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1.
Clin Pharmacol Ther ; 70(3): 280-6, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11557916

ABSTRACT

BACKGROUND: Elevations of inflammatory cytokines have been reported in animal models of acetaminophen (INN, paracetamol) toxicity. In addition, interleukin 8, a chemokine, has been found to be elevated in toxin-associated hepatic disease (ie, acute alcoholic hepatitis). The purpose of this study was to measure serum cytokine levels in children and adolescents with acetaminophen overdose and to evaluate relationships between cytokine elevation and hepatotoxicity. METHODS: Serum levels of tumor necrosis factor alpha, interleukin 1beta, interleukin 6, interleukin 8, and interleukin 10 were measured by ELISA in children and adolescents (n = 35) with acetaminophen overdose. Peak cytokine levels were examined relative to biochemical evidence of hepatocellular injury, nomogram risk assessment, and prothrombin time. RESULTS: Five patients had aspartate aminotransferase or alanine aminotransferase levels >1000 IU/L, and 4 patients had aspartate aminotransferase or alanine aminotransferase levels > or =100 IU/L and < or =1000 IU/L. No elevations of tumor necrosis factor alpha or interleukin 1beta were detected. Peak interleukin 8, but not interleukin 6 or interleukin 10, correlated with hepatotoxicity (Mann-Whitney exact test, P <.001). The peak interleukin 8 level was greater in patients at high risk by the nomogram combined with those presenting at >15 hours, as compared with other patients (Mann-Whitney U test, P <.01). The interleukin 8 level peaked before aspartate aminotransferase or alanine aminotransferase in 5 of the 9 patients with hepatotoxicity. In addition, interleukin 8 concentrations of >20 pg/mL were associated with peak prothrombin time values (Mann-Whitney exact test, P <.015). CONCLUSIONS: Interleukin 8 elevation in patients with acetaminophen hepatotoxicity corresponds with other common clinical measures that are predictive of hepatocellular injury. Further study is warranted to evaluate possible mechanistic relationships between inflammatory cytokines and acetaminophen hepatotoxicity in children and adults.


Subject(s)
Acetaminophen/poisoning , Analgesics, Non-Narcotic/poisoning , Drug Overdose/blood , Interleukin-8/blood , Acetylcysteine/therapeutic use , Adolescent , Chemical and Drug Induced Liver Injury/blood , Child , Child, Preschool , Female , Humans , Infant , Liver Function Tests , Male , Prothrombin Time
2.
J Clin Pharmacol ; 41(8): 846-51, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11504272

ABSTRACT

Acetaminophen-protein adducts are biomarkers of acetaminophen toxicity present in the centrilobular region of the liver of laboratory animals following the administration of toxic doses of acetaminophen. These biomarkers are highly specific for acetaminophen-induced hepatic injury and correlate with hepatic transaminase elevation. The objective of this prospective, multicenter study was to evaluate the clinical application of the measurement of acetaminophen-protein adducts in pediatric acetaminophen overdose patients. Serum samples were obtained from 51 children and adolescents with acetaminophen overdose at the time of routine blood sampling for clinical monitoring. Six subjects developed "severe" hepatotoxicity (transaminase elevation > 1,000 IU/L), and 6 subjects had transaminase elevation of 100 to 1,000 IU/L. Acetaminophen-protein adducts were detected in the serum of only 1 study subject, a patient with marked transaminase elevation (> 6,000 IU/L) and high risk for the development of hepatotoxicity according to the Rumack nomogram. While this study provides further support for the occurrence of covalent binding of acetaminophen to hepatic protein in humans following acetaminophen overdose, the detection of acetaminophen-protein adducts in serum with the current methodology requires significant biochemical evidence of hepatocellular injury.


Subject(s)
Acetaminophen/metabolism , Acetaminophen/poisoning , Analgesics, Non-Narcotic/metabolism , Proteins/metabolism , Adolescent , Alanine Transaminase/blood , Aspartate Aminotransferases/blood , Child , Child, Preschool , Drug Overdose , Humans , Infant , Infant, Newborn , Liver/drug effects
5.
Pediatr Emerg Care ; 15(3): 179-82, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10389953

ABSTRACT

BACKGROUND: Ketorolac is a parenteral, nonsteroidal analgesic that does not have a narcotic's risks of respiratory depression, hypotension, or dependence. Its usefulness in providing pain relief in pediatric patients with acute vaso-occlusive crisis of sickle cell disease has not been studied to date. METHODS: Twenty-nine patients with sickle cell disease between the ages of 5 and 18 years who presented to The Children's Hospital of Alabama emergency department (ED) with 41 distinct episodes of acute vaso-occlusive pain crisis were enrolled prospectively and randomized to receive either 0.9 mg/kg intravenous (IV) ketorolac or placebo in a double-blind fashion. All patients also received IV fluids and an initial 0.1 mg/kg of IV morphine. Subsequent standardized doses of morphine were given every 2 hours over a 6-hour observation period based upon severity of pain as scored by a 10-cm linear visual analog scale (VAS). Vital signs and pain severity were recorded initially and assessed hourly. Disposition was made at the end of the observation period. RESULTS: Patients receiving ketorolac and those receiving placebo were of similar age, weight, gender, number of prior ED visits, number of prior hospital admissions, duration of pain prior to presentation, and initial pain score. The total dose of morphine received, reduction in severity of pain as measured by VAS, rate of hospital admission, and rate of return to the ED for discharged patients did not differ significantly between the two groups. CONCLUSION: We were unable to demonstrate a synergistic analgesic effect for ketorolac in the treatment of pain from acute vaso-occlusive crisis in pediatric sickle cell disease. Further investigations involving larger samples of sickle cell patients may be needed to further define a role for ketorolac in the acute management of sickle cell vaso-occlusive pain.


Subject(s)
Analgesics, Non-Narcotic/therapeutic use , Anemia, Sickle Cell/drug therapy , Pain/drug therapy , Tolmetin/analogs & derivatives , Adolescent , Adult , Anemia, Sickle Cell/physiopathology , Blood Vessels/physiopathology , Child , Double-Blind Method , Female , Hospitalization/statistics & numerical data , Humans , Infant , Ketorolac , Male , Morphine/administration & dosage , Narcotics/administration & dosage , Pain/classification , Pain/etiology , Pain Measurement , Prospective Studies , Tolmetin/therapeutic use
8.
J Trauma ; 41(2): 310-4, 1996 Aug.
Article in English | MEDLINE | ID: mdl-8760542

ABSTRACT

BACKGROUND: Traumatic injuries of the cervical spine are uncommon in pediatrics. Children less than 8 years of age are reported to have "exclusively" upper cervical injuries. Recent experience at The Children's Hospital of Alabama (TCHA) challenged both of these notions. METHODS: A concurrent retrospective chart review of all cervical spine injuries treated at TCHA between January 1, 1992 and December 31, 1994 was performed. Data collected included patient demographics, date and time of injury, mechanism and site of injury, presence of associated injuries, clinical management, and outcome. RESULTS: Thirty-four patients with cervical spine injuries were seen at TCHA in the 36-month study period. The leading mechanism of injury was motor vehicle crashes (23/34 or 68%). Head injuries were associated with cervical spine injury in 53% of patients. Of the 20 patients aged 8 years or less, 10 (50%) had "low" cervical spine injuries (below C4). Overall mortality was 41% (14/34). Of the 15 vehicle occupants, 12 were unrestrained or inappropriately restrained. Two of those appropriately restrained were young school-aged children in lap-shoulder belts who sustained isolated cervical spine injuries. CONCLUSIONS: 1. The number of pediatric cervical spine injuries in our institution appears to be increasing. 2. Cervical spine injury in children less than 8 years of age are not exclusively confined to the region above C4. 3. Occurrence of cervical spine injuries despite lap-shoulder belt use suggests that efforts should be focused on refinement of motor vehicle restraint devices in young school-aged children.


Subject(s)
Cervical Vertebrae/injuries , Spinal Injuries/epidemiology , Accidents, Traffic/statistics & numerical data , Adolescent , Age Distribution , Alabama/epidemiology , Child , Child, Preschool , Female , Glasgow Coma Scale , Humans , Infant , Male , Retrospective Studies , Seat Belts , Spinal Injuries/classification , Spinal Injuries/mortality
9.
Arch Pediatr Adolesc Med ; 149(7): 808-11, 1995 Jul.
Article in English | MEDLINE | ID: mdl-7795774

ABSTRACT

OBJECTIVE: To determine whether an over-the-counter shampoo containing 1% selenium sulfide would have sporicidal activity equal to that of a 2.5% selenium sulfide prescription lotion in the adjunctive treatment of tinea capitis infection. DESIGN: Prospective randomized nonblinded clinical trial. SETTING: Outpatient clinics and emergency department of a children's hospital. PATIENTS: Fifty-four patients between the ages of 1 and 15 years with culture-proved tinea capitis infection caused by Trichophyton tonsurans enrolled during a 14-month period. METHODS: Patients were randomized to receive 2.5% selenium sulfide lotion, 1% selenium sulfide shampoo, or a bland, nonmedicated shampoo with which they were instructed to shampoo twice weekly. All received 15 mg/kg per day of griseofulvin. Dermatophyte cultures of the affected area of each patient's scalp were obtained on enrollment and every 2 weeks until a negative culture was obtained from a previously infected area. RESULTS: Survival data analysis demonstrated that both the 2.5% selenium sulfide and 1% selenium sulfide preparations were superior to the nonmedicated control shampoo in terms of the time required to eliminate shedding of viable spores. When compared with each other, there was no difference between the 2.5% selenium sulfide and 1% selenium sulfide preparations in time required to produce a negative culture. CONCLUSION: Commercially available 1% selenium sulfide shampoo is an equally effective yet less expensive alternative sporicidal therapy in the adjunctive treatment of tinea capitis infection.


Subject(s)
Hair Preparations , Selenium Compounds/therapeutic use , Tinea Capitis/drug therapy , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Selenium Compounds/administration & dosage , Spores, Fungal/drug effects , Survival Analysis , Treatment Outcome , Trichophyton/drug effects
10.
Pediatr Emerg Care ; 10(5): 253-5, 1994 Oct.
Article in English | MEDLINE | ID: mdl-7845848

ABSTRACT

The early initiation of comprehensive prenatal care is essential to avoid the complications associated with the more than one million adolescent pregnancies in the United States each year. Pediatric emergency physicians can play an important role in the initial diagnosis and appropriate referral of pregnant teenagers. However, previous studies have shown that the diagnosis of pregnancy can be difficult. The goals of this study were to characterize the spectrum of presenting complaints and to evaluate the assessment and disposition of pregnant teenagers presenting to a pediatric emergency department (PED). We retrospectively reviewed the medical records of 94 adolescents who presented with 95 pregnancies to our PED over an 18-month period. The mean age was 15.7 years (range 12 to 19 years). Only 8% mentioned pregnancy in their chief complaint at triage, and a concern about pregnancy was revealed by only 36% during the history of present illness. Ten percent denied they were sexually active. The most frequent complaints were gastrointestinal (77%); other complaints were gynecologic, urinary, or nonspecific. A concurrent sexually transmitted disease (32%) or urinary tract infection (31%) was frequently clinically suspected. At disposition, 26% were transported to an general emergency department for urgent obstetric evaluation; others were referred to a primary caregiver (23%) or obstetrician (39%). Pregnant teenagers present to the PED with a wide variety of complaints that may suggest other diagnoses. A high index of suspicion is required to diagnose pregnancy in adolescent girls so that appropriate care and referral can be initiated.


Subject(s)
Emergency Medical Services/statistics & numerical data , Pediatrics , Pregnancy in Adolescence , Adolescent , Adult , Child , Female , Humans , Medical Records , Pregnancy , Pregnancy in Adolescence/statistics & numerical data , Retrospective Studies , Sexually Transmitted Diseases/diagnosis
11.
Arch Intern Med ; 146(8): 1494-5, 1986 Aug.
Article in English | MEDLINE | ID: mdl-3729627
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