[A woman in her forties with cancer, syncope and spasms]. / En kvinne i 40-årene med kreft, synkope og kramper.

A female in her forties with advanced incurable rectal cancer presented to our emergency department after loss of consciousness followed by brief myoclonic jerks in her legs. A cerebral MRI was normal. Her electrocardiogram showed a prolonged QTc interval of 596 milliseconds and hypokalemia was present. She had no family history of congenital long QT syndrome or of cardiovascular disease. She was not on any medication apart from having ingested 100 g caesium carbonate over the previous 11 days as an alternative cancer treatment. Caesium chloride is postulated to increase pH and thereby induce apoptosis in cancer cells. In treatment doses caesium competes with potassium for membrane transport proteins in the cardiac cell membrane and in the reabsorption tubuli of the kidneys. A result is hypokalemia shortly after depolarization during the cardiomyocytes' repolarisation phase or delayed post-depolarisation. Torsade de pointes ventricular arrhythmias, ventricular tachycardia, pump failure and death can follow. A few case reports of adverse effects from caesium ingestion have been published, as well as reports on how caesium is used in animal models to induce ventricular tachycardia, but the hazards of caesium ingestion and its long half-life are not well known in the medical care profession or among patients. As this patient's QTc interval normalised slowly to 413 milliseconds 60 days after stopping caesium ingestion, we consider caesium intoxication and convulsive syncope from a self-terminating ventricular tachycardia as the most probable aetiology. The main message from this case is that alternative medicine can have life-threatening side effects.

Fatal cesium chloride toxicity after alternative cancer treatment.

BACKGROUND: Cesium chloride (CsCl) is sold as a treatment for several types of cancers. The purported mechanism of action is alkalinization of relatively acidic neoplastic cells. The efficacy of CsCl has not been demonstrated in controlled experiments. Oral and intravenous CsCl use has been associated with seizures, cardiotoxicity, syncope, and death. Although intratumoral treatment with various antineoplastic agents is described, no cases of intratumoral cancer treatment with CsCl have been found in the medical literature. The case described here appears to be of the first reported patient with CsCl toxicity secondary to subcutaneous exposure after attempted intratumoral injection. CASE DETAILS: A 61-year-old woman presented in cardiac arrest 20 hours after injecting 9 mL of an oral CsCl preparation around a mass in her breast. She had been taking the CsCl orally for approximately 1 year to treat her breast mass. The patient had a headache and nausea for several hours after injection and then experienced ventricular tachycardia arrest at home. She received advanced cardiac life support care and multiple antiarrhythmic medications and underwent electrical cardioversion early in the course of the arrest. After stabilization, her electrocardiogram revealed QT interval prolongation to >700 milliseconds. Upon discovery of her CsCl exposure, she was treated with Prussian blue. Her initial whole blood cesium level was 100,000 µg/L (reference range <10 µg/L). Her QT prolongation resolved after several days, but she experienced no meaningful postarrest neurologic recovery and died at home less than a week after exposure. DISCUSSION: CsCl is sold as an alternative treatment for cancer. There is no demonstrable efficacy, and clear evidence shows life-threatening toxicity. Reported here is a case of fatal CsCl toxicity after attempted intratumoral injection.

Evaluation of Cuprimine® and Syprine® for decorporation of radioisotopes of cesium, cobalt, iridium and strontium.

Cuprimine® and Syprine® are therapeutics approved by the USFDA to treat copper overload in Wilson Disease (a genetic defect in copper transport) by chelation and accelerated excretion of internally-deposited copper. These oral therapeutics are based on the respective active ingredients D-penicillamine (DPA) and N,N'-bis (2-aminoethyl) -1,2-ethanediamine dihydrochloride (Trien). Cuprimine is considered the primary treatment, although physicians are increasingly turning to Syprine as a first-line therapy. Both drugs exhibit oral systemic activity and low toxicity; their biological effects and safety are established. Previous in vivo studies using a rodent animal model established the decorporation potential of Cuprimine and Syprine for (60)Co and (210)Po. Currently these studies are being expanded to evaluate the in vivo decorporation efficacy of these drugs for several additional radionuclides. In this report, results of this investigation are discussed using the radionuclides (137)Cs, (60)Co, (192)Ir and (85)Sr. Short-term 48-h pilot studies were undertaken to evaluate DPA and Trien for their in vivo decorporation potential using male Wistar-Han rats. In these studies, a radionuclide solution was administered to the animals by intravenous (IV) injection, followed by a single IV dose of either DPA or Trien. Control animals received the radionuclide alone. Results show effective decorporation of (60)Co by DPA within the time frame evaluated. DPA and Trien were also modestly effective in decorporation of (137)Cs and (85)Sr, respectively. The study did not find DPA or Trien effective for decorporation of (192)Ir. Based on these encouraging findings, further studies to evaluate the dose-response profiles and timing of the chelator administration post exposure to radionuclides are warranted.

Ingestion doses in Finland due to (90)Sr, (134)Cs, and (137)Cs from nuclear weapons testing and the Chernobyl accident.

(90)Sr and (137)Cs in domestic foodstuffs and water have been analysed in Finland since the early 1960s, and (134)Cs since 1986. Using data on radionuclide deposition levels, agricultural production, and the processing and consumption of foodstuffs, the average intake and radiation dose from the ingestion of these radionuclides have been assessed. The estimated committed effective dose from the ingestion of (90)Sr, (137)Cs, and (134)Cs in food and water for the period 1960-2005 is 2.2 mSv, and for the period since the Chernobyl accident in 1986 it is 1.3 mSv.

Assessing the therapeutic and toxicological effects of cesium chloride following administration to nude mice bearing PC-3 or LNCaP prostate cancer xenografts.

PURPOSE: The purpose of this study was to assess the therapeutic and toxicological effects of cesium chloride (CsCl) administration in mice bearing prostate cancer tumors. METHODS: Three CsCl dose titration studies were completed in tumor-bearing and non-tumor-bearing athymic nude mice. All mice were administered either vehicle (controls), 150, 300, 600, 800, 1,000, or 1,200 mg/kg of CsCl once daily by oral gavage for 30 consecutive days. Body mass was measured daily, food and water consumption were measured every 2 days, and tumor volume was measured twice weekly. Histopathological analysis was conducted on tissues collected from each of the studies. Serum AST/ALT and creatinine were also measured. RESULTS: Administration of 800-1,200 mg/kg CsCl reduced PC-3 tumor growth but had no effect on LNCaP tumors. Administration of 800-1,200 mg/kg CsCl also resulted in increased water consumption, bladder crystal development, and higher prevalence of cardiac fibrin clots. An observed loss in body mass was dependent on the xenograft type and concentration of CsCl administered. CsCl did not affect serum AST/ALT and creatinine levels. CONCLUSIONS: CsCl may have a therapeutic effect against prostate cancer, but one cannot overlook the acute toxicities also described.

Isolation and characterization of I(Kr) in cardiac myocytes by Cs+ permeation.

Isolation of the rapidly activating delayed rectifier potassium current (I(Kr)) from other cardiac currents has been a difficult task for quantitative study of this current. The present study was designed to separate I(Kr) using Cs+ in cardiac myocytes. Cs+ have been known to block a variety of K+ channels, including many of those involved in the cardiac action potential such as inward rectifier potassium current I(K1) and the transient outward potassium current I(to). However, under isotonic Cs+ conditions (135 mM Cs+), a significant membrane current was recorded in isolated rabbit ventricular myocytes. This current displayed the voltage-dependent onset of and recovery from inactivation that are characteristic to I(Kr). Consistently, the current was selectively inhibited by the specific I(Kr) blockers. The biophysical and pharmacological properties of the Cs+-carried human ether-a-go-go-related gene (hERG) current were very similar to those of the Cs+-carried I(Kr) in ventricular myocytes. The primary sequence of the selectivity filter in hERG was in part responsible for the Cs+ permeability, which was lost when the sequence was changed from GFG to GYG, characteristic of other, Cs+-impermeable K+ channels. Thus the unique high Cs+ permeability in I(Kr) channels provides an effective way to isolate I(Kr) current. Although the biophysical and pharmacological properties of the Cs+-carried I(Kr) are different from those of the K+-carried I(Kr), such an assay enables I(Kr) current to be recorded at a level that is large enough and sufficiently robust to evaluate any I(Kr) alterations in native tissues in response to physiological or pathological changes. It is particularly useful for exploring the role of reduction of I(Kr) in arrhythmias associated with heart failure and long QT syndrome due to the reduced hERG channel membrane expression.

Blood and tissue concentration of cesium after exposure to cesium chloride: a report of two cases.

CONTEXT: Complementary alternative medicine therapies based on the use of cesium chloride preparations for the treatment of cancer and radiation poisoning, have generated therapeutic interest; but oral or intravenous administration of cesium chloride (CsCl) to cancer patients as an alternative mode of cancer therapy have not been approved by the US Food and Drug Administration (FDA). OBJECTIVE: Cesium (Cs) levels from human tissue were measured to determine exposure to an alternative medical treatment. Cesium levels are reported from two patients who were administered cesium chloride in conjunction with aloe vera as part of an alternative cancer treatment. DESIGN: The samples were analyzed by graphite furnace atomic absorption spectrometry with Zeeman background correction. As a reference, Cs was also determined in brain, liver, kidney, and whole blood from control case materials retrieved from the National Tissue Repository of the Armed Forces Institute of Pathology. RESULTS: High levels of cesium were found in brain, liver, kidney, bile, gastric content, and whole blood collected at autopsy as compared to reference levels. The administration of cesium chloride resulted in blood levels a factor of 1100 higher than normal. The highest Cs concentrations were found in the liver (1029 microg/g, dry wt), followed by the kidney (815 microg/g, dry wt) and brain (219 microg/g, dry wt). CONCLUSION: The high accumulation in the liver suggests that hepatotoxicity from Cs might be an initial presenting symptom in Cs-poisoning cases. This is the first report describing two cases with high Cs levels in human tissues.

Functional expression of the hyperpolarization-activated, non-selective cation current I(f) in immortalized HL-1 cardiomyocytes.

HL-1 cells are adult mouse atrial myocytes induced to proliferate indefinitely by SV40 large T antigen. These cells beat spontaneously when confluent and express several adult cardiac cell markers including the outward delayed rectifier K(+) channel. Here, we examined the presence of a hyperpolarization-activated I(f) current in HL-1 cells using the whole-cell patch-clamp technique on isolated cells enzymatically dissociated from the culture at confluence. Cell membrane capacitance (C(m)) ranged from 5 to 53 pF. I(f) was detected in about 30% of the cells and its occurrence was independent of the stage of the culture. I(f) maximal slope conductance was 89.7 +/- 0.4 pS pF(-1) (n = 10). I(f) current in HL-1 cells showed typical characteristics of native cardiac I(f) current: activation threshold between -50 and -60 mV, half-maximal activation potential of -83.1 +/- 0.7 mV (n = 50), reversal potential at -20.8 +/- 1.5 mV (n = 10), time-dependent activation by hyperpolarization and blockade by 4 mM Cs(+). In half of the cells tested, activation of adenylyl cyclase by the forskolin analogue L858051 (20 microM) induced both an approximately 6 mV positive shift of the half-activation potential and an approximately 37 % increase in the fully activated I(f) current. RT-PCR analysis of the hyperpolarization-activated, cyclic nucleotide-gated channels (HCN) expressed in HL-1 cells demonstrated major contributions of HCN1 and HCN2 channel isoforms to I(f) current. Cytosolic Ca(2+) oscillations in spontaneously beating HL-1 cells were measured in Fluo-3 AM-loaded cells using a fast-scanning confocal microscope. The oscillation frequency ranged from 1.3 to 5 Hz and the spontaneous activity was stopped in the presence of 4 mM Cs(+). Action potentials from HL-1 cells had a triangular shape, with an overshoot at +15 mV and a maximal diastolic potential of -69 mV, i.e. more negative than the threshold potential for I(f) activation. In conclusion, HL-1 cells display a hyperpolarization-activated I(f) current which might contribute to the spontaneous contractile activity of these cells.

Effects of low chronic doses of ionizing radiation on antioxidant enzymes and G6PDH activities in Stipa capillata (Poaceae).

Stipa capillata (Poaceae) seeds were harvested from a control area (displaying a gamma dose rate of 0.23 micro Sv h(-1)) (C plants) and from two contaminated areas (5.4 and 25 micro Sv h(-1)) on the Semipalatinsk nuclear test site (SNTS) in Kazakhstan. The plants were grown for 124 d in a greenhouse under controlled conditions and exposed to three different treatments: (0) control; (E) external gamma irradiation delivered by a sealed 137Cs source with a dose rate of 66 micro Sv h(-1); (E+I) E treatment combined with internal beta irradiation due to contamination by 134Cs and 85Sr via root uptake from the soil. The root uptake led to a contamination of 100 Bq g(-1) for 85Sr and 5 Bq g(-1) for 134Cs (of plant dry weight) as measured at harvest. The activity of SOD, APX, GR, POD, CAT, G6PDH, and MDHAR enzymes was measured in leaves. Under (0) treatment, all enzymes showed similar activities, except POD, which had higher activity in plants originating from contaminated areas. Treatment (E) induced an enhancement of POD, CAT, GR, SOD, and G6PDH activities in plants originating from contaminated areas. Only control plants showed any stimulation of APX activity. Treatment (E+I) had no significant effect on APX, GR, CAT, and POD activities, but MDHAR activity was significantly reduced while SOD and G6PDH activities were significantly increased. The increase occurred in plants from all origins for SOD, with a greater magnitude as a function of their origin, and it occurred only in plants from the more contaminated populations for G6PDH. This suggests that exposure to a low dose rate of ionizing radiation for almost a half century in the original environment of Stipa has led to natural selection of the most adapted genotypes characterized by an efficient induction of anti-oxidant enzyme activities, especially SOD and G6PDH, involved in plant protection against reactive oxygen species.

Induction of micronuclei in mouse polychromatic erythrocytes by the administration of non-radioactive CsCl by the oral and intraperitoneal route.

In the present study, we describe the effects of the concentration and route of administration of non-radioactive cesium chloride (CsCl) in inducing micronuclei in mouse bone marrow polychromatic erythrocytes (PCEs). When the dose of 500mg/kg body weight was administered perorally (p.o.), no significant incidence of micronuclei was detected. However, when the same dose was administered intraperitoneally (i.p.), a significant induction of micronuclei in PCEs was observed compared to control. At the dose of 1000mg/kg, both routes were efficient, with no significant difference in micronucleus frequencies. We conclude that both the p.o. and i.p. routes are efficient in inducing micronuclei, with the i.p. route being more efficient when lower CsCl doses are used.

Estimation of dietary 232Th, 238U, cesium, and strontium intakes in Vietnamese people from different geographical regions.

Diet samples were collected to estimate dietary intakes of 232Th, 238U, cesium, and strontium for Vietnamese adults using duplicate portion studies and market basket studies. Average concentrations of 232Th, 238U, cesium, and strontium in diet samples were 4.0 ng/g-dry, 2.5 ng/g-dry, 41 ng/g-dry, and 4.5 ng/g-dry, respectively. Daily intakes per person for 232Th, 238U, cesium, and strontium were estimated to be 0.99 microg, 0.66 microg, 10 microg, and 1.2 mg, respectively. Daily intakes of 232Th, 238U, and cesium differed statistically between northern and southern of Vietnam, depending on geological conditions and food habits. However, intakes of the four nuclides were similar to the global averages.

Polymorphic ventricular tachycardia in a woman taking cesium chloride.

A 47-year-old patient presented with syncope and recurrent episodes of polymorphic ventricular tachycardia. She had evidence of prolonged QT interval by ECG and had been taking cesium as a dietary supplement. Correction of the hypokalemia and discontinuation of the cesium resulted in normalization of the QT interval during follow-up with no further recurrence of ventricular arrhythmias. The use of this drug is potentially hazardous as it may induce fatal ventricular arrhythmias.

Cellular basis of ventricular arrhythmias and abnormal automaticity in heart failure.

The high incidence of sudden death in heart failure may reflect an increased propensity to abnormal repolarization and long Q-T interval-related arrhythmias. If so, cells from failing hearts would logically be expected to exhibit a heightened susceptibility to early afterdepolarizations (EAD). We found that midmyocardial ventricular cells isolated from dogs with pacing-induced heart failure exhibited an increased action potential duration and many more EAD than cells from nonpaced controls; this was the case both under basal conditions (P < 0.01) and after lowering external K(+) concentration ([K(+)](o)) to 2 mM and exposing cells to cesium (3 mM; P < 0.05). An unexpected finding was the occurrence of spontaneous depolarizations (SD, >5 mV) from the resting potential that were not coupled to prior action potentials. These SD were observed in 20% of failing cells (n = 5 of 25) under basal ionic conditions but in none of the normal cells (n = 0 of 27, P < 0.05). The net inward current that underlies SD is not triggered by Ca(2+) oscillations and thus differs fundamentally from the currents that underlie delayed afterdepolarizations. We conclude that cardiomyopathic canine ventricular cells are intrinsically predisposed to EAD and SD. Because EAD have been linked to the pathogenesis of torsade de pointes, our results support the hypothesis that sudden death in heart failure often arises from abnormalities of repolarization. The frequent occurrence of SD points to a novel cellular mechanism for abnormal automaticity in heart failure.

Elucidating the mechanism of cesium-induced sustained monomorphic ventricular tachycardia in rabbits.

The mechanisms of sustained ventricular tachycardia (VT) induced by large cumulative dose of cesium chloride (Cs) remains unclear. Seven anesthetized rabbits were intravenously injected with Cs (1 mmol/kg) 3 times at 20-min intervals. The surface ECG and monophasic action potential of the left ventricular endocardium were simultaneously recorded. In another 12 rabbits, transmembrane action potentials of right ventricular muscles were recorded with glass microelectrodes. In experiments in vivo, sustained monomorphic VT was induced after the third injection of Cs, whereas the early afterdepolarization (EAD)-related nonsustained polymorphic VT was induced after the second injection. Overdrive pacing during the sustained VT resulted in postdrive acceleration. The pacing and recovery cycle lengths showed an inverse relation. In experiments in vitro, preparations were superfused with Tyrode's solution containing 7.5 mM Cs. Cs initially induced EADs. Additional exposure to Cs depolarized the membrane potential, which consequently attained threshold, producing spontaneous activities. Further exposure resulted in an induction of sustained rhythms that were accelerated by overdrive pacing. Our results indicate that the sustained rhythms at low membrane potential induced by a long exposure to Cs in vitro may underlie an electrophysiologic mechanism for the sustained VT induced after large cumulative dose of Cs in vivo.

Chromosome aberrations in Syrian hamsters following very low radiation doses in vivo.

This paper addresses a report of a large increase (approximately 6- to 11-fold) in chromosome aberrations in lymphocytes of persons in Salzburg attributed to their exposure to fallout from the Chernobyl cloud. Their additional exposure, approximately 0.3 mGy in 1 year, comprised about a 30% increase in their normal background radiation dose. The report has attracted considerable attention because, if correct, it seriously challenges assumptions of linearity in the low-dose response for chromosomal damage and, by implication, the linear, no-threshold hypothesis for risk of induced cancer. An experiment has been carried out with Syrian hamsters treated with caesium-137 to produce a range of doses comparable with those calculated for the persons in Salzburg. No significant elevation in lymphocyte aberration yields was found in the hamsters, thus arguing against the conclusions of the Salzburg study.

Hepatic neoplasms from internally deposited 144CeCl3.

Fifty-five dogs were exposed by inhalation to graded activity levels of 144CeCl3, a relatively soluble form of the beta-emitting radionuclide. A large portion of the 144Ce translocated from lung to liver and skeleton. Significant radiation doses were delivered to the respiratory tract, liver, and skeleton; however, the liver received the greatest cumulative absorbed dose. Liver tumors were the most frequently observed neoplasms in these exposed dogs and included 7 primary hepatic hemangiosarcomas, 1 cholangiocarcinoma, 1 hepatocellular carcinoma, 1 fibrosarcoma, 4 biliary cystadenomas, and 1 fibroma. The dose to the liver in these dogs ranged from 11 to 250 Gy with a median of 57 Gy. Autoradiographs showed a relative uniform distribution of beta dose to the liver. All the malignant tumors and 1 cystadenoma were primary causes of death. The morphologic features of the hemangiosarcomas and associated hepatic lesions were similar to those described for hemangiosarcomas induced in people exposed to Thorotrast. Biliary cystadenomas were associated with degenerative lesions in the liver but not with other neoplasms in the liver. These results indicate that the liver is an important target organ for effects from internally deposited 144Ce.

The use of an in vitro technique to predict the absorption of dietary radiocaesium by sheep.

The validity of an in vitro extraction technique to predict the availability for absorption of radiocaesium in the sheep gut has been assessed. The technique (a 2-h extraction with caesium chloride) was found to be valid for sources with a low availability for transfer across the gut, but inappropriate for ionic radiocaesium or radiocaesium incorporated internally within herbage. For such radiocaesium sources, which have a high in vitro availability, no correlation was found between in vitro extraction and true absorption measurements. A true absorption value of 0.80 is recommended for these sources, although values for individual sheep in the range 0.60 to 1.00 should be expected.

Biological effects of 137CsCl injected in beagle dogs.

The toxicity of intravenously administered 137CsCl in the beagle dog was investigated as part of a program to evaluate the biological effects of internally deposited fission-product radionuclides. The intravenous route of exposure was chosen for simplicity and accuracy because it was known that after intravenous injection, inhalation or ingestion, internally deposited 137CsCl is rapidly absorbed and distributed throughout the body, exposing the whole body to beta-particle and gamma radiations. Fifty-four dogs were injected intravenously with 137Cs to provide one group of six dogs with mean initial body burdens of 141 MBq 137Cs/kg body mass and four groups of 12 dogs each with mean initial body burdens of 104, 72, 52 and 36 MBq 137Cs/kg. Twelve dogs were injected with isotonic saline as study controls. Because the number of study control dogs was small, data from an additional 49 control dogs from other studies at the Inhalation Toxicology Research Institute that were performed over a similar span of years were also used. There was a significant, dose-dependent decrease in survival of the 137Cs-injected dogs. Eleven 137Cs-injected dogs, including all six in the highest initial body burden group, died within 81 days after injection, primarily due to hematopoietic cell damage resulting in severe pancytopenia. An additional 25 dogs had transient hematological dyscrasia but survived for long times. All 137Cs-injected male dogs had marked damage to the germinal epithelium of the testicular seminiferous tubules with azoospermia in the long-term survivors. Benign and malignant neoplasms occurred in a variety of organs in 137Cs-injected dogs, rather than in a single target organ. When individual organs were considered, the incidence of malignant neoplasms was increased in the liver and in the nasal cavity and paranasal sinuses of the 137Cs-injected dogs. There was a 137Cs treatment effect in the incidence of malignant neoplasms (P < 0.001) in male dogs but no 137Cs-related treatment effect in female dogs. However, when malignant mammary neoplasms were excluded from the analysis, there was no gender difference, and there was a dose-related response (P < 0.001) in both males and females for the incidence of malignant neoplasms.