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PubMed1984

Studies on the mechanisms of thallium-mediated inhibition of hepatic mixed function oxidase activity. Correlation with inhibition of NADPH-cytochrome c (P-450) reductase.

Thallium (TlCl3) administration to rats produced a dose-dependent loss of hepatic NADPH-cytochrome c (P-450) reductase and microsomal mixed function oxidase activities within 2-4 hr following treatment. These changes occurred independently of apparent effects on microsomal heme or cytochrome P-450 content, both of which remained unchanged with respect to control levels despite transient inhibition of delta-aminolevulinic acid (ALA) synthetase and induction of heme oxygenase. These results are consistent with the recognized properties of thallium as both a flavoprotein antagonist and sulfhydryl inhibitor and differ uniquely from the action of other metals which impair mixed function oxidase activity through compromise of heme biosynthesis and heme depletion. The potential utility of thallium compounds in further evaluating the functional characteristics of NADPH-cytochrome c (P-450) reductase and its role in microsomal oxidative processes is suggested from these observations.

5-Aminolevulinate Synthetase↗
PubMed1991

Effectiveness of palladium matrix modification for the determination of thallium by graphite furnace atomic absorption spectrometry.

The effect of palladium matrix modification on the determination of thallium has been investigated. The effect of palladium combined either with ammonium nitrate or with magnesium nitrate on the sodium chloride interference was systematically studied and was compared with that of the classical sulfuric acid modifier. A combination of 6 micrograms palladium with 100 micrograms ammonium nitrate allows the direct determination of thallium in ten-fold diluted blood against matrix-free standards. The detection limit (3 sigma) in the undiluted blood was calculated to be 25 micrograms.1(-1). For the urine analysis the standard addition technique is recommended because a complete thallium recovery for all different urine samples studied was not always obtained.

Hot Temperature↗
PubMed1986

Specific inhibition of myelination by lead in vitro; comparison with arsenic, thallium, and mercury.

Lead induces peripheral nerve segmental demyelination in rats. Arsenic and thallium produce a peripheral neuropathy characterized by axonal degeneration in humans. Mercury and thallium appear to damage both the peripheral and the central nervous system. It is not known whether this difference in effect is due to different molecular forms of the elements, to differential access to various compartments of the nervous system, or to intrinsically different properties of the elements. Using an in vitro model system of dorsal root ganglion neurons and morphometry of neurite outgrowth and myelination, we demonstrated that mercury and arsenic produce 50% inhibition of neurite outgrowth at 3.9 and 9.6 X 10(-6) M, respectively, whereas the same degree of inhibition is produced by 1.3 X 10(-4) M thallium and 3.3 X 10(-4) M lead. Lead also produces complete inhibition of myelination at 1 X 10(-6) M, suggesting that a primary effect on myelination is present in this model system as well as in the intact rodent.

Animals↗
PubMed1975

Toxicity and pollution potential of thallium.

Toxicity and pollution potential of thallium are reviewed. Thallium is slightly more acutely toxic to mammals than mercury, and as acutely toxic as copper to fish. Its present industrial uses are too limited to generate pollution, but thallium, discharged in wastes from mines, ore-processing, and coal-burning plants, is contaminating the environment.

Animals↗
PubMed1988

Seasonal variation of thallium, lead, and chromium concentrations in airborne particulate matter collected in an urban area.

In November 1985 a research program started, with the aim to evaluate seasonal variations in the concentrations of organic and inorganic pollutants in the atmosphere of Genoa. The program provided for the collection of samples of airborne particulate in five different areas with distinct urban characteristics. First results for chromium, lead, and thallium concentrations in an industrial and in an urban area are reported. Lead showed the highest concentration at both locations (geometric mean: 1.037 and 0.476 microgram/m3, respectively) and appeared to be little affected by seasonal variation. Private traffic was confirmed as the main source of this pollutant. Chromium and thallium geometric mean concentrations were 0.006 and 0.014 microgram/m3 in site A and 0.017 and 0.015 microgram/m3 in site B, respectively. In the urban location a good negative linear correlation was found between chromium and thallium concentration and mean ambient temperature; the domestic heating plants were suspected as important emission sources of these two compounds.

Air Pollutants↗
PubMed1988

Urinary thallium: critical problems, reference values and preliminary results of an investigation in workers with suspected industrial exposure.

Using a sensitive ETA ASS method, urinary thallium (Tl-U) has been measured in a group of non-exposed individuals and in two groups of workers with suspected industrial exposure. In non-exposed subjects (72 healthy males aged 41 +/- 11 years) the Tl-U mean value was 0.22 mu/l (range 0.05-0.61). Significantly higher values were found in two groups of workers (30 and 21 subjects) employed in two cement factories and two cast iron foundries (mean Tl-U value: 0.38 and 0.33 mu/l, respectively; range 0.06-1.2). Thallium has been determined in coal, raw materials and, in one factory, also in environmental samples, but no detectable levels were found. The analytical problems connected to urinary thallium determination and the preliminary results of biological monitoring in non-exposed individuals and in workers are discussed.

Environmental Exposure↗
PubMed1983

Thallium-201 scanning to decide CCU admission in patients with non-diagnostic electrocardiograms.

To determine the value of thallium-201 scintigraphy as a decisive factor in admission policy for patients with acute chest pain and nondiagnostic electrocardiograms, we undertook a prospective study in 149 such patients. The interval between pain and scan never exceeded 12 hr. Of 57 patients in whom a defect was seen, 34 had an acute infarction, 7 developed infarction within 2 months, and in 11 coronary heart disease was proven by angiography or strongly suggested by stress tests (ECG and thallium-201 scan). In 13 patients with an equivocal scan, coronary heart disease was proven or strongly suggested in 5. Of 79 patients with a normal scan, only 1 had acute infarction, and stress tests were positive in 6 and negative in 72. In these 72 no cardiac event occurred during a 1-year follow-up. Thallium-201 scintigraphy can help to select those patients with acute chest pain and nondiagnostic electrocardiograms who need observation in a CCU.

Electrocardiography↗
PubMed1984

Influence of left ventricular function and severity of coronary artery disease on exercise-induced pulmonary thallium-201 uptake.

Pulmonary uptake of thallium-201 during exercise was measured in 58 patients with coronary artery disease and compared with the results from 21 patients with normal coronary arteries and 5 normal volunteers. A quantitative method was used to assess the pulmonary thallium uptake relative to cardiac activity (heart/lung ratio). This ratio was calculated for exercise and for redistribution imaging. The mean exercise heart/lung ratio for the group with coronary artery disease was 1.43 +/- 0.36 SD (n = 58); and for the "normal" group was 2.76 +/- 0.41 (n = 26) (P less than 0.001). Increased pulmonary uptake after exercise in the coronary disease group was reversible (mean redistribution heart/lung = 1.96 +/- 0.37 SD; P less than 0.001). The exercise heart/lung ratio differed significantly between groups with single-, two- and three-vessel disease; patients with and without prior infarction; and patients with exercise-induced ST segment depression and elevation. Linear regression analysis between ejection fraction calculated from equilibrium radionuclide angiography at rest and the exercise heart/lung ratio in the coronary artery disease group gave the equation: exercise heart/lung = 0.857 +/- 0.014 ejection fraction for n = 58; r = 0.695; P less than 0.001. It would appear that the exercise heart/lung ratio is a simple and valuable non-invasive index which should be used as part of routine thallium scan interpretation to provide additional information on left ventricular function after exercise and as an indicator of the severity of obstructive coronary artery disease.

Adult↗
PubMed1987

Thallium-201 exercise scintigraphy in patients having complete left bundle branch block with normal coronary arteries.

Eleven patients with left bundle branch block and chest pain suggestive of coronary arterial disease were analyzed using thallium-201 exercise scintigraphy, M-mode echocardiography and coronary arteriography. The coronary arteries were shown to be normal in all patients. A reversible anteroseptal defect on thallium-201 scintigraphy and an asynchronous septal motion on echocardiography were evident in eight patients. Thus, symptomatic patients with left bundle branch block may have reversible anteroseptal defects on thallium-201 scintigraphy which do not indicate coronary artery disease. Rather, they may be due to functional ischemia secondary to abnormal septal motion.

Adult↗
PubMed1988

Dipyridamole thallium testing: noncardiac side effects, cardiac effects, electrocardiographic changes and hemodynamic changes after dipyridamole infusion with and without exercise.

Thallium-201 scintigraphy in combination with intravenous dipyridamole has been reported to be useful in patients who are unable to perform maximal exercise stress testing. Few reports have dealt with side effects in large numbers of patients. For that reason noncardiac side effects, cardiac effects, electrocardiographic changes, as well as hemodynamic changes were studied in 301 consecutive patients, examined by dipyridamole thallium-201 imaging because of suspected coronary artery disease. The patients were divided into two groups (A and B). Patients in group A (101 patients) received an infusion of 0.14 mg/kg per minute dipyridamole for four minutes. Patients in group B (200 patients) received the same dose of dipyridamole followed by low level exercise (60 rpm/30 Watts) for three minutes to achieve maximal coronary blood flow and to diminish thallium-201 uptake in the gastrointestinal organs. The likelihood of having hemodynamically significant coronary artery disease was the same in both groups. Patients in group B experienced significantly less side effects than patients in group A (11% vs 43%, P less than 0.05). In group B changes in systolic blood pressure (P less than 0.05), heart rate (P less than 0.05), and rate pressure product (P less than 0.05) were more distinct. The occurrence of angina was the same in both groups (47% vs 44%, NS), but ischemic ST segment changes were significantly more frequent in group B than in group A (25% vs 12%, P less than 0.05). Thus, exercise added to dipyridamole infusion compared to dipyridamole infusion alone results in fewer noncardiac side effects, the same prevalence of angina pectoris, and a higher incidence of ST segment changes.

Adult↗
PubMed1987

Organothallium(III) reagents for modification of biomacromolecules: interaction of thallium derivatives with transfer RNA.

As an extension of work on the inhibition of enzymes by arylthallium(III) reagents, the thallium analogues of the organomercurials, we have studied the interactions of these molecules with transfer RNA. In contrast to thallous acetate, thallium(III) derivatives (thallic trifluoroacetate, p-methylphenylthallium(III) bis-trifluoroacetate (MPT) and o-carboxyphenylthallium(III) bis-trifluoroacetate) bound to Escherichia coli tRNA. The interaction was fully reversible upon Sephadex G-25 gel filtration, and binding constants and stoichiometries were evaluated by a number of procedures. The likely site of interaction was shown to be the thiouridine residue (s4U8) based on changes induced by MPT on the absorbance around 330 nm. No changes in stacking interactions could be detected from the absorption or circular dichroic spectra. The detailed structure of the groups on thallium(III) affected the interaction with tRNA. Thalliation at s4U8 affects the absorbance at 335 nm and the amino-acid uptake capacity of E. coli tRNAPhe in parallel, the latter being progressively inhibited by increasing amounts of MPT. In a model nucleoside system, uridine disulphide is probably formed from reduced thiouridine by the oxidative action of the Tl(III) reagents. No evidence of cross-linking of E. coli tRNA molecules under gel electrophoretic conditions was obtained in contrast to the model nucleoside. The easily reversible interaction of MPT with sulphur sites in E. coli tRNA contrasts with the stable (to gel filtration) bonds formed between MPT and (thiol) sites in enzymes.

Chromatography, Gel↗
PubMed1988

Dipyridamole-induced ST segment depression during thallium-201 imaging in patients with coronary artery disease: angiographic and hemodynamic determinants.

To examine the angiographic and hemodynamic determinants of dipyridamole-induced ST segment depression in patients with coronary artery disease, 41 patients with angiographically documented coronary disease who underwent dipyridamole-thallium-201 myocardial scintigraphy were studied. Dipyridamole-induced ST depression occurred in 14 (34%) of the 41 patients. Stepwise multivariate logistic regression was performed to compare the predictive value of angiographic findings (good coronary collateral vessels, jeopardized collateral vessels, multivessel disease), hemodynamic changes (changes in heart rate, systolic pressure, diastolic pressure and rate-pressure product), thallium-201 results (perfusion defect, thallium-201 redistribution) and demographic data (age, gender, medications). Only the presence of good coronary collateral vessels (p less than 0.02) and increases in rate-pressure product after dipyridamole infusion (p less than 0.02) were significant multivariate predictors of dipyridamole-induced ST depression. Good collateral vessels were more common in the group with ST depression (11 [79%] of 14) than they were in the group without ST depression (6 [22%] of 27; p less than 0.001). Rate-pressure product increased 2,835 +/- 1,648 beats/min.mm Hg in the group with ST depression compared with 1,179 +/- 1,417 beats/min.mm Hg in patients without ST depression (p less than 0.005). In conclusion, dipyridamole-induced ST segment depression in patients with coronary artery disease appears to be related to 1) the presence of good coronary collateral vessels, which may act by facilitating "coronary steal", and 2) increases in rate-pressure product, reflecting increased myocardial oxygen demand. These observations may explain the lack of prognostic value of dipyridamole-induced ST segment depression described in previous reports.

Aged↗
PubMed1988

Incomplete redistribution in delayed thallium-201 single photon emission computed tomographic (SPECT) images: an overestimation of myocardial scarring.

To determine if incomplete redistribution at 4 h in exercise tomographic thallium-201 studies is always due to a myocardial scar, 141 patients were evaluated before and after a total of 160 successful percutaneous transluminal coronary angioplasty procedures. Thallium studies were analyzed using polar "bull's-eye" maps. For both immediate and delayed images, abnormalities were quantified as a thallium score by calculating a standard deviation-weighted sum of pixels greater than 2.5 SD below gender-matched normal limits. One hundred forty-four of 160 studies indicated abnormalities before angioplasty. Of these 144, incomplete redistribution occurred in 111 (77%): 16 (14%) in patients with and 95 (86%) in patients without prior Q wave myocardial infarction. After angioplasty, improvement in delayed image score occurred in 8 (50%) of 16 patients with prior infarction and 72 (76%) of 95 patients without prior infarction (p less than 0.05). After angioplasty, delayed images were normal in 1 (6%) of 16 patients with prior infarction and 32 (34%) of the 95 without (p less than 0.05). Before angioplasty, delayed image scores were positively correlated with scores in the immediate postexercise images in patients with (r = 0.84) and those without (r = 0.69) prior infarction. To determine if additional delayed images could help differentiate scar from ischemia, an 8 to 24 h delayed image was obtained in each of 40 other patients with incomplete redistribution at 4 h. Of 28 patients without prior infarction, 15 had no redistribution, and 13 had further redistribution at 8 to 24 h.

Adult↗
PubMed1988

Safety and diagnostic accuracy of dipyridamole-thallium imaging in the elderly.

The noninvasive diagnosis of coronary artery disease in the elderly can occasionally be difficult. Intravenous dipyridamole-thallium imaging is a potentially useful diagnostic test to determine presence and severity of coronary disease; however, the safety of the procedure has not been determined in an older population. The side effect profile and frequency of severe ischemic responses after 0.56 mg/kg of intravenous dipyridamole were compared in 101 patients greater than or equal to 70 years old and 236 patients less than 70 years old. There were no side effects in 64% and 62% of patients greater than or equal to 70 and less than 70 years old, respectively (p = NS). Among the 337 patients tested, there were no complications of myocardial infarction or death. The most common cardiac side effect was chest pain, which occurred in 21 (21%) of the 101 patients aged greater than or equal to 70 years and in 64 (27%) of the 236 patients less than 70 years (p = NS). Aminophylline was required to reverse cardiac or noncardiac side effects in 15 (15%) and 36 (15%) of the patients greater than or equal to 70 and less than 70 years old, respectively (p = NS). A severe ischemic response occurred in 2% and 2.5% of patients greater than or equal to 70 and less than 70 years old, respectively (p = NS). The sensitivity of intravenous dipyridamole-thallium imaging for obstructive coronary artery disease was 86% (25 of 29) and 83% (68 of 82) in older and younger patients, respectively (p = NS); the specificity was 75% (6 of 8) and 70% (16 of 23), respectively (p = NS). Thus, intravenous dipyridamole-thallium imaging is a safe noninvasive method for assessment of older patients with obstructive coronary disease; its side effect profile and diagnostic accuracy are similar to those seen in younger patients. The technique is associated with severe ischemic responses in only a small minority of patients.

Adult↗
PubMed1989

Effect of exercise level on the ability of thallium-201 tomographic imaging in detecting coronary artery disease: analysis of 461 patients.

This study examined the effect of the level of exercise on the ability of thallium-201 imaging with single photon emission computed tomography (SPECT) to detect coronary artery disease. Patients in group 1 (n = 164) achieved adequate exercise end points, defined as positive exercise electrocardiograms or greater than or equal to 85% of maximal predicted heart rate. Patients in group 2 (n = 108) had submaximal exercise. The SPECT thallium-201 images showed perfusion defects in 74%, 88%, and 98%, respectively, of patients with one, two and three vessel coronary artery disease in group 1, compared with 52%, 84% and 79%, respectively, of such patients in group 2 (p less than 0.05). Perfusion defects showed partial or complete redistribution consistent with ischemia in 56%, 80% and 88%, respectively, of patients with one, two and three vessel coronary artery disease in group 1 compared with 35%, 58% and 56%, respectively, of such patients in group 2 (p = 0.08, less than 0.03 and less than 0.001, respectively). Of 58 patients with normal coronary angiograms or less than 50% diameter stenosis, 36 (62%) had normal SPECT images. In a separate group of 131 patients with less than 5% pretest probability of coronary artery disease, the specificity was 93%. The sensitivity of exercise SPECT imaging in group 1 was higher than that of ST segment depression (p less than 0.001). Thus, the level of exercise affects the results of SPECT thallium imaging in the localization and evaluation of the extent of coronary artery disease and the detection of ischemia.

Coronary Angiography↗
PubMed1991

Quantitative thallium-201 single-photon emission computed tomography during maximal pharmacologic coronary vasodilation with adenosine for assessing coronary artery disease.

The diagnostic value of maximal pharmacologic coronary vasodilation with intravenously administered adenosine in conjunction with thallium-201 single-photon emission computed tomography (SPECT) for detection of coronary artery disease was investigated in 101 consecutive patients who had concomitant coronary arteriography. Tomographic images were assessed visually and from computer-quantified polar maps of the thallium-201 distribution. Significant coronary artery disease, defined as greater than 50% luminal diameter stenosis, was present in 70 patients. The sensitivity for detecting patients with coronary artery disease using quantitative analysis was 87% in the total group, 82% in patients without myocardial infarction and 96% in those with prior myocardial infarction; the specificity was 90%. The sensitivity for diagnosing coronary artery disease in patients without infarction with single-, double-and triple-vessel disease was 76%, 86% and 90%, respectively. All individual stenoses were identified in 68% of patients with double-vessel disease and in 65% of those with triple-vessel disease. The extent of the perfusion defects, as quantified by polar maps, was directly related to the extent of coronary artery disease. In conclusion, quantitative thallium-201 SPECT during adenosine infusion has high sensitivity and specificity for diagnosing the presence of coronary artery disease, localizing the anatomic site of coronary stenosis and identifying the majority of affected vascular regions in patients with multivessel involvement.

Adenosine↗
PubMed1992

Equivalence between adenosine and exercise thallium-201 myocardial tomography: a multicenter, prospective, crossover trial.

OBJECTIVES: The study was designed to compare pharmacologic and exercise stress during thallium-201 single-photon tomography in a multicenter prospective crossover trial. BACKGROUND: Both exercise and adenosine myocardial perfusion imaging have high sensitivity and specificity for detection of coronary artery disease. However, few data are available comparing these two stress tests in the same patients. METHODS: The study group consisted of 175 subjects: 55 healthy volunteers and 120 patients with suspected coronary artery disease. All subjects underwent two thallium tomographic tests performed 30 days apart, one during intravenous administration of adenosine (140 micrograms/kg per min for 6 min) and one during exercise stress. All images were computer quantified and interpreted without knowledge of the stress test performed. Interpretation agreement was assessed by kappa and Z statistics. RESULTS: Agreement on the presence of normal or abnormal tomograms by adenosine and exercise scintigraphy was 82.8% by visual analysis with kappa and Z statistics of 0.65 (p less than 0.0001) and 11.1 (p less than 0.00001), respectively. The agreement by computer quantification was 86% with kappa and Z statistics of 0.709 (p less than 0.0001) and 12.2 (p less than 0.00001), respectively. Agreement on localization of the perfusion defect to a specific coronary vascular territory varied from 82.7% to 91.4% with highly significant kappa and Z statistics (p less than 0.0001). There was a good correlation between quantified perfusion defect size by adenosine and exercise (r = 0.80, p less than 0.0001), but the values for defect size were significantly greater by adenosine scintigraphy (p = 0.0073). Adenosine side effects were frequent but transient and ceased spontaneously in most subjects within 1 to 2 min after the infusion was discontinued. CONCLUSIONS: Adenosine thallium-201 scintigraphy provides diagnostic information similar to that of exercise scintigraphy, although values for defect sizes are greater with adenosine.

Adenosine↗
PubMed1992

Relation of perfusion defects observed with myocardial contrast echocardiography to the severity of coronary stenosis: correlation with thallium-201 single-photon emission tomography.

It has been previously shown that myocardial contrast echocardiography is a valuable technique for delineating regions of myocardial underperfusion secondary to coronary occlusion and to critical coronary stenoses in the presence of hyperemic stimulation. The aim of this study was to determine whether myocardial contrast echocardiography performed with a stable solution of sonicated albumin could detect regions of myocardial underperfusion resulting from various degrees of coronary stenosis. The perfusion defect produced in 16 open chest dogs was compared with the anatomic area at risk measured by the postmortem dual-perfusion technique and with thallium-201 single-photon emission tomography (SPECT). During a transient (20-s) coronary occlusion, a perfusion defect was observed with contrast echocardiography in 14 of the 15 dogs in which the occlusion was produced. The perfusion defect correlated significantly with the anatomic area at risk (r = 0.74; p less than 0.002). During dipyridamole-induced hyperemia, 12 of the 16 dogs with a partial coronary stenosis had a visible area of hypoperfusion by contrast echocardiography. The four dogs without a perfusion defect had a stenosis that resulted in a mild (0% to 50%) reduction in dipyridamole-induced hyperemia. The size of the perfusion defect during stenosis correlated significantly with the anatomic area at risk (r = 0.61; p = 0.02). Thallium-201 SPECT demonstrated a perfusion defect in all 14 dogs analyzed during dipyridamole-induced hyperemia; the size of the perfusion defect correlated with the anatomic area at risk (r = 0.58; p less than 0.03) and with the perfusion defect by contrast echocardiography (r = 0.58; p less than 0.03). Thus, myocardial contrast echocardiography can be used to visualize and quantitate the amount of jeopardized myocardium during moderate to severe degrees of coronary stenosis. The results obtained show a correlation with the anatomic area at risk similar to that obtained with thallium-201 SPECT.

Albumins↗