Geoffrey P. Davidson

A Novel Bocavirus Associated with Acute Gastroenteritis in Australian Children

Acute gastroenteritis (AGE) is a common illness affecting all age groups worldwide, causing an estimated three million deaths annually. Viruses such as rotavirus, adenovirus, and caliciviruses are a major cause of AGE, but in many patients a causal agent cannot be found despite extensive diagnostic testing. Proposing that novel viruses are the reason for this diagnostic gap, we used molecular screening to investigate a cluster of undiagnosed cases that were part of a larger case control study into the etiology of pediatric AGE. Degenerate oligonucleotide primed (DOP) PCR was used to non-specifically amplify viral DNA from fecal specimens. The amplified DNA was then cloned and sequenced for analysis. A novel virus was detected. Elucidation and analysis of the genome indicates it is a member of the Bocavirus genus of the Parvovirinae, 23% variant at the nucleotide level from its closest formally recognized relative, the Human Bocavirus (HBoV), and similar to the very recently proposed second species of Bocavirus (HBoV2). Fecal samples collected from case control pairs during 2001 for the AGE study were tested with a bocavirus-specific PCR, and HBoV2 (sequence confirmed) was detected in 32 of 186 cases with AGE (prevalence 17.2%) compared with only 15 controls (8.1%). In this same group of children, HBoV2 prevalence was exceeded only by rotavirus (39.2%) and astrovirus (21.5%) and was more prevalent than norovirus genogroup 2 (13.4%) and adenovirus (4.8%). In a univariate analysis of the matched pairs (McNemars Test), the odds ratio for the association of AGE with HBoV2 infection was 2.6 (95% confidence interval 1.2–5.7); P = 0.007. During the course of this screening, a second novel bocavirus was detected which we have designated HBoV species 3 (HBoV3). The prevalence of HBoV3 was low (2.7%), and it was not associated with AGE. HBoV2 and HBoV3 are newly discovered bocaviruses, of which HBoV2 is the thirdmost-prevalent virus, after rotavirus and astrovirus, associated with pediatric AGE in this study.

Mechanisms of gastro-oesophageal reflux in preterm and term infants with reflux disease

Background: Transient lower oesophageal sphincter relaxation (TLOSR) is the predominant mechanism of gastro-oesophageal reflux (GOR) in healthy infants but the mechanisms of GOR in infants with GOR disease (GORD) are poorly understood. Aims: To measure the occurrence of TLOSR, GOR, and gastric emptying (GE) rate in preterm and term infants with GORD. Patients: Thirty six infants were studied and grouped as normals or GORD based on a routine clinical assessment and confirmation of an assessment of GORD by reflux symptom charts and oesophageal pH monitoring. Methods: A micromanometric assembly incorporating a micro pH electrode recorded oesophageal motility and pH. GE rate was determined using the 13C-octanoic acid breath test. Results: TLOSR was the predominant mechanism of GOR, triggering 50–100% of GOR episodes (median 91.5%). Abdominothoracic straining significantly increased the occurrence of GOR in association with TLOSR. In infants with GORD, the number of TLOSRs overall was similar to normals but the proportion of TLOSRs accompanied by acid GOR was significantly higher than in normals (16.5% v 5.7%, respectively; p<0.001). Infants with GORD had a similar GE rate to normals. Conclusions: In infant GORD, acid reflux associated TLOSRs are abnormally common and likely to be a major contributing factor to the pathophysiology of GORD. Infants with GORD do not have delayed GE.

A Method to Objectively Assess Swallow Function in Adults With Suspected Aspiration

BACKGROUND & AIMS Pharyngeal manometry and impedance provide information on swallow function. We developed a new analysis approach for assessment of aspiration risk. METHODS We studied 20 patients (30-95 years old) with suspected aspiration who were referred for videofluoroscopy, along with controls (ages 24-47 years). The pharyngeal phase of liquid bolus swallowing was recorded with manometry and impedance. Data from the first swallow of a bolus and subsequent clearing swallows were analyzed. We scored fluoroscopic evidence of aspiration and investigated a range of computationally derived functional variables. Of these, 4 stood out as having high diagnostic value: peak pressure (PeakP), pressure at nadir impedance (PNadImp), time from nadir impedance to peak pressure (TNadImp-PeakP), and the interval of impedance drop in the distal pharynx (flow interval). RESULTS During 54 liquid, first swallows and 40 clearing swallows, aspiration was observed in 35 (13 patients). Compared to those of controls, patient swallows were characterized by a lower PeakP, higher PNadImp, longer flow interval, and shorter TNadImp-PeakP. A Swallow Risk Index (SRI), designed to identify dysfunctions associated with aspiration, was developed from iterative evaluations of variables. The average first swallow SRI correlated with the average aspiration score (r = 0.846, P < .00001 for Spearman Rank Correlation). An average SRI of 15, when used as a cutoff, predicted aspiration during fluoroscopy for this cohort (κ = 1.0). CONCLUSIONS Pressure-flow variables derived from automated analysis of combined manometric/impedance measurements provide valuable diagnostic information. When combined into an SRI, these measurements are a robust predictor of aspiration.

Effect of omeprazole on acid gastroesophageal reflux and gastric acidity in preterm infants with pathological acid reflux.

Introduction: Proton pump inhibitor (PPI) therapy is increasingly being used to treat premature infants with gastroesophageal reflux disease (GERD); however, the efficacy of PPI on acid production in this population has yet to be assessed in this patient group. The aim of this study was to determine the effect of 0.7 mg/kg/d omeprazole on gastric acidity and acid gastroesophageal reflux in preterm infants with reflux symptoms and pathological acid reflux on 24-h pH probe. Methods: A randomized, double blind, placebo-controlled, crossover design trial of omeprazole therapy was performed in 10 preterm infants (34–40 weeks postmenstrual age). Infants were given omeprazole for 7 d and then placebo for 7 d in randomized order. Twenty-four-hour esophageal and gastric pH monitoring was performed on days 7 and 14 of the trial. Results: Compared to placebo, omeprazole therapy significantly reduced gastric acidity (%time pH <4, 54% vs 14%, P < 0.0005), esophageal acid exposure (%time pH <4, 19% vs 5%, P < 0.01) and number of acid GER episodes (119 vs 60 episodes, P < 0.05). Conclusions: Omeprazole is effective in reducing esophageal acid exposure in premature infants with pathological acid reflux on 24-h pH probe; however, the far more complex issues of safety and efficacy have yet to be addressed.

Antro-pyloro-duodenal motor responses to gastric and duodenal nutrient in critically ill patients

Background: Gastric emptying is frequently delayed in critical illness which compromises the success of nasogastric nutrition. The underlying motor dysfunctions are poorly defined. Aims: To characterise antro-pyloro-duodenal motility during fasting, and in response to gastric and duodenal nutrient, as well as to evaluate the relationship between gastric emptying and motility, in the critically ill. Subjects: Fifteen mechanically ventilated patients from a mixed intensive care unit; 10 healthy volunteers. Methods: Antro-pyloro-duodenal pressures were recorded during fasting, after intragastric administration (100 ml; 100 kcal), and during small intestinal infusion of liquid nutrient (6 hours; 1 kcal/min). Gastric emptying was measured using a 13C octanoate breath test. Results: In healthy subjects, neither gastric nor small intestinal nutrient affected antro-pyloro-duodenal pressures. In patients, duodenal nutrient infusion reduced antral activity compared with both fasting and healthy subjects (0.03 (0–2.47) waves/min v 0.14 (0–2.2) fasting (p = 0.016); and v 0.33 (0–2.57)/min in healthy subjects (p = 0.005)). Basal pyloric pressure and the frequency of phasic pyloric pressure waves were increased in patients during duodenal nutrient infusion (3.12 (1.06) mm Hg; 0.98 (0.13)/min) compared with healthy subjects (−0.44 (1.25) mm Hg; p<0.02 after 120 minutes; 0.29 (0.15)/min; p = 0.0002) and with fasting (−0.06 (1.05) mm Hg; p<0.03 after 160 minutes; 0.49 (0.13)/min; (p = 0.0001). Gastric emptying was delayed in patients (gastric emptying coefficient 2.99 (0.2) v 3.47 (0.1); p = 0.015) and inversely related to the number of pyloric pressure waves (r = −0.563, p = 0.029). Conclusions: Stimulation of pyloric and suppression of antral pressures by duodenal nutrient are enhanced in the critically ill and related to decreased gastric emptying.

Bowel dysfunction in cystic fibrosis: importance of breath testing.

To investigate the prevalence of carbohydrate malabsorption and bacterial overgrowth in children with cystic fibrosis (CF) and abnormal stool pattern referred for breath hydrogen testing.

Management of cow's milk protein allergy in infants and young children: An expert panel perspective

Cows milk protein allergy is a condition commonly managed by general practitioners and paediatricians. The diagnosis is usually made in the first 12 months of life. Management of immediate allergic reactions and anaphylaxis includes the prevention of accidental food ingestion and provision of an adrenaline autoinjector, if appropriate. By contrast, the clinical course of delayed food‐allergic manifestations is characterised by chronicity, and is often associated with nutritional or behavioural sequelae. Correct diagnosis of these non‐IgE‐mediated conditions may be delayed due to a lack of reliable diagnostic markers. This review aims to guide clinicians in the: (i) diagnostic evaluation (skin prick testing or measurement of food‐specific serum IgE levels; indications for diagnostic challenges for suspected IgE‐ and non‐IgE‐mediated food allergy), (ii) dietary treatment, (iii) assessment of response to treatment, (iv) differential diagnosis and further diagnostic work‐up in non‐responders, (v) follow‐up assessment of tolerance development and (vi) recommendations for further referral.

A Novel Method for the Nonradiological Assessment of Ineffective Swallowing

OBJECTIVES:This validation study evaluates a new manometry impedance-based approach for the objective assessment of pharyngeal function relevant to postswallow bolus residue.METHODS:We studied 23 adult and pediatric dysphagic patients who were all referred for a videofluoroscopy, and compared these patients with 10 adult controls. The pharyngeal phase of swallowing of semisolid boluses was recorded with manometry and impedance. Fluoroscopic evidence of postswallow bolus residue was scored. Pharyngeal pressure impedance profiles were analyzed. Computational algorithms measured peak pressure (Peak P), pressure at nadir impedance (PNadImp), time from nadir impedance to PeakP (PNadImp–PeakP), the duration of impedance drop in the distal pharynx (flow interval), upper esophaghageal sphincter (UES) relaxation interval (UES-RI), nadir UES pressure (NadUESP), UES intrabolus pressure (UES-IBP), and UES resistance. A swallow risk index (SRI) was derived by the formula: SRI=(FI × PNadImp)/(PeakP × (TNadImp-PeakP+1)) × 100.RESULTS:In all, 76 patient swallows (35 with residue) and 39 control swallows (12 with residue) were analyzed. Different functional variables were found to be altered in relation to residue. In both controls and patients, flow interval was longer in relation to residue. In controls, but not patients, residue was associated with an increased PNadImp (suggestive of increased pharyngeal IBP). Controls with residue had increased UES-IBP, NadUESP, and UES resistance compared with patients with residue. Residue in patients was related to a prolonged UES-RI. The SRI was elevated in relation to residue in both controls and patients and an average SRI of 9 was optimally predictive of residue (sensitivity 75% and specificity 80%).CONCLUSIONS:We present novel findings in control subjects and dysphagic patients showing that combined manometry and impedance recordings can be objectively analyzed to derive pressure-flow variables that are altered in relation to the bolus residual and can be combined to predict ineffective pharyngeal swallowing.

Breath hydrogen response to milk containing lactose in colicky and noncolicky infants

In 122 healthy newborn infants, we studied the relationship between breath hydrogen (H2) production after feedings containing lactose (human milk or commercial formula) in colicky and noncolicky infants at 6 weeks and 3 months. Eighty-three infants (68%) developed colic (mild, moderate, or severe) by 2.6 +/- 1.8 weeks of age (mean +/- SD). Zero time (baseline) breath H2 values were significantly higher in colicky compared with noncolicky infants at both 6 weeks (40.6 +/- 41.4 vs 14.8 +/- 32.9 ppm) and 3 months (27.7 +/- 38.1 vs 8.5 +/- 18.2 ppm). There were significantly more positive breath H2 tests in colicky compared with noncolicky infants at 6 weeks (78% vs 36%) and 3 months (89% vs 45%). Failure to produce H2 throughout the breath H2 test was significantly more frequent in noncolicky compared with colicky infants at 6 weeks (50% vs 18%) and 3 months (43% vs 4%). These findings remained significant even when infants with mild colic (at 6 weeks and 3 months) were included in the noncolicky group. We conclude that colicky infants produce more breath H2 in the fasting state and in response to feedings containing lactose than noncolicky infants produce. This may represent increased lactose malabsorption, differences in colonic bacterial fermentation conditions, or differences in the handling of colonic gas produced.

Addition of pH-Impedance Monitoring to Standard pH Monitoring Increases the Yield of Symptom Association Analysis in Infants and Children with Gastroesophageal Reflux

OBJECTIVE To assess the additional yield of combined multichannel intraluminal pH-impedance (pH-MII) monitoring compared with standard pH monitoring on gastroesophageal reflux (GER) symptom associations in infants and children. STUDY DESIGN In 80 patients, 24-hour ambulatory pH-MII monitoring was performed. Tracings were analyzed with established pH-MII criteria. Symptoms of regurgitation and belching were excluded from analysis, because these were considered to be a direct consequence of GER. Standard GER-symptom correlation indices were calculated with: 1) standard pH monitoring; 2) MII detection of liquid and mixed bolus GER; 3) MII detection of all bolus GER (liquid, mixed, and gas); 4) pH-MII detection of all GER, including pH-only GER. RESULTS Fifty patients (21 children) were included. MII detection of all bolus GER yielded a significantly greater number of patients who were symptom-positive, 36 (72%) compared with 25 (50%) with standard pH-monitoring (P = .04). A positive symptom association was observed in 8 of 10 (80%) patients with pathological esophageal acid exposure and 28 of 40 (70%) patients with negative pH-findings. CONCLUSIONS A high proportion of patients with normal esophageal acid exposure had a positive symptom association on pH-MII monitoring. Including all MII-detected bolus GER and excluding pH-only GER for analysis optimizes the yield of GER-symptom associations in infants and children.