Colin Ainley

A randomized controlled study of evening primrose oil and fish oil in ulcerative colitis

In a placebo‐controlled study, 43 patients with stable ulcerative colitis were randomized to receive either MaxEPA (n= 16), super evening primrose oil (n= 19), or olive oil as placebo (n= 8) for 6 months, in addition to their usual treatment. Treatment with MaxEPA increased red‐cell membrane concentrations of eicosapentaenoic acid (EPA) at 3 months by three‐fold and at 6 months by four‐fold (both P < 0.01), and doubled docosahexaenoic acid (DHA) levels at 6 months (P < 0.05). Treatment with super evening primrose oil increased red‐cell membrane concentrations of dihomogamma‐linolenic acid (DGLA) by 40% at 6 months (P < 0.05), whilst treatment with placebo reduced levels of DGLA and DHA at 6 months (both P < 0.05). Clinical outcome was assessed by patient diary cards, sigmoidoscopy and histology of rectal biopsy specimens. Super evening primrose oil significantly improved stool consistency compared to MaxEPA and placebo at 6 months, and this difference was maintained 3 months after treatment was discontinued (P < 0.05). There was however, no difference in stool frequency, rectal bleeding, disease relapse, sigmoidoscopic appearance or rectal histology in the three treatment groups. Despite manipulation of cell‐membrane fatty acids, fish oils do not exert a therapeutic effect in ulcerative colitis, while evening primrose oil may be of some benefit.

Lack of efficacy of a reduced microparticle diet in a multi-centred trial of patients with active Crohn's disease.

Background and aims Dietary microparticles, which are bacteria-sized and non-biological, found in the modern Western diet, have been implicated in both the aetiology and pathogenesis of Crohns disease. Following on from the findings of a previous pilot study, we aimed to confirm whether a reduction in the amount of dietary microparticles facilitates induction of remission in patients with active Crohns disease, in a single-blind, randomized, multi-centre, placebo controlled trial. Methods Eighty-three patients with active Crohns disease were randomly allocated in a 2×2 factorial design to a diet low or normal in microparticles and/or calcium for 16 weeks. All patients received a reducing dose of prednisolone for 6 weeks. Outcome measures were Crohns disease activity index, Van Hees index, quality of life and a series of objective measures of inflammation including erythrocyte sedimentation rate, C-reactive protein, intestinal permeability and faecal calprotectin. After 16 weeks patients returned to their normal diet and were followed up for a further 36 weeks. Results Dietary manipulation provided no added effect to corticosteroid treatment on any of the outcome measures during the dietary trial (16 weeks) or follow-up (to 1 year); e.g., for logistic regression of Crohns disease activity index based rates of remission (P=0.1) and clinical response (P=0.8), in normal versus low microparticle groups. Conclusions Our adequately powered and carefully controlled dietary trial found no evidence that reducing microparticle intake aids remission in active Crohns disease.

The influence of zinc status and malnutrition on immunological function in Crohn's disease

Cellular immunity is likely to be important in the pathogenesis of Crohns disease; whether it is abnormal is not clear. The heterogeneity of patients with Crohns disease probably underlies the disparity of reports, but attempts to determine which clinical features influence cellular immunity have been largely unsuccessful. This is probably caused by the omission of nutritional status as a potential factor, even though zinc deficiency has frequently been linked with abnormal immunity. Therefore, a detailed study of nutritional and tissue zinc status, nonspecific cellular immunity, and a measure of phagocytic function was performed in 32 patients with Crohns disease and in a control group of 18 normal subjects and 12 patients with anorexia nervosa. Fourteen patients with Crohns disease, all patients with anorexia nervosa, but none of the normal controls were malnourished. Peripheral blood lymphocyte population levels were normal in patients with Crohns disease and in normal controls, but there was a small decrease in the levels of patients with anorexia nervosa. In vivo delayed hypersensitivity skin test responses were profoundly depressed in patients with anorexia nervosa and decreased in patients with Crohns disease who were malnourished or receiving systemic glucocorticoids. In vitro lymphocyte transformation was reduced in malnourished patients with Crohns disease, but there were only minor changes in patients with anorexia nervosa. There were alterations of in vitro immunoregulation in Crohns disease, but they were not responsible for the abnormal lymphocyte transformation responses in malnourished patients. In vitro phagocytic function was reduced in patients with active Crohns disease. These findings suggest that depressed in vivo and in vitro cellular immunity in malnourished patients with Crohns disease is caused by a qualitative lymphocyte defect and that depressed in vivo but normal in vitro cellular immunity in anorexia nervosa is caused by a quantitative defect. Thus, malnutrition in Crohns disease resembles kwashiorkor; in anorexia nervosa, it resembles marasmus. Tissue zinc status was mostly normal in Crohns disease and anorexia nervosa, and zinc deficiency was not responsible for depressed nonspecific cellular immunity in either condition.

Dietary minerals in the gastrointestinal tract: hydroxypolymerisation of aluminium is regulated by luminal mucins

The regulation of mineral absorption in the gastrointestinal tract is poorly understood. Recent work has identified an intracellular metal-ion transporter but considerable evidence suggests that both soluble and mucosally associated luminal metal-binding ligands regulate initial uptake. Molecules ranging from low molecular weight organic acids to large glycoproteins have been suggested but a definite role for any such species has remained elusive. Here, a series of analytical techniques, allowing for this wide variation in potential binding ligands, was applied to the study of intestinal contents and tissue of rats following different feeding protocols. Aluminium, that has a low endogenous background and maintains a high concentration in the gastrointestinal tract, was investigated as a suitable dietary metal with hydrolytic behaviour similar, for example, to copper, iron and zinc. High resolution nuclear magnetic resonance spectroscopy identified a number of endogenous low molecular weight weak ligands that are secreted into the intestinal lumen. These may slow the rate of hydroxy-polymerisation of hydrolytic metals, allowing their effective donation to less mobile, higher molecular weight binding ligands. Histochemical staining suggested that such species may be soluble mucins as these were consistently associated with luminal aluminium. Significantly, this interaction prevented hydroxy/phosphate precipitation of aluminium, even at supraphysiological levels of the element. This was confirmed with X-ray micro-analysis investigations of ex vivo luminal contents. Nevertheless, from phase distribution experiments, the majority (60-95%) of luminal aluminium was associated with the intestinal solid phase and further histochemistry confirmed this to be gelatinous mucus, chiefly as the mucosally adherent layer. All results suggest a major role for mucus in regulating the gastrointestinal absorption of aluminium. It is proposed that, initially, soluble luminal mucus prevents the hydroxy-precipitation of hydrolytic metals at intestinal pH, allowing their effective donation to the mucus layer. Based on the differing reported metal-mucus interactions, elements that bind well to mucus (Al3+, Fe3+), with kinetically slow rates of ligand exchange (Al3+ < Fe3+) will be less well absorbed than poorly bound elements with kinetically faster rates of ligand exchange (Cu2+, Zn2+ etc.). This mechanism would readily explain many of the reported observations on mineral availability, including the marked variation in absorption of different elements, the differential effects of dietary ligands on mineral uptake and the competition for absorption between different metals.

Polymorphonuclear leucocytes in Crohn's disease and ulcerative proctocolitis: association between enhanced adherence to nylon fibre and disease variables.

The adherence of polymorphonuclear leucocytes (PMN) to nylon fibre was investigated in patients with Crohns disease, ulcerative proctocolitis, and anorexia nervosa, and compared with changes of circulating PMNs, C reactive protein concentrations, erythrocyte sedimentation rates, and clinical assessment of disease activity. PMN adherence was in excess of the maximum value detected for healthy subjects in 14 of 25 patients with Crohns disease and two of 10 with proctocolitis, but it was within the normal range for all eight with anorexia nervosa. High adherence in Crohns disease, however, was not associated with quantitative or qualitative changes of PMN populations, absolute concentrations of C reactive protein, erythrocyte sedimentation rates, disease severity, drug regimens, malnutrition, or zinc deficiency. High PMN adherence in Crohns disease may therefore reflect the activation in vivo of normal PMN by humoral factors.

Analysis of human lymphocyte transformation responses to graded doses of T cell mitogens by curve fitting

The between-group comparison of complete lymphocyte transformation dose-response curves is complex. We have therefore derived a mathematical model of the dose-response characteristics of human mononuclear cells to stimulation by concanavalin A (ConA) and purified phytohaemagglutinin (PHA), in order to simplify such analyses. This model describes dose-response curves in terms of the magnitude of the peak response, the dose of mitogen that elicits the peak and an estimate of the range of mitogen doses which induce a response. Responses to ConA were described by the model more precisely than those to PHA. Furthermore, use of the model revealed differences between anorexia nervosa patients and healthy subjects in terms of the dose of mitogen necessary to elicit a peak response and the range of mitogen concentrations producing a response. It is proposed that this form of mathematical treatment may be of use for the comparison of lymphocyte transformation dose-response curves and for the valid rejection of suspect results.

3429 Biliary manometry recording and analysis enhanced by synchronised endoscopic video capture.

Background Biliary manometry requires measurement and analysis of sphincter of Oddi pressures at several stations during a pull-through technique. Smooth muscle relaxants routinely employed during papillary cannulation at ERCP cannot be used because of their relaxant effect on the sphincter. Consequently, marked duodenal motility is often present. This and patient movement can displace the manometry catheter from the intended recording station. Duodenal contractions may also alter the baseline against which biliary manometric readings are taken. Such events can limit the quality of the trace and its subsequent analysis, potentially influencing the interpretation of sphincter pressure values and sphincter pressure wave frequency and propagation. Although possible to annotate the trace during recording using most software, this is laborious and impossible to perform rapidly enough to describe all the events during the period of recording. Aim To improve the quality and reliability of biliary manometry using endoscopic images obtained at the procedure. Endoscopic image video capture The Sedia software for manometry recording allows for synchronised high quality video image capture of the endoscopic view, displayed on the same monitor as that showing the manometry tracing. This allows the manometry operator to visualise more easily duodenal contractions and catheter position, facilitating an immediate assessment of the quality and validity of the trace before advising the endoscopist to proceed to the next station. At subsequent analysis, the endoscopic view remains available, synchronised with the manometry recording. Scrolling through the manometry trace shows the endoscopic image at any given time point. Alternatively, the video loop can be played with simultaneous synchronised display of a marker progressing along the manometry trace. Thus duodenal activity and catheter position at the time of relevant manometric events can be viewed. Conclusion We believe this facility enhances the quality of the manometry tracing and the reliability of analysis, particularly if this is performed some time afterwards or by an analyst not present at the original recording. The full extent to which this equipment improves the conclusions from biliary manometry studies requires formal assessment, which is in progress. It is also a useful teaching addition when demonstrating the procedure.