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Particulate matter (PM) and its harmful components are significant contributors to respiratory diseases and impaired lung function, especially in children. Club cell secretory protein (CC16) is a maker of lung epithelium or club cell injuries. To date, the relationship between metals related with PM and CC16 and lung function impairment has been overlooked in children. We enrolled 603 schoolchildren exposed to different levels of PM in China. We found per doubling increase, urinary thallium, and iron was associated with a 3.42 % (95 % CI: 0.01, 6.72) and 3.09 % (95 % CI: 0.55, 5.56) decrease of serum CC16, respectively, whereas urinary cadmium was associated with a 4.74 % (95 % CI: 1.29, 8.31) increase of serum CC16. The Bayesian kernel machine regression (BKMR) model confirmed these associations and showed a potential synergistic interaction between thallium and cadmium. Urinary metal mixtures were associated with lower CC16 when they were below the 35th percentile compared with their median. Serum CC16 mediated 11.47 % (95 % CI: 0.06, 45.00) of the association between urinary thallium and FEV 1 /FVC decline. The inverted U-shaped association with CC16 and the mediation role of CC16 on associations with lung function provide insight into the mechanisms underlying lung injury induced by metals related with PM., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Thallium is a highly toxic metal, with most publications demonstrating poisoning from thallium salts. We report on a patient with elevated serum and urine thallium concentrations from an intentional ingestion of elemental thallium purchased from the internet for self-harm., Case Report: The regional poison center was contacted about an 18-year-old man who ingested a fragment from a 100-gram bar reported to be elemental thallium. Serial serum and urine thallium concentrations were obtained. Prussian blue was started on hospital day (HD) 2. A metal fragment was seen on abdominal x-ray and removed via colonoscopy on HD3. The ingested fragment was analyzed via inductively coupled plasma mass spectrometry (ICP-MS) and found to be 87.0% elemental thallium. The initial serum thallium concentration obtained on HD1 was 423.5 mcg/L (reference range < 5.1 mcg/L), which subsequently decreased to 4.5 mcg/L, 29 days after the ingestion. An initial random urine thallium concentration obtained on HD 3 was 1850.5 mcg/g creatinine (reference range < 0.4 mcg/g creatinine). The patient remained hospitalized for 23 days and, when seen in follow-up, had not developed any signs or symptoms of thallium toxicity., Discussion: Elemental thallium ingestion is a rare toxicologic exposure, with limited published clinical and analytical experience to guide management. This case report describes a patient with ingestion of elemental thallium who developed elevated serum and urine thallium concentrations and was treated with Prussian blue. Despite having elevated serum and urine thallium concentrations consistent with previous fatal exposures, more evidence is needed to understand the differences between elemental thallium and thallium salts., (© 2024. The Author(s).)

In our study, blood concentrations of lead (Pb), arsenic (As), and cadmium (Cd) and urine concentrations of thallium (Tl) were measured together with related symptoms of heavy metal poisoning in cigarette smoking volunteers diagnosed with schizophrenia, in cigarette smokers not diagnosed with schizophrenia, and in the control group of non-smokers and not diagnosed with schizophrenia volunteers. Our study was performed on 171 volunteers divided into the following subgroups: patients diagnosed with schizophrenia with at least 1 year of continuous cigarette smoking experience (56 participants), cigarette smokers not diagnosed with schizophrenia with at least one year of continuous smoking experience (58), and control group (not diagnosed with schizophrenia and non-smoking volunteers) (57). Smoking durations of cigarette smokers diagnosed with schizophrenia and cigarette smokers not diagnosed with schizophrenia are not similar (p = 0.431). Blood Pb, As, and Cd concentrations and urine Tl concentrations were the highest in the subgroup of cigarette smokers not diagnosed with schizophrenia, followed by the subgroup of cigarette smokers diagnosed with schizophrenia, and the control group. Only blood Pb concentrations were significantly higher (probability value p < 0.05) in the group of cigarette smokers not diagnosed with schizophrenia (5.16 μg/dL), comparing to the group of cigarette smokers diagnosed with schizophrenia (3.83 μg/dL) and to the control group (3.43 μg/dL). Blood Cd and As concentrations and urine Tl concentrations were significantly higher (p < 0.05) in cigarette smokers not diagnosed with schizophrenia than in the control group. The results revealed a statistically significant positive correlation (p < 0.001) in the cigarette smokers in the schizophrenia diagnosed group between blood Pb, blood As, and urine Tl concentrations and the duration of cigarette smoking., (© 2024. The Author(s).)

Several studies have suggested an association between exposure to various metals and the onset of type 2 diabetes (T2D). However, the results vary across different studies. We aimed to investigate the associations between serum metal concentrations and the risk of developing T2D among 8734 participants using a prospective cohort study design. We utilized inductively coupled plasmamass spectrometry (ICP-MS) to assess the serum concentrations of 27 metals. Cox regression was applied to calculate the hazard ratios (HRs) for the associations between serum metal concentrations on the risk of developing T2D. Additionally, 196 incident T2D cases and 208 healthy control participants were randomly selected for serum metabolite measurement using an untargeted metabolomics approach to evaluate the mediating role of serum metabolite in the relationship between serum metal concentrations and the risk of developing T2D with a nested casecontrol study design. In the cohort study, after Bonferroni correction, the serum concentrations of zinc (Zn), mercury (Hg), and thallium (Tl) were positively associated with the risk of developing T2D, whereas the serum concentrations of manganese (Mn), molybdenum (Mo), barium (Ba), lutetium (Lu), and lead (Pb) were negatively associated with the risk of developing T2D. After adding these eight metals, the predictive ability increased significantly compared with that of the traditional clinical model (AUC: 0.791 vs. 0.772, P=8.85×10 -5 ). In the nested casecontrol study, a machine learning analysis revealed that the serum concentrations of 14 out of 1579 detected metabolites were associated with the risk of developing T2D. According to generalized linear regression models, 7 of these metabolites were significantly associated with the serum concentrations of the identified metals. The mediation analysis showed that two metabolites (2-methyl-1,2-dihydrophthalazin-1-one and mestranol) mediated 46.81% and 58.70%, respectively, of the association between the serum Pb concentration and the risk of developing T2D. Our study suggested that serum Mn, Zn, Mo, Ba, Lu, Hg, Tl, and Pb were associated with T2D risk. Two metabolites mediated the associations between the serum Pb concentration and the risk of developing T2D., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The aim of this paper is to study the clinical features of severe intoxications with thallium salts and developing effective care schemes for the application of potassium hexacyanoferrate (II) and deferasirox for correction of detected disorders. A total of 39 patients diagnosed with severe thallium salt poisoning were examined in two groups. Group I comprised 20 patients with severe thallium salt poisoning, who were prescribed with potassium-iron hexacyanoferrate in a dose of 250 mg/kg/day per os, intravenous potassium infusions, furosemide intravenously in amount of 40 mg three times per, and hemodialysis until the thallium level in the blood dropped below 10 mg/L, lactulose 30 mL two times per day per os. Group II consisted of 19 people with severe thallium salt poisoning, which in addition to the above treatment, received Deferasirox in a dosage of 500 mg two times per day per os. The clinical picture of severe poisoning with thallium salts is characterized by lesions of the gastrointestinal tract, nervous system (central and peripheral), alopecia, heart rhythm disorders, and myocardial ischemia zones. Extension of standard therapy with potassium-iron by adding hexacyanoferrate deferasirox showed better effect on thallium elimination rate and improved functional state of liver and kidneys in patients with severe thallium salt poisoning.

The simultaneous detection of K + and Tl + can serve as a toxicological diagnostic tool for thallium poisoning. Colorimetric-reaction-based nanoprobes have emerged as promising sensors for the rapid and ultrasensitive detection of molecular species in simple systems. However, the development of viable screening tools for multicomponent analysis in complex systems remains challenging owing to interference from coexisting materials in the media. Herein, a simple chemical sensor array based on the peroxidase-like activity of gold nanoparticles modified with single-stranded DNA (AuNPs-ssDNA) and chemometrics was developed for the simultaneous detection of K + and Tl + in aqueous solutions and serum. The use of a K + adapter conferred high selectivity to the developed method. Optimized AuNPs-ssDNAs were used to construct a sensor array, which together with chemometrics provided fingerprints that can facilitate the simultaneous analysis of multiple components. The developed colorimetric reaction in combination with the chemometrics assay was directly used as a biosensor array, which exhibited detection limits of 107.33 nM for K + and 19.26 nM for Tl + . The developed method could potentially serve as a diagnostic technique for investigating thallium poisoning and toxicology., Competing Interests: Declaration of competing interest No conflict of interest exits in the submission of this manuscript, and manuscript is approved by all authors for publication. I would like to declare on behalf of my co-authors that the work described was original research that has not been published previously, and not under consideration for publication elsewhere, in whole or in part. All the authors listed have approved the manuscript that is enclosed., (Copyright © 2020. Published by Elsevier B.V.)

Context: Heavy metals, including thallium and lead, are introduced to illicit drug users' body as a result of using drugs such as cocaine and heroin., Objective: This study aimed to determine urine, blood, and hair thallium (Tl) concentrations in illicit opioid users along with the relevant clinical signs and symptoms consistent with thallotoxicosis and to compare them with the corresponding variables in the control non-opioid user group., Materials and Methods: This case-control study was conducted on 50 illicit opioid users who had abused opioids continuously for more than a year, referred to Amirie Drug Abuse Treatment Clinic in Kashan, Iran. The control group included 50 non-opioid users. Thallium concentrations in urine, blood, and hair were assessed in both groups ( n = 100) using electrothermal (graphite furnace) atomic absorption spectrometry (ET AAS, GF AAS)., Results: In the studied group, the median (interquartile range) concentrations of thallium in urine, blood, and hair were 54.8 ± 79.9 μg/L, 14.5 ± 11.1 μg/L, and 5.4 ± 3.7 µg/g, respectively; these values were 4.8 ± 5.2 μg/L, 2.5 ± 2.4 μg/L, and 1.4 ± 1.1 µg/g, respectively, in the control group. There were significant differences in urine, blood, and hair thallium concentrations between the study group and the control group ( p < 0.001). There were significant correlations between duration of illicit opioid use and urine thallium concentrations ( r = 0.394, p = 0.005) and hair thallium concentrations ( r = 0.293, p = 0.039), but not with blood thallium concentrations ( r = 0.246, p = 0.085). Urine and blood thallium concentrations of illicit opioid users with clinical signs and symptoms consistent with thallotoxicosis of weakness ( p = 0.01), depression ( p = 0.03), and headache ( p = 0.03) were higher than users without these problems., Discussion and Conclusion: The results of the study showed that thallium concentrations in urine, blood, and hair in illicit opioid users were significantly higher than the comparable concentrations in the control group. This can be due to the use of illicit opioids adulterated with thallium. Also, this study showed long-term illicit opioid use may lead to thallium exposure. In addition, cigarette smoking was associated with increased thallium exposure.

Thallium (Tl) is a highly toxic heavy metal that has been suggested to be responsible for oxidative stress and mitochondrial dysfunction. However, few studies have focused on the relationship of prenatal Tl exposure with children's neurobehavioural development. The purpose of our study was to investigate the association between prenatal Tl exposure and attention-deficit/hyperactivity disorder (ADHD) symptoms in 36-month-old children. We used data from 2851 mother-newborn pairs from the Ma'anshan Birth Cohort Study (MABC); serum Tl concentration was assessed in the first, second and third trimesters of pregnancy as well as in the umbilical cord blood. We assessed ADHD symptoms in the children using the Chinese version of the Conners abbreviated symptom questionnaire (C-ASQ). The adjusted odds ratio (OR) for the risk of ADHD symptoms was 2.00 [95% confidence interval (CI): 1.20, 3.32] and 2.08 (95% CI: 1.26, 3.43) for the third (60.25-75.21 ng/L) and fourth quartiles of serum Tl (>75.21 ng/L), respectively, in the second trimester of pregnancy, in comparison with the first quartile of serum Tl (<50.86 ng/L). The risk of ADHD symptoms was elevated among boys exposed to the fourth quartile of serum Tl in the second trimester of pregnancy (adjusted OR 2.08, 95% CI: 1.13, 3.83). Our results demonstrated that high levels of Tl exposure in the second trimester of pregnancy were related to a higher risk of ADHD symptoms in 36-month-old children, and the association of higher serum Tl exposure in the second trimester with ADHD symptoms was only found in boys., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Platelet-rich fibrin (PRF) is widely used blood-derived biomaterial which is directly applied to the surgical wounds. Depending on its autologous origin, PRF is thought as a safe material. However, it is not known to what extent the blood-derived toxins can be found in the PRF by considering the systemic exposure rates of the individuals to the toxins. The aim of this pilot study was to test the hypothesis whether PRF contains any blood-origin heavy metals (HMs) and smoking increases their concentrations as an environmental HM source. PRF samples were obtained from systemically healthy 30 non-smoker and 30 smoker volunteers. All liquid and dry fibrin parts of the PRF samples were analyzed in terms of 15 toxic elements using inductively coupled plasma mass spectrometry. All analyzed HMs were detected in all investigated PRF samples within various concentrations in both groups. In addition, significantly high levels of cadmium, arsenic, lead, manganese, nickel, chromium, and vanadium were detected in dry fibrin matrices of PRF samples of smokers comparing with non-smokers (p < 0.05). Only cadmium was at significantly high levels in the liquid part of PRF samples of smokers (p < 0.05). This is the first study evaluating toxic ingredients of PRF. The results revealed that PRF contains various toxic HMs. Additionally, systemic exposure to environmental HM sources such as smoking may significantly increase HM concentrations in PRF. Further studies are required to investigate the transmission potentials of HMs to the applied tissues and biological importance of PRF-origin HMs.

Thallium is highly toxic and its effects are cumulative. The clinical symptoms of thallium poisoning are non-specific, thereby delaying admission and treatment. This study aimed to summarize the clinical features and treatment experience of patients with delayed admission who experience thallium poisoning.We conducted a retrospective descriptive analysis of patients in our hospital from 2008 to 2018 who had thallium poisoning and experienced a delay in hospital admission. The time from symptom onset to admission was assessed. The patients were divided into 3 groups and descriptive analyses of their clinical characteristics, including basic patient information, symptoms, laboratory test results, examination findings, treatment methods, outcomes, and follow-up information, were conducted.A total of 34 patients with thallium poisoning were included: 8 were admitted to the hospital early or with mild delay, 9 had a moderate delay, and 17 had a severely delayed admission. The time from illness onset to admission was 13 (interquartile range, 7.5-26) days. Some patients with delayed admission had significant symptoms associated with central nervous system damage, and changes in magnetic resonance images and electroencephalograms were also noted. After admission, all patients received Prussian blue treatment, and some patients with relatively high blood concentration received blood purification treatments. Following treatment, the blood and urine thallium concentrations of all patients decreased significantly, and their symptoms were alleviated.Our results show that delayed patient admission in cases of thallium poisoning is associated with greater risk of central nervous system damage. Use of Prussian blue combined with blood purification treatments might improve patients' conditions.

Assessment of trace element levels in general population from the specific area is of importance for nutritional and occupational monitoring. In the current study, baseline blood levels of 12 toxic and/or essential metals and metalloids, including arsenic (As), cadmium (Cd), lead (Pb), mercury (Hg), chromium (Cr), thallium (Tl), manganese (Mn), copper (Cu), Zinc (Zn), calcium (Ca), iron (Fe), and magnesium (Mg), in general populations (n = 477) of Wuhan in central China were investigated by using inductively coupled plasma mass spectrometry (ICP-MS). The geometric means for As, Cd, Pb, Hg, Cr, Tl, Mn, and Cu were measured as 2.25, 0.70, 17.84, 1.90, 0.36, < 0.05, 12.40, and 783.76 μg/L, respectively. The geometric means for Zn, Ca, Fe, and Mg were 5.85, 56.66, 488.98, and 39.44 mg/L, respectively. We found the men had higher blood As, Pb, Hg, Zn, Fe, and Mg levels but had lower blood Cu and Ca levels than the women (p < 0.05). Age-related difference were found for blood Cu, Zn, Ca, Mg, Pb, Mn, As, Cd, and Hg levels (p < 0.05). Moreover, many metal concentrations were found correlated, with the strongest correlations between the pairs Fe-Mg (r = 0.57), Fe-Zn (r = 0.42), As-Hg (r = 0.46), Ca-Cu (r = 0.34), Pb-Hg (r = 0.36), Pb-Cd (r = 0.31), Pb-As (r = 0.25), and Ca-Fe (r = - 0.23). Compared with reports from other countries, most of our results were consistent, except that As Pb, Hg, Mn, and Cu showed different blood levels with European, Korea, or Beijing areas. Our study would be of importance for nutritional, environmental, and/or occupational monitoring of these metals in human.

Background: High blood glucose has been noted in case reports of acute thallium poisoning, however, effects of low-level exposure of thallium on risk of gestational diabetes mellitus (GDM) has not been explored yet., Objectives: We aimed to explore the association of serum thallium concentration (STC) in early pregnancy and risk of GDM., Methods: Data of 3013 women from the Ma'anshan birth cohort study (MABC), China was used. STC was measured by inductively coupled plasma mass spectrometry (ICP-MS). Multivariate logistic regression was performed to the association of STC and risk of GDM. Stratified analysis was carried out according to maternal age and pre-pregnancy BMI., Results: We documented 383 incident GDM (12.7%). The STC ranged from 0.011 to 0.232 μg/L with a median of 0.062 μg/L. Women with advanced age and higher pre-pregnancy BMI tended to have higher level of STC. Individuals in GDM-group have higher level of STC than that in non-GDM group (P =  0.007). Maternal STC in early pregnancy was associated with risk of GDM, but the association attenuated to non-significance after adjusted for pre-pregnancy BMI. In the advanced age (>30 years) group, STC was significantly associated with risk of GDM in a dose-response manner (P for trend <0.05). Compared with the Quintile 1, the odds ratios (ORs) (95% confidence interval, CI) of Quintile 2, Quintile 3, Quintile 4, and Quintile 5 were 1.48 (0.62-3.53), 2.70 (1.21-6.03), 2.85 (1.29-6.31), 2.30 (1.05-5.05) in the most adjusted model (including pre-pregnancy BMI)., Conclusions: Our study was the first study to demonstrate an association of maternal STC in early pregnancy and risk of GDM, and the association was partly mediated by pre-pregnancy BMI. This association exhibited as an age-dependent manner. Our study highlights even very low-level of thallium exposure could already pose a threat to human's health., (Copyright © 2018 Elsevier GmbH. All rights reserved.)

Rationale: This is the first reported severe thallium poisoning patient successfully treated with Prussian blue (PB) and plasma exchange (PE)., Patient Concerns: A 42-year-old woman in a coma owing to severe thallium poisoning was admitted to our department after day 44 of poisoning. At admission, blood and urine thallium concentrations were 380.0 and 2580.0 ng/mL, respectively., Diagnosis: The patient was diagnosed with toxic encephalopathy induced by thallium poisoning; in addition, she was also diagnosed with bilateral pneumonia, respiratory failure, moderate anemia, hypoproteinemia, and electrolyte imbalance based on her chest X-ray, blood gas analysis, Hb level, albumin levels, and serum electrolyte results., Interventions: The patient was intubated and treated with PB (6600 mg/d, 15 days in total) combined with PE (once daily, 5 days in total) as well as other symptomatic supportive care measures., Outcomes: After treatments, her blood and urinary thallium concentrations gradually decreased and on the 13th day after admission, the blood thallium concentration decreased to 0 ng/mL. The oxygenation index gradually improved, meantime, the patient gradually regained consciousness, and on the 50th day of admission, the patient's consciousness reverted to a clear-headed state. The patient recovered mostly after 37 months of follow-up., Lessons: Through this case, we learned that the gradual reduction in blood and urine thallium concentration and the patient's improved condition is correlated with PB and PE treatment. For patients with severe thallium poisoning, this treatment method might be effective; but the exact curative effect is unconfirmed, requiring further research to verify.

Objective: To investigate the relationship of thallium exposure and outcomes of births. Methods: A total of 3 236 mothers who had visited in Ma'anshan Maternal and Child Health-Care Hospital between May 2013 and September 2014 were included in this study and their thallium concentrations measured from samples of maternal and umbilical cord blood by inductively coupled plasma mass spectrometry. The results were correlated and evaluated with birth outcomes of the infants, using the multiple linear regression method. Results: The median ( P(25) - P(75) ) of thallium levels in first trimester, second trimester and umbilical cord blood were 61.7 (50.8-77.0), 60.3 (50.8-75.2) and 38.5 (33.6-44.1) ng/L, respectively. After adjustment for potential confounders, the thallium levels showed an inversely significant association with birth head circumference (unstandardized β coefficient=-0.41, 95 %CI : -0.76- -0.06) in the first trimester blood, and associated with reduced birth length (unstandardized β coefficient=-0.65, 95 %CI : -1.25- -0.05) in umbilical cord blood. However, there appeared no significantly associations with birth weight, length and head circumference ( P >0.05) in second trimester. On stratification by sex, in girls but not in boys, the thallium levels were adversely associated with birth head circumference (unstandardized β coefficient=-0.53, 95 %CI : -1.05--0.01) in the first trimester and were associated with decreased birth weight (unstandardized β coefficient=-277.08, 95 %CI : -485.13- -69.03) and length (unstandardized β coefficient=-1.39, 95 %CI : -2.26- -0.53) in umbilical cord blood thallium. Conclusions: Thallium exposure appeared a gender difference in newborn birth outcomes. In the first trimester, it was negatively associated with the birth head circumference, in the umbilical cord blood, and reduced birth weight and length in girls.

To follow time trends in exposure to environmental chemicals, three successive campaigns of the Flemish Environment and Health Study (FLEHS) have recruited and sampled in total 5825 participants between 2002 and 2014. Cord samples from newborns, urine and blood samples from 14 to 15 years old adolescents and from adults between 50 and 65 years old were analysed in geographical representative samples of the Flemish population. The data of the different campaigns were considered per age group and per biomarker after adjustment for predefined covariates to take into account differences in characteristics of the study populations over time. Geometric means were calculated. Multiple linear regression was used to evaluate time trends. The concentration of serum biomarkers for persistent organic pollutants (POPs), such as marker polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethylene (p,p'-DDE), the major metabolite of dichlorodiphenyltrichloroethane (DDT), and hexachlorobenzene (HCB) expressed per g lipid, decreased significantly with time. The levels of DDE in all age groups and those of PCBs in cord and adolescent serum samples were almost halved in a time period of ten years. HCB levels were reduced by a factor of 4 in adolescents and in adults. Mean serum concentrations of the more recently regulated perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) were significantly lower in cord samples of 2013 compared to samples of 2007. The decline was more pronounced for PFOS than for PFOA. In the same period, mean metabolite levels of di-2-ethylhexyl phthalate (DEHP) and of di-n-butyl phthalate (DBP) decreased significantly in urine samples of adolescents with sharper declines for DEHP than for DBP. Cadmium and lead levels in cord and adolescent blood samples were significantly lower in the recent campaigns than 10 years before. Also the mean urinary cadmium level in adults was 35% lower compared to adult samples of 2002. Such favourable trends were not observed for arsenic and thallium measured in cord blood. Similar, the concentrations of 1-hydroxypyrene, a marker for exposure to polycyclic aromatic hydrocarbons (PAHs), was not lower in urine from adolescents sampled in 2013 compared to 2003. In contrast, concentrations of t,t'-muconic acid, a marker of benzene exposure, showed clearly reduced levels. The FLEHS program shows that concentrations of well-regulated chemicals especially traditional POPs and cadmium and lead are decreasing in the population of Flanders. Response to regulatory measures seems to happen rapid, since concentrations in humans of specific regulated perfluorinated compounds and phthalates were significantly reduced in five years time. Biomarker concentrations for arsenic, thallium, and polyaromatic hydrocarbons are not decreasing in this time span and further follow up is warranted., (Copyright © 2016. Published by Elsevier GmbH.)

Objective: Colloidal palladium was used as chemical modifier in the determination of blood thallium by graphite furnace atomic absorption spectrometry., Methods: Blood samples were precipitated with 5% (V/V)nitric acid, and then determined by GFAAS with colloidal palladium used as a chemical modifier. 0.2% (W/V)sodium chloride was added in the standard series to improve the matrix matching between standard solution and sample., Results: The detection limit was 0.2 μg/L. The correlation coefficient was 0.9991. The recoveries were between 93.9% to 101.5%.The relative standard deviations were between 1.8% to 2.7%.The certified reference material of whole blood thallium was determined and the result was within the reference range Conclusion: The method is accurate, simple and sensitive, and it can meet the needs of detection thallium in blood entirely.

This study aimed to evaluate the influence of exposure to aluminum, nickel, thallium and uranium on the metabolism of essential elements in humans, as well as the relationship between uranium, thallium, nickel, and aluminum and essential elements (Ca, Mg, Zn, Se, Mn, Co, Cr, and Mo) in the whole blood and blood serum of healthy men who were occupationally exposed. This study included 97 healthy men, 31-64 years age, including 70 workers in a thermo power plant and 27 control subjects. The results showed that chronic, moderate exposure of trace elements (Al, Ni, Tl, and U) lead to decreased serum chromium (SCr) and blood molybdenum levels (BMo), whereas by the results achieved in terms of correlations between non-essential and essential elements, non-essential elements such as uranium, thallium, nickel, and aluminum, despite their concentration within the reference values, are strongly competitive with essential elements in biochemical processes.

Thallium poisoning is a rare condition that is often misdiagnosed, delaying appropriate treatment. Left untreated, thallium toxicity can permanently damage the nervous and digestive systems or, in severe cases, lead to paralysis and death. It is most often treated by an oral administration of Prussian blue. Thallium has a long physiological half-life, and Prussian blue cannot sequester thallium outside the digestive tract. Therefore, the first priority in treating severe thallium poisoning is to lower blood levels as soon as possible. We report the case of a patient with supralethal blood levels of thallium treated successfully using combined hemoperfusion (HP) and continuous veno-venous hemofiltration (CVVH). Three rounds of HP alone decreased blood thallium levels by 20.2%, 34.8%, and 32.2%, while each of the five subsequent rounds of CVVH reduced thallium blood levels by 63.5%, 64.2%, 42.1%, 18.6%, and 22.6%. The reversal of symptoms and prevention of lasting neurological damage indicates that HP, CVVH, 2,3-dimercaptopropane-1-sulfonate, neuroprotective agents along with supportive therapy were used successfully to treat a case of severe thallium poisoning.

A new simple, very sensitive, selective and accurate procedure for the determination of trace amounts of thallium(III) by solid-phase spectrophotometry (SPS) has been developed. The procedure is based on fixation of Tl(III) as quinalizarin ion associate on a styrene-divinylbenzene anion-exchange resin. The absorbance of resin sorbed Tl(III) ion associate is measured directly at 636 and 830 nm. Thallium(I) was determined by difference measurements after oxidation of Tl(I) to Tl(III) with bromine. Calibration is linear over the range 0.5-12.0 μg L(-1) of Tl(III) with relative standard deviation (RSD) of 1.40% (n=10). The detection and quantification limits are 150 and 495 ng L(-1) using 0.6 g of the exchanger. The molar absorptivity and Sandell sensitivity are also calculated and found to be 1.31×10(7) L mol(-1)cm(-1) and 0.00156 ng cm(-2), respectively. The proposed procedure has been successfully applied to determine thallium in water, urine and serum samples., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Thallium is a highly toxic compound and is occasionally involved in intentional overdoses or criminal poisonings. Accidental poisonings also occur, but are increasingly rare owing to restricted use and availability of thallium. We report a fatal suicidal ingestion of thallium sulfate rodenticide in which multi-dose activated charcoal (MDAC) and Prussian Blue (PB) were both used without changing the outcome., Case Report: A 36 year old man ingested an unknown amount of thallium sulfate grains from an old rodenticide bottle. He presented to an emergency department (ED) 45 minutes later with abdominal pain and vomiting. On examination he was agitated with a blood pressure of 141/60 mmHg and a heart rate of 146 beats per minute (bpm). He received MDAC during his initial ED management and was started on PB 18 hours post arrival; he was intubated on the following day for airway protection. The patient continued to be tachycardic and hypertensive and subsequently developed renal failure. On hospital day three, the patient developed hypotension that did not respond to fluids. The patient required vasopressors and was transferred to a tertiary care center to undergo continuous renal replacement therapy (CRRT). The patient died shortly after his transfer. His last blood thallium concentration was 5369 mcg/L, a spot urine thallium >2000 mcg/L, and a 24- hour urine thallium was >2000 mcg/L., Conclusion: Though extremely rare, thallium intoxication can be lethal despite early administration of MDAC and use of Prussian blue therapy. Rapid initiation of hemodialysis can be considered in cases of severe thallium poisoning, to remove additional thallium, to correct acid-base disturbance, or to improve renal function.

Determination of aluminum (Al), beryllium (Be), cadmium (Cd), chromium (Cr), mercury (Hg), manganese (Mn), nickel (Ni), lead (Pb), and thallium (Tl) concentrations in human blood using high-frequency modulation polarization Zeeman graphite furnace atomic absorption spectrometry (GFAAS) was performed. No sample digestion was used in the current study. Blood samples were diluted with deionized water or 0.1 % (m/v) Triton X-100 solution for Tl. Dilution factors ranged from 1/5 per volume for Be and Tl to 1/20 per volume for Cd and Pb. For Tl, Cd, and Hg, noble metals (gold, platinum, rhodium, etc.) were applied as surface modifiers. To mitigate chloride interference, 2 % (m/v) solution of NH(4)NO(3) was used as matrix modifier for Tl and Ni assessment. The use of Pd(NO(3))(2) as oxidative modifier was necessary for blood Hg and Tl measurement. Validation of the methods was performed by analyzing two-level reference material Seronorm. The precision of the designed methods as relative SD was between 4 and 12 % (middle of a dynamic range) depending on the element. For additional validation, spiked blood samples were analyzed. Limits of detection (LoDs, 3σ, n = 10) for undiluted blood samples were 2.0 μg L(-1) for Al, 0.08 μg L(-1) for Be, 0.10 μg L(-1) for Cd, 2.2 μg L(-1) for Cr, 7 μg L(-1) for Hg, 0.4 μg L(-1) for Mn, 2.3 μg L(-1) for Ni, 3.4 μg L(-1) for Pb, and 0.5 μg L(-1) for Tl. The LoDs achieved allowed determination of Al, Cd, Cr, Mn, Ni, and Pb at both toxic and background levels. Be, Hg, and Tl could be reliably measured at toxic levels only. The methods developed are used for clinical diagnostics and biological monitoring of work-related exposure.

Objective: To describe the clinical features and management of thallium poisoning in patients with delayed hospital admission., Methods: Fourteen patients (median age 36 years) were admitted 9-19 days after ingesting food poisoned with thallium. Clinical and laboratory data, including blood and urine thallium concentrations, were collected. Patients were treated with oral Prussian blue, a chelating agent sodium dimercaptosulfonate, and hemodialysis., Results: All patients experienced a triad of symptoms of acute gastrointestinal upset, painful combined polyneuropathy, and hair loss after consuming poisoned food. Fatigue and skin pigmentation were observed in all patients. Abnormal liver function tests were found in 6 (42.9%) and delirium and coma were identified in 4 (28.6%). Two weeks after the poisoning, the blood and urine thallium concentration ranged from 219.0 to 1414.4 μg/L (median: 535.3) and 956.5 to 11285.0 μg/L (median: 7460.0), respectively. One patient (7.1%) with a previous history of pulmonary fibrosis died of respiratory failure in hospital. Symptoms were improved and blood or urine thallium levels were normalized in the remaining 13 patients before discharge. After a 6.5 ± 1-month follow-up, 1 patient (7.1%) developed deep venous thrombosis in the left lower limb. In another patient (7.1%), numbness in the lower limbs remained., Conclusion: Acute thallium poisoning is commonly manifested by gastrointestinal upset, painful polyneuropathy, and significant hair loss. Treatment strategies included Prussian blue and hemodialysis, which were associated with a good outcome in this case series.

A 1-year-old dog ingested a mixture of blood agar and Mycoplasma agar plates. The Mycoplasma agar plates contained thallium acetate, which resulted in an estimated minimum dose of 5 mg thallium acetate/kg bodyweight. Clinical signs over the course of 2-3 weeks included vomiting, diarrhea, weight loss, alopecia, dysphonia, ataxia, paresthesia, intension tremors, megaesophagus with subsequent aspiration pneumonia, and several seizure episodes. The dog was treated with intravenous fluids and placement of a gastric feeding tube. Thallium concentrations in hair were 8.2 µg/g in samples taken on day 19, 16.4 µg/g in samples taken 3 months after exposure, 13.4 µg/g in samples taken 5 months after exposure, and nondetectable in samples taken 7 months after exposure. The blood thallium concentration was 190 µg/l on day 19 and nondetec table 3 months after exposure. Megaesophagus and dysphonia continued for 10 months after exposure. This case of thallium poisoning following ingestion of mycoplasma agar plates demonstrates that unusual sources of thallium still exist and suggests that thallium toxicosis should be included in the list of differential diagnoses in dogs presented with megaesophagus, especially if alopecia and other unexplained peripheral neuropathies are present. Hair and blood samples are useful specimens to reach an accurate diagnosis even if taken several weeks post exposure. The postexposure blood and hair thallium concentrations reported in this case are useful data for diagnosticians investigating dogs with potential thallium poisoning.

DL-penicillamine (DL-P) and Prussian blue (PB) given alone or in combination were tested as possible treatments against acute thallium toxicity. Rats were intoxicated by i.p. injection of thallium (I) acetate at LD(50) (32 mg/kg). A day later, pharmacological treatment was administered until day 4 as follows: (1) vehicles, (2) PB 50mg/kg, by oral route, twice a day, (3) DL-P 25mg/kg i.p. route, twice daily and (4) PB+DL-P. The Estimated Probability Survival (EPS) was recorded during the experiment for each treatment. DL-P alone did not show a significant effect on survival. However, when it was used in combination with PB, it increased the survival significantly (EPS=0.8, P<0.05) as compared to the control group (EPS=0.4). In a different experiment, using 16 mg/kg of Thallium I acetate, the metal levels were analyzed in blood, body organs and brain regions after treatments. DL-P given alone decreased slightly the thallium content in blood, organs and brain. Meanwhile, its administration in combination with PB diminished the thallium levels significantly (P<0.05) in the majority of tissues, at levels lower than those achieved in the PB group. Those results indicate that DL-P administered alone did not prevent the mortality nor accumulation of the metal in body tissues. Its combination with PB could be considered an alternative antidotal treatment in thallium toxicity, because this chelating agent given alone did not cause thallium redistribution to the brain. When given in combination with PB it has an additive effect in the treatment of acute thallotoxicosis., (Copyright © 2011 Elsevier B.V. All rights reserved.)

A new technique of blood thallium direct determination based on graphite furnace atomic absorption spectrometry with Zeeman background absorption correction system was designed. The developed technique does not require sample digestion. Sample treatment includes only a fivefold per volume dilution of blood sample with 0.1% (m/v) Triton X-100. L'vov integrated platform was modified with 400 μg of Rh. Matrix modifier (200 μg NH(4)NO(3) and 160 μg Pd(NO(3))(2)) was suggested for coping chloride and blood organic matter interferences. Standard reference material (Clincheck® Plasma Control for trace elements) analysis was used for validation. Additional validation was performed by analyzing spiked blood samples in the whole dynamic range. The dynamic range was 2-50 μg/L. Precision (RSD) was found <12%. Blood thallium limit of detection was 0.2 μg/L.

The present research aimed to characterize the potential efficiency of deferasirox in removing thallium after its administration for 30 days following two dose levels of 20 and 160 μm of thallium (III) chloride to male Wistar rats every day. After thallium administration some abnormal clinical signs such as red staining around the eyes, greenish mottling on the liver, weakness, loss of hair and weight, were observed in animals. Deferasirox was given orally to different groups of rats for a period of one week immediately after thallium administration. After chelation therapy, animals were killed by exsanguination from the abdominal aorta, and then thallium and iron concentrations in various tissues were determined by standard addition method. The chelation therapy results showed that deferasirox was able to remove thallium ions from the body and clinical symptoms were also reduced., (Copyright © 2010 John Wiley & Sons, Ltd.)

The problem of poisoning with thallium-containing substances continues to be of current concern. According to the Bureau of Forensic Medical Examination, Moscow, specimens of biological materials from more than 20 victims of such poisoning were delivered for analysis in 2006. The total number of thallium poisoning episodes during the period since 1996 exceeded 50. Materials for thallium determination in biological fluids (human blood and urine) using flame atomic absorption spectrometry were prepared by dry mineralization of accurately weighed samples; acidic solutions of the products of mineralization were used for analysis. Due to peculiar kinetic features of thallium ion absorption in the gastro-intestinal tract, blood could not be used as a biological marker of poisoning. The level of thallium in urine samples was found to vary from 1.00 to 4,600 mcg/l (with the estimation of confidence intervals in each case). Results of chemical analysis correlated with pathological symptoms derived from the patients' discharge summaries and literature reports on dose-effect relationships. Based on these findings, practically all the examined cases were characterized as severe acute poisoning.

The trafficking of titanium(IV) by human serum transferrin (HsTf) has been implicated in the physiology of this hydrolysis-prone metal. The current work broadens to include the further interactions of Ti(IV) in serum that bear on this model. Ti2HsTf (2 equiv) binds the transferrin receptor TfR1 with Kd1 = 6.3 +/- 0.4 nM and Kd2 = 410 +/- 150 nM, values that are the tightest yet measured for a metal other than iron but weaker than the corresponding ones for Fe2HsTf due to both slightly slower on rates and slightly faster off rates. Comparing the affinities of metals for HsTf with the affinities of the resulting M2HsTf species for TfR1, we speculate that the formation of an M2HsTf complex of high affinity may predict a lobe-closed conformation that leads to a favorable interaction with TfR1. Human serum albumin (HSA), an important serum competitor for metal binding, can bind up to 20 equiv of Ti(IV) supplied in several forms. With some ligands, Ti(IV) may bind to the N-terminal metal binding site of albumin, forming a ternary complex. However, the dominant type of HSA binding is via Ti(IV) in complex form, probably at surface sites. Notably, HSA greatly stabilizes the titanocene moiety of the drug candidate Cp2TiCl2 with respect to hydrolysis and precipitation. HSA binds Ti(IV) citrate supplied as a hydrolyzed or unhydrolyzed source, with 1 equiv of citrate remaining bound. Titanium(IV) monocitrate neither competes with the binding of reporter molecules known to dock at canonical drug sites I or II nor binds at the N-terminus. HsTf outcompetes HSA for soluble Ti(IV) in a direct competition, but once bound to albumin, the transfer of Ti(IV) from HSA to HsTf is quite slow. Each of these findings has implications for the metabolism of Ti(IV) in human serum.

A novel, simple, sensitive and effective method has been developed for preconcentration of thallium on 2,6-bis(N-phenyl carbamoyl)pyridine-naphthalene adsorbent in the pH range 5.0-10.0, prior to its spectrophotometric determination, based on the oxidation of bromopyrogallol red at lambda = 518 nm. This method makes it possible to quantitize thallium in the range of 3.0 x 10(-9) to 1.0 x 10(-5) M, with a detection limit (S/N=3) of 1.2 x 10(-9) M. This procedure has been successfully applied to determine the ultra trace levels of thallium in the environmental and biological samples, free from the interference of some diverse ions. The precision, expressed as relative standard deviation of three measurements is better than 4.17%.

Background: The dermatological features and skin biopsy findings of short-term thallium intoxication have been described. However, the correlation between the dermatological findings and the thallium concentration, the prognosis of peripheral neuropathy, and a cutaneous nerve biopsy study are lacking., Observations: Two patients initially developed perioral numbness, erythematous facial rashes, and polyneuropathy after ingesting thallium-containing water. Severe diffuse alopecia was noted, and a skin biopsy specimen revealed parakeratosis and vacuolar degeneration of the basal layer. Examinations of the hair mount demonstrated a tapered appearance of the anagen root. A serial cutaneous nerve biopsy study showed a loss of epidermal nerves 7 weeks and even 1 year after the thallium intoxication. A toxicology survey disclosed a high concentration of thallium (about 3124 mg/L) in the water. The clinical dermatological features subsided completely, but polyneuropathy with severe painful feet persisted. The blood and daily urinary thallium concentrations decreased slowly in the following 3-month period., Conclusions: The clinical dermatological features subsided completely, but painful polyneuropathy persisted. The series cutaneous nerve biopsy specimens showed persistent damage to the sensory nerve endings. The disappearance of the dermatological features and the appearance of Mees lines correlated with the decrease of blood and urinary thallium concentrations.

The authors report a 48-year-old Chinese woman who presented with acute peripheral neuritis with progressive alopecia. Laboratory examinations disclosed a high blood concentration of thallium (97 microg/L) versus a normal value (0.9 microg/L), and she was diagnosed as having acute thallotoxicosis. After her hospitalization, the cutantest of dimercaptopropansulfonate sodium was positive and the patient refused to take Prussian blue because it caused constipation. She rapidly entered remission after assistance via double-filtration plasmapheresis (DFPP), suggesting the potential efficacy of DFPP for thallotoxicosis.

We report here a highly accurate and efficient method for blood lead analysis (BLA) through the use of a disposable electrode. A new type of mercury-plated preanodized screen-printed carbon electrode, together with a thallium(III) internal standard, simplifies calibration and gives easily quantifiable signals for accurate BLA. A preanodization procedure improves the preconcentration ability of the working electrode through the effect of lead (Pb) complexing with an electrogenerated surface functional group, mainly >C=O. Under optimized conditions, the ratio of the anodic stripping peak currents of Pb and Tl (i.e., i(Pb)/i(Tl)) is linear against [Pb] in the window of 1-300 ppb with a correlation coefficient and detection limit (signal-to-noise ratio=3) of 0.999 and 0.23 ppb, respectively. This approach was used to analyze blood samples (n=55) from workers at a local battery factory. The results are consistent with those obtained from graphite furnace atomic absorption spectroscopy and confirm the applicability of the proposed method.

The neurologic manifestations of thallium poisoning include a severely painful ascending peripheral neuropathy, autonomic dysfunction, cranial nerve abnormalities, and a toxic encephalopathy. Although thallium has a short half-life, these neurologic manifestations commonly progress, even as the blood concentration of thallium decreases. This suggests either that thallium persists in neuronal tissues or that it initiates an injury cascade that takes time to fully manifest. As the latter mechanism is consistent with many toxin exposures, the concept of a central nervous system reservoir for thallium is often discounted. A recent case provided a unique opportunity to evaluate this possibility. A 48-year-old man was acutely and chronically thallium poisoned by his common-law wife. During his initial exposures, only gastrointestinal symptoms manifested. Following an acute ingestion, hospitalization was required. Over 3 days, his symptoms rapidly progressed from a severely painful neuropathy to slurred speech, ptosis, confusion, coma, respiratory insufficiency, and death. Because of considerations of alternative diagnoses, 2 lumbar punctures were performed, one on admission and another on the day of his death. Serum thallium concentrations obtained from stored blood samples were paired with spinal fluid concentrations from the same days. On day 1, serum and spinal fluid concentrations were 8700 mu/L and 1200 mu/L, respectively. On day 3, although the serum concentration had fallen to 7200 mu/L, the spinal fluid concentration had increased to 2100 mu/L. This case provides evidence to support the hypothesis that thallium distributes into the central nervous system more slowly than the blood compartment, and this may in part account for the progression of neurologic findings in the setting of decreasing serum concentrations.

Unlabelled: This study concerns the testicular uptake and dosimetry of Auger electron-emitting radionuclides that are used during routine diagnostic nuclear medicine procedures. To consider the possible effects of these radionuclides on spermatogenic cells, a study has been undertaken to obtain in vivo data for quantification of (111)In chloride and (201)Tl chloride uptake into the human testis after intravenous administration. Values have been determined for uptake into the testis as a whole and to the seminiferous tubules where the germ cells are located., Methods: Data were obtained from patients with prostate cancer who opted for orchidectomy to effect hormone suppression. Patients were administered intravenously 1.5 MBq of either (111)In chloride or (201)Tl chloride at 24 or 48 h before orchidectomy. Upon removal, the testes were analyzed to assess uptake of radionuclide. Conventional dosimetry has been used to estimate testicular radiation doses using our values of percentage uptake., Results: Uptake of both (111)In chloride and (201)Tl chloride into the testes was seen at a level above that explained by simple homogeneous distribution of the radionuclide throughout the body; the testes as a whole demonstrated increased uptake by factors of 3.56 and 4.01 compared with nonspecific uptake for (111)In and (201)Tl, respectively, at 24 h after administration. Both radionuclides gained access to the seminiferous tubules., Conclusion: The results obtained indicate that the values of testicular radiation doses quoted by the International Commission on Radiological Protection for (111)In might be too low by a factor of 4, whereas those for (201)Tl might be too high by a factor of 4. No data were obtained for uptake by individual germ cells within the testis and, therefore, no consideration of dosimetry at the cellular level was possible. However, it has been demonstrated that uptake of diagnostic Auger electron-emitting radionuclides by male germ cells within the testis is possible after intravenous administration.

Three children, aged 5, 10 and 16 years, poisoned with thallium were hospitalized. Two of them suffered from sensory-motor and third from sensory polyneuropathy and additionally in the youngest child severe encephalopathy was observed. The correlations between serum and urine thallium levels and the severity of the symptoms in the course of the disease were positive. The most severe symptoms and the highest thallium level were observed in the youngest child.

Antioxidants of the vitamin E family have protective effects against metal toxicity. We examined the protective effect of racemic LLU-alpha [2,7,8-trimethyl-2-(carboxyethyl)-6-hydroxychroman] a metabolite of gamma-tocopherol, in comparison to the effect of alpha- and gamma-tocopherol in rats treated with sodium dichromate (Cr) or thallium sulfate (Tl). We measured metal nephrotoxicity based on urinary protein excretion and discussed it with respect to the metal concentration in renal tissue. The ranking of antioxidant activity (iron stimulated lipid peroxidation, luminol and lucigenin amplified chemiluminescence) was determined in the following order: alpha-tocopherol

Unithiol (2,3-dimercapto-I-propanesulfonic acid, DMPS) and prussian blue (potassium ferric hexacyanoferrate (II), PB), given alone or in combination, were evaluated as antidotes to treat acute thallotoxicosis in male Sprauge-Dawley rats. Animals were poisoned with 20 mg thallium (TI)/ kg bw PO on day 0 using thallous sulfate. On day 1 (24 h later), treatments began and were continued through day 4 as follows: 50 mg PB/kg bw PO, 2/ d; 5 mg DMPS/kg bw IP, 6/d (day 1), 4/d (day 2), 2/d (days 3-4); or the combination. Animals were sacrificed 24 h after the last treatment (day 5), and TI concentrations in kidney, liver, heart, brain, whole blood and feces determined by electrothermal atomic absorption spectroscopy. The relative accumulation of TI was kidney>>heart>liver approximately equal brain. PB limited incorporation of TI in all tissues. DMPS failed to significantly decrease TI in any organ, but significantly decreased TI in whole blood. PB+DMPS treatment significantly decreased the TI content in all organs, but not to a greater extent than PB alone. PB and PB+DMPS treatments significantly increased TI in feces, whereas DMPS alone produced little effect. This study confirms that PB is beneficial in the treatment of acute thallotoxicosis in rats. The failure of DMPS to significantly affect TI in target organs suggests it is not useful in treating TI poisoning.

Thirteen blood samples of thallium-poisoned people were cytogenetically investigated. The thallium concentration in blood varied from 25 to 2700 microg/L. The mean frequency of chromosomal aberrations in the poisoned group significantly exceeded our control level (7.08+/--2.19% and 2.03+/--0.25, p<.001). The rate of single fragments was significantly higher in poisoned group (7.77+/-2.68% and 1.59+/-0.23%, p<.001) while the frequencies of other types of chromosomal aberrations were similar in both groups. It is possible that thallium is an S-dependent clastogenic agent because the majority of the structural aberrations are of the chromatid type. Irrespective of mechanisms, damage to genetic material was revealed in thallium-poisoned people.

Background: 99mTc-N-NOET (NOET) is a new myocardial perfusion imaging agent that redistributes over time. We sought to better define the redistribution kinetics of NOET using open-chest canine models of sustained low coronary flow (protocol 1) and transient coronary occlusion followed by reflow (protocol 2)., Methods and Results: In protocol 1 (n=10), NOET and 201Tl were injected during low flow in the left anterior descending coronary artery (LAD) that was sustained for 2 hours. Protocol 2 dogs (n=6) were injected with NOET during 20 minutes of LAD occlusion followed by 2 hours of reflow. In both protocols, serial NOET planar images were acquired, and myocardial flow and 2-hour tracer activities were determined by gamma-well counting. Defect resolution was observed on images in both protocols. Initial defect count ratios, reflecting flow disparity at injection (0.66+/-0.03 and 0.57+/-0.04, respectively), increased over 2 hours (0.73+/-0.02 and 0.75+/-0.04, respectively; P<.001 versus initial). Quantitative imaging showed that NOET redistribution resulted from greater clearance from normal areas versus low-flow or transiently occluded areas. In protocol 1, 2-hour NOET and 201Tl stenotic-to-normal tissue activity ratios were similar (0.76+/-0.06 versus 0.73+/-0.04, P=NS) and higher than injection flow ratios (0.52+/-0.06 and 0.56+/-0.07, respectively, P<.001), consistent with tracer redistribution. In protocol 2, NOET redistributed to an even greater extent (injection flow ratio, 0.27+/-0.04; 2-hour tissue activity ratio, 0.84+/-0.03, P<.001)., Conclusions: NOET is the first 99mTc-labeled myocardial imaging agent with kinetics similar to 201Tl in experimental models, permitting redistribution imaging. NOET appears to be a promising agent for assessing patients with coronary artery disease.

Case Report: We report a successfully treated case of severe thallium intoxication. In spite of very high serum thallium (5,240 micrograms/L), symptomatology was minor and recovery complete. Prussian Blue was administered, diuresis was enhanced by intravenous fluids and a prolonged hemodialysis was started early. High blood flows (300 mL/min) and intravenous potassium chloride supplements, to mobilize thallium from the tissues, resulted in good clearances (96 to 150 mL/min). In order to prevent the well known complications, we recommend aggressive treatment of severe thallium intoxication.

D-penicillamine (PCA) is used by some physicians in human thallium intoxication. With the aim of learning how the blood thallium altered kinetics and the modifications produced on the tissue accumulation, we administered PCA to white male thallium dosed rabbits. The method consisted of intravenous (i.v.) administration of thallium (10 mg/kg) to three groups of rabbits. The first group (control) received only the metal, the second group (treatment A) received PCA (25 mg/kg) at the 70th minute after thallium dose, the third group (treatment B) received the PCA at the same dose, 30 sec before the metal was administered. For kinetics studies, blood samples were collected in all groups at minutes 65, 70, 71, 73, 75, 80, 85 and 90. For thallium accumulation studies, bile, urine and tissue samples were collected. Thallium analyses were made by atomic absorption spectrophotometry. The results showed that in treatment A rabbits, the blood thallium concentration raised significantly at the 71st and 73rd minutes. Concerning metal in tissues, muscle mass accumulated significantly more thallium by the B-treatment, while brain accumulation was significantly greater with treatment A. In conclusion, the PCA modifies the blood thallium elimination acute kinetics for a few minutes and changes its accumulation in some tissues, suggesting that PCA extracts the metal from tissues and then re-distributes it throughout the organism.

30 minutes after drinking half a cup of rat poison a 16-year-old girl was admitted to hospital. In addition to various enteric detoxification measures forced dialysis was instituted and, after the urinary thallium level had become known (9 mg/l), haemodialysis was begun and ferric ferrocyanide (Prussian blue) administered (0.5 mg daily for six days). She had no symptoms at any time. After 10 days she was discharged. Five days after discharge she was again admitted, with colic-like abdominal pain, vomiting, paraesthesias of the hands and feet, and in a state of agitation. She had once again ingested rat poison, about one cup. Physical examination revealed little of consequence, except diffuse alopecia. Urinary thallium concentration was 37 mg/l. In the electrocardiogram the P-R interval was shortened to 0.11 s and T waves inverted in leads III and V1. Electronmicroscopy of cardiac and skeletal biopsies revealed lipid droplets, increased sarcoplasm and widening of some of the tubules. Treatment consisted of haemodialysis, forced diuresis (1 l urine/h), administration of ferric ferrocyanide, orthograde intestinal infusions and potassium substitution (serum level: 5 mmol/l). After 28 days the patient was discharged into psychiatric care.

In order to establish reference values of thallium in tissues of the general population the element was determined in blood (TlB) and urine (TlU) of 123 healthy inhabitants living in the Marche region, Central Italy. The analysis was carried out by inductively coupled plasma-mass spectrometry (ICP-MS; detection limit in our experimental conditions, 0.001 micrograms Tl/I), which was validated by neutron activation analysis (NAA) and laser induced fluorecence (LIF) spectroscopy. The check of pre-analytical factors indicated a low risk of contamination and loss of Tl during sampling, handling and storage before the instrumental analysis (blank of the entire procedure less than the detection limit). Mean values of TlU and TlB were 0.066 micrograms Tl/l and 0.063 micrograms Tl/l, respectively (median in both cases 0.057 microgram Tl/l). No conclusive evidence concerning the distribution followed by our data set, normal or log-normal, were drawn, although Lilliefors test and Kolmogorov's D-test showed a tendency for TlB to follow both the normal and the log-normal while TlU followed a log-normal distribution. Overall correlations between TlU and TlB are rather weak. A significant, but not high, correlation (P < 0.0004, r = 0.44) was observed in females. Age, sex, smoking habits and alcohol consumption did not seem to play any role on TlU and TlB. Tentatively proposed reference intervals are 0.019-0.17 microgram Tl/l (urine) and 0.014-0.19 microgram Tl/l (blood).