Derek Jewell - Academia.edu (original) (raw)

Papers by Derek Jewell

Scandinavian Journal of Gastroenterology, 1979

The lactulose hydrogen breath test has been evaluated as a diagnostic test for small-bowel bacter... more The lactulose hydrogen breath test has been evaluated as a diagnostic test for small-bowel bacterial overgrowth using the 14C-glycocholate breath test for comparison. Twenty-seven patients with suspected bacterial overgrowth and 37 control patients were studied. The lactulose test was positive in 8 out of 9 patients with Subsequently proven bacterial overgrowth, all of whom had positive 14C-glycocholate tests. However, 6 patients with ileal disease or resection had positive 14C-glycocholate tests but negative lactulose tests. subsequent bacteriological study of duodenal juice from these patients was negative. Negative results were obtained by both tests in the remaining 12 patients, none of whom were subsequently shown to have bacterial overgrowth. All 37 control subjects had negative lactulose tests. The lactulose breath test is a simple and promising diagnostic test for the detection of small-bowel bacterial overgrowth and, unlike the 14C-glycocholate test, has the advantage of being able to distinguish bacterial overgrowth from ileal disease.

BMJ, 1980

for designing the activities of daily living assessment unit; the department of medicine (Westem ... more for designing the activities of daily living assessment unit; the department of medicine (Westem General Hospital) for providing office accommodation; and the research staff who worked on the project between 1974 and 1979. We acknowledge the financial support given to the study by the

BMJ, 1972

This interim report on a controlled therapeutic trial of azathioprine in ulcerative colitis deals... more This interim report on a controlled therapeutic trial of azathioprine in ulcerative colitis deals with the first 40 patients to complete a one-year period of maintenance treatment with azathioprine or with dummy tablets. The patients all suffered from classical ulcerative colitis and were in an actual attack of the disease at the time of admission. The attack was treated with a standard corticosteroid regimen and the patients were assigned at random to maintenance treatment with real or dummy azathioprine tablets, using a stratified design. The treatment and control groups were closely similar at the beginning of the trial. The effect of treatment has been assessed on the basis of the number of relapses of the disease occurring during the one-year trial period, supplemented by an assessment of the sigmoidoscopic picture and of the histological findings on serial rectal biopsy. In the patients receiving azathioprine the disease ran a more favourable course than in the control group. After the attack had been treated 11 of the 20 patients on azathioprine were symptom-free throughout the rest of the one-year trial period compared with only 5 out of 20 in the control group. The only three patients classed as failures were all in the control group. These differences just fail to reach conventional levels of statistical significance. Azathioprine is not dramatically successful but may still be a useful addition to the medical treatment of ulcerative colitis, particularly if conventional medical treatment is ineffective and there are reasons for wishing to avoid radical surgery. In the dose used azathioprine was virtually free from undesirable side effects.

BMJ, 1999

Objectives To provide evidence of underdiagnosis of coeliac disease and to describe the main pres... more Objectives To provide evidence of underdiagnosis of coeliac disease and to describe the main presenting symptoms of coeliac disease in primary care. Design Case finding in a primary care setting by testing for coeliac disease by using the endomysial antibody test. Setting Nine surgeries in and around a market town in central England, serving a population of 70 000. Participants First 1000 patients screened from October 1996 to October 1997. Outcome measures Determination of endomysial antibody titre of patients fulfilling the study criteria, followed by small intestine biopsy of those with positive results. Results The 30 patients (out of 1000 samples) with positive results on the endomysial antibody test all had histological confirmation on small intestine biopsy. The commonest mode of presentation (15/30) was anaemia of varying severity. Most patients (25/30) presented with non-gastrointestinal symptoms. Specificity of the endomysial antibody test was 30/30. Conclusions Underdiagnosis and misdiagnosis of coeliac disease are common in general practice and often result in protracted and unnecessary morbidity. Serological screening in primary care will uncover a large proportion of patients with this condition and should be made widely available and publicised. Coeliac disease should be considered in patients who have anaemia or are tired all the time, especially when there is a family history of the disease.

Gut, Mar 1, 1996

Epidemiological studies have shown an increased risk of ulcerative colitis (UC) in non-smokers an... more Epidemiological studies have shown an increased risk of ulcerative colitis (UC) in non-smokers and particularly recent exsmokers. Patients with UC have an increased risk of pouchitis following ileal pouch-anal anastomosis, which may be a manifestation of the original disease susceptibility. The aim of this study was to test the hypothesis that smoking habit may influence the incidence of pouchitis. All patients with a functioning pouch ¢12 Gastroenterology Unit,

The Journal of Immunology

In diseases with a strong association with an HLA haplotype, identification of relevant T cell ep... more In diseases with a strong association with an HLA haplotype, identification of relevant T cell epitopes may allow alteration of the pathologic process. In this report we use a reverse immunogenetic approach to predict possible HLA class II-restricted T cell epitopes by using complete pool sequencing data. Data from HLA-DR2(B1*1501), -DR3(B1*0301), -DQ2(A1*0501, B1*0201), and -DQ8(A1*0301, B1*0302) alleles were used by a computer program that searches a candidate protein to predict ligands with a relatively high probability of being processed and presented. This approach successfully identified both known T cell epitopes and eluted single peptides from the parent protein. Furthermore, the program identified ligands from proteins in which the binding motif of the HLA molecule was unable to do so. When the information from the nonbinding N- and C-terminal regions in the pool sequence was removed, the ability to predict several ligands was markedly reduced, particularly for the HLA-DQ a...

Scandinavian Journal of Gastroenterology, 1995

Expression of adhesion molecules is increased in inflamed colonic mucosa, but little is known abo... more Expression of adhesion molecules is increased in inflamed colonic mucosa, but little is known about their functional activity in vascular endothelium. We studied in situ nitroblue tetrazolium reducing activity and expression of E-selectin, ICAM-1, CD31, and VCAM-1 by immunohistochemistry in the same biopsy specimen in controls and patients with ulcerative colitis (UC). VCAM-1 expression was negative in mucosal vessels. E-selectin-positive vessels were significantly increased in endoscopically active colitis compared with normal mucosa. ICAM-1-positive vessels were consistently found in normal, quiescent UC and active UC. CD31-positive vessels were not significantly increased in quiescent UC and active UC compared with control. Only E-selectin significantly correlated with the histologic grade of inflammation. Nitroblue tetrazolium reducing vessels were increased in inflamed mucosa, and these vessels expressed ICAM-1 and CD31. E-selectin positivity in association with nitroblue tetrazolium reduction was mainly seen in the large mucosal vessels, but capillaries showing nitroblue tetrazolium reduction were rarely positive for E-selectin. Phenotypic and functional activation of vascular endothelium might be involved in the recruitment of leukocytes and tissue destruction of inflamed colonic mucosa.

Clinical Science, 1992

1. Platelet-activating factor is an inflammatory mediator related to eicosanoids which is known t... more 1. Platelet-activating factor is an inflammatory mediator related to eicosanoids which is known to stimulate anion secretion in the distal colon. Since there are regional differences in ion transport within the colon, the influence of platelet-activating factors on ion transport and epithelial permeability has been studied in rabbit caecum and distal colon mounted in Ussing chambers. 2. The effect of platelet-activating factor (1–50 nmol/l) on net electrogenic ion transport was to stimulate a biphasic increase in short-circuit current in the distal colon but not in the caecum. The platelet-activating factor-induced rise in short-circuit current was shown by ion replacement and pharmacological inhibitor studies to be consistent with chloride and bicarbonate secretion in the early phase, but with chloride secretion alone in the later phase. The effect on ion transport was specific and reversible and was enhanced by 0.25% BSA. 3. Colonic permeability, assessed by transmucosal resistanc...

Transactions of the Royal Society of Tropical Medicine and Hygiene, 1992

Evidence for immune activation was investigated in 12 patients with a rare syndrome of self-limit... more Evidence for immune activation was investigated in 12 patients with a rare syndrome of self-limiting, delayed onset cerebellar dysfunction following an attack of falciparum malaria which occurred 18-26 d previously. Concentrations of tumour necrosis factor, interleukin 6 and interleukin 2 were all significantly higher in serum samples of patients during cerebellar ataxia than in recovery sera and in the sera of 8 patients who did not develop delayed cerebellar dysfunction following an attack of falciparum malaria. Cytokine concentrations in the cerebrospinal fluid were also significantly higher in ataxic patients than in controls. These findings suggest that immunological mechanisms may play a role in delayed cerebellar dysfunction following falciparum malaria.

Gastroenterology, 1986

Mononuclear cell (MNC) populations isolated from intestinal mucosa, mesenteric lymph nodes, and p... more Mononuclear cell (MNC) populations isolated from intestinal mucosa, mesenteric lymph nodes, and peripheral blood have been assessed for their natural killer (NK) (Leu-7+) cell proportions and NK cell activity against K-562 erythroleukemic target cells. In peripheral blood, normal proportions of Leu-7+ cells were found in patients with Crohn's disease or ulcerative colitis, whereas increased proportions in colorectal carcinoma may have been related to the higher mean age of these patients. Low proportions of Leu-7+ cells (less than 3%) were present in intestinal MNCs in Crohn's disease, ulcerative colitis, colon cancer, and miscellaneous intestinal diseases. All groups of patients had diminished NK activity of peripheral blood MNCs compared with a group of healthy controls. Intestinal NK cell activity from histologically normal mucosa correlated with autologous peripheral blood NK cell activity (p less than 0.001) but no such correlation was seen for patients with inflammatory bowel disease. Mucosal or nodal NK cell activity showed a wide range of activity but did not relate to the underlying disease, mucosal histopathology, drug therapy, or, in patients with cancer, Dukes' grading. Intestinal MNCs from all patient groups responded to stimulation with lymphoblastoid interferon, except in a small number of patients whose unstimulated activity was not detectable. In conclusion, the NK cell on intestinal mucosa behaves similarly in various intestinal diseases. However, the disparity between NK activity of autologous peripheral blood and intestinal MNCs in inflammatory bowel disease highlights the difficulty in extrapolating peripheral blood findings to mucosal immune events.

Clinical Science, 1990

1. This study investigates the acetylation of 5′-aminosalicylic acid by isolated human colonic ep... more 1. This study investigates the acetylation of 5′-aminosalicylic acid by isolated human colonic epithelial cells. 2. After incubation of intact cells with 0.1 mmol/l 5-aminosalicylic acid, N-acetyl-5-aminosalicylic acid was detected in a concentration of 141 (± 23.8 sem) nmol/g dry weight in the incubation medium, and 34.8 (± 5.5 sem) nmol/g dry weight intracellularly. No unchanged 5-aminosalicylic acid was detected inside the cell. 3. Acetylation of 5-aminosalicylic acid by a cell homogenate was very poor, but the addition of 1 mmol/l acetyl-CoA resulted in complete conversion of 0.1 mmol/l 5-aminosalicylic acid to N-acetyl-5-aminosalicylic acid. 4. N-Acetyltransferase activity was detected in the cytosol, with a mean of 3.3 nmol min−1 mg−1 of protein. There was no N-acetyltransferase activity in the brush border. There was no difference in enzyme activity between epithelial cells derived from normal, Crohn's disease or ulcerative colitis patients. 5. Preliminary characterizatio...