Acquisition of American sign language by a noncommunicating autistic child

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents. Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1-2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1-2 ppm, the clearance values for hemoperfusion were some 5-7 times higher than those for hemodialysis. In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquats less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.     

Approach to the poisoned patient

Routine poison management involves the following: (1) stabilization, (2) toxidrome recognition, (3) decontamination, (4) antidote administration, (5) enhanced elimination of toxin, and (6) supportive care. Stabilization involves airway, ventilation, and circulation support. In the patient with altered mental status, oxygen, naloxone, glucose, and thiamine should be administered. Symptom complexes that relate to specific classifications of toxins are referred to as toxidromes. Emesis by means of syrup of ipecac is rarely used for in-hospital gastric decontamination. Activated charcoal is a useful adsorbent for gastric decontamination. Whole bowel irrigation is useful for iron, lead, and lithium poisoning and for the body packer phenomenon. Enhancement of elimination may involve multiple doses of activated charcoal, hemodialysis, or charcoal hemoperfusion.     

Treatment of extrahepatic occlusive jaundice with activated charcoal hemoperfusion in dogs

To find the feasibility of treatment for congenital bile duct atresia, we studied the usefullness of extracorporeal hemoperfusion over activated charcoal in canine obstructive jaundice. One, three and five weeks after ligation and disection of common bile duct in 5 dogs we performed the hemoperfusion over activated charcoal extracorporeally (group 3). In this animals we examined hematological and blood coagulation studies, serum electrolyte levels, kidney function tests and liver chemistries. As control in 5 animals we carried out after sham operation the perfusion without common bile duct ligation (group 2) and in 5 animals only common bile duct ligation without perfusion (group 1). In the liver chemistries we found 2 weeks after 2nd and 3rd perfusion (5 and 7 weeks after bile duct ligation) lower levels of serum bilirubin, GOT, GPT and SDH in treated group than in non-treated jaundiced animals. It suggest the effectiveness of hemoperfusion with activated charcoal in the treatment of occlusive jaundice. There were no alteration in the hematological studies, serum electrolyte levels and kidney function tests. PT and PTT was prolonged in the jaundiced animals there were no significant differences with and without hemoperfusion.     

Acute carbamazepine poisoning treated with plasmapheresis. Description of a clinical case

A case of severe Carbamazepine poisoning initially misdiagnosed is reported. Treatment consisted in plasmapheresis (3.5 liters exchanged) repeated for 3 consecutive days, in conjunction with activated charcoal and advanced life support. It was obtained a rapid decay in Carbamazepine plasmatic level (with rebound phenomenon only after first treatment day) and a contemporary improvement in clinical conditions. The patient was discharged without complications after 6 days stay in ICU. Taking pharmacokinetic characteristics into account, it is suggested that plasmapheresis may be useful in this kind of poisoning.     

Mushroom poisoning. New possibilities for treatment

Poisonous species of fungi in Germany are very few. Dangerous is the ingestion of raw, spoiled or poisonous mushrooms. There exist no reliable tests to determine whether a mushroom is safe except by expert examination and identification of the mushroom. In clinical practice the classification of mushroom poisoning is possible in muscarine-syndrome, gastroenteritic syndrome and in two-phase-syndrome. 90-95% of lethal mushroom poisonings are due to ingestion of Amanita phalloides. In severe cases extensive hepatic necrosis occurs, characterized by profound abnormalities in liver function caused by hepatic coma. In deep coma mortality rates amount to 70% or more. A new therapeutic measure (coated charcoal hemoperfusion)-first applied in liver failure by Chang (1972) and Williams (1973)-has been performed in 3 patients with severe poisoning after ingestion of Amanita phalloides (each patient had eaten at least 7-10 fungi Amanita phalloides). Two of the patients survived.     

Hemoperfusion by means of encapsuled charcoal for the treatment of exogenous and endogenous intoxications

The method developed by Chang for using in collodion and albumin encapsuled charcoal as artificial cells for hemoperfusion has been studied in vitro. The capacity for the absorption of more or less dialysable exogenous substances (barbiturate, Diazepam, Parathion) and an endogenous toxic metabolite (p-hydroxyphenyl acetic acid) has been examined. With the absorption unit one can eliminate 80 to 90 per cent of the initial concentration of barbiturate, Diazepam and p-hydroxyphenyl acetic acid in about 90 min, of Parathion about 50 per cent in the same time, whereas bromide and ammonia are not absorbed. Attempts to avoid regional heparinisation by the incorporation of heparin into the capsule of charcoal granules were not successful. Assuming correct preparation of the hemoperfusion system, observance of steril precoutions and regional heparinisation, the use of the "detoxication shunt" is a promising means in the treatment of severe exogenous and endogenous intoxications which are not accessible by conventional therapeutic means.     

Germ cell-specific enhancer activity of a repeated element in a variable region of the mouse genome

The initial evaluation and management of poisoned patients should be comprehensive and include an accurate history whenever possible, stabilization of the patient's condition, a physical assessment to evaluate the extent of poisoning and the presence of concurrent conditions, decontamination of the gastrointestinal tract using activated charcoal, gastric lavage, administration of ipecac or irrigation, poison-specific treatment with administration of antidotes when indicated and proper disposition. Consultation with a poison control center is often helpful in assessing and treating these patients.     

Paracetamol poisoning

Administration of paracetamol (acetaminophen) has analgetic and antipyretic effect. After trauma paracetamol has an anti-inflammatory activity. It was presumed that paracetamol in therapeutic doses had fewer and more acceptable side-effects than other analgetic drugs such as acetylsalicylic acid and NSAID-drugs. However, in toxic concentrations, paracetamol is more life-threatening. The toxic effects of paracetamol most often occur in the liver and kidneys. Phosphate and lactate turn-over can also be impaired. Paracetamol poisoning can induce temporary liver disfunction or even irreversible liver failure with liver transplantation as the only therapeutic possibility. Chronic alcoholics are especially at risk, as liver damage may occur following paracetamol even in recommended doses. When intoxication with paracetamol is presumed, administration of N-acetylcysteine is vital. N-acetylcysteine therapy should be initiated not later than 15 hours after paracetamol intake. Moreover, the antitoxic effect has been observed even when N-acetylcysteine therapy is initiated 24-36 hours after presumed paracetamol intake. Measures of preventing further absorption of paracetamol from the gastrointestinal tract should be taken. Activated charcoal should be given if less than two hours have passed since paracetamol intake. Between two and four hours following paracetamol intake gastric lavage should be performed. During the last 10 years the incidence of paracetamol self-poisoning has increased, but death following paracetamol poisoning is relatively constant at around nine per year in Denmark. It is suggested that the incidence of serious cases of paracetamol poisoning could be reduced by simple measures. Special attention should be paid to the risk-group of chronic alcoholics.     

Clinical and toxicological data in fenthion and omethoate acute poisoning

This study paper reports on two cases of poisoning with the organophosphorus insecticides, fenthion and omethoate. The two victims were admitted in the Intensive Care Unit (ICU) a few hours after ingestion of the two insecticides. They received appropriate treatment for organophosphorous poisoning (gastric lavage, activated charcoal, atropine and pralidoxime) and supportive care. Both patients survived. Organophosphate blood levels were determined on admission (fenthion 2.9 micrograms/ml, omethoate 1.6 micrograms/ml) and during the hospitalisation and proved to be considerably high. Slow elimination rate of the poison already distributed in the body was indicated for both pesticides. The patient with omethoate poisoning remained clinically well (Glasgow Coma Scale: 15) and was discharged three days later. The patient with fenthion poisoning, who had also ingested 30 mg of bromazepam and 720 mg of oxetoron, developed cholinergic crisis six hours after admission and was intubated for 24 days, with concomitant complications.     

The influence of haemoperfusion on haemostasis and cellular constituents of the blood in the treatment of intoxications: a comparative study of three types of columns (Haemocol, Amberlite XAD-4, Gambro Adsorba 300 C)

The influence of haemoperfusion on blood-coagulation and cellular constituents of the blood was studied in three groups of patients. In four patients haemoperfusion was performed using a column containing acrylic-hydrogel coated activated charcoal (Haemocol), in five patients with a column containing uncoated XAD-4 nonionic polystyrene resin (Amberlite) and in five patients with a column containing cellulose coated activated charcoal (Gambro Adsorba 300 C). Perfusion was performed during 4 h with a flow of 300 ml/min. Before the start, 2 h after the start, at the end and 2 h after the end of the perfusion the haemoglobin concentration, haematocrit, leucocyte number, differential white cell count, thrombocyte number and heparin concentration were measured. Before the start and 2 h after the end prothrombin time, thrombin time, partial thromboplastin time, reptilase time, fibrinogen, prothrombin, factors V, VII, X, antithrombin III, bleeding time (Ivy), ethanol gelation test, fibrin split products and plasminogen were measured. The following conclusions can be drawn: haemoperfusion per se causes haemodilution; polystyrene resin causes in some patients a temporary reduction of the leucocyte number during haemoperfusion; polystyrene resin causes a significant reduction of thrombocyte number compared to coated activated charcoal; polystyrene resin and to a lesser extent acrylic-hydrogel-coated activated charcoal causes in some patients a prolongation of bleeding time probably by inducing alteration of thrombocyte function caused by release; polystyrene resin and probably also acrylic-hydrogel-coated activated charcoal causes an increased fibrinolytic activity without signs of disseminated intravascular coagulation.     

Successful treatment by direct hemoperfusion of coma possibly resulting from mitochondrial dysfunction in acute valproate intoxication

PURPOSE: We evaluated the efficacy of direct hemoperfusion (DHP) for treatment of acute valproate (VPA) intoxication and speculate on the biochemical perturbations that suggest a mechanism of coma induced by VPA overdose. PATIENT AND METHODS: The comatose patient was hospitalized approximately 6 h after ingesting 18 g VPA. DHP, with 200 g activated charcoal, was performed for 6 h. The plasma concentrations of VPA and Glasgow coma scale scores after admission were estimated. Before and after DHP, urine samples were tested in serial fashion for VPA metabolites, organic acids, and acyl carnitine esters of fatty acids. RESULTS: Plasma VPA was efficiently adsorbed on activated charcoal. The patient's plasma concentration of VPA decreased from 471 microg/ml (2,830 microM) to 45 microg/ml (270 microM), at which point the patient became alert. The half-life (t1/2) of VPA was calculated as 4.4 h before DHP and as 1.8 h during DHP. Before DHP, lactate and VPA-glucuronide markedly increased in urine samples, but beta-keto-VPA, a major mitochondrial metabolite, was not detected. Urinary excretion of carnitine esters of medium chain (C8-C10) dicarboxylic acids was increased. After DHP, lactate and VPA-glucuronide decreased, but a significant amount of beta-keto-VPA was demonstrated. Carnitine esters of medium chain dicarboxylic acids were decreased. CONCLUSIONS: DHP with activated charcoal was effective treatment for the patient with acute VPA intoxication and coma. The onset of coma may have been related to inhibition of beta-oxidation in the mitochondria, which was reversible by elimination of plasma VPA by DHP.     

Acetylsalicylic acid loaded poly(vinyl alcohol) hemodialysis membranes: effect of drug release on blood compatibility and permeability

Membranes developed from poly(vinyl alcohol) (PVA) have superior permeability because of the highly hydrophilic character of PVA. However, its blood compatibility needs to be further improved. For this we have developed acetylsalicylic acid (ASA, aspirin) loaded PVA membranes. It seems that the slow release of aspirin from the membrane provides a surface concentration of aspirin sufficient for partially inhibiting platelet adhesion. PVA membrane with 531 micrograms cm-2 of ASA loaded, may be selected for hemodialysis applications. This may help to reduce the amount of heparin infused during hemodialysis, thereby reducing the side-effects associated with the systemic administration of heparin.     

An N-substituted polyurea coating with high affinity for heparin

A new N-substituted polyurea with tertiary amino groups in the polycarbamidic chain (NPUTA) has been synthesized. The polymer is soluble in C1-C4 alcohols, has high adhesion to polar molds, and has high H2O uptake (130-150%). The material can be coated on many biomaterials (polyurethanes, charcoal hemosorbents, cellulosic hemodialysis membranes), and high amounts of heparin can be adsorbed onto treated surfaces. NPUTA cast from 0.5-3.5% ethanol solutions can absorb large amounts of heparin from anti-coagulant solution (40-60 micrograms/cm2) and heparinized plasma. Heparin release into phosphate buffered saline (PBS) solution or plasma is minimal. The influence of NPUTA solution concentration and pre-absorbed heparin on the protein adsorption, platelet adhesion, surface induced hemolysis, and complement activation of these films has been investigated. Radiolabeled protein assays, radiolabeled platelet assays, and other methods were used. It was shown that modified surfaces for the listed materials, with heparinization, demonstrate improved in vitro blood compatibility without any changes in functional properties. For example, treatment with NPUTA/heparin does not reduce sorption of middle molecules by activated charcoal hemosorbent, while markedly and significantly decreasing platelet adhesion and complement activation. NPUTA/heparin modified, glutaraldehyde treated bovine pericardium exhibited significantly reduced calcification in a rat subcutaneous implant model. Other ex vivo circulation experiments also confirm the blood compatibility of different NPUTA treated surfaces.     

Treatment of sepsis by extracorporeal elimination of endotoxin using fiber-immobilized polymyxin B

To remove endotoxin directly from the blood, an affinity adsorbent (PMX) has been developed. PMX is composed of a ligand of polymyxin B and a carrier of polystyrene fibers. We treated 16 patients, suffering from septic shock or multiple organ failure by PMX-F hemoperfusion. The pretreatment level of endotoxin decreased significantly from 80pg/ml to 21pg/ml on average 2 hours after the hemoperfusion. The hyperdynamic status in the cardiac index and the decreased systemic vascular resistance, which are characteristic to endotoxin shock, were normalized after the treatment. In septic shock patients with systolic pressure under 10mmHg, the systolic pressure increased significantly from pretreatment level. Nine of the sixteen patients remained alive for two weeks after the therapy, and seven out of the nine patients discharged alive. Hemoperfusion with PMX is likely to become an effective treatment for sepsis and septic shock.     

Cyclic changes of cervical mucus enzymes related to the time of ovulation II. Amino peptidase and esterase

Diconium bromide, 2-(3,4-dichloroanilino)-quinolizinium bromide, a potent antispasmodic in the lower bowel of the dog, was found in the present study to exert gastric acid-antisecretory and antiulcerogenic activities in the rat stomach. These effects were demonstrated by means of short- and long-term pyloric ligation, acetylsalicylic acid (ASA)-induced ulcerogenesis, and cold-and-restraint stress studies. A reduction of gastric acid concentration by the drug was probably responsible for the decrease in the degree of ulceration and hemorrhagic lesion formation. The drug's inhibition of stress hemorrhagic lesions may be related to an effect both on gastric HCl secretion and on the vasculature in the glabdular mucosa. The delay of gastric emptying by diclonium bromide results from its known antispasmodic or smooth-muscle depressant action. The toxicity of diclonium bromide, perorally, was low in rats and overt signs of drug effect were not evident until toxic doses were administered. It is concluded that diclonium bromide may represent a useful non-anticholinergic drug effective in treating both peptic ulcers and spasticity of the colon (irritable-colon syndrome) in man.     

Cholestyramine as an adsorbent in acute lindane poisoning: a murine model

STUDY OBJECTIVES: To compare the effectiveness of single-dose cholestyramine versus single-dose activated charcoal in preventing clinical toxicity after acute lindane ingestion. DESIGN: CD-1 mice received lindane by enteral (gavage) and parenteral (intraperitoneal) routes, followed by enteral administration of either cholestyramine (2.25 g/kg) or activated charcoal (2.25 g/kg), with subsequent observation for convulsions and death. MEASUREMENTS: The doses of lindane at which 50% of mice developed convulsions (CD50) and at which 50% of mice died (LD50) were established and compared among control, charcoal-, and cholestyramine-treated groups. RESULTS: For lindane administered by gavage, the differences in the CD50 and LD50 between the control and the activated charcoal groups were not statistically significant. However, a significant difference did exist in both the CD50 and the LD50 between the group receiving cholestyramine and the control group and between the cholestyramine and activated charcoal groups. After IP administration of lindane, the difference in CD50 or LD50 among control, activated charcoal, or cholestyramine groups was not significantly different. CONCLUSION: In the murine model, cholestyramine is more effective than activated charcoal in preventing absorption of lindane, thus preventing convulsions and death. These data support the need for clinical studies to determine whether cholestyramine may be a more effective treatment than activated charcoal for acute lindane ingestions in human beings.     

Excretion of endogenous and exogenous purine derivatives in sheep: effect of increased concentrate intake

The scintigraphic measurement of colonic transit is currently performed using 111In ion exchange resin pellets delivered to the colon in a capsule coated with a pH sensitive polymer, methacrylate, which dissolves in the distal ileum. However, in the USA, this requires an investigational drug permit. Our aim was to evaluate the in vitro binding characteristics of activated charcoal in milieus that mimicked gastric and small intestinal content. The in vitro incubation of activated charcoal was performed with Na99Tc(m)O4, 99Tc(m)-DTPA, 111InCl3, 111In-DTPA, 201TlCl and 67Ga-citrate in the pH range 2-4 and pH 7.2 at 37 degrees C. We estimated the association of radiopharmaceuticals with the activated charcoal over a 3 h in vitro incubation. With the exception of 67Ga-citrate, the association of activated charcoal with the other radiopharmaceuticals was approximately 100% throughout the 3 h incubation. In conclusion, activated charcoal appears to adsorb avidly with common radioisotopes, and appears promising as an alternative to resin ion exchange pellets used for the measurement of gastrointestinal transit by scintigraphy.     

Q-T prolongation and polymorphous ("torsade de pointes") ventricular arrhythmias associated with organophosphorus insecticide poisoning

It is not generally appreciated in the Western world that organophosphorus poisoning may be associated with a serious and often fatal cardiac complication: Q-T interval prolongation with malignant ventricular arrhythmias of the "torsade de pointes" type. This insidious complication may lead to delayed, sudden death after the patients appears to be well on the way to recovery from the other, more dramatic respiratory and neurologic symptoms. In this study 15 patients with organophosphorus poisoning are described. Q-T prolongation was observed in 14 and malignant tachyarrhythmias in 6. In view of the dismal prognosis of these patients, ventricular pacing, previously used with success in other conditions associated with this syndrome, was tried in four patients and successfully shortened the Q-T interval and eliminated the arrhythmias. Isoproterenol did the same in a fifth patient. Awareness of this lethal, but preventable complication of organophosphorus poisoning is called for. Careful electrocardiographic monitoring is necessary until the Q-T interval returns to normal. Electrical pacing appears to be the treatment of choice for the tachyarrhythmias.     

The significance of coagulation disorders and the inflammatory reaction in an infectious model of rheumatoid arthritis. II. Inhibition trials with antirheumatic drugs in the inflammatory reaction phase of erysipelas polyarthritis in rats

The arthritic activity in the initial phase and during manifestation of experimental erysipelas in rats, an animal model for human rheumatoid arthritis, was studied by plethysmometrical methods. The development of body weight and specific pathologic alterations peculiar to the model such as keratitis, thrombosis of the aorta and gangrene of the tip of the tail served as additional parameters. In the volumetric analysis it could be shown that the first arthritic swelling on both hind legs develops symmetrically up to day 6 post infection in rats with about 200 g of body weight-and in contrast-on the 2nd p.i. in younger animals with about 120 g. The first maximal paw volume was measured on day 9 p. i., the greatest decrease in body weight-a reduction of 25%-on day 10 p. i. In addition the reaction of the animal model following the application of steroid and non-steroid symptomatically as well as cytostatically acting antirheumatic drugs was tested. Daily treatment with acetylsalicylic acid, indomethacine or hydrocortisone provoked more or less significant inhibition of arthritic swelling in the paw. Only at the onset of arthritis acetylsalicylic acid was more effective than the other antiphlogistic drugs. No measurable increase of paw volume during cyclophosphamide treatment could be evaluated. None of the antirheumatics used had a positive effect on body weight developement. In hydrocortisone and also in cyclophosphamide treated rats a greater decrease was obtained than in the infected controls. No thrombosis developed after cytostasis with cyclophosphamide. The advantages of this systemic connective tissue disease with regard to its comparability with human rheumatoid arthritis and due to the course of its arthritic manifestation are discussed, together with the disadvantages specific to the model and the experimental conditions.     

Position statement: single-dose activated charcoal. American Academy of Clinical Toxicology; European Association of Poisons Centres and Clinical Toxicologists

In preparing this Position Statement, all relevant scientific literature was identified and reviewed critically by acknowledged experts using agreed criteria. Well-conducted clinical and experimental studies were given precedence over anecdotal case reports and abstracts were not usually considered. A draft Position Statement was then produced and subjected to detailed peer review by an international group of clinical toxicologists chosen by the American Academy of Clinical Toxicology and the European Association of Poisons Centres and Clinical Toxicologists. The Position Statement went through multiple drafts before being approved by the boards of the two societies and being endorsed by other societies. The Position Statement includes a summary statement for ease of use and is supported by detailed documentation which describes the scientific evidence on which the Statement is based. Single-dose activated charcoal should not be administered routinely in the management of poisoned patients. Based on volunteer studies, the effectiveness of activated charcoal decreases with time; the greatest benefit is within 1 hour of ingestion. The administration of activated charcoal may be considered if a patient has ingested a potentially toxic amount of a poison (which is known to be adsorbed to charcoal) up to 1 hour previously; there are insufficient data to support or exclude its use after 1 hour of ingestion. There is no evidence that the administration of activated charcoal improves clinical outcome. Unless a patient has an intact or protected airway, the administration of charcoal is contraindicated.