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Biomedical subjects

S Goldstein

Publications and source records attributed to S Goldstein.

At least 415 records · Page 23Linked to original sources

Analysis of cardiac symptoms preceding cardiac arrest.

Prodromal symptoms and cardiac history were examined in 227 patients with coronary artery disease who were successfully resuscitated after out-of-hospital cardiac arrest. Cardiac arrest was sudden--with either no symptoms or symptoms for less than 1 hour--in 71% of the patients. Nonsudden death--death occurring after more than 1 hour of symptoms--occurred in 29% of the patients. A history of cardiovascular disease was present in 85% of patients with sudden cardiac arrest and in 83% with nonsudden arrest. Cardiac arrest occurred without symptoms in 38% of the patients with sudden cardiac arrest and was the first expression of coronary artery disease in 4% of the entire study group. This study indicates that cardiac arrest usually occurs with symptoms and almost always in the setting of a history of cardiovascular disease.

Angina Pectoris↗

In vitro interaction of the photoactive anticancer porphyrin derivative photofrin II with low density lipoprotein, and its delivery to cultured human fibroblasts.

Low density lipoprotein (LDL) doped with the anticancer mixture of hematoporphyrin derivatives Photofrin II (P2) competes with native LDL for binding to fibroblast receptors, despite a slight increase in the negative net charge related to the presence of acidic residues of porphyrins. P2 delivery to fibroblasts can be achieved by LDL, HDL3 or albumin doped with P2 (LDL-P2, HDL-P2 or A-P2, respectively). P2 delivery to cells assessed by fluorescence measurement, is much more efficient, at low protein concentrations (10-20 micrograms/ml) by LDL-P2 than by HDL-P2 or A-P2. Moreover, P2 delivery to cells by LDL-P2 as a function of protein concentration is a saturable process, whereas P2 delivery by HDL-P2 or A-P2 is a linear process. Finally, reduction of the LDL-receptor number by preincubation of fibroblasts in medium supplemented with lipoproteins results in a decrease of P2 delivery by LDL-P2. These results suggest a special role of the LDL-receptor pathway in P2 delivery to cells and could be of interest in cancer phototherapy by porphyrins.

Antineoplastic Agents↗

Hemodynamic effects of a new type III phosphodiesterase inhibitor (CI-914) for congestive heart failure.

Hemodynamic response after intravenous and oral administration of a new phosphodiesterase inhibitor, CI-914, was studied in 13 patients with severe congestive heart failure. Comparable significant increases in cardiac index of 26% (p less than 0.01) and 19% (p less than 0.02) after intravenous and oral administration were observed. Systemic vascular resistance, right atrial and pulmonary artery wedge pressure decreased significantly after intravenous drug administration. Although similar changes occurred after oral administration, they were not statistically significant. Peak CI-914 plasma concentration occurred 2.3 +/- 2.2 hours after oral drug administration and exhibited measurable hemodynamic effects for up to 10 to 12 hours. Seven of the 13 patients received long-term oral CI-914 for as long as 12 weeks and exhibited an improvement in New York Heart Association functional class and exercise capacity. Five patients died with progressive heart failure, 1 patient died suddenly and 1 died of sepsis. The drug was well tolerated and appears to have potential as a cardiotonic agent.

Administration, Oral↗

Phorbol esters inhibit low density lipoprotein processing by cultured human fibroblasts.

A 24 h pretreatment of MRC5 fibroblasts with the protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA) induced a marked decrease in low density lipoprotein (LDL) internalization and degradation; the maximal effect (about 55% decrease) was observed for 10(-7) M TPA. LDL binding was reduced about 35-40%. A significant decrease (about 25%) in LDL internalization was observed after a 2 h incubation of cells with the drug, but longer incubation times (4-6 h) led to a greater effect. Another tumor promoter, phorbol 12,13-dibutyrate decreased LDL internalization by about 35%, whereas the non-tumor promoting 4 alpha-phorbol 12,13-didecanoate had no effect. The protein kinase C inhibitor alpha-cobrotoxin partially antagonized the inhibitory effect of TPA on LDL internalization. The non-phorbol tumor promoter mezerein, another protein kinase C activator, decreased LDL uptake by about 50%. Finally, it was found that TPA had no significant effect on the affinity of the receptor for the LDL. These results suggest a role for protein kinase C in the LDL pathway in cultured human fibroblasts.

Cell Line↗

Echocardiographic evaluation of left ventricular function during coronary artery angioplasty.

Balloon occlusion of a stenotic coronary artery during percutaneous coronary artery angioplasty provides a unique opportunity to study the effect of acute myocardial ischemia on left ventricular (LV) function. Simultaneous M-mode and 2-dimensional (2-D) echocardiograms and a 6-lead electrocardiogram were recorded during 20 episodes of coronary artery occlusion and release in 12 patients. No patient had previous myocardial infarction and all had normal LV function by angiography. All patients had isolated single coronary artery disease, with left anterior descending stenosis in 8 and right coronary stenosis in 4. In 18 of 20 episodes (90%), M-mode echocardiography during balloon occlusion revealed a significant (p less than 0.001) decrease in LV systolic, diastolic and percent systolic wall thickness; systolic excursion; systolic and diastolic endocardial velocities; and fractional shortening. These changes were observed in the area of the ventricular septum in patients with left anterior descending occlusion and posteroinferior wall in those with right coronary artery occlusion. Two-dimensional echocardiography revealed varying degrees of hypokinesia, akinesia and dyskinesia during balloon occlusion in 18 instances. The echocardiographic changes were observed within 15 to 20 seconds of balloon occlusion and resolved 10 to 20 seconds after balloon deflation. All patients who had echocardiographic changes during balloon occlusion also had concomitant electrocardiographic (ECG) ST-segment elevation, whereas 2 patients with normal LV function had no ECG changes. Both of these patients had profuse collateral blood supply to the stenotic coronary artery. The echocardiographic and ECG abnormalities increased proportionately to the length of balloon occlusion. This study confirms previous animal and recent human studies of transient LV dysfunction during coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Balloon↗

In vivo evaluation of intracellular pH and high-energy phosphate metabolites during regional myocardial ischemia in cats using 31P nuclear magnetic resonance.

Phosphorus-31 nuclear magnetic resonance spectroscopy (31P NMR) was used to assess the temporal changes of high-energy phosphate metabolites in the region of acute myocardial ischemia of open-chest cats. Eight anesthetized cats were studied following ligation of the left anterior descending coronary artery. Creatine phosphate showed a 79 +/- 16% (mean +/- SD) reduction by 4 min after the onset of ischemia. Prominent qualitative reductions of the spectral peak of creatine phosphate occurred by 40 s after ischemia. Adenosine triphosphate measured under the beta spectral peak (beta-ATP) decreased 37 +/- 9% by 20-25 min after ligation of the left anterior descending coronary artery. These reductions developed more slowly and were of smaller magnitude than those of creatine phosphate. Intracellular pH decreased from 7.39 +/- 0.07 to 7.13 +/- 0.09 units by 40 s after ischemia. By 30 min, pH decreased to 6.07 +/- 0.40 units. The study shows, therefore, the temporal changes of high-energy phosphate metabolites during ischemia in localized regions of the myocardium of open-chest animals.

Adenosine Triphosphate↗

The role and mechanism of metal ions and their complexes in enhancing damage in biological systems or in protecting these systems from the toxicity of O2-.

Copper complexes of 1,10-phenanthroline and some substituted 1,10-phenanthroline cleave DNA in the presence of a reducing agent and molecular oxygen. Generally, the damage is attributed to hydroxyl radicals which are formed through the Haber-Weiss reaction. It is assumed that this reaction occurs with the ternary metal complexes with the biological target and the mechanism is defined as the "site specific mechanism." In these systems, O2- drives the cycle through the reduction of copper(II). On the other hand, these same copper complexes catalyze the dismutation of O2- and thus should protect the systems from O2- toxicity. In this article, the toxicity of these complexes is explained on kinetic grounds. A general discussion on the various factors which could cause the metal ions or their complexes to act either as protectors from O2- toxicity or as sensitizers of toxic effects of O2- is given.

Biological Transport, Active↗

Detection of distinct receptors for native and acetylated low-density lipoproteins in human placental microvilli by ligand-immunoblotting.

Ligand-immunoblotting was used to detect distinct receptors for native low-density lipoprotein and for acetylated low-density lipoprotein on microvillous membranes from human term placentas. Antisera directed against native and modified low-density lipoproteins were prepared in rabbits and their specificities were assessed by immunodiffusion and immunoelectrophoresis. The receptor for low-density lipoprotein was detected as a 160 kDa protein and that for acetylated low-density lipoprotein as a 200 kDa protein. These receptors were compared with their counterparts in cultured human skin fibroblasts, bovine adrenal cortex and J774 macrophage-like cells. This is the first investigation that visualizes the presence of receptors for both native and modified low-density lipoproteins in a steroidogenic tissue.

Acetylation↗

Effect of propranolol in patients with myocardial infarction and ventricular arrhythmia.

The Beta-Blocker Heart Attack Trial was a placebo-controlled, randomized, double-blind clinical trial of the long-term administration of propranolol hydrochloride to patients who had had at least one myocardial infarction. Among 3,837 patients followed up for an average of 25 months, 3,290 (85.7%) had 24 hour ambulatory electrocardiograms performed at the baseline examination. Four classifications of arrhythmia were examined. One of these, the presence of complex ventricular arrhythmias (at least 10 ventricular premature beats/h, or at least one pair or run of ventricular premature beats or multiform ventricular premature beats) was the subgroup of major interest. Regardless of the classification, the presence of arrhythmia identifies a group of patients with a higher risk of total mortality, coronary heart disease mortality, sudden cardiac death and instantaneous cardiac death. The a priori subgroup hypothesis that sudden death would be preferentially reduced by propranolol in patients with complex ventricular arrhythmias was not supported. The relative benefit of propranolol in reducing sudden death for this subgroup was 28 versus 16% for the subgroup without ventricular arrhythmia (relative risk of 0.72 versus 0.84, a nonsignificant relative difference of 14%). There were similar findings for two of the three other classifications of arrhythmia and for the other response variables. Although propranolol does not appear to be of special relative benefit in patients with ventricular arrhythmia, the presence of the arrhythmia does identify a high-risk group. The mechanism by which propranolol reduces mortality is still unclear, but is probably not solely an antiarrhythmic one.

Adult↗

The epidemiology of tachyfibrillation in sudden death.

Although death occurs suddenly in coronary heart disease, it is associated with a prior history of cardiac disease in 85% and with prodromal symptoms in 73.8% of the patients resuscitated from cardiac arrest outside the hospital. Sudden death was the first expression of coronary heart disease in 3.6% of the patient population. The fact that out-of-hospital sudden death is usually secondary to myocardial infarction and ischemia is supported by this clinical study and is suggested by other clinical and pathological studies of individuals dying suddenly.

Coronary Disease↗

Premenstrual changes and changes in gonadal hormones.

Changes in plasma levels of estradiol and progesterone and their temporal relationship with changes in mood and behavior were studied along the menstrual cycle in 17 normal women with a wide range of severity and types of premenstrual changes (PMC). Emphasizing changes in hormonal levels over time as well as their rates of change, selective clinical features of premenstrual changes were found to be positively associated with peak levels of progesterone, its rate of decrease over time, and the ratio between the rates of decrease-over-time of progesterone and estradiol levels. A time-lag of 4-7 days between changes in plasma levels of progesterone and changes in clinical features was also found. Rate of change of estradiol was somewhat associated with clinical PMC. It is suggested that the association between gonadal hormones, other biological changes, and mood should be further studied as a diversified, dynamic, time-related process.

Adult↗

Semistarvation and exercise.

Nutritional intake plays an important role in determining metabolic and respiratory demands during both rest and exercise. This study examines the effects in normal subjects of 4 days of semistarvation with 440 kcal/day of intravenously infused dextrose followed by the infusion of 480 kcal/day of amino acids for 48 h on the metabolic and ventilatory response to exercise (1.25, 2.50, and 5.0 kg . m/s.). After 4 days of the dextrose infusion, arterial PCO2 (P less than 0.05), and the ventilatory equivalent for CO2 (VE/VCO2, P less than 0.05) were decreased at rest compared with control measurements made prior to the dextrose infusion. During all three levels of steady-state exercise, arterial PCO2 was significantly lower (P less than 0.05) than observed before the start of the dextrose infusion. The subsequent infusion of amino acids resulted in increases in O2 consumption (V02; P less than 0.05) and minute ventilation (VE; P less than 0.05), a decrease in arterial PCO2 (P less than 0.05), and little change in CO2 production (VCO2) at rest. During low levels of exercise, compared with the values obtained following the 4 days of dextrose infusion, there were larger increases in VE and VO2, whereas VCO2 changed little. Mechanical efficiency (kcal work/kcal energy utilized) during exercise increased after 4 days of dextrose and returned to near control levels with the amino acid infusion. The adaptive response characteristic of semistarvation with dextrose appears to be altered when isocaloric amounts of amino acids are subsequently administered for short periods.

Adult↗

Effect of propranolol after acute myocardial infarction in patients with congestive heart failure.

The incidence of congestive heart failure was studied in the Beta Blocker Heart Attack Trial in which postmyocardial infarction patients between the ages of 30 and 69 years, with no contraindication to propranolol, were randomly assigned to receive placebo (n = 1921) or propranolol 180 or 240 mg daily (n = 1916) 5 to 21 days after admission to the hospital for the event. Survivors of acute myocardial infarction with compensated or mild congestive heart failure, including those on digitalis and diuretics, were included in the study. A history of congestive heart failure before randomization characterized 710 (18.5%) patients: 345 (18.0%) in the propranolol group and 365 (19.0%) in the placebo group. The incidence of definite congestive heart failure after randomization and during the study was 6.7% in both groups. In patients with a history of congestive heart failure before randomization, 51 of 345 (14.8%) in the propranolol group and 46 of 365 (12.6%) in the placebo group developed congestive heart failure during an average 25 month follow-up. In the patients with no history of congestive heart failure, 5% in the propranolol group developed congestive heart failure and 5.3% in the placebo group developed congestive heart failure. Baseline characteristics predictive of the occurrence of congestive heart failure by multivariate analyses included an increased cardiothoracic ratio, diabetes, increased heart rate, low baseline weight, prior myocardial infarction, age, and more than 10 ventricular premature beats per hour.(ABSTRACT TRUNCATED AT 250 WORDS)

Heart Failure↗

Noninvasive evaluation of left ventricular performance based on peak aortic blood acceleration measured with a continuous-wave Doppler velocity meter.

Peak aortic blood acceleration is recognized to be a sensitive index of global left ventricular performance. In the present study peak acceleration was assessed noninvasively in patients with a continuous-wave Doppler velocity meter. Peak aortic blood velocity and peak blood acceleration were measured by placing the ultrasonic transducer at the suprasternal notch. Measurements were obtained in 36 patients undergoing diagnostic cardiac catheterization. Peak velocity and acceleration were measured at rest just before left ventriculography. In patients with ejection fractions greater than 60%, peak acceleration was 19 +/- 5 m/sec/sec. In patients with ejection fractions of 41% to 60%, peak acceleration was lower, at 12 +/- 2 m/sec/sec (p less than .001). In patients with ejection fractions of 40% or less, peak acceleration (8 +/- 2 m/sec/sec) was markedly lower than in patients with ejection fractions greater than 60% (p less than .001). Peak acceleration showed a good linear correlation with ejection fraction (r = .90), and a better power fit (r = .93). These results indicate that peak acceleration, measured noninvasively with a continuous-wave Doppler velocity meter, is a useful indicator of global left ventricular performance.

Aorta↗