was mediated through an alpha 1-adrenoceptor. The beating response required both alpha 1- and beta 1-adrenergic receptor stimulation. Alpha 1 stimulation alone produced enlarged cells that did not beat. Alpha 1 plus beta 1 stimulation induced contractile activity even when protein synthesis and hypertrophy were inhibited. Thus, the two alpha 1 responses could be dissociated, providing evidence for two independently-regulated cellular pathways for the dual alpha 1 trophic effects. One pathway leads to hypertrophy. The other, which requires concomitant beta 1 stimulation, controls the development of beating. Preliminary work raises the possibility that different products of inositol phospholipid hydrolysis might initiate the two alpha 1 trophic pathways. Other preliminary work suggests that the growth pathway is associated with the expression of specific genes and might reflect an action of the alpha 1-adrenoceptor on the cell nucleus. These studies define previously unsuspected trophic roles for the alpha 1-adrenergic receptor.

Animals↗

Evaluation of left ventricular function in chronic pulmonary disease by exercise gated equilibrium radionuclide angiography.

To assess left ventricular (LV) response to supine bicycle exercise, we studied 10 normal (group 1). 10 patients with coronary artery disease (CAD) (group 2), 12 patients with severe obstructive lung disease (COPD) (group 3), and eight patients with both CAD and COPD (group 4) by gated equilibrium radionuclide angiography. Most individuals in all groups also had pulmonary catheter-obtained measurements of LV filling pressures during exercise. Normal individuals increased their ejection fraction (EF) during exercise by increasing stroke volume (SV) and reducing end-systolic volume (ESV) without changing end-diastolic volume (EDV); pulmonary artery (PAP) and wedge (PAW) pressures were unaltered. CAD patients (group 2) showed no change in EF with increased EDV, ESV, SV, and PAW. COPD patients (group 3) exhibited decreases in EDV, ESV, and SV, accounting for abnormal EF responses in 6 of 12; PAW was unchanged and the marked elevation of PAP correlated with reduced EDV. Group 4 patients (CAD plus COPD) had abnormal EF responses with increased EDV and ESV without change in SV. Thus an abnormal LV function response to exercise in COPD patients may be multifactorial, thereby indicating the possible need for therapeutic modalities in addition to those employed in alleviating pulmonary parenchymal disease.

Adult↗

Left ventricular size and function after subcutaneous administration of terbutaline.

To assess the response of the left ventricle to subcutaneously administered terbutaline sulfate, a proposed beta-2 selective agonist, we evaluated 12 patients who had suffered previous myocardial infarctions using equilibrium radionuclide angiography. Six patients (group 1) had normal global left ventricular ejection fraction at rest less than 0.49). All patients had a marked decline in end-diastolic volume and end-systolic volume with a significant (P less than 0.01) increase in ejection fraction after terbutaline injection. Cardiac output increased 30 percent in group 2 patients because of an increase in stroke volume, with little change in heart rate (plus or minus 3.1 beats per minute, P equals NS). Cardiac output increased 7 percent in the patients in groups 1, due primarily to an increase in heart rate in 7 beats per minute (+9 percent) with little change in stoke volume. Systemic vascular resistance decreased significantly more in the patients with compensated heart failure than the subjects in group 1 (342 plus or minus 84 vs 90 plus or minus 35 dynes-sec cm(-5), P less than 0.05). We conclude that terbutaline exerts its most beneficial effect on the left ventricle in patients with depressed resting global function, and may prove to be a useful agent in the treatment of congestive heart failure.

Aged↗

A method for the estimation of right ventricular volume by equilibrium radionuclide angiography.

To develop a method for estimating right ventricular volume and to assess right ventricular volume at rest, we studied 45 persons with equilibrium radionuclide angiography. The study group comprised 15 normal control subjects (5 with atypical chest pain and normal coronary angiograms) and 30 patients with coronary heart disease (CHD). Each coronary patient and 5/15 control subjects had both right and left heart catheterization studies with intracardiac pressure measurements within 24 hours of the radionuclide study. Using a previously described method for generating right ventricular volume curves, we used the counts at end-diastole, corrected for frame time, the total number of processed heart beats, and blood radioactivity to derive right ventricular end-diastolic volume units. All normal controls (group 1) had a right ventricular ejection fraction greater than or equal to 0.40, with a right ventricular volume index less than or equal to 5.8. The CHD patients consisted of two subgroups: group 2 (N = 20) and group 3 (N = 10), with right ventricular end-diastolic pressures less than 10 mm Hg and greater than or equal to 10 mm Hg, respectively. In group 2, 19/20 had a normal right ventricular ejection fraction, and 18 had a normal end-diastolic volume. In group 3, 4/10 patients had a depressed ejection fraction (less than .40) and 9/10 an increased end-diastolic volume. We conclude that right ventricular volume can be estimated with radionuclide angiography, and that dilation may precede depression of the right ventricular ejection fraction in some patients with CHD.

Angiography↗

Assessment of early ventricular systole by first pass radionuclide angiography: useful method for detection of left ventricular dysfunction at rest in patients with coronary artery disease.

To identify abnormal left ventricular function without exercise stress in patients with coronary artery disease first-pass radionuclide angiograms were analyzed in 32 normal subjects (Group I); 31 patients with coronary disease and normal contrast ventriculograms (Group II); and 17 patients with coronary disease and depressed left ventricular function (Group III). Total ejection fraction (EF) was computed with standard angiographic methods and from each time-activity curve. During the first third of systole, ejection fraction was determined manually by averaging three to five beats and the value compared with that obtained with contrast ventriculography: (Formula: see text). Both total radionuclide ejection fraction (r = 0.95) and first-third ejection fraction (r = 0.91) correlated well with angiography. Intraobserver and interobserver variation was small, averaging 0.02 +/- 0.02 (range 0 to 0.05). The radionuclide first-third ejection fraction was 0.25 or greater in normal subjects and less than 0.25 in 29 of 31 patients (94 percent) in Group II and in all patients in Group III. It is concluded that the first-third ejection fraction obtained with first pass angiography identifies subtle abnormalities of left ventricular function at rest in more than 90 percent of patients with coronary disease that may not be recognized by total ejection fraction alone.

Adult↗

Reproducibility of ejection fraction and ventricular volume by gated radionuclide angiography after myocardial infarction.

To validate the repeated use of radionuclide equilibrium angiography for determining left ventricular (LV) ejection fraction (EF) and end-diastolic and end-systolic volumes (EDV and ESV), 25 patients were studied on an hourly basis an average of 9.1 days after acute myocardial infarction. Data were processed with a semi-automatic computer program which develops an averaged-volume curve from an assigned LV region-of-interest. LV EDV and ESV were derived from a previously described method which correlates well with contrast angiography (r = 0.977, y = 0.0255x - 0.121). Comparison between initial and subsequent equilibrium EF and between initial and subsequent volumes showed excellent correlation. Excluding three anginal episodes, the EF variation between studies averaged 0.03 +/- 0.02.

Acute Disease↗

Left ventricular volumes by gated equilibrium radionuclide angiography: a new method.

To compare radionuclide end-diastolic (EDV) and end-systolic (ESV) volumes with angiographic volume, we studied 52 patients with equilibrium radionuclide angiography using 99mTc-human serum albumin within 48 hours of contrast angiography. Each RR interval was divided into 20--28 equally timed frames and a time-activity curve generated. End-diastolic counts were taken at the early peak of the curve and end-systolic counts at its nadir. Counts were divided by the total number of processed heart beats and normalized for: 1) dose per body surface area; 2) plasma volume; and 3) counts/ml of plasma. A cardiac phantom was developed and serial volumes were studied using a normalization factor. Radionuclide values were expressed as dimensionless units and compared with either biplane angiographic volumes (in the patient studies) or known phantom volumes. Good correlations were obtained with methods 1 and 2 in 35 patients (r greater than 0.84), but the best correlation was obtained in 17 patients when normalization for counts/ml of plasma was used (r = 0.98; y = 0.255 x -0.121). The standard error of the estimate (SEE) was +/- 11.5 ml for EDV and +/- 7.3 ml for ESV. The phantom study also showed an excellent correlation (r = 0.99), with a SEE of +/- 6.5 ml. We conclude that a radionuclide method independent of geometric assumptions can be used to estimate left ventricular volume in man.

Adult↗