Oxygen saturation as a screening test for critical congenital heart disease: a preliminary study.

The aim of this study was to assess the utility of arm and leg oxygen saturation as a candidate screening test for the early detection of ductal-dependent left heart obstructive disease. We measured arm and leg oxygen saturation in 2876 newborns admitted to well baby nurseries and 32 newborns with congenital heart disease. Fifty-seven newborns in the well baby nurseries (0.02%) had an abnormal test (leg saturation less than 92% in room air or 7% lower saturation in the leg than in the arm). Four of the 57 had critical congenital heart disease, including 1 with coarctation of the aorta. Of the 32 newborns with congenital heart disease, 11/13 (85%) with left heart obstructive disease had abnormal oxygen saturation tests, as did 15/19 (79%) with other forms of congenital heart disease. Pulse oximetry deserves further study as a screening test for critical congenital heart disease.

Fludrocortisone acetate to treat neurally mediated hypotension in chronic fatigue syndrome: a randomized controlled trial.

CONTEXT: Patients with chronic fatigue syndrome (CFS) are more likely than healthy persons to develop neurally mediated hypotension (NMH) in response to prolonged orthostatic stress. OBJECTIVE: To examine the efficacy of fludrocortisone acetate as monotherapy for adults with both CFS and NMH. DESIGN: Randomized, double-blind, placebo-controlled trial conducted between March 1996 and February 1999. SETTING: Two tertiary referral centers in the United States. PATIENTS: One hundred individuals aged 18 to 50 years who satisfied Centers for Disease Control and Prevention criteria for CFS and had NMH provoked during a 2-stage tilt-table test. Eighty-three subjects had adequate outcome data to assess efficacy. INTERVENTION: Subjects were randomly assigned to receive fludrocortisone acetate, titrated to 0.1 mg/d (n = 50) or matching placebo (n = 50) for 9 weeks, followed by 2 weeks of observation after discontinuation of therapy. MAIN OUTCOME MEASURE: Proportion of subjects in each group with at least a 15-point improvement on a 100-point global wellness scale. RESULTS: Baseline demographic and illness characteristics between the groups were similar; CFS had been present for at least 3 years in 71%. Using an intention-to-treat analysis, 7 subjects (14%) treated with fludrocortisone experienced at least a 15-point improvement in their wellness scores compared with 5 (10%) among placebo recipients (P =.76). No differences were observed in several other symptom scores or in the proportion with normal follow-up tilt test results at the end of the treatment period. CONCLUSIONS: In our study of adults with CFS, fludrocortisone as monotherapy for NMH was no more efficacious than placebo for amelioration of symptoms. Failure to identify symptomatic improvement with fludrocortisone does not disprove the hypothesis that NMH could be contributing to some of the symptoms of CFS. Further studies are needed to determine whether other medications or combination therapy are more effective in treating orthostatic intolerance in patients with CFS.

The effect of Kawasaki disease on cognition and behavior.

OBJECTIVE: To determine whether there are associated long-term deficits in the cognitive, academic, or behavioral outcomes of children with a previous episode of Kawasaki disease. DESIGN: Cohort analytic study. SETTING: A tertiary care pediatric hospital in Ottawa, Ontario. PARTICIPANTS: Thirty-two patients with a past diagnosis of Kawasaki disease. Siblings of the patients with Kawasaki disease were eligible to be controls. MEASURES: A blinded psychometrist (Y.K.) assessed cognition by the appropriate Wechsler Intelligence scale, academic achievement by the Wechsler Individual Achievement Test, and behavior by the Achenbach Child Behavior Checklist. RESULTS: No differences were found in cognitive or academic measures and the mean scores corresponded closely to national norms. Parents rated their children who had Kawasaki disease as having significantly more internalizing (P<.03) and attentional (P<.02) behavior problems than controls; the risk of a clinically significant behavioral score was 3.3 times greater (P<.03; 95% confidence interval, 1.1-9.9) than for sibling controls. CONCLUSIONS: While no effect on cognitive development or academic performance was demonstrated, these results provide preliminary indication of a post-Kawasaki disease deficit in internalizing and attentional behavior.

Circulating inflammatory cytokine levels in hemolytic uremic syndrome.

Experimental data suggest that the host's inflammatory response is involved in the pathophysiology of verotoxin-producing Escherichia coli (VTEC)-associated hemolytic uremic syndrome (HUS). We compared the circulating levels of pro- [interleukin (IL)-6, IL-8] and anti-inflammatory [IL-10 and IL-1 receptor antagonist (Ra)] mediators on enrollment among children with HUS due to E. coli O157:H7, according to the severity of renal dysfunction. The latter was evaluated by the occurrence of oligoanuria, the requirement for dialysis, and a glomerular filtration rate (GFR)

Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome.

OBJECTIVE: To report chronic fatigue syndrome (CFS) associated with both Ehlers-Danlos syndrome (EDS) and orthostatic intolerance. STUDY DESIGN: Case series of adolescents referred to a tertiary clinic for the evaluation of CFS. All subjects had 2-dimensional echocardiography, tests of orthostatic tolerance, and examinations by both a geneticist and an ophthalmologist. RESULTS: Twelve patients (11 female), median age 15.5 years, met diagnostic criteria for CFS and EDS, and all had either postural tachycardia or neurally mediated hypotension in response to orthostatic stress. Six had classical-type EDS and 6 had hypermobile-type EDS. CONCLUSIONS: Among patients with CFS and orthostatic intolerance, a subset also has EDS. We propose that the occurrence of these syndromes together can be attributed to the abnormal connective tissue in dependent blood vessels of those with EDS, which permits veins to distend excessively in response to ordinary hydrostatic pressures. This in turn leads to increased venous pooling and its hemodynamic and symptomatic consequences. These observations suggest that a careful search for hypermobility and connective tissue abnormalities should be part of the evaluation of patients with CFS and orthostatic intolerance syndromes.

Is oral albuterol effective for acute cough in non-asthmatic children?

Fifty-nine non-asthmatic children with acute cough were randomized to receive oral albuterol or placebo for 7 d. There was a similar, rapid rate of resolution of acute cough for the two groups, but more shaking or trembling in those treated with albuterol (5/30 vs 0/29; p = 0.05). In ambulatory children with acute cough who have no history of asthma and a normal chest examination, oral albuterol does not reduce the frequency or duration of cough.

Role of the toxic neutrophil count in the early diagnosis of Kawasaki disease.

OBJECTIVE: To determine whether the toxic neutrophil count (TNC), defined as the sum of the number of peripheral blood neutrophils with vacuoles plus the number with toxic granulations per 100 neutrophils examined, can be used as an aid to early diagnosis of Kawasaki disease (KD). METHODS: Prospective evaluation at a tertiary care pediatric hospital of 56 acutely febrile children with at least one other clinical criterion for KD. Clinical characteristics and TNC were compared for 3 groups of patients: those with (1) definite KD, (2) probable KD, and (3) unlikely KD. The sensitivity and specificity of the TNC at various cutoff points was determined. RESULTS: We evaluated 56 patients (Group 1, N=27; Group 2, N=4; Group 3, N=25). Mean TNC (TNC/mm3) were higher in the patients with definite KD compared to patients with unlikely KD (38 vs 24; p=0.037). At a TNC cutoff of > or =70, the test had a specificity of 100%, but a sensitivity of only 18%. The likelihood ratio (the number of times more likely this TNC result is to be found in KD versus non-KD subjects) was 8.89. At a cutoff of > or =10, the test had a high sensitivity of 92% and specificity of 38%. CONCLUSION: No laboratory test replaced the need for careful clinical evaluation in cases of suspected KD. The TNC may be a useful adjunct to the clinical assessment of children with KD, particularly at the extremes of measurement.

Neuropsychological sequelae of haemolytic uraemic syndrome. Investigators of the HUS Cognitive Study.

BACKGROUND: Severe haemolytic uraemic syndrome (HUS) in childhood can cause stroke, hemiplegia, cortical blindness, and psychomotor retardation. These outcomes are evident at the time of discharge immediately after the acute illness. Less is known about the neuropsychological outcomes of less severely affected children who recover from acute HUS. AIMS: This multicentre case control study investigated the hypothesis that children who survive an acute episode of HUS without recognizable neurological injuries have greater impairment of cognitive, academic, and behavioural functions than controls. DESIGN: Children with HUS were eligible if they had no evidence of severe neurological dysfunction when discharged from one of six Canadian hospitals. Controls had been admitted to hospital for a non-HUS illness and were matched by age, sex, first language, and socioeconomic status. All subjects underwent evaluation of behaviour, academic achievement, cognitive function, and verbal abilities using standardised tests administered by a psychometrist blinded to the case or control status. RESULTS: Ninety-one case control pairs were enrolled. No important differences between patients with HUS and paired controls were evident on tests of IQ, behaviour, verbal abilities, or academic achievement. There was no increased risk of attention deficit disorder among patients with HUS. There was no correlation between the severity of acute renal failure and neuropsychological measures, although scores on some verbal ability tests were lower in those with the highest serum creatinine concentrations during illness. CONCLUSIONS: Children discharged from hospital without apparent neurological injury after an episode of acute HUS do not have an increased risk of subclinical problems with learning, behaviour, or attention.

Neurally mediated hypotension and chronic fatigue syndrome.

A substantial body of clinical evidence now supports an association between various forms of hypotension and both idiopathic chronic fatigue and the chronic fatigue syndrome (CFS). Patients with CFS have a high prevalence of neurally mediated hypotension, and open treatment of this autonomic dysfunction has been associated with improvements in CFS symptoms. Randomized trials are now in progress to evaluate the efficacy of treatments directed at neurally mediated hypotension in those with CFS patients, and the results of these trials should help guide more basic inquiries into the mechanisms of orthostatic intolerance in affected individuals.

Nebulized budesonide and oral dexamethasone for treatment of croup: a randomized controlled trial.

CONTEXT: The effectiveness of glucocorticoids for patients with croup is well established but it remains uncertain which glucocorticoid regimen is most effective. OBJECTIVE: To determine the effectiveness of 3 glucocorticoid regimens in patients with croup. DESIGN: Randomized controlled trial with parallel design. SETTING: Emergency departments of 2 Canadian pediatric tertiary care hospitals. PARTICIPANTS: Children with a clinical syndrome consistent with croup, aged 3 months to 5 years, with a croup score of 2 or greater following at least 15 minutes of mist therapy. INTERVENTIONS: Oral dexamethasone, 0.6 mg/kg, and nebulized placebo; oral placebo and nebulized budesonide, 2 mg; or oral dexamethasone, 0.6 mg/kg, and nebulized budesonide, 2 mg. MAIN OUTCOME MEASURES: Westley croup score (primary outcome), hospital admission rates, time spent in the emergency department, return visits to the emergency department, or ongoing symptoms at 1 week. RESULTS: The mean change in the croup score from baseline to the final study assessment was -2.3 (95% confidence interval [CI], -2.6 to -2.0) in the budesonide group (n = 65), -2.4 (95% CI, -2.6 to -2.2) in the dexamethasone group (n = 69), and -2.4 (95% CI, -2.7 to -2.1) in the budesonide and dexamethasone group (n = 64, P = .70). CONCLUSIONS: Based on the similar outcomes in the 3 groups, oral dexamethasone is the preferred intervention because of its ease of administration, lower cost, and more widespread availability.

Sensitivities and specificities of premier E. coli O157 and premier EHEC enzyme immunoassays for diagnosis of infection with verotxin (Shiga-like toxin)-producing Escherichia coli. The SYNSORB Pk Study investigators.

This study describes the performance of two rapid enzyme immunoassays, Premier E. coli O157 and Premier EHEC (Meridian Diagnostics Inc., Cincinnati, Ohio) for the detection in stools of Escherichia coli O157 and verotoxins (Shiga-like toxins), respectively. Both tests were performed on stools from 876 children presenting to eight emergency departments with diarrhea. Standard culture, including E. coli O157:H7 isolation, was performed, and paired sera were taken for anti-O157-lipopolysaccharide antibody determination. Stools from patients enrolled in the study, and those yielding discordant results, were sent to a reference laboratory for repeat testing and further investigation, including cytotoxicity and non-O157 verotoxin-producing E. coli culture. Results were classified as field results (obtained in the eight site laboratories) and resolved results (obtained after repeat testing in the central laboratory). The "gold standard" for sensitivity of both tests and for specificity of Premier E. coli O157 was isolation of E. coli O157:H7 or a fourfold anti-O157 antibody rise. Specimens positive by the Premier EHEC test and negative for E. coli O157 culture were examined for non-O157 verotoxin-producing E. coli. The field sensitivity of Premier E. coli O157 was 86%, that of Premier EHEC was 89%, and the specificity of Premier E. coli O157 was 98%. Ten of 13 discordant Premier E. coli O157 results were reassigned as true results after repeat testing. Ten non-O157 verotoxin-producing E. coli isolates were recovered from Premier EHEC-positive, E. coli O157 culture-negative stools. Only one specimen gave an unequivocally false-positive Premier EHEC result. Both tests are highly sensitive and are specific if correctly performed. The Premier EHEC test will be particularly valuable as a practical routine test for the detection of non-O157 verotoxin-producing E. coli.

Risk of hemolytic uremic syndrome after sporadic Escherichia coli O157:H7 infection: results of a Canadian collaborative study. Investigators of the Canadian Pediatric Kidney Disease Research Center.

OBJECTIVES: The objectives of this study were to better estimate the age-specific risks of hemolytic uremic syndrome (HUS) and hemolytic anemia after Escherichia coli O157:H7 infection among a representative cohort of both referred and nonreferred children with documented illness from the province of Alberta and to compare this with the rates in children evaluated at referral centers in the rest of Canada. STUDY DESIGN: Children with HUS or E. coli O157:H7 gastroenteritis were eligible if they were < 15 years of age. Hemoglobin, blood smear, urinalysis, and serum creatinine were obtained 8 to 10 days after the onset of diarrhea to ascertain for hemolysis, anemia, thrombocytopenia, and renal injury. Subjects were monitored for 1 month. RESULTS: From June 1991 to March 1994, HUS was diagnosed in 205 children. Of these 77% had evidence of E. coli O157:H7 infection. A further 582 children had E. coli O157:H7 gastroenteritis, of whom 18 had hemolytic anemia. The risk of HUS after E. coli O157:H7 infection in Alberta was 8.1% (95% confidence interval, 5.3 to 11.6) compared with 31.4% in referral centers in the rest of Canada. In Alberta the highest age-specific risk of HUS/hemolytic anemia was 12.9% in those < 5 years of age. CONCLUSIONS: These data will help guide clinical care and provide a basis for estimating the sample sizes required in future treatment trials for the secondary prevention of HUS.

Provocation of hypotension and pain during upright tilt table testing in adults with fibromyalgia.

OBJECTIVE: Fibromyalgia is a common but poorly understood problem characterized by widespread pain and chronic fatigue. Because chronic fatigue has been associated with neurally mediated hypotension, we examined the prevalence of abnormal responses to upright tilt table testing in 20 patients with fibromyalgia and 20 healthy controls. METHODS: Each subject completed a symptom questionnaire and underwent a three stage upright tilt table test (stage 1:45 minutes at 70 degrees tilt; stage 2, 15 minutes at 70 degrees tilt with isoproterenol 1-2 micrograms/min; stage 3, 10 minutes at 70 degrees tilt with isoproterenol 3-4 micrograms/min). An abnormal response to upright tilt was defined by syncope or presyncope in association with a drop in systolic blood pressure of at least 25 mm Hg and no associated increase in heart rate. RESULTS: During stage 1 of upright tilt, 12 of 20 fibromyalgia patients (60%), but no controls had an abnormal drop in blood pressure (P < 0.001). Among those with fibromyalgia, all 18 who tolerated upright tilt for more than 10 minutes reported worsening or provocation of their typical widespread fibromyalgia pain during stage 1. In contrast, controls were asymptomatic (P < 0.001). CONCLUSION: These results identify a strong association between fibromyalgia and neurally mediated hypotension. Further studies will be needed to determine whether the autonomic response to upright stress plays a primary role in the pathophysiology of pain and other symptoms in fibromyalgia.

Outpatient management of croup.

Now that there is widespread acceptance of glucocorticoids for inpatient treatment of croup, the focus of research has shifted to the effectiveness of glucocorticoids for outpatients with croup. Recent evidence from randomized controlled trials has shown that nebulized budesonide causes an acute improvement in croup symptoms, shortens stay in the emergency department, and significantly reduces admission rate. Intramuscular or oral dexamethasone also result in acute clinical improvement in patients with croup, and oral dexamethasone reduces the length of stay in an emergency department observation unit. There is accumulating evidence that patients receiving epinephrine do not necessarily require hospitalization but when treated simultaneously with dexamethasone may be safely discharged to home after a 3-hour observation period. Future trials in outpatients with croup need to determine the optimal dosing of oral dexamethasone, the utility of epinephrine therapy alone or in combination with glucocorticoids, and the optimal glucocorticoid regimen (budesonide, dexamethasone, or budesonide and dexamethasone).

The efficacy of nebulized budesonide in dexamethasone-treated outpatients with croup.

OBJECTIVE: To determine the added clinical benefit of nebulized budesonide in children with mild to moderate croup treated with 0.6 mg/kg oral dexamethasone. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Emergency department of a tertiary-care pediatric hospital with 47,000 visits per year. PARTICIPANTS: Children 3 months to 5 years of age with a syndrome consisting of hoarseness, inspiratory stridor, and barking cough and a croup score of 3 or greater after at least 15 minutes of mist therapy. Patients were excluded from the study if they had diagnoses of epiglottitis, chronic upper or lower airway disease (not including asthma), or severe croup or had received corticosteroids within the preceding 2 weeks. INTERVENTION: All patients received 0.6 mg/kg oral dexamethasone and were randomly assigned to receive 4 mL (2 mg) of budesonide solution (n=25) or 4 mL of 0.9% saline solution (n=25) by updraft nebulizer with a continuous flow of oxygen at 5 to 6 L/min. MAIN OUTCOME MEASURES: The primary outcome measure was the proportion of patients in each group who had clinically important changes (two points) in the croup score during the 4 hours after treatment. RESULTS: Eighty-four percent (n=21) of the patients who received budesonide had clinically important responses, compared with 56% (n=14) in the placebo group. The number of patients who would need to be treated with nebulized budesonide for one patient to have a clinically important response is four patients. CONCLUSIONS: Despite receiving simultaneous oral dexamethasone, pediatric outpatients with mild to moderate croup have added, clinically important improvement in respiratory symptoms after treatment with budesonide.

Eosinophilic esophagitis attributed to gastroesophageal reflux: improvement with an amino acid-based formula.

BACKGROUND & AIMS: Treatment for gastroesophageal reflux may be ineffective in patients with an eosinophilic infiltration of the esophagus. The aim of this study was to investigate whether unremitting symptoms of gastroesophageal reflux and biopsy abnormalities of the esophagus may be associated with the ingestion of certain foods. METHODS: Ten children previously diagnosed with gastroesophageal reflux by standard testing with long-standing symptoms (median, 34.3 months; range, 6-78 months) despite standard antireflux therapies, including Nissen fundoplication in 6 patients, were fed the elemental formulas Neocate or Neocate-1-Plus (Scientific Hospital Supplies Inc., Gaithersburg, MD) for a minimum of 6 weeks. Each child had repeat endoscopy followed by open food challenges. RESULTS: While receiving the formulas, patients had either resolution (n = 8) or improvement (n = 2) of symptoms. On follow-up esophageal biopsy, the maximal intraepithelial eosinophil counts decreased significantly before (median, 41; range, 15-100) to after (median, 0.5; range, 0-22) the formula trial (P = 0.005). Other reactive epithelial changes of the esophageal mucosa also improved significantly. All patients redeveloped their previous symptoms on open food challenges. CONCLUSIONS: Chronic gastrointestinal symptoms and histological changes of the esophagus unresponsive to standard treatments for gastroesophageal reflux were improved by the use of elemental formulas. Symptoms recurred when specific dietary proteins were reintroduced during open food challenges. The mechanism of these observations is unknown.

The relationship between neurally mediated hypotension and the chronic fatigue syndrome.

OBJECTIVE: To compare the clinical symptoms and response evoked by upright tilt-table testing in healthy individuals and in a sample of those satisfying strict criteria for chronic fatigue syndrome. DESIGN: Case-comparison study with mean (SD) follow-up of 24 (5) weeks. SETTING: Tertiary care hospital. PATIENTS AND OTHER PARTICIPANTS: A sample of 23 patients with chronic fatigue syndrome (five men and 18 women; mean age, 34 years), each of whom fulfilled the strict diagnostic criteria of the Centers for Disease Control and Prevention, was recruited from regional chronic fatigue support groups and from the investigators' clinical practices. There were 14 healthy controls (four men and 10 women; mean age, 36 years). INTERVENTIONS: Each subject completed a symptom questionnaire and underwent a three-stage upright tilt-table test (stage 1, 45 minutes at 70 degrees tilt; stage 2, 15 minutes at 70 degrees tilt with 1 to 2 micrograms/min of isoproterenol; and stage 3, 10 minutes at 70 degrees with 3 to 4 micrograms/min of isoproterenol). Patients were offered therapy with fludrocortisone, beta-adrenergic blocking agents, and disopyramide, alone or in combination, directed at neurally mediated hypotension. MAIN OUTCOME MEASURES: Response to upright tilt and scores on symptom questionnaires prior to and during follow-up. RESULTS: An abnormal response to upright tilt was observed in 22 of 23 patients with chronic fatigue syndrome vs four of 14 controls (P < .001). Seventy percent of chronic fatigue syndrome patients, but no controls, had an abnormal response during stage 1 (P < .001). Nine patients reported complete or nearly complete resolution of chronic fatigue syndrome symptoms after therapy directed at neurally mediated hypotension. CONCLUSIONS: We conclude that chronic fatigue syndrome is associated with neurally mediated hypotension and that its symptoms may be improved in a subset of patients by therapy directed at this abnormal cardiovascular reflex.

A phase I study of chemically synthesized verotoxin (Shiga-like toxin) Pk-trisaccharide receptors attached to chromosorb for preventing hemolytic-uremic syndrome.

A double-blind, placebo-controlled study was conducted to document possible side effects associated with oral consumption of synthetic verotoxin (VT, shiga-like toxin) Pk-trisaccharide receptor sequences attached to Chromosorb (Synsorb-Pk) by healthy adult volunteers. Synsorb-Pk reclaimed from volunteer stool samples was also analyzed to determine if its VT-binding activity was affected by exposure to the pH extremes and digestive processes of the human gastrointestinal tract. No participant reported any Synsorb-Pk-related adverse reactions, and no clinically important trends in laboratory data were evident. Synsorb-Pk recovered from stools retained its ability to absorb VT in polymyxin extracts of VT-producing Escherichia coli and also neutralized VT when mixed in vitro with VT-positive stools from children with hemorrhagic colitis or hemolytic-uremic syndrome (HUS). These results suggest a potential use for Synsorb-Pk in preventing HUS in patients infected with VT-producing E. coli.