Search

Amyl nitrite has been recommended as a cyanide antidote for several decades. Its antidotal properties were initially attributed to induction of methemoglobin and later to a nitric oxide mediated hemodynamic effect. The ease of administration and alleged rapid clinical effect would recommend its wide use in the pre-hospital management of mass casualty cyanide poisoning; yet there are concerns regarding the use of amyl nitrite for this indication.Review the data on amyl nitrite in cyanide poisoning and evaluate its efficacy and safety in mass casualty cyanide poisoning.A literature search utilizing PubMed, Toxnet, textbooks in toxicology and pharmacology, and the bibliographies of the articles retrieved identified 17 experimental studies and human reports on the use of amyl nitrite in cyanide poisoning, and 40 additional articles on amyl nitrite's properties and adverse effects. One paper was excluded as it was a conference abstract with limited data.The antidotal properties of amyl nitrite were attributed initially to induction of methemoglobinemia and later to nitric oxide mediated vasodilation.Animal studies on the use of amyl nitrite in cyanide poisoning are limited, and their results are inconsistent, which makes their extrapolation to humans questionable.Clinical reports are limited in number and the part played by amyl nitrite relative to the other treatments administered (e.g. life support, sodium nitrite, and sodium thiosulfate) is unclear.Amyl nitrite can be associated with potentially serious adverse reactions such as hypotension, syncope, excessive methemoglobinemia, and hemolysis in G6PD deficient patients. These effects are more pronounced in young children, in the elderly, and in patients with cardiac and pulmonary disorders. Dose regimen. The method of administration of amyl nitrite (breaking pearls into gauze or a handkerchief and applying it intermittently to the victim's nose and mouth for a few minutes) is not easily controlled, might result in under- or over-dosing, can prevent the caregiver from administering life support, and possibly expose him/her to amyl nitrite's adverse effects.Administration of amyl nitrite in mass casualty cyanide poisoning can result in unnecessary morbidity and may interfere with the proper management of the incident and the required supportive treatment and rapid evacuation. In the authors' opinion these drawbacks make the use of amyl nitrite in pre-hospital mass casualty cyanide poisoning unwarranted.

Methods: We conducted a prospective, representative-sample nationwide study on morbidity related to 3,4, methylenedioxymethamphetamine (MDMA; ‘ecstasy’) as determined from admissions to 5 geographically representative emergency departments (EDs) and from data from the poison information center (PIC). MDMArelated ED admissions were analyzed over a 7-month period and the records of all PIC calls were reviewed. Results: There were 52 (age 15—44 years, 32 males) ecstasy-related ED admissions during the study period. Most (68%) admissions presented to the ED at night, 52% on weekends and 44% consumed the drug at clubs and parties. Forty-six percent of the patients took between 1/2 to 3 tablets and 29 patients (56%) had taken ecstasy before. Twenty-two subjects (42%) reported poly-drug use. Fifteen subjects (29%) required hospitalization, six of them (11%) to the intensive care unit. The most common manifestations were restlessness, agitation, disorientation, shaking, high blood pressure, headache and loss of consciousness. More serious complications were hyperthermia, hyponatremia, rhabdomyolysis, brain edema and coma. Conclusion: The image of ecstasy as a safe party drug is spurious. The results of this study confirm that the drug bears real danger of physical harm and of behavioral, psychological and psychiatric disturbances.

The objective of this study was to determine the reliability of denial of acetaminophen ingestion in intentional drug overdose patients. All intentional drug overdose patients admitted to an emergency department who were able to provide a history were included. A detailed history was obtained on names, timing and number of medications ingested, and serum acetaminophen was assayed. Multidrug ingestion was defined as the reporting of ≥2 medications. Patients were considered ‘reliable’ if they reported acetaminophen ingestion and had detectable acetaminophen levels or the other way around. Validity parameters of acetaminophen history were assessed by sensitivity, specificity and positive and negative predictive values. A total of 154 patients were included. History was significantly more reliable in patients who denied ingestion of acetaminophen (n = 107) compared with patients who reported it (n = 47; 95.3% vs 65.9%, respectively; p < 0.0001, 95% CI of the difference 17.5%—41.2%). No suicidal patient who denied both acetaminophen and multidrug ingestions had a detectable acetaminophen level (negative predictive value 1, 95% CI 0.93—1.0). It is suggested that denial of both acetaminophen and multidrug ingestions by intentional drug overdose patients after a thorough history taking can be considered reliable for acetaminophen history. In facilities with limited resources, these patients may not require routine acetaminophen screening.

Venous PCO(2) and PO(2) in the presence of normal arterial PCO(2) and PO(2) in patients with alcoholic intoxication have not been previously evaluated. The objective of this study was to compare arterial and venous blood gases in patients with alcoholic intoxication and healthy controls. Sixteen patients with alcoholic intoxication and 20 controls underwent simultaneous blood sampling from a radial artery and an antecubital vein for acid-base analysis. Osmolality and ethanol blood concentration was estimated. Elevated venous pO(2) were found in 56% of patients with alcoholic poisoning compared with 15% of controls. A formula was found describing possible arterio-venous shunt accounting for elevated venous pO(2) and enabling calculation of the relevant venous carbon dioxide content and CO(2) product. The values of the venous pO(2) and arterio-venous shunt were more significant in the alcohol group than in controls (p = 0.002, p = 0.001, respectively). Percentage of patients with a-v shunts was significantly higher in the alcohol group (81%) than in controls (25%) (p = 0.002, OR 2.6, 95% CI 0.13-6.52). The relevant venous CO(2) and CO(2) product had the non-significant trend to be higher in the alcohol group. In conclusion, this study reports ethanol-induced venous pO(2) and pCO(2) elevation. This may be associated with the effects of tissue perfusion stealing and high oxygen consumption. On the other hand, possible beneficial consequences may occur: acceleration of alcohol elimination and reduction of alcohol-induced tissue damage.

Background. Many species of the genus Inocybe (family Cortinariaceae, higher Basidiomycetes) are muscarine-containing mycorrhizal mushrooms, ubiquitous around the world. The few published reports on the poisonous Inocybe mushrooms are often limited by the inadequate identification of the species. The clinical course of patients with typical muscarinic manifestations, in whom Inocybe spp. was unequivocally identified, is reported. Case series. Between November 2006 and January 2008 14 consecutive patients with typical muscarinic syndrome after mushroom ingestion were recorded. The clinical manifestations included combinations of nausea, vomiting, diarrhea, abdominal pain, hypersalivation, diaphoresis, tachycardia, bradycardia, hypotension, lacrimation, blurred vision, miosis, tremor, restlessness, flushing, and syncope. Time to onset of toxicity ranged between 15 min and 2 h after consumption, 5 h in one patient. Treatment was supportive, including intravenous fluids, antiemetics, and 1 mg atropine intravenously. Full recovery ensued within 12 h. In all the cases, an expert mycologist unequivocally identified the leftovers of the consumed mushrooms as Inocybe fastigiata, Inocybe geophylla, and Inocybe patouillardii. Conclusion. In this case series of patients who ingested identified muscarine-containing mushrooms supportive treatment and atropine resulted in recovery in all cases.

Publisher Summary After the establishment of the State of Israel in 1948, the discipline of Toxicology received a tremendous uplift throughout the country. The importance of the discipline has been increasingly recognized and Toxicology has been pursued and developed in university departments and governmental agencies. Attention is being drawn to the adverse effects of pollution. The marketing and utilization of pesticides are regulated by the Ministries of Agriculture and Environmental Protection. Air quality is closely monitored by the Ministry of Environmental Protection. Disposal of hazardous wastes is regulated and specific sites have been allocated. The Israel Institute of Standards has established standards which are being regularly updated for the protection of human health and the environment. The Ministry of Health regulates and controls the marketing and utilization of medications as well as of water and food quality.

Many uncertainties exist in regard to counseling women with occupational exposures during pregnancy. This is due to limited knowledge of the reproductive toxicologic effects of industrial agents, lack of safety standards aimed at protecting the fetus, and limitations in assessing the extent of exposure. The approach to this subject taken by the Motherisk Program and a review of the three most common occupational exposures are presented. Epidemiologic studies and measurements of radiation do not suggest a reproductive hazard for video display terminals. Exposure to organic solvents is hard to quantitate, and information is sparse and sometimes contradictory, and therapeutic decisions are difficult to reach. To date there is no convincing evidence that working with organic solvents within safety regulations would harm a fetus, in contradistinction to detrimental fetal effects of solvent abuse. The reproductive risks of lead are well documented, fetal exposure can be assessed, and effective treatment exists, but its effects on the pregnancy have not been fully established. However, new evidence suggests that maternal levels that are much lower than the accepted adult limits may be damaging to the fetus.

We report our experience with the use of tissue plasminogen activator to treat 12 infants and children with various thromboembolic states after conventional thrombolytic agents had failed. The dosage range was between 0.1 to 0.5 mg/kg per hour. Complete clot dissolution occurred in seven cases after 2 hours to 3 days of therapy. Partial clot dissolution and clinical improvement were noted in another four patients. Bleeding complications were noted in 6 of the 12 patients and included bruising, oozing from various venipuncture sites, and bleeding; these complications were controlled by clinically available means. In all cases with bleeding the dose rate was in the higher range (0.46 to 0.50 mg/kg per hour). In one patient, restlessness, agitation, and screaming were noted during administration of tissue plasminogen activator and when it was reinstituted. We conclude that tissue plasminogen activator is effective in inducing clot lysis in children. Because the effective dose appears to overlap with those causing bleeding, we recommend that a dose of 0.1 mg/kg per hour be started and increased gradually if clot dissolution does not occur, with close monitoring for bleeding.

REFERENCES 1. Gentz J, Johansson S, Lindblad B, Lindstedt S, Zetterstrom R. Excretion of delta-aminolevulinic acid in hereditary tyrosinemia. Clin Chim Acta 1969;23:257-63. 2. Grant DP, Larochelle J, Lambert M, et al. Neurologic crises in hereditary tyrosinemia. N Engl J Med 1990:432-7. 3. Tschudy DP, Lamon JP. Porphyrin metabolism and the porphyrias. In: Bondy PK, Rosenberg LE, eds. Metabolic control and disease. Philadelphia: WB Saunders, 1980:939-1007. 4. Pierach C. Hematin therapy for the porphyric attack. Semin Liver Dis 1982;2:125-31. 5. Linblad B, Lindstedt S, Steen G. On the enzymic defects in hereditary tyrosinemia. Proe Natl Acad Sci USA 1977; 74:4641-5. 6. Kang ES, Gerald PS. Hereditary tyrosinemia and abnormal pyrrole metabolism. J PED1ATR 1970;77:397-406. 7. Yamamoto M, Hayashi N, Kikuchi G. Regulation of synthesis and intracellular translocation of delta-aminolevulinate synthase by heine and its relation to the heme saturation of tryptophan pyrrolase in rat liver. Arch Biochem Biophys 1981;209:451-9. 8. Mustajoki P, Tenhunen R, Pierach C, Volin L. Heine in the treatment of porphyrias and hematological disorders. Semin Hematol 1989;26:1-9. 9. Tuchman M, Freese DK, Sharp HL, Ranaraine M, Ascher N, Bloomer JR. Contribution of extrahepatic tissues to biochemical abnormalities in hereditary tyrosinemia type 1: study of three patients after liver transplantation. J PEDIATR 1987; 110:399-403.

Scombroid fish poisoning is an acute illness caused by consumption of fish containing high concentrations of histamine. Improper handling of fish leads to bacterial contamination. Bacterial enzymes convert histidine to histamine. Symptoms develop quickly and resemble an immunoglobulin E-mediated allergic reaction. The diagnosis is often missed. Serious complications (e.g., bronchospasm, hypotension) are infrequent.To evaluate the prevalence and characteristics of scombroid fish poisoning in Israel as reported to the national poison information center.We conducted a retrospective poison center chart review from January 2005 to December 2007.During the study period, 21 events of scombroid poisoning involving 46 patients were recorded. Tuna was the commonest fish consumed (84.7%). Clinical manifestations developed within 20 minutes in 65.2% of the patients. The main clinical manifestations included rash (41%), flushing (37%), gastrointestinal complaints (37%) and headache (30.4%). About 25% had abnormal vital signs; two patients developed hypotension. Treatment was supportive and included mainly H1-antagonists (65.2%) and fluids (13%). Five patients were initially misdiagnosed as having an allergic reaction and were treated with corticosteroids (four patients) and epinephrine (one patient).Scombroid fish poisoning should be suspected in patients with histamine-like manifestations that are temporally related to fish (mainly tuna) consumption, especially in outbreaks. Although scombroid poisoning is often self-limited and responds well to antihistamines, prolonged observation may be required as severe toxicity can supervene. Proper handling of fish and urgent notification of the Ministry of Health are mandatory in order to prevent this potentially serious public heath problem.

The Israel National Poison Information Center, Rambam Health Care Campus, provides telephone consultations on clinical toxicology as well as drug and teratogen information around the clock. The Center participates in research, teaching and regulatory activities and also provides laboratory services.To analyze data on the epidemiology of poisonings and poison exposures in Israel.We conducted computerized queries and a descriptive analysis of the medical records database of the IPIC during 2007.Overall, 26,738 poison exposure cases were recorded, a 118.5% increase compared to 1995. Children under 6 years old were involved in 45% of cases; 73% of the calls were made by the public and 25.5% by physicians; 74.4% of exposures were unintentional and 9.2% intentional. Chemicals were involved in 37.9% of cases, pharmaceuticals in 44.2%, bites and stings in 4.3% and poisonous plants in 1.2%. Substances most frequently involved were analgesics, cleaning products and antimicrobials. Clinical severity was moderate/major in 3.5%. Substances most frequently involved in moderate/major exposures were insecticides, drugs of abuse and corrosives. Eight fatalities were recorded - three unintentional exposures (all chemicals) and five intentional (chemicals, medications, drugs of abuse).The rates of poison exposures and poisonings in Israel have increased significantly, contributing substantially to morbidity and mortality. The IPIC database is a valuable national resource for collecting and monitoring cases of poison exposure and can be used as a real-time surveillance system. It is recommended that reporting to the IPIC become mandatory and that its activities be adequately supported by national resources.

Due to extensive activity at sea, certain human populations, especially fishermen, are exposed to direct contact with the sea's inhabitants, including dangerous marine animals.To characterize and assess the extent of injuries caused by marine organisms along the Mediterranean coast of Israel, their type, severity and the medical treatment given.Data were obtained from a survey on injuries from marine organisms conducted among professional fishermen along the Mediterranean coast of Israel and from medical records reporting toxicological consultations provided by the Israel Poison Information Center.Injuries caused by marine organisms are not rare in Israel, but most cases are not severe. The most common injuries reported by fishermen were caused by stingrays (30%), weever fish (22%), rabbit fish (13%), and marine catfish (10%) - a new Red Sea immigrant. Most fishermen tend to treat such injuries themselves and sought medical help only when an unknown venomous fish was involved. Most cases of severe toxicity were due to secondary infection. Data from the IPIC indicated that 64% of the calls were from the general public and the rest came from physicians in health care facilities. Four sources of injuries were identified: cleaning and preparing fish for consumption, during leisure water sport activities, handling marine aquaria, and fishing. Most cases from the IPIC were graded as minor severity (85%) and were treated symptomatically.We recommend that medical facilities be installed at the fishing anchorages and that a separate category be established for injuries by marine organisms to facilitate epidemiological data collection from health care facilities.

Exposure to ionizing radiation can be a source of anxiety for many pregnant women and their health care providers. An awareness of the radiation doses delivered by different techniques and the acceptable exposure thresholds can help both patients and practitioners. We describe exposure to radiodiagnostic procedures during pregnancy and suggest an approach to assess the potential risk.

Background: Vipera palaestinae is the most common venomous snake in Israel. We report a case of V. palaestinae bite and antivenom-induced serum sickness during pregnancy and discuss the unique considerations relevant to the treatment of a pregnant woman envenomated by a snake. Case Report: A 46-year-old woman, G6P5, 14 weeks gestation, was admitted after a V. palaestinae bite on her right toe. On admission to the Emergency Department, physical examination included the following vital signs and findings: pulse 76 beats/min, blood pressure 90/60 mm Hg, nausea, vomiting, foot and distal leg swelling, and normal fetal monitoring. She was treated with intravenous fluids, analgesics, and V. palaestinae antivenom. Eight days later she developed serum sickness, was treated with prednisone, and fully recovered. A healthy baby was born at term, with normal examination at 2 months post-delivery. Conclusion: To our knowledge, this is the first reported case of V. palaestinae bite complicated by antivenom-induced serum sickness during pregnancy. No adverse pregnancy outcome due to the antivenom treatment or serum sickness was observed. Careful hemodynamic, hematologic, and obstetric monitoring (including ultrasound) of pregnant snakebite victims is warranted. Antivenom administration should be considered according to published indications to prevent maternal complications and fetal compromise. Patients treated with antivenom should be followed for possible development of serum sickness.

The threat of using chemical compounds by terrorists as weapons of mass casualties has been a rising concern in recent years. Carbamates, a group of reversible acetylcholinesterase inhibitors, could be potentially involved in such toxic mass casualty events because they can cause cholinergic crisis that could lead to fatality, similar to that of organophosphate poisoning. The medical management of carbamate poisoning consists of supportive measures and specific antidotal treatment, that is, the anticholinergic compound atropine. The administration of oximes, acetylcholinesterase reactivators, in carbamate poisoning is controversial because of the potential toxicity of oximes in conjunction with carbamate especially in the case of the carbamate--"carbaryl" poisoning. However, recent data suggest that this concern may be unwarranted. In this article, we review the current data regarding the pros and cons of using oximes against carbamates poisoning in a mass casualties event scenario. We also propose a new decision-making algorithm for the medical first responders in a mass casualties event suspected to be caused by a cholinergic substance (organophosphate or carbamate). According to this algorithm, treatment should consist of atropine and oxime regardless of the exact toxic compound involved. We speculate that in a mass casualties event, the benefits of using oximes outweigh the low level of potential risk.

Busulphan (1, 4-bis [methanesulfonyl-y] butane) is a bi-functional alkylating agent that, in combination with cyclophosphamide, has been commonly used in conditioning regimens before hematological stem cell transplantation (HSCT) for nearly 20 years. Busulfan has a very narrow therapeutic index, and acute toxicity may be related to absorption and disposition of the drug and metabolites. Precise delivery of the oral formulation is compromised by erratic gastrointestinal absorption, particularly in infants and small children. An intravenous busulfan formula was approved nearly 40 years after the approval of the oral formulation. Busulfan levels expressed as the area under the concentration-time curve (AUC) higher than 1500 microM* minute were reported to increase the risk of developing veno-occlusive disease (VOD), while low levels may result in engraftment failure or disease relapse. VOD occurs in 11-40% of patients undergoing HSCT and is associated with death in 3.3% of patients. Measurement of individual plasma busulfan levels during oral or intravenous dosing to obtain an AUC is likely to provide the necessary elements to monitor the drug disposition, ensuring efficacy and preventing toxicity of patients undergoing HSCT. It is also important to consider the busulfan drug-drug interactions and adverse drug reactions that can develop during the therapeutic process. Busulfan therapeutic drug monitoring and dose-adjustment should be performed in specialized laboratories staffed by well-trained personnel.

Background The Suez Canal permits migration of fish from the Indo-Pacific Ocean to the Mediterranean Sea. This phenomenon (Lessepsian migration) has enabled poisonous fish species to colonize the Mediterranean Sea. Objective To report clinical tetrodotoxin poisoning after consumption of the Lessepsian immigrant fish Lagocephalus sceleratus caught on the Israeli coast of the eastern Mediterranean. Case series Thirteen patients aged 26–70 years were admitted after consuming L. sceleratus . Signs of toxicity appeared within 1 h. The main manifestations included vomiting, diarrhea, headache, paraesthesias, slurred speech, muscle weakness, dyspnea, hypertension, tachycardia, respiratory arrest, seizures and coma. Treatment was supportive, including mechanical ventilation (two patients). Patients recovered within 4 days. All fish were identified as L. sceleratus , a species known to contain tetrodotoxin. Discussion The diagnosis of tetrodotoxin poisoning was suggested by typical clinical manifestations together with temporal proximity to consumption of tetrodotoxin-containing fish. To the best of our knowledge, this is the first case series of tetrodotoxin poisoning reported from the eastern Mediterranean and due to L. sceleratus . Man made disruption of the ecological balance has resulted in the spread of tetrodotoxin-containing fish from the Indo-Pacific region to the Mediterranean Sea. Increased awareness is required to identify tetrodotoxin poisoning in an atypical fauna.

The use of deferoxamine for iron chelation in transfusion-dependent thalassemia major is limited by serious neurotoxicity (hearing and vision loss). We assessed whether interpatient variability in handling deferoxamine and resultant accumulation of the drug may account for the neurotoxicity. We studied steady-state deferoxamine pharmacokinetics during intravenous infusion in two groups of patients--one group exhibited severe manifestations of auditory and visual loss and one group was asymptomatic. The groups were matched for age, sex distribution, weight, treatment period, ferritin levels, and hemoglobin levels. Similarly, doses of deferoxamine at the time of the study were not different. Clearance rates were not different between the symptomatic and asymptomatic patients (39.83 +/- 4.54 versus 30.66 +/- 4.39 ml/min.kg). However, patients who exhibited toxicity received significantly higher daily doses of subcutaneous deferoxamine at the time of diagnosis of neurotoxicity (9.03 +/- 0.96 and 5.58 +/- 0.61 mg/kg.hr, respectively; p less than 0.005). These data suggest that deferoxamine induced neurotoxicity is dose-dependent and cannot be attributed to accumulation of the drug caused by slower clearance rates.

Khat leaves (mainly cathinone and cathine) have been chewed for centuries as stimulants. Hagigat (capsules of 200 mg cathinone) have been marketed in Israel as a natural stimulant and aphrodisiac. The consequences of illicit exposure to cathinone are reported.Prospective observational study of calls to the Poison Center regarding exposure to Hagigat during the course of 10 months. Demographic and clinical data were abstracted from patients' records and telephone follow up was performed.Data of 34 consecutive patients aged 16-54 years were analyzed. The amount consumed was (1/2)-6 capsules (ingestion-32, sniffing-2). Main clinical manifestations were headache, vomiting, hypertension, nausea, tachycardia, dyspnea, chest pain, and myalgia. Main complications were myocardial ischemia (3), pulmonary edema (2), and intracerebral hemorrhage (1), all in young subjects. Treatment was supportive; one patient underwent neurosurgery.Exposure to illicitly synthesized cathinone is associated with serious cardiovascular and neurological toxicity, even in young subjects.

Background. The consumption of edible fish (e.g., Siganus spp) was assumed to have caused ciguatera poisoning at an atypical site, the eastern Mediterranean. This pilot study assesses the presence of ciguatoxin-like substances in edible fish on the eastern Mediterranean coast of Israel. Methods. Samples of Siganus rivulatus from polluted seawater (Haifa Bay), Siganus rivulatus from relatively clean seawater (Dor), and fish from the freshwater Sea of Galilee not inhabited by toxic algae were analyzed during summertime. Ciguatoxin-like substances were tested by a membrane immunobead assay that yields a color reaction (positive, weakly positive, negative). Results. Significantly more large and small fish from Haifa Bay yielded positive color reactions compared to fish from Dor. Sea of Galilee fish gave no positive color reactions. Conclusions. Our results suggest the presence of ciguatoxin-like substances in edible fish of the eastern Mediterranean. Additional analyses are needed to determine whether these s...

Background:Iron continues to be a common cause of poisoning in young children, in part due to its widespread use and easy accessibility.Objective:To determine differences in the epidemiology and outcome of unintentional iron ingestion by young children in populations practicing selective (eg, US) versus universal (eg, Israel) iron supplementation to infants.Methods:All cases of unintentional iron ingestion in children younger than 7 years in a one year period were identified through the poison control center databases of 2 sites (Illinois and Israel). Parameters compared include patient sex and age; type, form, and dose of iron preparation; circumstances and clinical manifestations; management; and outcome.Results:A total of 602 children were identified: 459 in Illinois and 143 in Israel. The majority of Illinois children ingested multivitamin preparations (94%), whereas Israeli children ingested single-ingredient iron preparations (78%) (p < 0.001). Iron doses ingested were higher in Israel (median 14.5 vs 6.6 mg/kg; p < 0.001) but remained within the nontoxic range for most children. No deaths or severe poisonings were reported, and 93% of children in both groups were asymptomatic. The majority of ingestions in both locations were due to unintentional self-ingestion. However, parental miscalculation occurred more frequently in Israel (16%) than in Illinois (1%).Conclusions:Universal iron supplementation to infants was not associated with a negative impact on the outcome of pediatric unintentional ingestions. Low-dose exposures were safely managed by on-site observation.

Cinnarizine, a piperazine derivative, is a widely prescribed medication for the treatment of vestibular disorders and motion sickness. Cinnarizine has antihistaminic, antiserotoninergic, antidopaminergic, and calcium channel–blocking properties. We present the first report in the English literature of cinnarizine poisoning and toxicokinetics. A 30-month-old toddler ingested 225 mg of cinnarizine, 18 times the recommended dose for older children. Four hours later, she became jittery with a wide-based gait and vomited 3 times. She was examined by her family physician, who reported stupor and twitching in both hands. On admission to the hospital, 6 hours after the ingestion, she was stuporous and had 3 short, generalized tonic-clonic convulsions that were controlled with a single dose of midazolam. Full clinical recovery was seen 10 hours after ingestion. Serum cinnarizine levels were 7407, 2629, and 711 ng/mL on admission and at 4 and 12 hours thereafter, respectively, 26.9 times higher than the therapeutic levels in adults. Elimination rate constant, calculated by linear regression of the ln concentrations of the 3 data points, was 0.19. Half-life, calculated from the equation t1/2 = 0.693/kel, where kel is the elimination rate constant, was 3.65 hours. The manufacturing company revealed that their database contains 23 reports of cinnarizine overdose (adult and children), received between 1972 and 2004. Clinically, these cases reflect mainly symptoms of alterations in consciousness ranging from somnolence to stupor and coma, vomiting, extrapyramidal symptoms, and hypotonia. In a small number of young children, convulsions developed; recovery was uneventful in 4 cases and not reported in 1. The neurologic complication may be explained by the antihistaminic effect of cinnarizine because central nervous system depression and convulsions are known complications of antihistaminic overdose. It is hypothesized that cinnarizine-induced convulsions also are related to the antidopaminergic effect of the drug. Apart from the convulsions, no other adverse effects related to calcium channel–blocking properties, such as bradycardia or hemodynamic instability, were observed. Pediatric patients with cinnarizine overdose need to be observed in a health care facility for potential neurologic complications and be treated symptomatically. The delay to onset of clinical effect should be considered in the observation period.

Carbon monoxide, a byproduct of incomplete hydrocarbon combustion, has been responsible for many accidental poisonings worldwide. The signs and symptoms of poisoning are diverse, ranging from headache, dizziness, and confusion to cardiac and neurological disturbances. Oxygen is the cornerstone of treatment, because it accelerates the dissociation of carbon monoxide from heme proteins. The role of hyperbaric oxygen in the treatment of CO poisoning is still questionable. Only a few randomized, controlled studies have been conducted, and their results are inconsistent. In the present review, we discuss the conclusions of four randomized controlled studies and propose a hyperbaric oxygen treatment protocol based on these conclusions.

Background The use of inhaled corticosteroids (ICS) via spacers in childhood asthma is increasing. However, concern has been raised about its long-term impact. Hypercalciuria is a known adverse effect of treatment with systemic corticosteroids. The urinary calcium to creatinine ratio (UCa : Cr) is a simple, reliable and non-invasive tool for evaluation of hypercalciuria. Aim To determine whether ICS can induce hypercalciuria in children with asthma. Setting Outpatient clinic in a referral hospital. Methods The UCa : Cr was determined in 25 children aged 3–6 years with mild-to-moderate persistent asthma before and after a 2-month course of inhaled budesonide 400 μg/day via an aerochamber. Children who had received oral corticosteroids, diuretics, antibiotics or theophylline were excluded. Statistics Paired Student’s t-test and Fisher’s exact test. Results The mean UCa : Cr was similar in the children with asthma before and after 2 months’ administration of budesonide (0.10 ± 0.10 and 0.11 ± 0.08, respectively; p = 0.601). The numbers of hypercalciuric children were two and five, respectively (p = 0.417). In 68% of patients, the UCa : Cr increased and in 16% the increase indicated hypercalciuria (UCa : Cr > 0.2). Conclusions Although the treatment of childhood asthma with budesonide 400 μg/day via an aerochamber does not appear to be associated with hypercalciuria, the existence of a subgroup of patients in whom ICS may induce hypercalciuria is plausible. This needs to be further evaluated in a larger study.

Background: Vipera palaestinae antivenom has been successfully used to treat systemic and progressive local manifestations inflicted by this snake. The clinical course of several envenomations created the impression that the recommended fixed dose regimen of antivenom (50 ml) may not always be sufficient. Objective: To evaluate the V. palaestinae antivenom fixed dose regimen and to assess the need for repeated antivenom administration as well as possible adverse effects. Methods: Retrospective review of prospectively collected poison center data over a one-year period. Results: One hundred and twelve patients were evaluated, 48% of whom were treated with antivenom. Antivenom treatment resulted in complete disappearance of systemic manifestations with no relapse. Three patients required additional doses of antivenom for marked progressive local signs—one initially received 50 ml of antivenom and two others only 30 ml. Anaphylaxis and serum sickness were each observed in 3.7% of the treated patients. Conclusion: The fixed dose regimen of 50 ml V. palaestinae antivenom is efficacious for the treatment of systemic and progressive local manifestations caused by this snake. There is insufficient data on whether smaller doses can be successfully used for systemic manifestations and whether initial larger doses are justified for marked progressive local signs (e.g. involvement of an entire limb). Randomized prospective controlled studies are needed to elucidate these issues.

Scorpion venom causes excessive adrenergic discharge and cardiotoxicity. Publications on scorpion stings using mainly admission data, has led to the belief that most scorpion stings are severe and mandate an observation period of at least 12 h regardless of symptomatology. We to assessed the characteristics of scorpion sting victims with emphasis on severity and time to presentation by retrospective poison center chart review of 225 calls over 12-mo. Thirteen percent of patients were asymptomatic and 72% and 15% were mild or moderately to severely ill, respectively. The most frequent manifestations were pain (97.3%), cardiovascular signs (23.1%) and ECG changes (13.7%). Ninety-four percent of the patients presented within 6 h; 86% within 3 h. Ninety-two percent of moderate to severe patients, including those with moderate to severe cardiotoxicity, presented within 3 h; 100% within 6 h. Clinical severity of the stings was greater in females than in males. No association was found between degree of severity and time to presentation and age. Most scorpion stings in Israel (at least those occurring in the north and central regions) are mild. The majority of envenomated patients present for medical assistance within 3 h including all patients with moderate to severe cardiotoxicity. Because of severity of potential complications, that scorpion sting victims should be observed in the emergency department for 6 h from the time of sting and should be admitted if symptoms other than local pain develop. Reduction of unnecessary in-hospital observation time is expected to save public health money.

Background . Vipera palaestinae is the commonest venomous snake in Israel. V. palaestinae -specific antivenom is indicated for both systemic effects and marked progressive local signs. In our experience, clinicians are often not aware of the morbidity associated with the local effect of the venom and consequently do not administer the antivenom in envenomations with local effects only. Objective . To describe unusual local complications of inadequately treated V. palaestinae envenomation. Case series . Three cases of V. palaestinae bites involving distal parts of the limbs are reported. Within 36–48 h tense swelling progressed to the trunk. Swelling involved the neck in two patients and was severe enough to cause dysphagia and to suggest impending upper airway obstruction. In the third patient, the swelling led to urine retention necessitating introduction of urinary catheter. V. palaestinae antivenom administration resulted in regression of swelling in two patients and in allergic reaction in the third. Conclusion . Inadequately treated swelling caused by V. palaestinae envenomation may involve the trunk even when the site of the bite is remote. In some cases this may pose a threat to the function of vital structures such as the upper airways, call for unnecessary interventions and prolong hospitalization. It is recommended that V. palaestinae antivenom be administered whenever there is marked and progressive swelling even in the absence of systemic signs.

Early treatment of organophosphate (OP) poisoning with oximes results in reactivation of acetylcholinesterase and patient recovery. Data on efficacy of late administration of oximes, particularly obidoxime, is limited. A 42-y old woman swallowed 60 ml of 50% malathion in a suicide attempt. Characteristic muscarinic, nicotinic and central manifestations of OP poisoning appeared: atropine and 250 mg obidoxime i.v., resulted in marked improvement. Several hours after the last dose, clinical manifestations recurred and ventilation was required. After 10 d cholinesterase was still low and liver enzymes were elevated. Obidoxime was reinstituted after the 9 d interruption and muscle strength improved with the first dose. The patient could be disconnected from the ventilator and within24 h was extubated. Oxime therapy should be considered even late in the course of untreated or partially treated OP intoxications, especially when the etiologic agent is a lipid-soluble compound (ie malathion) that can cause a protracted course of poisoning. The clinical course of this patient did not support a cause-and-effect relationship between obidoxime and the abnormal liver function.

Ciguatera poisoning is the commonest fish-borne seafood intoxication. It is endemic to warm water tropical areas and is caused by consumption of bottom-dwelling shore reef fish, mostly during spring and summer. The causative agent, ciguatoxin, is a heat-stable ester complex that becomes concentrated in fish feeding on toxic dinoflagellates. The common clinical manifestations are a combination of gastrointestinal and neurologic symptoms. Severe poisoning may be associated with seizures and respiratory paralysis.To describe a series of patients who sustained ciguatera poisoning in an uncommon region and from an unexpected source.Two families complained of a sensation of "electrical currents," tremors, muscle cramps, nightmares, hallucinations, agitation, anxiety and nausea of varying severity several hours after consuming rabbitfish ("aras"). These symptoms lasted between 12 and 30 hours and resolved completely. The temporal relationship to a summer fish meal, the typical clinical manifestations along with the known feeding pattern of the rabbitfish suggested ciguatera poisoning.The Eastern Mediterranean basin is an unusual region and the rabbitfish an unusual source for ciguatera poisoning. There are no readily available and reliable means for detecting ciguatoxin in humans. A high index of suspicion is needed for diagnosis and a thorough differential diagnosis is essential to eliminate other poisonings, decompression sickness and encephalitis. Supportive therapy is the mainstay of treatment.

Background: Volatile substance abuse is practiced mainly by adolescents and young adults. Its effects are central nervous system excitation followed by central nervous system depression, at times accompanied by seizures. It may cause sudden death as a result of ventricular arrhythmias, reflex vagal inhibition, respiratory depression, and anoxia. Chronic toxicity may involve the nervous system, heart, kidney, and liver. Toluene-based adhesives are among the most commonly inhaled substances. Case Report: A 14-year-old female presented with confusion, hallucinations, and intermittent laughing and crying after having inhaled contact glue several times daily in the course of 5 days. Her condition improved within 3 h. Urinary hippuric acid was 93.9 g/g creatinine indicating heavy toluene exposure (biological exposure index, BEI, is 1.6 g/g creatinine). Conclusion: In this patient, urinary hippuric acid was a biomarker for her toluene abuse.

A 4.6 kg infant with Wiskott-Aldrich syndrome received an accidental overdose of busulfan during preparation for allogeneic stem cell transplantation. Pharmacokinetic analysis of plasma busulfan levels alerted staff to the dosing error. Hemodialysis was immediately performed and resulted in accelerated clearance of busulfan. There were no acute neurologic and hepatic side-effects of the busulfan overdose, and despite 2 months of cough accompanied by rales, the patient is now free of pulmonary symptoms. Stable partial donor chimerism occurred after transplantation. At present, the patient is thriving and infection-free 12 months after transplantation, although his platelet count remains at the lower limit of normal.

Ecbalium elaterium is a plant endemic to the Mediterranean basin. Its roots and cucumber-shaped fruit have been used in folk medicine since antiquity. The alleged uses of the fruit juice are as a potent cathartic, analgesic, and antiinflammatory agent. Cucurbitacin B, a triterpene derivative is the active antiinflammatory principal.We present a series of 13 patients who were exposed to the juice of Ecbalium elaterium in its natural form. In 3 patients, exposure was intranasal for the treatment of sinusitis or liver cirrhosis. In 3 other cases, children ingested the fruit unwittingly. In 6 patients, exposure was ocular and, in one, dermal. Within minutes of exposure, the patients exhibited irritation of mucous membranes at various degrees of severity manifested as edema of pharynx, dyspnea, drooling, dysphagia, vomiting, conjunctivitis, corneal edema, and erosion, depending on the route of the exposure. Recovery began within several to 24 hours after administration of oxygen, steroids, antihistamines, and beta-2-agonists. Ocular exposures responded to topical steroid and antibiotic eyedrops within a few days. The toddler with the dermal exposure remained asymptomatic.Exposure to the juice of Ecbalium elaterium, mainly in its undiluted form, may cause irritation of mucous membranes, supposedly of inflammatory nature. Patients exposed orally or intranasally should be closely followed for upper airway obstruction. Patients exposed ocularly should have their eyes promptly irrigated to prevent corneal and conjunctival injury.

Due to its high cost and need for parenteral administration, the standard iron chelator deferoxamine is not used in many individuals with acute and chronic iron poisoning worldwide. Deferiprone is the first oral iron chelator to be shown to be effective in chronically iron overloaded thalassemia patients. Its efficacy, by oral administration, in acute iron poisoning has not been tested. Our objective was to determine whether orally administered deferiprone can reduce the mortality of rats following acute, toxic, oral doses of iron. Rats were administered 612 mg/kg elemental iron orally, corresponding to LD50 in the species tested. Two other groups received the same oral dose of iron followed by oral deferiprone: 800 mg/kg and 800 mg/kg, followed by another dose of 800 mg/kg 2 hours later. Coadministration of 800 mg/kg deferiprone with the iron decreased mortality from 30% to 6.6% after 2 hours (P = .02), from 40% to 16.6% after 12 hours (P = .04), and from 53.3% to 20% after 24 hours (P = 0.007). Mortality was also significantly decreased among animals coadministrated 2 repeated doses of deferiprone of 800 mg/kg with iron, to 0%, 9%, and 18%, and 2, 12, and 24 hours postdrug administration, respectively (P = .04, .05, .04, respectively). Histologically, there was a dose-dependent decrease in iron accumulation in the gastrointestinal tract. Orally administered deferiprone can decrease morbidity and mortality caused by acute iron overdose in rats. Oral deferiprone holds promise in the treatment of iron poisoning in humans.

The recommended maintenance dosage interval for digoxin in infants and children is 12 hours] ,2 whereas in adults the drug is administered once daily. Because target trough and peak values in children do not differ from those in adults, and because elimination half-life.is not shorter, it is not clear why digoxin should be administered twice daily. On the basis of available studies, the elimination half-life of digoxin averages between 20 hours in infants and up to 40 hours in children. 3-5 In our study, we compared serum concentrations and clinical observations in infants and children during once-daily and twice-daily administration of the cardiac glycoside.

When ingested, concentrated paraquat can cause either rapid death from multisystem failure and cardiovascular shock or delayed death from progressive pulmonary fibrosis. Diquat ingestion does not usually cause pulmonary fibrosis, but produces early onset acute renal failure.A 52-year-old male ingested approximately 50 mL of a solution containing 13% paraquat and 7% diquat (about 6650 mg of paraquat and 3500 mg of diquat), and subsequently developed adult respiratory distress syndrome and pulmonary fibrosis. Survival prediction employing the criteria of Hart et al. for paraquat plasma levels was 30%. From the probable amount of paraquat ingested, severe toxicity was expected. The clinical course was not consistent with significant diquat toxicity. Treatment included oral Fuller's earth, forced diuresis, hemofiltration, N-acetylcysteine, methylprednisolone, cyclophosphamide, vitamin E, colchicine, and delayed continuous nitric oxide inhalation. The patient recovered and pulmonary function was subsequently normal.It is unclear which, if any, of the above treatments contributed to recovery, but the encouraging outcome suggests a possible benefit of nitric oxide inhalation in paraquat poisoning which deserves further study.

A 24-year-old female diabetic patient was hospitalized because of ketoacidosis and a necrotic wound on the hand. Debridement and antibiotic therapy failed to halt the process. After demonstration of Mucor in cultures from the wound, the patient underwent extensive surgery and amphotericin B was administered. When the necrotic process continued despite these measures, adjunctive hyperbaric oxygen (100% O2 at 2.5 ATA for 90 minutes) was administered daily for a total of 21 treatment sessions. She gradually improved, and at 2 months follow-up most of the wound had healed. Although the mortality rate of cutaneous/soft-tissue zygomycosis is markedly lower than that of the rhinocerebral form, morbidity is still considerably high. Successful use of hyperbaric oxygen has been reported in rhinocerebral zygomycosis, and it may have been of benefit in this high-risk patient by preventing local and systemic spreading of the fungus. This report is the first case of the use of hyperbaric oxygen for cutaneous/soft-tissue zygomycosis. It is suggested that hyperbaric oxygen be considered for this indication in diabetic patients as an adjunct to surgery and amphotericin B.

OBJECTIVE: To report a severe and unusual reaction to minocycline and the use of in vitro immunologic assays. CASE SUMMARY: A 46-year-old white man developed severe respiratory distress with pulmonary infiltrates on chest X-ray and eosinophilia in blood, bronchoalveolar lavage fluid, and biopsied lung tissue during exposure to minocycline. Additional manifestations included pleuropericardial effusion, liver function abnormality, and bone marrow eosinophilia. Macrophage inhibition factor and mast cell degranulation assays were positive to minocycline. DISCUSSION: The patient's manifestations were compatible with the diagnosis of eosinophilic pneumonia. After excluding other possible etiologies, minocycline was identified as the offending agent. Generalized damage was suggested by the presence of a combination of extrapulmonary manifestations previously not reported. Results of the in vitro immunologic assays supported the hypersensitivity nature of the disease and confirmed the diagnosis. CONCLUSIONS: Minocycline-induced eosinophilic pneumonia may involve extrapulmonary sites. It is suggested that in vitro immunoassays be used for confirmation of the diagnosis rather than rechallenge or invasive procedures.

Vipera xanthina palaestinae is the most widely distributed venomous snake in Israel, accounting for most envenomations. A specific equine antivenin is efficacious against both systemic and local manifestations if given within hours. This study sought to determine if delayed vipera xanthina palaestinae antivenin can be effective.Patients who had been bitten by vipera xanthina palaestinae during 1991-1995 were evaluated. Those who continued to deteriorate beyond 24 h post envenomation, in spite of treatment or because of delayed diagnosis, were given vipera xanthina palaestinae antivenin.Ten patients were included in the study. Vipera xanthina palaestinae was identified in seven and diagnosis was considered probable in three patients. On admission, eight patients had local signs and seven patients had mild to severe systemic manifestations. The local signs were remarkable and progressive in all patients. In five, systemic signs and laboratory abnormalities were delayed as well. The time range for delayed antivenin administration was 1-6 days after envenomation. Following antivenin administration, progression of local signs ceased in all patients and swelling regressed within 24 h. In nine patients this occurred within 6 h.Vipera xanthina palaestinae antivenin administration should be considered in patients with envenomations complicated by marked and progressive local signs, delayed systemic signs and laboratory abnormalities more than 24 h after envenomation.

Hydrofluoric acid is used for different purposes in industry and in the home as a rust remover. Most exposures are accidental and may result in severe superficial and deep tissue injury as well as systemic toxicity. There is uncertainty regarding the optimal treatment of hydrofluoric acid eye injury. A patient in whom a solution of 49% hydrofluoric acid induced a large corneal erosion is described. Repeated instillation of 1% calcium gluconate eye drops combined with the conventional treatment of acid eye burns resulted in a complete and quick recovery.

Obidoxime is an oxime used in several countries as an antidote in organophosphate intoxication. Its pharmacokinetics were studied in a 20 year-old female with severe and complicated methamidophos intoxication. Obidoxime elimination half life was 6.9 h, volume of distribution 0.845 L/kg, total body clearance 85.4 mL/min, and renal clearance 69 mL/min (creatinine clearance 54 mL/min). Eighty percent of the dose was excreted in the urine over 5 h. Possible reasons for the different pharmacokinetic values as compared with values previously reported in healthy volunteers are discussed. Obidoxime dose should be adjusted according to renal function. More studies are needed to establish the therapeutic window of obidoxime in patients with organophosphate intoxication.

Sodium hydroxide (NaOH) is well known for its corrosive properties and its ability to generate heat on contact with water. The respiratory effects of industrial exposure to NaOH have, however, never been reported. A 63 year old man worked daily for 20 years cleaning large industrial jam containers by boiling lye (NaOH) solution without using respiratory protective equipment. Physical examination, chest x ray film, pulmonary function tests, and arterial blood gases were all compatible with severe obstructive airway disease with significant air trapping. It is probable that this massive and prolonged occupational exposure to the corrosive effect of NaOH mists induced irritation and burns to the respiratory system, eventually leading to severe obstructive airway disease.

Iron is an essential element for body homoeostasis, but there is no effective mechanism for elimination of an excess of this mineral. Deferoxamine (desferrioxamine) is currently the treatment of choice for iron overload states from both acute iron intoxication and transfusion-dependent anaemias. The pharmacokinetics of deferoxamine are confounded both by its ability to chelate endogenous and exogenous iron and by the laboratory techniques used for its determination. Its iron-complex (ferrioxamine) has different pharmacokinetic properties. Because of its effectiveness, the use of deferoxamine is becoming more common, involving long term and high dose regimens. As a result of this, more and more toxicities that were not known in the past have been described and characterised. The most serious of these include hypotension, renal insufficiency, neurotoxicity, growth retardation and opportunistic infections: some of these side effects may be attributed to or aggravated by ferrioxamine. The pharmacological and toxicological literature on deferoxamine, and possible mechanisms for its toxicity, are reviewed and discussed.

The objective of this study was to assess the effect of endogenous digoxin-like substances on the interpretation of excessive concentrations of digoxin in children. After the development of a high-pressure liquid chromatography (HPLC) method for digoxin in our laboratories, we analyzed sera of children in whom the fluorescence polarization immunoassay identified potentially toxic concentrations of the glycoside (greater than 3 nmol/L; 2.3 ng/ml). Sixteen of them were receiving long-term digoxin therapy, and one had an accidental overdose. The immunoassay yielded significantly higher concentrations (4.1 +/- 1.2 nmol/L; 3.2 +/- 0.9 ng/ml) than the HPLC method (3.3 +/- 1.6 nmol/L; 2.6 +/- 1.2 ng/ml; p less than 0.01). In five cases (30%) these differences were clinically significant because administration of digoxin had been discontinued in the presence of true digoxin concentrations within the therapeutic range and the lack of clinical toxic effects. These data suggest that therapeutic drug monitoring using immunoassays of digoxin may be too inaccurate to detect potential toxic effects, and that much more weight should be focused on clinical monitoring. The HPLC method for assay of digoxin is extremely meticulous and will not become clinically available; therefore the development of better immunoassays should be encouraged.