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Biomedical subjects

P W Keeling

Publications and source records attributed to P W Keeling.

At least 19 recordsLinked to original sources
PubMed2001

Impact of cortisol on buspirone stimulated prolactin release: a double-blind placebo-controlled study.

Buspirone is known to stimulate prolactin release. Clinical studies (e.g. in chronic fatigue syndrome) suggest that the response may be influenced by baseline cortisol levels. We conducted a double-blind placebo-controlled study to examine the relationship between the prolactin response to buspirone challenge and baseline cortisol level. Fifty healthy volunteers took part in the study. Buspirone was found to consistently elevate PRL levels above those seen following placebo administration. The PRL response as measured by area under the curve was highly correlated with the baseline cortisol level.

Adult↗
PubMed2001

Potential impact of magnetic resonance cholangiopancreatography on endoscopic retrograde cholangiopancreatography workload and complication rate in patients referred because of abdominal pain.

BACKGROUND AND STUDY AIMS: Endoscopic retrograde cholangiopancreatography (ERCP) has a significant mortality, morbidity, and failed cannulation rate. Magnetic resonance cholangiopancreatography (MRCP) is a safer, noninvasive method of imaging the pancreaticobiliary tree. A substantial number of patients are referred for ERCP because of abdominal pain, a high proportion of whom have normal ducts or pathology not requiring interventional ERCP. The aim was to assess the potential impact of MRCP on overall ERCP workload and patient outcome if MRCP were the primary investigation in patients referred for ERCP because of abdominal pain. PATIENTS AND METHODS: 1758 consecutive ERCPs performed in 1148 patients over a 3-year period in a single tertiary referral center in the pre-MRCP era were reviewed. Cannulation failure, ERCP findings, need for follow-up ERCP and all 30-day major complication rates were analyzed with regard to clinical indications. RESULTS: The overall workload comprised 1108 (63 %) successful initial ERCPs, 188 (11 %) failed cannulation attempts and 462 (26 %) follow-up ERCPs. Of the patients, 299 (27 %) had normal ERCP findings, 331 (30 %) had choledocholithiasis and 246 (22 %) had strictures. lf MRCP had been used as the primary imaging investigation in the 451 patients (39 %) referred for ERCP because of abdominal pain, we estimate that 197 patients (44 %) would have avoided ERCP, and the overall ERCP workload would have been reduced by 13 %. Initial MRCP in suspected gallstone pancreatitis and certain miscellaneous groups, it was estimated, would have further decreased ERCP workload by 9 %. Four of 40 major ERCP-related complications (3.5 %) and one of four ERCP-related deaths (0.35 %) would potentially have been avoided. CONCLUSIONS: Initial MRCP in patients referred with abdominal pain would potentially have avoided ERCP in 44 % of cases, reduced ERCP workload by 13 % and significantly reduced patient morbidity and mortality. The relatively small reduction in ERCP workload among these patients reflects the fact that over half of them had probable sphincter dysfunction, a significant proportion of whom might have benefited from biliary manometry and/or endoscopic intervention despite a normal MRCP. Furthermore, a small number of patients with calculi and subtle biliary and pancreatic strictures would be missed by this approach.

Abdominal Pain↗
PubMed2000

High multidrug resistance (P-glycoprotein 170) expression in inflammatory bowel disease patients who fail medical therapy.

BACKGROUND & AIMS: The multidrug resistance (MDR) gene codes for a drug efflux pump P-glycoprotein 170 (Pgp-170) expressed on the surface of lymphocytes and intestinal epithelial cells. Inflammatory bowel disease (IBD) poorly responsive to medical therapy may relate to MDR expression because glucocorticoids are known Pgp-170 substrates. METHODS: Using flow cytometry, we measured peripheral blood lymphocyte (PBL) MDR in 153 IBD patients and 50 healthy volunteers, and assessed the relationship between PBL, mucosal intraepithelial lymphocyte (IEL), and mucosal epithelial cell (EC) MDR expression in a further 20 IBD patients and 19 controls. RESULTS: Compared with controls, PBL MDR was significantly elevated in patients with Crohn's disease who required bowel resection for failed medical therapy (mean +/- SEM, 26.7 +/- 2.8 vs. 11.9 +/- 1.0; P <0.0001) and patients with ulcerative colitis who required proctocolectomy for failed medical therapy (20.3 +/- 2.5 vs. 11.9 +/- 1.0; P = 0.001). PBL MDR remained stable over time and was not influenced by disease activity or glucocorticoid therapy. Both PBL and mucosal MDR expression appeared independent of disease activity, and there was a significant correlation between PBL MDR expression and both IEL expression (r = 0.92; P < 0.0001) and EC expression (r = 0.54; P < 0.001). CONCLUSIONS: PBL and mucosal MDR expression may play an important role in determining the response of IBD patients to glucocorticoid therapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Randomized comparison of unfractionated heparin with corticosteroids in severe active inflammatory bowel disease.

BACKGROUND: Heparin therapy may be effective in steroid resistant inflammatory bowel disease. AIM: A randomized pilot study, to compare unfractionated heparin as a first-line therapy with corticosteroids in colonic inflammatory bowel disease. METHODS: Twenty patients with severe inflammatory bowel disease (ulcerative colitis, n=17; Crohn's colitis, n=3) were randomized to either intravenous heparin for 5 days, followed by subcutaneous heparin for 5 weeks (n=8), or high-dose intravenous hydrocortisone for 5 days followed by oral prednisolone 40 mg daily, reducing by 5 mg per day each week (n=12). After 5 days, non-responders in each treatment group were commenced on combination therapy. Response to therapy was monitored by: clinical disease activity (ulcerative colitis: Truelove and Witt Index; Crohn's colitis: Harvey and Bradshaw Index), stool frequency, serum C-reactive protein and alpha1 acid glycoprotein, endoscopic and histopathological grading. RESULTS: The response rates were similar in both treatment groups: clinical activity index (heparin vs. steroid; 75% vs. 67%; P=0.23), stool frequency (75% vs. 67%; P=0.61), endoscopic (75% vs. 67%; P=0.4) and histopathological grading (63% vs. 50%; P=0.67). Both treatments were well-tolerated with no serious adverse events. CONCLUSION: Heparin as a first line therapy is as effective as corticosteroids in the treatment of colonic inflammatory bowel disease. Large multicentre randomized comparative studies are required to determine the role of heparin in the management of inflammatory bowel disease.

Administration, Oral↗
PubMed2000

Increased incidence of non-Hodgkin's lymphoma in inflammatory bowel disease patients on immunosuppressive therapy but overall risk is low.

BACKGROUND: There is concern that the incidence of non-Hodgkin's lymphoma (NHL) will rise with increasing use of immunosuppressive therapy. AIMS: Our aim was to determine the risk of NHL in a large cohort of patients with inflammatory bowel disease (IBD), and to study the association between IBD, NHL, and immunosuppressive therapy. METHODS: We studied 782 IBD patients (238 of whom received immunosuppressive therapy) who attended our medical centre between 1990 and 1999 (median follow up 8.0 years). Standardised incidence ratios (SIRs) and 95% confidence intervals (CI) were calculated. Expected cases were derived from 1995 age and sex specific incidence rates recorded by the National Cancer Registry of Ireland. RESULTS: There were four cases of NHL in our IBD cohort (SIR 31.2; 95% CI 2.0-85; p=0.0001), all of whom had received immunosuppressive therapy: azathioprine (n=2), methotrexate (n=1), and methotrexate and cyclosporin (n=1). Our immunosuppressive group had a significantly (59 times) higher risk of NHL compared with that expected in the general population (p=0.0001). Three cases were intestinal NHL and one was mesenteric. Mean age at NHL diagnosis was 49 years, mean duration of IBD at the time of NHL diagnosis was 3.1 years, and mean duration between initiation of immunosuppressive therapy and diagnosis of NHL was 20 months. CONCLUSIONS: Although underlying IBD may be a causal factor in the development of intestinal NHL, our experience suggests that immunosuppressive drugs can significantly increase the risk of NHL in IBD. This must be weighed against the improved quality of life and clinical benefit immunosuppressive therapy provides for IBD patients.

Adult↗
PubMed1996

Reflux symptom relief with omeprazole in patients without unequivocal oesophagitis.

BACKGROUND: As many as 50% of patients with reflux symptoms have no endoscopic evidence of oesophagitis. This multicentre study was designed to assess symptom relief after omeprazole 20 mg once daily in patients with symptoms typical of gastro-oesophageal reflux disease but without endoscopic evidence of oesophagitis. METHODS: Patients (n = 209) were randomized in a double-blind study to receive either omeprazole 20 mg once daily (n = 98) or placebo (n = 111) for 4 weeks. Symptoms were assessed at clinic visits and using daily diary cards, with patient-completed questionnaires providing additional data on symptoms and on psychological disturbance. RESULTS: On completion, symptom relief favoured omeprazole: 57% of patients on omeprazole were free of heartburn (vs. 19% on placebo), 75% were free of regurgitation (47%) and 43% were completely asymptomatic (14%), each with P < 0.0001. Fewer patients in the omeprazole group required alginate/antacid relief medication (P < 0.05). Symptom relief (time to first heartburn-free day) was more rapid with omeprazole (2 vs. 5 days on placebo; P < 0.01). A greater reduction in anxiety occurred in the omeprazole group (P < 0.05). CONCLUSION: Omeprazole 20 mg once daily is effective in providing relief of the symptoms typical of gastro-oesophageal reflux disease in patients with essentially normal oesophageal mucosa.

Adult↗
PubMed1996

Carcinoma of the ampulla of Vater: a tumour with a poor prognosis?

OBJECTIVE: To assess the overall prognosis of patients with ampullary carcinomas and evaluate the presentation, diagnosis, pathology and management of these potentially highly curable tumours, attempting to relate these factors to overall survival. PATIENTS AND METHODS: Forty patients with ampullary carcinoma were reviewed. Age, Sex, nature and duration of history, laboratory information at admission, results of diagnostic radiology, endoscopic retrograde cholangiopancreatograms and pathological findings were considered. Both curative and palliative management strategies were reviewed. RESULTS: The overall median survival was 19 months. The median duration of history was 5.9 +/- 5.4. weeks, with no significant difference in survival between patients with short and those with long histories (P = 0.46). Twenty nine (73%) patients were potentially resectable, but only 15 (37%) underwent potentially curative surgery. The difference in survival between the Whipple's (13) and the endoscopically stented (20 ) groups was not significant (p = 0.08). The Whipple's group were significantly younger than the stented group (P = 0.001) and had a significant operative morbidity, re-operation rate (38%) and post-operative mortality (15%). Only five of 13 patients were alive following Whipple's treatment after a mean follow-up of 18.9 months. Sphincterotomy before Whipple's treatment improved survival significantly (P = 0.04); absence of jaundice, exophytic macroscopic appearance, well-differentiated tumours and early stage were also associated with good survival. Endoscopic retrograde cholangiopancreatography has a high diagnostic yield and a low associated morbidity and mortality, with endoscopic papillectomy aiding cannulation while effective palliation was provided through stenting, endoscopic papillectomy and laser debulking of obstructing tumours. Little benefit was obtained from chemoradiotherapy. CONCLUSION: Despite the potential for curative resection in patients with ampullary carcinoma, the majority of such patients are unsuitable for curative surgery on grounds of age, general health status or advanced disease; since only 37% of patients undergo potentially curative surgery the condition has a poor prognosis.

Aged↗
PubMed1996

Helicobacter pylori increases proliferation of gastric epithelial cells.

The direct and indirect effects of helicobacter pylori on cell kinetics of gastric epithelial cell line AGS were investigated by flow cytometric analysis of Ki-67 positive cells and by MTT assay. Flow cytometric analysis of Ki-67 positivity permits detection of cells that are in S-phase, whereas the MTT assay is a colometric measure of the number of viable cells. In the absence of added stimulants, 23.06 (4.88)% mean (SD) of AGS cells were Ki-67 positive. When cells were preincubated in the presence of H pylori, there was a significant increase in Ki-67 positivity (66.20 (7.89)%, p < 0.001). This increase was not seen in cells cultured in the presence of Campylobacter jejuni (24.63 (8.11)% or Escherichia coli (21.66 (9.78)%). Pre-incubation of AGS cells with supernatants from both H pylori and mitogen activated peripheral blood lymphocytes also increased the per cent of cells that were Ki-67 positive (72.93 (8.68) and 69.96 (12.35)%; p, 0.001) respectively. Similar results were also found in MTT assay. These data show that both H pylori directly and the immune/inflammatory response to H pylori indirectly can influence the rate of epithelial cell proliferation, suggesting this bacterium may be an initiating step in gastric carcinogenesis and an important co-carcinogenic factor in H pylori positive subjects.

Antibodies, Monoclonal↗
PubMed1996

Expression of CD44 and its variants on gastric epithelial cells of patients with Helicobacter pylori colonisation.

BACKGROUND: Studies have suggested that expression of the adhesion molecule CD44 may be of prognostic importance in gastric cancer. In addition, there is strong evidence that Helicobacter pylori has a role in gastric cancer. AIMS: To determine the expression of CD44 and its variants (v6, v9) and HLA class II molecules on human gastric epithelial cell and intraepithelial lymphocytes in patients with and without H pylori infection. PATIENTS: Eighteen patients (seven men and 11 women) attending for endoscopic evaluation because of upper gastrointestinal symptoms were included. An additional 10 patients (five men and five women) were analysed for CD44 variant expression). METHODS: Biopsy specimens were taken from the gastric antrum during endoscopy. Gastric epithelial cells and intraepithelial lymphocytes were examined by two colour flow cytometry and compared in patients with and without H pylori infection. RESULTS: Expression of CD44 and its variants (CD44 v9) was increased in epithelial cells but not in intraepithelial lymphocytes. Both epithelial cells and intraepithelial lymphocytes expressed higher levels of HLA class II molecules (DR and DP), possibly as a result of local cytokine production. Furthermore, results showed upregulation of CD44 on a gastric epithelial cell line (AGS) by cytokines and peripheral blood mononuclear cell supernatant. CONCLUSIONS: These data suggest that H pylori, either directly or through a local inflammatory response, is responsible for increased expression of CD44 and its variant CD44 v9. These data are of potential importance in relation to increased expression of CD44 and CD44 v9 on gastric carcinoma.

Adult↗
PubMed1996

Endoscopic papillectomy: a novel approach to difficult cannulation.

BACKGROUND: Selective cannulation of the biliary and pancreatic ducts is considered to be the most difficult and rate limiting aspect of diagnostic endoscopic retrograde cholangiopancreatography (ERCP). AIMS/METHODS: A novel technique for difficult cannulation is described and its potential role in relieving malignant duodenal obstruction secondary to ampullary carcinoma. A diagnostic endoscopic papillectomy was performed in 10 patients in whom previous attempts at cannulation had failed. Five patients had exophytic ampullary carcinomas, one had carcinoma of the head of pancreas, two had an oedematous ampulla secondary to low common bile duct stones, while two had protuberant ampullae with ectopic orifices. The technique entails snaring the ampulla flush with the duodenal wall using a polypectomy snare and in a similar fashion to polypectomy removing the ensnared ampulla with diathermy using a coagulation current. The underlying exposed ducts can then be cannulated while the ensnared ampulla can be retrieved to aid histological diagnosis. RESULTS: Successful cannulation was achieved in all 10 cases with significant haemorrhage in one patient (10%). Four of the snared ampullary carcinomas (80%) were retrieved enabling a histological diagnosis to be made. CONCLUSIONS: This study demonstrates the potential role for endoscopic papillectomy as a means of cannulation in difficult circumstances, however larger comparative studies are required.

Aged↗
PubMed1996

Eating patterns in functional dyspepsia: a case control study.

OBJECTIVE: To determine whether eating patterns differ between patients with endoscopically determined functional dyspepsia and non-dyspeptic controls. DESIGN: Case-control study (50 per group). A seven-day record of food consumption with time of food consumption was determined. SETTING: Endoscopy clinic, St. James' Hospital and the Clinical Nutrition Laboratory at the Trinity College Medical School. MAIN OUTCOME MEASURES: Meal eating pattern and their temporal distribution; consumption of food categories and their temporal distribution; data for all subjects and for employed vs unemployed subjects. RESULTS: There was no evidence to suggest that the pattern of food and meal intake throughout the day was in any way influenced by endoscopically determined functional dyspepsia. CONCLUSION: The widely held belief that patients with functional dyspepsia eat differently to healthy controls to relieve or prevent symptoms of dyspepsia is not supported by these findings.

Adult↗
PubMed1995

Effect of IL-4 on peripheral blood lymphocyte proliferation: implication in immunopathogenesis of H. pylori infection.

Interleukin (IL) 4 is a type 2 cytokine which has a negative immunoregulatory role in human infection. IL-4 suppresses the production of interferon-gamma and enhances IL-10 synthesis. However, the effect of IL-4 on proliferative response of lymphocytes remains to be elucidated. We have previously reported an increase in production of IL-4 in subjects with Helicobacter pylori (H. pylori) infection. To evaluate whether the increased IL-4 is responsible for the down-regulation of immune responses in H. pylori infection, we observed the proliferative response of peripheral blood lymphocytes (PBL) co-cultured with phythaemagglutinin (PHA) or H. pylori in the presence and absence of added IL-4. As we have previously shown, PHA and H. pylori may increase PBL proliferation (P < 0.001). An increase in PBL proliferation was observed when PBL were co-cultured with PHA (P < 0.001) or H. pylori (P < 0.001) in the presence of IL-4 compared to that in the absence of IL-4. The optimal dose of IL-4 to give maximal lymphocyte proliferation is 50 pg/ml for the PHA-stimulated group or 100 pg/ml for the H. pylori-stimulated group. The data suggest that the increased IL-4 does not directly contribute to suppressed lymphocyte proliferation in H. pylori infection. Further studies will be required to determine the role of IL-4 in other aspects of down-regulation of immune responses in H. pylori infection.

Cells, Cultured↗
PubMed1995

Molecular analysis of Helicobacter pylori populations in antral biopsies from individual patients using randomly amplified polymorphic DNA (RAPD) fingerprinting.

In the present study, randomly amplified polymorphic DNA (RAPD) fingerprinting has been used to analyse multiple single colony isolates of Helicobacter pylori from antral biopsies in an attempt to ascertain whether or not multiple strains are present in individual patients using single biopsy samples. The RAPD fingerprints derived from single colonies obtained from the same biopsy specimen were in all cases indistinguishable. The previously noted heterogeneity between H. pylori strains from different individuals was confirmed. RAPD fingerprinting, combined with a simple method of template preparation, was shown to be an excellent method for H. pylori strain differentiation. The results of this study indicate that the H. pylori population is homogeneous in individual patients at a single gastric site.

Bacterial Typing Techniques↗
PubMed1995

Up-regulation of CD44 and ICAM-1 expression on gastric epithelial cells by H. pylori.

Interaction between lymphocytes and epithelial cells may play a key role in Helicobacter pylori (H. pylori)-associated gastric mucosal inflammation. This interaction process is at least partially mediated by various cell adhesion molecules. The aims of the present study were to assess using flow cytometric analysis whether H. pylori directly or supernatants from H. pylori-activated peripheral blood mononuclear cells (PBMC) can affect the expression of adhesion molecules on the gastric epithelial cell line AGS in vitro. The results showed that resting AGS cells expressed CD44 and ICAM-1. Co-culture of AGS with H. pylori or cytokine-rich supernatants from H. pylori-activated PBMC resulted in up-regulation of expression of CD44 and ICAM-1 on AGS cells. These data suggest that H. pylori directly and indirectly through inflammatory cytokines may contribute to alternations in adhesion molecule expression on gastric epithelial cells. This may be of pathological significance in H. pylori-associated gastric mucosal inflammation and carcinogenesis.

Epithelium↗
PubMed1995

Omeprazole 10 mg or 20 mg once daily in the prevention of recurrence of reflux oesophagitis. Solo Investigator Group.

This study determined the optimal maintenance dose of omeprazole in reflux oesophagitis. One hundred and ninety three patients rendered asymptomatic and healed after four or eight weeks omeprazole were randomised double blind to 10 mg omeprazole once daily (n = 60 evaluable), 20 mg omeprazole once daily (n = 68), or placebo (n = 62) for one year or until symptomatic relapse. Each omeprazole regimen was superior to placebo in preventing both symptomatic relapse (life table analysis, p < 0.001) and endoscopically verified relapse (p < 0.001). At 12 months, the life table endoscopic remission rates (proportions of patients without grade > or = 2 oesophagitis) were: 50% (95% confidence intervals 34 to 66%) with 10 mg omeprazole once daily, 74% (62 to 86%) with 20 mg omeprazole once daily, and 14% (2 to 26%) with placebo. At 12 months, the life table symptomatic remission rates (proportions of patients asymptomatic or with mild symptoms) were: 77% (64 to 89%) with 10 mg omeprazole once daily, 83% (73 to 93%) with 20 mg omeprazole once daily, and 34% (16 to 52%) with placebo. Both 10 mg and 20 mg omeprazole once daily were effective in prolonging the remission of reflux oesophagitis: 10 mg may be appropriate to start longterm treatment, though the existence of a dose response relation means that 20 mg once daily may be effective in patients for whom 10 mg once daily is suboptimal.

Adult↗