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Protection against thallium hepatotoxicity by silymarin.

The effect of silymarin (100 mg/kg i.p.) on the biochemical indicators of liver damage induced by thallium (10 mg/kg p.o.) was studied in rats. The production of malondialdehyde and the content of reduced glutathione in the liver were measured as indicators of lipid peroxidation. Thallium intoxication increased the serum activities of glutamic pyruvic transaminase, gamma-glutamyl transpeptidase, alkaline phosphatase and the liver concentration of triglycerides. Thallium decreased the activity of alkaline phosphatase and increased that of gamma-glutamyl transpeptidase in the liver cell membrane. It also abolished the membrane activity of Na+/K+ ATPase. Lipid peroxidation was enhanced by thallium as malondialdehyde production was increased and the content of reduced glutathione was decreased in the liver. Silymarin completely prevented all these changes. It is suggested that thallium toxicity is due, at least in part, to the promotion of lipid peroxidation. The membrane stabilizing effect of silymarin observed in this and in other models of liver toxicity is due to some antioxidant property, possibly related to its ability to scavenge free oxygen radicals.

Animals↗

Relationship between physicochemical properties of prussian blue and its efficacy as antidote against thallium poisoning.

In the present work we established a relationship between some physicochemical properties of two different batches of Prussian blue (PB) and their in vivo efficacy as an antidote against thallium poisoning. The physicochemical properties studied were crystallite size and thallium-adsorbing capacity. One of the batches was synthesized and the other was obtained from commercial sources. The synthesized PB batch with the smallest crystallite size had both the highest adsorption capacity and antidotal efficacy. Synthesized PB protected 100% of the animals against one LD50 thallium dose, whereas the commercial PB batch protected only 80%. Thallium content in blood and tissues (liver, kidney, brain) was also analysed after antidotal PB treatment in rats previously intoxicated with a sublethal dose of T1+. Animals treated with synthesized PB showed significantly less thallium in blood and tissue contents than those values of commercial PB-treated rats, indicating better antidotal properties of the synthesized PB. According to the present study we suggest an in vivo evaluation of the compound before distribution of the product to toxicological units, if X-ray diffractometric analysis is not available, in order to identify and determine the crystallite size of the compound as it plays an important role in the efficacy of PB.

Adsorption↗

Thallium-induced achondroplasia in chicken embryos and the concept of critical periods during development.

Achondroplasia was induced in chicken embryos by in ovo application of 0.6 mg/egg thallium sulfate. The critical (sensitive) period for production of achondroplasia began on day 5 of incubation and ended at the start of HH stage 35 (8.5 days). The end of the critical period was accurately timed and found to be 205-207 hours of incubation and to coincide with a 66% decrease in growth rate of the embryos. Treatment resulted in reduced tibial growth one day later, tibial angulation two days later, and chrondrocytic necrosis four days later. The last was therefore not the cause of the angulation. Tibias were taken from thallium-treated and control donor embryos of various ages and grafted to the chorioallantoic membranes of treated and control host embryos of various ages during and outside the critical period and achondroplastic changes induced in grafted tibias exposed to thallium while on the chorioallantoic membrane. The critical period was extended into day 10 of incubation in such grafted tibias. Tibias maintained for seven days in organ culture were achondroplastic if pretreated with thallium at seven or eight days of incubation but not at ten days. Exposure of as little as 0.5 hour was sufficient to elicit micromelia when the tibias were grafted or organ cultured. Thallium therefore rapidly binds to skeletal tissues during a critical period of embryonic development but this critical period may be extended when tibias are removed from the embryo.

Abnormalities, Drug-Induced↗

Twenty-four-hour quantitative thallium imaging for predicting beneficial revascularization.

To determine the utility of 24-h thallium single-photon emission tomographic imaging for the assessment of myocardial viability, 40 patients with persistently decreased uptake on 3-h delayed imaging after exercise were studied before and after bypass surgery (n = 34) or coronary angioplasty (n = 6). Wall motion improvement after revascularization was also analysed in 23 patients with respect to the segments with and without 24-h redistribution. Of a total of 113 segments without redistribution at 3-h imaging after exercise, 62 (55%) demonstrated redistribution at 24 h. After revascularization 57 (92%) of these 62 segments revealed improvement of thallium uptake. On the other hand 40 (78%) of the 51 segments with persistently decreased thallium uptake until 24 h did not show improvement of uptake after revascularization. Of the 15 segments with > 50% relative thallium uptake and without redistribution on 24-h images, ten showed improvement of thallium uptake after revascularization. Hence higher uptake even without 24-h redistribution may indicate viability. Regional wall motion improved in 22 of 23 segments with redistribution on 24-h images, and did not improve after revascularization in 19 of 22 segments without redistribution at 24 h. These data suggest that 24-h late imaging with quantitative analysis may provide reliable information about reversible myocardial ischaemia in segments that demonstrate a fixed perfusion abnormality on conventional 3-h delayed imaging.

Angioplasty, Balloon, Coronary↗

Comparison of thallium-201 and technetium-99m teboroxime myocardial single photon emission tomography with coronary arteriography.

Myocardial single photon emission tomography (SPET) using technetium-99m teboroxime (teboroxime) was studied and the results compared with those of thallium-201(thallium) SPET and coronary arteriography in 19 patients. Resting teboroxime SPET was performed initially. Two hours later, exercise teboroxime SPET was performed. Exercise ergometer tests for both teboroxime and thallium were carried out in a supine position. The levels of exercise achieved for both tests were similar. Agreement for the identification of myocardial segments between thallium SPET and teboroxime SPET was 147/171(86%) (NS). When a significant stenosis was defined as greater than or equal to 75% or greater than or equal to 50%, agreement between two radiopharmaceuticals for the detection of diseased vessels was 89% (NS, k = 0.601) or 88% (NS, k = 0.713), respectively. In only 2/19 cases were inferior and posterior segments (3/171) difficult to interpret in teboroxime SPET due to hepatic activity. Thus, teboroxime SPET with a short data acquisition time resulted in a rapid completion for each study and had a good correlation with thallium SPET.

Adult↗

Acute cardiovascular toxicity of thallium (I) ions.

The acute cardiovascular toxicity of thallium (I)-ions was studied in anesthetized rats and also in some isolated preparations. In pentobarbital-anesthetized rats, intravenously applied Tl2SO4 (range 3 to 100 mg/kg) caused a significant, dose-dependent decrease in mean arterial blood pressure and heart rate. In spontaneously beating guinea pig isolated atria, thallium (I)-ions (10(-5) to 10(-3) M) caused a concentration-dependent decrease in frequency, which was not influenced by atropine, cocaine, or by considerable changes in the potassium concentration of the medium. A direct influence of Tl+ on the sinus node is presumed. Thallium decreases contractile force probably as a result of its negative chronotropic properties, since the amplitude of contraction remained uninfluenced in electrically driven atria. Thallium (I)-ions were readily taken up by the guinea pig isolated atria. At a bath concentration of 5 times 10(-5) M Tl+ a tissue/medium ratio of approximately 45 was achieved. Probably, an exchange against cellular potassium takes place. Relaxation of vascular smooth muscle by Tl+ was demonstrated both in isolated aortic strips (rabbit) and in the isolated perfused rabbit ear preparation. Both the vascular smooth muscle relaxation and the decrease in heart rate would explain the acute hypotensive effect of thallium.

Animals↗

A comparison of rest sestamibi and rest-redistribution thallium single photon emission tomography: possible implications for myocardial viability detection in infarcted patients.

Thirty patients (26 men, 4 women, mean age 61 +/- 8 years) who had suffered myocardial infarction 15 +/- 6 months previously, were submitted to (1) standard stress-redistribution thallium-201 single photon emission tomography (SPET), (2) rest-redistribution 201T1 SPET and (3) stress-rest technetium-99m sestamibi SPET. Uptake modifications in relation to exercise-induced defects were evaluated in a total of 390 myocardial segments. Tracer uptake was scored as normal (=0), mildly reduced (=1), apparently reduced (=2), severely reduced (=3) or absent (=4). Comparison of stress studies failed to show any statistical difference (58% segmental abnormalities with sestamibi vs 61% with thallium). Uptake abnormalities (score 1-4) were detected in 55% of the segments with sestamibi, 55% with standard thallium redistribution, 55% with early imaging after thallium injection at rest and 54% with 3-h delayed rest imaging (P = NS). Absence of tracer uptake (score = 4) under resting conditions was recorded in 75 (19%) segments with standard 201T1 redistribution, 75 (19%) with rest sestamibi, 70 (18%) with rest 201T1 imaging and 62 (16%) with rst-redistribuion 201T1 (P < 0.05 vs other imaging modalities). Thus, 3-h delayed rest thallium imaging detected reversibility of uptake defects in a significantly higher number of myocardial segments. This finding might have important implications for both tracer and technique selection when myocardial viability is the main clinical issue.

Cell Survival↗

Decrease in the ability to detect elevated lung thallium due to delay in commencing imaging after exercise.

Post-exercise elevation of the lung/myocardial thallium ratio and a high lung clearance rate between initial and delayed images have been reported to be markers for exercise-induced left ventricular (LV) dysfunction associated with coronary artery disease (CAD). We performed thallium exercise tests on 60 patients, 42 with CAD, in order to determine the effect of delaying initial imaging on detection of elevated lung thallium. In addition to images obtained at 2 minutes and at 2 hours after exercise, 18-minute images were also obtained to simulate such a delay. Because of rapid isotope clearance in those with initially elevated lung activity, there was decreased sensitivity of both the initial lung/myocardial ratio and lung thallium clearance for detecting CAD, using the 18-minute image as the initial post exercise study. We conclude that initial imaging should be done in the anterior view early after exercise to optimize detection of elevated lung thallium.

Adult↗

Resting thallium-201 myocardial perfusion patterns in patients with severe left ventricular dysfunction: differences between patients with primary cardiomyopathy, chronic coronary artery disease, or acute myocardial infarction.

This study examined the value of resting thallium-201 imaging in differentiating patients with primary cardiomyopathy from those with ischemic cardiomyopathy. There were 15 patients with primary cardiomyopathy (group I); 20 with chronic CAD (group II); and 25 with acute Q wave myocardial infarction (group III). All patients had LVEF less than or equal to 35%. The thallium score was less than 50 (maximum 60) in one patient (7%) in group I, in 17 patients (85%) in group II, and in 25 patients (100%) in group III (p less than 0.0001, I vs II and III). The number of normal segments was 11.4 +/- 4.9 in group I, 6.9 +/- 2.9 in group II, and 7.0 +/- 2.2 in group III (p less than 0.0001, I vs II, III). Reversible defects were present in three patients in group II, three in group III, and none in group I. Abnormal right ventricular thallium uptake was observed in 27% of patients in group I, 25% in group II, and 40% in group III (p = NS). Abnormal lung thallium uptake was observed in 33% in group I, 20% in group II, and 20% in group III (p = NS). Thus, rest thallium imaging is useful in separating patients with primary cardiomyopathy from those with ischemic cardiomyopathy.

Adolescent↗

Differentiation of viable and nonviable myocardium after acute reperfusion using serial thallium-201 imaging.

This study was performed to determine if differences in regional myocardial thallium clearance rates could differentiate salvaged from nonsalvaged myocardium after reperfusion. Twenty-one dogs underwent 2 hours of left anterior descending coronary artery ligation followed by reperfusion. Thallium was administered 5 minutes later and serial images were acquired over 3 hours. Of the 21 dogs, 15 had infarctions of which nine had initially reduced anterior wall thallium activity (group 1) and six had normal or increased activity (group 2). Six dogs did not have an infarction (group 3). All group 1 dogs demonstrated reduced clearance rates in the anterior wall (T1/2 = 15.0 +/- 4.7 hours, SD) compared to the posterior wall (T1/2 = 9.0 +/- 4.4 hours; p less than 0.001). Group 2 dogs demonstrated increased clearance rates in the anterior wall (T1/2 = 5.7 +/- 2.0 hours) compared to the posterior wall (T1/2 = 10.5 +/- 4.6 hours; p less than 0.001). Group 3 dogs demonstrated no difference in clearance rates. In conclusion, although thallium uptake is frequently reduced in nonsalvaged myocardium, tracer uptake can be normal or increased if perfusion has been completely restored. However, an increased clearance rate from the reperfused zone compared to the normal zone is a reliable indicator of nonsalvaged myocardium, despite normal initial thallium uptake.

Animals↗

Effect of maintenance oral theophylline on dipyridamole-thallium-201 myocardial imaging using SPECT and dipyridamole-induced hemodynamic changes.

To evaluate the effect of maintenance oral theophylline therapy on the diagnostic efficacy of dipyridamole-thallium-201 single photon emission computed tomography (SPECT) imaging for coronary artery disease, dipyridamole-thallium-201 SPECT imaging was performed in eight men with documented coronary artery disease before initiation of theophylline treatment and repeated while these patients were receiving therapeutic doses of oral theophylline. Before theophylline treatment, intravenous dipyridamole caused a significant increase in heart rate, decrease in blood pressure, angina in seven of eight patients, and ST segment depression in four of eight patients. While they were being treated with theophylline, none of the patients had angina or ST segment depression, and there were no hemodynamic changes with intravenous dipyridamole. Before theophylline treatment, dipyridamole-thallium-201 SPECT imaging showed reversible perfusion defects in myocardial segments supplied by stenotic coronary arteries. With theophylline treatment, dipyridamole-thallium-201 SPECT showed total absence of reversible perfusion defects. Treatment with theophylline markedly reduced the diagnostic accuracy of dipyridamole-thallium-201 imaging for coronary artery disease.

Administration, Oral↗

Dilatation of the left ventricular cavity on dipyridamole thallium-201 imaging: a new marker of triple-vessel disease.

To investigate the significance and mechanism of dilatation of the left ventricular cavity on dipyridamole thallium-201 imaging, we performed both dipyridamole thallium-201 imaging and dipyridamole radionuclide angiography on 83 patients with known angiograms. The dipyridamole/delayed ratio of the left ventricular dimension from the thallium-201 image was defined as the left ventricular dilatation ratio (LVDR). An LVDR greater than the mean + two standard deviations in patients without coronary artery disease was defined as abnormal. Twenty-two of 83 patients showed an abnormal LVDR, and 18 of the 22 patients (82%) had triple-vessel disease. By defect and washout analysis, the sensitivity and specificity for correctly identifying the patients as having triple-vessel disease was 72% and 76%, respectively, whereas LVDR had a sensitivity of 72% and a specificity of 93%. When LVDR was used in combination with the defect and washout criteria, sensitivity increased to 84% without a loss of specificity. In those 22 patients with abnormal LVDRs, end-diastolic volume measured by radionuclide angiography did not change after dipyridamole infusion. Dilatation of the left ventricular cavity on dipyridamole thallium-201 imaging reflected relative subendocardial hypoperfusion induced by dipyridamole rather than actual chamber enlargement. The LVDR was moderately sensitive and highly specific for triple-vessel disease and provided complementary information to dipyridamole thallium-201 imaging.

Adult↗

Side effects during adenosine thallium imaging with single-port or double-port infusion protocols.

The double-port infusion protocol during adenosine thallium imaging involves the use of two infusion systems, one for adenosine and one for thallium. The single-port infusion protocol, on the other hand, uses one infusion system; both adenosine and thallium are injected via a "Y" connection. This study examined the possibility that the single infusion system, by displacing a column of blood filled with adenosine, may be responsible for a greater incidence of side effects. In a parallel study, 140 patients underwent adenosine thallium imaging with the single-port system (group 1) and 140 patients underwent imaging with the double-port system (group 2). Both groups were comparable in age (67 +/- 10 years vs 64 +/- 11 years), gender (men comprised 56% of patients in group 1 and 64% in group 2), resting heart rate, and systolic blood pressure. More patients in group 1 had chest pains (57% vs 44%; p = 0.03), ST-segment depression (25% vs 9%; p = 0.005), nausea (11% vs 4%; p = 0.04), and second- or third-degree atrioventricular block (11% vs 5%; p less than 0.08) than did patients in group 2. The other side effects were similar, and peak heart rate and peak systolic blood pressure were also similar. The thallium images that used single-photon emission computed tomography were abnormal in 61% of patients in group 1 and in 65% of patients in group 2 (p = not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

Determination of perioperative cardiac risk by adenosine thallium-201 myocardial imaging.

To determine the predictive value of adenosine thallium-201 myocardial imaging for perioperative cardiac events, 60 consecutive patients referred for preoperative cardiac evaluation were studied before vascular (n = 25), orthopedic (n = 14), or general (n = 21) surgery. Tomographic (n = 52) and planar (n = 8) thallium-201 imaging was performed after adenosine infusion at a rate of 140 micrograms/kg/min for 6 minutes. Two blinded expert observers graded results of adenosine thallium-201 studies as normal (33%), fixed defect only (2%), reversible defect only (48%), and combined (fixed and reversible) defects (17%). After 6 +/- 3 months of follow-up, 81% proceeded to surgery and 43% underwent preoperative coronary angiography. Clinical variables that correlated with perioperative cardiac events were a history of diabetes mellitus (p = 0.05), left bundle branch block (p = 0.02), and left ventricular hypertrophy (p = 0.06) on the resting ECG. This clinically "high-risk" group had an event rate of 22% as compared with no cardiac events in patients in the "low-risk" group without these clinical characteristics (p = 0.005). Stepwise logistic regression analysis revealed that the presence of a combined (fixed and reversible) adenosine thallium-201 defect (p = 0.0007), three-vessel coronary artery disease (p = 0.001), and left bundle branch block (p = 0.02) was predictive of subsequent cardiac events with relative risk ratios of 4.9, 2.9, and 2.2, respectively. Therefore the presence of an adenosine thallium-201 perfusion defect is correlated with and predictive of an increased risk of perioperative cardiac events in patients referred for preoperative risk evaluation.

Adenosine↗

Variables associated with a poor prognosis in patients with an ischemic thallium-201 exercise test.

To determine the exercise workload, ECG, and thallium-201 image parameters that are most closely associated with a poor prognosis from ischemic heart disease, the test results of 268 patients were reviewed. Only patients with unequivocal thallium-201 redistribution were selected. A multivariate analysis was performed to find the variables that were most strongly associated with the outcomes of coronary revascularization, myocardial infarction, and cardiac death during a follow-up period of 25 +/- 19 months. Patients who underwent early elective revascularization had poorer exercise tolerance and more thallium image abnormalities than those with no events. In the remaining patients myocardial infarction was most closely related to the extent and severity of thallium ischemia (p = 0.0086), whereas cardiac death was associated with abnormal thallium lung uptake (p = 0.0082) and an inability to exercise to 9.6 MET (p = 0.0144). Thus unlike myocardial infarction, cardiac death is best predicted by variables that reflect poor left ventricular function rather than those that indicate ischemia.

Aged↗

Usefulness of exercise SPECT-thallium to detect asymptomatic restenosis in patients who had angina before coronary angioplasty.

The usefulness of exercise single photon emission computed tomography (SPECT)-thallium for detecting asymptomatic restenosis was assessed prospectively in 62 patients with angina before angioplasty, who underwent < or = 6-month re-angiography and exercise SPECT-thallium imaging. Among patients with restenosis, nine had recurrence of angina but eight did not. These two subgroups had equivalent percentages of restenosis (71 +/- 16% vs 64 +/- 16%, NS) and extent of reversible thallium defects (2.8 +/- 1.7 vs 4.1 +/- 2.6, NS), and both subgroups had poorer hemodynamic responses to exercise compared with patients without restenosis (maximal) rate-pressure product [X 100], 258 +/- 54 and 239 +/- 33 vs 302 +/- 61; p < 0.05 and p < 0.01, respectively). Exercise testing detected fewer patients with restenosis compared to exercise SPECT-thallium imaging, especially among asymptomatic patients (25% vs 100%, p < 0.005). Asymptomatic restenosis occurs frequently, induces an amount of stress ischemia equivalent to that of symptomatic restenosis, and is efficiently detected by exercise SPECT-thallium with rest-reinjection but not by exercise testing.

Aged↗

Biplane transesophageal pacing echocardiography compared with dipyridamole thallium-201 single-photon emission computed tomography in detecting coronary artery disease.

TPE is a new diagnostic technique that uses simultaneous graded transesophageal left atrial pacing and biplane transesophageal echocardiography for the detection of pacing-induced wall motion abnormalities. In a prospective study 30 patients underwent biplane TPE, dipyridamole thallium-201 single-photon emission computed tomography (SPECT), and coronary arteriography. The sensitivity (86% vs 95%, p = not significant [NS]), specificity (89% vs 56%, p = NS), positive predictive value (95% vs 73%, p = NS), and negative predictive value (83% vs 83%, p = NS) of biplane TPE and thallium-201 SPECT in identifying patients with significant coronary artery disease was similar. In the 90 vascular territories analyzed, the agreement between biplane TPE and thallium-201 SPECT for presence or absence of significant disease was 71%. Analysis of the three major vascular territories demonstrated that each imaging modality had a high sensitivity and specificity in the left anterior descending and right coronary artery segments. However, the two techniques demonstrated poorly sensitivity in the segmental distribution of the circumflex coronary artery. In conclusion, biplane TPE compared favorably with thallium-201 SPECT in terms of safety and accuracy for detecting significant coronary artery disease. Accordingly, biplane TPE may be a suitable alternative for those patients with nondiagnostic thallium-201 SPECT studies and in those with contraindications to adenosine or dipyridamole.

Aged↗

Correlation of adenosine echocardiography and thallium scintigraphy.

Echocardiography and thallium-201 imaging with coronary vasodilators such as dipyridamole have been shown to be useful in detecting the presence and prognostic significance of coronary artery disease. Adenosine, a potent and direct coronary vasodilator, has a shorter physiologic half-life than dipyridamole, which exerts its effect by blocking the cellular uptake of adenosine. Because of the potential advantage of dipyridamole, we undertook this study to determine the correlation of adenosine echocardiography with thallium scintigraphy. Forty-two patients (18 men and 24 women; mean age 64) who were unable to undergo treadmill exercise and were known or suspected to have coronary artery disease were studied. A baseline echocardiogram was obtained in four standard views followed by adenosine infusion at a rate of 140 micrograms/kg/min for 6 minutes. Thallium-201 was administered 3 minutes into the infusion while a second echocardiogram was performed. Thallium-201 imaging was begun immediately after the infusion of adenosine and repeated 4 hours later. Sixteen patients underwent coronary angiography within 1 month of the adenosine echocardiogram and thallium-201 study. At the peak infused dose of adenosine there was a significant increase in heart rate (12 beats/min; p = 0.0001) and rate-pressure product (1.3 x 10(3) beats/min x mm Hg; p = 0.02) and statistically insignificant decreases in systolic and diastolic blood pressures. Sixty-two percent of patients experienced side effects during the adenosine infusion, with chest pain, shortness of breath, and flushing occurring most frequently. These side effects resolved within 1 to 2 minutes after the infusion was stopped. Ischemic electrocardiographic changes occurred in 19% of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗