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B T Cooper

Publications and source records attributed to B T Cooper.

At least 19 recordsLinked to original sources

Measurement of small intestinal permeability markers, lactulose, and mannitol in serum: results in celiac disease.

To date, tests of small intestinal passive permeability have involved the ingestion of test molecules whose permeation is assessed indirectly by measuring their urinary recovery. Excretion ratios of marker molecules (eg, lactulose-to-mannitol excretion ratio, LMER) are useful clinically. Measurement of permeability markers in serum would improve the convenience of the tests. Our aim was to assess small intestinal permeability in celiac patients using serum lactulose and mannitol levels with calculation of lactulose to mannitol serum ratios (LMSR) and to compare the results with the standard methods using urinary recoveries. Twenty-four newly diagnosed celiacs and 10 control subjects were studied; 10 celiacs were restudied while established on a gluten-free diet. Test subjects and patients ingested 10 g lactulose and 2.5 g mannitol in 50 ml water. In 10 untreated celiacs and the controls, blood was taken from 0 to 120 min and all urine was collected for 6 hr. The remaining 14 untreated and the 10 treated celiacs had a single serum sample taken 60 min after ingestion of the test solution. At 1 hr after ingestion, the mean mannitol level in normals (0.156 mmol/liter) was significantly higher than in untreated celiacs (0.06 mmol/liter). The 1-hr mean serum lactulose level in normals (0.125 micromol/liter) was significantly lower than in untreated celiacs (0.56 micromol/liter). The median 1-hr LMSR in untreated celiacs was 0.42 compared with 0.039 in normals and 0.08 in treated celiacs. There was a significant correlation between LMSR and LMER. Permeability testing using serum measurements of lactulose and mannitol gave comparable results in celiac patients to the tests using urinary recovery of the permeability markers and may prove to be more convenient, especially in pediatric patients.

Adolescent

Sucrosemia in untreated celiac disease: a potential screening test.

During studies to develop serum tests of small intestinal permeability, we detected an unidentified disaccharide in HPLC traces of sera from untreated celiacs. This present study aimed to identify the disaccharide and determine whether the presence of the disaccharide in the serum after an oral challenge had potential as a simple screening test for celiac disease. The disaccharide was identified as sucrose by incubation studies of sera with disaccharidases. Twenty untreated celiacs, 15 treated celiacs, and 20 normal or dyspeptic controls were studied for the presence of sucrose in their serum after an oral load (8 g). The results in celiacs were compared with the presence of serum IgA endomysial antibodies. The 10 normal controls were also given a larger sucrose challenge (50 g). Ten of the untreated celiacs and 10 controls had their brush border disaccharidase activities measured. Sucrose eluted in the same position as the unidentified disaccharide in the HPLC trace and the latter could be removed by incubation with sucrase. All untreated celiacs but none of the treated celiacs had sucrose in their serum after the 8-g oral challenge. None of the controls had sucrose in their serum after the 8-g or 50-g challenges. Three untreated celiacs were IgA endomysial antibody negative as were all the treated cases. Brush border sucrase activity was low in untreated celiac disease. The presence of sucrose in the serum after an oral load shows promise as a noninvasive test for celiac disease.

Adult

Incidence of duodenal ulcer healing after 1 week of proton pump inhibitor triple therapy for eradication of Helicobacter pylori. The Lansoprazole Helicobacter Study Group.

BACKGROUND: A number of clinical studies have assessed the efficacy of short-term twice-daily Helicobacter pylori eradication regimens but few have investigated the proportion of patients in whom duodenal ulcer disease was healed with these regimens. AIM: To compare the safety and efficacy of four 1-week H. pylori eradication regimens in the healing of H. pylori associated duodenal ulcer disease. METHODS: Following endoscopic confirmation of duodenal ulcer disease and a positive CLO test, patients underwent a 13C-urea breath test to confirm H. pylori status. Treatment with one of four regimens: LAC, LAM, LCM or OAM, where L is lansoprazole 30 mg b.d., A is amoxycillin 1 g b.d., M is metronidazole 400 mg b.d., C is clarithromycin 250 mg b.d., and O is omeprazole 20 mg b.d., was assigned randomly to those patients who were H. pylori positive, with 62 (LAC), 64 (LAM), 61 (LCM) and 75 (OAM) patients in each treatment group. Follow-up breath tests and endoscopies were performed at least 28 days after the end of treatment. RESULTS: Duodenal ulcer disease was healed 28 days after treatment in 53/62 (85.5%) patients who were treated with LAC, 52/64 (81.3%) of patients treated with LAM, 49/61 (80.3%) of patients treated with LCM and 60/75 (80.0%) of patients treated with OAM (intention-to-treat analysis, n = 262, assumed unhealed if no follow-up endoscopy was performed). All the treatments were of similar efficacy (P = 0.85, chi-squared test) with regard to the healing of duodenal ulcer disease. CONCLUSIONS: The four 1-week treatment regimens were equally effective in healing H. pylori associated duodenal ulcer disease.

2-Pyridinylmethylsulfinylbenzimidazoles

Continuous treatment with omeprazole 20 mg daily for up to 6 years in Barrett's oesophagus.

BACKGROUND: Because of the malignant potential of Barrett's oesophagus, an aim of treatment is to cause the columnar epithelium to regress. A logical approach is to decrease acid reflux which is an important aetiological factor in Barrett's oesophagus. Treatment with omeprazole 20-80 mg over 1-3 years has yielded conflicting but largely disappointing results. AIM: To determine if treatment of Barrett's oesophagus with omeprazole 20 mg daily for up to 6 years can cause regression of the Barrett's epithelium. PATIENTS AND METHODS: Forty-seven patients with Barrett's oesophagus were treated in an open prospective study. Nine patients were treated for 2 years, 12 for 3 years, 10 for 4 years, eight for 5 years and eight for 6 years. Patients were endoscoped at 1-2-year intervals and endoscoped at the end of the treatment period. RESULTS: No significant shortening of the length of the Barrett's segment was seen during any treatment period, although omeprazole controlled reflux symptoms and was well tolerated. Macroscopic squamous islands appeared in 55% of patients, mostly in the first 2-3 years although in five patients they appeared later in treatment. CONCLUSION: Treatment of Barrett's oesophagus with omeprazole 20 mg daily for periods of up to 6 years did not cause regression in the length of the Barrett's segment, but it did lead in over half of the patients to partial re-epithelialization in the form of squamous islands.

Adult

Lactase haplotype frequencies in Caucasians: association with the lactase persistence/non-persistence polymorphism.

A genetic polymorphism is responsible for determining that some humans express lactase at high levels throughout their lives and are thus lactose tolerant, while others lose lactase expression during childhood and are lactose intolerant. We have previously shown that this polymorphism is controlled by an element or elements which act in cis to the lactase gene. We have also reported that 7 polymorphisms in the lactase gene are highly associated and lead to only 3 common haplotypes (A, B and C) in individuals of European extraction. Here we report the frequencies of these polymorphisms in Caucasians from north and south Europe and also from the Indian sub-continent, and show that the alleles differ in frequency, the B and C haplotypes being much more common in southern Europe and India. Allelic association studies with lactase persistence and non-persistence phenotypes show suggestive evidence of association of lactase persistence with certain alleles. This association was rather more clear in the analysis of small families, where haplotypes could be determined. Furthermore haplotype and RNA transcript analysis of 11 unrelated lactase persistent individuals shows that the persistence (highly expressed) allele is almost always on the A haplotype background. Non-persistence is found on a variety of haplotypes including A. Thus it appears that lactase persistence arose more recently than the DNA marker polymorphisms used here to define the main Caucasian haplotypes, possibly as a single mutation on the A haplotype background. The high frequency of the A haplotype in northern Europeans is consistent with the high frequency of lactase persistence.

Alleles

An analytical method for the quantitation of mannitol and disaccharides in serum: a potentially useful technique in measuring small intestinal permeability in vivo.

An electrochemical-HPLC method for the determination of mannitol and lactulose is presented which may facilitate routine testing of intestinal permeability by requiring only a single blood sample instead of a 6-hour urine collection. Chromatographic conditions are described which allow separation of the closely related sugars lactulose and the dietary disaccharides lactose and sucrose. Preliminary results in normal controls and patients with untreated coeliac disease are presented.

Adult

Severe hepatitis E infection during pregnancy.

In areas with endemic hepatitis E virus (HEV), acute liver failure secondary to hepatitis E infection is common in pregnancy and associated with a mortality rate of up to 20%. However, there is little information on the clinical course of severe hepatitis E infection during pregnancy in non-endemic areas such as the UK. Here we describe two cases of severe hepatitis E in pregnancy in patients returning from the Indian subcontinent. These cases were diagnosed by the detection of IgM anti-HEV antibody using an enzyme immunoassay with recombinant hepatitis E viral antigens. The first case describes acute hepatic failure, with coagulopathy and encephalopathy, warranting intensive therapy and elective ventilation. In the other case, the patient had severe hepatitis with coagulopathy. Both cases spontaneously resolved with no foetal loss. These cases highlight the need for suspicion of HEV infection in patients returning from endemic areas and presenting with acute non-A non-B hepatitis, especially when pregnant. Furthermore, the intensive treatment of acute liver failure caused by HEV may reduce the high mortality reported in Asia.

Adult

One week triple therapy for Helicobacter pylori: a multicentre comparative study. Lansoprazole Helicobacter Study Group.

BACKGROUND: Eradication of Helicobacter pylori cures and prevents the relapse of duodenal ulceration and also results in histological resolution of chronic active gastritis. AIM: To compare four treatment regimens lasting seven days of a proton pump inhibitor and two antibiotics in the eradication of H pylori. PATIENTS: Men or women with H pylori positive duodenal ulceration or gastritis, or both. METHODS: A single blind, prospectively randomised, parallel group, comparative, multicentre study. After a positive CLO test, patients underwent histology, H pylori culture, and a 13C urea breath test to confirm H pylori status. Treatment with one of four regimens: LAC, LAM, LCM, or OAM, where L is 30 mg of lansoprazole twice daily, A is 1 g of amoxycillin twice daily, M is 400 mg of metronidazole twice daily, C is 250 mg of clarithromycin twice daily, and O is 20 mg of omeprazole twice daily, was assigned randomly. A follow up breath test was done at least 28 days after completing treatment. RESULTS: H pylori eradication (intention to treat) was 104/121 (86.0%) with LAC, 87/131 (66.4%) with LAM, 103/118 (87.3%) with LCM, and 94/126 (74.6%) with OAM. There was a significant difference (p < 0.001) in the proportion of patients in whom eradication was successful between LAC and LCM when compared with LAM, but no significant difference (p = 0.15) between LAM and OAM. Metronidazole resistance before treatment was identified as a significant prognostic factor with regard to eradication of H pylori. The regimens which contained metronidazole were significantly less effective than those without metronidazole in the presence of pretreatment resistant H pylori. There was no difference among the treatment groups with regard to the incidence and severity of adverse events reported. CONCLUSIONS: All four treatment regimens were safe and effective in eradicating H pylori in the patient population studied. LAC was the most efficacious treatment in patients with pretreatment metronidazole resistant H pylori, and was significantly better than LAM and OAM in this group of patients.

2-Pyridinylmethylsulfinylbenzimidazoles

Lansoprazole versus ranitidine in the maintenance treatment of reflux oesophagitis.

AIMS: To assess the relative efficacies of lansoprazole 15 mg once daily, lansoprazole 30 mg once daily and ranitidine 300 mg b.d. in the maintenance treatment of reflux oesophagitis for 12 months. METHODS: Multicentre, out-patient, double-blind, parallel group, prospectively randomized clinical trial. Patients with grade 0, asymptomatic oesophagitis after 8 weeks of treatment with lansoprazole 30 mg once daily were randomized to receive lansoprazole 30 mg once daily (L30) (n = 75), lansoprazole 15 mg once daily (L15) (n = 86) or ranitidine 300 mg b.d. (R600) (n = 74) for 12 months. Endoscopy was repeated at 6 and 12 months, and symptomatic assessment was made every 3 months. Efficacy was primarily assessed by the time to endoscopically confirmed relapse (oesophagitis grade > or = 1) and the proportion of patients who relapsed during the 12-month study period. Severity of symptoms were secondary efficacy measures. RESULTS: For all patients randomized with at least one post-baseline endoscopy (intent-to-treat principle) both lansoprazole 15 mg (P < 0.001) and lansoprazole 30 mg (P < 0.001) were significantly superior to ranitidine 600 mg with respect to time to endoscopic relapse. There was no difference between the lansoprazole groups (P = 0.11). There was evidence of relapse in 27 of 86 (31.4%), 15 of 75 (20.0%) and 50 of 74 (67.6%) of the patients treated with lansoprazole 15 mg and 30 mg and ranitidine 600 mg, respectively. Patients receiving treatment with either lansoprazole dosages experienced significantly less severe heartburn and regurgitation than those patients treated with ranitidine. There were no differences between the treatment groups with respect to the severity or incidence of adverse events. No clinically significant laboratory changes were observed in any of the treatment groups. Serum gastrin levels were elevated in all treatment groups, and most markedly in those patients receiving lansoprazole, but there was no significant difference between the treatments. Morphological and immunohistochemical examination of the gastric biopsies revealed no clinically relevant changes from baseline in any of the treatment groups. CONCLUSION: Both lansoprazole 15 mg and lansoprazole 30 mg once daily are significantly more effective than high-dose ranitidine in maintaining reflux oesophagitis in remission.

2-Pyridinylmethylsulfinylbenzimidazoles

Small intestinal permeability to mannitol and lactulose in the three ethnic groups resident in west Birmingham.

BACKGROUND/AIMS: Asymptomatic residents of tropical countries have differences in small intestinal morphology and permeability compared with residents of temperate zones. The aim of this study was to investigate small intestinal permeability and morphology in three ethnic groups resident in Birmingham, UK. METHODS: 28 white patients, 101 Indian (Indian subcontinent), and 49 Afro-Caribbean adult patients with dyspepsia had endoscopic distal duodenal biopsies and a hyperosmolar lactulose/mannitol permeability test. Twenty normal white subjects had the permeability test. RESULTS: Lactulose/mannitol excretion ratios (LMER) were: white subjects 0.022 (median), white patients 0.022, Indians 0.031, Afro-Caribbeans 0.033. Differences between the immigrant groups and the two white groups were significant (p < 0.001); 33% of Indians and 45% of Afro-Caribbeans had LMER outside the range of the white groups. Afro-Caribbeans born in the UK had significantly lower LMER than those born abroad (p < 0.05); a similar trend was seen in Indians. Villous height/mucosal thickness ratios, calculated from small intestinal biopsy specimens, were lower in the immigrant groups and correlated inversely with LMER (r = 0.28; p < 0.05). Time resident in the tropics also correlated inversely with LMER. CONCLUSIONS: There were significant differences in small intestinal permeability and morphology between immigrants resident in a Western country and the native white population. The data suggested that these differences were related to environmental factors.

Adolescent

Effect of water-loading on the performance of polyethylene glycol as a marker of small intestinal permeability.

1. Polyethylene glycol has been used extensively to measure small intestinal permeability in vivo. However, polyethylene glycol seems to traverse the intestinal mucosa in much greater quantities than sugar molecules of equivalent M(r). In addition, the recovery of the lowest M(r) polymers of administered polyethylene glycol has been found to be both low and unreliable. 2. To compare the behaviour of a range of polyethylene glycol polymers with sugar probes in vivo, a combined polyethylene glycol/mannitol/lactulose probe was administered sequentially to healthy individuals in the fasted state and under conditions of water-loading. Timed hourly urine collections were made for 6 h. 3. Mannitol and lactulose recoveries were all within the normal range and were unaffected by co-administration of water. The lactulose/mannitol recovery ratios did not vary significantly over the 6 h collection period. In contrast, the recovery of total polyethylene glycol was significantly greater when subjects were water-loaded. Furthermore, proportionally greater quantities of polyethylene glycol M(r) 370 than M(r) 854 were recovered towards the end of the collection period than at the start. 4. Our results show that, in contrast to lactulose and mannitol, excretion of low-medium M(r) polyethylene glycol polymers is highly dependent on co-administration of water. Furthermore, the differential rate of excretion of the low compared with the high M(r) polyethylene glycol polymers suggests that the volume of distribution of the individual polymers may vary with M(r), and smaller polyethylene glycol molecules may undergo considerable renal tubular reabsorption.

Adult

Long term continuous omeprazole treatment of patients with Barrett's oesophagus.

BACKGROUND: The metaplastic columnar epithelium in Barrett's oesophagus has malignant potential. AIM: To determine whether decreasing acid reflux leads to regression of Barrett's epithelium. METHOD: Twenty-four patients with Barrett's oesophagus were treated with omeprazole 20 mg o.m. in an open, prospective study; 11 were treated for 12 months, and 13 for 24 months. Another group of 17 patients with Barrett's oesophagus was treated with an H2-receptor antagonist in standard dosage for 12-36 (mean 23) months. Patients were assessed endoscopically. RESULTS: No evidence of significant shortening of the length of Barrett's oesophagus was seen in any patient treated for 12 or 24 months with omeprazole. Similarly, no shortening of the length of Barrett's oesophagus was seen in any patient treated with an H2-receptor antagonist. However, 6 of 11 patients treated with omeprazole for 12 months, and 7 of 13 treated for 24 months, developed macroscopic squamous islands visible below the squamo-columnar junction. This was not seen in any patient treated with an H2-receptor antagonist. CONCLUSION: Although there can be reappearance of squamous epithelium in Barrett's oesophagus of some patients during treatment with omeprazole 20 mg o.m. over 12-24 months, a significant shortening of the columnar lined segment is not seen.

Adult

Endoscopy and computed tomography in the diagnosis and follow up of oesophageal leiomyoma.

Leiomyoma of the oesophagus, although the commonest benign oesophageal tumour, is still rare compared with malignant tumours of the oesophagus. Leiomyomas of the oesophagus are usually diagnosed on barium swallow or histological examination after section. Five cases of leiomyoma of the oesophagus are reported where diagnosis was made by the combination of barium swallow, upper gastrointestinal endoscopy, and computed tomography and all but one patient were followed up for one to four years. The endoscopic biopsy specimens were non-specific in all five patients but none showed any evidence of malignancy. None of the five patients had a history of dysphagia. This paper describes a conservative approach to medical treatment in asymptomatic oesophageal leiomyoma rather than surgical excision as commonly published. It also emphasises the importance of negative endoscopic pinch biopsy specimens and the role of computed tomography in the diagnosis of oesophageal leiomyoma.

Biopsy, Needle

Symptomatic cardiomyopathy as a presentation in Whipple's disease.

A patient presenting with congestive cardiac failure and anaemia underwent investigation which led to the diagnosis of Whipple's disease, associated with dilated cardiomyopathy. Conventional antibiotic therapy for Whipple's disease resulted in resolution of the traditional features of Whipple's disease and a marked improvement in the patient's heart failure.

Aged