[Thallium, in The Pale Horse: Diagnostic and Therapeutic Considerations].

Thallium poisoning is described in Agatha Christie's mystery novel, The Pale Horse. Thallium, a tasteless, odorless, and water-soluble element is known to be associated with many accidents and adverse events. Although thallium is not easily available in recent years, thallium poisoning continues to occur. However, diagnosis of thallium poisoning is challenging. In this article, we discuss diagnosis and management of thallium poisoning.

An unusual case of serial poisoning of family members.

The authors present an unusual criminal case of delusionally motivated, serial intrafamilial killings by a psychotic offender. Because the offender retained instrumental rationality and killed his victims by stealth, viz. surreptitious poisoning, the killing of his first victims went undetected. Persecutory delusions of being poisoned not uncommonly result in defensive violence, whereas in this case, religious delusions resulted in the mentally ill person killing others by poisoning them. Here, the psychotic offender killed his victims by means of poisoning based upon motivation driven by religious delusions. This case illustrates the importance of index of suspicion and appropriate investigation of mysterious deaths, and careful forensic psychiatric assessment to distinguish delusional versus extreme overvalued belief-motivated killings in addressing the insanity defense.

Complexions therapy and severe intoxication by Thallium salts.

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.

Thallium toxicity due to audultered infusion with thallium sulfate in eight members belonging to the same family nucleus: Autopsy findings and ICP-MS analysis (inductively coupled plasma mass spectrometry) in a triple homicide.

The banning of the heavy metal thallium (Tl) in many Countries, because of its toxicity, led to a remarkable reduction of the number of cases of poisoning both accidental and homicidal forcing us to better study the pharmacokinetics of this poison using new technologies. The Authors, in this work, are reporting the case of a collective thallium toxicosis caused by voluntary adulteration of an infusion with thallium sulfate, occurred in 8 members of the same familial nucleus; the administration of Prussian Blu resulted to be ineffective for 3 of these members that died at a later time. The most peculiar aspects of this rare manner of poisoning are discussed; the analytical procedures used, Inductively Coupled Plasma Mass Spectrometry (ICP-MS) in particular, resulted to be fundamental in the forensic diagnosis process of acute poisoning cause by thallium.

Clinical characteristics and treatment of thallium poisoning in patients with delayed admission in China.

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.

Successful treatment of a patient with severe thallium poisoning in a coma using Prussian blue and plasma exchange: A case report.

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.

Details of a thallium poisoning case revealed by single hair analysis using laser ablation inductively coupled plasma mass spectrometry.

Heavy metals pose significant morbidity and mortality threats to humans in connection with both acute and chronic exposure. The often-delayed manifestations of some toxic effects and the wide-spectrum of symptoms caused by heavy metal poisoning may perplex the clinical diagnosis and, when involved in crimes, complicate the forensic investigation. To investigate the original intoxication process of a thallium poisoning case, which occurred in China more than two decades ago, laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used to analyze several hairs of the victim from before, during and after the poisoning period. Ablation line scans of the entire length of a ∼7cm hair revealed ∼4months of repeated exposure to thallium with increased doses and frequency toward the end, while scan of a ∼0.7cm hair revealed ∼2weeks of constant ingestions of large doses of thallium accompanied by elevated amount of lead. The endogenous origin of thallium was confirmed by the preservation of the same longitudinal distribution profile in the inner part of hair, but the source of lead could not be unambiguously determined due to the intrinsic limitation of hair analysis to distinguish ingested lead from exogenous contaminants. The overall thallium distribution profiles in the analyzed hairs suggested both chronic and acute thallium exposures that correlated well with the sequential presentation of a plethora of symptoms experienced by the victim. Aligning the time-resolved thallium peaks with symptoms also provided clues on possible routes of exposure at different poisoning stages. This work demonstrated the capability of using single hair LA-ICP-MS analysis to reconstitute a prolonged and complicated heavy metal poisoning case, and highlighted the necessity of assessing multiple elements in the medico-legal investigation of suspicious heavy metal poisonings.

Changes in thallium distribution in the scalp hair after an intoxication incident.

In cases of criminal thallium poisoning, forensic investigation is required to identify the amount and time of thallium exposure. Usually, blood and urine thallium levels are respectively used as biomarkers. Additionally, hair has the unique potential to reveal retrospective information. Although several studies have attempted to clarify how thallium is distributed in hair after thallium poisoning, none have evaluated the time course of changing thallium distribution. We investigated changes in the distribution of thallium in hair at different time points after exposure in five criminal thallotoxicosis patients. Scalp hair samples were collected twice, at 2.6 and 4.2-4.5months after an exposure incident by police. Results of our segmented analysis, a considerable amount of thallium was detected in almost all hair sample segments. The thallium exposure date estimated from both hair sample collections matched the actual exposure date. We found that determination of thallium amounts in hair samples divided into consecutive segments provides valuable information about exposure period even if a considerable time passes after exposure. Moreover, when estimating the amount of thallium exposure from a scalp hair sample, it is necessary to pay sufficient attention to individual differences in its decrease from hair.

[Efficacy analysis of prussian blue or its combination with hemoperfusion in the treatment of acute thallium poisoning].

OBJECTIVE: To investigate the efficacy of prussian blue (PB) or its combination with hemoperfusion (HP) in the treatment of acute thallium poisoning. METHODS: Forty-seven patients with acute thallium poisoning with complete data hospitalized in the 307th Hospital of PLA from September 2002 to December 2017 were enrolled, and they were divided into mild poisoning group (blood thallium < 150 µg/L, urinary thallium < 1 000 µg/L) and moderate-severe poisoning group (blood thallium ≥ 150 µg/L, urinary thallium ≥ 1 000 µg/L) according to the toxic degrees. All patients were given symptomatic supportive treatments such as potassium supplementation, catharsis, vital organ protections, neurotrophic drugs, and circulation support. The mild poisoning patients were given PB with an oral dose of 250 mg×kg-1×d-1, while moderate-severe poisoning patients were given PB combined HP continued 2-4 hours each time. The PB dose or frequency of HP application was adjusted according to the monitoring results of blood and urine thallium. Data of gender, age, pain grading (numeric rating scale NRS), clinical manifestations, blood and urine thallium before and after treatment, length of hospitalization and prognosis were collected. RESULTS: Of the 47 patients, patients with incomplete blood and urine test results, and used non-single HP treatment such as plasmapheresis and hemodialysis for treatment were excluded, and a total of 29 patients were enrolled in the analysis. (1) Among 29 patients, there were 20 males and 9 females, median age of 40.0 (34.0, 49.0) years old; the main clinical manifestations were nervous system and alopecia, some patients had digestive system symptoms. There were 13 patients (44.8%) in the mild poisoning group with painless (grade 0) or mild pain (grade 1-3) with mild clinical symptoms, the length of hospitalization was 17.0 (14.2, 21.5) days. There were 16 patients (55.2%) in the moderate-severe poisoning group with moderate pain (grade 4-6) or severe pain (grade 7-10) with severe clinical symptoms, the length of hospitalization was 24.0 (18.0, 29.0) days. (2) After treatment, the thallium concentrations in blood and urine in the mild poisoning group were significantly lower than those before treatment [µg/L: blood thallium was 0.80 (0, 8.83) vs. 60.00 (40.00, 120.00), urine thallium was 11.30 (0, 70.10) vs. 370.00 (168.30, 610.00), both P < 0.01], the thallium concentrations in blood and urine in the moderate-severe poisoning group were also significantly lower than those before treatment [µg/L: blood thallium was 6.95 (0, 50.50) vs. 614.50 (245.00, 922.00), urinary thallium was 20.70 (1.95, 283.00) vs. 5 434.00 (4 077.20, 10 273.00), both P < 0.01]. None of the 29 patients died, and their clinical symptoms were improved significantly. All the 27 patients had good prognosis without sequela in half a year follow-up, and 2 patients with severe acute thallium poisoning suffered from nervous system injury. CONCLUSIONS: In the acute thallium poisoning patients, on the basis of general treatment, additional PB in mild poisoning group and PB combined with HP in moderate-severe poisoning group can obtain satisfactory curative effects.

Efficacy analysis of prussian blue or its combination with hemoperfusion in the treatment of acute thallium poisoning / 中华危重病急救医学

OBJECTIVE@#To investigate the efficacy of prussian blue (PB) or its combination with hemoperfusion (HP) in the treatment of acute thallium poisoning.@*METHODS@#Forty-seven patients with acute thallium poisoning with complete data hospitalized in the 307th Hospital of PLA from September 2002 to December 2017 were enrolled, and they were divided into mild poisoning group (blood thallium < 150 μg/L, urinary thallium < 1 000 μg/L) and moderate-severe poisoning group (blood thallium ≥ 150 μg/L, urinary thallium ≥ 1 000 μg/L) according to the toxic degrees. All patients were given symptomatic supportive treatments such as potassium supplementation, catharsis, vital organ protections, neurotrophic drugs, and circulation support. The mild poisoning patients were given PB with an oral dose of 250 mg×kg-1×d-1, while moderate-severe poisoning patients were given PB combined HP continued 2-4 hours each time. The PB dose or frequency of HP application was adjusted according to the monitoring results of blood and urine thallium. Data of gender, age, pain grading (numeric rating scale NRS), clinical manifestations, blood and urine thallium before and after treatment, length of hospitalization and prognosis were collected.@*RESULTS@#Of the 47 patients, patients with incomplete blood and urine test results, and used non-single HP treatment such as plasmapheresis and hemodialysis for treatment were excluded, and a total of 29 patients were enrolled in the analysis. (1) Among 29 patients, there were 20 males and 9 females, median age of 40.0 (34.0, 49.0) years old; the main clinical manifestations were nervous system and alopecia, some patients had digestive system symptoms. There were 13 patients (44.8%) in the mild poisoning group with painless (grade 0) or mild pain (grade 1-3) with mild clinical symptoms, the length of hospitalization was 17.0 (14.2, 21.5) days. There were 16 patients (55.2%) in the moderate-severe poisoning group with moderate pain (grade 4-6) or severe pain (grade 7-10) with severe clinical symptoms, the length of hospitalization was 24.0 (18.0, 29.0) days. (2) After treatment, the thallium concentrations in blood and urine in the mild poisoning group were significantly lower than those before treatment [μg/L: blood thallium was 0.80 (0, 8.83) vs. 60.00 (40.00, 120.00), urine thallium was 11.30 (0, 70.10) vs. 370.00 (168.30, 610.00), both P < 0.01], the thallium concentrations in blood and urine in the moderate-severe poisoning group were also significantly lower than those before treatment [μg/L: blood thallium was 6.95 (0, 50.50) vs. 614.50 (245.00, 922.00), urinary thallium was 20.70 (1.95, 283.00) vs. 5 434.00 (4 077.20, 10 273.00), both P < 0.01]. None of the 29 patients died, and their clinical symptoms were improved significantly. All the 27 patients had good prognosis without sequela in half a year follow-up, and 2 patients with severe acute thallium poisoning suffered from nervous system injury.@*CONCLUSIONS@#In the acute thallium poisoning patients, on the basis of general treatment, additional PB in mild poisoning group and PB combined with HP in moderate-severe poisoning group can obtain satisfactory curative effects.

Thallium Toxicity: General Issues, Neurological Symptoms, and Neurotoxic Mechanisms.

Thallium (Tl+) is a ubiquitous natural trace metal considered as the most toxic among heavy metals. The ionic ratio of Tl+ is similar to that of potassium (K+), therefore accounting for the replacement of the latter during enzymatic reactions. The principal organelle damaged after Tl+ exposure is mitochondria. Studies on the mechanisms of Tl+ include intrinsic pathways altered and changes in antiapoptotic and proapoptotic proteins, cytochrome c, and caspases. Oxidative damage pathways increase after Tl+ exposure to produce reactive oxygen species (ROS), changes in physical properties of the cell membrane caused by lipid peroxidation, and concomitant activation of antioxidant mechanisms. These processes are likely to account for the neurotoxic effects of the metal. In humans, Tl+ is absorbed through the skin and mucous membranes and then is widely distributed throughout the body to be accumulated in bones, renal medulla, liver, and the Central Nervous System. Given the growing relevance of Tl+ intoxication, in recent years there is a notorious increase in the number of reports attending Tl+ pollution in different countries. In this sense, the neurological symptoms produced by Tl+ and its neurotoxic effects are gaining attention as they represent a serious health problem all over the world. Through this review, we present an update to general information about Tl+ toxicity, making emphasis on some recent data about Tl+ neurotoxicity, as a field requiring attention at the clinical and preclinical levels.

Tardily accelerated neurologic deterioration in two-step thallium intoxication.

Thallium intoxication was reported in cases with accidental ingestion, suicide attempt, and criminal adulteration. Reported cases were mostly one-time ingestion, therefore, the clinical course of divisional ingestion has not been fully known. Here, we report a case with two-step thallium intoxication manifesting as tardily accelerated neurologic deterioration. A 16-year-old adolescent was cryptically poisoned with thallium sulfate twice at an interval of 52days. After the first ingestion, neurologic symptoms including visual loss, myalgia, and weakness in legs developed about 40days after the development of acute gastrointestinal symptoms and alopecia. After the second ingestion, neurologic symptoms deteriorated rapidly and severely without gastrointestinal or cutaneous symptoms. Brain magnetic resonance imaging exhibited bilateral optic nerve atrophy. Nerve conduction studies revealed severe peripheral neuropathies in legs. Thallium intoxication was confirmed by an increase in urine thallium egestion. Most of the neurologic manifestations ameliorated in two years, but the visual loss persisted. The source of thallium ingestion was unraveled afterward because a murder suspect in another homicidal assault confessed the forepast adulteration. This discriminating clinical course may be attributable to the cumulative neurotoxicity due to the longer washout-time of thallium in the nervous system than other organs. It is noteworthy that the divisional thallium intoxication may manifest as progressive optic and peripheral neuropathy without gastrointestinal or cutaneous symptoms.

Thallium intoxication. Case Report.

We report a rare case of serious voluntary intoxication by laboratory thallium monobromate combined with alcohol intake by a 24-years old man. The diagnosis of thallium intoxication was based on history, nonspecific but typical clinical symptoms including gastrointestinal complaints, painful polyneuropathy, alopecia, and confirmed by the finding of increased thallium concentration in the urine. The treatment, performed at the due time, consisted of decontamination of the stomach by irrigation, administration of active charcoal and Prussian blue, correction of water and mineral dysbalance, symptomatic treatment, and led to complete recovery.

Thallium exists in opioid poisoned patients.

BACKGROUND: Thallium (Tl) is a toxic heavy metal that exists in nature. Tl poisoning (thallotoxicosis) may occur in opioid addicts. This study was designed to evaluate the frequency and level of urinary Tl in opioid abusers. In addition, clinical findings were evaluated. METHODS: A total of 150 subjects were examined. Cases with a history of at least 3 years of abuse were admitted in the Imam Reza Hospital as the case group; 50 non-opioid abusers from the target population were included as the control group. Twenty-four hour urinary qualitative and quantitative Tl analyses were performed on both groups. RESULTS: Out of the 150 subjects, 128 (85 %) were negative for qualitative urinary Tl, followed by 5 % (trace), 7 % (1+), 2 % (2+), and 1 % (3+). Mean (standard error (SE), Min-Max) quantitative urinary Tl level was 14 µg/L (3.5 µg/L, 0-346 µg/L). Mean urinary Tl level in the case group was 21 µg/L (5 µg/L, 0-346 µg/L) and that in the controls was 1 µg/L (0.14 µg/L, 0-26 µg/L), which were significantly different (P = 0.001). The most frequent clinical findings were ataxia (86 %), sweating (81 %), and constipation (54 %). In all cases (n = 150), the mean (SE) value for cases with positive qualitative urinary Tl was 26.8 µg/L (0.9 µg/L) and that in the negative cases was 2.3 µg/L (0.2 µg/L), which were significantly different (P = 0.002). CONCLUSIONS: This study showed that long-term opioid abuse may lead to Tl exposure. In opioid abusers with the clinical manifestation of thallotoxicosis, urinary Tl should be determined.

Human fatality due to thallium poisoning: autopsy, microscopy, and mass spectrometry assays.

Thallium has been responsible for many intoxications since its discovery; however, toxicological profiles for thallium in human fatalities have not been updated recently. Autopsy, microscopic investigations, and toxicological analyses were performed on a married couple who died from thallium sulfate intended homicidal poisoning. The distribution of thallium was established by inductively coupled plasma mass spectrometry with hair samples showing the highest thallium concentration. Electron microscopy revealed a dystrophic condition of hair with disorganized cuticle and atrophy of the hair bulb. Thallium interacts with cells at different levels, with prominent ultrastructural injuries in the mitochondria and endoplasmic reticulum, and high concentration of electron dense granules observed in the cytoplasm and mitochondria of several organs. Alopecia, toxic encephalopathy, and peripheral neuropathy were diagnosed in the victims and suggested to be crucial implications for thallium poisoning. The analytical procedures used in this case are of considerable forensic importance in the diagnosis of thallium poisoning.

Misdiagnosis and long-term outcome of 13 patients with acute thallium poisoning in China.

PURPOSE: To analyze clinical feature and evaluate long-term outcome of patients with thallium poisoning. MATERIALS AND METHODS: An observational series of cases with acute thallium poisoning was analyzed retrospectively in West China Hospital of Sichuan University between 2000 and 2010. The clinical data including symptom, determination of thallium level, treatment, neurophysiological examination, and neuropsychological evaluation were analyzed. The patients were followed up until December 2012. RESULTS: Seven men and six women were enrolled in the study. The median patient age was 37 years (range: 15-53 years). The median duration of hospitalization was 44 days (range: 7-72). All the patients were misdiagnosed initially. One patient died in the hospital. The other 12 patients were followed for a median of 7 years (range: 1-12 years) after discharge from hospital. One patient died from leukemia in the first year of follow-up. Long-term outcome results showed peripheral neuropathy improved substantially. However, many patients have mild or moderate sequelae in sensory nerve fibers of distal lower extremity. A sural nerve biopsy in one patient revealed shrunken axons, distorted myelin sheath, and myelinated fibers loss. During follow-up period, problem of intelligence (4/12 patients, 33%), memory impairment (4/12, 33%), anxiety (6/12, 50%), and depression (5/12, 42%) were demonstrated. CONCLUSIONS: Neurological symptoms may lead to misdiagnosis of thallium poisoning. Mild or moderate neurological sequelae may last for a long time after thallium poisoning.