Acute appendicitis is characterized by a uniform and highly selective pattern of inflammatory gene expression.

Acute appendicitis (AA) is the most common life-threatening surgical emergency in pediatrics. To characterize the nature of the inflammatory response in AA, gene expression profiles were generated. We found remarkable uniformity in the genes that were differentially expressed between patients with appendicitis and control groups. Sixty-four probe sets were differentially expressed in samples from patients with both severe and mild appendicitis compared to control samples, and within this group we were able to identify four dominant clusters. Interestingly, expression levels of interleukin (IL)-8 significantly correlated with histologic score, and expression of IL-8 protein was observed within both neutrophils and mononuclear cells by immunohistochemistry, suggesting a possible role in the etiology of appendicitis. Although there was some overlap between genes reported to be differentially expressed in Crohn's disease (CD) and those observed in AA, differential expression of genes involved in interferon responses that characterize CD was not observed.

Pretreatment of CD-1 mice with 4-methylpyrazole blocks toxicity from the gamma-hydroxybutyrate precursor, 1,4-butanediol.

1,4-Butanediol (1,4-BD) is the dihydroxy precursor of gamma-hydroxybutyrate (GHB), a popular recreational drug that has been banned by the United States Food and Drug Administration (FDA) and controlled as a federal schedule I drug. 1,4-BD is enzymatically converted in vivo to GHB by alcohol dehydrogenase (ADH), and overdoses can result in coma, severe respiratory depression, bradycardia, hypothermia, seizures, and death. Presently, there is no antidote. We pretreated CD-1 mice with the ADH antagonist, 4-methylpyrazole (4-MP), to determine if blocking ADH can prevent or decrease toxicity from 1,4-BD overdose. Pretreatment with 4-MP increased the Toxic Dose-50 (TD(50)) of 1,4-BD for the righting reflex from 585 mg/kg (95% CI, 484-707 mg/kg) in control mice to 5,550 mg/kg (95% CI, 5,353-5,756 mg/kg) in pretreated mice. Pretreatment with 4-MP also increased the TD(50) of 1,4-BD for the rotarod test from 163 mg/kg (95% CI, 136-196 mg/kg) in control mice to 4,900 mg/kg (95% CI, 4,812-4,989 mg/kg) in pretreated mice. Pretreatment with 4-MP significantly decreased the toxicity of 1,4-BD in CD-1 mice, presumably by inhibiting its ADH biotransformation to GHB. 4-MP warrants further investigation as a potential antidote for this increasingly abused drug.

Nalmefene for elective reversal of procedural sedation in children.

Nalmefene is a newer, long-acting opioid antagonist. Its use in children for the elective reversal of emergency department procedures has not been investigated. The objective was to evaluate the safety of nalmefene in children. An open-label pediatric clinical trial was performed. The study was conducted at the emergency department of an urban, university-affiliated children's hospital and consisted of children aged 6 months to 12 years who required procedural sedation where an opioid agent was administered. Patients were excluded if there was altered mental status, history of head trauma, history of opioid allergy, or the anticipated need for opioid agents for pain relief after the procedure. At the completion of the procedure, nalmefene was administered in a dose of 0.25 microg/kg increments (max 10 microg) until sedation was resolved, or to a maximum of 1.0 microg/kg (max 40 microg). Serial ECGs, vital signs, and oxygen saturation were recorded. Sedation was assessed using the Clinical Global Impression Scale (CGIS) at baseline, 2, 4, 6, 8, and 10 minutes after the initial nalmefene dose. The observer's assessment of alertness and sedation (OAA/S) was measured at baseline, 10, 30, 60, 90, and 120 minutes after the first dose of nalmefene. Episodes of resedation were recorded. All patients received follow-up by telephone at 4 and 24 hours after the initial dose of nalmefene to identify any potential late adverse effects. Over the study interval 15 patients were enrolled. Mean age was 59.1 +/- 41.5 months. Procedures involved fracture reduction (n=8), laceration repair (n = 4), abscess drainage (n = 2), and arthrocentesis (n = 1). All patients received IV fentanyl and midazolam. The mean dosage of fentanyl and midazolam was 3.21 +/- 1.03 microg/kg and 0.07 +/- 0.03 mg/kg, respectively. The mean dose of nalmefene at the time of complete response (CGIS = 1 or 2) was 0.55 +/- 0.29 microg/kg. The median number of nalmefene doses was 2. All but one patient (93%) had a complete response based on CGIS at 10 minutes after the initial dose of nalmefene was given. Nalmefene resulted in a significant improvement in CGIS (1.60 +/- 0.82 v 3.26 +/- 0.88, P =.001) and OAA/S (median score 5 v 4) when compared at baseline with 10 minutes after the initial dose of nalmefene. Nalmefene also resulted in increased diastolic blood pressure (62.6 +/- 10.5 v 55.8 +/- 10.7, P =.04) as well as improved oxygen saturation when compared at 120 minutes to baseline (99.5 +/- 0.74% v 98.5 +/- 0.4%, P =.03). There were no significant changes in pulse, systolic blood pressure, respiratory rate, and ECG. None of the patients became resedated after nalmefene was given. One patient developed nausea and vomiting within the first 2 hours after nalmefene; this resolved without intervention before discharge. No adverse events occurred in any of the patients at 4 and 24 hours postadministration. The results of this study showed that nalmefene is effective and safe for reversal of procedural sedation by opioids in children.

Childhood methanol ingestion treated with fomepizole and hemodialysis.

Fomepizole (4-methylpyrazole; Antizol) is used increasingly in the treatment of methanol toxicity in adults. Little experience exists with this drug in the pediatric population, however. We present a case of methanol poisoning in a child in whom the use of fomepizole averted intravenous ethanol infusion and the attendant side effects of this therapy.

Technical report: mercury in the environment: implications for pediatricians.

Mercury is a ubiquitous environmental toxin that causes a wide range of adverse health effects in humans. Three forms of mercury (elemental, inorganic, and organic) exist, and each has its own profile of toxicity. Exposure to mercury typically occurs by inhalation or ingestion. Readily absorbed after its inhalation, mercury can be an indoor air pollutant, for example, after spills of elemental mercury in the home; however, industry emissions with resulting ambient air pollution remain the most important source of inhaled mercury. Because fresh-water and ocean fish may contain large amounts of mercury, children and pregnant women can have significant exposure if they consume excessive amounts of fish. The developing fetus and young children are thought to be disproportionately affected by mercury exposure, because many aspects of development, particularly brain maturation, can be disturbed by the presence of mercury. Minimizing mercury exposure is, therefore, essential to optimal child health. This review provides pediatricians with current information on mercury, including environmental sources, toxicity, and treatment and prevention of mercury exposure.

False-positive tricyclic antidepressant drug screen results leading to the diagnosis of carbamazepine intoxication.

Ingestion of toxic substances is a common problem in pediatrics. When presented with the limited history of an unknown ingestion in a patient with altered mental status, a clinician depends on the physical examination and a toxic screen to determine the ingested substance(s). Some toxic screens yield false-positive or false-negative results that confound identification of ingested toxins. Three cases are presented in which carbamazepine ingestions were identified because of the false-positive tricyclic antidepressant serum toxic screen result in each case. Carbamazepine ingestion is one of the most common pediatric overdoses. Side effects include altered mental status, tachycardia, mydriasis, seizures, coma, and death. Several other substances also cause false-positive tricyclic antidepressant toxic screen results, including certain antipsychotic medications, antihistamines, and the muscle relaxant cyclobenzaprine. Specific tests and drugs causing false-positive results are presented in table form. More modern methods, specifically gas chromatographic-mass spectrometric, are more reliable in distinguishing these drugs. Knowledge of which substances commonly cause false-positive results on a given toxic screen can still lead the clinician to the correct diagnosis. tricyclic, carbamazepine, ingestion, intoxication, drug screen.

Adverse effects of reduced-dose d-penicillamine in children with mild-to-moderate lead poisoning.

BACKGROUND: Oral chelation therapy with d-penicillamine (d-PCN) has been proven to be effective in the treatment of mild-to-moderate lead poisoning. However, d-PCN is associated with a relatively high incidence of adverse effects when given in the standard dose of 25-30 mg/kg/d. Lower doses of d-PCN may reduce the rate of adverse effects without a significant reduction in the drug's efficacy. OBJECTIVE: To examine the incidence of rash, white blood cell and platelet count depression, and abnormal urinalysis with d-PCN when given in a dose of 15 mg/kg/d to children with blood lead concentrations <40 microg/dL. METHODS: Retrospective analysis of a clinical treatment course of children who received d-PCN during 1996 in the Lead and Toxicology Clinic of Children's Hospital, Boston. All children were treated under a reduced-dose d-PCN chelation protocol. RESULTS: During the study period, 55 children (mean age 37.4 mo) received 66 courses of d-PCN. Mean blood lead concentration before chelation was 24 microg/dL (range 15-37), with a corresponding erythrocyte protoporphyrin concentration of 42 microg/dL. After 77 days of treatment with d-PCN, blood lead concentration was reduced to mean 16 microg/dL (mean fall 35%; p = 0.005) and erythrocyte protoporphyrin was reduced to 28 microg/dL (p = 0.009). During chelation therapy, the white blood cell count fell below 5,000/mm3 in seven cases (9.7%); there were no episodes of platelet counts falling below 150,000/mm3. No cases of abnormal urinalysis were reported; three episodes of rash (4.5%) were recorded. The only patients prematurely terminated from therapy were those who developed rash; in all three cases, drug eruption was an isolated occurrence, which resolved within 48 hours of diphenhydramine therapy. All adverse effects were transient and resolved during or immediately after chelation therapy. CONCLUSIONS: Reduced-dose d-PCN appears to maintain efficacy at reducing blood lead concentrations. Reduced-dose d-PCN also appears to be associated with a rate of adverse effects lower than previously reported; observed adverse effects appear to be benign and transient.

Association between iron deficiency and low-level lead poisoning in an urban primary care clinic.

OBJECTIVES: The purpose of this study was to examine the association between iron deficiency and low-level lead poisoning. METHODS: Data were collected in an urban primary care clinic from 3650 children aged 9 to 48 months. Iron deficiency was defined as a red cell mean corpuscular volume (MCV) of less than 70 fL and a red cell distribution width (RDW) of more than 14.5 in children younger than 2 years, and an MCV of less than 73 fL and RDW of more than 14.5 in those 2 years or older. RESULTS: After adjustment for age, hemoglobin concentration, and insurance status, the odds ratios for iron deficiency predicting blood lead levels greater than or equal to 5 micrograms/dL and greater than or equal to 10 micrograms/dL were 1.63 (95% confidence interval [CI] = 1.29, 2.04) and 1.44 (95% CI = 1.004, 2.05). CONCLUSIONS: Iron deficiency is significantly associated with low-level lead poisoning in children aged 9 to 48 months.

Effect of iron deficiency anemia on lead distribution after intravenous dosing in rats.

OBJECTIVE: To determine the effect of iron deficiency anemia on blood and tissue lead distribution. METHODS: 24 weanling rats were divided into 2 groups. One group received an iron replete diet (200 ppm); the other received a low iron diet (20 ppm). After 24 days, each group was further subdivided into two doses of lead (5 mg/kg and 10 mg/kg) which was administered intravenously. Rats were continued on their respective diets for 7 days post-lead injection to allow tissue distribution, then sacrificed and blood and tissue lead concentration measured. RESULTS: Prior to lead administration, baseline blood lead concentrations were not significantly different between groups. At sacrifice, whole blood lead levels were significantly higher in iron deficient animals than in iron replete at both 5 and 10 mg/kg administered lead. Iron deficient animals had comparable lead concentrations to iron replete animals in brain, kidney and liver. Femur lead concentrations were higher at 10 mg/kg administered lead. CONCLUSION: Iron deficiency alters lead distribution such as that increased lead is found in blood for a given exposure.

Baclofen overdose: drug experimentation in a group of adolescents.

BACKGROUND: Baclofen, a lipophilic analog of gamma-aminobutyric acid, is clinically used to control spasticity. We report a mass exposure to baclofen in adolescents seeking intoxication; toxicokinetic data are included. CASE SERIES: A group of adolescents became symptomatic after ingesting 3 to 30 20-mg tablets of baclofen during a party at a suburban Boys' Club. Several children were noted to be very lethargic by chaperones, ingestion was suspected, and paramedics were called. Some white tablets were found in a couch at the site of the party. The Massachusetts Poison Control Center was called, and the tablets were identified as baclofen (20 mg). Fourteen patients were taken to local hospitals; 9 required intubation. Eight adolescents were transferred to our institution. In these 8 patients, symptoms were noted within 1 to 2 hours after overdose. The most common clinical findings included coma (7), hypothermia (6), bradycardia (5), hypertension (4), and hyporeflexia (8). Mean length of mechanical ventilation was 40 hours. Three patients had unifocal premature ventricular contractions. Two patients had tonic-clonic seizures. A single dose of activated charcoal was given to all patients. Drugs administered included nifedipine (1), flumazenil (1), naloxone (1), lorazepam (2), and phosphenytion (2). All patients recovered and were discharged home within 5 days of ingestion. Serial serum baclofen levels were obtained in all intubated patients (range, 0.049 to 6.0; normal, 0.08 to .40 microgram/mL). Levels obtained 14 hours after ingestion showed a linear correlation with length of mechanical ventilation (R2 = 0.9863). Persistent symptoms were noted in some patients, despite nondetectable baclofen levels. Toxicologic screening for drugs of abuse was negative except in 2 patients with ethanol levels, both < 5 mg/dL. CONCLUSION: Baclofen overdose may result in coma, apnea, autonomic disturbances, cardiac conduction abnormalities, and seizures. Levels obtained shortly after overdose correlate with length of mechanical ventilation.