The influence of fibrin sealant on the healing colonic anastomosis : an experimental study in rats

The experiments described in this thesis were performed in order to find methods to influence and improve colonic anastomotic wound healing. It is known that inflammation may affect the healing of colonic anastomoses. Eicosanoids are known mediators of the inflammatory process, being a part of the healing process. In order to influence the healing process anti inflammatory drugs may be used. To evaluate the possible role of eicosanoids in uncomplicated healing of colon anastomosis we decided to measure eicosanoid synthesis in colon tissue and peritoneal macrophages. Activity of peritoneal macrophages was studied based on the HPLC profile of eicosanoids. Colon tissue was studied as well in order to compare both profiles to establish which cell type is active in the healing colon (Chapter IV). Colonic anastomoses may be covered with fibrin sealant in order to promote wound healing and prevent leakage. Presently, this is already performed in many clinical situations. However data from experimental animal studies are conflicting, and prospective clinical studies are lacking. The influence of human· and rat fibrin sealant on the mechanical strength en collagen metabolism of a sutured colonic anastomoses is investigated (Chapter V). Ischemia of the wound margins is a high-risk condition in the healing colonic anastomosis, with a considerable chance of anastomotic dehiscence. The effect of fibrin sealant on the healing ischemic anastomosis is tested (Chapter VI). Another known risk-factor is the presence of peritonitis. The role of fibrin sealant in the presence of faecal peritonitis is described in Chapter VII. A technical imperfect anastomosis may result in leakage of intestinal contents. In order to examen the effect of fib

Advanced glycation end products as a biomarker for incisional hernia

Background: Incisional hernia is one of the most frequent complications after abdominal surgery, with incidences up to 30%. A reliable biomarker for the prediction of this complication is lacking. Advanced glycosylation end products (AGEs), also known as non-enzymatic collagen crosslinks, are correlated with aging, smoking, hyperglycemia, hyperlipidemia and oxidative stress. In this study the accumulation of AGEs and the relation between AGEs and incisional hernia were investigated. Materials and methods: In an explorato

A Randomized Controlled Trial to Examine the Effect of 2-Year Vitamin B12 and Folic Acid Supplementation on Physical Performance, Strength, and Falling: Additional Findings from the B-PROOF Study

Elevated homocysteine concentrations are associated with a decline in physical function in elderly persons. Homocysteine-lowering therapy may slow down this decline. This study aimed to examine the effect of a 2-year intervention of vitamin B12 and folic acid supplementation on physical performance, handgrip strength, and risk of falling in elderly subjects in a double-blind, randomized placebo-controlled trial. Participants aged ≥65 years with elevated plasma homocysteine concentrations [12–50 µmol/L (n = 2919)] were randomly assigned to daily supplementation of 500 µg vitamin B12, 400 µg folic acid, and 600 I

Low vitamin D status is associated with more depressive symptoms in Dutch older adults

Purpose: The existence of vitamin D receptors in the brain points to a possible role of vitamin D in brain function. We examined the association of vitamin D status and vitamin D-related genetic make-up with depressive symptoms amongst 2839 Dutch older adults aged ≥65 years. Methods: 25-Hydroxyvitamin D (25(OH)D) was measured, and five ‘vitamin D-related genes’ were selected. Depressive symptoms were measured with the 15-point Geriatric Depression Scale. Results were expressed as the relative risk of the score of depressive symptoms by quartiles of 25(OH)D concentration or number of affected alleles, using the lowest quartile or minor allele group as reference. Results: A clear cross-sectional and pr

Evaluation of low-dose aspirin in the prevention of recurrent spontaneous preterm labour (the APRIL study) : A multicentre, randomised, double-blinded, placebo-controlled trial

Funding: MdB, LV, TN, BM, MO and CdG received funding from ZonMw, The Dutch Organisation for Health Research and Development (grant number 836041006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Effect of Vitamin B<inf>12</inf> and Folic Acid Supplementation on Bone Mineral Density and Quantitative Ultrasound Parameters in Older People with an Elevated Plasma Homocysteine Level: B-PROOF, a Randomized Controlled Trial

High plasma homocysteine (Hcy) levels are associated with increased osteoporotic fracture incidence. However, the mechanism remains unclear. We investigated the effect of Hcy-lowering vitamin B12 and folic acid treatment on bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) parameters. This randomized, double-blind, placebo-controlled trial included participants aged ≥65 years with plasma Hcy levels between 12 and 50 µmol/L. The intervention comprised 2-year supplementation with either a combination of 500 µg B12, 400 µg folic acid, and 600 IU vitamin D or placebo with 600 IU vitamin D only. In total, 1111 participants underwent repeated dual-energy X-ray assessment and 1165 participants underwent QUS. Femoral neck (FN) BMD, lumbar spine (LS) BMD, calcaneal broadband ultrasound attenuation (BUA), and calcaneal speed of sound (SOS) were assessed. After 2 years, FN-BMD and BUA had significantly decreased, while LS-BMD significantly increased (all p 80 years (estimated marginal mean 64.4 dB/MHz for the intervention group and 61.0 dB/MHz for the placebo group, p = 0.04 for difference). In conclusion, this study showed no overall effect of treatment with vitamin B12 and folic acid on BMD or QUS parameters in elderly, mildly hyperhomocysteinemic persons, but suggests a small beneficial effect on BUA in persons >80 years who were compliant in taking the supplement

Cognitive performance: a cross-sectional study on serum vitamin D and its interplay with glucose homeostasis in Dutch older adults

Objectives First, the association between serum 25-hydroxyvitamin D (25[OH]D) and cognitive performance was examined. Second, we assessed whether there was evidence for an interplay between 25(OH)D and glucose homeostasis in the association with cognitive performance. Design, Setting, and Participants Associations were studied using cross-sectional data of 776 (3 domains) up to 2722 (1 domain) Dutch community-dwelling older adults, aged 65 years or older. Measurements Serum 25(OH)D, plasma glucose, and insulin concentrations were obtained. Cognitive performance was assessed with an extensive cognitive test battery. Prevalence ratios (PRs) were calculated to quantify the association between 25(OH)D and cognition; poor performance was defined as the worst 10% of the distribution of the cognitive scores. Results The overall median MMSE score was 29 (IQR 28–30). Higher serum 25(OH)D was associated with better attention and working memory, PR 0.50 (95% CI 0.29–0.84) for the third serum 25(OH)D tertile, indicating a 50% lower probability of being a poor performer than participants in the lowest tertile. Beneficial trends were shown for 25(OH)D with executive function and episodic memory. Serum 25(OH)D was not associated with plasma glucose or insulin. Plasma insulin only modified the association between serum 25(OH)D and executive function (P for interaction: .001), suggesting that the improvement in executive function with high 25(OH)D concentrations is stronger in participants with high plasma insulin concentrations compared with those with low plasma insulin concentrations. Conclusion Higher 25(OH)D concentrations significantly associated with better attention and working memory performance. This study does not demonstrate an interplay between serum 25(OH)D and glucose homeostasis in the association with cognitive performance