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Biomedical subjects

R A Goldstein

Publications and source records attributed to R A Goldstein.

At least 73 records · Page 4Linked to original sources
PubMed1989

Economic analysis of clinical positron emission tomography of the heart with rubidium-82.

This report describes a cost analysis for clinical positron emission tomography (PET) of the heart using generator produced rubidium-82 (82Rb). Considered sequentially are the clinical problem, current noninvasive radionuclide methods, positron emission tomograph, and the cost of PET per study. Also analyzed are the costs of PET versus thallium imaging in the management of chest pain, for screening asymptomatic men at high risk for coronary artery disease and for evaluating myocardial viability after myocardial infarction or thrombolytic therapy. Noninvasive assessment of coronary artery stenosis and myocardial ischemia/viability in symptomatic or asymptomatic subjects remains a major medical problem because the sensitivity and specificity of thallium imaging are only 70-85% and 50-70%, respectively, in recent studies. Cardiac positron imaging has an accuracy for noninvasive diagnosis of coronary artery disease in symptomatic or asymptomatic patients with a sensitivity and specificity of 95-98%. It can also be used for assessing physiologic stenosis severity, for imaging myocardial infarction and viability, for assessing effects of interventions such as thrombolysis, percutaneous transluminal coronary angioplasty (PTCA) or bypass surgery on myocardial perfusion, metabolism or coronary flow reserve, for assessing collateral function noninvasively in man, and for diagnosing cardiomyopathy not due to coronary artery disease. Although the cost for cardiac PET with 82Rb may be modestly higher than for 201Tl, the greater diagnostic yield of PET results in comparable or lower overall medical management costs than no diagnostic tests/interventions and lower overall costs compared to thallium imaging for evaluating patients with chest pain, asymptomatic high risk males, and patients after acute myocardial infarction/thrombolysis for myocardial viability.

Adult↗
PubMed1987

Efficacy and safety of sustained (48 hour) intravenous infusions of milrinone in patients with severe congestive heart failure: a multicenter study.

Milrinone is a new bipyridine inotrope that has shown promise in initial clinical testing when administered intravenously or orally. The present multicenter study was designed to evaluate the clinical effectiveness and safety of sustained (48 hour) intravenous infusions of different doses of milrinone, as would be used clinically, in a controlled fashion using invasive hemodynamic monitoring. Entry was limited to adult patients with chronic heart failure of functional class III or IV, with a cardiac index less than or equal to 2.5 liters/min per m2 or a pulmonary capillary wedge pressure greater than or equal to 15 mm Hg, or both. After stable baseline hemodynamic recordings were obtained, milrinone was given as loading (microgram/kg per 10 min) and maintenance infusions (microgram/kg per min) to 189 patients in one of four loading/maintenance dosage regimens: 37.5/0.375 (low dose, n = 26), 50/0.50 (intermediate dose, n = 95), 75/0.75 (high dose, n = 15) and 50/0.25 (lowest dose, n = 53). The lowest dose was shown to be ineffective for maintenance therapy. Effective individual patient responses were defined as greater than or equal to 20% increase in cardiac index or decrease in pulmonary capillary wedge pressure, or both. During early therapy (less than or equal to 3 hour), 99% of patients showed an effective maximal response, and 90% an effective mean response. An effective mean response was observed during days 1 and 2 in 80% of patients, with a positive dose-response trend (69% response, low dose; 80%, intermediate dose; 93%, high dose; day 1). Each loading regimen was effective, with maximal mean response occurring at 15 minutes. Cardiac index initially increased by an average of 24 to 42% for all patients in the three groups, whereas pulmonary capillary wedge pressure decreased by 24 to 33%. Initial decreases in systemic vascular resistance averaged 15 to 31%. Initial changes in heart rate (+4 to +13%) and mean arterial pressure (-2 to -13%) were modest. Significant mean hemodynamic responses were maintained over the 48 hours. Increases in cardiac index for days 1 and 2 averaged 38 and 39% for those completing constant low dose drug, 34 and 37% for intermediate dose and 73 and 44% for high dose. Decreases in pulmonary capillary wedge pressure for all patients averaged 18 to 32% on days 1 and 2, with little dose response. Heart rate changes were modest and variable, averaging -9 to 9%.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1987

Relation between geometric dimensions of coronary artery stenoses and myocardial perfusion reserve in man.

To determine the relation between stenosis anatomy and perfusion in man, 31 patients had quantitative coronary arteriography and positron imaging (PET) with Rb-82 or N-13 ammonia at rest and after dipyridamole-handgrip stress. 10 patients were also studied after angioplasty (total stenoses = 41). Percent narrowing and absolute cross-sectional luminal area were related through a quadratic function to myocardial perfusion reserve determined with PET. Arteriographically determined coronary flow reserve was linearly related to relative myocardial perfusion reserve as expected, based on the derivation of equations for stenosis flow reserve. All of the correlations had considerable scatter, indicating that no single measurement derived by coronary arteriography was a good indicator of perfusion reserve by PET in individual patients. This study provides the relation between all anatomic dimensions of coronary artery stenoses and myocardial perfusion reserve in man, and suggests that PET indicates the functional significance of coronary artery stenoses for clinical purposes.

Arterial Occlusive Diseases↗
PubMed1987

Pharmacologic therapy for patients with congestive cardiomyopathy.

Treatment in congestive heart failure is directed at improving cardiac output and decreasing preload and afterload without significantly increasing the oxygen requirements of the heart. This paper reviews the current approach to heart failure with inotropic and vasodilator drugs in patients with heart failure.

Journal Article↗
PubMed1987

Changes in myocardial perfusion reserve after PTCA: noninvasive assessment with positron tomography.

The effect of percutaneous transluminal coronary angioplasty (PTCA) on myocardial perfusion reserve has not been previously determined. Accordingly, 11 patients underwent positron imaging with [13N]ammonia or 82Rb at rest and following dipyridamole + handgrip stress before and after PTCA. The ratio of stress to rest activity (S:R) was determined for each region of interest. Relative myocardial perfusion reserve by positron tomography (RMPR) was calculated by dividing S:R of the stenotic area by a corresponding value from a normal reference area of the same patient. Automated quantitative coronary arteriography was used to objectively measure the percent diameter (%D) and the percent area narrowing (%A) of the stenoses. In nine patients with successful PTCA, %D and %A improved (68 +/- 10 to 49 +/- 15% and 92 +/- 3 to 72 +/- 5%) and RMPR increased from 0.79 +/- 0.07 to 0.96 +/- 0.05. In the two patients in whom PTCA was unsuccessful, RMPR was unchanged. Changes in RMPR correlated inversely with changes in %D (r = -0.68) and %A (r = -0.92) and directly with improved coronary flow reserve derived from all stenosis measurements (r = 0.73, p less than 0.001 for each). This study suggests that dipyridamole + handgrip stress imaging with PET can be used to assess changes in myocardial perfusion reserve before and after PTCA with the potential for determining restenosis noninvasively.

Adult↗
PubMed1986

Electrophysiologic effects of milrinone in patients with congestive heart failure.

The electrophysiologic effects of milrinone, a new inotropic agent, have not been characterized in humans. Accordingly, 10 patients with class III or IV congestive heart failure underwent hemodynamic and electrophysiologic testing before and during an infusion of milrinone (0.5 micrograms/kg/min). Cardiac index increased from a mean of 1.65 +/- 0.51 to 2.19 +/- 0.68 liters/min/m2 (p less than 0.03) and pulmonary artery capillary pressure decreased from 30 +/- 9 to 22 +/- 9 mm Hg (p less than 0.01), without a significant change in systemic arterial pressure. Holter monitoring was performed for 48 hours at baseline and during infusion of milrinone. Frequency of ventricular premature complexes and ventricular couplets did not change significantly. Frequency of ventricular tachycardia (VT) increased significantly, although no patients would be classified as having a proarrhythmic effect based on a clinical model. PR, QRS, QTc, heart rate, AH, HV, atrial, atrioventricular and ventricular effective and functional refractory periods were not affected. Milrinone decreased 1:1 atrioventricular maximal conduction from 399 +/- 133 to 374 +/- 111 ms (p less than 0.01); ventriculoatrial conduction was not significantly affected. During programmed right ventricular stimulation, 5 patients had inducible VT at baseline (3 sustained, 2 non-sustained), whereas after drug administration, none had it (p less than 0.05). Thus, intravenous milrinone is an effective inotropic drug that also enhances atrioventricular conduction and may decrease the incidence of inducible VT in patients with congestive heart failure.

Adult↗
PubMed1986

Efforts by the United States to coordinate the prevention of occupational allergic diseases in the workplace.

The investigator who studies OADs must realize that results may impact social, ethical, and moral issues and create economic dilemmas. This is different from most research endeavors, which create warm appreciation for research findings. Finally, the researcher may be asked to support, defend, or deny a position that argues or extrapolates beyond the scientific findings--a situation that does not usually occur in "pure" research. Many investigators are poorly equipped to deal with these broader issues, and thus confusion and distrust occasionally result. Working on OAD requires enormous understanding from the interested parties. Task force recommendations that fail to consider nonmedical and nonscientific needs for industry and labor are not likely to be welcomed or implemented.

Humans↗
PubMed1986

Noninvasive assessment of coronary stenoses by myocardial perfusion imaging during pharmacologic coronary vasodilation. VIII. Clinical feasibility of positron cardiac imaging without a cyclotron using generator-produced rubidium-82.

The purpose of this study was to determine the clinical feasibility of diagnosing significant coronary artery disease by positron imaging of myocardial perfusion without a cyclotron, using generator-produced rubidium-82 (82Rb). Fifty patients underwent positron emission tomography of the entire heart using a multislice positron camera and intravenous 82Rb or nitrogen-13 ammonia (13NH3) before and after intravenous dipyridamole combined with handgrip stress. Images were read by two observers blinded as to clinical or arteriographic data. Automated quantitative coronary arteriography was obtained for the arteriographic determination of coronary flow reserve, previously demonstrated to be a single integrated measure of stenosis severity accounting for all its geometric dimensions of length, absolute diameter, percent narrowing and asymmetry by quantitative analysis of cine films. Significant coronary artery disease was defined as an arteriographically determined coronary flow reserve of less than 3.0 based on all stenosis dimensions. Any single geometric measure of stenosis severity alone was an inadequate reference standard for comparison with perfusion images. Sensitivity of identifying patients with coronary artery disease having an arteriographically determined coronary flow reserve of less than 3.0 was 95% by positron imaging with a specificity of 100%. The single case that was missed, studied with 13NH3, had a 43% diameter narrowing of a small ramus intermedius off the left coronary artery with no significant narrowing of the major coronary arteries. Positron emission tomography of myocardial perfusion before and after intravenous dipyridamole combined with handgrip stress utilizing generator-produced 82Rb provides sensitive and specific diagnosis of reduced coronary flow reserve due to coronary artery disease in humans.

Coronary Angiography↗
PubMed1986

Positron imaging of myocardial infarction with rubidium-82.

Positron imaging provides tomographic images of regional myocardial perfusion but has required an on-site cyclotron. Rubidium-82 (82Rb) is a short-lived (T1/2 = 75 sec) positron emitter available from a generator. In order to determine the feasibility for its use to image acute myocardial infarction, 18 patients with transmural infarctions who had coronary arteriography were given 30-40 mCi of 82Rb intravenously and positron tomographic imaging was carried out within 96 hr after onset of symptoms. Nine simultaneous transaxial slices were obtained for each patient with a positron camera. Images were also reconstructed in a long-axis, short-axis, and three-dimensional display. One study could not be interpreted because of excessive lung activity. Fourteen normals were also studied. The infarct related artery determined by angiography was correctly diagnosed by positron imaging in all 17 patients as were all three prior infarcts by readers blinded to the clinical data. No defects were observed in normals or in noninfarcted myocardial regions. This study indicates that 82Rb should be useful for perfusion imaging in patients with acute myocardial infarction. The short half-life of 82Rb should make it ideal for providing serial assessment of perfusion in patients undergoing thrombolytic therapy.

Acute Disease↗
PubMed1986

Clinical effects of intravenous amrinone in patients with congestive heart failure.

Hemodynamic effects of intravenous administration of amrinone include increases in dP/dt, cardiac output, and stroke work with decreases in left ventricular filling pressure and systemic vascular resistance. Unlike other injectable positive inotropic agents, it does not increase myocardial oxygen consumption, a distinct advantage in patients with coexisting ischemic disease. Amrinone does not have deleterious effects on atrioventricular conduction and appears to have little arrhythmogenic potential. Side effects of intravenous administration are generally minor but include a reversible thrombocytopenia. Additional studies conducted in short-term low-output states are needed to define more completely its role in the treatment of this condition.

Aminopyridines↗
PubMed1986

Rubidium-82 kinetics after coronary occlusion: temporal relation of net myocardial accumulation and viability in open-chested dogs.

Serial assessment of perfusion and viability during myocardial infarction has not been feasible, in part, because of the long half-lives of available tracers. Rubidium-82 (82Rb) is a generator-produced, positron-emitting potassium analog with a short half-life (75 sec) that permits repeated studies. To determine the temporal relation of net myocardial 82Rb accumulation to loss of viability during prolonged ischemia, a 2-3 mCi bolus of 82Rb was given to 46 open-chested dogs while regional myocardial time-activity curves were obtained with beta probes at baseline, and serially after coronary occlusion lasting 1-6 hr. Hearts were then stained with triphenyl tetrazolium chloride (TTC) to assess the viability of the epicardium under the probe to a depth corresponding to the range of positrons. Irreversible injury occurred in two out of 16 experiments at 1 hr and ten out of 15 experiments at 3 hr and also at 6 hr (p less than 0.05 vs. 1 hr). In viable myocardial samples, rubidium extraction increased with low flow as compared with nonischemic controls for all time periods but was unchanged (failed to increase) in nonviable tissue. Net 82Rb accumulation decreased during 1 to 6 hr of occlusion in irreversibly injured samples (0.28 +/- 0.19 to 0.16 +/- 0.07, p less than 0.05) but remained unchanged in myocardial tissue subsequently shown to be viable. For myocardial samples that were nonviable at 3 and 6 hr, changes in net accumulation of tracer became abnormal only after 6 hr of occlusion. The mechanisms primarily responsible for the decrease in net accumulation of 82Rb at 6 hr appeared to be leakage of tracer after first pass. Therefore, failure to increase extraction at low flows may be an early indicator of cell death, whereas membrane leakage occurs several hours after loss of viability.

Animals↗
PubMed1985

Pulmonary hypertension. A common but often overlooked condition.

Pulmonary hypertension accompanies many primary disorders and produces common symptoms. However, measurement of pulmonary blood pressure is not routine, and as a result, symptoms are often overlooked. Pulmonary hypertension may lead to cor pulmonale, which has an unfavorable prognosis. Drug treatment for pulmonary hypertension and cor pulmonale may improve prognosis and prolong life. In cases of irreversible primary disease, therapy is palliative. Vasodilator therapy appears to benefit certain patients with primary pulmonary hypertension.

Constriction, Pathologic↗
PubMed1985

Electrophysiologic effects of amrinone.

Patients with congestive heart failure (CHF) have a high prevalence of complex ventricular arrhythmias. Accordingly, the electrophysiologic effects of new drugs for the treatment of CHF should be studied to determine whether they are safe in this population of patients. Fifteen patients with New York Heart Association functional classes II to IV CHF underwent hemodynamic and electrophysiologic testing during control conditions, and after 10 to 20 micrograms/kg/min of intravenous amrinone (dosages that increased cardiac output and decreased left ventricular filling pressures). All cardioactive drugs were stopped for at least 5 half-lives before entry into the study. Amrinone decreased the atrial effective refractory period from 256 to 240 ms (p = 0.015) and the AV nodal functional refractory period from 374 to 356 ms (p less than 0.05), and enhanced maximal 1:1 AV nodal conduction from 371 to 334 ms (p = 0.006). Prolonged HV intervals were present in 9 of 15 patients and were not affected by amrinone. Holter monitoring was performed in 10 patients during acute oral administration of amrinone. There were no significant changes in the frequency of ventricular extrasystoles or ventricular tachycardia, although the frequency of ventricular couples tended to increase slightly. Amrinone therefore enhances AV conduction and does not appear to have significant arrhythmogenic potential during acute administration.

Adult↗
PubMed1985

Effect of magnetic fields on the triplet state lifetime in photosynthetic reaction centers: Evidence for thermal repopulation of the initial radical pair.

The lifetime of the molecular triplet state formed by recombination of the radical ion pair in quinonedepleted bacterial photosynthetic reaction centers is found to depend on applied magnetic field strength. It is suggested that this magnetic field effect results from thermally activated repopulation of the same radical ion pair that generates the triplet. Consistent with this hypothesis, the magnetic field effect on the triplet lifetime disappears at low temperature where the triplet state decays exclusively by ordinary intersystem crossing. This activated pathway for the decay of the triplet state can explain the strong temperature dependence of the triplet decay rate. A detailed theoretical treatment of the problem within a set of physically reasonable assumptions relates the observed temperature dependence of the triplet decay rate to the energy gap between the radical ion pair intermediate and the triplet state. This energy gap is estimated to be about 950 cm(-1) (0.12 eV). Combined with an estimate of the energy of the donor excited state, we obtain an energy gap between the excited singlet state of the donor and the radical ion pair of 2,250 cm(-1) (0.28 eV).

Journal Article↗
PubMed1985

Special presentation: self-management of asthma programs in the USA.

In the USA during the past 5 years, there has been a renaissance of scientific interest and research into health education and programs of self-management. It has not, however, always been possible to translate gains in healthy individuals into similar progress for persons with chronic illness. Among chronic disorders affecting children, asthma ranks as a prominent cause of morbidity and school absenteeism. To accomplish this, NIH and NIAID has supported a variety of asthma self-management programs aimed at enhancing knowledge of disease among patients and parents. A further goal has been to translate this knowledge to changes in behavior in order to reduce morbidity of disease. The most successful programs have been conducted by non-physician health care professionals (nurses, social workers, teachers). The least successful programs have included mass distribution of printed materials by pharmaceutical companies and lay organizations. It is believed that broader application of such programs will help not only the patient but the physician improve the care of asthmatic individuals.

Asthma↗