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One for all--a multi-use dialysis system for effective treatment of severe thallium intoxication.

Guided by the idea of providing a stable electrolyte composition of the dialysate, the late Bernd Tersteegen designed a machine ingeniously combining the advantages of a closed tank hemodialysis system with the efficacy and bacteriological safety of a single-pass system. Several thousand dialysis sessions have been performed with this system in the chronic hemodialysis population. Recently, highly efficient (i.e. high volume) dialysis systems have been successfully introduced for the treatment of critically ill patients in the intensive care unit as extended dialysis. Furthermore, they can also be a safer, more effective and less costly alternative to traditional extracorporeal techniques in the treatment of severe intoxication. In a case-based approach, we review the increasing use of such a system.

Critical Care↗

Neuropathologic findings of bromethalin toxicosis in the cat.

Ten random source male domestic shorthair cats, 2 to 6 years old and 3.0-4.4 kg body weight, were each given a single oral dose (1.5 mg/kg) of bromethalin (cat Nos. 1-5) or bait vehicle carrier (cat Nos. 6-10). Bromethalin-dosed cats developed a toxic syndrome characterized by ataxia, focal motor seizures, vocalization, decerebrate posture, decreased conscious proprioception, recumbency, depression, and semicoma. Bromethalin-dosed cats were euthanatized if seizure activity or hindlimb paralysis developed. Survival times were 48 hours (cat No. 1), 89 hours (cat No. 2), 90 hours (cat No. 3), and 97 hours (cat No. 4). Control cats (cat Nos. 6-10) and one bromethalin-dosed cat (cat No. 5) were euthanatized on day 20 after dosing. Spongy change (edema--characterized by the formation of vacuoles in extracellular spaces and myelin lamellae), hypertrophied fibrous astrocytes, and hypertrophied oligodendrocytes were observed in the white matter of the cerebrum, cerebellum, brain stem, spinal cord, and optic nerve of all bromethalin-dosed cats. Spongy change occasionally extended into contiguous cerebellar Purkinje cell layer and cerebral cortical gray matter. The severity of lesions varied among cats but was most pronounced in cat No. 5 (480 hours after dosing). A leukocytic inflammatory response, gitter cell (macrophage) response, or axonal degeneration was not observed in the vacuolated areas. Ultrastructural findings included separation of myelin lamellae at the interperiod lines with the formation of intramyelinic vacuoles (intramyelinic edema), rupture and coalescence of intramyelinic vacuoles into larger extracellular spaces (spongy change), and pronounced cytosolic edema of astrocytes and oligodendroglial cells.

Aniline Compounds↗

Superwarfarin (brodifacoum) poisoning.

A case of self-ingestion of brodifacoum that resulted in spontaneous intra-abdominal haemorrhage, circulatory shock, rhabdomyolysis and acute renal failure is reported. Current knowledge and management of superwarfarin poisoning are discussed.

4-Hydroxycoumarins↗

Specific anti-digoxin Fab fragments: an available antidote for proscillaridin and scilliroside poisoning?

The purpose of this study was to evaluate the capacity of specific anti-digoxin Fab fragments to bind to and neutralize scilliroside and proscillaridin in acute poisoning. Apparent affinity constants were determined with values of 2.6 10(8)M-1 for scilliroside and 3.8 10(7)M-1 for proscillaridin. These results are in accordance with a possible in-vivo neutralization of these toxins.

Antibody Affinity↗

Persistence of sodium monofluoroacetate in livestock animals and risk to humans.

1. Sodium monofluoroacetate (1080), a vertebrate pesticide widely used in New Zealand, was administered orally to sheep and goats at a dose level of 0.1 mg kg-1 body weight to assess risk to humans of secondary poisoning from meat. Blood, muscle, liver, and kidney were analysed for 1080 residues. 2. The plasma elimination half-life was 10.8 h in sheep and 5.4 h in goats. Concentrations of 1080 in muscle (0.042 microgram g-1), kidney (0.057 microgram g-1), and liver (0.021 microgram g-1) were substantially lower than those in plasma (0.098 microgram ml-1) at 2.5 h after dosing. 3. Only traces of 1080 (< 0.002 to 0.008 microgram g-1) were found in sheep tissues after 96 hours. 4. Livestock are normally excluded from areas where 1080 is being used for pest control, reducing the risk of secondary poisoning. Even with accidental exposure to a sublethal dose 1080 would not persist in tissues for more than a few days because it is cleared rapidly from the body. Therefore the occurrence of 1080 in meat intended for human consumption is highly unlikely.

Animals↗

Persistence of sodium monofluoroacetate in rabbits and risk to non-target species.

1. Sodium monofluoroacetate (1080), a vertebrate pesticide used in New Zealand, was administered orally to rabbits at two dose levels (sub-lethal and lethal) to determine how long 1080 would persist in plasma, liver, kidney, and muscle so that the risk of consumption of meat from lethally or sub-lethally poisoned rabbits by non-target species could be assessed. 2. The plasma elimination half-life in rabbits receiving a sub-lethal dose was 1.1 h. Retention of 1080 in tissue was greater in rabbits dosed with a lethal dose than in those that received a sub-lethal dose. Irrespective of the dose level, concentration of 1080 in muscle, kidney, and liver was substantially lower than in the plasma. 3. Poisoning of dogs is possible because of their extreme susceptibility to 1080. Poisoning of birds is less likely. The risk of secondary poisoning is reduced as the concentration of 1080 declines in putrefying carcasses.

Administration, Oral↗

Covert poisoning with difenacoum: clinical and toxicological observations.

1. The coumarin anticoagulant difenacoum was detected by high performance liquid chromatography (HPLC) with multi-wavelength UV detection in plasma from a 41 years old man who presented with a severe deficiency of vitamin K-dependent clotting factors of unknown aetiology. A longitudinal toxicological study of the consequent coagulopathy is described. 2. Plasma concentrations of difenacoum declined from 0.97 to 0.11 mgl-1 in 47 days with a terminal half life of 11.7 days. Rifampacin (300 mg bd) had no apparent effect on the terminal half life of the drug. Subsequently plasma concentrations of difenacoum and descarboxyprothrombin (DCP) unexpectedly increased. 3. Seven months after exposure clotting times were prolonged. The patient continued to have episodes of epistaxis, haematoma, purpurae and bruising and he required frequent treatment with Fresh Frozen Plasma in additional to oral phylloquinone (200 mg day-1). 4. Intermittent and unexpected increases in plasma concentrations of difenacoum and descarboxypro-thrombin suggested that covert, repeated ingestion of the anticoagulant was the most likely cause of the poisoning. The measurement of low concentrations of plasma phylloquinone except following supervised ingestion of the vitamin indicated that as an outpatient, the subject was not compliant with treatment despite his protestations to the contrary. He continued to deny this even when confronted by laboratory findings and at no time did he ever admit to self-poisoning.

4-Hydroxycoumarins↗

Chlorophacinone exposure causing an epizootic of acute fatal hemorrhage in lambs.

This report describes an epizootic of chlorophacinone toxicosis in lambs with severe acute hemorrhages. Eleven lambs, approximately 1-2 months of age, suddenly developed epistaxis, respiratory distress, and facial and cervical swelling. Affected animals died within 1-2 hours from the onset of clinical signs. Two lambs were available for complete postmortem examination. Gross lesions included mucosal and organ pallor, icterus, melena, and lung edema, as well as thymic, cervical muscle, and intra-articular hemorrhage. Histologically hepatocellular centrolobular necrosis was observed. The anticoagulant chlorophacinone was detected in the livers at 0.58 ppm and 0.50 ppm (wet weight), respectively. The source of exposure to chlorophacinone was old bait material placed between the wall studs of the building housing the ewes and lambs. The lambs were able to reach the bait through a hole in the plywood interior wall of the building.

Animals↗

Diagnosis of bromethalin toxicosis in the dog.

Dogs given a single oral dose of bromethalin at 6.25 mg/kg developed a toxic syndrome characterized by hyperexcitability, tremors, seizures, depression, and death within 15-63 hours after bromethalin administration. Gross lesions included mild cerebral edema (2/5) and mild pulmonary congestion (2/5). Histologic lesions included diffuse white matter spongiosis (5/5), mild microgliosis (3/5), optic nerve vacuolization (3/5), mild thickening of Bowman's capsule (2/5), and occasional splenic megakaryocytes (2/5). Ultramicroscopic examination of midbrain stem revealed occasional swollen axons, intramyelinic vacuolization, and myelin splitting at the intraperiod line. Bromethalin was detected in kidney, liver, fat, and brain tissues, using gas chromatography with electron capture detection. Photodegradation of extracted bromethalin may limit accurate quantification of tissue residues.

Adipose Tissue↗

Comparison of transcriptional responses in liver tissue and primary hepatocyte cell cultures after exposure to hexahydro-1, 3, 5-trinitro-1, 3, 5-triazine.

BACKGROUND: Cell culture systems are useful in studying toxicological effects of chemicals such as Hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), however little is known as to how accurately isolated cells reflect responses of intact organs. In this work, we compare transcriptional responses in livers of Sprague-Dawley rats and primary hepatocyte cells after exposure to RDX to determine how faithfully the in vitro model system reflects in vivo responses. RESULTS: Expression patterns were found to be markedly different between liver tissue and primary cell cultures before exposure to RDX. Liver gene expression was enriched in processes important in toxicology such as metabolism of amino acids, lipids, aromatic compounds, and drugs when compared to cells. Transcriptional responses in cells exposed to 7.5, 15, or 30 mg/L RDX for 24 and 48 hours were different from those of livers isolated from rats 24 hours after exposure to 12, 24, or 48 mg/Kg RDX. Most of the differentially expressed genes identified across conditions and treatments could be attributed to differences between cells and tissue. Some similarity was observed in RDX effects on gene expression between tissue and cells, but also significant differences that appear to reflect the state of the cell or tissue examined. CONCLUSION: Liver tissue and primary cells express different suites of genes that suggest they have fundamental differences in their cell physiology. Expression effects related to RDX exposure in cells reflected a fraction of liver responses indicating that care must be taken in extrapolating from primary cells to whole animal organ toxicity effects.

Animals↗

Hemodynamic abnormalities in sodium monofluoroacetate intoxication.

Hypotension is one of the most important predictors of mortality in sodium monofluoroacetate (SMFA) intoxication. This paper reports the hemodynamic response in one fatal and another survival case of SMFA intoxication. Despite correction of hypovolemia and with inotropic support, the patients remained in shock. Hemodynamic observations have provided evidence that shock after SMFA intoxication is due to diminished systemic vascular resistance and increased cardiac output. This is the first report in which such an invasive hemodynamic investigation has been recorded in a clinical case of SMFA intoxication.

Adult↗