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Biomedical subjects

S Goldstein

Publications and source records attributed to S Goldstein.

At least 505 records · Page 28Linked to original sources

Report of a newly redesigned Peak Flow Whistle.

A redesigned Peak Flow Whistle is described. It was evaluated and compared to the Wright Peak Flow Meter (WPFM) and the Vitalograph Pulmonary Monitor (VPM) using a laboratory flow system. These devices were evaluated for accuracy at steady flows, resistance characteristics, measurement of drift and dynamic accuracy. All devices tested correlated to a significant degree for accuracy at steady flows. The resistance of the WPFM and VPM increased with higher flows, whereas the Cardboard Peak Flow Whistle (CPFW) decreased. After pulsing the CPFW did not show any drift in calibration. The dynamic accuracy of the CPFW was excellent. Thus the accuracy of the CPFW and its lower cost makes it a practical device for measuring peak flows.

Asthma↗

Mitochondrial DNA in mortal and immortal human cells. Genome number, integrity, and methylation.

Mitochondrial DNA was quantitated in total DNA of various normal and mutant strains of human diploid fibroblasts (finite replicative lifespan) and permanent cell lines, using Southern-transfer hybridization to 32P-labeled pure mtDNA probe and saturation hybridization to 3H-labeled cRNA copied from mtDNA. In six normal fibroblast strains, mtDNA copy number increased during serial passage roughly in proportion to cell volume or protein content, whereas normalized mtDNA content per pg of protein depended upon in vivo donor age but not passage level ("in vitro" age). Copy numbers for mtDNA varied much more widely in individual fibroblast clones than in mass cultures, but were not well correlated with longevity or growth rate. Five mutant fibroblast strains associated with reduced replicative lifespan, and four permanent cell lines, were also examined; in each group, mtDNA values were observed both lower and higher than any obtained for normal fibroblasts. No evidence was found of petite-type deletions from human mtDNA, either at late passage or in individual clones of fibroblasts. Methylation of mtDNA genomes was strikingly non-random and apparently decreased with culture age.

Adult↗

Intracoronary fibrinolytic therapy in acute myocardial infarction. Report of a prospective randomized trial.

We performed a randomized trial comparing intracoronary administration of streptokinase versus dextrose placebo within six hours after the onset of symptoms of acute myocardial infarction in 40 patients. The base-line clinical, hemodynamic, and angiographic findings were similar in the control and streptokinase-treated groups. Reestablishment of flow occurred in 12 of 20 patients treated with streptokinase and in 2 of 20 given placebo (P less than 0.05). Left ventricular function, angiographic ejection fraction, and regional wall motion, measured before and immediately after intervention, and serial radionuclide ejection fractions, measured at treatment, at 12 days, and at 5 months, were compared according to type of treatment (streptokinase vs. placebo) and outcome of therapy (reperfusion vs. no reperfusion). No statistically significant differences between groups were found. Thus, although streptokinase was more effective than placebo in achieving reperfusion, we detected no improvement of left ventricular function as a result of reestablished coronary flow.

Adult↗

Echo-phonocardiographic features of regurgitant porcine mitral and tricuspid valves presenting with musical murmurs.

Echophonographic findings of three patients with spontaneous degeneration of porcine tricuspid and mitral valves presenting with musical murmurs are reported. Echocardiography in all these patients revealed systolic or diastolic cusp flutter similar in frequency to the musical murmur on simultaneously recorded phonocardiogram. Porcine tricuspid regurgitation is usually well tolerated and can be followed clinically for many years. However, patients with mitral porcine valves usually become symptomatic or present with congestive heart failure and usually require valve surgery soon after clinical or echo-phonocardiographic findings of valve regurgitation appear.

Aged↗

Echocardiographic evaluation of porcine bioprosthetic valves: experience with 309 normal and 59 dysfunctioning valves.

To determine the clinical value of echocardiographic evaluation of porcine bioprosthetic valves, the findings in all patients who had porcine bioprosthetic valve replacement and adequate quality echocardiographic studies from 1978 to 1982 were analyzed. The study includes 309 normal and 59 dysfunctioning valves. Valve dysfunction resulted from spontaneous cusp degeneration in 39 (34 valve regurgitations, 5 stenoses), infective endocarditis in 12, paravalvular regurgitation in 5, regurgitation of redundant cusps, mitral valve thrombi, and aortic stent stenosis in 3 others. Echocardiographic findings were correlated with gross surgical pathologic or autopsy findings in 45 of the 59 dysfunctioning valves. Echocardiographic abnormalities were demonstrated in 41 of 59 (69%) dysfunctioning valves. A systolic mitral or diastolic aortic valve flutter was diagnostic of a regurgitant valve caused by a torn or unsupported cusp margin and was observed in 28 of 34 (82%) regurgitant valves with no false-positive studies. Echocardiographic cusp thickness of greater than or equal to 3 mm correctly identified all regurgitant and stenotic valves with gross anatomic evidence of localized or generalized cusp thickening or calcific deposits. Echocardiographic valve abnormalities were observed in only 4 of 12 patients with infective endocarditis and in 1 of 5 with paravalvular regurgitation. Thus, echocardiography provides important information regarding the function of porcine bioprosthetic valves and is of value in the decision to replace these valves, especially when dysfunction is due to spontaneous cuspal degeneration. Echocardiography is neither sensitive nor specific in patients with infective endocarditis and paravalvular regurgitation.

Echocardiography↗

Some aspects of cellular aging.

Studies were carried out on cultured human fibroblasts in order to elucidate the biology of aging and the origins of age-dependent diseases. The replicative life span of cultures was inversely proportional to the chronological age of the tissue donor, and cultures derived from subjects with two inherited disorders of premature aging, progeria and Werner syndrome, had more severely impaired growth capacity. Studies on circular outgrowths whereby cell division is restricted to a circumferential rim of cells indicated that the replicative life span is controlled by a mitotic counter to a critical limit. The response of progeria cells to a hormone preparation with insulin-like activity was decreased, while in normal cells this decrease occurred as a function of passage level with a "shift to the right" of the dose-response curve. Cyclic AMP content of fibroblasts at late passage fell in response to PGE1 stimulation but rose in response to epinephrine, likely due to altered expression of genes for the receptors for each of these two hormones. This system of cultured human fibroblasts is useful in explaining various concomitants of biological aging including decreased tissue cellularity and impaired hormone and drug responsiveness.

Aging↗

Density distribution, characterization and comparative aspects of plasma lipoproteins in the salamander, Pleurodeles waltii.

Blood plasma from a Urodele amphibian, Pleurodeles waltii, has been found to contain very-low density, low-density and high-density lipoproteins (VLDL, LDL and HDL, respectively). HDL and LDL predominated (concentration range 72-114 and 51-101 mg/dl) with lesser quantities of VLDL (23-51 mg/dl). Following isolation by density gradient ultracentrifugation, the physicochemical properties (morphology, particle size, hydrated density, electrophoretic mobility, and chemical composition) of the three major classes resembled, but were not identical with, those of the corresponding fractions in normal human plasma. The protein moieties of VLDL and LDL consisted mainly of polypeptides of high molecular weight (Mr greater than 60,000), which in their solubility were akin to human apo-B; smaller amounts of another protein migrated to the position of human apo-C-III in basic polyacrylamide gels. The major HDL apolipoproteins were of Mr 31,000 and 27,000, with minor amounts of 13,000, 61,000 and 76,000 components; in alkaline, urea-containing polyacrylamide gels, these major proteins migrated faster than the major components (apo-AI and apo-AII) of human HDL. Immunochemically, lipoproteins with pre-beta-, beta- and alpha-mobility were detected in the VLDL, LDL and HDL, respectively. Salamander VLDL and LDL were found to share an antigenic site(s) with the LDL of trout, chicken and guinea-pig, suggesting the presence of an apo-B-like protein. The chemical compositions and immunochemical reactions of salamander lipoproteins indicate that their structure and metabolism resemble that of other amphibia, reptiles and fish rather more closely than that of most mammals and birds.

Animals↗

Comparison of radionuclide and enzymatic estimate of infarct size in patients with acute myocardial infarction.

A comparison was made of the estimated size of the myocardial infarction occurring in 26 patients with a first infarction using creatine kinase (CK) enzyme release between radionuclide gated blood pool measurement of total and regional ventricular function and thallium-201 scintigraphic measurement of myocardial perfusion defects. Creatine kinase estimates of infarct size (enzymatic infarct size) correlated closely with the percent of abnormal contracting regions, left ventricular ejection fraction and thallium-201 estimates of percent of abnormal perfusion area (r = 0.78, 0.69 and 0.74, respectively, p less than 0.01). A close correlation also existed between percent abnormal perfusion area and percent of abnormal contracting regions (r = 0.81, p less than 0.01) and left ventricular ejection fraction (r = 0.69, p less than 0.01). Enzymatic infarct size was larger in anterior (116 +/- 37 CK-g-Eq) than inferior (52 +/- 29 CK-g-Eq) myocardial infarction (p less than 0.01) and was associated with significantly more left ventricular functional impairment as determined by left ventricular ejection fraction (33 +/- 7 versus 60 +/- 10%) (p less than 0.01) and percent abnormal perfusion area (58 +/- 14 versus 13 +/- 12) (p less than 0.01). No significant correlation was observed between enzymatic infarct size and right ventricular ejection fraction. These different methods of estimating infarct size correlated closely with each other in these patients with a first uncomplicated myocardial infarction.

Adult↗

Local nasal immunotherapy for ragweed-allergic rhinitis. III. A second year of treatment.

In 1979, pre-seasonal local nasal immunotherapy (LNIT) was found to be an effective treatment for ragweed hay fever. In 1980, this study was continued to evaluate the clinical and immunologic responses of a second year of LNIT. Patients received either pre-seasonal treatment with an unmodified ragweed extract (RW) or a polymerized ragweed extract (PRW), or no treatment. The results of the second year of treatment were the same as the first year. Adverse reactions were significantly higher in the RW-treated group than in the PRW-treated group (P less than 0.001). Symptom/medication scores (SMS) in the RW-treated group were significantly lower than in the control group (P less than 0.005). Although SMS in the PRW-treated group were lower than in the control group, this difference was not significant. The immunologic response was evaluated by measurements of serum (S) RW-specific IgE and IgG and nasal secretory (NS) RW-specific IgE, IgG, and IgA. After treatment, serum IgE titres and secretory IgA titres rose in the RW-treated patients. Nasal secretory-IgG and NS-IgA titres increased with PRW treatment. The only immunologic response observed in the control group was a rise in S-IgE titres after the ragweed season. There was no substantial difference in immunologic measurements observed in the 1979 and 1980 seasons, except that the pre-treatment NS-IgE level was higher in 1980 (P less than 0.02). No significant correlations were found between antibody response and SMS. This study supports the efficacy of LNIT but does not support the protective role for NS-ragweed-specific IgA or IgG.

Adult↗

The Beta-Blocker Heart Attack Trial in perspective.

Recently completed Beta-Blocker Heart Attack Trial in which propranolol was administered to patients following an acute myocardial infarction resulted in a 26% decrease in total mortality and a 23% decrease in total coronary events in the propranolol-treated patients as compared to the placebo patients during the average follow-up of 25 months. In addition to the decrease in mortality and morbidity, the drug was well tolerated in the patients treated with the drug when compared to those who received placebo. In the patients who received propranolol, there was a decreased incidence of ventricular arrhythmias. These results, coupled with the results of other trials using beta-adrenergic blocking agents including sotalol and timolol, strongly supports the beneficial effect of the routine administration of these beta blocking agents in the postmyocardial infarction patients.

Adrenergic beta-Antagonists↗

Butyrate increases type-A and type-R virus-like particles in BKV-transformed hamster spleen cells.

A cell line derived from hamster spleen transformed by human papovavirus BK was adapted to grow in 5 mM butyrate. Ultrastructurally, the butyrate-adapted cells were found to contain large numbers of type-R and intracytoplasmic type-A virus-like particles (VLP). In contrast, the unadapted cells contained only rare VLP. Treatment of the unadapted cells with nontoxic and toxic concentrations of butyrate for 24 and 48 hr failed to induce VLP, indicating the importance of butyrate adaptation in the induction of VLP. The increase in type-R VLP was stable after removal of the adapted cells from butyrate; however, the increase in type-A VLP was not.

Animals↗

Propranolol therapy in patients with acute myocardial infarction: the Beta-Blocker Heart Attack Trial.

The Beta-Blocker Heart Attack Trial was a multicenter, randomized, double-blind, placebo-controlled trial of propranolol therapy in 3837 men and women with acute myocardial infarction. The patients began their treatment 5-21 days after hospital admission (mean 13.8 days). During an average follow-up of 25 months, there were statistically significant reductions in total mortality (26%), cardiovascular mortality (26%), arteriosclerotic heart disease (27%), sudden death (28%) and coronary incidence (definite nonfatal reinfarction plus coronary heart disease mortality) (23%). There was no group difference in incidence of congestive heart failure. Of the many potential side effects that were monitored, broncho-spasm, cold hands and feet, and fatigue occurred more frequently in the propranolol group. Propranolol not only reduced coronary mortality and morbidity, but also was administered with a great degree of safety. Based on these results, its use is recommended for at least 3 years in patients with no contraindications to beta blockade who have had a recent myocardial infarction.

Adult↗

Surgical results of anomalous left coronary artery.

After undergoing a ligation of the anomalous left coronary artery from the pulmonary artery and a saphenous vein bypass graft surgery, a 53-year-old woman has had improvement in exercise tolerance and congestive heart failure for up to two years of follow-up. Comparison of the preoperative and postoperative noninvasive studies disclose that surgery improved the left ventricular volume overload and perfusion. However, there was no change in the resting or exercise ejection fraction as assessed by stress multiple-gated acquisition isotope scan.

Coronary Vessel Anomalies↗

Interclonal variation in methylation patterns for expressed and non-expressed genes.

A mass culture of human diploid fibroblasts, and eight clones isolated from that mass culture, were examined for methylation patterns in several regions of DNA. Plasmid-inserted cDNA sequences were used as probes for alpha-hCG, beta-globin, A gamma- and G gamma-globin, and beta- and gamma-actin gene regions. Each probe revealed a different clone-specific pattern of DNA methylation, indicating a striking degree of inter-clonal heterogeneity, for those gene regions which are not normally expressed in diploid fibroblasts (alpha-hCG, gamma-globin and beta-globin). Intra-clonal variation was also evident in many instances, implying that heterogeneity could arise de novo in pure cell clones during serial passage. Thus methylation patterns, in particular for repressed genes, appear to be unstably inherited in these cells, and this instability may lead to random derepression in some cell lineages during mitotic growth.

Actins↗

Familial deficiency of apolipoproteins A-I and C-III and precocious coronary-artery disease.

We studied two sisters 29 and 31 years old who had skin and tendon xanthomas, corneal clouding, and severe coronary atherosclerosis. Histologic examination showed collections of lipid-laden histiocytes in the skin. The patients' plasma cholesterol concentrations were 177 and 135 mg per deciliter (4.58 and 3.49 mmol per liter). Levels of high-density-lipoprotein cholesterol were 4 and 7 mg per deciliter (0.1 and 0.2 mmol per liter). Only traces of apolipoprotein A-I were detected in whole plasma. The plasma density fraction from 1.06 to 1.21 g per milliliter contained no high-density lipoprotein on high-pressure liquid chromatography, no apolipoprotein A-I on sodium dodecyl sulfate electrophoresis, and only traces of apolipoprotein A-I on radioimmunoassay. Apolipoprotein C-III was also not detectable. The activity of lecithin-cholesterol acyltransferase was 40 per cent of normal. The half-life of infused normal high-density lipoprotein was three days (normal, 5.8 days). The parents and children of these two patients had low levels of high-density-lipoprotein cholesterol and apolipoprotein A-I. These cases support the hypothesis that low concentrations of high-density lipoprotein promote atherosclerosis.

Adult↗