Seasonal recurrence of food bolus obstruction in eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is a newly recognised condition that is apparently increasing in prevalence, and the aetiology is poorly understood. The role of aeroallergens in EoE is controversial, given the success of dietary therapy. Massive aeroallergen exposure leading to food bolus obstruction events (FBOE) has been described, and the diagnosis of EoE by esophageal biopsy noted to be more common in the pollen season according to previous case series. AIM: To determine if a seasonal variation and a geographical variation occurred in EoE presenting as FBOE in adults, and to track the prevalence of FBOE and EoE over time. METHOD: A retrospective case-control study analysis was performed from January 2002 to January 2012 to identify all FBOE in adults presenting to five tertiary hospitals in Melbourne, Australia. Endoscopy, histopathological reports, case notes and blood tests were examined, and postcodes recorded. Records of pollen counts were obtained. Cases were defined according to esophageal biopsy and grouped based on month of diagnosis. All other causes of FBOE served as controls. RESULTS: One thousand, one hundred and thirty-two FBOE were identified. Biopsies were only performed in 278 of these cases, and 85 patients were found to have EoE after biopsy. Patients with EoE were younger (mean age 38 years, range 18-72) compared with those with alternative diagnosis (mean age 64.4 range 22-92), more likely to be male (M : F = 4:1 compared with 1.68:1 ) and had a higher eosinophil count in venous blood. Overall no seasonality was demonstrated in FBOE secondary to any diagnosis, although the six cases of recurrent FBOE secondary to EoE mainly occurred in the grass pollen season in subsequent years. FBOE cases were evenly distributed throughout metropolitan Melbourne irrespective of population density. EoE as a percentage of FBOE increased over time. CONCLUSION: Seasonal aeroallergens may be important for a subgroup of patients with EoE presenting as recurrent FBOE. Esophageal biopsies are performed in a minority of patients, representing a significant departure from ideal management and contributing to recurrent unnecessary FBOE. EoE is an increasingly important cause of FBOE.

Risk factors for eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic antigen driven disease, whereby food and/or aeroallergens result in inflammation and luminal narrowing, and the clinical symptoms of dysphagia and food bolus obstruction events (FBOE). Established risk factors are male gender, Caucasian race and atopy. Increased risk amongst family members, and a single nucleotide polymorphism (SNP) in a gene coding thymic stromal lymphopoietin (TSLP) on the pseudoautosomal region of the X and Y chromosomes supports a genetic predisposition. Environmental factors including the timing and nature of food and aeroallergen exposure to the developing immune system may be important, whilst esophageal barrier function integrity and the influence of microbiota are worthy of future research.

Drug-induced gastrointestinal disorders.

Drug-induced gastrointestinal disorders can mimic conditions, such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) and, hence, recognition can prevent unnecessary investigations and treatment. While the knowledge and awareness relating to the adverse gastrointestinal effects of some medications, such as non-steroidal anti-inflammatory drugs are well established, other commonly prescribed drugs, such as antipsychotics, antidepressants and metformin are less well understood and warrant further study. This review attempts to integrate recent information regarding adverse drug reactions and place this in a useful clinical context.

Allergy tests do not predict food triggers in adult patients with eosinophilic oesophagitis. A comprehensive prospective study using five modalities.

BACKGROUND: The use of allergy tests to guide dietary treatment for eosinophilic oesophagitis (EoE) is controversial and data are limited. Aeroallergen sensitisation patterns and food triggers have been defined in Northern Hemisphere cohorts only. AIMS: To determine if allergy tests that are routinely available can predict food triggers in adult patients with EoE. To define the food triggers and aeroallergen sensitisation patterns in a novel Southern Hemisphere (Australian) cohort of patients. METHODS: Consecutive patients with EoE who elected to undergo dietary therapy were prospectively assessed, demographic details and atopic characteristics recorded, and allergy tests, comprising skin-prick and skin-patch tests, serum allergen-specific IgE, basophil activation test and serum food-specific IgG, were performed. Patients underwent a six-food elimination diet with a structured algorithm that included endoscopic and histological examination of the oesophagus a minimum of 2 weeks after each challenge. Response was defined as <15 eosinophils per HPF. Foods defined as triggers were considered as gold standard and were compared with those identified by allergy testing. RESULTS: No allergy test could accurately predict actual food triggers. Concordance among skin-prick and serum allergen-specific IgE was high for aeroallergens only. Among seasonal aeroallergens, rye-grass sensitisation was predominant. Food triggers were commonly wheat, milk and egg, alone or in combination. CONCLUSIONS: None of the currently-available allergy tests predicts food triggers for EoE. Exclusion-rechallenge methodology with oesophageal histological assessment remains the only effective investigation. The same food triggers were identified in this southern hemisphere cohort as previously described.

A prospective open clinical trial of a proton pump inhibitor, elimination diet and/or budesonide for eosinophilic oesophagitis.

BACKGROUND: Elimination diets and high-dose proton pump inhibitors (PPI) are advocated as first-line treatments in patients with eosinophilic oesophagitis (EoE). AIM: To record the treatment outcome for patients with EoE prospectively managed according to a clinical algorithm. METHODS: Patients with oesophageal eosinophilia commenced esomeprazole 40 mg twice daily for 8 weeks. Those in histological remission were re-classified as PPI-responsive oesophageal eosinophilia. Nonresponders were offered the 6-food elimination diet with a PPI, or topical budesonide monotherapy (1 mg orally twice daily as an aqueous gel). Once disease control was achieved remission was reassessed at 3 months (all modalities) and an additional 6 months (diet group). RESULTS: Of 107 patients who completed 8 weeks of PPI, 25 (23%) were PPI-responsive. 56 of 81 (69%) of patients with EoE chose the elimination diet with PPI. 29 (52%) had complete remission, 23 completed dietary reintroduction and food triggers were identified in 20 (36%). 25 chose budesonide with 23/25 (92%) responding. Remission was sustained in >85% of patients at 3 months with all treatment modalities. At 9 months, only 10/18 (55%) of patients who responded to the elimination diet with PPI remained complaint and sustained remission. CONCLUSIONS: Many patients previously diagnosed with EoE will respond to PPI. Initial response >50% is possible with the elimination diet plus PPI, but many will fail to undergo food reintroduction, or will cease the diet and relapse, resulting in only one in four patient sustaining remission at 9 months. Budesonide is very effective short term, but longer term study is needed.

Dyspepsia in the community is linked to smoking and aspirin use but not to Helicobacter pylori infection.

BACKGROUND: The relationship between Helicobacter pylori infection and symptoms remains controversial. We aimed to determine if an association exists between unexplained dyspepsia (pain or discomfort centered in the upper part of the abdomen) and H pylori. METHODS: A validated questionnaire was completed by 592 healthy blood donors. Helicobacter pylori serologic values (via enzyme-linked immunosorbent assay), blood group status, and Rh status were measured; 4.9% of subjects who had a history of peptic ulcer disease were excluded from the analyses. RESULTS: The prevalence of dyspepsia and no ulcer history was 11% (95% confidence interval [CI], 8.6%-13.8%); 15.4% of subjects with dyspepsia had H pylori while 14.6% of subjects without dyspepsia were infected (P=.90). The mean dyspepsia impact scores (combining frequency and severity) in those with and without H pylori were 4.7 and 5.4, respectively (P=.20). The median H pylori optical density values in dyspepsia vs no dyspepsia were not significantly different (P=.30). Independent risk factors for dyspepsia were the use of aspirin (odds ratio [OR], 2.2; 95% CI, 1.3-3.7) and smoking (OR, 2.1; 95% CI, 1.3-3.6) but not age, sex, marital status, educational level, income, or the use of alcohol, coffee, or nonsteroidal anti-inflammatory drugs. Independent risk factors for H pylori were increasing age (OR, 1.8 per decade; 95% CI, 1.5-2.3), male sex (OR, 2.1; 95% CI, 1.3-3.4), and net family income (OR, 1.8; 95% CI, 1.2-3.3). CONCLUSION: Dyspepsia in the community is linked to smoking and aspirin use, but not to H pylori infection.

Relationship between body mass index, diet, exercise and gastro-oesophageal reflux symptoms in a community.

BACKGROUND: Body mass index (BMI) is a risk factor for gastro-oesophageal reflux but may simply be explained by diet and lifestyle. AIM: We aimed to determine the contribution of BMI, diet and exercise to GER. METHODS: Community subjects (n = 211, mean age = 36 years, 43% males) completed validated questionnaires on gastro-oesophageal reflux, energy expenditure (Harvard Alumni Activity Survey), dietary intake (Harvard Food Frequency Questionnaire) and measures of personality and life event stress. Diet, exercise, BMI and other potential risk factors for reflux were analysed using logistic regression analyses. RESULTS: The overall mean (+/- s.d.) BMI was 26.6 (+/- 5.7); 79 (37%) reported infrequent (< weekly) reflux and 16 (8%) reported frequent (> or = weekly) reflux. The median caloric intake was 2097 cal/day and the median daily energy expenditure was 1753 cal/day. Among those with BMI > 25, 10% reported frequent reflux compared to 4% of those with BMI < or = 25. In a model which included age, sex and Symptom Checklist-90 somatisation T-score, BMI was associated with reflux (OR per 5 units = 1.9, 95% CI: 1.2, 3.0). In models which included diet and exercise variables, BMI but not diet or exercise was associated with reflux. CONCLUSION: BMI may be associated with symptomatic gastro-oesophageal reflux independent of diet and exercise.

The Case Western Reserve University hybrid gait orthosis.

Six individuals with paraplegia and injury levels from C-1 through T-12 participated in a study to evaluate the functional capabilities of a hybrid gait orthotic system. Subjects learned to use a custom-built reciprocal gait orthosis without stimulation and with electrical stimulation activating between 4 and 16 muscles. Outcomes were scored with standard physical therapy measures including the Tinetti test, a timed get up and go, Borg rating of perceived exertion, and the Functional Index Measure (FIM). Subjects have successfully accomplished sit to stand, stand to sit, and walking maneuvers measured for time, speed, and distance. Metabolic consumption was measured for walking in the light work region of 5.1 to 6.5 metabolic equivalents (METs) 1 MET = 3.5 ml of O2/kg/min with hybrid gait orthosis. Perceived exertion as measured with the Borg scale indicated that use of the bracing system with functional electrical stimulation was "easier" than without stimulation. Subjects using a hybrid system were able to walk up to 350 m at average speeds of 0.25 m/s. Walking speeds for 30- and 50-meter distances reached 0.45 m/s. Additionally, walking distances with stimulation were 2 times greater than those of non-stimulated reciprocal gait. FIM scores indicated that system users would become slightly more independent in mobility. Results were used to determine the most useful brace modifications for the next generation of Case Western Reserve University hybrid gait orthoses to allow an expanded function that will include stair climbing and side stepping.

Drug-induced gastrointestinal disorders.

Drug-induced gastrointestinal disorders can mimic conditions, such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) and, hence, recognition can prevent unnecessary investigations and treatment. While the knowledge and awareness relating to the adverse gastrointestinal effects of some medications, such as non-steroidal anti-inflammatory drugs are well established, other commonly prescribed drugs, such as antipsychotics, antidepressants and metformin are less well understood and warrant further study. This review attempts to integrate recent information regarding adverse drug reactions and place this in a useful clinical context.

Physiology of diffuse esophageal spasm (DES)--when normal swallows are not normal.

BACKGROUND: Diffuse esophageal spasm (DES) is characterized on manometry by a combination of simultaneous contractions and normal swallows. The aim of this study was to examine the manometric characteristics of simultaneous and 'normal' swallows in patients with DES patients compared with normal controls. METHODS: Manometric studies from 69 patients with DES and 20 controls were analysed to determine the proportion of normal, hypertensive, ineffective and simultaneous contractions, and the velocity of propagation along the esophagus, the duration and amplitude of contraction and the relaxation characteristics (nadir and duration) of the lower esophageal sphincter. KEY RESULTS: The propagation velocity was the only significant difference between normal swallows and simultaneous contractions in DES patients (middle third: 49.2 VS 101.2 mm s(-1), P ≤ 0.001 lower third: 44.1 VS 88.7 mm s(-1), P ≤ 0.001). 'Normal' swallows in patients with DES had a greater velocity of propagation than those in age-matched control subjects (middle third: 49.2 VS 37.0 mm s(-1), P = 0.02, lower third: 44.1 VS 23.3 mm s(-1), P ≤ 0.001). CONCLUSIONS & INFERENCES: As expected, simultaneous contractions of DES patients differ from 'normal' swallows in DES patients mainly regarding the velocity of propagation of contraction but are similar in amplitude, however 'normal' swallows of DES patients are also more rapidly propagated along the esophagus than normal swallows of a control group suggesting that all swallows in DES are affected to some degree by the same process.

Clinical trial: the treatment of gastro-oesophageal reflux disease in primary care--prospective randomized comparison of rabeprazole 20 mg with esomeprazole 20 and 40 mg.

BACKGROUND: A trial of empirical PPI therapy is usual practice for most patients with symptoms of gastro-oesophageal reflux disease (GERD) in primary care. AIM: To determine if the 4-week efficacy of rabeprazole 20 mg for resolving heartburn and regurgitation symptoms is non-inferior to esomeprazole 40 mg or 20 mg. METHODS: In all, 1392 patients were randomized to rabeprazole 20 mg, esomeprazole 20 mg or 40 mg once daily. Patients, doctors and assessors were blinded. Symptom resolution data were collected on days 0-7 and day-28 using the Patient Assessment of Upper Gastrointestinal Disorders Symptom Severity Index with a shortened version used on days 8-27. RESULTS: Rabeprazole 20 mg was non-inferior to esomeprazole 40 mg for complete resolution of regurgitation and satisfactory resolution of heartburn and regurgitation. For complete heartburn resolution, the efficacy of rabeprazole 20 mg and esomeprazole 40 mg was statistically indistinguishable, although the non-inferiority test was inconclusive. Rabeprazole 20 mg was non-inferior to esomeprazole 20 mg for all outcomes. CONCLUSIONS: In uninvestigated GERD patients, rabeprazole 20 mg was non-inferior to esomeprazole 40 mg for complete and satisfactory relief of regurgitation and satisfactory relief of heartburn, and not different for complete resolution of heartburn.

Measurement of faecal fat excretion: an evaluation of attitudes and practices of Australian gastroenterologists.

BACKGROUND: Although faecal fat excretion over 72 h is the gold standard for quantifying fat malabsorption, there has been a push from chemical pathology laboratories to discontinue this test, arguing that it is unreliable and of limited clinical value. AIMS: To assess attitudes, knowledge and practices of Australian gastroenterologists in relation to the test and to gauge opinion as to whether it should remain available. METHODS: A self-administered questionnaire was developed to assess attitudes towards, patterns of use and understanding of 72-h faecal fat collections. This was posted to all members of the Gastroenterological Society of Australia. RESULTS: Of 429 eligible gastroenterologists, 124 (29%) responded. Eighty-two per cent utilized the test; 62% at least once per year. Main indications were suspected steatorrhoea (55%), unexplained chronic diarrhoea (39%) or weight loss (29%). Thirty-eight per cent ordered the test to determine stool volume. Only 26% attempted to appropriately fat load patients and approximately half did not recognize the potential influence of medications and stool volume. This was also reflected in poor interpretation of results in specific clinical scenarios. Of those who use the test at least once per year, 97% wanted its continued availability and 51% felt their practice would be significantly affected if the test was discontinued. CONCLUSIONS: Although continued availability of 72-h faecal fat estimation is supported by many Australian gastroenterologists, the test appears to be often performed and interpreted suboptimally. Rather than discard the test, efforts should more appropriately be directed to improving baseline knowledge to ensure its optimal performance and interpretation.

Barrett's esophagus: the long and the short of it.

Specialized intestinal epithelium occurs more frequently at the gastroesophageal junction than previously anticipated. It can occur either within tongues of mucosa (short segment Barrett's) or just beneath a normal z-line (intestinal metaplasia at the gastroesophageal junction). Whether the etiopathogenesis and the natural history of these two conditions are the same is as yet unclear. The role of gastroesophageal reflux disease (GERD), Helicobacter pylori, and inflammation at the gastroesophageal junction in the pathogenesis of short segment Barrett's and intestinal metaplasia at the gastroesophageal junction needs to be carefully documented. Intestinal metaplasia at the gastroesophageal junction, short segment Barrett's, and Barrett's may represent a continuum of the same disease process. Recent evidence suggests, however, that short segment Barrett's shares similar characteristics with Barrett's but may be distinct from intestinal metaplasia at the gastroesophageal junction. It is conceivable that short segment Barrett's may remain steady or even regress if and when the noxious influence wanes but, with continuing stimulation, short segment Barrett's may lengthen further to become what we observe to be Barrett's. If correct, endogenous or exogenous factors that induce progression need to be identified. Acid and bile reflux and H. pylori are possible candidates acting either singly or synergistically. Finally, the true neoplastic potential of short segment Barrett's needs clarification.

Epidemiology and natural history of reflux disease.

Gastro-oesophageal reflux disease (GORD) is a highly prevalent condition in Western countries; at least 20% of the population have weekly symptoms. The incidence appears to be rising in the West and in some developing countries. Heartburn, based on a carefully elicited history, is reasonably specific for identifying GORD if it is a predominant complaint. Symptoms, however, appear to correlate poorly with oesophagitis; hence, severe symptoms do not indicate there is greater oesophageal damage. Only one-third to one-half of patients with GORD undergoing endoscopy have oesophagitis. GORD is usually a chronic disease but one-third may lose their symptoms over time. An ill-defined subset of patients over time may progress to develop abnormal acid exposure or oesophagitis, or both, when none existed at baseline. GORD has a significant negative impact on quality of life to the same degree as other chronic medical conditions, but impairment in quality of life is independent of oesophagitis.

Percutaneous implantation of iliopsoas for functional neuromuscular stimulation.

Hip flexion is required for walking and stair climbing. Percutaneous electrical stimulation of the iliopsoas muscle is a potentially useful and reliable method of providing hip flexion in individuals who are paralyzed. In this study, groin, lateral abdominal, and paraspinal approaches of percutaneous electrode implantation for electrical stimulation of the iliopsoas muscle are described. The paraspinal approach using stimulation of the second and third lumbar roots gave the best hip flexion response; however, it often was accompanied by unwanted stimulation of the hip adductor and abdominal muscles. Wire breakage and electrode movement were the most common causes for failure of maintaining hip flexion. The paraspinal approach, using double helix electrodes, provided an average of 110 weeks of functional hip flexion sufficient for walking. It is feasible to implant electrodes in the iliopsoas muscle. An open technique for permanent implantation of intramuscular electrodes is being developed to selectively stimulate the iliopsoas, which will extend the range and duration of hip flexion that will allow stair climbing in individuals who are paraplegic.

Esophageal histology does not provide additional useful information over clinical assessment in identifying reflux patients presenting for esophagogastroduodenoscopy.

We prospectively evaluated the value of histology in identifying gastroesophageal reflux disease (GERD) in consecutive patients enrolled for upper endoscopy. GERD was defined as heartburn occurring at least weekly. Macroscopic esophagitis was graded and an esophageal biopsy was taken 2 cm above the gastroesophageal junction. Histological esophagitis was identified by: (1) basal cell hyperplasia >15%, (2) increased papillary length >66%, and (3) infiltration by leukocytes/eosinophils. The sensitivity, specificity, and positive and negative predictive value of histological esophagitis in patients with and without typical reflux symptoms, with and without endoscopic changes, or both were evaluated. Of 178 patients, reflux symptoms were present in 59% (N = 105) and esophageal erosions in 19% (N = 34); 75 patients had reflux symptoms but no erosions. While the specificity of histology was adequate (78%), it was insensitive (30%). The positive and negative predictive values were 67% and 44%, respectively. No single individual parameter was better than any other. Thus, histology appears to be of no additional value in identifying GERD.