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Biomedical subjects

S Goldstein

Publications and source records attributed to S Goldstein.

At least 451 records · Page 25Linked to original sources

Evaluation of atrioventricular septal defect by magnetic resonance imaging.

Electrocardiographically gated magnetic resonance imaging (MRI) was successfully performed in 9 patients with atrioventricular (AV) septal defect: 6 had complete AV canal and 3 had partial AV canal. The defect was readily visualized in all patients on transverse scans taken at the level of the AV valve. The size and extent of the defect could be easily determined. All patients demonstrated a similar underlying morphologic pattern on MRI scans, consisting of deficiency of the primum atrial septum and inlet ventricular septum and a "common" AV valve ring with absence of the cardiac crux. The 3 patients with isolated atrial septal defect could be distinguished from the 6 with complete AV canal by the dense, fibromuscular bridging tissue, which coursed from the AV valve to the crest of the ventricular septum, obliterating the interventricular communication. Four patients had angiographically proved ventricular hypoplasia, which was also detected by MRI. AV valves and their patterns of chordal attachment were accurately imaged in 7 patients on systolic sections; accessory chordae were identified in 6 patients. MRI is a useful noninvasive imaging modality that can depict the underlying morphologic abnormalities in AV septal defect as well as important anatomic variations.

Adolescent↗

Distichiasis, congenital heart defects and mixed peripheral vascular anomalies.

We report on a previously apparently unreported syndrome of distichiasis with congenital heart defects and with mixed peripheral vascular anomalies in a mother and her four children. The mother had a ventricular septal defect; both daughters had surgery for patent ductus arteriosus. Sinus bradycardia alone (elder son), with stress induced asystole (younger son), and with wandering atrial pacemaker (both daughters) are documented electrocardiographically. Three of the five have edema, two have visible varicosities, three have symptoms consistent with chronic venous disease of the legs, and the older daughter has complaints consistent with arterial disease in the legs. Doppler flow studies demonstrated post-phlebitic syndrome in all but the younger daughter, and vasospastic disease in the mother, older daughter, and second son.

Adolescent↗

Extrachromosomal circular DNA and aging cells.

A DNA sequence situated in the human genome between Alu-repeat clusters ("Inter-Alu" DNA) is progressively amplified in extrachromosomal DNA, including covalently closed DNA circles, during serial passage of diploid fibroblasts. A single size-class of Inter-Alu circles is also amplified in lymphocytes from 16 of 24 old donors and yet is not detected in cells from 18 young donors.

Cell Survival↗

Protein synthetic fidelity in aging human fibroblasts.

The fidelity of protein synthesis was measured in human diploid skin fibroblasts as a function of passage level ("aging in vitro") and physiological age of tissue donor ("aging in vivo") using two different test systems. First, in cell-free extracts the ratio of delta leu/delta phe incorporation into peptide linkage following in the latter case using cells derived from elderly normal donors and from subjects with the premature aging disorders of Hutchinson-Gilford progeria and the Werner syndrome. Similar results were obtained using a second system of intact cells whereby histidine starvation induces quantifiable satellite spots resolved by two dimensional electrophoresis on polyacrylamide gels on the acidic side of the native actin species due to substitution of the neutral amino acid glutamine for the basic histidine. In fact, error frequencies appeared to decrease during aging in vitro, likely due to selection for clonal subpopulations with the highest fidelity of protein synthesis. The only increases were seen in the intact cell system where SV40-transformed cells showed a three-to-five fold greater error frequency compared to nontransformed fibroblasts. In total, these data fail to support the error catastrophe theory of cellular aging.

Adult↗

The effect of bystander CPR on survival of out-of-hospital cardiac arrest victims.

The effect of bystander cardiopulmonary resuscitation (CPR) was studied in 2142 emergency medical service (EMS) cardiac arrest runs. When bystander CPR was administered to cardiac arrest victims, 22.9% of the victims survived until they were admitted to the hospital and 11.9% were discharged alive. In comparison, the statistics for cardiac arrest victims who did not receive bystander CPR were 14.6% and 4.7%, respectively (p less than 0.001). A critical factor in patient survival was the amount of time that elapsed before the EMS personnel arrived and administered CPR. Patients who received bystander CPR were more likely to have ventricular fibrillation when the EMS arrived. Other factors relating to patient survival were the location of the victim at the time of the cardiac arrest and the age of the victim. Understanding these factors is important in developing community strategies to treat patients with cardiac arrest out of hospital.

Adult↗

Chronic arthropathy in long-term hemodialysis.

Acute arthritis and periarthritis are known to develop in patients undergoing long-term hemodialysis; however, the long-term consequences of hemodialysis on joint structure and function have not been thoroughly evaluated in a cohort of patients. All patients (11) undergoing hemodialysis for 10 or more years were evaluated for symptoms, joint function, and radiographic abnormalities. Eight patients had joint symptoms, excluding those from a septic or traumatic process. Only four patients had acute episodes of arthritis. Nine patients had abnormalities on physical examination, including decreased range of motion, joint effusion, crepitance, or deformity. Nine patients had abnormal findings on radiography, including narrowing, erosions, and calcification. Those with more severe disease were younger and had been receiving dialysis treatments longer. It is concluded that prolonged hemodialysis is associated with a progressive deterioration of joint structure and function with or without acute episodes of synovitis.

Adult↗

Nutrition and somatomedin--XII. Fractionation of somatomedins and somatomedin inhibitors in normal and diabetic rats.

Bioassayable somatomedins and somatomedin inhibitors were examined after chromatographic separation, using serum from normal rats (enriched in somatomedins) and diabetic rats (enriched in somatomedin inhibitors). At neutral pH, gel filtration on Sephacryl S-300 revealed somatomedins at mol. wt approximately 140,000 (presumably carrier-bound) and inhibitors at mol. wts approximately 250,000, approximately 24,000 and approximately 1,000. At acid pH, gel filtration on Sephadex G-50 revealed somatomedins at mol. wt approximately 8,000 (presumably carrier-free) and a single inhibitor at mol. wt approximately 21,000. Ion exchange chromatography revealed that the inhibitor(s) may be more acidic than the somatomedins, but only low quantities of somatomedins were recovered. Sephadex G-50 fractionation was applied to pathophysiologic models in rats: 3 days of fasting were associated with a 62% fall in somatomedins and a 159% rise in inhibitors; 2 days of diabetes were associated with a 60% fall in somatomedins and a 344% rise in inhibitors. Since chromatography on Sephadex G-50 at pH 2.4 appears to provide adequate separation of somatomedins and somatomedin inhibitors with good estimated recovery of biological activity, this simple approach may be a probe useful in examining the regulation of somatomedins and somatomedin inhibitors in vivo.

Animals↗

Different pattern of association of beta-endorphin and cortisol responses to dextroamphetamine in postmenopausal women and young men.

A negative correlation between plasma beta-endorphin and cortisol responses to 0.15 mg/kg dextroamphetamine i.v. was found in a group of seven normal postmenopausal women, while the responses of the two hormones were positively correlated in nine normal young men. These results suggest that even though the adrenocorticotropic hormone (ACTH)-cortisol and beta-endorphin are usually regulated by the same mechanism (both ACTH and beta-endorphin are derived from proopiocortin), there are situations in which these systems can be associated in a different pattern. The elucidation of these situations may contribute to the understanding of regulatory mechanisms of the two systems.

Adult↗

Identification of specific binding sites for acetylated low density lipoprotein in microvillous membranes from human placenta.

The ability of microvillous membranes isolated from human placenta to specifically bind human low density lipoprotein (LDL) modified by acetic anhydride has been investigated. The presence of saturable high affinity binding sites specific for [125I]acetyl-LDL was demonstrated. Scatchard analysis of the binding data, obtained at 4 degrees C, revealed a single class of sites with a mean KD value of 3.63 +/- 1.16 micrograms acetyl-LDL protein/ml, and a maximal binding capacity of 335.1 +/- 148.8 ng acetyl-LDL protein/mg of membrane protein. At 37 degrees C, the binding capacity was increased, while the KD value was not modified. The specificity of these binding sites was assessed by competition studies: unlabelled acetyl-LDL were effective competitors, whereas native LDL, VLDL and HDL3 were ineffective. Conversely, unlabelled acetyl-LDL failed to prevent the binding of native [125I]LDL to placental microvilli. The [125I]acetyl-LDL binding was partially inhibited (about 35%) by dextran sulfate and fucoidin, and was abolished by a pretreatment of the microvillous membranes with pronase. The binding sites specific for acetyl-LDL are present during all the gestation and are distinctly different from the binding sites for native LDL, previously characterized in placental microvilli. These 2 types of binding sites may be related to the high amount of cholesterol required by the human placenta for progesterone synthesis and trophoblastic growth.

Acetylation↗

Mechanism and reaction products of the oxidation of Cu(I)-phenanthroline by H2O2.

We have suggested a possible reaction mechanism for the oxidation of the cuprous phenanthroline complex by H2O2 in the presence of formate and methanol. The cuprous phenanthroline complex was generated by pulse and gamma radiolysis. We measured the decay kinetics of this complex as well as the chain length of this reaction. Our observations indicate that in this reaction OH. is not formed directly, but through the decomposition of a metal-peroxo complex. This mechanism does not necessarily operate with other copper compounds, especially with copper complexes bound to a biological target.

Chemical Phenomena↗

Idiopathic degeneration of the aortic valve: a common cause of isolated aortic regurgitation.

To establish the etiology of isolated aortic valvular regurgitation, histologic examination was carried out on 27 consecutive surgically removed aortic valves from patients with aortic regurgitation. In 12 patients, the regurgitation was due to rheumatic or syphilitic valvular disease or a congenital bicuspid aortic valve. In the remaining 15, no etiology was apparent. In the latter group, seven aortic valves were identified by the surgeon as redundant and eight as thickened and retracted. Despite these gross differences, the histologic features of the 15 valves were similar and consisted of increased and disorganized elastic and collagen fibers, with variable quantities of acid mucopolysaccharide and calcium. Although small foci of myxomatous stroma were present, they did not differ substantially from those observed in age-matched competent aortic valves removed at necropsy, nor were they as extensive as described in reports of floppy aortic valves. Idiopathic degeneration was the most common cause of aortic regurgitation, occurring in more than half of the surgically treated patients. An underlying defect in the synthesis of collagen or elastic fibers, similar to that described in mitral valve prolapse, may be an important feature in aortic valve degeneration.

Adult↗

"Ischemia at a distance" during intermittent coronary artery occlusion: a coronary anatomic explanation.

The mechanism of electrocardiographic ST segment changes during acute coronary occlusion was evaluated in 28 consecutive patients with single vessel coronary artery disease undergoing coronary angioplasty. Patients were continuously monitored with a six lead electrocardiogram. Twenty-three patients showed ST changes in the primary zone of occlusion, and 13 of these had additional ST changes in a remote zone. Ten of these 13 had unusually extensive arteries supplying the remote zone. The balloon occluded two adjacent normal arteries in two patients, and no coronary anatomic explanation was evident in one patient. Ten patients with striking primary zone ST changes showed no remote change. Seven had nonextensive primary zone arteries, and three others had abundant collateral vessels. Five patients showed no electrocardiographic changes in primary or remote zones. Four had collateral vessels, and one had left ventricular hypertrophy on the baseline electrocardiogram. It was concluded that remote electrocardiographic changes are probably due to occlusion of unusually extensive coronary arteries and are not simply reciprocal.

Angioplasty, Balloon↗

Association of digitalis therapy with mortality in survivors of acute myocardial infarction: observations in the Beta-Blocker Heart Attack Trial.

The influence of digitalis therapy on survivors of acute myocardial infarction was examined in the placebo-treated patients from the Beta-Blocker Heart Attack Trial (BHAT). Two hundred fifty (13%) of the 1,921 placebo-treated patients were receiving digitalis at the time of randomization. Patients receiving digitalis differed from those not receiving digitalis in such baseline characteristics as age, prior history of heart failure, prior myocardial infarction and angina pectoris. They also experienced a higher proportion of in-hospital complications including pulmonary edema, persistent hypotension, atrial fibrillation and heart failure in addition to a greater prevalence of complex ventricular premature beats. The total mortality rate over a mean 25 month follow-up period for digitalis-treated patients was 20.4% compared with 8.2% for patients not receiving digitalis; the odds ratio was 2.87 (p less than 0.05). When the mortality rates were adjusted for heart failure and ventricular premature beat complexity, patients receiving digitalis again demonstrated a higher mortality rate, although the adjusted odds ratio was now lower (1.70). When the patients receiving or not receiving digitalis were compared by a multiple logistic regression analysis adjusting for 17 independent variables predictive of mortality, the use of digitalis was no longer independently predictive of total mortality (adjusted odds ratio 1.07). These data indicate that patients receiving digitalis had more extensive cardiovascular disease and greater morbidity than patients not receiving digitalis. Their subsequent higher mortality rate was probably related to these factors rather than to digitalis therapy.

Adult↗

The effect of renal function on enalapril kinetics.

Enalapril maleate (MK-421), a nonmercapto-containing angiotensin converting enzyme (ACE) inhibitor, is converted in vivo to enalaprilat (MK-422), the active diacid. We evaluated serum profiles and urinary excretion of oral enalapril maleate in patients with renal disease (group I, creatinine clearance less than 3 ml/min, patients undergoing dialysis, n = 10; group II, creatinine clearance 10 to 79 ml/min, n = 9) compared with healthy subjects (group III, creatinine clearance greater than 80 ml/min, n = 10). Group I received a 10 mg dose during a day while not receiving dialysis and a 10 mg dose 1 hour before dialysis 2 weeks later. Groups II and III received a single 10 mg dose. Blood samples and urine were collected for 48 hours. Impaired renal function resulted in elevated serum and plasma concentrations of enalapril maleate and decreased excretion rates and urinary recovery of enalapril maleate and enalaprilat. The data suggest an apparent increase in the extent of metabolism of enalapril maleate to enalaprilat or an increase in nonrenal elimination of unchanged enalapril maleate in renal disease compared with normal health. Enalaprilat was dialyzable.

Administration, Oral↗

Assessment of papillary muscle function in the intact heart.

A technique is described to localize the anterolateral papillary muscle and to assess its performance in vivo. Using this technique, we measured sequentially the pressure generated within the anterolateral papillary muscle and its changes in length during the cardiac cycle in eight open-chest anesthetized dogs. Pressure within the anterolateral papillary muscle was measured with a 1.6 mm diameter micromanometer probe. Its dimensional changes were measured with ultrasonic crystals. Pressure within the anterolateral papillary muscle exceeded left ventricular pressure throughout the entire cardiac cycle. A difference of 200 +/- 23 mm Hg was present between systolic pressure in the anterolateral papillary muscle and left ventricular systolic pressure (348 +/- 25 vs 149 +/- 6 mm Hg) (p less than .001). Shortening of the anterolateral papillary muscle began 25 +/- 2 msec after the upstroke of the aortic pressure, continued throughout isovolumic relaxation, and was maximal 68 +/- 5 msec after the apex of the aortic incisura. The extent and velocity of shortening of the anterolateral papillary muscle were maximal when pressure within the muscle was lowest. This temporal dissociation between pressure and dimensional changes of the anterolateral papillary muscle appeared to result from cyclic changes of loading imposed on the muscle.

Animals↗