Pharyngeal flow interval: a novel impedance-based parameter correlating with aspiration.

BACKGROUND: The role of pharyngeal impedance recording for assessing pharyngeal function is yet to be established. The aim of this study was to evaluate impedance flow interval, a novel parameter, in relation to bolus residue and the occurrence of aspiration. The effect of catheter configuration was also assessed. METHODS: We studied 12 children (1.8-13.5years) with cerebral palsy, who were all referred for a videofluoroscopy due to suspected aspiration risk. Pharyngeal impedance patterns during bolus swallowing were recorded simultaneously with fluoroscopy. Two different catheter configurations were used: Catheter 1, 1.9mm diameter with 1cm electrodes and Catheter 2, 3.2mm diameter with 2cm electrodes. The flow interval was based on the objective assessment of impedance drop and recovery across multiple impedance segments and was correlated with fluoroscopic evidence of postswallow bolus residue and deglutitive aspiration. KEY RESULTS: One hundred and thirty two liquid swallows were evaluated. Patient swallows with aspiration compared to those without aspiration had a longer flow interval (Cath 1 P=0.005; Cath 2 P<0.001). Patient swallows with residue had a longer flow interval, however this was only significant for swallows recorded using Catheter 2 (P=0.004). Multiple logistic regressions showed that higher flow interval was a better marker of the presence of aspiration [odds ratio (OR) 13.4 (3.0, 59.2); P<0.001] than the presence of residue [OR 3.8 (1.4, 10.3); P=0.01]. CONCLUSIONS & INFERENCES: We present novel findings suggesting that impedance measurement can detect alterations in flow characteristics of pharyngeal swallow that have the potential to predict to deglutitive aspiration risk.

Characterization of intraluminal impedance patterns associated with gas reflux in healthy volunteers.

UNLABELLED: Multichannel intraluminal impedance (MII) recording allows assessment of flow through the oesophagus and differentiation between liquid and gas contents. Existing MII criteria for recognition of gas gastro-oesophageal reflux (GOR) have not been validated during known gas GOR in humans. AIMS: (i) Characterize MII patterns of known gas GOR and optimize criteria. (ii) Clarify interrelationships between magnitude of maximal impedance change, luminal diameter and electrode-mucosa contact. Ten healthy volunteers (six male, 21-37 years) were studied using an oesophageal MII-manometry catheter. After catheter placement, subjects were asked to drink 600 mL of carbonated soft drink. Recordings were made for 20 min and the protocol repeated. Reported belches confirmed manometrically (triggered by transient lower oesophageal sphincter relaxations) were included for analysis. Those episodes were compared against commonly used criteria. Another five subjects (three male, 26-52 years) underwent simultaneous MII and videofluoroscopy using the same protocol. Videofluoroscopic images were analyzed for luminal diameter and the presence of electrode-mucosa contact. All analyzed gas GOR episodes (n = 88) were associated with a pattern of impedance rise which was either retrograde (62.5%), synchronous (19.3%) or antegrade (18.2%). Depending on the exact criteria used, sensitivity ranged from 33% to 75%. A multivariate regression model including luminal diameter and the presence of electrode-mucosa contact as independent factors accounted for 53% of all variation in impedance changes. In conclusion, a significant number of gas GOR episodes does not meet criteria for their recognition. New criteria are proposed to include specific antegrade patterns of impedance rise. Luminal diameter and the extent of contact between the oesophageal mucosa and MII-electrodes influence the magnitude and patterning of impedance change.

Detection of treatable neonatal liver disease by expanded newborn screening.

Two neonates were identified at age 48 h by expanded newborn screening, with abnormal methionine and tyrosine concentrations, which were confirmed on repeat samples. Evidence of previously unsuspected liver disease was found at recall, and there was radiological and biochemical evidence of severe liver disease with hepatic synthetic failure. After inborn errors of metabolism (IEMs) were excluded, both were considered to have neonatal haemochromatosis, on the basis of raised ferritin, iron saturation, and very high α-fetoprotein and confirmed by a mildly hyperferritinaemic sibling in the first case, and raised ferritin and iron saturation in the second. However, it was not feasible to obtain tissue confirmation as the requirement for early therapy precluded biopsy. The babies were treated with antioxidants and iron-chelating agents, and the coagulopathy and hypoalbuminaemia were corrected. Both made a complete recovery and remain well after follow-up. Newborn screening programmes could consider advising clinicians, when tyrosine and methionine values are elevated, that once IEMs are excluded liver disease from other causes must be sought. Neonatal haemochromatosis is an example of one such disease that is potentially treatable.

Yoghurts containing probiotics reduce disruption of the small intestinal barrier in methotrexate-treated rats.

Small intestinal permeability was employed to assess the efficacy of commercially available yoghurts containing probiotics in a rat model of methotrexate (MTX)-induced mucositis. Male Sprague-Dawley rats were allocated to four groups (n = 8): MTX + water, MTX + cow's milk yoghurt (CY; fermented with Lactobacillus johnsonii), MTX + sheep's milk yoghurt (SY; containing Lactobacillus bulgaricus and Streptococcus thermophilus), and saline. Treatment gavage occurred twice daily for 7 days pre-MTX and 5 days post-MTX. Intestinal permeability was assessed on days -7, -1, 2, and 5 of the trial. Intestinal sections were collected at sacrifice for histological and biochemical analyses. Histology revealed that rats receiving CY and SY did not have a significantly damaged duodenum compared to controls. However, an improved small intestinal barrier function was evident, determined by a decreased lactulose/mannitol ratio. Probiotics containing SY and CY may be useful in preventing disruption to intestinal barrier function in MTX-induced mucositis.

Multipoint measurement of intragastric pH in healthy preterm infants.

BACKGROUND: The diagnostic use of 24 hour oesophageal pH monitoring in infants is controversial because of the impact of feed buffering of gastric acidity. AIM: To re-evaluate the effect of feeding on gastric pH and reflux using multipoint pH measurements. SUBJECTS: Fifteen healthy premature infants fed every four hours. METHODS: Oesophageal pH and intragastric pH at 3, 6, and 9 cm below the lower oesophageal sphincter were simultaneously measured using a four channel pH probe for four hours after bolus feeding. Parameters of pH were compared for the different levels within the stomach. During reflux episodes, the nadir pH was compared with intragastric pH at all levels. RESULTS: The proximal stomach was more significantly buffered by feeding and slower to re-acidify postprandially than the mid and distal stomach (42.2% of the time at pH < 4 compared with 58.7% and 55.7% respectively). During 27 of 62 gastro-oesophageal reflux episodes, nadir oesophageal pH was lower than the pH of the proximal stomach but always equal to or higher than the pH of the distal stomach. CONCLUSIONS: These data indicate that previous studies may have overestimated the effect of feeding on gastric acidity and reflux.

The successful medical management of severe duodenal strictures secondary to eosinophilic gastroenteritis in an infant.

Eosinophilic gastroenteritis is an uncommon condition of unknown etiology that has only been relatively recently reported. Its clinical manifestations range from a mild disease to more severe forms resembling Crohn's disease. Enteric strictures are a rare but recognized complication of this condition. We report a case of eosinophilic gastroenteritis in an infant presenting with severe duodenal strictures that was successfully managed with oral prednisolone. We believe that this is the first reported case of duodenal strictures secondary to eosinophilic gastroenteritis.

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 (13)C-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.

Patterns of antropyloric motility in fed healthy preterm infants.

BACKGROUND: Antropyloric motility is important for regulation of gastric emptying and has not been adequately characterised in premature infants. AIM: To evaluate fed patterns of antropyloric motility in premature infants. SUBJECTS: Forty three healthy premature infants, 30-38 weeks of postmenstrual age. METHODS: Postprandial antropyloric motility was measured using a micromanometric feeding assembly (outer diameter 1.8 mm) incorporating a pyloric sleeve sensor. The occurrence of isolated pyloric pressure waves (IPPWs) and antral pressure wave sequences (PWSs) was characterised. Sequences were further classified as being antegrade, synchronous, antegrade-synchronous, and retrograde according to the direction of propagation. RESULTS: A total of 7289 pressure wave events were recorded, 48% IPPWs and 52% PWSs (18% antegrade, 12% synchronous, 13% antegrade-synchronous, 2% retrograde, and 7% undefined). IPPWs predominated in the first postprandial hour, peaking at 30-60 minutes. PWSs predominated in the period after one hour postprandially. Mean (SEM) half gastric emptying time was 42 (4) minutes. CONCLUSIONS: Monitoring of antropyloric motor patterns in healthy premature infants indicates that the neuroregulatory mechanisms responsible for the coordination of antropyloric motility and gastric emptying are well developed by 30 weeks of postmenstrual age.

Characterization of anorectal pressure and the anorectal inhibitory reflex in healthy preterm and term infants.

OBJECTIVES: To evaluate anorectal motor function in healthy premature and term infants with the use of micromanometric techniques. STUDY DESIGN: Anorectal manometry was performed in 22 healthy neonates (9 female) with a mean postmenstrual age of 32 weeks (range, 30 to 38 weeks) with a micromanometric anorectal assembly (od 2.0 mm). The assembly incorporated a 2-cm-long sleeve sensor for measurement of resting anal sphincter pressures and relaxation, and 4 sideholes recorded anal and rectal pressures. Rectal distension was performed with a latex balloon or direct air insufflation to elicit the anorectal inhibitory reflex (AR). RESULTS: The mean anal sphincter pressure, rectal pressure, and rhythmic wave frequency were 40 mm Hg (range, 7 to 65 mm Hg), 11 mm Hg (range, 1 to 27 mm Hg), and 10/min (range, 8 to 14/min), respectively. A normal AR could be elicited in 21 of the 22 infants studied. CONCLUSION: An anorectal micromanometric sleeve catheter is suitable for use in evaluating anorectal pressures in preterm and term neonates. Insufflation of air without the use of a balloon to elicit the AR is reliable and suitable for use in infants <34 weeks. Premature infants older than 30 weeks' postmenstrual age have normal anorectal pressures and a normal AR.

Pathophysiological mechanisms of gastroesophageal reflux disease in children.

Gastroesophageal reflux (GER) is an extremely common pediatric problem, but only in the past few years have we developed a better understanding of its pathophysiology. This is related to the wider use of investigative tools such as flexible endoscopy, 24-hour pH monitoring, and more recently, micromanometric methods and noninvasive breath tests, which have been particularly useful in infants. This paper reviews our current understanding of the esophageal and gastric mechanisms contributing to the pathophysiology of GER. In this context, we also highlight areas where new therapeutic approaches may be beneficial.

Survival of rotavirus antibody activity derived from bovine colostrum after passage through the human gastrointestinal tract.

BACKGROUND: Rotavirus is a major cause of infectious diarrhea in infants and young children. Several studies have shown that hyperimmune bovine colostrum, derived from cows immunized with rotavirus, can prevent rotavirus diarrhea when given passively. The objective of this study was to determine whether colostral antibody activity survived transit through the gut by measuring the level of rotavirus antibody activity in the feces. METHODS: Hyperimmune colostrum containing different levels of rotavirus antibody was administered to 105 children attending nine Adelaide childcare centres. Subjects were asked to drink 100 ml of whole milk supplemented with colostrum 3 times a day, for a period of 6 days. Stool samples were collected from the subjects before, during, and after consumption of the study product. Rotavirus activity was determined using a novel virus reduction enzyme-linked immunosorbent assay (ELISA) and a virus neutralization assay. RESULTS: Rotavirus antibody activity was detected in 521 (86%) of 602 fecal specimens obtained during the study using the virus reduction ELISA. The antibody activity was detected as early as 8 hours after ingestion of hyperimmune colostrum and up to 72 hours after consumption had ceased. There was a strong relation (r = 0.81) between the titer of rotavirus antibody administered to subjects and the level of antibody activity detected in the feces. CONCLUSIONS: The results show that antirotavirus activity survived passage through the gut. Therefore, passive immunotherapy may be used to prevent or treat infectious diseases that affect the entire length of the gastrointestinal tract.

Effect of cisapride on gastric emptying in premature infants with feed intolerance.

OBJECTIVE: To assess the effect of cisapride on gastric emptying and gastro-oesophageal reflux (GOR) symptoms in preterm infants with feed intolerance. METHODS: Sixteen preterm infants (gestational age 24-35 weeks) with feed intolerance were enrolled in the study. Infants were randomized to receive 7 days of cisapride 0.2 mg/kg four times a day, immediately followed by 7 days of placebo or vice versa. Gastric emptying was measured using the [13C]-octanoic acid breath test prior to study entry and repeated on day 5, 6 or 7 after randomization and 5, 6 or 7 days after crossover. The symptoms of GOR were monitored during the study period using a standardized reflux chart. Weight was recorded daily. RESULTS: There was no change in gastric emptying in infants prescribed cisapride (gastric half-emptying time (t1/2) 31.9 +/- 4.7 vs 34.2 +/- 3.9 min for placebo vs cisapride, respectively; P = 0.65). Infants on cisapride had slower growth and there was no change in reflux symptoms. CONCLUSIONS: The use of cisapride in preterm infants with feed intolerance cannot be recommended.

Probiotics in pediatric gastrointestinal disorders.

Probiotics have been defined most recently as living microorganisms which, upon ingestion in certain numbers, exact health benefits beyond inherent general nutrition. They have been a part of human nutrition for centuries, but in recent years they have been more closely studied for their potential to improve health and treat disease. This review of probiotics is not extensive, highlighting the most recent reviews and well controlled clinical studies in both animals and humans. The safety issues are also discussed as well as potential mechanisms of action. The importance of studying each probiotic bacterium individually in each condition where a health benefit is claimed is highlighted by Lactobacillus GG, the most widely studied probiotic which has proven benefit in reducing the severity and duration of viral diarrhea but no benefit against bacterial diarrhea.

Reflux in children.

Gastro-oesophageal reflux (GOR) is an extremely common paediatric problem that often runs a harmless and self-limited course. Physiological GOR however can lead to marked parental anxiety, many unnecessary investigations and often unwarranted and potentially harmful therapeutic interventions. Our ability to better define GOR and gastro-oesophageal reflux disease (GORD) has improved in the past 15 years with a better understanding of the pathophysiology in infants and children due to the development and wider use of flexible endoscopy, 24-hour oesophageal pH monitoring and, more recently, the use of micromanometric methods for studying oesophageal motility. This will be further enhanced in the future with the development of non-invasive breath testing to study gastrointestinal motility and the use of electrical impedance to study fluid movement. Our therapeutic interventions have also improved particularly in the areas of acid suppression, improved surgical techniques and most recently laparoscopic fundoplication. This chapter reviews these advances in the paediatric area especially with regard to pathophysiology, diagnostic testing and therapeutic intervention.

Analysis of the breath hydrogen test for carbohydrate malabsorption: validation of a pocket-sized breath test analyser.

OBJECTIVE: To assess the validity and clinical application of a hand-held breath hydrogen (H2) analyzer (BreatH2, Europa Scientific, Crewe, UK). METHODOLOGY: Breath samples of patients referred to the Gastroenterology Unit, Women's and Children's Hospital, North Adelaide, South Australia, for confirmation of the diagnosis of carbohydrate malabsorption were analysed with the Quintron microlyzer (Quintron Instrument Co., Milwaukee, USA) and the BreatH2 analyser, using the Quintron microlyzer as the gold standard. RESULTS: Twenty-nine breath H2 tests (BHT) were performed in 29 patients aged 2 months to 61 years. The sensitivity and specificity of the BreatH2 analyser in detecting a positive BHT using the Quintron microlyser as the gold standard were 0.90 and 0.95 with positive and negative predictive values of 0.90 and 0.95, respectively. There was one false positive and one false negative reading. Bland-Altman plots showed a high degree of agreement between the values obtained with two different methods. CONCLUSIONS: The diagnosis of carbohydrate malabsorption, using a portable breath H2 analyser (BreatH2), achieved an acceptable degree of sensitivity and specificity, enabling it to be used where no alternative is available.

Malrotation with recurrent volvulus presenting with cholestasis, pruritus, and pancreatitis.

A patient aged 16 years was referred following numerous episodes of intense pruritus associated with persistently altered liver function tests. Ultrasound (US) demonstrated the superior mesenteric vein positioned more to the left than usual and abnormal orientation of the duodenum, consistent with a midgut malrotation. Endoscopic retrograde cholangiopancreatography the common bile duct, suggesting a malrotation with chronic or recurrent volvulus. A classic malrotation with 180 degrees volvulus was noted at operation. A second child previously thought to have recurrent idiopathic pancreatitis was noted to have ampullary distortion secondary to malrotation following presentation with an intestinal obstruction. Pruritus and pancreatitis have not been previously reported with malrotation, although cholestatic jaundice has been described. The diffculties in diagnosis and the role of US are discussed. Ladd's procedure is the appropriate treatment for this condition.

Behavior and gastroesophageal reflux in the premature neonate.

BACKGROUND: The belief that behavioral observations assist in the clinical diagnosis of gastroesophageal reflux (GER) disease in premature neonates has not been formally tested. The purpose of this study was to determine whether esophageal acidification was associated with a recognizable pattern of behavioral changes in these infants. METHODS: The behavior of 14 healthy premature infants was recorded by a video camera while esophageal pH was simultaneously monitored. For each of 20 acid GER episodes recorded, a 10-minute video epoch, encompassing the onset of acid GER and lasting at least 4 minutes after the onset of GER, was examined. Two independent observers each scored reflux-associated epochs of "general" infant behavior and behavior previously shown to be indicative of reflux in normal term infants. RESULTS: The occurrence of esophageal acidification due to reflux did not significantly alter scores for general behavior. Infants frequently demonstrated reflux-specific behavior, including discomfort, head retraction, and mouthing; however, none of these behavioral patterns was temporally associated with the occurrence of acid GER. CONCLUSIONS: These data indicate that reflux-specific behavioral criteria, established in older term infants, may be inappropriate as diagnostic criteria for GER in premature neonates and may lead to the unnecessary use of antireflux therapy.

Non-alcoholic steatohepatitis in children and adolescents.

We describe 17 children with non-alcoholic steatohepatitis. All had elevated levels of serum liver enzymes and 16 were morbidly obese. Liver biopsy showed variable steatosis and fibrosis in nine patients. At follow-up, 12 of 14 patients had persistent morbid obesity and 11 had elevated liver enzyme levels.

Factors affecting the validity of the 13C-urea breath test for in vivo determination of Helicobacter pylori infection status in a mouse model.

BACKGROUND: The mouse model using a human isolate of Helicobacter pylori is being widely accepted as an economical means of studying gastric infection. A noninvasive monitoring method would be useful for repeated testing to establish the time course of infection and the efficacy of treatments. In this study, we describe factors that affected interpretation of 13C urea breath test results for the assessment of H. pylori infection status in this model. MATERIALS AND METHODS: Female C57B1/6 mice that underwent gavage with H. pylori or saline were breath-tested using 50 micrograms of 13C urea at intervals up to 2 months after inoculation. The generation of 13CO2 (excess delta 13CO2) by infected mice was compared to that of uninfected controls. The effects of diet, fasting, and coprophagy on the reliability of the 13C urea breath test were quantitated. RESULTS: Both commercial and synthetic mouse diets exhibited marked in vitro urease activity. A minimum fasting time of 13 hours prior to breath testing significantly reduced this dietary contribution to excess delta 13CO2 values. The coprophagic tendency of the mice caused spuriously high excess delta 13CO2 counts in the breath of both control and H. pylori-infected mice. CONCLUSIONS: Although the dietary contribution to spuriously high values of excess delta 13CO2 in mice breath-tested for H. pylori infection was reduced by fasting, the high nonspecific urease activity generated by coprophagy severely limited the reliability of the urea breath test in the assessment of H. pylori infection status.