Yedidia Bentur

Technion - Israel Institute of Technology, H̱efa, Haifa, Israel

Are you Yedidia Bentur?

Claim your profile

Publications (97)227.73 Total impact

  • Ophir Lavon · Yedidia Bentur
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Exposure to silica gel, a common desiccant, is considered common and non-toxic although data are limited. Objectives: To evaluate the characteristics of silica gel ingestion, and to attempt to estimate the associated health care costs. Methods: We conducted a one year retrospective review of charts of a national poison information center to characterize ingestions of silica gel and estimate its direct cost to health care services. Cost evaluation was based on emergency department and community clinic tariffs (NIS 807/US$ 213 and NIS 253/US$ 67, respectively). Results: A total of 546 cases were recorded, 2.1% of the annual calls to the poison information center. Most ingestions occurred in children younger than 6 years old (91.4%, 65.2% < 2 years). Median monthly exposure was 42; the peak (74) occurred in April, before the Passover holiday. Sixty calls (11%) came from health care facilities and the rest were reported by the public; 2.7% were symptomatic, mainly mild self-limited mouth and throat discomfort. The direct annual treatment cost of patients who referred themselves to health care facilities without consulting first with the Poison Center (n=60) was NIS 24,598/US$ 6507 (emergency department and community clinic visit fees). Conclusions: Silica gel ingestion is relatively common, occurring mainly in young children; it is rarely symptomatic but is a source of unnecessary referrals to health care facilities. The potential annual saving by preventing unnecessary referrals due to poison information center advice was estimated at NIS 375,678/US$ 99, 383. The availability of poison information center services may prevent unnecessary referrals to health care facilities and thus save costs.
    No preview · Article · Oct 2015 · The Israel Medical Association journal: IMAJ
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Liquid chromatography with mass spectrometry (LC-MS/MS) is the method of choice for the determination of everolimus whole blood concentrations but is not always available. Therefore, immunoassays have been developed for clinical monitoring of everolimus. In previous studies, the Quantitative Microsphere System (QMS) immunoassay had a positive bias compared with LC-MS/MS, but was judged acceptable, although clinical agreement (eg, 95% limits of agreement) was not reported. The objective of this study was to assess whether the agreement between the QMS assay and an LC-MS/MS method was clinically acceptable for use interchangeably in therapeutic everolimus monitoring. Methods: Whole blood samples from organ-transplanted patients on everolimus therapy were analyzed by both QMS (on Architect ci4100 analyzer) and LC-MS/MS. Paired results were compared using paired Student t test, Bland-Altman plots, and Deming regression analysis. The proportions of falsely supratherapeutic and sub-therapeutic results on the QMS assay compared with the LC-MS/MS were calculated. Results: Among 250 samples (169 patients), mean everolimus concentrations determined by LC-MS/MS and QMS assays were 4.8 +/- 2.1 ng/mL and 6.3 +/- 2.1 ng/mL, respectively (P < 0.001), with 95% lines of agreement between 22.1 and 5.2 ng/mL, a range corresponding to 152% of the mean concentration. When stratified by the type of transplant, a similar positive bias was found in each subgroup (all P < 0.014). Sixty-nine percent of the samples yielding supratherapeutic concentrations (>8 ng/mL) on the QMS assay were within the therapeutic range on the LC-MS/MS. Conclusions: The everolimus QMS immunoassay, using the Architect ci4100 analyzer, had a significant positive bias compared with LC-MS/MS, with a wide range between the limits of agreement. The lack of agreement may result in inadequate everolimus dose adjustments, suggesting that the QMS assay cannot be used interchangeably with the LC-MS/MS method for therapeutic everolimus monitoring in organ-transplanted patients.
    No preview · Article · Apr 2015 · Therapeutic Drug Monitoring
  • [Show abstract] [Hide abstract]
    ABSTRACT: Indoor group water-pipe smoking (WPS), especially in coffee shops, has gained worldwide popularity OBJECTIVE: Comprehensive laboratory and clinical evaluation of the acute effects of active and passive indoor group WPS. Comparative study evaluating pre- and post-30 minute active and passive indoor group WPS. Outcome parameters: carboxyhemoglobin (COHb), nicotine and cotinine levels, complete blood count, and cardio-respiratory parameters. Exhaled breath condensate (EBC) cytokines and endothelial function (utilizing the EndoPat device) were measured only in active smokers. Statistics: Student's t-test, Wilcoxon, Fisher exact, ANOVA, and Neuman-Keuls, where relevant. Sixty-two volunteers were included; age 24.9.6±2 years, 47 active and 15 passive smokers. COHb increased post-active WPS (2.0±2.9% vs.17.6±8.8%, respectively, p<0.00001); >25% in six (12.7%) subjects, >40% in two (4.2%). Plasma nicotine level increased post-active WPS (1.2±4.3 vs.18.8±13.9 ng/mL respectively, p<0.0001); plasma cotinine, and urinary nicotine and cotinine levels also increased significantly. EBC IL4, IL5, IL10, IL17, and gamma interferon decreased significantly with post-active smoking; endothelial function did not change. WPS was associated with adverse cardio-respiratory changes. In passive smokers, COHb level increased (0.8±0.25 vs. 1.2±0.8%, respectively, p=0.003), as did respiratory rate. One session of indoor group active WPS resulted in significant increases in COHb and serum nicotine levels (8- and 18-fold, respectively), and was associated with adverse cardio-respiratory health effects. The minor effects found in passive smokers suggest that they too may be affected adversely by exposure to WPS. Our results call for action to limit the continuing global spread of WPS in coffee shops.
    No preview · Article · Oct 2013 · Chest
  • Source
    Ophir Lavon · Adi Ben-Zeev · Yedidia Bentur
    [Show abstract] [Hide abstract]
    ABSTRACT: Medication errors (ME) are a major concern to healthcare systems. Most studies evaluated ME occurring in healthcare facilities; only few focused on ME outside them. The objective was to characterise ME occurring outside healthcare facilities. A prospective observational follow-up study evaluating all ME occurring outside healthcare facilities reported to a national poison information centre during a 5-month period. For each ME case, a detailed questionnaire was filled and a follow-up call was made within 7 days. The collected data included demographics, circumstances, type of error and outcome. Of 1381 consecutive ME cases were included; 97.8% involved a single incident and 88.3% one drug. The main characteristics of the ME were as follows: children younger than 6 years old (58.9%), parents responsible for 55.6% of cases, wrong dose 34.5% and different medication 30.1%. Analgesics (27.4%) and antimicrobials (12.2%) were the most common pharmaceuticals. The main reasons for the ME were look-alike packaging (31.4%) and misunderstood instructions (28%). Most followed up patients (97.1%) were asymptomatic or mildly affected; there was one severe case and no mortality. Most ME occurring outside healthcare facilities are single incidents, involving young children who were administered a wrong dose or medication due to look-alike packaging or misunderstood instructions with asymptomatic or mild outcome. Improved packaging, labelling and patient education are suggested to reduce ME.
    Preview · Article · Oct 2013 · Basic & Clinical Pharmacology & Toxicology
  • Yael Lurie · Merav Slotky · Doron Fischer · Ron Shreter · Yedidia Bentur
    [Show abstract] [Hide abstract]
    ABSTRACT: Context. Corrosive substance ingestion is a toxicological emergency with relatively high mortality requiring rational surgical decisions. Objective. Evaluate the role of chest and abdominal computed tomography (CT) in assessing the severity of acute corrosive ingestion. Methods. A retrospective study of adults admitted due to corrosive ingestion, who underwent gastrointestinal endoscopy and CT within 48 h of admission. Endoscopy findings were graded as 0, 1, 2a, 2b, 3a, and 3b (Zargar's criteria), CT findings were graded as 0, 1, 2, and 3. For each patient endoscopy and CT grades were compared, and sensitivity and specificity for predicting mortality or emergency laparotomy were calculated. Results. Twenty-three patients were included, aged 18-87 years; seven underwent emergency laparotomy, five died. Endoscopy grading was higher than CT grading in 14 patients (66%). The sensitivities of endoscopy grades 2b and 3 to predict mortality and emergency laparotomy were 1 and 0.8, respectively; the specificities were 0.38 and 0.37, respectively. The sensitivities of CT grade 3 to predict mortality and emergency laparotomy were 0.4 and 0.28, respectively; the specificities were 0.94 and 0.93, respectively. Three patients had pulmonary infiltrates on CT but not on chest X-ray. Discussion. CT tends to underestimate the severity of corrosive ingestion compared with endoscopy. It has lower sensitivity and higher specificity than endoscopy in predicting major outcome. CT can provide important information on lung injury, and when endoscopy cannot be completed. Conclusion. CT should not be the only basis for surgical decisions during the initial phase of acute corrosive ingestions.
    No preview · Article · Sep 2013 · Clinical Toxicology
  • Ophir Lavon · Yedidia Bentur

    No preview · Article · May 2013 · Clinical Toxicology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Introduction. The Analytic Laboratory of Israel Police processes illicit drug files. In recent years, workers of this laboratory have complained of health problems. Limited information exists on the effect of occupational exposure to illicit drugs; biomonitoring was never done. Objective. To assess health effects and systemic absorption of illicit drugs in workers of the Analytic Laboratory occupationally exposed to illicit drugs. Methods. A prospective cohort study using health and occupational questionnaires, clinical assessments, and monitoring of urinary excretion of illicit drugs was conducted. The study included three blocks of one week each. At each week workers were assessed at the beginning (baseline), and the assessments were repeated at the end of the three working days. Urine specimens were analyzed for illicit drugs in an independent laboratory. Demographic, clinical, occupational, and laboratory data were subjected to descriptive analysis, and paired Student's t-test, chi-square analysis, and repeated measures model. Results. Twenty-seven workers (age, 39.2 ± 8.3 years; 77.8% females) were included, yielding 122 paired samples. The following parameters were reduced at the end of shift compared with baseline: diastolic blood pressure (71.2 ± 11.2 and 77.2 ± 13.6 mmHg, respectively, p < 0.0001), FEV1 (98.3 ± 14.6% and 100.7 ± 12.7%, respectively, p < 0.0001), FVC (101.4 ± 13.7% and 103.7 ± 14.0%, respectively, p = 0.003), and FEF25-75 (85.7 ± 18.0% and 89.6 ± 18.7%, respectively, p = 0.01). Main health complaints included headache, fatigue, and dry eyes. No illicit drug was detected in the urine specimens. Conclusion. It is suggested that the health concerns of the laboratory workers were not related to the absorption of illicit drugs; environmental conditions (e.g. inadequate ventilation and respirable dust) can contribute to these concerns.
    No preview · Article · Mar 2013 · Clinical Toxicology
  • Miguel Glatstein · Dennis Scolnik · Yedidia Bentur
    [Show abstract] [Hide abstract]
    ABSTRACT: Background. Sulfonylureas are used extensively for treating type-2 diabetes mellitus. Sulfonylurea poisoning can produce sustained and profound hypoglycemia refractory to IV dextrose, particularly in children and the elderly. Objective. To review the use of octreotide, a long-acting somatostatin analog, in the treatment of sulfonylurea-induced hypoglycemia. Methods. A computerized search of U.S. National Academy of Medicine, Embase, PubMed and Toxline databases was undertaken using the keywords "octreotide", "sulfonylurea", "poisoning", "intoxication", "overdose" and "children". Textbooks of Clinical Toxicology and Pharmacology and the articles cited in their bibliographies were also searched. Twenty-four publications (19 articles and five conference abstracts) were identified; no publication was excluded. Pharmacology of octreotide. Octreotide, a synthetic peptide analog of somatostatin, binds to G protein-coupled somatostatin-2 receptors in pancreatic beta-cells, resulting in decreased calcium influx and inhibition of insulin secretion. Octreotide markedly inhibited insulin secretion and decreased the number of hypoglycemic events and supplemental dextrose requirements in animal studies. In humans octreotide markedly inhibited insulin release, increased serum glucose concentration, reduced dextrose requirement, prevented recurrent hypoglycemia and was superior to IV dextrose and diazoxide after administration of sulfonylureas. Efficacy of octreotide in pediatric sulfonylurea poisoning. Fourteen pediatric patients were reported; 13 ingested second-generation sulfonylureas, with time to hypoglycemia of 1.5-16 hours. IV dextrose (10-25%) was administered before and after octreotide therapy. Octreotide was given after failure to correct hypoglycemia with IV dextrose in doses of 0.51-2 μg/kg IV or SC; two also required an IV octreotide infusion. Seven patients (50%) had recurrent hypoglycemia and received IV dextrose and additional octreotide. Efficacy of octreotide in adult sulfonylurea poisoning. Fifty-three patients were reported in prospective controlled (n = 22) and retrospective (n = 9) studies, case series (n = 6) and case reports. Fifty-one ingested second-generation sulfonylureas with time to hypoglycemia of 1-13 hours. All received IV dextrose (10-50%) before and after octreotide treatment. Octreotide 40-100 μg SC or IV was administered followed by additional doses in most patients; three patients also required an IV infusion. Octreotide significantly increased serum glucose concentrations, decreased dextrose requirement and recurrent hypoglycemic events compared with IV dextrose. Recurrent hypoglycemia was recorded in 22-50% of the patients treated with octreotide. Therapeutic recommendations. Based on the published clinical and pharmacokinetic data of sulfonylureas and octreotide, we suggest the following dose regimens: in children, octreotide 1-1.5 μg/kg IV or SC, followed by 2-3 more doses 6 hours apart. In adults, octreotide 50 μg SC or IV, followed by three 50 μg doses every 6 hours. During this treatment IV dextrose infusion should be gradually tapered off. Adverse events. Hypertension and apnea were recorded in one pediatric patient 30 minutes after IV octreotide; the relationship to octreotide is unclear. One adult patient with chronic renal failure treated with atenolol developed severe hyperkalemia. Conclusions. Although relatively limited, the available data suggest that octreotide should be considered first-line therapy in both pediatric and adult sulfonylurea poisoning with clinical and laboratory evidence of hypoglycemia. Maintenance doses of octreotide may be required to prevent recurrent hypoglycemia.
    No preview · Article · Oct 2012 · Clinical Toxicology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Bronchial hyper-reactivity (BHR) provides a tool for asthma diagnosis, assessment of severity and response to treatment. The effect of beclomethasone dipropionate in ultrafine particles (BDP-HFA) on BHR as measured by the adenosine challenge test in young children has not yet been determined. Our aim was to determine the effect of BDP-HFA (100 μg twice daily) on BHR as evaluated by a reduction of 20% from baseline FEV1 (PC20-FEV1) values in young asthmatic children. Twenty-one young children (13 males), mean age 4.95 ± 1.05 years, with partially controlled or controlled asthma completed a double-blind randomized, placebo-controlled, cross-over study. Each child received 4 weeks of treatment with either 100 μg BDP-HFA twice daily or placebo, and after a 2-week washout period the other way around. Primary outcomes were PC20-FEV1 concentration, and the stage number at which FEV1 values dropped by 20%. Following 4 weeks of treatment, median PC20-FEV1 was 81.28 mg/mL while on BDP-HFA, compared with 9.64 mg/mL on placebo (p < 0.001). The median increase in stages required to achieve PC20 on BDP-HFA compared with placebo was three (95% CI 2.28-4.86). Four weeks of treatment with BDP-HFA resulted in significantly decreased BHR in young children.
    No preview · Article · Jan 2012 · Acta Paediatrica
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Paramethoxymethamphetamine (PMMA) is a hallucinogenic synthetic substituted amphetamine that was not included in the Israeli Controlled Substance Act (CSA). To report a severe PMMA and paramethoxyamphetamine (PMA) outbreak. The Israeli national forensic toxicology laboratory analyzes the body fluids of unnatural deaths by means of screening immunoassays and chromatographic confirmation and quantification. Samples are referred to this laboratory by the Israeli Forensic Medicine Institute and by hospitals following consultation with the Israel Poison Information Center. The forensic toxicology laboratory began determining PMMA and PMA in February 2007. In all fatal cases with a positive immunoassay screen for amphetamines, a chromatographic analysis of PMA and PMMA was performed. The laboratory and demographic data of consecutive patients in whom PMMA or PMA were detected, were collected during 1 year and subjected to descriptive analysis. Of 108 fatal cases with a positive screen for amphetamines, 32 were confirmed. Twenty-four of the 32 cases tested positive for PMMA and PMA--age 27 ± 5 years, 79.2% males, post mortem whole blood PMMA and PMA concentrations 0.35 ± 0.24 and 2.72 ± 1.67 mcg/mL, respectively. Co-exposures were detected in 17 (70.8%) fatalities; including methylenedioxymethamphetamine, methylenedioxyamphetamine, cocaine, cannabinoids, cathinone derivatives, ephedrine/pseudoephedrine, opiates, and ethanol. In addition, five non-fatal male cases were identified; age 32 ± 5 years, four had co-exposures to cocaine, cathinone derivatives, and cannabinoids. These findings led to the inclusion of PMMA in the CSA in July 2007, resulting in only three more fatalities in the following year. We report an outbreak of PMMA and PMA poisoning resulting in 24 fatalities, and the post mortem whole blood and urine concentrations of these two compounds. PMA was probably the result of PMMA metabolism. Stimulant co-exposures may have contributed to the severity of the poisoning. Forensic laboratory and poison center co-operation is important in identifying a new drug of abuse.
    Full-text · Article · Dec 2011 · Clinical Toxicology
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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. 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.
    No preview · Article · Apr 2011 · Human & Experimental Toxicology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There are limited data on the acute effects of water-pipe tobacco smoking, commonly known as water-pipe smoking (WPS), on cardiopulmonary parameters. This study evaluated the acute effects of a single 30-min session of WPS on carboxyhemoglobin (COHb) levels, pulmonary function test results, vital signs, fractional exhaled nitric oxide (Feno) levels, and exhaled breath condensate (EBC) cytokine levels in volunteers in a domestic, open-air, group smoking setting. This prospective study evaluated the above-noted outcome parameters before and after 30 min of WPS. The primary outcome parameter was the change in COHb levels. Forty-five volunteers (30 men, 15 women), aged 32.35 ± 15.33 years, were recruited. After one session of WPS, the COHb levels rose significantly, from 1.47% ± 0.57% (median 1.4) to 9.47% ± 5.52% (median 7.4), P < .001. Systolic and diastolic BP levels significantly increased after smoking (systolic, 119.52 ± 12.07 mm Hg vs 131.98 ± 17.8 mm Hg; diastolic, 74.84 ± 7.89 mm Hg vs 82.98 ± 12.52 mm Hg, respectively; P < .001). Heart rates increased from 80.39 ± 9.92 beats/min to 95.59 ± 17.41 beats/min, P < .001; and respiratory rates increased from 14.36 ± 1.63 breaths/min to 16.68 ± 2.24 breaths/min, P < .001. There were decreases in forced expiratory flow between 25% and 75% of FVC, peak expiratory flow rate, Feno levels, percentage of eosinophils in peripheral blood, and 8-isoprostane levels in EBC. This study shows that one session of WPS causes acute biologic changes that might result in marked health problems. It adds to the limited evidence that WPS is harmful and supports interventions to control the continuing global spread of WPS, especially among youth. Trial registry:; No.: NCT01157832; URL:
    Full-text · Article · Oct 2010 · Chest
  • [Show abstract] [Hide abstract]
    ABSTRACT: Poisonings are a significant cause of pediatric morbidity and mortality. The Israel Poison Information Center provides clinical consultations on poisonings and drug information 24 hours a day. To evaluate the epidemiologic characteristics of pediatric poison exposures in Israel. We reviewed computerized queries and performed a descriptive analysis of the Poison Center database pertaining to patients under 18 years old during 2007. A total of 15,005 pediatric poison exposures were recorded, 80.3% of them occurring in children under 6 years old. Of the calls to the Poison Center, 78.6% were made by the public, 20.7% by physicians, and in 74.4% the call was within 2 hours of exposure. Most exposures occurred at home (89.3%) and were unintentional (89.5%). Among adolescents, most exposures were intentional (49.3%, 38.2% suicides), the time lapse until consultation was longer (37% > 2 hours), and more physicians (54.8%) consulted the Poison Center. Most cases were asymptomatic or mildly affected (92.3%), 54.4% in adolescents. The commonest substances involved in single poison exposure were detergents, antimicrobials, topical preparations, acetaminophen and scale removers; in adolescents the most common substances were acetaminophen, methylphenidate, non-steroidal anti-inflammatory drugs, atropine and ethanol. Moderate to severe toxicity was commonly associated with organophosphates, alkali, ethanol, Vipera palaestinae and neuroleptics. Most patients could be observed at home (66.6%), while more adolescents were referred to emergency departments (42.2% vs. 9.9%) or hospitalized (14.5% vs. 1.9%). Pediatric poisonings are a significant health problem. The magnitude of the problem is greater in the young age group but more severe in adolescence, probably due to deliberate self-poisoning. Greater national efforts should be directed towards improved poison prevention, rational management of pediatric poisoning, and creating a national poisoning registry.
    No preview · Article · Sep 2010 · The Israel Medical Association journal: IMAJ
  • Ophir Lavon · Yedidia Bentur
    [Show abstract] [Hide abstract]
    ABSTRACT: 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. MECHANISMS OF ACTION: The antidotal properties of amyl nitrite were attributed initially to induction of methemoglobinemia and later to nitric oxide mediated vasodilation. EXPERIMENTAL STUDIES: 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. HUMAN STUDIES: 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. ADVERSE EFFECTS: 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.
    No preview · Article · Jul 2010 · Clinical Toxicology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Colchicine is used mainly for the treatment and prevention of gout and for familial Mediterranean fever (FMF). It has a narrow therapeutic index, with no clear-cut distinction between nontoxic, toxic, and lethal doses, causing substantial confusion among clinicians. Although colchicine poisoning is sometimes intentional, unintentional toxicity is common and often associated with a poor outcome. We performed a systematic review by searching OVID MEDLINE between 1966 and January 2010. The search strategy included "colchicine" and "poisoning" or "overdose" or "toxicity" or "intoxication." TOXICOKINETICS: Colchicine is readily absorbed after oral administration, but undergoes extensive first-pass metabolism. It is widely distributed and binds to intracellular elements. Colchicine is primarily metabolized by the liver, undergoes significant enterohepatic re-circulation, and is also excreted by the kidneys. THERAPEUTIC AND TOXIC DOSES: The usual adult oral doses for FMF is 1.2-2.4 mg/day; in acute gout 1.2 mg/day and for gout prophylaxis 0.5-0.6 mg/day three to four times a week. High fatality rate was reported after acute ingestions exceeding 0.5 mg/kg. The lowest reported lethal doses of oral colchicine are 7-26 mg. DRUG INTERACTIONS: CYP 3A4 and P-glycoprotein inhibitors, such as clarithromycin, erythromycin, ketoconazole, ciclosporin, and natural grapefruit juice can increase colchicine concentrations. Co-administration with statins may increase the risk of myopathy. MECHANISMS OF TOXICITY: Colchicine's toxicity is an extension of its mechanism of action - binding to tubulin and disrupting the microtubular network. As a result, affected cells experience impaired protein assembly, decreased endocytosis and exocytosis, altered cell morphology, decreased cellular motility, arrest of mitosis, and interrupted cardiac myocyte conduction and contractility. The culmination of these mechanisms leads to multi-organ dysfunction and failure. REPRODUCTIVE TOXICOLOGY AND LACTATION: Colchicine was not shown to adversely affect reproductive potential in males or females. It crosses the placenta but there is no evidence of fetal toxicity. Colchicine is excreted into breast milk and considered compatible with lactation. Colchicine poisoning presents in three sequential and usually overlapping phases: 1) 10-24 h after ingestion - gastrointestinal phase mimicking gastroenteritis may be absent after intravenous administration; 2) 24 h to 7 days after ingestion - multi-organ dysfunction. Death results from rapidly progressive multi-organ failure and sepsis. Delayed presentation, pre-existing renal or liver impairment are associated with poor prognosis. 3) Recovery typically occurs within a few weeks of ingestion, and is generally a complete recovery barring complications of the acute illness. History of ingestion of tablets, parenteral administration, or consumption of colchicine-containing plants suggest the diagnosis. Colchicine poisoning should be suspected in patients with access to the drug and the typical toxidrome (gastroenteritis, hypotension, lactic acidosis, and prerenal azotemia). Timely gastrointestinal decontamination should be considered with activated charcoal, and very large, recent (<60 min) ingestions may warrant gastric lavage. Supportive treatments including administration of granulocyte colony-stimulating factor are the mainstay of treatment. Although a specific experimental treatment (Fab fragment antibodies) for colchicine poisoning has been used, it is not commercially available. Although colchicine poisoning is relatively uncommon, it is imperative to recognize its features as it is associated with a high mortality rate when missed.
    Full-text · Article · Jun 2010 · Clinical Toxicology
  • Yedidia Bentur · Yael Lurie · Ada Tamir · Daniel C Keyes · Fuad Basis
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    No preview · Article · Mar 2010 · Human & Experimental Toxicology
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    No preview · Article · Nov 2009 · The American journal of emergency medicine
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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. In this case series of patients who ingested identified muscarine-containing mushrooms supportive treatment and atropine resulted in recovery in all cases.
    No preview · Article · Jul 2009 · Clinical Toxicology
  • Source
    Yedidia Bentur · Doreen Matsui · Gideon Koren
    [Show abstract] [Hide abstract]
    ABSTRACT: QUESTION: A 29-year-old woman had a carbon 14 urea breath test for diagnosis of Helicobacter pylori infection. At time of consultation, it had been 6 weeks since her last menstrual period. Four weeks after her last menstrual period, the results of a urine pregnancy test were negative. On that day, she received an ionizing radiation dose of 74 KBq (2 microCi) carbon 14 urea, followed by the breath test 30 minutes thereafter. Four days later, when the urine pregnancy test results turned positive, she was concerned about the possible effect of her exposure to ionizing radiation on the developing fetus. ANSWER: The amount of radiation used in these tests is extremely low-much lower than the amount a pregnant woman is absorbing through natural sources.
    Preview · Article · Jun 2009 · Canadian family physician Medecin de famille canadien
  • S. Ratnapalan · Y. Bentur · G. Koren

    No preview · Article · Apr 2009 · Canadian Medical Association Journal

Publication Stats

1k Citations
227.73 Total Impact Points


  • 2000-2015
    • Technion - Israel Institute of Technology
      • • Ruth and Bruce Rappaport Faculty of Medicine
      • • Rambam Medical Center
      H̱efa, Haifa, Israel
  • 1997-2009
    • Rambam Medical Center
      • • Israel Poison Information Center
      • • Faculty of Medicine
      H̱efa, Haifa District, Israel
  • 2005
    • Assaf Harofeh Medical Center
      Ayun Kara, Central District, Israel
  • 1989-1994
    • SickKids
      • • Division of Clinical Pharmacology and Toxicology
      • • Division of Hematology/Oncology
      Toronto, Ontario, Canada
  • 1988-1989
    • University of Toronto
      • • Hospital for Sick Children
      • • Department of Pharmacology and Toxicology
      Toronto, Ontario, Canada