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C C Ainley

Publications and source records attributed to C C Ainley.

At least 19 recordsLinked to original sources

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.

Aluminum↗

Electrophysical factors influencing endoscopic sphincterotomy.

BACKGROUND: Analog computer techniques were used to measure electrosurgical power during sphincterotomy in experimental models and patients. METHODS: Total energy and transient changes in power were measured during sphincterotomy of bile ducts in the livers of pigs, ampullae of humans post mortem, and during clinical sphincterotomy. The effect of waveform on hemostasis was studied in experiments on canine mesenteric arteries. RESULTS: Electrosurgical waveforms (CUT, COAG, BLEND) were measured. Halving wire contact length halved energy needed to initiate cutting. The CUT waveform rarely initiated cutting at lower power settings than the BLEND waveform. With CUT, BLEND, and COAG waveforms, approximately the same energy initiated cutting. Efficiency of cutting increased linearly with power. The COAG waveform required higher power settings than BLEND or CUT to initiate cutting (p < 0.05). Force and wire diameter influenced cutting. BLEND was more effectively hemostatic than CUT (p < 0.05). COAG was significantly more hemostatic than BLEND and CUT. Cutting efficiency during clinical sphincterotomy was poor. CONCLUSIONS: This work has practical implications. Shortening wire contact length was effective in starting a cut at suboptimal settings, whereas changing from BLEND to CUT made little difference. Increasing power setting may help if cutting does not start. BLEND stops bleeding better than CUT. COAG stops bleeding better than BLEND but cuts poorly. Cutting during clinical sphincterotomy is inefficient and can be improved.

Analog-Digital Conversion↗

Characterisation of inorganic microparticles in pigment cells of human gut associated lymphoid tissue.

Macrophages at the base of human gut associated lymphoid tissue (GALT), become loaded early in life with dark granular pigment that is rich in aluminium, silicon, and titanium. The molecular characteristics, intracellular distribution, and source of this pigment is described. Laser scanning and electron microscopy showed that pigmented macrophages were often closely related to collagen fibres and plasma cells in GALT of both small and large intestine and contained numerous phagolysosomes, previously described as granules, that are rich in electron dense submicron sized particles. Morphological assessment, x ray microanalysis, and image electron energy loss spectroscopy showed three distinct types of microparticle: type I - spheres of titanium dioxide, 100-200 nm diameter, characterised as the synthetic food-additive polymorph anatase; type II - aluminosilicates, < 100-400 nm in length, generally of flaky appearance, often with adsorbed surface iron, and mostly characteristic of the natural clay mineral kaolinite; and type III - mixed environmental silicates without aluminium, 100-700 nm in length and of variable morphology. Thus, this cellular pigment that is partly derived from food additives and partly from the environment is composed of inert inorganic microparticles and loaded into phagolysosomes of macrophages within the GALT of all human subjects. These observations suggest that the pathogenicity of this pigment should be further investigated since, in susceptible individuals, the same intracellular distribution of these three types of submicron particle causes chronic latent granulomatous inflammation.

Aluminum Silicates↗

Intestinal perfusion of dietary levels of aluminium: association with the mucosa.

An aluminium (93 microM) sulphate solution freshly adjusted to pH 7.0 was perfused through the rat small bowel to mimic the reported physiological conditions that follow dietary aluminium ingestion. One third of this aluminium was taken up from the perfusate, but > 90% of this was then recovered from the intestinal mucus/mucosa and most (> 70%) from the distal third of the small bowel. The fresh perfusate was shown by ultrafiltration to contain largely particulate/colloidal aluminium-hydroxide, and this probably adhered to intestinal mucus which may be an important barrier to the gastrointestinal absorption of aluminium.

Alum Compounds↗

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.

Aged↗

Gallbladder sepsis after stent insertion for bile duct obstruction: management by percutaneous cholecystostomy.

Of 364 patients undergoing insertion of a biliary endoprosthesis in 1989, six (1.6 per cent) developed gallbladder sepsis. Three patients had cholangiocarcinoma, two had carcinoma of the pancreas and one had a benign biliary stricture. Two of the five patients with malignancy had gallbladder stones, and the patient with a benign stricture developed stones after 3 years of stenting. Three patients developed gallbladder sepsis early after endoprosthesis insertion (less than 6 days), while in the other three it occurred late (greater than 6 months). All six patients failed to respond to antibiotics and were successfully managed by percutaneous cholecystostomy; the patient with a benign biliary stricture also had cholecystolithotomy. The gallbladder drainage tubes were removed or became dislodged at intervals varying from 2 weeks to 6 months without complications. Percutaneous cholecystostomy is the treatment of choice for gallbladder sepsis unresponsive to antibiotics in patients with a biliary endoprosthesis in situ.

Adenoma, Bile Duct↗

The source of Campylobacter pylori.

Sera from 98 abattoir workers were tested for IgG as well as for IgA to Campylobacter pylori, C. jejuni and Klebsiella. Clerical workers had significantly lower C. pylori and C. jejuni antibody levels than any of the groups in direct contact with freshly cut animal parts. No difference was found for antibodies to Klebsiella. Twenty-nine non-clerical workers with high IgG antibody levels against C. pylori consented to upper gastrointestinal endoscopy. C. pylori associated gastritis was found in all 29, and 4 weeks of colloidal bismuth subcitrate (240 mg/twice daily) was prescribed. On repeat testing at 3 months, all showed a decrease in IgG antibody levels to C. pylori but not to C. jejuni, whereas 18 untreated non-endoscoped workers showed no change. These findings raise the possibility that C. pylori infection is a zoonosis.

Abattoirs↗

Non-operative management of gallstones--a preliminary review.

We describe our initial experience with extracorporeal shock-wave lithotripsy, direct solvent dissolution with methyl tert-butyl ether and mechanical extraction, in 17 symptomatic patients without significant gall-bladder wall disease using existing criteria for selection. Extracorporeal shock-wave lithotripsy and mechanical extraction are promising techniques. Methyl tert-butyl ether therapy has been fraught with difficulty.

Adult↗

Is alcohol hepatotoxic in the baboon?

The baboon is the only animal in which alcoholic fibrosis and cirrhosis of the liver has been produced with a nutritionally adequate diet. Zinc deficiency is associated with alcoholic liver disease and may contribute to liver damage. We have therefore investigated whether zinc supplementation would reduce liver damage in ten baboons receiving ethanol and an adequate diet. Eight received ethanol at up to 25 g/kg/day (70% of calories) for up to 60 months (four were supplemented with 50 mg zinc/day). All animals gained weight, and blood concentrations of ethanol were 63-342 mg/dl. Changes in liver blood tests were slight. Liver histology only showed fatty change in six animals, severe in two, and minor inflammatory changes but no significant fibrosis or cirrhosis. In one of the animals with severe fatty change there were also degenerative changes in parenchymal cells. There was thus no significant hepatic fibrosis or cirrhosis in baboons given large amounts of ethanol and an adequate diet for up to 5 years.

Animals↗

Zinc status in inflammatory bowel disease.

1. The zinc contents of plasma, erythrocytes, polymorphonuclear leucocytes and mononuclear leucocytes from 18 normal control subjects, 31 patients with Crohn's disease and 15 patients with ulcerative colitis were measured. 2. Plasma zinc levels were low in Crohn's disease, particularly in malnourished patients, and related to plasma albumin concentrations, but were normal in ulcerative colitis. 3. Erythrocyte zinc levels were normal in both Crohn's disease and ulcerative colitis. 4. Mean polymorphonuclear leucocyte zinc levels were normal in Crohn's disease and ulcerative colitis. Ten per cent of Crohn's disease patients had subnormal levels, which were associated with inactive disease, while 10% had elevated levels, which were associated with active disease. Seven per cent of ulcerative colitis patients had subnormal levels. Mononuclear leucocyte zinc levels were normal in Crohn's disease and in ulcerative colitis. 5. Tissue zinc depletion occurs in only a few patients with Crohn's disease and ulcerative colitis.

Adolescent↗

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 Crohn's 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 Crohn's disease and two of 10 with proctocolitis, but it was within the normal range for all eight with anorexia nervosa. High adherence in Crohn's 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 Crohn's disease may therefore reflect the activation in vivo of normal PMN by humoral factors.

Adolescent↗

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.

Anorexia Nervosa↗

Teeth and benign oesophageal stricture.

In patients undergoing upper gastrointestinal endoscopy, benign oesophageal strictures were significantly more frequent (p less than 0.01) in those with severe tooth loss than in controls of the same age. This may be because of edentulous patients eating less solid and more liquid food, which would otherwise dilate the lower oesophagus, or poor salivary flow leading to both tooth loss and impaired neutralisation of refluxed gastric acid, or malnutrition. No association was found, however, between either oesophagitis or hiatus hernia and dentition.

Adult↗

Transit time in ulcerative proctitis.

Whole-gut transit time was measured by the time taken for an orally administered dose of brilliant blue dye to disappear from the stool in 20 patients with ulcerative proctitis and in 20 age- and sex-matched controls. Ten of the patients had active, and 10 inactive disease. The dye usually appeared in the stool with the next bowel movement after ingestion in both patients and controls; however, the time at which the dye disappeared from the stool (transit time) was prolonged to 76.1 h in the patients, compared with 50.2 h in the controls (p less than 0.01). This delay occurred both in patients with active disease at 70.5 h (p less than 0.05) and in those with inactive disease at 81.8 h (p less than 0.05). This prolongation of transit time may be relevant to both the pathogenesis and treatment of ulcerative proctitis.

Benzenesulfonates↗

Interleukin 1 in Crohn's disease.

A number of the activities currently ascribed to the mediator interleukin 1 (IL-1) are relevant to chronic inflammatory bowel disease. Using the mouse thymocyte stimulation assay, lymphocyte-activating factor (LAF) activity was measured in plasma samples and supernatants from cultures of peripheral blood mononuclear cells from 16 patients with Crohn's disease, six with ulcerative colitis, and 10 healthy subjects. Results were compared with disease activity, drug therapy, granulocyte count, and plasma levels of zinc and C-reactive protein (CRP). Very low levels of LAF were detected in a few plasma samples from each of the subject groups. Mononuclear cells from healthy subjects produced LAF only when cultured with lipopolysaccharide, but stimulated cells from patients produced greater amounts. Moreover, cells from six patients with Crohn's disease, not receiving steroids, produced LAF spontaneously. Crohn's disease patients also had low plasma zinc but elevated levels of CRP and granulocytes. This enhanced production of LAF in vitro may reflect a primary cellular defect in Crohn's disease, or a secondary consequence of monocyte activation.

Adult↗

Diminished phospholipid incorporation of essential fatty acids in peripheral blood leucocytes from patients with Crohn's disease: correlation with zinc depletion.

Peripheral blood leucocytes from patients with Crohn's disease have been shown to have lower zinc content than those from a normal population. Since zinc influences essential fatty acid metabolism, incorporation of 14C-linoleic and 3H-arachidonic acids was studied in peripheral blood leucocytes from controls and patients with Crohn's disease. The zinc content of the leucocytes was also measured. After incubation for 2 h, content of 3H-arachidonic acid, but not 14C-linoleic acid, was greater in Crohn's disease leucocytes than in controls. In the Crohn's disease leucocytes, incorporation of both labelled fatty acids into the phosphatidylcholine fraction was significantly lower than in controls, whereas the amount of both fatty acids remaining in the leucocytes as free fatty acids was increased by 70%. In Crohn's disease, leucocyte zinc level was positively associated with the percentage of 3H-arachidonic acid incorporation into phosphatidylcholine. We conclude that peripheral blood leucocytes from patients with Crohn's disease have abnormal essential fatty acid metabolism and that 3H-arachidonic acid incorporation into the phosphatidylcholine fraction of leucocyte lipids in Crohn's disease varies as the zinc content of the leucocytes.

Adult↗