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Biomedical subjects

R A Goldstein

Publications and source records attributed to R A Goldstein.

At least 109 records · Page 6Linked to original sources

A comparison of digoxin and dobutamine in patients with acute infarction and cardiac failure.

The hemodynamic effects of dobutamine were compared with those of digoxin in six patients with cardiac failure within 24 hours of onset of acute myocardial infarction. Dobutamine (8.5 microgram per kilogram of body weight per minute) was given intravenously for 30 minutes and then discontinued until hemodynamics returned toward base line. Digoxin (12.5 microgram per kilogram) was then given intravenously, and hemodynamics were recorded for 90 minutes. Dobutamine decreased left ventricular filling pressure (from 22.3 to 9.8 mm Hg, P < 0.02) and systemic vascular resistance (1686 +/- 188 to 1259 +/- 108 dynes . sec . cm-5), and increased cardiac index (from 2.4 to 3.2 liters per minute per square meter of body-surface area, P < 0.005) and stroke work index (from 24.6 to 36.6 g . m per square meter, P < 0.02), without changing heart rate or arterial pressure. In contrast, digoxin had no effect on filling pressure (18.3 versus 17.0) and only a slight effect on cardiac index (2.2 versus 2.4, P < 0.05) and stroke work index (21.9 versus 27.6, P < 0.05). Thus, dobutamine markedly increased cardiac output, decreased filling pressure, and relieved pulmonary congestion. Digoxin, did not affect preload or afterload.

Aged↗

Adult respiratory distress syndrome and gonococcemia.

A case of adult respiratory distress syndrome (ARDS) is described that was secondary to conococcal septicemia. The patient had severe hypoxemia and diffuse pulmonary infiltrates. The diagnosis of disseminated gonorrhea was confirmed by the isolation of Neisseria gonorrhoeae from one of several typical appearing skin lesions. The patient did not require mechanical ventilation and made a prompt recovery after a regimen of antibiotics was started. The association between ARDS and gonococcemia is extremely rare. It occurrence may be related to unusual properties of the gonococcal endotoxin or to the host response.

Adult↗

Relative effects of nitroglycerin and nitroprusside during experimental acute myocardial ischemia.

When given during acute myocardial infarction (AMI), vasodilators such as nitroglycerin (TNG) and nitroprusside (NP) improve some of the hemodynamic determinants of myocardial oxygen demand. TNG has been shown to reduce ischemic injury during AMI, but variable results have been noted with NP therapy. To compare the effects of these two agents, 8 closed chest sedated dogs with pre-existing multi-vessel coronary constrictions underwent repeated, random-order, acute 15-min balloon occlusions of the left anterior descending coronary artery during the following conditions: (1) saline infusion (control), (2) TNG infusion, and (3) NP infusion. The severity of myocardial ischemia was estimated by summating the ST-segment elevations (xi ST) measured from 7 intramyocardial electrodes; mean left atrial pressure (LAP), heart rate (HR), and mean systemic arterial pressure (SAP) were also measured. No dog had left ventricular failure either before or after occlusion. Since HR and SAP responses to TNG and NP are different, the dogs were randomized into two subgroups: TNG and NP were infused in 4 dogs to produce similar increases in HR (10--20% greater than control), and in the other 4 to produce similar decreases in SAP (15--20% less than control). In each subgroup, xi ST was significantly lower following TNG than following NP. Moreover, in the total group of 8 dogs, xi ST after 10 min of occlusion averaged 38 +/- 10 mV during TNG treatment compared to 46 +/- 10 mV during control occlusion (P less than 0.05). In contrast, xi ST after 10 min of occlusion averaged 57 +/- 11 mV during NP treatment (P less than 0.01 compared to control occlusion). Thus, (1) when given to achieve similar hemodynamic changes following acute coronary occlusion, TNG reduced while NP increased myocardial ischemia, (2) although both 'vasodilators', TNG and NP appear to have different actions on various vascular beds, and (3) the hemodynamic changes induced by vasodilators do not in themselves provide an accurate index of directional alterations in myocardial ischemia.

Animals↗

External assessment of myocardial metabolism with C-11 palmitate in vivo.

The externally detected rate of clearance of C-11 palmitate ([11C]palmitic acid) from isolated hearts varies directly with CO2 production from neutral lipids and with physiological indexes of myocardial oxygen consumption. The present study was performed to determine whether myocardial metabolism could be quantified noninvasively in vivo in a fashion analogous to that in the isolated heart. Opened chest, male rabbits were injected with C-11 palmitate (100-200 muCi) and coincidence counts were detected externally with two NaI(TI) crystals so placed that their colinear field of view encompassed the heart. The monoexponential rate of clearance of tracer--obtained from the portion of the residue-detection curve reflecting metabolism of fatty acid incorporated into neutral lipids--correlated directly with induced changes in tension-time index after injections into the left atrium (r = 0.96, n = 12), right atrium (r = 0.86, n = 14), and ear vein (r = 0.93, n = 14). Clearance of labeled palmitate from the vascular pool within the field of detection (determined with both C-14 palmitate and red blood cells labeled with C15O-hemoglobin) was rapid and did not significantly affect measurements of palmitate clearance from the heart itself.

Animals↗

Detection of myocardial ischemia before infarction, based on accumulation of labeled pyruvate.

To determine whether ischemic, but not irreversibly injured myocardium, can be differentiated from normal tissue based on accumulation of labeled pyruvate, isolated hearts were perfused with buffer containing [14C]pyruvate under conditions of normal or low flow. Fifteen minutes after the hearts were exposed to labeled material, myocardial radioactivity was fourfold greater in ischemic compared to control hearts, due to accumulation of label in sequestered lactate produced from the pyruvate. Open-chest rabbits subjected to coronary occlusion exhibited a 1.73:1 ratio of radioactivity in ischemic compared with normal myocardium 15 min after systemic injection of [14C]pyruvate. The results obtained suggest that zones of myocardial ischemia should be detectable in vivo by positron tomography after systemic administration of [11C]pyruvate as well.

Animals↗

Immunoregulation in infection caused by Mycobacterium tuberculosis: the presence of suppressor monocytes and the alteration of subpopulations of T lymphocytes.

This study was designed to characterize qualitative and quantitative alterations, occurring before and during chemotherapy, in the mononuclear cells of patients with infections caused by Mycobacterium tuberculosis. A hemolytic plaque-forming (PFC) assay indicated that the production of antibody to sheep red blood cells by pokeweed mitogen (PWM)-stimulated lymphocytes was suppressed in treated and untreated patients as compared with that in normal adult donors (P less than 0.001). The removal of adherent cells from the suspensions of mononuclear cells significantly enhanced the responses to the PFC assay for both the untreated (P less than 0.01) and treated (P less than 0.05) patients. Mononuclear cells from patients with tuberculosis, however, did not suppress the PFC responses of allogeneic normal mononuclear cells (P greater than 0.02). Thymus-derived (T) lymphocytes were proportionally reduced in untreated subjects (P less than 0.001) but returned to normal levels after four to six weeks of therapy (P greater than 0.2). Both groups of patients had a consistent reduction in the absolute number of circulating T cells. However, untreated patients had a relative increase in the percentage of TG cells (the subpopulation of T cells with receptors for the Fc portion of IgG) (P less than 0.001) and a concomitant decrease in TM cells (the subpopulation with Fc receptors for IgM) (P less than 0.05). These alterations in the subsets of T cells were reversed after four to six weeks of therapy.

Adult↗

External assessment of myocardial metabolism with [11C]palmitate in rabbit hearts.

To determine whether the rate of fatty acid utilization, reflecting myocardial oxygen consumption under steady-state conditions, can be assessed noninvasively, we assayed positron emission from [11C]palmitate (100 muCi) in isolated rabbit hearts and after intra-atrial injection in vivo. In 11 isolated hearts, clearance of 11C-radioactivity during a monoexponential portion of residue detection curves correlated with tension-time index (TTI)(r = 0.86) and peak dP/dt (r = 0.89). Among 9 hearts prelabeled with [14C]palmitate, 14CO2 production from neutral lipid stores correlated with TTI (r = 0.83). In vivo the decline of 11C-radioactivity was 1st order and constant when physiological conditions were maintained constant (slope of the semilog plot = 0.099 +/- 0.002 (SE) in counts/min) (n = 2 animals, 7 injections). Decline of activity changed predictably when oxygen requirements were increased by administration of methoxamine. Thus, residue detection of [11C]palmitate 1) permits external assessment of global myocardial metabolism in vitro, and 2) reflects effects of interventions that alter the rate of substrate utilization in vivo, and should, therefore, permit comparison of rates of regional myocardial metabolism in patients with detection of radioactivity by positron-emission transaxial tomography.

Animals↗

HLA-Bw15 and tuberculosis in a North American black population.

Peripheral blood lymphocytes from 60 black patients with Mycobacterium tuberculosis disease proved by culture and 100 healthy black persons were HLA phenotyped using a standard lymphocytotoxicity test. Statistical analysis of the results showed that only Bw15 antigen had a significantly increased frequency among patients with tuberculosis when they were compared to healthy persons. Furthermore, examination of disease manifestations among patients with tuberculosis demonstrated that patients with Bw15 had significantly more far-advanced pulmonary disease with cavitation than did patients without Bw15. These observations suggest that Bw15 may influence both susceptibility to tuberculosis and the course of the disease.

Adult↗

Surgical complications and results of modified Marshall-Marchetti-Krantz procedure for urinary incontinence.

At the Mayo Clinic from January 1960 through December 1975, 673 patients underwent a modification of the Marshall-Marchetti-Krantz operation as a primary or secondary procedure for recurrent stress incontinence. There were 96 patients (14%) lost to follow-up, and 28 patients have died; 549 patients have been followed for 2-16 years. Of the 549 patients, 227 underwent the procedure as a primary operative effort; 91% of these were cured or much improved from socially disabling stress urinary incontinence, 7% were unchanged, and 2% became worse. There were 322 patients who underwent surgery for persistent or recurrent stress incontinence. This group had had a total of 740 previous unsuccessful operations (an average of 2.3 per patient) specifically for stress incontinence; 90% of these patients were cured or much improved, 5.3% were unchanged, and 4.7% became worse. The Marshall-Marchetti-Krantz operation is an effective and safe procedure associated with minimal morbidity and no mortality.

Follow-Up Studies↗

Studies on the absorption of desmosine and isodesmosine.

Intestinal absorption of desmosine and isodesmosine was investigated in several animal species. Hamsters given desmosine injections intraperitoneally excreted 70% of the injected dose in the urine. When desmosines or elastin were given via gastric intubation, desmosines failed to appear in the urine, indicating a lack of desmosine absorption. Additional studies with everted hamster intestine in vitro showed that norleucine was actively transported from the mucosal to the serosal side but that desmosines and lysinonorleucine were not transported. Intestinal slice experiments with hamster, rabbit, and dog intestine indicated desmosines only in the extracellular space and not absorbed by the mucosal cells. These studies strongly suggest that desmosines are not absorbed via the gastrointestinal tract. The importance of this study rests with the conclusion that desmosines recovered in the urine must represent the degradation products of elastin destruction in the tissue. Newly synthesized elastin cannot interfre, since elastin precursor molecules do not contain desmosines. Thus quantitation of urinary desmosines may be of clinical value as a method of evaluating elastin catabolism.

Amino Acids↗

Cell-mediated immune responses in sarcoidosis.

In an attempt to understand divergent observations regarding the in vitro lymphocyte responsiveness to antigens and mitogens, the frequency of cutaneous reactivity, and the relationship of these variables to clinical features of sarcoidosis, we examined cell-mediated immune responses in 75 untreated patients. In vitro lymphocyte responses to phytohemagglutinin and concanavalin A were significantly decreased among the group of patients with chronic active disease. In vitro lymphocyte responses to streptococcal antigen paralleled the patient's cutaneous reactivity; however, when compared to healthy persons, patients with sarcoidosis responded significantly less often to streptococcal skin tests. Twelve of 13 persons expected to be tuberculin positive by clinical history were found to be dermally reactive, and 11 these 12 exhibited positive in vitro lymphocyte responses to purified protein derivative. Among the remaining 62 patients, failure to respond to all stimuli in vivo and in vitro occurred in only 10. No evidence was found to support the general view that sarcoidosis is characterized by anergy to specific antigens. The patterns of responses to mitogens were neither characteristic nor unique for sarcoidosis. In patients in whom diminished specific cellular immune reactivity was observed, no correlation was evident with specific clinical features of the disease.

Adult↗

Urinary excretion of elastin peptides containing desmosin after intratracheal injection of elastase in hamsters.

The intratracheal injection of pancreatic elastase results in an acute loss of elastin from the lungs of hamsters and the development of emphysema. We used measurements of the unique covalent cross linking amino acids of elastin, desmosine and isodesmosine, to quantitate elastin. Direct measurements on the lungs estimated an average loss of elastin of 57% after elastase injection. Elastin breakdown products were also quantitated in the urine and feces after injection. An average of 8.8 nmol of desmosines was recovered from the urine of each hamster. This amount represented the desmosines from 61% of the elastin lost from the lungs. Desmosine and isodesmosine existed in the urine in peptide fractions that ranged from 9 to 27,000 daltons with an average of 13,000. Only trace quantities of desmosines could be detected in feces. Desmosines injected intraperitoneally were completely recovered in the urine, and radioactive tracer studies failed to reveal in vivo catabolism of injected desmosines. These results suggest that measurement of urinary desmosines holds promise for the study of elastin turnover.

Animals↗

Accumulation of lysophosphoglycerides with arrhythmogenic properties in ischemic myocardium.

Lysophosphoglycerides, products of membrane phospholipid catabolism known to influence membrane function in several systems, appeared in the effluents of anoxic isolated rabbit hearts perfused at low flow and accumulated in perfused hearts and myocardium rendered ischemic in situ. Comparable concentrations of lysophosphoglycerides bound to albumin markedly and reversibly altered action potentials of isolated canine Purkinje fibers in vitro. Changes induced included diminution of the maximum diastolic potential, peak dV/dt of phase zero, amplitude, and action potential duration--alterations resembling those seen in ischemic myocardium in vivo. These electrophysiological alterations are compatible with changes implicated in predisposing to dysrhythmia dependent on reentry, a phenomenon potentiated by the presence of zones of decreased conduction. Thus, accumulation of lysophosphoglycerides induced by ischemia may contribute to the genesis of malignant dysrhythmia early after its onset.

Action Potentials↗

Strontium-87m lung scans in pulmonary aspergillosis.

Experimental observations have indicated that radioactive strontium localizes in lesions infected with Aspergillus species. Preliminary clinical studies have recommended use of strontium lung scanning to evaluate patients thought to have pulmonary manifestations of aspergillosis. In view of the difficulty in accurately interpreting the clinical significance of recovery of Aspergillus species from sputum of patients with pulmonary disorders as well as the varied clinical presentations of pulmonary aspergillosis, we have attempted to confirm these reports. Ten patients with proven pulmonary aspergillosis and five selected control subjects without aspergillosis but with other pulmonary disorders were scanned after the injection of 2-3 mCi 87mSr citrate. The strontium lung scan correlated with the chest radiograph in four of 10 patients with aspergillosis; false positive scans were found in three of five patients with other pulmonary disorders. We conclude that strontium lung scans at present have no role in the diagnostic evaluation of patients suspected of clinically significant infections with aspergillus.

Adult↗

Regional contractility. Selective depression of ischemic myocardium by verapamil.

The effects of verapamil (0.02-0.2 mg/kg) on contractility in normal and partially ischemic myocardium were compared with the changes following propranolol (0.01-1.0 mg/kg). Regional contractile function was studied in open-chest dogs with ultrasonic crystals and ischemia was controlled by graded occlusion of a carotid-to-coronary artery shunt. Reduction in shunt perfusion pressure (40-55 mm Hg) resulted in hypokinesia. Verapamil depressed contractility in ischemic myocardium in 5/5 dogs, but did not alter the maximum velocity of shortening (max V) or end-diastolic segment length in normal myocardium. Propranolol in doses sufficient to depress ischemic myocardium also depressed contractile function in normal myocardium. In two dogs without coronary occlusion, verapamil (up to 1.0 mg/kg) increased end-diastolic segment length but did not reduce max V. We conclude that verapamil selectively depresses ischemic myocardium, a finding that may have clinical implication since ischemic injury can be decreased by reducing contractility (and thereby MVO2).

Animals↗