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Geochemistry of water in relation to cardiovascular disease

Description: Relations between trace and major element chemistry of drinking water and cardiovascular diseases are reviewed and documented. Several aspects of the problem, related both to the pathway that drinking water takes to man and to its transit through man, are reviewed. Several steps in the pathogenesis of cardiovascular disease that could be affected by water factors were explored. There is little evidence bearing on the contribution from drinking water to human tissue levels of cadmium, chromium, or zinc. Copper and magnesium levels of tissues may be related to drinking water, but confirmatory evidence is needed. Lead levels in blood and other tissues are most certainly affected by lead levels in drinking water in areas where these levels are unusually elevated. There is little evidence that relatively low levels of lead are toxic to the cardiovascular system, except for the causation of cardiomyopathy. The protective action of selenium and zinc applies mainly to cadmium toxicity. The mode of the protective action of silicon, if any, is unclear at present. Some epidemiological associations between the cadmium level or cadmium:zinc ratio and cardiovascular disease have been reported, but are contradictory. Some epidemiological support exists for a protective effect by selenium; results for zinc are equivocal. Interactions within the human system involving calcium and selected trace elements might be very important for the cardiovascular system. Review of the epidemiological literature indicates that there may be a water factor associated with cardiovascular disease. Its effects, if any, must be very weak in comparison with the effects of known risk factors. The reported inverse relationship between mortality from cardiovascular diseases and hardness of local drinking water supplies appears to be considerably less distinctive in small regional studies. (ERB)
Date: January 1, 1979
Partner: UNT Libraries Government Documents Department

The development of iodine-123-methyl-branched fatty acids and their applications in nuclear cardiology

Description: Continued Interest in the use of iodine-1 23-labeled fatty acids for myocardial Imaging results from observations from a variety of studies that in many types of cardiac disease, regional fatty acid myocardial uptake patterns are often different than regional distribution of flow tracers. These differences may reflect alterations in important parameters of metabolism which can be useful for patient management or therapeutic strategy decision making. In addition, use of iodine-I 23-labeled fatty acid distribution may represent a unique metabolic probe to relate some aspects of the metabolism of these substrates with the regional viability of cardiac tissue. The use of such viability markers could provide important prognostic information on myocardial salvage, helping to identify patients for revascularization or angioplasty. Clinical studies are currently in progress with the iodine-123-labeled 1 5-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) fatty acid analogue at several institutions. The goals of this paper are to discuss development of the concept of metabolic trapping of fatty acids, to briefly review development and evaluation of various radioiodinated methyl-branched fatty acids and to discuss recent patient studies with iodine-123 (BMIPP) using single photon emission computerized tomography (SPECT).
Date: January 1, 1993
Creator: Knapp, F.F. Jr.; Ambrose, K.R. (Oak Ridge National Lab., TN (United States)); Kropp, J.; Biersack, H.J. (Bonn Univ. (Germany). Inst. fuer Klinische und Experimentelle Nuklearmedizin); Goodman, M.M. (University of Tennessee Medical Center, Knoxville, TN (United States). Dept. of Radiology); Franken, P. (Free Univ. Hospital, Brussels (Belgium). Nuclear Medicine Dept.) et al.
Partner: UNT Libraries Government Documents Department

Genetic influence on brain catecholamines: high brain norepinephrine in salt-sensitive rats

Description: Rats genetically sensitive to salt-induced hypertension evinced higher levels of plasma norepinephrine and epinephrine than rats genetically resistant to hypertension. The hypertension-sensitive rats showed higher hypothalamic norepinephrine and lower epinephrine than resistant rats. In response to a high salt diet, brain stem norepinephrine increased in sensitive rats while resistant rats exhibited a decrease on the same diet.
Date: January 1, 1980
Creator: Iwai, J; Friedman, R & Tassinari, L
Partner: UNT Libraries Government Documents Department

Myocardial uptake of cocaine and effects of cocaine on myocardial substrate utilization and perfusion in hypertensive rats

Description: Cocaine abuse is a problem causing world-wide concern and the number of deaths following cocaine use is increasing. Cardiovascular complications following cocaine include severe tachyarrythmias, pulmonary edema, myocardial infarction, and acute renal failure, which are major problems confronting emergency facilities. While the studies of cocaine effects on the brain have been given the most attention, it is clear that the effects of cocaine on the cardiovascular system are of great importance, given the increasing number of reports on sudden death and myocardial infarctions in young adults related to cocaine use. The precise mechanisms of cardiotoxic actions of cocaine are unclear. We investigated the whole-body distribution of C-14-labeled cocaine to determine the cocaine-binding sites, including blocking experiments to determine the nature of regional binding sites, and differential response of the normal vs. diseased heart (hypertensive cardiomyopathy) in an animal model to mimic a potentially high risk population. We investigated the acute effects of cocaine on myocardial metabolism using two myocardial energy substrate analogs, fatty acid and glucose with comparison with regional perfusion.
Date: January 1, 1992
Creator: Som, P.; Wang, G.J. (Brookhaven National Lab., Upton, NY (United States)); Oster, Z.H. (State Univ. of New York, Stony Brook, NY (United States)); Knapp, F.F. Jr. (Oak Ridge National Lab., TN (United States)); Yonekura, Y. (Kyoto Univ. (Japan). Faculty of Medicine); Fujibayashi, Y. (Kyoto Univ. (Japan). Hospital) et al.
Partner: UNT Libraries Government Documents Department

(Non-invasive evaluation of the cardiac autonomic nervous system by PET)

Description: The proposed research addresses the development, validation and application of cardiac PET imaging techniques to characterize the autonomic nervous system of the heart. PET technology has significantly matured over the last two decades. Instrument design, image processing and production of radiochemical compounds have formed an integrative approach to provide a powerful and novel imaging modality for the quantitative in vivo evaluation of the autonomic nervous system of the heart. Animal studies using novel tracers for the sympathetic and parasympathetic nerve terminals will be employed to characterize the functional integrity of nerve terminals. This work will be complemented by the development of agents which bind to postsynaptic receptor sites. The combined evaluation of presynaptic and postsynaptic neuronal function will allow a unique characterization of neuronal function. Initial development in animal studies will be followed by feasibility studies in humans. These studies are designed to test sophisticated imaging protocols in the human heart and validate the scintigraphic findings with independent markers of autonomic innervation. Subsequent clinical application in various cardiac diseases is expected to provide new insights into the neuropathophysiology of the heart.
Date: January 1, 1992
Partner: UNT Libraries Government Documents Department

Genetic influence on hypertension induced by cadmium in Dahl hypertension-resistant and hypertension-sensitive rats

Description: Dahl hypertension-resistant (R) and hypertension-sensitive (S) rats, with opposite genetically controlled propensities for hypertension, were used to determine if cadmium-induced hypertension was also dependent upon genetic predisposition. When intraperitoneal injections of cadmium (1 and 2 mg/kg) were given to male and female R and S rats maintained under ordinary laboratory conditions, female S rats manifested a significant increase in blood pressure which persisted for 16 weeks, whereas the R rats and the male S rats showed no significant changes in blood pressure. Cadmium had no effect on body weight. The concentrations of cadmium in hepatic and renal tissues of cadmium-injected male and female S rats were significantly higher than that of R rats. The kidneys of female S rats given cadmium showed renal vascular changes in accord with renal hypertension of moderate degree. We concluded that differences in genetic substrate influence the pathogenesis of experimental cadmium-induced hypertension.
Date: January 1, 1976
Creator: Ohanian, E V; Dahl, L K & Iwai, J
Partner: UNT Libraries Government Documents Department

Relation of air pollution to mortality: a critique. [SO/sub 2/ in New York City air]

Description: A study of the relation between SO/sub 2/ and smoke-shade in the surface air of New York City and deaths resulting from respiratory and heart diseases is discussed. The need to use data from a number of sampling stations in any epidemiological study on the health effects of air pollutants is stressed. It is pointed out that the complicated effects of weather on the environmental transport of air pollutants and the variations in statistical methods used may lead to eronious conclusions as to the cause of deaths.
Date: December 1, 1977
Creator: Goldstein, I F; Goldstein, M & Landovitz, L
Partner: UNT Libraries Government Documents Department

Biology and Medicine Division: Annual report 1986

Description: The Biology and Medicine Division continues to make important contributions in scientific areas in which it has a long-established leadership role. For 50 years the Division has pioneered in the application of radioisotopes and charged particles to biology and medicine. There is a growing emphasis on cellular and molecular applications in the work of all the Division's research groups. The powerful tools of genetic engineering, the use of recombinant products, the analytical application of DNA probes, and the use of restriction fragment length polymorphic DNA are described and proposed for increasing use in the future.
Date: April 1, 1987
Partner: UNT Libraries Government Documents Department

What has happened to the survivors of the early Los Alamos nuclear accidents

Description: Two nuclear accidents involving a plutonium sphere just subcritical in size occurred at the Los Alamos Laboratory, LA-1 in 1945 and LA-2 in 1946. Because remote control devices were deemed unreliable at the time, the tamper material (tungsten carbide bricks in LA-1 and beryllium hemispheres in LA-2) was added by hand with the operator standing next to the assembly. In each case the critical size of the assembly was accidentally exceeded and the resultant exponentially increasing chain reaction emitted a burst of neutrons and gamma rays. Ten persons were exposed to the radiation bursts which were largely composed of neutrons. The doses ranged from fatal in the case of the two operators, to small in the case of some survivors. The two operators died within weeks as a result of acute radiation injury. Only six of the eight survivors were available for follow-up study ten or more years after the accident. Four of these six survivors are now dead, but the two living survivors are in excellent health with no clinical or laboratory evidence of late radiation injury. Two of the deceased died of acute myelogenous leukemia, another died at age 83 of refractory anemia, and the fourth of myocardial infarction. The heart attack could have been precipitated by the myxedema assumed to have been the result of the radiation exposure.
Date: January 1, 1979
Creator: Hempelman, L.H.; Lushbaugh, C.C. & Voelz, G.L.
Partner: UNT Libraries Government Documents Department

Positron emission tomographic imaging of tumors using monoclonal antibodies

Description: This research project is developing methods for utilizing positron emission tomography (PET) to increase the clinical potential of radiolabeled monoclonal antibodies (MAbs). This report describes the development of methods for labeling MAbs and their fragments with positron-emitting halogen nuclides, fluorine-18 and iodine-124. These nulides were selected because of the widespread availability of F-18 and because of our extensive experience in the development of new protein radiohalogenation methods.
Date: August 1, 1992
Creator: Zalutsky, M.R.
Partner: UNT Libraries Government Documents Department

(Radioiodinated free fatty acids)

Description: The traveler participated in the Second International Workshop on Radioiodinated Free Fatty Acids in Amsterdam, The Netherlands where he presented an invited paper describing the pioneering work at the Oak Ridge National Laboratory (ORNL) involving the design, development and testing of new radioiodinated methyl-branched fatty acids for evaluation of heart disease. He also chaired a technical session on the testing of new agents in various in vitro and in vivo systems. He also visited the Institute for Clinical and Experimental Nuclear Medicine in Bonn, West Germany, to review, discuss, plan and coordinate collaborative investigations with that institution. In addition, he visited the Cyclotron Research Center in Liege, Belgium, to discuss continuing collaborative studies with the Osmium-191/Iridium-191m radionuclide generator system, and to complete manuscripts and plan future studies.
Date: December 11, 1987
Creator: Knapp, Jr., F. F.
Partner: UNT Libraries Government Documents Department

Regional myocardial blood flow, metabolism and function assessed noninvasively by positron emission tomography

Description: Positron emission computed tomography is a new technique for the noninvasive measure of myocardial blood flow, mechanical function and, in particular, metabolism. The capability of this new study means is due to the technological innovations of the imaging device and the availability of radioactive tracers that are specific for blood flow and metabolism. The device permits recording of cross-sectional images of the left ventricular myocardium that reflect quantitatively regional tracer tissue concentrations. By employing tracer kinetic models this new technique permits the measurement of regional glucose and fatty acid metabolism of the heart. While already an important new tool for investigative studies into cardiac physiology and pathophysiology, the clinical utility of positron emission tomography remains to be defined.
Date: January 1, 1979
Creator: Schelbert, H.R.; Phelps, M.E.; Hoffman, E.; Huang, S. & Kuhl, D.E.
Partner: UNT Libraries Government Documents Department

Noninvasive measurement of regional myocardial glucose metabolism by positron emission computed tomography. [Dogs]

Description: While the results of regional myocardial glucose metabolism measurements using positron emission computed tomography (/sup 13/N-ammonia) are promising, their utility and value remains to be determined in man. If this technique can be applied to patients with acute myocardial ischemia or infarction it may permit delineation of regional myocardial segments with altered, yet still active metabolism. Further, it may become possible to evaluate the effects of interventions designed to salvage reversibly injured myocardium by this technique.
Date: June 1, 1980
Creator: Schelbert, H.R. & Phelps, M.E.
Partner: UNT Libraries Government Documents Department

Labeling cellular elements of blood with Technetium-99m

Description: The purpose of this proposal is to develop new technique of labeling platelets and white cells with Tc-99m radionuclide. The conditions of labeling canine platelets and white cells with the lipid-soluble Tc-99m HMPAO have been optimized. The function of labeled platelets were evaluated by the determination of platelet survival time and recovery and these values were compared with that of In-111 tropolone labeled platelets. We developed the bilateral femoral catheterization model for the evaluation of platelet-thrombosis on control and heparin-bonded catheters in dogs. We are evaluating platelet thrombosis in the hollow-fiber hemodialyzer with Tc-99m and In-111 labeled platelets. We have developed the flow-loop for in vitro studies and are using a pig model for quantitation of platelet-consumption during hemodialysis. We are currently evaluating the new technique of platelet and white cell-labeling with Tc-99m and testing them in animal models of thrombosis and infection (osteo-myelitis). We are also using the Tc-99m HMPAO labeled mixed white cells in the early diagnosis (3-hour post-injection) of acute and chronic infection in patients and comparing the results with that of IN-111 oxine labeled white cells.
Date: August 1, 1990
Creator: Dewanjee, M.K.
Partner: UNT Libraries Government Documents Department

Interactive radiopharmaceutical facility between Yale Medical Center and Brookhaven National Laboratory. Progress report, November 1, 1980-October 31, 1981

Description: Research conducted in three principal areas is discussed and summarized. (1) Investigation of the influence of antiarrhythmic agents, such as lidocaine and procainamide, on the chemotaxis and nylon fiber adherence of indium-111-labelled human polymorphonulcear leukocytes (PMNs) in vitro revealed that at normal therapeutic levels of lidocaine and procaine, the adherence and chemotactic function of In-111-PMNs remain unaltered. Results with higher therapeutic blood levels are also discussed. (2) An improved method for labeling human platelets with In-111-oxine is outlined, and the influence of centrifugal force, oxine, ethanol, and radiation on platelet function is reported. Results indicate that normal labeling procedures induce no gross changes in platelet function. (3) The chemical preparation of radioiodinated arachidonic acid (AA) and nonradioactive acid ester of AA, and the analysis of metabolites of these compounds following myocardial ischemia were investigated in dogs. The tissue uptake of /sup 131/I-AA was compared to that of thallium-201.
Date: unknown
Creator: Gottschalk, A.
Partner: UNT Libraries Government Documents Department

Nuclear medicine technology. Progress report, quarter ending March 31, 1980

Description: The successful detection of experimentally produced myocardial infarctions in rats and dogs using /sup 123m/Te-9-telluraheptadecanoic acid (9-(/sup 123m/Te)-THDA) is described. Preferential localization of radioactivity in normal myocardial tissue of rats that had experimentally produced infarctions was also demonstrated by tissue distribution studies following injection of 9-(/sup 123m/Te)-THDA. The effects of chain length on the myocardial uptake of /sup 75/Se-labeled long-chain fatty acids was also studied further. Selenium-75-labeled 13-selenaheneicosonic acid (H/sub 3/C-(CH/sub 2/)/sub 7/-/sup 75/Se-(CH/sub 2/)/sub 11/-COOH, 13-(/sup 75/Se)-SHCA) shows the highest heart uptake in rats of the agents studied. These results indicate that myocardial imaging may be possible with 13-(/sup 75/Se)-SHCA and also suggest that potential positron emission tomography of the myocardium with the /sup 73/Se-labeled agent should be explored. The results of continuing studies with /sup 11/C and /sup 195m/Pt-labeled agents are also described. A variety of /sup 11/C-labeled amino acids were prepared and tested as pancreas and tumor localizing agents in a Medical Cooperative Program with the Oak Ridge Associated Universities. The microscale synthesis of /sup 195m/Pt-labeled cis-dichloro-trans-dihydroxy-bis-(isopropylamine)platinum(IV) (/sup 195m/Pt-CHIP) was developed further and preliminary tissue distribution studies with this important second-generation antitumor drug were completed in rats. Platinum-195m-labeled cis-dichlorodiammineplatinum(II) (/sup 195m/Pt-cis-DDP) was supplied for testing to a number of Medical Cooperative Programs. Studies of arsenic trioxide (As/sub 2/O/sub 3/) toxicity for human cells in the diffusion chamber assay system have continued. Further investigation of this arsenic-induced cytotoxicity has demonstrated a linear dose-response relationship and a difference in the permanence of the growth inhibitory effect using different doses.
Date: October 1, 1980
Creator: Knapp, F.F. Jr.
Partner: UNT Libraries Government Documents Department