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Near fatal subacute thallium poisoning necessitating prolonged mechanical ventilation
Toxicology
NearFatalSubacute Thallium Poisoning Necessitating ProlongedMechanical Ventilation PHILIPPE L. VERGAUWE, MD,* DANIEL C. KNOCKAERT, TONY J. VAN TITTELBOOM, MD+ The authors describe a case of severe sensory-motor polyneumpathy caused by subacute thallium-intoxication rapidly progressing to respiratory failure due to complete muscle paralysis. After more than 2 months of mechanical ventilation, weanlng from the ventilator was possible. Further intensive physical rehabllltation required an additional 6 months hospital stay, and 16 months later, neumloglcal recovery was complete except for the distal lower limbs muscles. The authors discuss the different forms of tballotoxtcosis and the present treatment Is reviewed. Maximal prolonged therapeutic support should be offered in severe thallotoxicosis because of possible near complete recovery. (Am J Emerg Med lggO;6:546-550. 0 1990 by W.6. Saunders Company.)
Thallium (Tl) is one of the most toxic metals. Several industrial applications for it exist, eg, the production of optical glasses, artificial jewels, fiberglasses, semiconductors, lowtemperature thermometers, and photoelectric cells.’ In our country it is still available as a rodenticide. The medical applications of Tl, such as a depilatory agent in hirsutism or tinea capitis and prevention against tuberculous sweating, belong to the history of medicine.* At present Tl intoxication results from accidental, suicidal, or criminal ingestion.’ Acute intoxication can cause death within 12 hours to 14 days from heart failure or brain damage. Subacute and chronic ingestion gives rise to a variety of gastrointestinal and neurological symptoms followed by alopecia.’ We describe a case of subacute intoxication in a woman who became totally paralysed, for 2 months.
necessitating
mechanical
ventilation
CASE REPORT A 50-year-old woman was admitted to the hospital because of severe burning pain in the thighs and feet. She was a housewife and her medical history showed breast cancer treated by right mastectomy and radiotherapy 10 years ago. The physical examination was normal except for lymphoedema of the right arm. The patient had no skin, nail, or oral lesions. There were no autonomic dysfunctions. The results of a complete neurological examination were normal.
MD,*
Electromyography showed no abnormalities, nor did liver and kidney function tests. A raised bloodsugar (180 mg/dL) was noted. Investigations for tumor recurrence including laboratory tests, thorax radiographs, abdominal ultrasonography, and computed axial tomography of the brain were normal. Porphyrins in blood, urine, and stools were within normal limits. A urine screening for heavy metals (thallium, cadmium, lead, and mercury) was negative. The patient was discharged on her request, but a week later she was readmitted because of increasing pain in all limbs, anorexia, constipation, and diffuse alopecia. Her husband had noticed periods of confusion. Another electromyography showed a severe sensorymotor polyneuropathy and a rapidly progressive ascending paresis was noticed. A toxic level of Tl (7.1 mg/L urine) confirmed the clinical suspicion of thallotoxicosis. The same day intubation and mechanical ventilation were required because of respiratory arrest. This downhill course could not be explained by electrolyte abnormalities. Treatment with forced diuresis was started. The colloidal form of Prussian blue (150 mg/ kg/d) dissolved in mannitol (15%) was administered by a duodenal tube. The initial delayed gastrointestinal transit was normalised by using mannitol as osmotic laxative. For 3 weeks this therapy was continued with intensive physiotherapy encompassing passive mobilisation, electrostimulation, and iontophoresis. Daily (24 hours) urine Tl excretion is shown in Table 1. After 4 weeks of complete paralysis, motoric recovery began in the upper limbs. After 10 weeks of continuous mechanical ventilation, complicated by a pneumonia, the patient could be weaned from the ventilator without many problems. In another 2 months, sensibility of the arms was fully recovered, but the proximal muscles of the lower limbs remained paretic and all muscles under the knees were still paralysed. Eight months after the second admission, the patient could be discharged from the hospital with persistent paresis of the distal lower limbs. Intensive physical rehabilitation was continued at home. Except for a minimal paresis of the feet, complete neurological recovery was noted 18 months after the second admission. The source of intoxication could not be discovered despite intensive investigation by the legal authorities. No other members of the family had symptoms or signs of thallium poisoning, but thallium levels were not determined.
DISCUSSION From the *Departments of Internal Medicine and Emergency Medicine, Catholic University, Leuven, Belgium TNational Poison Control Center, Brussels, Belgium. Manuscript received August 1, 1989; revision accepted January 8, 1990. Address reprint requests to Dr Knockaert: Department of Internal Medicine, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. Key Words: Thallium poisoning, mechanical ventilation. 0 1990 by W.B. Saunders Company. 0735-8757/90/0808-0018$5.00/O 548
Tl intoxication resulting from accidental suicidal or criminal ingestion is well known and may cause different clinical pictures.‘** The presentation of our case, a rapidly ascending motor weakness leading to respiratory failure mimicking Guillain-Barre syndrome, is rarely reported. ’ A single ingestion of a lethal dose (more than 10 to 15 mg/kg) of Tl causes gastroenteritis with nausea, vomiting, and sometimes initial diarrhea, followed by untractable heart failure and neurological symptoms (eg, seizures and coma),
VERGAUWE, KNOCKAERT, TITTELBOOM n NEAR FATAL SUBACUTE THALLIUM POISONING
TABLE1.
Urinary Thallium Excretion
Cay
Dosage (mg/L)
volume (L/24 hr)
Total Amount (mg124 hr)
1 2 5 6 16
7.1 3.5 ct.94 0.43 0.07
3.1 4.97 7.4 6.0 7.0
21.3 17.5 7.0 3.0 0.5
resulting in death within 12 hours to 14 days. This is the so-called acute form of thallotoxicosis.’ If the patient survives, constipation ensues and a variety of neurological symptoms occur. Orthosympathic nerve disturbance may give rise to tachycardia and sweating.3 In our patient, an extremely painful ascending polyneuropathy, followed by alopecia without abdominal symptoms except for constipation, was the initial presentation. This presentation and the subsequent motor weakness constitute the subacute form of thallotoxicosis.‘.2 Motoric axonal degeneration may cause paralysis with respiratory failure due to respiratory muscle failure. Central nervous symptoms, such as confusionpresent in our patient-seizures, or coma, are ominous signs. Alopecia is a constant phenomenon, but occurs only after 2 to 3 weeks.3 The chronic form caused by low grade exposure is characterized by vague symptoms, mild polyneuropathy, and partial alopecia.’ A temporarily increased blood sugar level is a common finding. After ingestion of Tl a rapid raise of the plasma level occurs during the first 4 hours. This level decreases to a stable level 24 hours after ingestion by intracellular uptake. After 24 hours, only minor plasma level changes occur by daily excretion of Tl, mainly in urine and stools.4 In humans 3.2% of the total body amount is eliminated daily by the kidneys.’ The half-life of TI in humans is between 9.5 and 30 days. If we assume that the urinary excretion of 21.3 mg of thallium (Table I), documented about 6 weeks after the initial complaint, represents 3.2% of the total body amount, our patient should have ingested more than 665 mg and probably more than 1 g. We caution that this is only a rough estimate. The clinical suspicion of thallotoxicosis had to be confirmed by determination of Tl in the urine or blood. Measurement of plasma levels is of limited value in view of the rapid decrease after ingestion. In view of the delay of several weeks, plasma levels were not determined in our case. Atomic absorption spectroscopy is the classic method. Although calorimetric methods are less cumbersome,5 falsepositive reactions are not uncommon6 and our first screening test was false-negative by this method. False-positive results are caused by interference with other substances, such as detergents,6 but we cannot explain our false-negative result. Microscopic examination of a hair-root 3 to 4 days after intoxication showed a typical pigmentation pattern.‘,’ This analysis was neither pathognomonic for Tl nor commonly used in clinical practice. The urinary excretion was low because of low plasma levels and important tubular reabsorption; a value of 300 &L contirmed this hypothesis.’ Fecal excretion was the result of the salivary excretion minus the colonic reabsorption. The highest tissue concentrations were found in the kidneys, the heart, the hair roots, and the salivary glands. Three months
549
after a single Tl-intake the metal was still found in urine, and in the hair and bone even after 6 months.’ Despite intensive treatment in our case, Tl was still present in the urine in a toxic level after 16 days. In the differential diagnosis, intoxications by other metals (arsenic, cadmium, lead, and mercury), porphyria, GuillainBarre syndrome, and botulism must be excluded. Our experience stresses that attention must be given to the respiratory status of the patient as well as the specific poisoning treatment. Gastric lavage to diminish the Tl uptake is worthless unless administered in the first hours after intoxication. An extemporaneously prepared sodium-iodide 1% solution results in the formation of an unsoluble Tl-iodine complex and this sodium-iodide solution is the best choice for gastric lavage.’ In the great majority of cases, the only therapeutic possibility is to raise the excretion of the metal. Intravenously administered potassium causes a redistribution of Tl from intra- to extracellular with subsequent higher excretion due to the increased plasma level. However, this treatment is rather harmful because the higher plasma level may result in more pronounced central nervous symptoms.2*3 Because of the enteroenteric recycling, the main treatment is the binding of Tl in the gastrointestinal tract. Although good results with activated charcoal have been reported, Prussian blue (K+-fenihexacyanoferraat) is the therapy of choice in Europe. 2*4S8 The standard dose is 150 to 250 mg/kg/d of the colloidal form, divided into 4 doses. Prussian blue binds thallium by an exchange of potassium and formation of a nonresorbable complex.’ The Prussian blue powder has to be dissolved in 15% mannitol because of the thallium-induced tendency to constipation. This treatment may be stopped when the daily urinary excretion of Tl is less than 0.5 mg.* Forced diuresis is probably useful particularly in the first hours or days, before a steady-state plasma level is reached. In view of the intracellular distribution of Tl there is no consensus about the value of extracorporal elimination techniques. **‘*In acute intoxication the combination of haemodialysis and charcoal hemopetfusion seems to be the best method4~“.iz although the clearing is rather small, especially after the steady-state plasma level has been reached.13 After a single ingestion of 8 g Tl, only 1.9% of the Tl amount could be eliminated by this method during a 4-hour period with a clearance of 100 mL/min.14 The prognosis of thallotoxicosis depends on the total amount ingested, the time course of the ingestion, and an individual susceptibility. Although recovery is unpredictable, it is influenced by the severity of symptoms. Hair regrowth occurs almost always. Neurological recovery often takes a very long time and is frequently incomplete. Even 30 years after intoxication, sequellae are described.15 Our experience shows that prolonged intensive care with mechanical ventilation is warranted in the case of complete paralysis persisting for weeks. Additional electrostimulation and intensive physical rehabilitation are necessary to promote the motoric and sensory recovery. We conclude that Tl poisoning may cause life-threatening respiratory muscle paralysis mimicking Guillain-Barre syndrome. Despite long lasting complete paralysis, weaning from the respirator could be accomplished without many problems.
550
AMERICAN JOURNAL OF EMERGENCY MEDICINE n Volume 8, Number 6 n November 1990
REFERENCES 1. Friberg L, Nordberg GF, Vouk VB: Handbook on the Toxicology of Metals. Vol2: Specific Metals (ed 2). Elsevier, Amsterdam, 1986 2. Thompson DF: Management of thallium poisoning. Clin Toxicol 1981;18:979-990 3. Bank WJ, Pleasure DE, Suzuki K, et al: Thallium poisoning. Arch Neurol 1972;26:456-464 4. De Groot G, van Heijst A: Toxicokinetic aspects of thallium ooisoning. Methods of treatment by toxin elimination. Sci Total’Environi988;71:411-418 5. Bessems GJH. Westerhuis LW, Baadenhuiisen H: A comparison of two methods for the determination-of thallium in urine. Ann Clin Biochem 1983;20:321-326 6. Blackman N: Thallium poisoning: An epidemic of false positives-Georgetown, Guyana. MMWR 1987;36:481-488 7. Moeschlin S: Thallium poisoning. Clin Toxicol 1980; 17:133-146 8. Kamerbeek HH, Rauws AG, van Heijst ANP: Prussian blue in therapy of thallotoxicosis. Acta Med Stand 1971;189:321-324
9. Forth W: Thallium-Vergiftung. Munch Med Wschr 1983;125:45-50 10. Talas A, Pretschner DP, Wellhoner HH: Pharmacokinetic parameters for thallium (I)-Ions in man. Arch Toxicol 1983;53:1-7 11. Debacker W, Zachee P, Verpooten GA, et al: Thallium intoxication treated with combined hemoperfusion-hemodialysis. J Toxicol Clin Toxicol 1982;19:259-264 12. De Groot G, Van Heijst A, van Kesteren R: An evaluation of the efficacy of charcoal hemoperfusion in the treatment of three cases of acute thallium poisoning. Arch Toxicol 1985;57:61-66 13. Heath A, Ahlmen J: Thallium-poisoning-toxic elimination and therapy in three cases. J Toxicol Clin Toxicol 1983;20:451463 14. Aoyama H, Yoshida M, Yamamura Y: Acute poisoning by intentional ingestion of thallous malonate. Hum Toxicol 1986;5:389-392 15. Barnes MP, Murray K, Tilley PJB: Neurological deficit more than thirty years after chronic thallium intoxication. Lancet 1984;562
NearFatalSubacute Thallium Poisoning Necessitating ProlongedMechanical Ventilation PHILIPPE L. VERGAUWE, MD,* DANIEL C. KNOCKAERT, TONY J. VAN TITTELBOOM, MD+ The authors describe a case of severe sensory-motor polyneumpathy caused by subacute thallium-intoxication rapidly progressing to respiratory failure due to complete muscle paralysis. After more than 2 months of mechanical ventilation, weanlng from the ventilator was possible. Further intensive physical rehabllltation required an additional 6 months hospital stay, and 16 months later, neumloglcal recovery was complete except for the distal lower limbs muscles. The authors discuss the different forms of tballotoxtcosis and the present treatment Is reviewed. Maximal prolonged therapeutic support should be offered in severe thallotoxicosis because of possible near complete recovery. (Am J Emerg Med lggO;6:546-550. 0 1990 by W.6. Saunders Company.)
Thallium (Tl) is one of the most toxic metals. Several industrial applications for it exist, eg, the production of optical glasses, artificial jewels, fiberglasses, semiconductors, lowtemperature thermometers, and photoelectric cells.’ In our country it is still available as a rodenticide. The medical applications of Tl, such as a depilatory agent in hirsutism or tinea capitis and prevention against tuberculous sweating, belong to the history of medicine.* At present Tl intoxication results from accidental, suicidal, or criminal ingestion.’ Acute intoxication can cause death within 12 hours to 14 days from heart failure or brain damage. Subacute and chronic ingestion gives rise to a variety of gastrointestinal and neurological symptoms followed by alopecia.’ We describe a case of subacute intoxication in a woman who became totally paralysed, for 2 months.
necessitating
mechanical
ventilation
CASE REPORT A 50-year-old woman was admitted to the hospital because of severe burning pain in the thighs and feet. She was a housewife and her medical history showed breast cancer treated by right mastectomy and radiotherapy 10 years ago. The physical examination was normal except for lymphoedema of the right arm. The patient had no skin, nail, or oral lesions. There were no autonomic dysfunctions. The results of a complete neurological examination were normal.
MD,*
Electromyography showed no abnormalities, nor did liver and kidney function tests. A raised bloodsugar (180 mg/dL) was noted. Investigations for tumor recurrence including laboratory tests, thorax radiographs, abdominal ultrasonography, and computed axial tomography of the brain were normal. Porphyrins in blood, urine, and stools were within normal limits. A urine screening for heavy metals (thallium, cadmium, lead, and mercury) was negative. The patient was discharged on her request, but a week later she was readmitted because of increasing pain in all limbs, anorexia, constipation, and diffuse alopecia. Her husband had noticed periods of confusion. Another electromyography showed a severe sensorymotor polyneuropathy and a rapidly progressive ascending paresis was noticed. A toxic level of Tl (7.1 mg/L urine) confirmed the clinical suspicion of thallotoxicosis. The same day intubation and mechanical ventilation were required because of respiratory arrest. This downhill course could not be explained by electrolyte abnormalities. Treatment with forced diuresis was started. The colloidal form of Prussian blue (150 mg/ kg/d) dissolved in mannitol (15%) was administered by a duodenal tube. The initial delayed gastrointestinal transit was normalised by using mannitol as osmotic laxative. For 3 weeks this therapy was continued with intensive physiotherapy encompassing passive mobilisation, electrostimulation, and iontophoresis. Daily (24 hours) urine Tl excretion is shown in Table 1. After 4 weeks of complete paralysis, motoric recovery began in the upper limbs. After 10 weeks of continuous mechanical ventilation, complicated by a pneumonia, the patient could be weaned from the ventilator without many problems. In another 2 months, sensibility of the arms was fully recovered, but the proximal muscles of the lower limbs remained paretic and all muscles under the knees were still paralysed. Eight months after the second admission, the patient could be discharged from the hospital with persistent paresis of the distal lower limbs. Intensive physical rehabilitation was continued at home. Except for a minimal paresis of the feet, complete neurological recovery was noted 18 months after the second admission. The source of intoxication could not be discovered despite intensive investigation by the legal authorities. No other members of the family had symptoms or signs of thallium poisoning, but thallium levels were not determined.
DISCUSSION From the *Departments of Internal Medicine and Emergency Medicine, Catholic University, Leuven, Belgium TNational Poison Control Center, Brussels, Belgium. Manuscript received August 1, 1989; revision accepted January 8, 1990. Address reprint requests to Dr Knockaert: Department of Internal Medicine, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium. Key Words: Thallium poisoning, mechanical ventilation. 0 1990 by W.B. Saunders Company. 0735-8757/90/0808-0018$5.00/O 548
Tl intoxication resulting from accidental suicidal or criminal ingestion is well known and may cause different clinical pictures.‘** The presentation of our case, a rapidly ascending motor weakness leading to respiratory failure mimicking Guillain-Barre syndrome, is rarely reported. ’ A single ingestion of a lethal dose (more than 10 to 15 mg/kg) of Tl causes gastroenteritis with nausea, vomiting, and sometimes initial diarrhea, followed by untractable heart failure and neurological symptoms (eg, seizures and coma),
VERGAUWE, KNOCKAERT, TITTELBOOM n NEAR FATAL SUBACUTE THALLIUM POISONING
TABLE1.
Urinary Thallium Excretion
Cay
Dosage (mg/L)
volume (L/24 hr)
Total Amount (mg124 hr)
1 2 5 6 16
7.1 3.5 ct.94 0.43 0.07
3.1 4.97 7.4 6.0 7.0
21.3 17.5 7.0 3.0 0.5
resulting in death within 12 hours to 14 days. This is the so-called acute form of thallotoxicosis.’ If the patient survives, constipation ensues and a variety of neurological symptoms occur. Orthosympathic nerve disturbance may give rise to tachycardia and sweating.3 In our patient, an extremely painful ascending polyneuropathy, followed by alopecia without abdominal symptoms except for constipation, was the initial presentation. This presentation and the subsequent motor weakness constitute the subacute form of thallotoxicosis.‘.2 Motoric axonal degeneration may cause paralysis with respiratory failure due to respiratory muscle failure. Central nervous symptoms, such as confusionpresent in our patient-seizures, or coma, are ominous signs. Alopecia is a constant phenomenon, but occurs only after 2 to 3 weeks.3 The chronic form caused by low grade exposure is characterized by vague symptoms, mild polyneuropathy, and partial alopecia.’ A temporarily increased blood sugar level is a common finding. After ingestion of Tl a rapid raise of the plasma level occurs during the first 4 hours. This level decreases to a stable level 24 hours after ingestion by intracellular uptake. After 24 hours, only minor plasma level changes occur by daily excretion of Tl, mainly in urine and stools.4 In humans 3.2% of the total body amount is eliminated daily by the kidneys.’ The half-life of TI in humans is between 9.5 and 30 days. If we assume that the urinary excretion of 21.3 mg of thallium (Table I), documented about 6 weeks after the initial complaint, represents 3.2% of the total body amount, our patient should have ingested more than 665 mg and probably more than 1 g. We caution that this is only a rough estimate. The clinical suspicion of thallotoxicosis had to be confirmed by determination of Tl in the urine or blood. Measurement of plasma levels is of limited value in view of the rapid decrease after ingestion. In view of the delay of several weeks, plasma levels were not determined in our case. Atomic absorption spectroscopy is the classic method. Although calorimetric methods are less cumbersome,5 falsepositive reactions are not uncommon6 and our first screening test was false-negative by this method. False-positive results are caused by interference with other substances, such as detergents,6 but we cannot explain our false-negative result. Microscopic examination of a hair-root 3 to 4 days after intoxication showed a typical pigmentation pattern.‘,’ This analysis was neither pathognomonic for Tl nor commonly used in clinical practice. The urinary excretion was low because of low plasma levels and important tubular reabsorption; a value of 300 &L contirmed this hypothesis.’ Fecal excretion was the result of the salivary excretion minus the colonic reabsorption. The highest tissue concentrations were found in the kidneys, the heart, the hair roots, and the salivary glands. Three months
549
after a single Tl-intake the metal was still found in urine, and in the hair and bone even after 6 months.’ Despite intensive treatment in our case, Tl was still present in the urine in a toxic level after 16 days. In the differential diagnosis, intoxications by other metals (arsenic, cadmium, lead, and mercury), porphyria, GuillainBarre syndrome, and botulism must be excluded. Our experience stresses that attention must be given to the respiratory status of the patient as well as the specific poisoning treatment. Gastric lavage to diminish the Tl uptake is worthless unless administered in the first hours after intoxication. An extemporaneously prepared sodium-iodide 1% solution results in the formation of an unsoluble Tl-iodine complex and this sodium-iodide solution is the best choice for gastric lavage.’ In the great majority of cases, the only therapeutic possibility is to raise the excretion of the metal. Intravenously administered potassium causes a redistribution of Tl from intra- to extracellular with subsequent higher excretion due to the increased plasma level. However, this treatment is rather harmful because the higher plasma level may result in more pronounced central nervous symptoms.2*3 Because of the enteroenteric recycling, the main treatment is the binding of Tl in the gastrointestinal tract. Although good results with activated charcoal have been reported, Prussian blue (K+-fenihexacyanoferraat) is the therapy of choice in Europe. 2*4S8 The standard dose is 150 to 250 mg/kg/d of the colloidal form, divided into 4 doses. Prussian blue binds thallium by an exchange of potassium and formation of a nonresorbable complex.’ The Prussian blue powder has to be dissolved in 15% mannitol because of the thallium-induced tendency to constipation. This treatment may be stopped when the daily urinary excretion of Tl is less than 0.5 mg.* Forced diuresis is probably useful particularly in the first hours or days, before a steady-state plasma level is reached. In view of the intracellular distribution of Tl there is no consensus about the value of extracorporal elimination techniques. **‘*In acute intoxication the combination of haemodialysis and charcoal hemopetfusion seems to be the best method4~“.iz although the clearing is rather small, especially after the steady-state plasma level has been reached.13 After a single ingestion of 8 g Tl, only 1.9% of the Tl amount could be eliminated by this method during a 4-hour period with a clearance of 100 mL/min.14 The prognosis of thallotoxicosis depends on the total amount ingested, the time course of the ingestion, and an individual susceptibility. Although recovery is unpredictable, it is influenced by the severity of symptoms. Hair regrowth occurs almost always. Neurological recovery often takes a very long time and is frequently incomplete. Even 30 years after intoxication, sequellae are described.15 Our experience shows that prolonged intensive care with mechanical ventilation is warranted in the case of complete paralysis persisting for weeks. Additional electrostimulation and intensive physical rehabilitation are necessary to promote the motoric and sensory recovery. We conclude that Tl poisoning may cause life-threatening respiratory muscle paralysis mimicking Guillain-Barre syndrome. Despite long lasting complete paralysis, weaning from the respirator could be accomplished without many problems.
550
AMERICAN JOURNAL OF EMERGENCY MEDICINE n Volume 8, Number 6 n November 1990
REFERENCES 1. Friberg L, Nordberg GF, Vouk VB: Handbook on the Toxicology of Metals. Vol2: Specific Metals (ed 2). Elsevier, Amsterdam, 1986 2. Thompson DF: Management of thallium poisoning. Clin Toxicol 1981;18:979-990 3. Bank WJ, Pleasure DE, Suzuki K, et al: Thallium poisoning. Arch Neurol 1972;26:456-464 4. De Groot G, van Heijst A: Toxicokinetic aspects of thallium ooisoning. Methods of treatment by toxin elimination. Sci Total’Environi988;71:411-418 5. Bessems GJH. Westerhuis LW, Baadenhuiisen H: A comparison of two methods for the determination-of thallium in urine. Ann Clin Biochem 1983;20:321-326 6. Blackman N: Thallium poisoning: An epidemic of false positives-Georgetown, Guyana. MMWR 1987;36:481-488 7. Moeschlin S: Thallium poisoning. Clin Toxicol 1980; 17:133-146 8. Kamerbeek HH, Rauws AG, van Heijst ANP: Prussian blue in therapy of thallotoxicosis. Acta Med Stand 1971;189:321-324
9. Forth W: Thallium-Vergiftung. Munch Med Wschr 1983;125:45-50 10. Talas A, Pretschner DP, Wellhoner HH: Pharmacokinetic parameters for thallium (I)-Ions in man. Arch Toxicol 1983;53:1-7 11. Debacker W, Zachee P, Verpooten GA, et al: Thallium intoxication treated with combined hemoperfusion-hemodialysis. J Toxicol Clin Toxicol 1982;19:259-264 12. De Groot G, Van Heijst A, van Kesteren R: An evaluation of the efficacy of charcoal hemoperfusion in the treatment of three cases of acute thallium poisoning. Arch Toxicol 1985;57:61-66 13. Heath A, Ahlmen J: Thallium-poisoning-toxic elimination and therapy in three cases. J Toxicol Clin Toxicol 1983;20:451463 14. Aoyama H, Yoshida M, Yamamura Y: Acute poisoning by intentional ingestion of thallous malonate. Hum Toxicol 1986;5:389-392 15. Barnes MP, Murray K, Tilley PJB: Neurological deficit more than thirty years after chronic thallium intoxication. Lancet 1984;562