Showing papers by "Primary Children's Hospital published in 2002"

Genome sequence and comparative microarray analysis of serotype M18 group A Streptococcus strains associated with acute rheumatic fever outbreaks

Abstract: Acute rheumatic fever (ARF), a sequelae of group A Streptococcus (GAS) infection, is the most common cause of preventable childhood heart disease worldwide. The molecular basis of ARF and the subsequent rheumatic heart disease are poorly understood. Serotype M18 GAS strains have been associated for decades with ARF outbreaks in the U.S. As a first step toward gaining new insight into ARF pathogenesis, we sequenced the genome of strain MGAS8232, a serotype M18 organism isolated from a patient with ARF. The genome is a circular chromosome of 1,895,017 bp, and it shares 1.7 Mb of closely related genetic material with strain SF370 (a sequenced serotype M1 strain). Strain MGAS8232 has 178 ORFs absent in SF370. Phages, phage-like elements, and insertion sequences are the major sources of variation between the genomes. The genomes of strain MGAS8232 and SF370 encode many of the same proven or putative virulence factors. Importantly, strain MGAS8232 has genes encoding many additional secreted proteins involved in human-GAS interactions, including streptococcal pyrogenic exotoxin A (scarlet fever toxin) and two uncharacterized pyrogenic exotoxin homologues, all phage-associated. DNA microarray analysis of 36 serotype M18 strains from diverse localities showed that most regions of variation were phages or phage-like elements. Two epidemics of ARF occurring 12 years apart in Salt Lake City, UT, were caused by serotype M18 strains that were genetically identical, or nearly so. Our analysis provides a critical foundation for accelerated research into ARF pathogenesis and a molecular framework to study the plasticity of GAS genomes.

An Epidemiological Investigation of a Sustained High Rate of Pediatric Parapneumonic Empyema: Risk Factors and Microbiological Associations

Abstract: We investigated the increasing incidence of pediatric empyema during the 1990s at Primary Children’s Medical Center in Salt Lake City. Of 540 children hospitalized with community-acquired bacterial pneumonia (CAP) who were discharged from 1 July 1993 through 1 July 1999, 153 (28.3%) had empyema. The annual population incidence of empyema increased during the study period from 1 to 5 cases per 100,000 population aged !19 years. Streptococcus pneumoniae was identified as the most common cause of CAP with or without empyema; serotype 1 accounted for 50% of the cases of pneumococcal empyema. Patients with empyema were more likely to be13 years old, to have 7 days of fever, to have varicella, and to have received antibiotics and ibuprofen before admission to the hospital, compared with patients without empyema ( for each P ! .0001 factor). The increasing incidence of empyema was associated with infection due to S. pneumoniae serotype 1, outpatient treatment with certain antibiotics, ibuprofen use, and varicella.

Clinical Pharmacokinetics of Morphine

Abstract: Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is the standard against which new analgesics are measured. A thorough understanding of the pharmacokinetics of morphine is required in order to safely and effectively use this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and January 2002 relevant to the pharmacokinetics of morphine. These publications were reviewed and the literature summarized regarding unique and clinically important elements of morphine disposition relative to its parenteral administration (including intravenous, intramuscular, subcutaneous, epidural and intrathecal administration), absorption profile (immediate release, controlled release, and sublingual/buccal, and rectal administration), distribution, and its metabolism/excretion. Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.

Inhaled Nitric Oxide as a Preoperative Test (INOP Test I): the INOP Test Study Group.

Abstract: Background This study was performed to determine whether a preoperative hemodynamic evaluation with oxygen and inhaled nitric oxide identifies patients with pulmonary hypertension who are appropriate candidates for corrective cardiac surgery or transplantation more accurately than an evaluation with oxygen alone. Methods and Results At 10 institutions, 124 patients with heart disease and severe pulmonary hypertension underwent cardiac catheterization to determine operability. The ratio of pulmonary and systemic vascular resistance (Rp:Rs) was determined at baseline while breathing ∼21% to 30% oxygen, and in ∼100% oxygen and ∼100% oxygen with 10 to 80 parts per million nitric oxide to evaluate pulmonary vascular reactivity. Surgery was performed in 74 patients. Twelve patients died or developed right heart failure secondary to pulmonary hypertension following surgery. Rp:Rs<0.33 and a 20% decrease in Rp:Rs from baseline were chosen as 2 criteria for operability to determine, in retrospect, the efficacy of ...

The Effect of Rapid Respiratory Viral Diagnostic Testing on Antibiotic Use in a Children's Hospital

Abstract: Background Acute viral respiratory disease is the most common reason for pediatric hospitalization in the United States. Viral illnesses may be mistaken for bacterial infection, and antibiotic therapy may be prescribed. Overprescribing of antimicrobials for viral illness is a factor contributing to increasing antimicrobial resistance among bacterial pathogens encountered in pediatrics. Objective To determine if the availability of a rapid diagnostic test for respiratory viruses would affect antibiotic use in a children's hospital. Design Retrospective medical record review. Setting A 232-bed urban children's hospital. Participants All hospitalized infants and children who underwent rapid testing (SimulFluor Respiratory Screen; Chemicon International Inc, Temecula, Calif) for respiratory viruses by direct fluorescent assay (DFA) during 2 successive winter seasons. Main Outcome Measures Rates of antibiotic prescribing in DFA-positive and DFA-negative patients during the 2 study periods. Results During the first winter season, DFA-positive patients had fewer days using intravenous antibiotics (2.4 vs 4, P = .04), fewer days using oral antibiotics (0.25 vs 2.5, P = .04), and fewer discharge prescriptions for oral antibiotics (37% vs 52%, P = .02) when compared with DFA-negative patients. Intravenous antibiotics were initiated less often for DFA-positive patients during the second winter season than during the first (26% vs 44%, P = .008). Conclusions Direct fluorescent assay testing was associated with a decrease in inappropriate antibiotic use. The availability of rapid viral diagnostics is an important tool for decreasing antibiotic prescribing in pediatric patients.

Does Abciximab Enhance Regression of Coronary Aneurysms Resulting From Kawasaki Disease

Abstract: Objective. Acute Kawasaki disease can result in the development of large coronary artery aneurysms that may persist. Abciximab, a platelet glycoprotein IIb/IIIa receptor inhibitor, is associated with resolution of thrombi and vascular remodeling in adults with acute coronary syndromes. The purpose of this study was to compare changes in aneurysm diameter at early follow-up in patients who had Kawasaki disease and received abciximab in addition to standard therapy with those who were treated with standard therapy alone. Methods. Patients with Kawasaki disease and large aneurysms were divided into 2 groups on the basis of acute therapy: 1) abciximab in addition to standard therapy and 2) standard therapy alone. Echocardiograms were reviewed for coronary aneurysms (lumen diameter 1.5 times that of the adjacent vessel). Maximum aneurysm diameter was determined during the acute/subacute phase of Kawasaki disease ( Results. Six patients had 20 aneurysms in the abciximab group, and 9 patients had 30 aneurysms in the standard therapy group. Early follow-up data were available for 19 of the 20 aneurysms in the abciximab group and 19 of the 30 aneurysms in the standard therapy group. Patients who were treated with abciximab demonstrated greater regression in aneurysm size at early follow-up than patients who were treated with standard therapy alone (percentage decrease: 41 ± 19% vs 17 ± 27%). In the abciximab group, 68% (13 of 19) of aneurysms resolved at early follow-up compared with 35% (7 of 19) in the standard therapy group. Conclusions. Patients who were treated with abciximab demonstrated greater regression in aneurysm diameter at early follow-up than patients who received standard therapy alone. These findings suggest that treatment with abciximab may promote vascular remodeling in this population and warrants further study.

Characterization of Two Novel Pyrogenic Toxin Superantigens Made by an Acute Rheumatic Fever Clone of Streptococcus pyogenes Associated with Multiple Disease Outbreaks

Abstract: The pathogenesis of acute rheumatic fever (ARF) is poorly understood. We identified two contiguous bacteriophage genes, designated speL and speM, encoding novel inferred superantigens in the genome sequence of an ARF strain of serotype M18 group A streptococcus (GAS). speL and speM were located at the same genomic site in 33 serotype M18 isolates, and no nucleotide sequence diversity was observed in the 33 strains analyzed. Furthermore, the genes were absent in 13 non-M18 strains tested. These data indicate a recent acquisition event by a distinct clone of serotype M18 GAS. speL and speM were transcribed in vitro and upregulated in the exponential phase of growth. Purified SpeL and SpeM were pyrogenic and mitogenic for rabbit splenocytes and human peripheral blood mononuclear cells in picogram amounts. SpeL preferentially expanded human T cells expressing T-cell receptors Vβ1, Vβ5.1, and Vβ23, and SpeM had specificity for Vβ1 and Vβ23 subsets, indicating that both proteins had superantigen activity. SpeL was lethal in two animal models of streptococcal toxic shock, and SpeM was lethal in one model. Serologic studies indicated that ARF patients were exposed to serotype M18 GAS, SpeL, and SpeM. The data demonstrate that SpeL and SpeM are pyrogenic toxin superantigens and suggest that they may participate in the host-pathogen interactions in some ARF patients.

Tufted angiomas: variability of the clinical morphology.

Abstract: In 1989 Wilson Jones and Orkin first described tufted angioma, which has the unifying histologic feature of circumscribed angiomatous tufts and lobules within the dermis. Tufted angioma may take unusual forms clinically. We describe five children less than 3 years of age with tufted angiomas, demonstrating the variability of the morphology of this vascular tumor. Two of the lesions were congenital. Three presented as indurated, vascular-appearing plaques, one of which had associated hypertrichosis. One lesion appeared clinically compatible with a hemangioma of infancy, but continued to enlarge after the child was 32 months old. The remaining lesion was a nearly circumferential, soft tissue tumor of the left forearm with tortuous vessels and a smaller overlying vascular stain. All of these lesions demonstrated the characteristic histology of tufted angioma. The clinical and histopathologic differential diagnosis as well as treatment options for tufted angioma are reviewed.

Molecular Analysis of Group A Streptococcus Type emm18 Isolates Temporally Associated with Acute Rheumatic Fever Outbreaks in Salt Lake City, Utah

Abstract: Acute rheumatic fever (ARF) and subsequent rheumatic heart disease are rare but serious sequelae of group A Streptococcus (GAS) infections in most western countries. Salt Lake City (SLC), Utah, and the surrounding intermountain region experienced a resurgence of ARF in 1985 which has persisted. The largest numbers of cases were encountered in 1985-1986 and in 1997-1998. Organisms with a mucoid colony phenotype when grown on blood agar plates were temporally associated with the higher incidence of ARF. To develop an understanding of the molecular population genetic structure of GAS strains associated with ARF in the SLC region, 964 mucoid and nonmucoid pharyngeal isolates recovered in SLC from 1984 to 1999 were studied by sequencing the emm gene. Isolates with an emm18 allele were further characterized by sequencing the spa, covR, and covS genes. Peak periods of ARF were associated with GAS isolates possessing an emm18 allele encoding the protein found in serotype M18 isolates. Among the serotype M18 isolates, the difference in the number of C repeats produced three size variants. Variation was limited in spa, a gene that encodes a streptococcal protective antigen, and covR and covS, genes that encode a two-component regulatory system that, when inactivated, results in a mucoid phenotype and enhanced virulence in mouse infection models. Pulsed-field gel electrophoresis showed a single restriction profile for serotype M18 organisms isolated during both peak periods of ARF. In SLC, the incidence of ARF coresurged with the occurrence of GAS serotype M18 isolates that have very restricted genetic variation.

Cholesterol and development: the rsh ("smith-lemli-opitz") syndrome and related conditions

Abstract: The half-century of lipophobia in the United States may be abating with some return of sanity on the discussion of health and dietary fat [Taubes, 2001]. The youngest victims of this collective, decades long madness are those infants deprived for one reason or another of breast milk. They are unable to speak for themselves at a time of greatest need for cholesterol during growth, the most critical period of myelination of central and peripheral nervous system, formation of bone and bile, and of every steroid hormone. Some of the commercial formulas they are fed contain only 1 or 2 mg of cholesterol per 100 g edible portion contrasted with almost 14 mg in breast milk. One can only hope that the confidence in their endogenous ability to synthesize sufficient amounts of cholesterol is not misplaced. Pediatric pathology has learned that when this endogenous ability fails during embryogenesis on the basis of mutations in the postsqualene biosynthesis of cholesterol, a startling variety of developmental pathology may present itself ranging from lethal forms of "idiopathic" hydrops, microcephaly with cerebral dysgenesis and dysmyelinization, agenesis of corpus callosum, cerebellar vermis dysgenesis, cataracts, cleft palate, many different forms of congenital heart defect, pyloric stenosis and/or Hirschsprung dysganglionosis, adrenal (cortical) insufficiency, cholestatic liver disease, limb malformations, and genital ambiguity in genetic males. Population genetic considerations suggest a hypothetical birth prevalence of the RSH (so-called Smith-Lemli-Opitz) syndrome, the commonest of these Garrodian errors of cholesterol biosynthesis, of 1/2500; since only about 1/15,000 to 1/20,000 homozygotes are liveborn and biochemically confirmed, over 80% prenatal or perinatal mortality must occur and deserves the most discerning of services from birth attendants, perinatologists, neonatologists, and fetal/pediatric pathologists. An easy, reliable, economical biochemical test for the presence of 7-dehydrocholesterol is available and the commonest mutation, the IVS8-1G-->C mutation, is quickly and reliably tested for molecularly. Thus, the successful diagnosis, even after death, will contribute substantially to correct genetic counseling, carrier detection, prenatal diagnosis, and treatment in those known to be affected prenatally andplanned to be liveborn. Thus, developmental pathology plays an integral, vital role in preventive medicine.

A cost-effectiveness analysis of endoscopic third ventriculostomy.

Abstract: OBJECTIVE Endoscopic third ventriculostomy (ETV) is currently the principal alternative to cerebrospinal fluid shunt placement in the management of pediatric hydrocephalus. Cost-effectiveness analysis can help determine the optimal strategy for integrating these different approaches. METHODS All patients (n = 28) who underwent ETV at British Columbia's Children's Hospital between 1989 and 1998 were matched for age, pathogenesis, and number of previous shunt procedures, with patients treated with cerebrospinal fluid shunts. To perform a cost-effectiveness analysis, hydrocephalus-related resource consumption and outcome (determined as the number of hydrocephalus treatment-free days during follow-up) were then retrospectively identified. Cost data were linked to resource use to provide a total cost for all resources used. Costs and outcomes were discounted annually at 5% by standard economic analysis methods. RESULTS Twenty-four of 28 ETV patients had obstructive hydrocephalus. Over equivalent follow-up periods (median, 35 mo), the ETV success rate (defined by need for reoperation) was 54%. One hydrocephalus-related death and one hemiparesis occurred in the ETV group. No permanent procedure-related morbidity or mortality was seen in the shunt group. The cost/effect ratios for the two groups were similar. The additional incremental resource use by the shunt group included six readmissions and eight reoperations. ETV mean costs per patient were $10,570 +/- $7628, versus $10,922 +/- $8722 for the shunt group (Canadian dollars for the year 2000). Costs accrued more quickly for the shunt group as time passed. The additional incremental outcome benefit to the endoscopy group was 86 treatment-free days (3.07 d per patient [95% confidence interval, -7.56 to 13.70 d]). Neither of these differences was statistically significant. CONCLUSION In this matched cohort, ETV was not significantly less costly or more effective over a median 35 months of follow-up, with a 54% initial ETV success rate, even before the additional morbidity and mortality encountered were taken into account. The time course for the accrued costs suggests that a larger cohort, longer follow-up, or higher success rates are needed to demonstrate the cost-effectiveness of this therapy.

Tooth eruption symptoms: a survey of parents and health professionals

Abstract: UNLABELLED It is commonly believed that teething in infants can cause a variety of signs and symptoms. Previous studies have suggested an association between teething and fever, irritability, drooling, rashes, vomiting, diarrhea, night crying, and convulsions. PURPOSE The objective of this study was to evaluate differences in the beliefs of pediatricians, pediatric dentists and parents regarding symptoms caused by teething in infants. METHODS A survey consisting of demographic information and questions concerning commonly reported symptoms associated with teething was administered to 100 randomly selected Iowa pediatricians, all practicing pediatric dentists in Iowa (n = 33) and a convenience sample of 120 parents from the greater Iowa City area. Responses were analyzed using the Chi-square test. RESULTS Response rates for each group were: pediatricians 45%; pediatric dentists 76%; and parents 50%. The majority of individuals in each group believed that teething in infants can cause swollen gums, drooling, irritability, inflamed gums, restlessness, sleeplessness, and fever. There were significant differences in the percent of agreement relating to drooling (p = 0.001), inflamed gums (p = 0.001), and sleeplessness (p = 0.027). A greater percentage of pediatric dentists and parents agreed that these symptoms were caused by teething than did pediatricians. The largest difference between groups was related to the association between teething and diarrhea. The majority of parents (56.7%) and pediatric dentists (52.0%) believed that diarrhea is associated with teething compared to just 9.1% of pediatricians. CONCLUSIONS These results support the hypothesis that differences regarding beliefs about teething symptoms exist between parents, pediatricians, and pediatric dentists. There is more agreement between parents and pediatric dentists than between either of these groups and pediatricians.

Intermediate effects of treatment with metoprolol or carvedilol in children with left ventricular systolic dysfunction.

Abstract: The use of β-blocking agents in adults with congestive heart failure has been shown to improve symptoms and outcome; however, experience in pediatric patients with left ventricular systolic dysfunction is limited. We identified 12 pediatric patients treated with β-blocking agents for left ventricular systolic dysfunction and reviewed echocardiographic indices of left ventricular systolic performance prior to initiation of β-blocker therapy and at intermediate follow-up. Left ventricular fractional shortening and ejection fraction increased significantly from baseline to intermediate follow-up (13 ± 4% to 21 ± 8% [p = 0.01] and 26 ± 8% to 41 ± 17% [p = 0.04], respectively). When added to conventional therapy, β-blocker therapy resulted in an increase in ejection-phase indices of left ventricular systolic performance at intermediate follow-up in pediatric patients with systolic dysfunction.

Gastrointestinal complications of Russell-Silver syndrome: a pilot study.

Abstract: Russell-Silver syndrome (RSS) is a genetic syndrome with clinical manifestations of intrauterine and postnatal growth retardation, normal head circumference, body asymmetry, and distinctive facial appearance. We followed an infant diagnosed with RSS who had occurrence of multiple gastrointestinal complications. Although there are a number of published reports describing gastrointestinal problems associated with RSS, specific gastrointestinal diseases have not been recognized as major features. We hypothesize that gastrointestinal complications may be more frequent in RSS cases than previously reported. To address our hypothesis, we developed a pilot study of RSS cases to identify and characterize associated gastrointestinal complications. Surveys were distributed by MAGIC, a support group for individuals with RSS. Surveys included information on the objective and subjective characteristics used to diagnose RSS, as well as descriptions of gastrointestinal problems. Completed surveys were returned on 135 individuals. We used strict diagnostic guidelines to determine affected status of children reported in our survey. Of the 135 surveys completed, 65 were determined to have clear-cut RSS. The diagnoses were made without knowledge of the gastrointestinal symptoms of any of the subjects. Of the 65 subjects with "clear cut" RSS, 50 (77%) had gastrointestinal symptoms. Major specific symptoms included gastroesophageal reflux disease (34%), esophagitis (25%), food aversion (32%), and failure to thrive (63%). A common theme in gastrointestinal complications of RSS is significant gastroesophageal reflux that includes esophagitis and food aversion. Results of this survey suggest that there is an association of gastrointestinal complications with RSS that should be addressed in diagnosis as well as management protocols for children with this condition.

A survey of albuterol administration practices in intubated patients in the neonatal intensive care unit.

Abstract: INTRODUCTION Aerosolized albuterol is commonly used in the treatment of neonatal respiratory illnesses. Clinical and in vitro studies have identified numerous factors that affect aerosol drug delivery during neonatal mechanical ventilation, including the choice of metered-dose inhaler (MDI) or nebulizer, the use of a holding chamber, time between actuations, the volume of nebulized solution, and the position and placement of the nebulizer or MDI. Because there is no consensus on the optimal method of administration, there is probably substantial variability among institutions in how aerosolized albuterol is administered to mechanically ventilated infants in the neonatal intensive care unit (NICU). OBJECTIVE Survey academic medical centers in the United States regarding their practices of administering aerosolized albuterol to intubated newborns in the NICU. METHODS A survey instrument was developed that queried 18 aspects of albuterol administration in mechanically ventilated infants, including the frequency of MDI and nebulizer use, the average and maximum dose, the time between MDI actuations and following the final actuation, the use of a holding chamber, and the placement location of the holding chamber or nebulizer. Respiratory therapists and respiratory therapy managers having direct knowledge of neonatal clinical practices in their neonatal fellowship program NICUs were surveyed via telephone. Those who did not respond via telephone were surveyed via fax. RESULTS Eighty institutions were surveyed and there were 68 respondents (85% response rate). Responders averaged 35 +/- 13 NICU beds and 11 +/- 5 ventilators/d. Nineteen percent of the respondents reported administering albuterol via MDI 100% of the time; 22% use MDIs 75-99% of the time; 9% use MDIs 50-74% of the time; 4% use MDIs 25-49% of the time; and 43% never use MDIs to deliver albuterol. The average dose via MDI was: 1 puff: 30%; 2 puffs: 65%; and 4 puffs: 5%. The maximum dose via MDI was: 2 puffs: 30%; 3 puffs: 14%; 4 puffs: 36%; 6 puffs: 11%; and 8 puffs: 6%. Thirty-one percent of the respondents place the holding chamber in-line with the ventilator circuit, 56% administer the aerosol via manual ventilation, and 13% use both methods. Fifty-six percent place the in-line holding chamber between the endotracheal tube and ventilator circuit, and the other 44% place the in-line holding chamber in the inspiratory limb. The time between MDI actuations depended on whether the holding chamber was placed in-line or the aerosol was administered via manual ventilation (MV): < or = 0.5 min: 18% in-line and 28% MV; 1 min: 47% in-line and 43% MV; 2 min: 6% in-line and 4% MV; 3 min: 6% in-line and 0% MV. Eighty-three percent of respondents indicated that dead space introduced by a holding chamber/spacer was not a concern. Forty-three percent use nebulizers exclusively to administer albuterol to mechanically ventilated patients. Seventy-four percent of centers that nebulize albuterol use a dose of 1.25-2.5 mg. Eighty-eight percent of the surveyed institutions place nebulizers in-line with the ventilator circuit, and the other 12% use manual ventilation to administer the nebulized aerosol. Of those that use in-line nebulization, 95% place the nebulizer in the inspiratory limb of the circuit, and the other 5% place the nebulizer between the endotracheal tube and circuit Y-piece. Among centers that place the nebulizer in the inspiratory limb, 52% place it adjacent to the circuit Y-piece, 36% place it midway upstream in the inspiratory limb, and 12% place it near the humidifier. CONCLUSION There is substantial variability among NICUs in albuterol administration to mechanically ventilated infants, with the majority of institutions now administering albuterol via MDI.

Cytodifferentiation and clinical outcome after chemotherapy and radiation therapy for rhabdomyosarcoma (RMS).

Abstract: Background Second-look surgery after therapy for rhabdomyosarcoma (RMS) may yield prognostic information regarding tumor responsiveness to treatment. Favorable outcome is suggested by tumor cells which have undergone maturation (cytodifferentiation). Procedure Specimens from patients treated on Intergroup RMS Study-IV (IRSG-IV) were studied before and after treatment. All patients received chemotherapy and most received radiation therapy. Post-treatment specimens were graded according to the quantity of tumor showing cytodifferentiation (0 = absent, 1 = mild, 2 = moderate, 3 = extensive). Proliferative activity by MIB-1, topoisomerase II-alpha, and p53 protein expression were measured. Results 19/31 cases from IRSG-IV were adequate for analysis. Six out of nineteen patients failed therapy within 1.3 years of treatment. Grade 3 cytodifferentiation was present in 10 cases (2 BRMS, 8 ERMS)† ; none failed therapy. Grade 2 cytodifferentiation was present in 5 cases (1 ERMS, 2BRMS, 2ARMS)†; 2 patients with ARMS failed therapy. Grade 0–1 cytodifferentiation was present in 4 cases (1 ERMS and 3 ARMS); all failed therapy. Proliferative activity by MIB-1 and topoisomerase II-alpha immunohistochemistry decreased or was unchanged after treatment for all ERMS/BRMS, and 4/5 cases of ARMS. p53 immunohistochemistry showed no consistent pattern of reactivity. Sparse persistent tumor cells were present in 9/10 ERMS, 3/4 BRMS, 5/5 ARMS. Conclusions Extensive cytodifferentiation is more commonly seen in ERMS/BRMS compared with less evidence for cytodifferentiation in ARMS suggesting fundamentally different mechanisms of cellular response to therapy in RMS. Sparse persistent tumor cells in post treatment ERMS/BRMS specimens does not appear to affect outcome. Med Pediatr Oncol 2002;38:398–404. © 2002 Wiley-Liss, Inc.

Evidence for lack of myocardial injury in children with acute rheumatic carditis.

Abstract: Despite pathologic evidence of myocardial inflammation, the significance of myocarditis in children with acute rheumatic carditis remains controversial. Elevations in cardiac troponin I have been demonstrated in other forms of myocarditis. The purpose of our study was to determine if levels of cardiac troponin I are elevated, suggesting myocardial injury, in patients with acute rheumatic carditis. We identified all those patients with acute rheumatic fever, presenting between July 1998 and December 2000, who had clinical evidence of carditis, such as a new murmur of mitral or aortic regurgitation, and who had an echocardiogram, measurements of levels of cardiac troponin I, erythrocyte sedimentation rate, and/or C-reactive protein performed at the time of presentation. Their charts were reviewed for demographic and clinical data. Echocardiograms were reviewed for severity of aortic and mitral regurgitation, and measurements made of left ventricular ejection fraction, fractional shortening, and end-diastolic dimension. We found 16 patients with acute rheumatic carditis, ranging in age from 2.0 to 16.1 years, with just over one-third having symptoms of congestive heart failure. All patients had evidence of acute inflammation. There was a significant relationship between symptoms and severity of mitral regurgitation. No patient had elevated levels of cardiac troponin I level. The fact that levels of cardiac troponin I are not elevated in the serum of children with acute rheumatic carditis suggests that there is minimal myocytic necrosis in this setting. This supports the concept that acute valvar regurgitation is the major hemodynamic abnormality in these patients.

Neurodevelopmental outcome for extended cold water drowning: A longitudinal case study

Abstract: There is little longitudinal data examining outcome of pediatric near-drowning. Most literature tracks status 5 years or less post insult, focusing primarily on gross neurologic status as opposed to more subtle neurocognitive deficits. The present case tracks the neuropsychological profile of a child who was submerged for 66 min, the longest time documented. Acute medical support was aggressive, and recovery was dramatic, being featured in multiple media reports. Although an article published 6 years after the near-drowning described the child as “recovering completely,” the longitudinal profile indicates a pronounced pattern of broad cognitive difficulties, particularly notable for global memory impairment. Neuropsychological test results were significant despite the fact that the patient's recent MRI and MEG were within normal limits. This case demonstrates the need for long-term neuropsychological follow-up of pediatric patients with histories of neurologic injury, as gross neurological examination and MRI and MEG scans may not reveal underlying brain dysfunction. (JINS, 2002, 8, 588–595.)

The Use of Haloperidol in Agitated Critically Ill Children

Abstract: Sedation, analgesia, and muscle relaxants are often used to control agitation and facilitate mechanical ventilation in children with acute hypoxic respiratory failure. In most children, adequate sedation can be achieved with a combination of parenteral benzodiazepines and opioids. However, long-term continuous infusions of opioids and benzodiazepines often result in physiologic tolerance and the need for dose escalation in order to maintain an appropriate level of sedation. Occasionally, mechanically ventilated children remain anxious, agitated, or combative despite escalating doses of opioids and benzodiazepines. In some children, additional doses of these agents seem to exacerbate agitation and combative-

Antioxidant Status of Young Children: Response to an Antioxidant Supplement

Abstract: Objective To study oxidative stress indicators in healthy young children and their response to a commercially available fruit- and vegetable-based antioxidant supplement. Design Healthy children were randomly assigned to a placebo and a supplement (commercial antioxidant supplement produced from dried fruit and vegetable extracts and fortified with antioxidants, resembling a gummy-type candy). The placebo and the supplement were taken in 2 doses per day for 21 days. Subjects Participants were 39 children (26 boys and 13 girls) aged 5 to 10 years. Research was conducted at Primary Children's Medical Center and the University of Utah, Salt Lake City. Main outcome measures Breath and urine samples were collected on days 1 and 21 and assayed for breath pentane and urine 8-hydroxydeoxyguanosine, malondialdehyde, nitrites, and 8-isoprostane as noninvasive indicators of oxidative stress. Urine oxygen radical absorbance capacity was measured at days 1 and 21 as an indirect indicator of the antioxidant capacity of the body. Three-day food records were collected at the beginning and end of the study to measure intake of dietary fruit; vegetable; and antioxidant vitamins A, C, and E. Statistical analysis Descriptive statistics, repeated measures analysis of variance, paired t tests, and Pearson r correlations. Results Markers of oxidative stress were not significantly different between the placebo and supplement groups at day 1 or day 21. The oxidative stress indicators of the healthy children in this study appear to be similar to those of healthy adults and were not changed by antioxidant supplementation. The diet record analyses indicated that mean fruit and vegetable intakes (2.75 servings/day) were similar to the national average intake for children in the United States. Applications/conclusions This research presents original information on the subject of oxidative stress in healthy children. The results of this study may be useful as reference baseline markers to use in conjunction with clinical dietary evaluations and for future research with healthy children and with children in disease states who are subject to elevated levels of oxidative stress. J Am Diet Assoc. 2002; 102:1652-1657.

Pediatric Laboratory MedicineCurrent Challenges and Future Opportunities

Abstract: The practice of pediatric laboratory medicine involves unique challenges related to development, nutrition, growth, and diseases during different periods of infancy, childhood, and adolescence. This article discusses key aspects of pediatric laboratory medicine faced by clinical pathologists, clinical laboratory scientists, and clinicians, including point-of-care testing, preanalytic variables, analytic factors, age-specific reference intervals, esoteric laboratory tests, clinical impact, and future opportunities. Although challenging, pediatric laboratory testing offers many opportunities for improved patient care, clinical- and laboratory-based research, and education.

Unintentional victims: development of a protocol for the care of children exposed to chemicals at methamphetamine laboratories.

Abstract: In 1999, the staff at Primary Children’s Medical Center Emergency Department (PCMC ED) noticed an increase in the number of children being brought in either by the police or by the Division of Children and Family Services (DCFS). These children had been found at homes where a methamphetamine laboratory had been raided. When this began, there was confusion and frustration among those involved as to how to provide care for these children. Also, the staff was not familiar with the toxic chemicals involved or with the complicated social issues associated with methamphetamine abuse.

Demonstration of electrical and anatomic connections between Marshall bundles and left atrium in dogs: implications on the generation of P waves on surface electrocardiogram.

Abstract: Marshall Bundle and P Wave.Introduction: The muscle bundles within the ligament of Marshall (LOM) are electrically active. The importance of these muscle bundles (Marshall bundle [MB]) to atrial activation and the generation of the ECG P wave is unclear. Methods and Results: We used optical mapping techniques to study epicardial activation patterns in isolated perfused left atrium in four dogs. In another seven dogs, P waves were studied before and after in vivo radiofrequency (RF) ablation of the connection between coronary sinus (CS) and the LOM. Computerized mapping was performed before and after RF ablation. Optical mapping studies showed that CS pacing resulted in broad wavefronts propagating from the middle and distal LOM directly to the adjacent left atrium (LA). Serial sections showed direct connection between MB and LA near the orifice of the left superior pulmonary vein in two dogs. In vivo studies showed that MB potentials were recorded in three dogs. After ablation, the duration of P waves remained unchanged. In the other four dogs, MB potentials were not recorded. Computerized mapping showed that LA wavefronts propagated to the MB region via LA-MB connection and then excited the CS. After ablation, the activation of CS muscle sleeves is delayed, and P wave duration increased from 65.3 ± 14.9 msec to 70.5 ± 17.2 msec (P = 0.025). Conclusion: In about half of the normal dogs, MB provides an electrical conduit between LA free wall and CS. Severing MB alters the atrial activation and lengthens the P wave. MB contributes to generation of the P wave on surface ECG.

Accidental Carbon Monoxide Poisoning With Severe Cardiorespiratory Compromise in 2 Children

Abstract: Carbon monoxide is a colorless, odorless gas produced as a by-product of incomplete combustion. Carbon monoxide poisoning accounts for approximately 3500 deaths in the United States annually. Carbon monoxide in exhaust fumes from motor vehicles accounts for most deaths due to carbon monoxide poisoning; however, poorly functioning heating systems, inhaled smoke, and propane-operated forklifts also can cause carbon monoxide poisoning. We report 2 cases of severe cardiorespiratory compromise in 3-year-old identical twin girls that occurred after they were exposed for an estimated 12 to 18 hours to a faulty furnace producing high levels of carbon monoxide.

Airway clearance strategies for the pediatric patient.

Abstract: Clinicians who care for cystic fibrosis (CF) patients have many techniques to choose from to facilitate mucus clearance. Little has been published about when to introduce the various techniques and in what order to teach them. Debates have occurred over these issues in the CF community, and there is now consensus on some topics. It is very important to teach adherence to therapy at an early age. Adherence to an airway clearing regimen assists in maintaining good pulmonary function in CF patients. Knowing when and how to introduce airway clearance techniques beyond chest physiotherapy (CPT) is clinically relevant and useful. A 5-position modified CPT routine can be used with infants and children, and it takes less time and may improve adherence. Infants and toddlers can be taught breathing games that eventually lead them to perform diaphragmatic breathing and huffing. Once they have mastered diaphragmatic breathing and huffing, children can be taught the active cycle of breathing technique. Modified CPT can be phased out at that point. Positive expiratory pressure therapy can usually be introduced around 6-7 years of age. High-frequency chest wall oscillation, oscillating positive expiratory pressure, and autogenic drainage all follow. CF patients should be given every opportunity to learn and master various techniques to promote mucus clearance.