Jean P. Turgeon

Randomized, controlled trial of antibiotic therapy for Escherichia coli O157:H7 enteritis.

We undertook a prospective, controlled study to evaluate the effect of trimethoprim-sulfamethoxazole in children with proven Escherichia coli O157:H7 enteritis on the duration fo symptoms, on fecal excretion of pathogen, and on the risk of progression to hemolytic-uremic syndrome. There was no statistically significant effect of treatment on progression of symptoms, fecal pathogen excretion, or the incidence of HUS (2/22 vs 4/25; p = 0.67). Our results suggest that a multicentric trial using rapid diagnostic methods to permit early randomization should be carried out.

Cellular immunity is activated and a TH-2 response is associated with early wheezing in infants after bronchiolitis

OBJECTIVE To determine whether abnormalities of cellular immunity are present and linked to early wheezing after bronchiolitis. METHODS We prospectively studied 26 infants hospitalized for a first episode of bronchiolitis and without any prior immune, cardiac, or respiratory disease. Blood was obtained at the time of enrollment and 5 months later for the assessment of the total cellular and differential counts, CD4+ (helper) and CD8+ (suppressor/cytotoxic) lymphocytes, and the activation markers CD23 (low-affinity immunoglobulin E receptor) and CD25 (interleukin-2 (IL-2) receptor). The cytokines interferon gamma (T-helper (TH) type-1 cytokine) and IL-4 (TH-2) were measured in plasma and in vitro after stimulation with IL-2 or with the house-dust mite (Dermatophagoides farinae) antigen. A daily log of episodes of wheezing was kept by parents after discharge. RESULTS We found an increase in blood eosinophils, an increased percentage of CD4+, CD25+, and CD23+ lymphocytes in subjects at 5 months compared with the time of bronchiolitis and with healthy subjects of the same age (p < 0.05). Plasma IL-4 levels, although not different from those of healthy subjects, also increased significantly. Peripheral blood lymphocytes from infants who wheezed produced more IL-4 in vitro, 5 months after bronchiolitis, in response to D. farinae antigen. In babies who wheezed, a positive correlation was found between the total number of days that wheezing occurred and the blood eosinophil count. Babies who wheezed more often (> 20 days) had more peripheral blood basophils and eosinophils, and peripheral blood lymphocytes obtained from these subjects at the time of bronchiolitis produced less interferon gamma on stimulation with IL-2. CONCLUSIONS Bronchiolitis is followed by activation of cellular immunity, and early wheezing in infants is associated with a TH-2 response.

Circulating inflammatory cytokine levels in hemolytic uremic syndrome

Abstract 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) ≤80 ml/min per 1.73 m2 measured 1 year later. Increased levels of IL-6 (P<0.0001), IL-10 (P<0.0001), and IL-1Ra (P<0.07) were found among patients with HUS compared with normal controls. Children with severe renal dysfunction also had tenfold increased levels of IL-6 and higher concentrations of IL-10 and IL-1Ra. Both the IL-6/IL-10 (4.9±8.3 vs. 0.5±0.4, P=0.01) and the IL-6/IL-1Ra ratios (0.10±0.20 vs. 0.01±0.01, P=0.04) were significantly increased. GFR correlated well with IL-6 levels, IL-6/IL-10 and IL-6/IL-1Ra ratios. Our data demonstrate that the inflammatory response of the host is associated with the severity of renal dysfunction during classic HUS. An imbalance between the pro- and the anti-inflammatory responses may be involved in the pathophysiology of VTEC-associated HUS.

Inflammatory mediators in Escherichia coli O157:H7 hemorrhagic colitis and hemolytic-uremic syndrome.

BACKGROUND Recent experimental data suggest that the inflammatory response of the host to verotoxin and/or lipopolysaccharides of Escherichia coli is involved in the pathophysiology of verotoxin-producing E. coli (VTEC) infections. METHODS We measured the circulating concentrations of cytokines [TNF-alpha, interleukin (IL)-1-beta, IL-1 receptor antagonist (Ra), IL-6, IL-8, IL-10] and soluble leukocyte adhesion molecules (L-selectin, P-selectin, E-selectin, intracellular cell adhesion molecule-1, vascular cell adhesion molecule-1) by sandwich enzyme-linked immunosorbent assay among (1) normal controls (n = 12), (2) disease controls with hemorrhagic colitis (HC) not associated with VTEC infections (n = 57), (3) patients with uncomplicated HC caused by E. coli O157:H7 (n = 30), and (4) children with hemolytic-uremic syndrome (HUS) (n = 28). Patients with HUS were matched with children who presented an uncomplicated HC caused by E. coli O157:H7 for the time interval elapsed between the onset of HC and that of blood sample collection. RESULTS Concentrations of TNF-alpha and IL-1-beta were undetectable. Children with HUS were characterized by increased amounts of IL-6 and IL-8, lower values of soluble L-selectin as well as increased levels of IL-10 and IL-1Ra. The circulating concentrations of IL-1Ra were higher among children with O157:H7 HC who subsequently developed HUS. CONCLUSIONS Increased pro- and antiinflammatory cytokine responses are produced by the host during the development of HUS among children with VTEC infections. Further studies are needed to determine their relative contribution to the pathophysiology of classic HUS.

Impact of a false positive blood culture result on the management of febrile children.

OBJECTIVE To evaluate the impact of a preliminary positive blood culture result, subsequently confirmed to be a false positive blood culture result on rate of hospitalization, antibiotic therapy and use of microbiologic tests. DESIGN Retrospective chart review. PATIENTS AND METHODS Children between 1 month and 18 years old on whom a blood culture was performed were eligible, excluding those with an underlying condition for whom a false positive blood culture may be difficult to assess. During the 1-year study period 9959 blood cultures were performed of which 778 (7.8%) produced growth. Charts of 81 patients with a false positive blood culture were reviewed and compared with those of 162 patients with a true negative blood culture. Patients already hospitalized when blood culture was drawn (n = 24) were analyzed separately from those who were not (n = 219). Among these, patients were divided into those who were followed as outpatients (n = 104) and hospitalized (n = 115). RESULTS Both groups (false positive vs. true negative) were comparable for age, sex, temperature at consultation, white blood cell count and illness severity. Twenty-six percent of patients followed as outpatients who had a false positive blood culture were hospitalized because of a preliminary positive blood culture result. Among patients hospitalized at the initial assessment, the frequency of antibiotic therapy (91% vs. 71%, P < 0.01), the frequency of use of intravenous antibiotics (80% vs. 58%, P < 0.01) and the percentage of unwarranted antibiotic prescription (13% vs. 0%, P < 0.01) were significantly greater in the false positive group than in the true negative group. The same results were found for each of these outcomes among the group of patients followed as outpatients (61% vs. 28%, P < 0.01, 17% vs. 0%, P < 0.01 and 39% vs. 0%, P < 0.01) for false positive vs. true negative, respectively. Patients with false positive blood cultures had more blood cultures drawn subsequently (P < 0.01). Children already hospitalized when the blood culture was obtained did not show significant differences in main outcomes. CONCLUSIONS False positive blood culture results generate unnecessary hospitalizations, antibiotic therapy and use of microbiologic tests.

Circulating levels of transforming growth Factor-β1 and lymphokines among children with hemolytic uremic syndrome

Verotoxin-producing Escherichia coli (VTEC) cause hemorrhagic colitis (HC) and hemolytic uremic syndrome (HUS). The aim of this study was to compare the circulating levels of transforming growth factor-beta 1 (TGF-beta1), T helper (T(H))1 (interferon [IFN]-gamma, interleukin [IL]-2), and T(H)2-associated lymphokines (IL-4, IL-13) in children with uncomplicated Escherichia coli O157:H7 HC and patients who developed HUS. Circulating levels of IL-2, IL-4, and IL-13 were undetectable, and those of IFN-gamma were low and comparable among groups. Concentrations of TGF-beta1 were higher in children with uncomplicated O157:H7 HC than among those who developed HUS (934 +/- 680 versus 514 +/- 497 pg/mL, respectively; P < 0.04). The circulating levels of TGF-beta1 were also higher among children who did not take antidiarrheal agents (P < 0.008) and those who have been immediately discharged from the emergency room (P < 0.03). Our results did not show an imbalanced T(H)1/T(H)2-associated lymphokine response during the development of HUS. Increased circulating levels of TGF-beta1 in children with milder O157:H7 or uncomplicated HC most likely reflect appropriate intestinal tissue repair mechanisms rather than a remote systemic endocrine effect on the kidneys.

Comparison of inhaled terbutaline administered by either the Turbuhaler dry powder inhaler or a metered-dose inhaler with spacer in preschool children with asthma.

We compared the bronchodilator response of terbutaline delivered either by a dry powder inhaler, the Turbuhaler, or by a metered-dose inhaler attached to a Nebuhaler inhaler in 10 children with stable asthma who were 3 to 6 years of age. The bronchodilator response did not differ between the two inhalational devices. The dry powder inhaler Turbuhaler is a suitable alternative to a metered-dose inhaler in the delivery of terbutaline to preschool children with stable asthma if adequate inhalational technique is used.

Congenital malformations and medical conditions associated with orofacial clefts in children in Burkina Faso

BackgroundOrofacial clefts are usually isolated cases but can be associated with other congenital malformations that are either recognised or unrecognised syndromes. The reported prevalence and pattern of such associated malformations, however, vary among studies. Objectives: To assess the frequencies and aetiologies of congenital malformations and associated medical conditions in children with orofacial clefts in Burkina Faso (Western Africa).MethodsA retrospective descriptive study was carried out at the El Fateh-Suka Clinic in Ouagadougou, Burkina Faso. All children who attended surgery for the repair of a cleft lip and/or palate were included in this study.ResultsThe frequency of congenital malformations associated with cleft lip and/or palate was 39/185 (21.1%). In the group with multiple congenital malformations of unknown origin (34 patients; 18.4%), 66.7% had cleft lip and palate, followed by isolated cleft lip (27.4%) and isolated cleft palate (5.9%). The digestive system (35.3%), the musculoskeletal system (19.6%), and eye, ear, face, and neck (15.7%) were the most affected systems. In the group of syndromic malformations (five patients; 2.7%), amniotic band syndrome (one patient), Van der Woode syndrome (one patient), Goltz syndrome (one patient), and holoprosencephaly (two patients) were identified. Medical conditions included anaemia (39.4%), infections (9.2%), malnutrition (7.5%), and haemoglobinopathies (4.3%).ConclusionsCongenital malformations and medical co-morbidities were frequent in children with OFCs. Further studies and a National Malformations Registry are needed to improve the comprehension of OFCs in Burkina Faso.

Immune response to verotoxin 1 and 2 in children with Escherichia coli O157:H7 hemorrhagic colitis and classic hemolytic uremic syndrome.

OBJECTIVES To compare neutralizing antibody titres against verotoxin (vt)-1 and vt-2 between children with uncomplicated hemorrhagic colitis (hc) and those with classic hemolytic uremic syndrome (hus). vt antibody titres were also compared in children with hc who received trimethoprim-sulfamethoxazole with those who did not. DESIGN Prospective study. SETTING Tertiary pediatric hospital. POPULATION STUDIED Children with hc (n=41) or classic hus (n=12). INTERVENTIONS Serum antibodies against vt-1 and vt-2 were determined by quantitative neutralization. MAIN RESULTS Antibodies were detected in 40% (21 of 53) of serum samples for vt-1 and in 100% (53 of 53) of samples for vt-2. A positive immune response, defined as a fourfold increase in vt antibody titres or as a single titre of 1/64 or greater, was found in 0% (0 of 12) of patients with hus compared with 7% (three of 41) of those with hc for vt-1 (P=0.4); and in 17% (two of 12) of patients with hus compared with 22% (nine of 41) of those with hc for vt-2 (P=0.3). The rate of seroconversion against either vt-1 or vt-2 was comparable in treated and untreated patients with uncomplicated hc. CONCLUSIONS There was no evidence that neutralizing antibody levels against vt-1 or vt-2 in classic hus or after antibiotic therapy are substantially different from those in patients with uncomplicated hc.