Showing papers in "Clinical Toxicology in 2002"
TL;DR: The H oximes appear to be very promising antidotes against nerve agents because they are able to protect experimental animals from toxic effects and improve survival of animals poisoned with supralethal doses.
Abstract: The cholinesterase-inhibiting organophosphorus compounds referred to as nerve agents (soman, sarin, tabun, GF agent, and VX) are particularly toxic and are considered to be among the most dangerous...
362 citations
TL;DR: Benzylpenicillin (Penicillin G) alone and in association was the most frequently utilized chemotherapy but showed little efficacy and future clinical research should focus on confirming the efficacy of silybin, N-acetylcysteine, and detoxication procedures.
Abstract: Background: Amatoxin poisoning is a medical emergency characterized by a long incubation time lag, gastrointestinal and hepatotoxic phases, coma, and death. This mushroom intoxication is ascribed t...
337 citations
TL;DR: The lack of enhancement of acetaminophen toxicity by phenytoin and in fact, the potential for reduction of toxicity with that agent is a good example of the evolution of knowledge.
Abstract: The acetaminophen nomogram including its uses and limitations is discussed as well as the development of the N-acetylcysteine protocol. While it has taken many years to elucidate the genetic variability and true multiplicity of the cytochrome P450 “mixed function oxidase system” many publications early on looked at the enzyme system as a single entity. Numerous articles indicated that barbiturates, anticonvulsants, and others could induce “P450” and add to the toxicity of acetaminophen. It rapidly became apparent that just because “P450” was induced when measured as a whole, not all other substrates would have changed metabolic activity. The role of diet and ethanol induction and inhibition on CYP2E1, the enzyme of greatest interest for acetaminophen is multifaceted. The lack of enhancement of acetaminophen toxicity by phenytoin and in fact, the potential for reduction of toxicity with that agent is a good example of the evolution of our knowledge. Further complicating our understanding is the introductio...
282 citations
TL;DR: The pharmacology and toxicology of valproic acid toxicity is reviewed and the use of controversial adjunctive therapies, including extracorporeal drug elimination and l-carnitine supplementation, will be discussed.
Abstract: Acute valproic acid intoxication is an increasing problem, accounting for more than 5000 calls to the American Association of Poison Control Centers in 2000. The purpose of this paper is to review ...
218 citations
TL;DR: In the acute phase of organophosphate poisoning, low serum acetylcholinesterase (>50% of minimum normal value) supports the diagnosis of organophile poisoning but it does not show a significant relationship to the severity of poisoning (NS).
Abstract: Objective: The aim of this study is to investigate the prognostic value of serum acetylcholinesterase levels and their relationship with neurological syndromes (Type 1 syndrome, intermediate syndro...
185 citations
TL;DR: This report summarizes scientific evidence on health effects of low-level exposure to persistent organic pollutants and endocrine disrupting chemicals and indicates that the nature and severity of health outcomes may depend on the developmental time-period during which chemical exposure occurs.
Abstract: Persistent organic pollutants are lipophilic, man-made chemicals that are highly resistant to degradation. Due to their persistence, they have become distributed in small quantities throughout the world. They bioaccumulate in thefood chain and are stored in fatty tissues. Biomagnifications up the food chain result in potential widespread human exposure to these chemicals. Exposure to persistent organic pollutants has been associated with many adverse human health effects, including impaired neurodevelopment, immune and reproductive function. Many persistent organic pollutants also possess the ability to disrupt the normal functioning of the endocrine system. There is an increasing concern that low-level exposure to these endocrine disrupting chemicals may have adverse health impacts, particularly during fetal, neonatal, and childhood development. Both the nature and severity of health outcomes may depend on the developmental time-period during which chemical exposure occurs. This report summarizes scientific evidence on health effects of low-level exposure to persistent organic pollutants and endocrine disrupting chemicals.
116 citations
TL;DR: The results of this study have implications regarding low-level solvent exposure, as in the occupational setting, suggesting that MRI may be a more useful tool to sort out the presence of neurological abnormalities rather than neuropsychological tests.
Abstract: Objective: Individuals chronically abusing organic solvents have been reported in the medical literature for almost four decades to have a variety of neurological abnormalities. Most have been sing...
114 citations
TL;DR: Health authorities must be aware of the hazards of recreational γ-hydroxybutyrate, and physicians must be cognizant of this recent cause of coma among youths presenting to the emergency departments.
Abstract: Background: Previously used as a general anesthetic, γ-hydroxybutyrate is now used as a recreational drug. Not surprisingly, an increasing number of acute overdose cases requiring emergency medical care have been reported and described, especially in the United States. Objectives: To determine the number and percentage of γ-hydroxybutyrate overdoses over a 15-month period and to describe the clinical hallmarks and course of this new drug in overdose. Methods: All toxicological emergencies, including those caused by illicit drug consumption, were recorded for 15 months in an urban public hospital emergency department. Accurate toxicological history was obtained from the patients and, if γ-hydroxybutyrate was suspected, confirmation was performed by urine mass spectrometry. The study data were compared with data recorded in the same emergency department in 1989. Results: The total number of toxicological emergencies attended in our emergency department have remained unchanged during the last decade, with a ...
102 citations
TL;DR: Data from this prospective hospital-based study provide important preliminary information on the pattern of symptomatic poisonings in this south-east part of this country.
Abstract: Background:The objective of this prospective hospital-based study was to evaluate the rate and characteristics of acute human poisoning in our province (Gaziantep City, Turkey). Methods: All cases of acute human poisonings admitted to the emergency department of the Gaziantep University Hospital, Gaziantep, Turkey, between January 2000 and December 2001, were included in the study. The rate and causes of mortality from poisoning as well as demographic data of the patients were investigated. Results: There were 179 (0.7%) poisoning cases among 25,605 patients who admitted to the emergency department. Of the poisoning cases, 64.3% were female and 35.6% were male patients. The poisoning made a peak between the ages of 16 and 25. The majority of poisonings resulted from oral ingestion with deliberate intake accounting for 78.7% of the cases. Most of the suicide attempt cases were also females. Analgesics were the most common agents (42.4%) among the drugs incriminated in poisoning. Twenty-four patients (13.7%...
96 citations
Journal Article•
83 citations
TL;DR: Metformin was cleared by the continuous veno-venous hemodialysis modality of continuous renal replacement therapy in this metformin overdose, which resulted in death.
Abstract: Background: Metformin is prescribed with an increasing frequency for patients with Type II diabetes mellitus; the increasing availability increases the risk of intentional overdoses. Metformin may cause severe lactic acidosis in overdose, especially when accompanied by co-ingestants or other medical conditions that alter lactate handling or metformin elimination. Though the clearance of therapeutic metformin by hemodialysis is known, the clearance in the setting of a large overdose has not been reported. Case Report: A 58-year-old man with a history of Type II diabetes, hypertension, bipolar disease, and decreased renal function presented after ingestion of approximately 40 500-mg metformin tablets and 20 240-mg diltiazem sustained-release tablets. Clinical manifestations of poisoning included somnolence, hypotension, bradycardia, severe lactic acidosis, and ultimately death. Gastric decontamination was attempted with gastric lavage, multiple dose activated charcoal, and whole bowel irrigation. Hemodynami...
TL;DR: Although dialysis clears formate, it did not significantly enhance endogenous elimination in the authors' series of patients, and low pH, low bicarbonate, and elevated anion gap correlate independently with formate presence.
Abstract: Objective: We sought to describe the kinetics, dialysis clearance, and laboratory markers of formate (FA), the toxic metabolite of methanol (meOH). Methods: Data were obtained from a prospective, multicenter study of fomepizole±dialysis for methanol poisoning. Inclusion criteria confirmed methanol exposure or suspicion of exposure plus either acidemia or abnormal osmolar gap. Dialysis indications were [meOH]>50 mg/dL, pH<7.1, refractory acidosis, or visual toxicity. Serial plasma formate, methanol, pH, and electrolyte measurements were made. Formate was determined by gas chromatography. Endogenous and dialysis elimination half-lives were calculated as t1/2=0.693/Ke, with Ke (elimination constant) derived from the slope of log (FA) vs. time. Half-lives were compared with an unpaired Student's t-test. Dialysis clearance was calculated using the Fick Principle. Pearson correlation analysis compared initial formate with initial pH, serum bicarbonate, and anion gap. Results: Eleven patients were treated in the...
TL;DR: Children have unusual patterns of exposure to environmental chemicals, and they have vulnerabilities that are quite distinct from those of adults.
Abstract: Children have unusual patterns of exposure to environmental chemicals, and they have vulnerabilities that are quite distinct from those of adults. Increasingly, children's exposures to chemicals in the environment are understood to contribute to the causation and exacerbation of certain chronic, disabling diseases in children including asthma, cancer, birth defects, and neurobehavioral dysfunction. The protection of children against environmental toxins is a major challenge to modern society.
TL;DR: Analysis of databases created from prospective studies will not only answer questions about the effects of different species, but will ultimately allow the development of evidence-based methods to identify animals based on the circumstances and effects of bites, rather than requiring formal identification of the culprit.
Abstract: Clinical toxinology suffers from a long history of poor data collection. A 20-year review of MEDLINE illustrates the lack of randomized controlled trials and prospective studies in clinical toxinol...
TL;DR: In this article, the authors review recent findings on the toxicological interactions between alcohol (ethanol) and benzodiazepines, and the combined use of benzodiazines and alcohol in fatal poisoning.
Abstract: Background: We review recent findings on the toxicological interactions between alcohol (ethanol) and benzodiazepines, and the combined use of benzodiazepines and alcohol in fatal poisoning. Acute ingestion of alcohol combined with benzodiazepines is responsible for several toxicological interactions that can have significant clinical implications. In general, metabolism of these drugs is delayed when combined with acute alcohol ingestion although some reports suggest otherwise. Alternately, the drugs metabolized during chronic alcohol ingestion have an increased clearance. The net effect may also be influenced by internal (e.g., disease, age) and external (e.g., environment, diet) factors. Fatal poisoning involving coadministration of alcohol and benzodiazepine, especially triazolam, continues to be a serious problem.
TL;DR: Poisoning caused by ingesting insecticides containing permethrin, xylene, and surfactant manifests primarily gastrointestinal tract symptoms and signs, but the involvement of the central nervous system and lungs were less common, but clinically more significant.
Abstract: Background: Forty-eight patients poisoned with insecticide formulations containing permethrin (a Type I pyrethroid insecticide), xylene, and surfactants are reported here. These patients were diagnosed and treated in the Chang Gung Memorial Hospital in Taiwan from January 1987 to June 1999. Ten patients ingested permethrin in error and 38 patients attempted suicide. Gastrointestinal tract signs and symptoms were most common (35/48; 73%), and included sore throat, mouth ulcerations, dysphagia, epigastric pain, and vomiting. Pulmonary abnormalities were documented in 29% (14/48) of patients. Aspiration pneumonitis occurred in eight patients, including one fatal case. Pulmonary edema was observed in two patients. Sixteen patients (33%) had central nervous system involvement including confusion (6/48; 13%), coma (10/48; 21%), and seizures (4/48; 8%). Cardiovascular symptoms in 3/48 (7%) patients were limited to arrhythmias and shock. Mild renal and hepatic dysfunction was found in 5/48 (10%) and 3/48 (6%) of ...
TL;DR: A 34-year-old male with lumbar disc disease and surgery was placed on gabapentin daily for chronic back pain and remained on a steady dose of 8000 mg/day for 9 months, almost doubled what is considered therapeutic.
Abstract: A 34-year-old male with lumbar disc disease and surgery was placed on gabapentin daily for chronic back pain. He remained on a steady dose of 8000 mg/day for 9 months, almost doubled what is considered therapeutic. He ran out of medication, was unable to refill his prescription for 2 days and presented to the emergency department in status epilepticus. There was no previous history of seizure disorder and he was on no other medications. A medical evaluation for an alternative etiology of his seizures was negative. Although gabapentin withdrawal has been previously reported and usually consists of anxiety, diaphoresis, and palpitations, this is the first reported patient with generalized seizures and status epilepticus secondary to gabapentin withdrawal.
TL;DR: Special attention has to be given to children's unique differences in order to evaluate the clinical consequences of their toxic exposures, and the key roles of poison centers, clinical toxicologists, and pediatricians can collaborate on the identification, assessment, and surveillance of toxic risk for child health and development.
Abstract: Children represent the largest subpopulation of those susceptible to the adverse effects of air pollution. Compared to adults, children express a greater vulnerability, which can be explained by differences in: the circumstances of exposure related to age, their activities, their child status, differences in lung anatomy and physiology, differences in the clinical expression of disease, and their organ maturity. Many factors have to be assessed in order to evaluate the severity of toxic exposures: pollutant solubility, particle size, concentration, reactivity of pollutants, and pattern of ventilation. Within the numerous air pollutants, some are of special concern for children. For example, ozone has been shown to affect the lungs of healthy school children, especially asthmatics. Airborne particles, nitrogen oxides, sulfur oxides, and acid aerosols have also been shown to induce acute respiratory symptoms, asthma, and bronchitis. Of particular importance is carbon monoxide, which, under certain circumstances, may be found in highly toxic concentrations indoors where children spend most of their time. Special attention has to be given to children's unique differences in order to evaluate the clinical consequences of their toxic exposures. This circumstance emphasizes the key roles of poison centers, clinical toxicologists, and pediatricians, all of whom can collaborate on the identification, assessment, and surveillance of toxic risk for child health and development.
TL;DR: A case of fatal myeloencephalopathy secondary to inadvertent intrathecal administration of vincristine was inadvertently injected into a twelve-year-old girl with acute lymphocytic leukemia, in which patient survival was achieved with the same treatment.
Abstract: Background: Vincristine, an antineoplastic agent, must never be injected intrathecally because of its devastating neurotoxic effects, which are usually fatal. We report a case of fatal myeloencephalopathy secondary to inadvertent intrathecal administration of vincristine. Case Report: Intrathecal vincristine was inadvertently injected into a twelve-year-old girl with acute lymphocytic leukemia. The error was immediately recognized and treated with cerebrospinal fluid drainage and cerebrospinal fluid exchange. Clinical evolution during the 83 days until death is described. Multiple samples of cerebrospinal fluid were assayed for vincristine sulfate. Neuropathological post-mortem changes in the brain and spinal cord are reported. Conclusion: We compare our case with other previously reported cases in which patient survival was achieved with the same treatment. We summarize preventive measures to avoid such unfortunate occurrences.
TL;DR: Although breast-fed children were exposed postnatally to elevated levels of polychlorinated biphenyls from maternal milk, the adverse effects associated with prenatal exposure were markedly stronger in the children who were not breast- fed, and the fetus is particularly vulnerable to this exposure.
Abstract: Polychlorinated biphenyls are a family of synthetic hydrocarbon compounds that were used historically for a broad range of industrial purposes. Although banned in the 1970s, they continue to be ubiquitous in landfills, sediments, and wildlife. Prenatal polychlorinated biphenyl exposure was evaluated in a sample of children born to women who had eaten relatively large quantities of polychlorinated biphenyl-contaminated Lake Michigan fish. This exposure was found to be associated with poorer intellectual function after controlling statistically for a broad range of potential confounding variables. Deficits included poorer recognition memory in infancy, lower scores on a preschool IQ test, and poorer verbal IQ and reading comprehension at 11 years of age. Although breast-fed children were exposed postnatally to elevated levels of polychlorinated biphenyls from maternal milk, the adverse effects associated with prenatal exposure were markedly stronger in the children who were not breast-fed. It is not clear w...
TL;DR: The probable cause of the trancelike state of the Priestess (the Pythia) at the oracle of Delphi during her mantic sessions was produced by inhaling ethylene gas or a mixture of ethylene and ethane from a naturally occurring vent of geological origin.
Abstract: Ancient historical references consistently describe an intoxicating gas, produced by a cavern in the ground, as the source of the power at the oracle of Delphi. These ancient writings are supported by a series of associated geological findings. Chemical analysis of the spring waters and travertine deposits at the site show these gases to be the light hydrocarbon gases methane, ethane, and ethylene. The effects of inhaling ethylene, a major anesthetic gas in the mid-20th century, are similar to those described in the ancient writings. We believe the probable cause of the trancelike state of the Priestess (the Pythia) at the oracle of Delphi during her mantic sessions was produced by inhaling ethylene gas or a mixture of ethylene and ethane from a naturally occurring vent of geological origin.
TL;DR: Methanol poisonings continue to occur in the United States with toddlers at the highest risk for exposure, but adolescents and adults at thehighest risk for life-threatening intoxications.
Abstract: Objectives: We investigated US methanol-poisoning exposures since little recent information is available about the frequency, sources of methanol, or outcomes of individuals who consume methanol Methods: We reviewed human methanol exposures reported to the American Association of Poison Control Centers Toxic Exposure Surveillance System 1993–1998 Results: The mean number of cases per year was 2254 Each year 167 cases had an outcome of moderate effect, major effect, or death One death occurred in every 183 exposures to methanol Symptomatic cases increased abruptly from 18 to 25% for infants and children, from 141 to 123% for adolescents and adults, while the intentional exposures increased from <1 to 21% for adolescents, and 11% for adults Cases occurred in every decade of life but toddlers had the highest number of exposures In 68 methanol fatalities, confusion developed followed by coma, hypotension, respiratory depression, and cerebral edema Blood methanol levels were above 100 mg/dL (70%)
TL;DR: The evidence base of clinical toxicology suffers in comparison to other clinical disciplines because of an excess of case reports and case series with little in the way of case control or cohort studies, and very few randomized controlled trials.
Abstract: The evidence base of clinical toxicology suffers in comparison to other clinical disciplines. There is an excess of case reports and case series with little in the way of case control or cohort studies, and very few randomized controlled trials. While randomized controlled trials are rightly regarded as the gold standard for interventional studies, they have limitations that are particularly evident in the practice of clinical toxicology. Properly conducted observational studies using quantitative, epidemiological methods [nonrandomized trials, cohort studies (prospective and retrospective), case control methods] can provide answers that may be impossible to obtain from randomized controlled trials. Development of a strong evidence base is essential for progress in clinical toxicology. Whether that evidence base is derived from randomized controlled trials or observational studies, it is essential to collect data. Important observations can be made from basic clinical data and systematic collection of those data into some form of electronic database has siginificant advantages. A clinical database provides accurate information in the areas of clinical practice, quality assurance (audit), and research. In the area of research, an appropriately designed database can be both a source of hypotheses as well as a vehicle to test them. It can also serve as a repository of research data in subsequent randomized controlled trials.
TL;DR: Neurotransmitters, receptors, endogenous opioids, and baseline sympathetic tone determine the clinical response to clonidine as well as the potential response to drug therapy followingClonidine overdose.
Abstract: The incidence of clonidine overdose is increasing, yet there is a paucity of new information regarding treatment options for clonidine toxicity. Reported treatment approaches vary widely, demonstrating the lack of science on which current treatment is based. Available research needs to be reassessed. Neurotransmitters, receptors, endogenous opioids, and baseline sympathetic tone determine the clinical response to clonidine as well as the potential response to drug therapy following clonidine overdose. This article reviews aspects of clonidine toxicity that need to be further investigated. Multicenter research trials will be required to evaluate new treatment options.
TL;DR: This is a report of status epilepticus associated with wide complex tachycardia after carbamazepine overdose, which may be resistant to conventional therapy.
Abstract: We report two patients who experienced status epilepticus after carbamazepine overdose. The first patient was an 18-year-old female with a history of epilepsy. She experienced 4 hour of persistent and prolonged seizures resistant to sodium amytal therapy. The status epilepticus ended with her death. The second patient was an 18-year-old male with a history of bipolar disorder. He experienced 5 hour of persistent and prolonged seizures that appeared to be resistant to diazepam, phenytoin, and phenobarbital. The seizures abated with the infusion of midazolam. This is a report of status epilepticus associated with wide complex tachycardia after carbamazepine overdose, which may be resistant to conventional therapy.
TL;DR: Although enquiries to the National Poisons Information Centre in Sri Lanka averaged only 0.5% of poisoning hospitalizations, they were sufficiently representative of the national pattern to predict that increasing utilization of the NPIC would offer a much needed service, both for children currently under-represented in telephone inquiries, and for suicidal events where the mortality far exceeds that of other countries.
Abstract: Introduction: Poisoning is a major health concern in Sri Lanka, which has a very high morbidity and mortality from pesticide poisoning. Poisoning, which continues to be in the first five leading causes of death, accounts for about 80,000 hospitalizations and over 3000 deaths per year. The National Poisons Information Centre in Sri Lanka, the first such centre to be established in South Asia, completed 10 years service in 1997. The 4070 calls received in the first 10 years are analyzed and compared with the national hospitalization pattern. Methods: The recorded data sheets of all enquiries received from 1988 to 1997 were analyzed retrospectively to study (1) purpose of enquiry, (2) category of enquirer, (3) circumstances of poisoning, (4) gender of victim, (5) age of victim, (6) type of poison, and (7) outcome. Items (6) and (7) were compared with the national hospital statistics for 1998. Results: Of the 4070 enquiries, 92% concerned specific patients and 6% were for information on poisons. Almost 90% of...
TL;DR: This monograph describes the toxicity of Herba Asari (Herba cum Radice Asari).
Abstract: This monograph describes the toxicity of Herba Asari (Herba cum Radice Asari). Jou-Feng Deng was a guest editor of this monograph series. Note: Numbering of references in this monograph is not sequential because it represents numbering throughout the database.
TL;DR: In overdose, levetiracetam is sedating and causes respiratory depression, however, recovery is rapid with supportive care and serial serum concentrations suggest first-order elimination even at concentrations 10–40 fold higher than therapeutic.
Abstract: Background: Levetiracetam (Keppra®) is a new anticonvulsant used to treat partial complex seizures that is also being investigated for its mood-stabilizing properties. Although its precise mechanis...
TL;DR: The resultant database and monographs represent the first reviews specifically on the toxicity of individual Chinese herbs with toxicological grades based on the evidence of published studies and should assist in promoting the safe and effective use of Chinese herbal medicine.
Abstract: Background: Use of Chinese herbal medicine has increased steadily in the West and adverse reactions have been reported. However, information is not readily available on the toxicity of the herbs and the management of poisoning. The goals of this project were to retrieve and evaluate scientific evidence on the toxicity of Chinese herbal medicine, to grade the toxicity of individual herbs, and to summarize relevant herb data via a searchable electronic database. Methods: English and Chinese primary studies were systematically retrieved via journal abstracting databases and key toxicity texts. Partial translation of published research was achieved via an audited process utilizing data extraction forms. Methods for grading herb toxicity (in therapeutic use or overdose) were developed based on a combination of the quality of reports, severity of adverse reaction, supporting animal studies, extrapolation from pharmacology and empirical evidence. Results: Good quality studies on the toxicity of Chinese herbs are...
TL;DR: This study compares Hexafluorine with water rinsing plus topical calcium and with waterRinsing alone, finding that the former has a better effect than the latter on rats with acid-exposed skin areas.
Abstract: Background: Calcium gluconate gel, applied after initial rinsing with water, has a documented effect as first aid treatment for hydrofluoric acid burns. Hexafluorine® is a novel liquid compound developed especially for emergency decontamination of hydrofluoric acid eye and skin exposures. However, scientific documentation of the effect of Hexafluorine is insufficient. This study was undertaken to compare Hexafluorine with water rinsing plus topical calcium and with water rinsing alone. Methods: Thirty-five Sprague–Dawley rats were anesthetized and their backs shaved. Four filter papers 10 mm in diameter were soaked in 50% hydrofluoric acid and applied on the shaved area of each rat for 3 minutes. Thirty seconds later, the acid-exposed skin areas were rinsed with 500 mL Hexafluorine for 3 minutes (group H, n=10), 500 mL water for 3 minutes (group W, n=10) or 500 mL water for 3 minutes followed by a single application of 2.5% calcium gluconate gel (group Ca, n=10), or received no treatment (controls, n=5). ...