A prospective randomised trial of a "test and treat" policy versus endoscopy based management in young Helicobacter pylori positive patients with ulcer-like dyspepsia, referred to a hospital clinic.

BACKGROUND: Management of dyspepsia remains a controversial area. Although the European Helicobacter pylori study group has advised empirical eradication therapy without oesophagogastroduodenoscopy (OGD) in young H pylori positive dyspeptic patients who do not exhibit alarm symptoms, this strategy has not been subjected to clinical trial. AIMS: To compare a "test and treat" eradication policy against management by OGD. PATIENTS: Consecutive subjects were prospectively recruited from open access OGD and outpatient referrals. METHODS: H pylori status was assessed using the carbon-13 urea breath test. H pylori positive patients were randomised to either empirical eradication or OGD. Symptoms and quality of life scores were assessed at baseline and subsequent reviews over a 12 month period. RESULTS: A total of 104 H pylori positive patients aged under 45 years were recruited. Fifty two were randomised to receive empirical eradication therapy and 52 to OGD. Results were analysed using an intention to treat policy. Dyspepsia scores significantly improved in both groups over 12 months compared with baseline; however, dyspepsia scores were significantly better in the empirical eradication group. Quality of life showed significant improvements in both groups at 12 months; however, physical role functioning was significantly improved in the empirical eradication group. Fourteen (27%) in the empirical eradication group subsequently proceeded to OGD because of no improvement in dyspepsia. CONCLUSIONS: This randomised study strongly supports the use of empirical H pylori eradication in patients referred to secondary practice; it is estimated that 73% of OGDs in this group would have been avoided with no detriment to clinical outcome.

The effect of treating reflux oesophagitis with omeprazole on quality of life.

BACKGROUND/AIMS: Despite the commonplace nature of heartburn and reflux oesophagitis, little is known of their impact on patients' quality of life. The aim of this study was to assess quality of life in oesophagitis patients before and after medical therapy and compare the results with a sample of the general population. METHODS: Consecutive attenders with frequent heartburn and grade II-III oesophagitis on endoscopy were recruited from one of two centres and treated with omeprazole 20 mg BD for 8-14 weeks. A symptomatic questionnaire, including the Short Form-36 (SF-36) quality of life questionnaire, was completed before and at the end of treatment. Actual quality of life scores were compared with 'expected' scores derived from a sample (n = 3015) of the Northern Ireland population. RESULTS: Seventy two (83%) of the 87 patients recruited were healed after 14 weeks therapy and 77 completed the SF-36 before and after therapy. Three quality of life parameters (bodily pain, vitality and social function) were significantly lower before treatment than the 'expected' scores. Seven of the quality of life parameters measured by the SF-36 showed a significant improvement after treatment and the eighth (mental health) just failed to achieve a significant improvement (P = 0.06). Comparison of the improvements in SF-36 scores for those who were healed with scores for those who were not healed showed no significant difference. CONCLUSIONS: Patients with grade II-III oesophagitis and frequent heartburn have lower quality of life scores for some parameters than would be expected in the general population. Treatment of the oesophagitis with omeprazole 20 mg BD causes a significant improvement not just in reflux symptoms but in several physical and mental aspects of quality of life regardless of whether or not the oesophagitis is healed.

Three- to 4.5-year prospective study of prognostic indicators in gastro-oesophageal reflux disease.

BACKGROUND: Data on the long-term natural history of gastro-oesophageal reflux disease (GORD) are sparse. This prospective study was designed to determine the clinical outcome on the basis of therapeutic requirements 3 to 4.5 years after initial diagnosis of GORD and to identify specific prognostic indicators of a poor outcome. METHODS: One hundred and one GORD patients were followed up by symptomatic questionnaire 3 to 4.5 years after diagnosis and offered repeat investigation with endoscopy and oesophageal pH monitoring if symptoms persisted. RESULTS: Seventy-seven (76%) patients responded (mean follow-up period, 39 months; range, 32-54 months); of these, 28 had grade-II or -III oesophagitis at initial endoscopy, 17 had normal endoscopy but abnormal pH monitoring, and 32 had normal investigations but frequent heartburn. At follow-up 32 (42%) were taking acid suppression therapy, and a further 15 patients started acid suppression therapy after repeat investigation indicated a need to do so, giving a total of 47 (61%) patients receiving acid suppression. The following factors predicted a need for acid suppression at follow-up: oesophagitis on initial endoscopy (P = 0.009), abnormal pH monitoring (P = 0.0005), increased age (P < 0.0005), and increased body mass index (BMI) (P = 0.001). Gender, smoking status, alcohol intake, and lower oesophageal sphincter pressure had no prognostic value. Regression analysis confirmed that age (P = 0.0007), BMI (P = 0.04), and endoscopy result (P = 0.04) all independently affected outcome. CONCLUSIONS: Most GORD patients still require acid suppression therapy 3 to 4.5 years after initial diagnosis. Age, BMI, and presence of oesophagitis at initial endoscopy all independently predict those who will require long-term acid suppression therapy.

Rapid serological diagnosis of Helicobacter pylori: a need for caution and re-evaluation.

Screening for Helicobacter pylori in dyspeptic patients may improve selectivity for gastroscopy. Rapid serological tests based on ELISA technique are cheap, readily available and simple to use in the clinical setting. However local evaluation is essential in order to validate these techniques. Fifty-six dyspeptic patients (aged less than 45 yr) had a rapid serological test (Helisal) performed prior to gastroscopy. At gastroscopy H. pylori status was assessed using culture and histology. The Helisal sensitivity was 80 per cent, specificity 82 per cent. Screening patients with the Helisal test would have missed 6 patients with peptic ulcer disease and 2 with oesophagitis. The Helisal test did not perform satisfactorily as a screening test in selection of patients for gastroscopy.

The effect of healing oesophagitis on oesophageal motor function as determined by oesophageal scintigraphy and ambulatory oesophageal motility/pH monitoring.

BACKGROUND: Oesophagitis has been shown by standard manometry to be associated with impaired oesophageal motility, but it remains unclear if this abnormality improves with healing of oesophagitis. AIM: To determine if healing of oesophagitis improves oesophageal motility using solid bolus oesophageal transit scintigraphy and combined ambulatory oesophageal motility/pH monitoring. METHODS: Patients with grade II-III oesophagitis underwent ambulatory motility/pH monitoring (using a Konigsberg catheter with four pressure transducers at 5 cm intervals) and solid bolus scintigraphy before and after treatment with omeprazole 20 mg b.d. for 8-14 weeks. RESULTS: Three (11%) of the 28 patients failed to heal. Initial scintigraphy was abnormal in 18 (67%) of 27 patients (one refused scintigraphy). Twenty-three of the 25 healed patients had repeat studies showing no significant change in the number which were abnormal (16 (64%), P = 1.0) or the overall oesophageal transit time (P = 0.65). Due to intolerance of the technique, only 11 patients had ambulatory motility/pH performed both before and after healing, giving the study 90% power to detect a 5 mmHg increase in peristaltic amplitude. No significant improvement was seen in any motility or pH parameter after healing of oesophagitis. CONCLUSION: Analysis of oesophageal motility showed no improvement in peristaltic activity after healing of oesophagitis, suggesting that the abnormal motility is either a primary disorder or an irreversible consequence of mucosal damage.

Casein kinase 2 phosphorylation of recombinant rat osteopontin enhances adhesion of osteoclasts but not osteoblasts.

Osteopontin (OP) is a highly phosphorylated bone matrix protein and contains the RGD cell-binding motif, which mediates cell adhesion through integrin receptors that include alpha(v)beta3. Casein kinase 2 (CK2) is a factor-independent serine/threonine kinase, which may be the predominant physiologically relevant kinase for OP phosphorylation. This study was designed to examine the effects of unphosphorylated recombinant rat OP, and CK2-phosphorylated OP (P-OP), on the adhesion and function of mouse osteoclasts (OC) and osteoblast-like cells (UMR 201-10B and UMR 106-06) in vitro. OP significantly increased OC adhesion compared to plastic alone, and cell attachment was further increased at least twofold on OP phosphorylated with CK2. Attachment was dependent on the integrity of the RGD domain and was completely abolished in the presence of 1 mM RGD peptide. Neither CK2 phosphorylation of mutant OP, in which the RGD was converted to RGE or RAD, nor protein kinase C (PKC) phosphorylation of wild-type OP enhanced OC attachment. An antibody to the beta3 integrin subunit, but not anti-mouse CD44 antibody, specifically blocked the proportion of attachment due to phosphorylation of OP. Actin ring formation in OC was increased by plating cells onto OP, with no further increase by phosphorylation. Both OP and CK2-phosphorylated OP enhanced attachment of the two osteoblastic cell lines, compared to plastic, but in contrast to OCs, there was no significant difference with phosphorylation. Osteoblast attachment was totally blocked by 1 mM RGD peptide, but was not influenced by the beta3 integrin antibody. Plating of UMR 201-10B cells onto OP further increased retinoic acid-induced alkaline phosphatase expression. The results suggest that specific phosphorylation of OP is important for interaction with OCs, compared with osteoblastic cells, and that alternative integrins may be important in the interaction between osteoblastic cells and OP compared with OCs.

The breath test--a call for more regional use.

OBJECTIVE: Although the 13C-urea breath test is commonly used for detection of Helicobacter pylori infection and eradication, access to commercial testing centres for analysis may at times limit its use. We have addressed this issue by establishing a regional-based means of analysis as a Hospital-University collaboration. DESIGN/METHODS: A blind comparison was undertaken of 13C-urea breath test results performed 'in house' by the stable isotope laboratory in Queen's University Belfast and a commercially available 13C-urea breath test. RESULTS: The H. pylori status of the patients (n = 110) agreed for all patients (kappa score = 1). The excess values showed good agreement. The cost of the 'in house' breath test was less than 20 pounds compared with 32.90 pounds for the commercial breath test. CONCLUSION: Regional access to the 13C-urea breath test could decrease costs, increase availability of testing, improve local health services and economy and increase collaborative research opportunities.

Maintenance therapy with cisapride after healing of erosive oesophagitis: a double-blind placebo-controlled trial.

BACKGROUND: There are few data on the role of prokinetic agents as maintenance therapy in moderately severe reflux oesophagitis despite the high relapse rate of this condition after healing. AIMS: To determine whether cisapride is more effective than placebo as maintenance therapy after healing of moderate erosive oesophagitis in two respects: first, in preventing symptomatic relapse and preserving quality of life; and, second, in improving oesophageal motor function. PATIENTS: Forty-two patients whose grade II-III oesophagitis had been healed with omeprazole were randomized to receive either cisapride 20 mg nocte or placebo for 6 months. Oesophageal pH monitoring and manometry were performed before starting maintenance therapy and after 4 weeks, and symptomatic status and quality of life were assessed at weeks 0, 4, 13 and 26. RESULTS: After 4 weeks of maintenance therapy, lower oesophageal sphincter pressure improved in the cisapride group (16.4-21.9 mmHg, P = 0.01) but not in the placebo group (25.5-22.7 mmHg, P = 0.2). Oesophageal pH monitoring showed no significant changes in either group. Sixteen (76%) cisapride patients and 12 (57%) placebo patients withdrew within 4 weeks owing to symptomatic relapse (P = 0.2). After 26 weeks, 21 (100%) cisapride and 17 (81%) placebo patients had relapsed (log-rank analysis of survival time P = 0.07). Quality of life parameters deteriorated in both treatment groups to a similar degree. CONCLUSION: Maintenance therapy with cisapride 20 mg nocte improves the lower oesophageal sphincter pressure in patients whose oesophagitis has been healed with omeprazole. However, cisapride is no better than placebo in preventing symptomatic relapse or deterioration in quality of life.

Disease progression in gastro-oesophageal reflux disease as determined by repeat oesophageal pH monitoring and endoscopy 3 to 4.5 years after diagnosis.

OBJECTIVES: Reflux oesophagitis may progress to complications such as Barrett's mucosa and stricture formation. However, few studies have assessed long-term disease progression in oesophagitis patients and fewer still have considered disease progression in the significant proportion of gastro-oesophageal reflux disease (GORD) patients who do not have oesophagitis at diagnosis. The aim of this study was to reassess GORD patients 3 to 4 years after initial diagnosis and determine whether or not disease progression had occurred. METHODS: Prospective follow-up of 101 GORD patients at least 32 months after initial assessment with oesophageal pH monitoring and upper gastrointestinal endoscopy. Patients were invited to complete a symptomatic questionnaire and undergo repeat investigation with the same techniques. RESULTS: Seventy-seven (76%) patients responded (mean follow-up period 39 months, range 32-54 months) of whom 28 initially had oesophagitis (group A), 17 had normal endoscopy but abnormal pH monitoring (group B) and 32 had normal investigations but typical reflux symptoms (group C). At the time of follow-up, 57 (74%) patients either had frequent heartburn or were taking daily acid suppression therapy. Fifty-two (68%) responders had at least one repeat investigation: 44 (57%) had repeat pH monitoring; 43 (56%) had repeat endoscopy. Three (11% of the 28 responders) group A patients had developed Barrett's mucosa, 4 (24% of responders) group B patients had developed oesophagitis and 10 (31% of responders) group C patients had developed abnormal pH monitoring (4), oesophagitis (4) or both (2). CONCLUSION: Three-quarters of GORD patients still have troublesome symptoms at least 3 years after diagnosis and a significant proportion show endoscopic progression of the condition's severity.

Natural history of reflux oesophagitis: a 10 year follow up of its effect on patient symptomatology and quality of life.

BACKGROUND: Although oesophagitis is the most common diagnosis made at upper gastrointestinal endoscopy, data on the longterm outcome of affected patients are sparse. AIMS: This study assessed the level of reflux symptoms, quality of life, drug consumption, and complications in patients at least 10 years after diagnosis of oesophagitis at one centre. PATIENTS: One hundred and fifty two patients with typical reflux symptoms and a first time diagnosis by endoscopy of grade I-III oesophagitis between 1981 and 1984, were followed up using a postal questionnaire and telephone interview. RESULTS: Eighteen of 152 patients had died, 33 failed to respond, and 101 replied (mean follow up 11 years, range 121-160 months). Over 70% of patients still had heartburn at least daily (32%) or weekly (19%) or required daily acid suppression treatment (20%). Two patients (2%) had developed oesophageal strictures and one had Barrett's oesophagus. Two of eight quality of life scores (physical function and social function) measured by the Short Form-36 were significantly lower than Northern Ireland population scores. CONCLUSION: Nearly three quarters of patients previously diagnosed as having oesophagitis still had significant morbidity related to gastro-oesophageal reflux disease more than 10 years after diagnosis. Some quality of life scores were significantly lower than those of the general population.

Effect of acute stress on oesophageal motility in patients with gastro-oesophageal reflux disease.

BACKGROUND AND AIM: Sixty four per cent of people with heartburn believe that it is exacerbated by stress. An alteration in oesophageal motility is one possible mechanism for this apparent change with stress. This study aimed to assess the effect of acute stressors on oesophageal motility in patients with gastro-oesophageal reflux disease (GORD). METHODS: Sixty patients were studied. Twenty had oesophagitis, 20 had increased oesophageal acid exposure on pH monitoring but no endoscopic oesophagitis, and 20 had neither oesophagitis nor abnormal oesophageal acid exposure. Oesophageal motility was studied in these patients during psychological stress (Stroop test) and physical stress (cold pressor test). RESULTS: Blood pressure (BP) and heart rate increased in response to both stressors (mean systolic BP increased by > 10 mm Hg, diastolic BP by > 4 mm Hg and heart rate by > 3 beats per minute (p < 0.00001). The amplitude, duration, and velocity of propagation of oesophageal peristaltic contractions were not altered by the stressors. The percentage of simultaneous waves increased in patients with oesophagitis during the cold pressor test (median increase in these patients was 6% (p < 0.05)). This effect was not noted in the patients without oesophagitis. CONCLUSION: Acute stressors did not induce significant changes in oesophageal motility in patients with GORD but no oesophagitis. For these patients, dysmotility is not likely to be a cause of oesophageal symptoms which are exacerbated by stress. There was, however, a significant increase in simultaneous waves during cold pressor stress in patients with oesophagitis.

The application of microridge analysis in the diagnosis of gastro-oesophageal reflux disease.

BACKGROUND: The percentage of epithelial surface area covered by microridges (%MR) seen during scanning electron microscopy of oesophageal biopsy specimens has previously been shown to correlate with symptomatic reflux disease, a result < or = 35% being abnormal. The aim of this study was to compare %MR with endoscopy, light microscopy, and pH monitoring results. METHODS: Sixty-seven patients with heartburn were divided into oesophagitis or none on the basis of endoscopy and light microscopy findings and into those with and without abnormal acid reflux on the basis of pH monitoring. RESULTS: The endoscopic and light microscopic oesophagitis groups had significantly greater degrees of acid reflux than those without oesophagitis (p < 0.05), even though neither the specific %MR nor the number of patients below the 35% cutoff showed any difference between those with and without endoscopic oesophagitis, light microscopic oesophagitis or those with normal and abnormal acid reflux on pH monitoring. CONCLUSION: Despite the significant relationship between endoscopic and light microscopic oesophagitis and abnormal pH monitoring microridge analysis did not correlate with any of these variables

Elemental diet in the treatment of pneumatosis coli.

BACKGROUND: Pneumatosis cystoides coli (PCC) is a rare condition characterized by gas-filled cysts in the bowel wall. Our aim was to assess the response of PCC to treatment with an elemental diet. METHODS: Two patients with PCC were treated with an elemental diet. Both patients had experienced debilitating symptoms for at least a year and were unresponsive to other therapies. Elemental 028 comprises readily absorbed amino acids, fats, simple sugars, minerals, vitamins, and trace elements. After colonoscopically documented resolution at 2 weeks, low-residue foods were gradually added to the diet. RESULTS: Both patients' symptoms disappeared within 3-4 days of commencing the diet, and colonoscopy at 2 weeks confirmed complete resolution of the cysts. One patient relapsed with the introduction of high-residue foods and was again controlled within days by recommencing the elemental diet. CONCLUSION: An elemental diet can successfully treat both the initial presentation of PCC and any subsequent relapse.

Chronic suppurative lung disease with associated vasculitis.

We report a patient with chronic bronchiectasis who developed systemic vasculitis. The patient was initially treated with immunosuppression; however, the addition of antibiotic therapy improved control of her vasculitis and the need for immunosuppression was reduced. Chronic bronchial suppuration may have an aetiological role in the pathogenesis of this condition.

Acid perception in gastro-oesophageal reflux disease is dependent on psychosocial factors.

BACKGROUND: Our aim was to contrast the psychosocial profiles of patients with gastro-oesophageal reflux disease whose symptoms correlate well with acid reflux against those whose symptoms do not. METHODS: One hundred and one patients presenting with heartburn for the first time underwent oesophageal pH monitoring, and 82 (81%) experienced symptoms during the recording. On the basis of how well their symptoms correlated with acid reflux, patients were divided into symptom-positive and symptom-negative groups. These two groups were then compared on the basis of four questionnaires looking at different psychosocial factors. RESULTS: Symptom-negative patients displayed significantly higher levels of trait anxiety (44.5 versus 38.7; p < 0.05) and hysteria (5.6 versus 4.1; p < 0.05). The adequacy of their social support structures was significantly lower (6.2 versus 7.3; p < 0.05). No difference in daily hassles or uplifts was found. CONCLUSION: Significant psychosocial differences are noted in patients with poor symptom-reflux correlation. These differences may help explain the aetiology of such patients' symptoms.

Are esophageal symptoms reflux-related? A study of different scoring systems in a cohort of patients with heartburn.

OBJECTIVE: To assess three different methods of correlating symptoms with episodes of acid reflux in gastroesophageal reflux disease. METHODS: One hundred and one consecutive patients with heartburn were recruited. Patients were divided into those with and those without endoscopic esophagitis. Three different symptom indices were used, one of which was based on the binomial formula. It took into account not only the ratio of acid-related symptoms to all symptoms, but also the quantity of acid reflux. RESULTS: There was complete agreement between all three indices in 78% of the patients. All three indices were positive significantly more often (p < 0.001) in patients with esophagitis than in patients with no esophagitis. CONCLUSIONS: All indices gave similar results. The binomial symptom index offers theoretical advantages, but a prospective study of response to acid suppression would be required to evaluate further its merits.

A comparison of esophageal motility in response to bread swallows and water swallows.

Studies of esophageal manometry during eating have demonstrated abnormal motility in patients with dysphagia in whom standard water-swallow manometry was normal. However, there have been few concurrent motility studies making a direct comparison of food swallows with water swallows. This paper presents the results of such a study in 20 healthy volunteers. A comparison of bread swallows with water swallows revealed that both peristaltic amplitude in the proximal esophagus and peristaltic duration throughout the esophagus were significantly increased (p < 0.05). Peristaltic propagation velocity was significantly decreased in the proximal and mid-esophagus (p < 0.05). Percentages of nonconducted and nonperistaltic contractions were significantly increased (p < 0.05-0.001) during bread-swallow manometry. Therefore, the response of the normal esophagus to food has been shown to be different from its response to water swallows. In particular, the high percentage of nonpropagated swallows in normal subjects when eating indicates that the results of food manometry in patients with dysphagia must include wider limits of normality.