Review article: reflux and its consequences--the laryngeal, pulmonary and oesophageal manifestations. Conference held in conjunction with the 9th International Symposium on Human Pepsin (ISHP) Kingston-upon-Hull, UK, 21-23 April 2010.

BACKGROUND: Gastro-oesophageal reflux disease (GERD) is one of the commonest diseases of Western populations, affecting 20 to 30% of adults. GERD is multifaceted and the classical oesophageal symptoms such as heartburn and regurgitation often overlap with atypical symptoms that impact upon the respiratory system and airways. This is referred to as extra-oesophageal reflux disease (EERD), or laryngopharyngeal reflux (LPR), which manifests as chronic cough, laryngitis, hoarseness, voice disorders and asthma. AIM: The 'Reflux and its consequences' conference was held in Hull in 2010 and brought together a multidisciplinary group of experts all with a common interest in the many manifestations of reflux disease to present recent research and clinical progress in GERD and EERD. In particular new techniques for diagnosing reflux were showcased at the conference. METHODS: Both clinical and non-clinical key opinion leaders were invited to write a review on key areas presented at the `Reflux and its consequences' conference for inclusion in this supplement. RESULTS AND CONCLUSION: Eleven chapters contained in this supplement reflected the sessions of the conference and included discussion of the nature of the refluxate (acid, pepsin, bile acids and non-acid reflux); mechanisms of tissue damage and protection in the oesophagus, laryngopharynx and airways. Clinical conditions with a reflux aetiology including asthma, chronic cough, airway disease, LPR, and paediatric EERD were reviewed. In addition methods for diagnosis of reflux disease and treatment strategies, especially with reference to non-acid reflux, were considered.

New effective treatment regimen for children infected with a double-resistant Helicobacter pylori strain.

BACKGROUND: The increasing number of pediatric patients infected with multiresistant Helicobacter pylori strains calls for evaluation of treatment regimens. Second-line antibiotics such as tetracycline or quinolones are not licensed for children. Because in vivo resistance to metronidazole may be overcome in vivo by a high dose and prolonged intake, we evaluated the eradication rate and side effects of a high-dose triple therapy in pediatric patients with culture-proven double resistance. PATIENTS AND METHODS: In this open multicentre trial, 62 children (<18 years, body weight >15 kg) infected with an H pylori strain resistant to metronidazole and clarithromycin were treated according to body weight classes with amoxicillin (∼ 75 mg/kg/day), metronidazole (∼ 25 mg/kg/day) and esomeprazole (∼ 1.5 mg/kg/day) for 2 weeks. Adherence and adverse events were assessed by a 2-week diary and telephone interviews at days 7 and 14 of treatment. Primary outcome was a negative C-urea breath test after 6 weeks. RESULTS: Of 62 patients, 5 were lost to follow-up, 12 were nonadherent, and 45 treated per protocol. Eradication rates were 66% (41/62) [confidence interval 54-78] (intention to treat) and 73% (33/45) [confidence interval 60-86] (per protocol). Success of treatment was not related to dose per kilogram body weight. Mild to moderate adverse events were reported by 21 patients, including nausea (10.8%), diarrhoea (8.9%), vomiting (7.1%), abdominal pain (5.4%), and headache (3.6%), and led to discontinuation in 1 child. CONCLUSION: High-dose amoxicillin, metronidazole, and esomeprazole for 2 weeks is a good treatment option in children infected with a double resistant H pylori strain.

Impact of skin to skin care, prone and supine positioning on cardiorespiratory parameters and thermoregulation in premature infants.

BACKGROUND: Skin to skin care (SSC), prone (PP) and supine (SP) positions are standard positions in daily care for premature infants. Their influence on cardiorespiratory parameters and thermoregulation is discussed controversially. OBJECTIVES: We compared SSC with PP, the recommended position for preterm infants, and SP, the safest position for term infants, and tested the hypothesis that SSC has no impact on cardiorespiratory parameters and thermoregulation. METHODS: In 18 spontaneously breathing premature infants [median gestational 28 weeks (24-32); chronological age 36 days (7-64), and weight 1,543 g (750-2,100)], heart and respiratory rate, breathing pattern, episodes of desaturation (<85 but >or=80 and <80%), oxygen saturation and rectal temperature were analyzed with polygraphy (Alice 3(R) and 3.5(R)) in a 6-hour measuring cycle of three subsequent series (120 min each in SP, SSC and PP) and compared (Wilcoxon test). RESULTS: During SSC, we found no increase in apneic attacks and bradycardic episodes and no difference in respiratory rate, breathing pattern, oxygen saturation, episodes and duration of desaturation compared to SP and PP. Episodes of desaturation <85 but >or=80 and <80% were more frequent in SP compared to PP (p = 0.0421 and p = 0.0319). Heart rate increased in SSC and PP compared to SP (154.86 bpm, SD 11.55, and 153.33 bpm, SD 15.95 vs. 150.25 bpm, SD 14.64; p = 0.0013 and p = 0.0346). Temperature level was not significantly higher during SSC and PP compared to SP except a rise between the start and the end of the 6-hour measuring cycle (37.05 degrees C, SD 0.2 vs. 37.30 degrees C, SD 0.3; p = 0.0436). CONCLUSION: We found no significant SSC-mediated changes in quality and quantity of desaturations and in body temperature compared to PP in preterm infants.

[Pediatric bowel MRI--accelerated parallel imaging in a single breathhold]. / MRT des darms bei kindern--beschleunigte bildgebung in einem atemzug.

PURPOSE: To compare highly accelerated parallel MRI of the bowel with conventional balanced FFE sequences in children with inflammatory bowel disease (IBD). MATERIALS AND METHODS: 20 children with suspected or proven IBD underwent MRI using a 1.5 T scanner after oral administration of 700 -1000 ml of a Mannitol solution and an additional enema. The examination started with a 4-channel receiver coil and a conventional balanced FFE sequence in axial (2.5 s/slice) and coronal (4.7 s/slice) planes. Afterwards highly accelerated (R = 5) balanced FFE sequences in axial (0.5 s/slice) and coronal (0.9 s/slice) were performed using a 32-channel receiver coil and parallel imaging (SENSE). Both receiver coils achieved a resolution of 0.88 x 0.88 mm with a slice thickness of 5 mm (coronal) and 6 mm (axial) respectively. Using the conventional imaging technique, 4 - 8 breathholds were needed to cover the whole abdomen, while parallel imaging shortened the acquisition time down to a single breathhold. Two blinded radiologists did a consensus reading of the images regarding pathological findings, image quality, susceptibility to artifacts and bowel distension. The results for both coil systems were compared using the kappa-(kappa)-coefficient, differences in the susceptibility to artifacts were checked with the Wilcoxon signed rank test. Statistical significance was assumed for p = 0.05. RESULTS: 13 of the 20 children had inflammatory bowel wall changes at the time of the examination, which could be correctly diagnosed with both coil systems in 12 of 13 cases (92 %). The comparison of both coil systems showed a good agreement for pathological findings (kappa = 0.74 - 1.0) and the image quality. Using parallel imaging significantly more artifacts could be observed (kappa = 0.47) without impairing the diagnostic impact. The comparison of the bowel distension showed no significant differences. CONCLUSION: The highly accelerated parallel MRI using the SENSE technique and a 32-channel surface coil enables the examination of the entire bowel in a single breathhold without relevant restrictions in image quality and diagnostic impact.

Effect of Gaviscon Infant on gastro-oesophageal reflux in infants assessed by combined intraluminal impedance/pH.

BACKGROUND: Gaviscon Infant (GI) has been recommended for gastro-oesophageal reflux (GOR) in infants. Its efficacy has not been examined with a physiologically appropriate denominator to define the degree of GOR. AIM: To investigate the influence of Gaviscon Infant on GOR in infants using combined pH and intraluminal impedance measurement. METHODS: Twenty infants (mean age 163.5 days, range 34-319 days) exclusively bottle fed, with symptoms clinically suggestive of GOR, underwent 24 hour studies of intra-oesophageal 6 channel impedance and dual channel pH monitoring, during which six random administrations (3+3) of Gaviscon Infant (625 mg in 225 ml milk) or placebo (mannitol and Solvito N, 625 mg in 225 ml milk) were given in a double blind fashion. Impedance/pH reflux data were recorded and analysed blind by one observer. RESULTS: The median number of reflux events/hour (1.58 v 1.68), acid reflux events/hour (0.26 v 0.43), minimum distal or proximal pH, total acid clearance time per hour (time with pH below pH 4), and total reflux duration per hour were not significantly different after GI than after placebo. Reflux height was marginally lower after GI (median 66.6% v 77.3% oesophageal length) compared with placebo. CONCLUSIONS: Results showed a marginal but significant difference between Gaviscon Infant and placebo in average reflux height, and raises questions regarding any perceived clinical benefit of its use.

Association of apnea and nonacid gastroesophageal reflux in infants: Investigations with the intraluminal impedance technique.

An association of apnea and gastroesophageal reflux (GER) was proposed previously. However, pH metry as the standard diagnostic tool for GER only measures acid reflux (pH < 4). It is difficult to interpret studies in infants with a presumed association between apnea and GER based on pH metry because the buffering effect of feeding may result in predominantly nonacid GER. The aim of this study was to investigate the temporal association of apnea and GER with the pH-independent intraluminal impedance technique (IMP). Infants with recurrent regurgitation or respiratory symptoms suggestive of apnea were investigated simultaneously with IMP, pH monitoring, and polygraphy. IMP patterns, pH, oronasal flow, and chest wall movement were recorded and analyzed. In 22 infants, 364 GER episodes were recorded by IMP. One hundred and sixty five apneas were documented by visual validation of polygraph records. Forty-nine apneas (29.7%) were associated with GER; 11 (22.4%) of these showed acid reflux (pH < 4). A significant correlation between the time spent apneic and GER was found (P < 0.001). There is marked association between apnea and gastroesophageal reflux in infants. Patients potentially at risk cannot be reliably identified by pH metry. Its exclusive use is therefore not suitable for the detection of all GER-associated apneas in infants. The pH-independent intraluminal impedance technique has proven to be a sensitive diagnostic tool for this approach.

Intraluminal impedance: an ideal technique for evaluation of pediatric gastroesophageal reflux disease.

Gastroesophageal reflux (GER) in infants becomes gastroesophageal reflux disease (GERD) through association with distinct clinical symptoms. Monitoring of pH is considered the standard diagnostic tool through which episodes of acidity can be detected. Apparently, however, the major amount of GER occurs in the physiologic esophageal pH range, which is concealed to pHmetry. Intraluminal impedance is a new method for pH-independent detection of esophageal bolus movement. Long-term measurements and combination with other diagnostic methods, e.g., pHmetry or polygraphic recordings, are possible. Intraluminal impedance has proved especially useful in diagnosing GER and GERD in infants. It may develop into the ideal technique for this group of patients.

Procedure for the semi-automatic detection of gastro-oesophageal reflux patterns in intraluminal impedance measurements in infants.

The diagnosis of gastro-oesophageal reflux (GOR) is of great interest for paediatric gastroenterologists. pH monitoring is the commonly used procedure for GOR diagnosis but a major amount of postprandial GOR is missed due to the mostly non-acidic gastric contents in infants. The multiple intraluminal impedance technique is based on the recording of the impedance changes during bolus transport inside the oesophagus. It is the first method which allows the pH-independent, long-term registration of GOR. The use of the impedance technology in clinical practice has been limited so far by the time-consuming, visual evaluation of the impedance traces. The new approach of a semi-automatic analysis of the impedance measurements allows the automated detection of reflux patterns. It is based on event marking and an optimised feature description of the impedance traces combined with a fuzzy system for pattern recognition. The classifier is developed and tested on 50 investigations in infants. Compared to the comprehensive, multiple visual evaluation the achieved precision is 75% sensitivity and 48% positive prediction. In comparison to a single visual evaluation the analysis of the automatically proposed patterns corresponds to a 96% reduction of the evaluation time with no loss of precision. Thus the applicability of the impedance technology is enhanced significantly. A combined measurement of pH and impedance gives evidence about the occurrence of GOR, its pH and the acidic exposure of the oesophagus.

Gastroesophageal reflux and respiratory phenomena in infants: status of the intraluminal impedance technique.

BACKGROUND: The coincidence of recurrent respiratory symptoms and gastroesophageal reflux (GER) is a well-known phenomenon in infants. Twenty-four-hour pH metry is the presumed gold standard of diagnostic tools for this symptom complex, but with this method, only acid (pH <4) and alkaline (pH >7) GER can be detected. Gastroesophageal reflux with an esophageal pH in the physiological range (pH 5-6.8) may represent many cases of clinically relevant GER unrecognized by pH metry. In this study the intraluminal multiple electrical impedance (IMP) procedure for complete registration of GER was compared with pH metry for its diagnostic value in the presence of respiratory symptoms. METHODS: Twenty-two infants with recurrent regurgitation or pulmonary problems were investigated simultaneously with IMP, pH metry, and polygraphy during two feeding periods. Heart rate, oxygen saturation, sleep states, and oronasal flow were recorded, among other parameters. RESULTS: Three hundred sixty-four occurrences of GER were detected by IMP; only 11.4% had a pH less than 4 and were therefore recognized by pH metry. Three hundred twelve (84.8%) occurrences were associated with breathing abnormalities, and 11.9% of these were detected by pH metry. Nineteen instances were accompanied by a decrease of oxygen saturation of more than 10% of the initial value. Only three (15.8%) of these had a pH less than 4. The remaining 16 reflux episodes were recognized by IMP only. After software-aided preselection, 165 instances of apnea were visually validated, 49 of which were accompanied by GER. Thirty-eight (77.6%) of these were exclusively recorded by IMP. CONCLUSIONS: The use of pH metry alone cannot detect most GER incidents accompanied by respiratory symptoms and therefore does not appear to be suitable for this approach. The pH-independent IMP technique promises to be a reliable tool for presumably GER-associated respiratory symptoms.

Pharmacokinetics of oral fluconazole in premature infants.

UNLABELLED: Systemic infections with Candida albicans in neonates are a frequent and well recognized problem. The therapeutic gold standard in this situation is the combined intravenous antimycotic treatment with amphotericin B and flucytosine. Potential adverse effects of this regimen have encouraged the search for desirable alternatives. We report on the use of oral fluconazole in neonates with Candida albicans septicaemia. Three premature infants were treated with four courses of therapy. Pharmacokinetic studies were performed during each course. At oral doses of 4.5-6 mg/kg once a day, serum levels of fluconazole were within the therapeutic range during the entire dosage interval. Follow up showed microbiological and clinical cure in all patients with no side-effects. In one patient a dosage of 4 mg/kg per day lead to a microbiological relapse with sub-therapeutic serum levels. CONCLUSIONS: Oral fluconazole seems to be a safe and effective treatment for Candida albicans septicaemia even in premature infants.