A bull's eye subtraction polar map for assessing thallium redistribution (1). Comparison with quantitative redistribution

A new bull's eye subtraction polar (BS) map has been developed for quantitative assessment of redistribution on stress-delayed thallium-201 SPECT studies. BS map was created after subtraction of a normalized stress bull's eye polar map from a normalized delayed polar map in 10 normal subjects and 33 patients with coronary artery disease to compare BS map with qualitative redistribution scores. The BS map showed less than 15% in all of the 50 segments in the normal subjects. Of 27 segments exhibiting persistent defect without redistribution, the BS map showed less than 10% in 20 segments (74%) and 10-15% in 6 segments (22%). On the other hand, of 34 segments exhibiting redistribution, the BS map showed greater than or equal to 15% in 25 segments (74%) and 10-15% in the remaining 9 segments (26%). Thus, significant redistribution was evident in the areas showing greater than or equal to 10-15% on the BS map. We conclude that the BS map is valuable for quantitative assessment of redistribution on stress-delayed thallium-201 SPECT imaging.     

Postmortem redistribution of THC in the pig

To improve the knowledge of the postmortem redistribution of Δ⁹-tetrahydrocannabinol (THC), an animal model using the Large White pig has been developed, whereby 15 pigs received an intravenous injection of THC (200 µg/kg body weight) and were euthanized 2 h after administration. An autopsy was performed on three pigs immediately after being euthanized while the others were stored in supine position at ambient temperature for 6, 15, 24, or 48 h. THC concentration in blood from the vena cava decreased after death whereas left or right cardiac blood concentrations increased. No blood specimens collected from different sites of the carcasses adequately reflected the perimortem THC concentrations. The highest concentrations of THC at anytime were observed in lung tissue, and brain tissue seemed to present the most stable concentrations over time. This study can assist toxicologists in determining which specimens can, most appropriately, be used for interpretation of cannabinoid concentrations in postmortem specimens.     

Postmortem distribution and redistribution of synthetic cathinones

Purpose

Synthetic cathinones are powerful psychostimulants that have been associated with fatal intoxications. Because of changes that take place following death, postmortem toxicology results require careful interpretation. The purpose of this study was to evaluate the distribution of synthetic cathinones in postmortem specimens in a series of 50 cathinone-positive fatalities.

Methods

Liquid chromatography–quadrupole time-of-flight-mass spectrometry was used to quantitatively identify cathinones in central blood (n = 51), peripheral blood (n = 31), urine (n = 33), liver (n = 22), vitreous humor (n = 1) and stomach contents (n = 1). The distribution of cathinones and the potential for postmortem redistribution was assessed.

Results

Among the 50 cases investigated, a total of nine synthetic cathinones (α-PVP, ethylone, methylone, butylone, MDPV, methedrone, pentylone, 4-MEC, and MDPBP) were identified in 139 specimens. The number of specimens per case ranged from one to six. In cases that included central blood or liver, together with a peripheral blood source, the central/peripheral (C/P) or liver/peripheral (L/P) ratio was calculated to estimate the potential for postmortem redistribution (n = 21 C/P; n = 11 L/P). Methylone and ethylone appeared to exhibit the greatest potential for postmortem redistribution, producing C/P ratios of 4.0 (1.5–6.1) and 2.9 (0.5–9.2), respectively. In contrast, the C/P ratio for α-PVP was 1.1 (0.5–1.9). Differences in C/P ratios between methylone and α-PVP were statistically significant (α = 0.05).

Conclusions

Although synthetic cathinones may exhibit low to moderate postmortem redistribution, significant variability exists due to site- and time-dependent factors. This, in combination with their overall instability, necessitates careful interpretation of postmortem toxicology results.

     

Reverse redistribution: Revisited with myocardial contrast echocardiography

The aim of this study is to better understand the pattern and nature of reverse redistribution (RR) in myocardial perfusion imaging. In 20 consecutive acute myocardial infarction (MI) patients, frequency of RR was correlated with that of subendocardial MI that was detected by myocardial contrast echocardiography (MCE). RR was judged to be present when there was more than one grade of worsening in perfusion on 24 hr delayed images compared with the initial rest images. MCE evaluated no opacification in the subendocardial myocardium to suggest subendocardial MI. Kendall's nonparametric correlation coefficiency was calculated. Concordant cases were 15 of 20 (75%) and correlation was statistically significant (p = 0.0285). Our results suggested that RR was correlated with MCE-detected nontransmural MI.     

Post-mortem redistribution of three beta-blockers in the rabbit

To consider the role of the physico-chemical properties of drugs in their post-mortem redistribution, we designed the present study to investigate the influence of lipophilicity using an experimental rabbit model. Three beta-blockers (BB), atenolol, metoprolol and propranolol, with a similar dissociation constant (pK _a) and increasing partition coefficient (K _p) were administered intravenously to 18 rabbits. One hour after the last administration, the animals were killed by thiopental injection and placed in a supine position at room temperature. Autopsies were performed at 0, 2, 6, 12, 24 and 48 h post-mortem. Concentrations of the three BB were determined in fluids (right and left cardiac blood, peripheral blood, urine, bile, stomach content, vitreous humour) and tissues (cardiac muscle, lungs, liver, brain, diaphragm, iliopsoas muscle) using a previously published, validated liquid chromatography–electrospray–mass spectrometry method. Our results show that lipophilicity influences post-mortem redistribution of the molecules in a certain number of anatomical sites such as the stomach, lungs, cardiac muscle, cardiac blood or liver, but does not appear to intervene in other sites such as the brain or the vitreous humour.Electronic supplementary material Supplementary material is available in the online version of this article at and accessible for authorised users.This work was presented in part at the 40th International Meeting of The International Association of Forensic Toxicologists, 26–30 August 2002, Paris, France, and at the 11th Annual Meeting of the Société Française de Toxicologie Analytique, 11–13 June 2003, Dinard, France.     

Effect of ribose on thallium-201 myocardial redistribution

Myocardial 201Tl redistribution after transient ischemia may be too slow to allow identification of a reversible myocardial defect within the routine 201Tl imaging period. To determine whether 201Tl redistribution could be affected by a metabolic intervention, intravenous ribose was administered postischemia. Seventeen domestic swine were subjected to a 10-min ischemic period followed by either a 30-min i.v. ribose (n = 8) or saline (n = 9) infusion. Thallium-201 was injected during ischemia and myocardial 201Tl activity was continuously monitored in ischemic and nonischemic regions with miniature CdTe radiation detection probes. Coronary flow in the ischemic region was reduced to 25% of that in the nonischemic regions in both saline and ribose groups. The 201Tl time-activity curves demonstrated a significant enhancement of % 201Tl redistribution in the ribose-treated animals at the end of ribose infusion: Ribose (48 +/- 11%), Saline (20 +/- 4%), p less than 0.05. Alteration of 201Tl kinetics by ribose may permit earlier recognition of 201Tl myocardial redistribution after transient ischemia.     

Autoradiographic analysis of iodoamphetamine redistribution in experimental brain ischemia

The pathophysiologic significance of iodoamphetamine (IMP) redistribution was analyzed using a double radionuclide autoradiography technique in experimental brain ischemia in the rat. Within 4 hr after unilateral arterial occlusion, IMP almost completely redistributed at 150 min postinjection in the affected areas. At 2 min postinjection, both a remarkable decrease of IMP accumulation and histopathologic change of diminished staining were observed in these areas. The redistribution amplitude was higher in the affected hemisphere, especially in the regions surrounding the ischemic core than in the unaffected hemisphere. These findings were consistent with computer simulation studies of the time course of brain activity based on the standard diffusible tracer model. The results suggest that IMP redistribution in the ischemic area is due to differences of the temporal changes of the brain activity between the unaffected and affected areas and that it is a "physical" phenomenon (only flow related) rather than a "biologic" one.     

201Tl-reverse redistribution in a case with stunned myocardium

A 58-year-old man was admitted to our hospital because of chest pain. Electrocardiogram showed giant negative T waves in leads I, II, III, aVl, aVf and V2 through V6. Echocardiogram showed anterior wall motion abnormality. Rest-redistribution thallium scan obtained 3 days after admission revealed reverse redistribution in antero-apical area. Coronary angiogram showed no significant stenotic lesions and left ventriculogram in chronic stage showed improvement of wall motion abnormality. Repeat thallium scan in chronic stage showed disappearance of perfusion defect in apical area. It was difficult to diagnose myocardial viability in our case with stunned myocardium because rest-redistribution thallium scan showed reverse redistribution. As the mechanism of this finding, early coronary recanalization in acute stage of the event was suspected.     

Genotype-dependent radiosensitivity: clonogenic survival, apoptosis and cell-cycle redistribution

PURPOSE: We describe variations of three radiation-induced endpoints on the basis of cell genotype: Clonogenic survival, expression of apoptosis and cell-cycle redistribution. METHODS: Clonogenic survival, apoptosis and cell-cycle redistribution are measured in multiple cell lines after exposure to radiation between 2 and 16 Gy. Cell lines varied in clonogenic radiosensitivity and expression of specific genes. RESULTS: Clonal radiosensitivity is genotype-dependent, associating with four specific genes: A mutated form of Ataxia telangiectasia mutated (mutATM); with two forms of TP53, the gene that is template for tumor protein p53, wildtype TP53 (wtTP53) and mutated TP53 (mutTP53); and an unidentified gene in radioresistant glioblastoma cells. Apoptosis is also genotype-dependent showing elevated levels in cells that express mutATM and abrogated 14-3-3sigma (an isoform of the 14-3-3 gene) but less variation for different forms of TP53. Cell-cycle redistribution varied in mutATM cells. Kinetics of apoptosis are biphasic for both time and dose; cell lines did not express apoptosis at doses below 5 Gy or times before 24 hours. Kinetics of cell-cycle redistribution changed dynamically in the first 24 hours but showed little change after that time. CONCLUSIONS: Clonogenic survival, radiation-induced apoptosis and radiation-induced redistribution in the cell-cycle vary with cell genotype, but not the same genotypes. There is temporal, not quantitative, correlation between apoptosis and clonal radiosensitivity with apoptosis suppressed by lower, less toxic doses of radiation (<5 Gy) but enabled after larger, more toxic doses. Kinetic patterns for apoptosis and redistribution show a common change at approximately 24 hours.     

Myocardial redistribution of technetium-99m-methoxyisobutyl isonitrile (SESTAMIBI)

To determine whether technetium-99m-hexakis-2-methoxyisobutyl isonitrile (SESTAMIBI) remains fixed in the myocardium following its initial uptake or undergoes time-related redistribution, anesthetized dogs underwent occlusion of the anterior descending coronary artery for 6 min, followed by 3-hr reperfusion. Technetium-99m-SESTAMIBI and thallium-201 (201Tl) were injected intravenously after 1 min occlusion and regional myocardial blood flow was measured with radioactive microspheres. Tomographic imaging of Tc-SESTAMIBI revealed a perfusion defect with slight but definite filling in over 2 hr. Quantitative analysis indicated a significant rise in the nadir and decrease in the width of the defect in circumferential profile curves. After 3-hr of reperfusion, Tc-SESTAMIBI activity in the previously ischemic area was always greater than the activity of microspheres injected during coronary occlusion (mean normalized values, 0.32 versus 0.11, p less than 0.0001). Our results indicate that following transient ischemia and reperfusion, Tc-SESTAMIBI clearly undergoes myocardial redistribution, although more slowly and less completely than 201Tl.