Martin G. Belson

Risk Factors for Acute Leukemia in Children: A Review

Although overall incidence is rare, leukemia is the most common type of childhood cancer. It accounts for 30% of all cancers diagnosed in children younger than 15 years. Within this population, acute lymphocytic leukemia (ALL) occurs approximately five times more frequently than acute myelogenous leukemia (AML) and accounts for approximately 78% of all childhood leukemia diagnoses. Epidemiologic studies of acute leukemias in children have examined possible risk factors, including genetic, infectious, and environmental, in an attempt to determine etiology. Only one environmental risk factor (ionizing radiation) has been significantly linked to ALL or AML. Most environmental risk factors have been found to be weakly and inconsistently associated with either form of acute childhood leukemia. Our review focuses on the demographics of childhood leukemia and the risk factors that have been associated with the development of childhood ALL or AML. The environmental risk factors discussed include ionizing radiation, non-ionizing radiation, hydrocarbons, pesticides, alcohol use, cigarette smoking, and illicit drug use. Knowledge of these particular risk factors can be used to support measures to reduce potentially harmful exposures and decrease the risk of disease. We also review genetic and infectious risk factors and other variables, including maternal reproductive history and birth characteristics.

Bupropion exposures: clinical manifestations and medical outcome.

Bupropion is an antidepressant and smoking cessation aid. Limited toxicological information exists for intentional and unintentional bupropion-only exposures. A retrospective review of all bupropion-only exposures reported to the Toxic Exposure Surveillance System from 1998 through 1999 was conducted. Data for the three bupropion products, Wellbutrin, Wellbutrin SR, and Zyban, included demographics, reason for exposure, clinical effects, therapy, and medical outcome. A total of 7,348 bupropion-only exposures were reported: 56% female and 61% unintentional. The majority of exposures involved Wellbutrin SR; however, Wellbutrin exposures involved a higher percentage of intentional overdoses and serious clinical effects. Clinical effects related to bupropion were noted in 2,247 (31%) exposures; 8% of all children <6-years-old compared to 46% of all teenagers. Seizures developed in 15% of all intentional exposures. Cardiovascular disturbances were extremely uncommon after overdose. The majority of unintentional bupropion-only exposures result in minimal or no clinical toxicity; however, a significant number of intentional overdoses result in seizures.

Utility of comprehensive toxicologic screens in children

This study was undertaken to evaluate the clinical utility and cost-effectiveness of the limited component versus the high performance liquid chromatography (HPLC) component of comprehensive toxicologic screens in children. A retrospective patient series was studied at the emergency department (ED) of Hughes Spalding Childrens Hospital, an urban, tertiary-care ED, consisting of all patients younger than 19 years of age who had a comprehensive toxicologic screen between January 1994 and July 1995. The comprehensive test included a broad-spectrum HPLC component as well as a limited component that examined serum for ethanol, aspirin, and acetaminophen and urine for benzodiazepines, barbiturates, amphetamines, cocaine, phencyclidine, and opiates. All toxicologic screens were reviewed for the presence of exogenous toxins, followed by a chart review of all patients with positive screens and a selection of negative screens. Toxins were categorized as (1) iatrogenic or noniatrogenic, (2) clinically or nonclinically suspected by history and physical, and (3) clinically or nonclinically significant. Comprehensive toxicology screens were performed in 463 cases during the study period; 234 (51%) were positive for exogenous toxins. In 227 of 234 positive screens (97%), toxins were either suspected by history and/or physical, were present on the limited portion of the toxicology screen, or were clinically insignificant. The remaining 7 of the 234 positive screens (3%) were clinically significant and detected solely by the broad-spectrum HPLC portion of the comprehensive screen. However, in none of these 7 cases was patient management clinically altered as a result of the positive screen. The total additional cost for the HPLC component was

The utility of toxicologic analysis in children with suspected ingestions

16,205 (

Perchlorate exposure from infant formula and comparisons with the perchlorate reference dose

35x463), an average distributive charge of

CHRONIC ACETAMINOPHEN TOXICITY: A CASE REPORT AND REVIEW OF THE LITERATURE

2,315 per patient in whom the HPLC portion provided additional clinical information (

Public Health Investigation After the Discovery of Ricin in a South Carolina Postal Facility

16,205/7). Although adding significant charges to the evaluation of suspected toxic exposures in children, the HPLC component of the comprehensive drug screen was of no additional clinical benefit compared with its limited component alone.

Recognition of illness associated with covert chemical releases

OBJECTIVE To evaluate the usefulness of toxicologic studies on the management of children with suspected ingestions. DESIGN Prospective, consecutive case series. SETTING Two tertiary care childrens hospital emergency departments. PATIENTS All children < or =18 years of age presenting with a suspected ingestion. STUDY DESIGN Pediatric emergency physicians completed a 14-point questionnaire on each identified patient that included demographics, signs, and symptoms, and if applicable, the extent of drug analysis performed. Pre-test and post-test utility values were determined by the ordering physician using an 11-point scale (0 = least valuable, 10 = most valuable). Physicians also assessed how positive or negative drug analyses affected patient management. RESULTS Two hundred twenty patients met study criteria. Median age was 5 years, with males making up 53% of patients. Drug analysis was ordered in 72% (158/220) of cases, with 59% of these tests obtained for a history of ingestion and 27% obtained for altered mental status (AMS). The most common suspected ingestions were acetaminophen and cold preparations. Seventy-eight of 158 (49%) patients had positive toxicology tests, with 17 unsuspected findings. Patient management was affected in 53/158 (34%; 95% CI, 27-41%) cases. Unsuspected findings affecting management were found in only 4/158 (3%; 95% CI, 1-6%) cases. Significant differences in pre-test and post-test utility values occurred for serum assays (mean difference +0.4, P = 0.008), patients presenting with AMS (mean difference -0.8, P = 0.005), and patients having a negative drug test (mean difference -0.5, P = 0.003). Although negative drug analysis gave the physician reassurance in 39/80 (49%; 95% CI, 38-60%) cases, patient management was altered in only 8/80 (10%; 95% CI, 5-18%) cases. CONCLUSIONS Seventy-two percent of children presenting with suspected drug ingestions had toxicologic analysis performed as part of their evaluation. Analysis was most valuable to physicians when evaluation of overdoses required serum drug levels. Qualitative urine drug screens provided minimal useful information. Unexpected findings on urine drug screening leading to changes in management were uncommon.

Medical toxicology and public health: Update on research and activities at the centers for disease control and prevention

Perchlorate exposure may be higher in infants compared with older persons, due to diet (infant formula) and body weight versus intake considerations. Our primary objective was to quantitatively assess perchlorate concentrations in commercially available powdered infant formulas (PIFs). Secondary objectives were: (1) to estimate exposure in infants under different dosing scenarios and compare them with the perchlorate reference dose (RfD); (2) estimate the perchlorate concentration in water used for preparing PIFs that would result in a dose exceeding the RfD; and (3) estimate iodine intakes from PIFs. We quantified perchlorate levels in three samples (different lot numbers) of reconstituted PIF (using perchlorate-free water) from commercial brands of PIF in each of the following categories: bovine milk-based with lactose, soy-based, bovine milk-based but lactose-free, and elemental (typically consisting of synthetic amino acids). Exposure modeling was conducted to determine whether the RfD might be exceeded in 48 dosing scenarios that were dependent on age, centile energy intake per unit of body weight, body weight percentile, and PIF perchlorate concentration. We obtained three different samples in each of the five brands of bovine- and soy-based PIF, three different samples in each of the three brands of lactose-free PIF, and three different samples in two brands of elemental PIF. The results were as follows: bovine milk-based with lactose (1.72 μg/l, range: 0.68–5.05); soy-based (0.21 μg/l, range: 0.10–0.44); lactose-free (0.27 μg/l, range: 0.03–0.93); and elemental (0.18 μg/l, range: 0.08–0.4). Bovine milk-based PIFs with lactose had a significantly higher concentration of perchlorate (P<0.05) compared with all. Perchlorate was a contaminant of all commercially available PIFs tested. Bovine milk-based PIFs with lactose had a significantly higher perchlorate concentration perchlorate than soy, lactose-free, and elemental PIFs. The perchlorate RfD may be exceeded when certain bovine milk-based PIFs are ingested and/or when PIFs are reconstituted with perchlorate-contaminated water.

Ricin poisoning: a comprehensive review.

Acetaminophen is one of the most frequently used medications in the United States. While usual dosing of acetaminophen is considered harmless, both acute and chronic overdoses can be fatal. The majority of reported cases of chronic acetaminophen toxicity in adults occur in chronic alcohol abusers, patients taking P450-inducing medications, or following massive dosing. We describe a case of toxic hepatitis free of the aforementioned risk factors associated with chronic ingestion of moderately excessive doses of acetaminophen. Our patient ingested approximately 5.0 to 6.5 g of acetaminophen daily for 6 to 8 weeks via multiple medications. The inclusion of acetaminophen in numerous medications combined with the frequency of use of acetaminophen necessitates an increased concern for not only acute but also chronic acetaminophen toxicity.