Why children with inflammatory bowel disease are diagnosed at a younger age than their affected parent.

Background: Genetic anticipation has been proposed to explain observed age differences at diagnosis of Crohn's disease in affected parents and offspring.

Aims: To compare affected parent-child pairs with Crohn's disease and ulcerative colitis with a control group of non-familial patients with inflammatory bowel disease (IBD) in order to quantify whether ascertainment bias could account for this effect.

Methods: 137 affected parent-child pairs from 96 families and 214 patients with sporadic IBD were studied.

A genomewide analysis provides evidence for novel linkages in inflammatory bowel disease in a large European cohort.

Inflammatory bowel disease (IBD) is characterized by a chronic relapsing intestinal inflammation, typically starting in early adulthood. IBD is subdivided into two subtypes, on the basis of clinical and histologic features: Crohn disease and ulcerative colitis (UC). Previous genomewide searches identified regions harboring susceptibility loci on chromosomes 1, 3, 4, 7, 12, and 16.

The interferon-gamma gene as a positional and functional candidate gene for inflammatory bowel disease.

Epidemiological and genome-wide linkage analyses have provided firm evidence for a genetic component in the pathogenesis of inflammatory bowel disease. The linkage regions on chromosomes 12 and 16 have been replicated in several independent samples. These represent the best positional evidence in the search for inflammatory bowel disease susceptibility genes.

Effect of vitamin E and selenium supplementation of cockerel diets on glutathione peroxidase activity and lipid peroxidation susceptibility in sperm, testes, and liver.

The phospholipids of avian spermatozoa are characterized by high proportions of arachidonic (20:4n-6) and docosatetraenoic (22:4n-6) fatty acids and are therefore sensitive to lipid peroxidation. Alpha-tocopherol and glutathione peroxidase [GSH-Px] are believed to be the primary components of the antioxidant system of the spermatozoa. The present study evaluates the effect of vitamin E and vitamin E plus Se supplementation of the cockerel diet on GSH-Px activity, vitamin E accumulation, and lipid peroxidation in the spermatozoa, testes, and liver.

Children's exposure to traffic and pedestrian injuries.

Objectives: The purpose of this study was to estimate children's exposure to traffic (number of streets crossed) and to determine the role of exposure in pedestrian injury.

Methods: Questionnaires were distributed to a random sample of 4080 first- and fourth-grade children in 43 Montreal schools.

Results: When analyzed by police district, injury and exposure rates were positively correlated (r2 = 0.

Intestinal permeability and inflammation in patients on NSAIDs.

Background: The frequency with which non-steroidal anti-inflammatory drugs (NSAIDs) increase small intestinal permeability and cause inflammation is uncertain.

Aims: To examine small intestinal permeability and inflammation in a large number of patients on long term NSAIDs.

Methods: Sixty eight patients receiving six different NSAIDs for over six months underwent combined absorption-permeability tests at three different test dose osmolarities (iso-, hypo-, and hyperosmolar).

Genetic analysis of inflammatory bowel disease in a large European cohort supports linkage to chromosomes 12 and 16.

Background & Aims: Inflammatory bowel disease (IBD) is a complex disorder of unknown etiology. Epidemiological investigations suggest a genetic basis for IBD. Recent genetic studies have identified several IBD linkages.

The effect of oral selenium supplementation on human sperm motility.

Objectives: To determine whether the decline in selenium intake and selenium status in men in the West of Scotland might be a contributory factor to male subfertility.

Patients And Methods: Two semen samples were collected from patients attending a subfertility clinic and those patients with samples showing reduced motility were invited to participate in an ethically approved double-blind clinically controlled trial with informed consent. Sixty-nine patients were recruited and received either placebo, selenium alone or selenium plus vitamins A, C and E daily for 3 months.

Effect of supplementing the hen's diet with vitamin A on the accumulation of vitamins A and E, ascorbic acid and carotenoids in the egg yolk and in the embryonic liver.

1. The effect of a range of supplementations of vitamin A to the laying hen on the concentration of vitamins A, E, ascorbic acid and carotenoids in the maternal liver, the egg yolk and the embryonic liver were investigated. 2.

Mitochondrial damage: a possible mechanism of the "topical" phase of NSAID induced injury to the rat intestine.

Background: The "topical" effect of non-steroidal anti-inflammatory drugs (NSAIDs) seems to be an important cause of NSAID induced gastrointestinal damage.

Aim: To examine the possible mechanism of the "topical" phase of damage in the small intestine.

Methods: Electron microscopy and subcellular organelle marker enzyme studies were done in rat small intestine after oral administration of indomethacin (doses varied between 5 and 30 mg/kg).

Intestinal tolerability of nitroxybutyl-flurbiprofen in rats.

Background: Nitric oxide derivatives of non-steroidal anti-inflammatory drugs (NSAIDs) are thought to be much less ulcerogenic than their parent compounds.

Aim: To compare the effect and potency of flurbiprofen and nitroxybutyl-flurbiprofen to uncouple mitochondrial oxidative phosphorylation (an early pathogenic event in NSAID enteropathy), increase intestinal permeability (transitional stage), and cause macroscopic small intestinal damage.

Methods: In vitro uncoupling potency was assessed using isolated coupled rat liver mitochondria and in vivo by electron microscopy of rat small intestinal mucosa (two hours after the drugs).

CD4+ T cell down-regulation in human intestinal mucosa: evidence for intestinal tolerance to luminal bacterial antigens.

T cells from the intestinal mucosal proliferate poorly in vitro, and the contribution of Ag-specific recognition to this hyporesponsiveness is unclear, since the Ag repertoire of intestinal mucosal T cells is unknown. In this study, T cell proliferation in response to Ag-prepulsed autologous peripheral blood-derived APC was examined. Whereas T cells from peripheral blood proliferated to inner membrane and cytoplasmic Escherichia coli proteins, T cells from intestinal mucosa responded only to purified component Ags of these proteins and not to their combination.

Protection against tetanus toxin in mice nasally immunized with recombinant Lactococcus lactis expressing tetanus toxin fragment C.

Mice inoculated intranasally (i.n.) with a recombinant strain of live Lactococcus lactis expressing tetanus toxin fragment C (TTFC), produced both serum and secretory antibodies to TTFC.

Reduced bone density in patients with inflammatory bowel disease.

Background: Reduced bone mineral density in patients with inflammatory bowel disease is thought to be due to disturbances in calcium homeostasis or the effects of corticosteroid treatment.

Aims: To assess the prevalence and mechanism of reduced bone mineral density in 79 patients with inflammatory bowel disease (44 with Crohn's disease, 35 with ulcerative colitis) who did not have significant risk factors for low bone densities.

Methods: Dual x ray absorptiometry was used to measure bone mineral density and serum and urinary markers of osteoblast (alkaline phosphatase, procollagen 1 carboxy terminal peptide and osteocalcin) and osteoclast (pyridinoline, deoxypyridinoline, and type 1 collagen carboxy terminal peptide) activities to assess bone turnover.

A randomized, double-blind, crossover comparative endoscopy study on the gastroduodenal tolerability of a highly specific cyclooxygenase-2 inhibitor, flosulide, and naproxen.

Background: Inhibition of constitutively expressed cyclooxygenase (Cox-1) is thought to play an important role in the gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs (NSAID), while their therapeutic action may be due to inhibition of the enzyme Cox-2, which is specifically expressed at sites of inflammation. NSAIDs with high affinity and specifity for Cox-2 hold the promise of maintaining efficacy without the gastrointestinal side effects of conventional NSAIDs.

Methods: We assessed the gastrointestinal tolerability of flosulide (20 mg twice a day), a highly selective Cox-2 inhibitor with that of naproxen (500 mg twice a day), which has equal affinity for Cox-1 and -2 in 19 patients with osteoarthrosis in a randomized, double blind, crossover endoscopy study.

Effect of supplementation with selenium on whole blood glutathione peroxidase activities and on plasma and tissue selenium concentrations in lambs.

In recent years the selenium (Se) intake of the human population of the UK has shown a marked decline from 60 micrograms/d in 1978 to around 30 micrograms/d in 1990 owing largely to a significant reduction in the importation of North American wheat for bread-making flour. Other countries (Finland, for example) in similar situations have instituted fertilization programs in order to raise cereal Se concentrations and thus boost dietary intakes. An alternative approach would be to increase the Se concentration of carcass meat by supplementation of meat animals for a limited period prior to slaughter.

Intestinal inflammation, ileal structure and function in HIV.

Objectives: This study examines small intestinal absorption-permeability, intestinal inflammation and ileal structure and function in HIV-positive male homosexuals.

Methods: Thirty HIV-seropositive male homosexuals at various stages of disease underwent intestinal absorption permeability and 111indium leukocyte studies (for quantification of intestinal inflammation). Twenty-six men with AIDS had a dual radioisotopic ileal function test (whole body retention of tauro 23-[75Se]-selena 25-homocholic acid and 58cobalt-labelled cyanocobalamine), and 17 underwent ileocolonoscopy with terminal ileal biopsy.

Evaluation of differential disaccharide excretion in urine for non-invasive investigation of altered intestinal disaccharidase activity caused by alpha-glucosidase inhibition, primary hypolactasia, and coeliac disease.

Background/aim: The reliability of a quantitative method for the non-invasive assessment of intestinal disaccharide hydrolysis was assessed.

Methods: Differential excretion of intact disaccharide, expressed as ratios of lactulose to appropriate hydrolysable disaccharides in urine collected following combined ingestion, has been investigated in healthy volunteers with drug induced alpha-glucosidase inhibition, in subjects with primary hypolactasia, and patients with coeliac disease.

Results: Oral administration of the alpha-glucosidase inhibitor 'Acarbose' (BAY g 5421, 200 mg) together with sucrose and lactulose increased the urinary sucrose/lactulose excretion ratios (% dose/10 h) fivefold.

Factors affecting the immunogenicity of tetanus toxin fragment C expressed in Lactococcus lactis.

The relative immunogenicity of tetanus toxin fragment C (TTFC) has been determined in three different strains of inbred mice when expressed in Lactococcus lactis as a membrane-anchored protein (strain UCP1054), as an intracellular protein (strain UCP1050), or as a secreted protein which is partly retained within the cell wall (strain UCP1052). Protection against toxin challenge (20 x LD50) could be obtained without the induction of anti-lactococcal antibodies. When compared in terms of the dose of expressed tetanus toxin fragment C required to elicit protection against lethal challenge the membrane-anchored form was significantly (10-20 fold) more immunogenic than the alternative forms of the protein.

Mucosal antibodies in inflammatory bowel disease are directed against intestinal bacteria.

In contrast with normal subjects where IgA is the main immunoglobulin in the intestine, patients with active inflammatory bowel disease (IBD) produce high concentrations of IgG from intestinal lymphocytes, but the antigens at which these antibodies are directed are unknown. To investigate the specificities of these antibodies mucosal immunoglobulins were isolated from washings taken at endoscopy from 21 control patients with irritable bowel syndrome, 10 control patients with intestinal inflammation due to infection or ischaemia, and 51 patients with IBD: 24 Crohn's disease (CD, 15 active, nine quiescent), 27 ulcerative colitis (UC, 20 active, seven inactive). Total mucosal IgG was much higher (p < 0.

Selenium content of convenience and fast foods in Ayrshire, Scotland.

Selenium concentrations were determined via hydride generation atomic absorption spectrometry in more than 100 convenience and fast foods including 34 vegetarian dishes. The foods were purchased mainly in Ayrshire, Scotland but some came from other parts of the UK. The results indicate a considerable amount of selenium in certain mushrooms, spinach, fish, offals and chicken-based products.