A demonstration pilot trial for colorectal cancer screening in the United Kingdom: a new concept in the introduction of healthcare strategies.
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Aged↗
Biomedical subjects
N A Mowat
Publications and source records attributed to N A Mowat.
Distal proctocolitis and n-3 polyunsaturated fatty acids (n-3 PUFAs): the mucosal effect in situ.
It has been postulated that patients with ulcerative colitis (UC) have altered reactivity of gut-associated lymphoid tissue. In such cases there is intense infiltration of the mucosa with immune competent cells and associated tissue damage. We have shown previously that the dietary supplementation with the n-3 polyunsaturated fatty acids (n-3 PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) results in significant systemic immune suppression. The aim of this study, therefore, was to evaluate the in situ effect of n-3 PUFAs on distal proctocolitis. Each patient received either fish oil extract (EPA 3.2 g, DHA 2.4 g) (n = 9) or sunflower oil (n = 9) daily in a double blind manner for six months. Monthly assessment included: (1) disease activity using clinical, sigmoidoscopic, and histological scores and (2) immunohistochemical analysis (immunoglobulins, CD profiles) of rectal biopsy specimens (before and after six months supplementation) using monoclonal antibodies and quantitative computer-assisted video image analysis. Prior to receiving supplementation, patients with proctocolitis (n = 18) showed significantly higher numbers of cells expressing CD3 (pan T cells) and HLA-DR and IgM containing cells compared with non-colitic controls (n = 8). Six months supplementation with n-3 PUFAs resulted in significant reduction in the number of cells expressing CD3 and HLA and the percentage of cells containing IgM. There was no significant change in the CD20 nor the percentage of IgG or IgA containing cells in either group of patients with procto-colitis. In patients receiving n-3 PUFA supplementation, there was improvement in the disease activity and histological scores, compared with pretreatment evaluation. This study has demonstrated both evidence of suppression of in situ immune reactivity and concurrent reduction in disease activity in patients with proctocolitis receiving n-3 PUFA supplementation. This may have important implication for therapy in patients with ulcerative colitis.
Animals↗
Distal procto-colitis, natural cytotoxicity, and essential fatty acids.
OBJECTIVES: Recently, it has been postulated that patients with ulcerative colitis have altered natural cytotoxicity, in particular natural killer (NK) and lymphokine-activated killer (LAK) cell activities. These cellular mechanisms have been postulated to play an etiological role in the pathogenesis of the disease process. We have shown previously that the essential fatty acids (EFA) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) specifically inhibit natural cytotoxicity. Our aim was to evaluate the role of omega-3 EFA in the modulation of natural cytotoxicity and disease activity in patients with distal procto-colitis. METHODS: In this pilot study patients were randomized into two groups. Each patient received either fish oil extract (EPA, 3.2 g, and DHA, 2.4 g) (n = 9) or sunflower oil (placebo) (n = 9) daily in a double-blind manner for 6 months. Monthly assessments of disease activity (clinical and sigmoidoscopic scores) and histological evaluation of mucosal biopsies were carried out. Also, the circulating levels and activities of NK and LAK cells, using flow cytometric analysis (CD16+ CD56+) and in vitro 51 chromium release assays (K562), respectively, were monitored. RESULTS: After 6 months' supplementation with EFA, there was improvement in the clinical activity compared with pretreatment evaluation. There was significant reduction in the sigmoidoscopic and histological scores in the EFA group compared with the placebo group. Essential fatty acid supplementation for 6 months also induced significant reduction in the circulating numbers of CD16+ and CD56+ cells and the cytotoxic activity of NK cells, compared with the placebo group. CONCLUSIONS: This pilot study has demonstrated that omega-3 fatty acids can suppress natural cytotoxicity and reduce disease activity in patients with distal procto-colitis. These findings suggest a therapeutic strategy for managing patients with inflammatory bowel disease.
Adult↗
Fertility and pregnancy in inflammatory bowel disease.
OBJECTIVE: A retrospective study of women with inflammatory bowel disease, aged 16-45 years during the 20-year period 1967-1986, was carried out in North East Scotland. METHOD: Five-hundred and three women were identified: 15 patients had died from unrelated causes and 22 had emigrated, but 409 of the remaining 466 patients (88%) replied to the study questionnaire. RESULTS: Women with ulcerative colitis and Crohn's disease had normal fertility when compared with the general population of north east Scotland. However, unresolved infertility problems were more frequent in women who had undergone surgery for inflammatory bowel disease compared with those who had not (12% vs. 5% for Crohn's disease; 25% vs. 7% for ulcerative colitis). Disease relapse rates did not increase in pregnancy. CONCLUSIONS: Overall, at conception women with active disease were as likely to have a normal full-term pregnancy as those in remission. However, spontaneous abortion occurred in five (36%) pregnancies of women who had undergone previous surgery for Crohn's disease and had evidence of recurrent disease. Three of these pregnancies were associated with active disease.
Abortion, Spontaneous↗
The role of an open-access bleeding unit in the management of colonic haemorrhage. A 2-year prospective study.
BACKGROUND: Major colonic haemorrhage poses difficult diagnostic and therapeutic problems and, in contrast to upper gastrointestinal bleeding, has no generally accepted plan of management. METHODS: We report community-based prospective data accumulated over 2 years (1991-93) on 1602 patients referred to an open-access bleeding unit with suspected gastrointestinal haemorrhage. RESULTS: Of 278 (17%) admissions with suspected lower GI haemorrhage, 252 were confirmed. Forty-eight per cent were defined as "significant' bleeds, with a decrease in haemoglobin and cardiovascular compromise. Of 102 significant bleeds in subjects more than 60 years old, 29% rebled, and 12.6% required emergency surgery. Diverticular disease (24%) was the commonest diagnosis, with tumours, infective colitis, and inflammatory colitis each at 10%. The overall 30-day mortality for colonic bleeding was 5.1% (13 of 252), with only 1 death occurring in the group less than 60 years old. CONCLUSIONS: This study provides a unique database for the natural history of colonic bleeding and its management within the setting of a specialized bleeding unit.
Adult↗
Improving the selection of patients for upper gastrointestinal endoscopy.
A retrospective study was undertaken to investigate how endoscopies yielding positive findings differ a priori from those yielding negative findings: and how those judged 'helpful' (in the sense of influencing management) differ a priori from those judged 'unhelpful'. A total of 483 patients undergoing endoscopy was sampled and a wide range of data abstracted, including 48 patient characteristics available to the gastroenterologist at the time of the decision to perform endoscopy. Sixty nine per cent of endoscopies were positive. Multivariate statistical analysis identified four variables which taken together were strongly predictive of a positive endoscopy. The resulting mathematical formula correctly predicted the outcome of 76% of endoscopies. Eighty two per cent of the endoscopies were retrospectively classified by the gastroenterologists as helpful. Six variables were strongly predictive of a helpful endoscopy. The corresponding formula correctly predicted the finding of 84% of endoscopies. Comparison of the two analyses shows that the two sets of predictions differ substantially. Thus it is important that decision tools should be based not on the crude distinction between positive and negative, but on the more useful distinction between helpful and unhelpful in influencing management.
Adolescent↗
Pyoderma faciale in a patient with Crohn's disease.
We wish to report the progress of a patient with pyoderma faciale and Crohn's disease. The patient is interesting in that on two occasions the relapse in her skin condition coincided with the introduction of non-steroidal anti-inflammatory drugs. Therapy with isotretinoin was effective and well tolerated.
Adult↗
The value of prescribed 'high-fibre' diets for the treatment of the irritable bowel syndrome.
The symptoms of 72 patients with irritable bowel syndrome were assessed by questionnaire before and 6 months after a high-fibre diet had been prescribed, to find whether those who achieved the highest fibre intake did any better than those with smaller intakes. Dietary fibre intakes were measured after 6 months by a 7-day weighed food inventory. There was a significant inverse association between the presence of symptoms and fibre intake for: incomplete defaecation, urgency and hard stools with total fibre intake; urgency and hard stools with cereal fibre intake; and borborygmi with fibre intake at breakfast. All patients with constipation, mucus, urgency or watery stools at the beginning of the study, and who were consuming more than 30 g fibre by the end, reported an improvement in these symptoms. Increasing intakes of fibre were not related in any way to abdominal distension, diarrhoea, flatulence or patient's feelings about the working of their bowels. Therefore, this study suggests that the symptoms which benefit most from the prescription of a high-fibre diet are hard stools, constipation and urgency.
Adult↗
Zinc metabolism in celiac disease.
The turnover of a radiolabeled (65Zn) pool of endogenous zinc was monitored by using a whole-body counter in eight patients with celiac disease (CD) and analyzed by using a two-compartment model. The biological half-life of the first compartment (1-3 wk postadministration) was similar in healthy volunteers (122 +/- 34 d, means +/- SD) and untreated patients (97 +/- 21 d). The second compartment in the patients (3-12 wk postadministration) was shorter (159 +/- 22.5 d. p less than 0.001) than were reference values (218 +/- 27 d) but increased (291 +/- 71 d) after the patients started gluten-free diets. The percentage absorption of 65Zn (9.25 kBq) from a test meal containing 31 mumol (2 mg) zinc was similar in untreated patients (30.0 +/- 13%) and healthy volunteers (32.5 +/- 12.4%). These data show that in mild untreated CD increased turnover and loss of endogenous zinc occurs whereas the absorption of zinc from a customary zinc intake may be normal. The pathophysiological basis of this loss was not investigated.
Adult↗
The safety and efficacy of tripotassium dicitrato bismuthate (De-Nol) maintenance therapy in patients with duodenal ulceration.
Seventy-one patients whose duodenal ulcers had healed after a 4-week treatment period with tripotassium dicitrato bismuthate (TDB) were randomly allocated to receive maintenance treatment with either one TDB swallow tablet nocte (equivalent to 120 mg Bi2O3) or an identical placebo. During 12 months of follow-up, no side-effects were reported by TDB-treated patients, blood bismuth levels did not rise above discontinuation threshold concentrations (greater than 50 micrograms/L in the first 6 months, or greater than 100 micrograms/L in the second 6 months), and there were no adverse effects on haematological or biochemical indices. Ulcer relapse was significantly less in TDB-treated patients (P less than 0.025). Cumulative relapse rates at 6 and 12 months were 51% and 66%, respectively, for placebo-treated patients and 26% and 31%, respectively, for those who received TDB. It is likely that TDB is a safe and effective maintenance treatment for patients with duodenal ulcer disease.
Adult↗
D-lactic acidosis in short bowel syndrome--an examination of possible mechanisms.
Two patients, both with short bowel syndrome, presented with severe D-lactic acidosis associated with subacute small bowel obstruction and bizarre neurological signs. In neither patient were D-lactic acid-producing organisms isolated from the upper intestine. In both, upper intestinal aspirates yielded a glucose-fermenting yeast, Torulopsis glabrata. Although intestinal aspirates from both contained significant quantities of ethanol alcohol could not be detected in concomitant blood samples. A glucose load test produced a rise in blood D-lactic acid in both. One patient has evidence of mild persisting renal tubular damage. The same patient responded to oral antibiotics but the other relapsed frequently despite continuous antibiotic treatment. He was shown to be thiamine deficient and since the administration of oral thiamine he has had no recurrence of symptoms or of D-lactic acidosis.
Acidosis, Lactic↗
Reversible toxicity in poisoning with colloidal bismuth subcitrate.
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Acute Kidney Injury↗
Neuropsychological deficits and morphological MRI brain scan abnormalities in apparently healthy non-encephalopathic patients with cirrhosis. A controlled study.
By means of psychometric testing, we have determined the frequency of latent hepatic encephalopathy in a group of 19 cirrhotics with no clinical evidence of encephalopathy. Magnetic resonance imaging (MRI) of the brain was performed in order to determine whether morphological cerebral abnormalities were associated with latent encephalopathy. Nineteen age and educationally matched patients with normal liver function acted as controls. Significant differences (P less than 0.05) between cirrhotics and controls were found in tests of short-term visual memory and speed of reaction to light (cirrhotics 316 +/- 132 ms vs. controls 225 +/- 36 ms), sound (cirrhotics 361 +/- 152 ms vs. controls 236 +/- 52 ms) and choice (cirrhotics 651 +/- 190 ms vs. controls 406 +/- 101 ms) stimuli (all values mean +/- S.D.). Reitan trail test performance, however, was similar in both groups. (Trail A: cirrhotics 43 +/- 19 s vs. controls 35 +/- 13 s; Trail B: cirrhotics 105 +/- 66 s vs. controls 93 +/- 36 s.) In patients with cirrhosis, MRI revealed statistically significant increases in the maximum fissure width of right frontal sulci, right and left parietal sulci, inter-hemispheric fissure width and in bicaudate index. These changes, indicating cerebral atrophy, were largely confined to alcoholics. There was poor correlation between measurements of cerebral morphology and neuropsychological performance, only 10% of associations achieving statistical significance.
Adult↗
Inorganic zinc and the intestinal absorption of ferrous iron.
The effect of inorganic zinc on the absorption of inorganic iron (Fe+2) from a solution was assessed in two studies on healthy male volunteers. In the first study coadministration of 344 mumol of zinc had no effect (p less than 0.5) on the absorption of 842 mumol of radiolabeled Fe, assessed by the area under plasma Fe increment time curve during the 3 (AUC3) and 6 (AUC6) h postadministration (Fe alone AUC3 = 176.4 +/- 39.3; AUC6 = 387 +/- 101; Fe + Zn AUC3 = 180 +/- 33.1; AUC6 = 396 +/- 73.1 mumol.h-1.L-1), total plasma content of 59Fe, and whole-body retention of 59Fe. In the second study only the plasma appearance of Fe was monitored. After administration of 421 mumol of Fe alone, the AUC3 and AUC6 were 167 +/- 21.2 and 429.4 +/- 57 mumol.h-1.L-1, respectively; these were reduced to 56.4 +/- 17 and 119 +/- 34 (p less than 0.002) by 421 mumol Zn and further reduced by 1048 mumol Zn to 33 +/- 15 and 43.4 +/- 23.8 mumol.h-1.L-1 (p less than 0.001), respectively. It is concluded that Zn can impair the intestinal absorption of Fe.
Adult↗
The effects of propranolol on hepatic encephalopathy in patients with cirrhosis and portal hypertension.
Beta adrenoreceptor blocking drugs have been used for the prevention of haemorrhage from oesophageal varices. However, it is possible that these agents, by virtue of their effects on hepatic blood flow, may impair liver function and precipitate hepatic encephalopathy. We have therefore studied the effect of the beta blocking drug propranolol on hepatic encephalopathy in patients with cirrhosis and portal hypertension. Twenty patients were randomly assigned to receive 4 weeks treatment with propranolol or an identical-looking placebo, the former given in a dose sufficient to reduce resting pulse rate by greater than or equal to 25%. Before and after treatment patients were assessed for the severity of liver disease and the presence of encephalopathy. EEG mean cycle frequency and fasting arterial ammonia concentrations were also measured, and in order to detect latent hepatic encephalopathy, each patient underwent a battery of psychometric tests. Patients were blinded as to their treatment, as were those assessing their responses. Neither propranolol nor placebo had any significant effect on the parameters measured. On propranolol median EEG mean cycle frequency fell from 9.08 ct s-1 (range 8.63-11.0 ct s-1) to 8.73 ct s-1 (range 8.27-11.44 ct s-1), and median fasting arterial ammonia concentration fell from 66 mumol litre-1 (range 40-329 mumol litre-1) to 49 mumol litre-1 (range 37-188 mumol litre-1). Psychometric test values, while initially abnormal and suggestive of latent hepatic encephalopathy in the majority of patients, did not change significantly during the study.
Adult↗
Familial Crohn's disease, including spouse.
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Adolescent↗
Protease inhibitors in liver disease.
Measurements of the principal protease inhibitors were carried out in patients with two types of chronic liver disease: alcoholic cirrhosis and primary biliary cirrhosis. Measurement of the two major protease inhibitors operative in the haemostatic mechanism--that is, antithrombin III and alpha 2-antiplasmin--showed significantly reduced levels in the alcoholic cirrhosis group, who satisfied clinical and biochemical criteria of impaired hepatocellular function, but not in the primary biliary cirrhosis group, who had relatively good preservation of hepatocellular function. Significant correlation of levels of both these major protease inhibitors with the serum albumin concentration was also found. No evidence of disseminated intravascular coagulation was detected, and therefore failure of synthesis by the liver is the likely explanation of the low levels noted.
Adult↗
Deficiency of serum "pregnancy-associated" alpha 2-glycoprotein alpha 2-PAG): association with disease.
The serum concentrations of "pregnancy-associated" alpha 2-glycoprotein (alpha 2-PAG) were measured in 129 healthy women and 141 healthy men to establish a normal range, using a sensitive enzyme linked immunosorbent assay. In the normal population 2.8% of men and 5.4% of women had low serum alpha 2-PAG concentrations. Low concentrations occur, however, much more commonly in patients, particularly male patients, with certain diseases, including dermatitis herpetiformis (three of 12 or 25%) and urticaria (two of five or 40%). One female patient with absolute deficiency was also identified. In view of the recently confirmed association of alpha 2-PAG with IgA and the fact that alpha 2-PAG seems to have immunosuppressive properties, it seems likely that deficiency of alpha 2-PAG could result in the subject becoming sensitised to various dietary antigens. Interestingly, none of the 24 patients with IgA deficiency showed concomitant deficiency of alpha 2-PAG.
Adolescent↗