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Biomedical subjects

P R Gibson

Publications and source records attributed to P R Gibson.

At least 19 recordsLinked to original sources
PubMed2007

Review article: fructose malabsorption and the bigger picture.

Fructose is found widely in the diet as a free hexose, as the disaccharide, sucrose and in a polymerized form (fructans). Free fructose has limited absorption in the small intestine, with up to one half of the population unable to completely absorb a load of 25 g. Average daily intake of fructose varies from 11 to 54 g around the world. Fructans are not hydrolysed or absorbed in the small intestine. The physiological consequences of their malabsorption include increasing osmotic load, providing substrate for rapid bacterial fermentation, changing gastrointestinal motility, promoting mucosal biofilm and altering the profile of bacteria. These effects are additive with other short-chain poorly absorbed carbohydrates such as sorbitol. The clinical significance of these events depends upon the response of the bowel to such changes; they have a higher chance of inducing symptoms in patients with functional gut disorders than asymptomatic subjects. Restricting dietary intake of free fructose and/or fructans may have durable symptomatic benefits in a high proportion of patients with functional gut disorders, but high quality evidence is lacking. It is proposed that confusion over the clinical relevance of fructose malabsorption may be reduced by regarding it not as an abnormality but as a physiological process offering an opportunity to improve functional gastrointestinal symptoms by dietary change.

Adolescent↗
PubMed2006

Comparison of the efficacy and safety of Eudragit-L-coated mesalazine tablets with ethylcellulose-coated mesalazine tablets in patients with mild to moderately active ulcerative colitis.

BACKGROUND: There are no comparative studies of coated mesalazine. AIM: To compare the efficacy and tolerability of Eudragit-L- and ethylcellulose-coated mesalazine tablets in patients with mild to moderately active ulcerative colitis. METHODS: A double-blind, double-dummy, randomized parallel group trial was performed across 18 centres in Australia, and 20 in Eastern Europe. Patients were treated with 3 g mesalazine for 8 weeks with the primary efficacy end point being clinical remission. RESULTS: Of 215 patients, 69% achieved clinical remission in both treatment groups (P < 0.001; chi-square test) with no differences in frequency of adverse events. In the Australian cohort (n = 63), the Eudragit-L group had a higher remission rate (73% vs. 36%) and responded 13 days faster, compared with those in the European group (67% vs. 84%, and 2 days respectively). No clear reasons for differences in treatment responses were identified. CONCLUSIONS: Eudragit-L and ethylcellulose-coated mesalazine tablets are well tolerated and equally effective in achieving remission in mild-moderately active ulcerative colitis over 8 weeks.

Administration, Oral↗
PubMed2006

Measurement of faecal fat excretion: an evaluation of attitudes and practices of Australian gastroenterologists.

BACKGROUND: Although faecal fat excretion over 72 h is the gold standard for quantifying fat malabsorption, there has been a push from chemical pathology laboratories to discontinue this test, arguing that it is unreliable and of limited clinical value. AIMS: To assess attitudes, knowledge and practices of Australian gastroenterologists in relation to the test and to gauge opinion as to whether it should remain available. METHODS: A self-administered questionnaire was developed to assess attitudes towards, patterns of use and understanding of 72-h faecal fat collections. This was posted to all members of the Gastroenterological Society of Australia. RESULTS: Of 429 eligible gastroenterologists, 124 (29%) responded. Eighty-two per cent utilized the test; 62% at least once per year. Main indications were suspected steatorrhoea (55%), unexplained chronic diarrhoea (39%) or weight loss (29%). Thirty-eight per cent ordered the test to determine stool volume. Only 26% attempted to appropriately fat load patients and approximately half did not recognize the potential influence of medications and stool volume. This was also reflected in poor interpretation of results in specific clinical scenarios. Of those who use the test at least once per year, 97% wanted its continued availability and 51% felt their practice would be significantly affected if the test was discontinued. CONCLUSIONS: Although continued availability of 72-h faecal fat estimation is supported by many Australian gastroenterologists, the test appears to be often performed and interpreted suboptimally. Rather than discard the test, efforts should more appropriately be directed to improving baseline knowledge to ensure its optimal performance and interpretation.

Adult↗
PubMed2006

Management of iron deficiency in patients admitted to hospital: time for a rethink of treatment principles.

BACKGROUND: Iron deficiency is very common in patients admitted to hospital. Its management is changing with new insights into iron absorption and therapeutic options. AIMS: The aims of this study were to develop guidelines for the correction of iron deficiency in patients admitted to hospital and to compare these with current practice. METHODS: Based on current published evidence, guidelines were developed. All patients in whom iron deficiency was detected during hospital admission over a 2.5 year period were retrospectively studied. Their management was compared with that of the guidelines developed. RESULTS: Three clinical scenarios were identified--(A) urgent attention to haemoglobin required: blood transfusion followed by i.v. iron recommended, (B) Semiurgent iron repletion: i.v. iron recommended and (C) non-urgent iron repletion: oral or i.v. repletion recommended. A total of 119 patients was identified, age 18-99 (median 77) years, 29% men, and haemoglobin 33-130 (87) g/L. Of 66 given blood transfusion, 17 had subsequent i.v. iron, 25 oral iron and 24 no other form of iron repletion. Of the other 53, nine had i.v. iron, 32 oral iron and 12 had no treatment. Fifty-five per cent of patients were managed according to the proposed guidelines and this occurred less frequently (9%) in those presenting with cardiovascular problems than in those with anaemia, gastrointestinal bleeding or other medical problems (all >60%; P < 0.0001, Fisher's exact test). CONCLUSION: Current management is haphazard, with underutilization of i.v. iron and failure to initiate any regimen for iron repletion being common. It may be time for a change in approach to repletion of iron in ill patients.

Administration, Oral↗
PubMed2006

Safety of iron polymaltose given as a total dose iron infusion.

An audit of the in-hospital safety and tolerability of 401 infusions of iron polymaltose in 386 patients has shown no cases of anaphylaxis or other cardiorespiratory compromise. The infusion was terminated prematurely because of adverse events in six patients (1.6%). No adverse events occurred within the first 15 min of the infusion. Premedication (in 24%) was not associated with fewer adverse events. Fear of anaphylaxis should not inhibit the use of total dose iron infusion and the practices of premedication and of medical supervision during the first 15 min of the infusion should be abandoned.

Adolescent↗
PubMed2005

Personal view: food for thought--western lifestyle and susceptibility to Crohn's disease. The FODMAP hypothesis.

Susceptibility to the development of Crohn's disease involves a combination of genetic and environmental factors. The association of Crohn's disease with westernization has implicated lifestyle factors in pathogenesis. While diet is a likely candidate, evidence for specific changes in dietary habits and/or intake has been lacking. A new hypothesis is proposed, by which excessive delivery of highly fermentable but poorly absorbed short-chain carbohydrates and polyols (designated FODMAPs--Fermentable Oligo-, Di- and Mono-saccharides And Polyols) to the distal small intestinal and colonic lumen is a dietary factor underlying susceptibility to Crohn's disease. The subsequent rapid fermentation of FODMAPs in the distal small and proximal large intestine induces conditions in the bowel that lead to increased intestinal permeability, a predisposing factor to the development of Crohn's disease. Evidence supporting this hypothesis includes the increasing intake of FODMAPs in western societies, the association of increased intake of sugars in the development of Crohn's disease, and the previously documented effects of the ingestion of excessive FODMAPs on the bowel. This hypothesis provides potential for the design of preventive strategies and raises concern about current enthusiasm for putative health-promoting effects of FODMAPs. One of the greatest challenges in defining the pathogenesis of Crohn's disease is to identify predisposing environmental factors. Such an achievement might lead to the development of preventive strategies for, and the definition of, possible target for changing the natural history of this serious disease. The present paper describes a new hypothesis for one such environmental factor.

Crohn Disease↗
PubMed2005

Mechanisms by which food intake elevates circulating levels of hyaluronan in humans.

OBJECTIVES: Plasma hyaluronan is a potentially useful clinical test, especially in liver disease. It rises after eating, but mechanisms by which this occurs are not known. The study aimed at defining the effect of different food and liquid intake on plasma hyaluronan and to address mechanisms. DESIGN: The effects on plasma hyaluronan of ingestion of high-fat and low-fat meals, glucose solution, and saline, and of intravenous metoclopramide and oral cisapride were defined in healthy fasted subjects by serial measurements over 5 h. Hyaluronan was measured by a radiometric assay. RESULTS: After test meals and glucose ingestion, plasma hyaluronan rose to 1.7-13 times the fasting levels in 11 healthy volunteers. Peak values were observed in most subjects 45-90 min after ingestion and reached levels in six subjects that might suggest the presence of hepatic fibrosis or cirrhosis. No change occurred after ingestion of 0.48 L iso-osmotic NaCl solution, equal in bulk to the glucose solution. Stimulation of gastrointestinal motility with metoclopramide had no effect but oral cisapride induced a pattern of elevated plasma hyaluronan which mimicked that induced by foodstuffs. CONCLUSIONS: Displacement of hyaluronan from gastrointestinal tissues prevails over the increased clearance expected from elevated portal blood flow. The heightened flux of tissue fluid necessary to displace tissue hyaluronan is best explained by vasodilatation in response to ingestion of nutrients, and subsequent increase in intestinal lymph flow, rather than by fluid absorption, together with gut contraction. The discriminating value of plasma hyaluronan in clinical practice may be greatly enhanced by sampling in fasted subjects at rest.

Administration, Oral↗
PubMed2005

Reinforcing the mucus: a new therapeutic approach for ulcerative colitis?

Luminal delivery of phosphatidyl rich phospholipids appears to reduce mucosal inflammatory activity in a high proportion of patients with chronically active ulcerative colitis. The simplicity and apparent safety of this therapeutic approach offers new insights into the importance of the mucus barrier in the pathogenesis and treatment of ulcerative colitis.

Colitis, Ulcerative↗
PubMed2003

Dietary fibre: a roughage guide.

The concept of dietary fibre is a complex one that incorporates the physical and physiological functions of fibre and its effects both systemically and local to the gastro-intestinal tract. Dietary fibre can be usefully classified according to its solubility and fermentability, which allows rational clinical application. Fibres may act in several ways including by gel-forming effects in the stomach and small intestine, by its fermentation by colonic bacteria, by a 'mop and sponge' effect, and via concomitant changes in other aspects of the diet. These actions lead to potentially beneficial effects in the gastro-intestinal tract and systemically, such as lowering serum cholesterol and improving glycaemic control. Dietary fibre has been implicated in multiple clinical situations but, although an extensive literature on putative actions and proposed physiological bases is available, high-level evidence of efficacy is limited. Nevertheless, encouraging the intake of a high-fibre diet is likely to have a range of health benefits and physicians are encouraged to follow simple practical guidelines in their everyday practice.

Australia↗
PubMed2002

Effect of dietary fatty acids on the intestinal permeability of marker drug compounds in excised rat jejunum.

The aim of this study was to explore the effects of diets containing saturated fatty acids (SFA), monounsaturated fatty acids (MUFA), and omega-3 and omega-6 polyunsaturated fatty acids (omega-3 and omega-6 PUFA, respectively) on the passive and active transport properties of rat jejunum using marker compounds. Rats were fed diets supplemented with 18.4% (w/w) lipid (4 groups) or standard rat chow (1 group) for a period of 30 days. At the end of the dietary period, mucosal scrapings were taken for the determination of membrane phospholipids, and the apparent jejunal permeability of radiolabelled marker compounds was determined using modified Ussing chambers. Changes in the phospholipid content of the brush border membrane reflected the different lipid content of the diets. The passive paracellular permeability of mannitol was not significantly affected by the fatty acid composition of the diet, although there was a trend toward decreased mannitol permeability in the rats fed both the omega-3 and omega-6 PUFA diets. In comparison, the transcellular diffusion of diazepam was reduced by 20% (P < 0.05) in rats fed diets supplemented with omega-3 and omega-6 PUFA. In the lipid-fed rats, the serosal to mucosal flux of digoxin, an intestinal P-glycoprotein substrate, was reduced by 20% (P < 0.05) relative to the chow-fed group, however there were no significant differences between the different lipid groups. The active absorption of D-glucose via the Na+-dependent transport pathway was highest in the SFA, MUFA and PUFA omega-3 dietary groups, intermediate in the low-fat chow group and lowest in the PUFA omega-6 group, and was positively correlated with short-circuit current. These studies indicate that dietary fatty acid changes can result in moderate changes to the active and passive transport properties of excised rat jejunum.

Analysis of Variance↗
PubMed2001

Dietary fiber and colorectal neoplasia.

PURPOSE: Dietary fiber has been implicated in colorectal neoplasia, despite conflicting evidence. This is a review of the currently available data on the role of dietary fiber in colorectal carcinogenesis. METHODS: A literature search was conducted using the MEDLINE database. All case-control, longitudinal, and randomized, controlled studies published in English between 1988 and 2000 were identified, as were animal model studies in the period 1986 to 2000. Data from the various studies were tabulated and systematically analyzed, with particular emphasis on the effect of dietary fiber on tumor incidence and luminal parameters such as short chain fatty acids. RESULTS: Epidemiologic correlation studies show a high intake of dietary fiber to be associated with a lower risk of colorectal neoplasia. Thirteen of the 24 case-control studies reviewed demonstrated a protective effect of dietary fiber against colorectal neoplasia, and 16 showed a protective effect of vegetables or vegetable fiber. On the other hand, of 13 longitudinal studies in various cohorts, only 3 demonstrated a protective effect of fiber and 4 a protective effect of vegetables or vegetable fiber. The five published randomized, controlled trials all investigated the effect of increased fiber intake on short-term adenoma recurrence; however, none showed any significant protective effect. Among 19 experimental studies in animal models, 15 showed a protective effect of fiber against tumor induction compared with controls. Animal studies also showed that poorly fermentable fibers (e.g., wheat bran and cellulose) were more protective than soluble fibers (e.g., guar gum and oat bran), which sometimes enhanced carcinogenesis. No clear correlation was found between luminal pH or short chain fatty acids and tumor induction. CONCLUSIONS: On the basis of current data, there is little evidence to support the use of dietary fiber supplements to reduce the risk of colorectal neoplasia. Lifelong and early exposure may be important but are difficult to study. Other risk factors interact with the effects of dietary fiber.

Animals↗
PubMed2001

Early Australian experience with infliximab, a chimeric antibody against tumour necrosis factor-alpha, in the treatment of Crohn's disease: is its efficacy augmented by steroid-sparing immunosuppressive therapy? The Infliximab User Group.

BACKGROUND: Tumour necrosis factor-alpha (TNF-alpha) plays an important role in the pathology of Crohn's disease. Infliximab, a chimeric antibody against TNF-alpha, has been shown in controlled clinical trials to be effective in two-thirds of patients with refractory or fistulating Crohn's disease. The factors that determine a clinical response in some patients but not others are unknown. AIMS: To document the early Australian experience with infliximab treatment for Crohn's disease and to identify factors that may determine a beneficial clinical response. METHODS: Gastroenterologists known to have used infliximab for Crohn's disease according to a compassionate use protocol were asked to complete a spreadsheet that included demographic information, Crohn's disease site, severity, other medical or surgical treatments and a global clinical assessment of Crohn's disease outcome, judged by participating physicians as complete and sustained (remission for the duration of the study), complete but unsustained (remission at 4 weeks but not for the whole study) or partial clinical improvement (sustained or unsustained). RESULTS: Fifty-seven patients were able to be evaluated, with a median follow-up time of 16.4 (4-70) weeks, including 23 patients with fistulae. There were 21 adverse events, including four serious events. Fifty-one patients (89%) had a positive clinical response for a median duration (range) of 11 (2-70) weeks. Thirty patients (52%) had a remission at 4 weeks, 10 of whom had remission for longer than 12 weeks. Forty-two per cent of fistulae closed. Sustained remission (P = 0.065), remission at 4 weeks (P = 0.033) and a positive clinical response of any sort (P = 0.004) were more likely in patients on immunosuppressive therapy, despite there being more smokers in this group. CONCLUSION: This review of the first Australian experience with infliximab corroborates the reported speed and efficacy of this treatment for Crohn's disease. The excellent response appears enhanced by the concomitant use of conventional steroid-sparing immunosuppressive therapy.

Adolescent↗
PubMed2001

Resistance to butyrate-induced cell differentiation and apoptosis during spontaneous Caco-2 cell differentiation.

BACKGROUND & AIMS: The short-chain fatty acid butyrate induces cell cycle arrest, differentiation, and apoptosis in colon cancer cells, but often induces opposite effects in normal colonic epithelial cells. We determined whether response to butyrate is dependent on the basal differentiation status of colonic epithelial cells. METHODS: Caco-2 cells at progressive stages of differentiation were treated with butyrate, and endpoints were measured. RESULTS: Response of Caco-2 cells to butyrate was dependent on their differentiation status. Butyrate maximally stimulated cell cycle arrest, apoptosis, alkaline phosphatase activity, transepithelial resistance, cell migration, urokinase receptor expression, and interleukin 8 secretion in undifferentiated Caco-2 cells, whereas differentiated Caco-2 cells were essentially resistant to these effects. Consistently, butyrate selectively induced histone hyperacetylation in undifferentiated Caco-2 cells. This resistance was also observed during HT29cl.19A cell differentiation, but not in the nondifferentiating SW620 cell line. Finally, the rate of butyrate use significantly increased as Caco-2 cells underwent spontaneous differentiation. CONCLUSIONS: Colonic epithelial cells become progressively more refractory to the effects of butyrate during absorptive cell differentiation. We postulate that this resistance is caused by the rapid use of butyrate by differentiated Caco-2 cells, which likely results in low intracellular concentrations and subsequently in its inability to inhibit histone deacetylase.

Acetylation↗
PubMed2001

Insulin-like growth factor-II renders LIM 2405 human colon cancer cells resistant to butyrate-induced apoptosis: a potential mechanism for colon cancer cell survival in vivo.

Butyrate has potent anti-tumorigenic effects on many colon cancer cell lines, including inhibition of growth and promotion of apoptosis in vitro. Nevertheless, despite the butyrate concentration in the colonic lumen being sufficient to result in the death of almost all cells in vitro, colon cancers still develop and grow in vivo, suggesting that cancer cells must develop mechanisms by which they escape the effects of butyrate observed in vitro. Insulin-like growth factor-II (IGF-II) is an autocrine growth factor in many colon cancer cells. The aim of this study was to determine whether IGF-II influences butyrate-mediated apoptosis in LIM 2405 human colon cancer cells. Butyrate and trichostatin A, both of which are histone deacetylase inhibitors although the latter is more specific, induced apoptosis as determined by floating cell counting, Hoechst 33258 staining, DNA laddering and a cell death detection ELISA. IGF-II inhibited the effects of both agents. Butyrate but not trichostatin A also induced LIM 2405 cell migration. In contrast to the above results, IGF-II enhanced butyrate-induced cell migration. Levels of IGF binding protein-3 (IGFBP-3), which may induce apoptosis by IGF-dependent or -independent mechanisms, were increased by butyrate and trichostatin A; IGF-II augmented this effect. It is therefore unlikely that IGFBP-3 mediates butyrate-induced apoptosis. We suggest that IGF-II inhibits the pro-apoptotic effect of butyrate downstream of histone deacetylase inhibition. In contrast, IGF-II promotes histone deacetylase-dependent IGFBP-3 expression and histone deacetylase-independent migration. IGF-II may promote tumour growth by mediating the development of resistance to the pro-apoptotic effects of butyrate.

Apoptosis↗
PubMed2000

Short-chain fatty acids reduce expression of specific protein kinase C isoforms in human colonic epithelial cells.

LIM1215 colon cancer cells were used as a model of human colonic epithelium to examine the effects of butyrate on protein kinase C (PKC) activity and isoform expression. On Western blot analysis, LIM1215 cells express the PKC isoforms alpha, beta, epsilon, zeta, and lambda, but not gamma, straight theta, or micro. Treatment with 2 mM butyrate for 48 h reduced cellular PKC activity up to 50% and specifically reduced the expression of PKC alpha and PKC epsilon. Similar results were obtained using Caco-2 colon cancer cells. These effects were neither a consequence of the induction of differentiation itself nor the result of direct or indirect activation of PKC. Although dependent on gene transcription and protein synthesis, the effect was not due to a reduction in the synthesis of PKC protein. Butyrate's effect was independent of its beta-oxidation but was mimicked, at least in part, by trichostatin A, an inhibitor of histone deacetylase.

Butyrates↗
PubMed2000

Divergent phenotypic patterns and commitment to apoptosis of Caco-2 cells during spontaneous and butyrate-induced differentiation.

Caco-2 cells differentiate spontaneously when cultured in confluence and on exposure to the physiologically relevant short-chain fatty acid, butyrate. This study aimed to compare the phenotype induced by these pathways and their relations to cell turnover. Caco-2 cells were treated with butyrate at a nontoxic concentration of 2 mM for 3 days, or allowed to spontaneously differentiate for 0-21 days. Brush border hydrolase activities and carcinoembryonic antigen (CEA) expression, transepithelial resistance and dome formation, expression of components of the urokinase system, and cell turnover by flow cytometry, and the degree of DNA fragmentation were quantified. Butyrate induced increases in alkaline phosphatase activity and CEA expression but not the activities of other hydrolases, while culture alone induced progressive increases in the activities/expression of all markers. Butyrate induced a significantly greater increase in transepithelial resistance (TER) than occurred during culture alone but the densities of domes were similar. Butyrate induced a ninefold increase in urokinase receptor expression and twofold increase in urokinase activity, while culture alone induced a significantly smaller increase in receptor expression, an increase in plasminogen activator inhibitor-1 but no change in activity. While both stimuli induced cell cycle arrest, only butyrate increased the proportion of cells undergoing apoptosis. In conclusion, differentiation of Caco-2 cells can proceed along multiple pathways but does not necessarily lead to apoptosis. The phenotypic changes during spontaneous differentiation mimic those that occur in normal colonic epithelial cells in vivo during their migration from the crypt base to neck, while butyrate-induced effects more closely follow those occurring when normal colonic epithelial cells migrate from crypt neck to the surface compartment.

Alkaline Phosphatase↗
PubMed2000

Effect of hepatobiliary disease, chronic hepatitis C and hepatitis B virus infections and interferon-alpha on porphyrin profiles in plasma, urine and faeces.

BACKGROUND: Documentation of the profiles of porphyrins in hepatobiliary disease is limited. Strong associations of hepatitis B and C virus infections with porphyria cutanea tarda have suggested causal relationships. This study aimed to determine the nature of porphyrin abnormalities in hepatobiliary disease and the effect of interferon-alpha on porphyrin profiles. METHODS: Total porphyrins were measured in the plasma, urine and faeces of 83 patients with hepatobiliary disease (37 hepatitis C, 20 hepatitis B, 26 other causes) and 12 clinical controls, and porphyrin profiles were determined by high-performance liquid chromatography. RESULTS: Porphyrins were elevated in the plasma of 11 and urine of 23 patients with hepatobiliary disease, as a result of elevated coproporphyrin I. This was reflected in increased coproporphyrin I:III ratios. Abnormal total porphyrin levels had a significant negative correlation with plasma albumin, and a positive correlation with bilirubin and alkaline phosphatase, but not with aminotransferases. Total urinary porphyrins were elevated in three control patients, but coproporphyrin I:III ratios were normal. Although not seen in plasma or urine, porphyrins that are specific for porphyria cutanea tarda were found in the faeces of six patients, but this occurred with similar frequency in hepatitis B or C infection (four of 50) as in the clinical controls (two of 12). Interferon-alpha had no effect during or after therapy in six patients with hepatitis C. CONCLUSIONS: Reduced biliary excretion of coproporphyrin I occurs in more severe cholestasis and/or hepatic dysfunction. A causal relationship between viral liver disease and porphyria cutanea tarda which is unlikely to be precipitated by interferon-alpha, is not supported.

Adult↗