Inulin is a soluble dietary fibre, also classified as a prebiotic, extracted from chicory roots. The present study aimed to determine the effect of consumption of native chicory inulin on the stool frequency of middle-aged to older adults (40-75 years old) with uncomfortably but not clinically relevant low stool frequency, specified as two to four days without bowel movements per week. Two randomised, double blind, placebo-controlled crossover trials were conducted using similar protocols in differing populations.
View Article and Find Full Text PDFCurrent guidelines advocate using fixed-doses of oral vitamin K to reverse excessive anticoagulation in warfarinised patients who are either asymptomatic or have minor bleeds. Over-anticoagulated patients present with a wide range of International Normalised Ratio (INR) values and response to fixed doses of vitamin K varies. Consequently a significant proportion of patients remain outside their target INR after vitamin K administration, making them prone to either haemorrhage or thromboembolism.
View Article and Find Full Text PDFVitamin K is essential, for the activation of clotting proteins, as well as the biosynthesis of osteocalcin in bones and the activation of matrix-Gla protein needed in maintaining vasculature health. Cytochrome p450 4F2 (CYP4F2) enzyme is involved in vitamin K catabolism. Genetic polymorphism in CYP4F2 is thus likely to affect vitamin K systemic availability.
View Article and Find Full Text PDFGraefes Arch Clin Exp Ophthalmol
April 2017
Purpose: Intravitreal anti-vascular endothelial growth factor (VEGF) agents are effective in the treatment of central involving diabetic macular oedema (DMO). Vitreoretinal interface abnormalities (VRIA) are common in patients with DMO, and the effect of these on the response to anti-VEGF treatment is unclear. Furthermore the effect of anti-VEGF agents on the VRIA itself is uncertain.
View Article and Find Full Text PDFPurpose: A dissociated optic nerve fibre layer (DONFL) is a characteristic change noted in inner retinal morphology after internal limiting membrane (ILM) peeling. It is thought to be due to trauma to Muller cells as the ILM is peeled from their attached end plates. In this study, we aimed to determine the extent and size of Muller cell debris on the retinal side of excised ILM and assess whether this correlated with the extent of DONFL observed postoperatively.
View Article and Find Full Text PDFPatella resurfacing during primary total knee arthroplasty (TKA) remains controversial. Variation in published results for patella resurfacing may potentially be explained by differences in design between TKA brands. We interrogated NJR-PROMs data to ascertain whether there is an early functional benefit to resurfacing the patella, both overall and for each of the five most popular primary knee designs through use of the Oxford Knee Score.
View Article and Find Full Text PDFAims: Previous genome-wide linkage analysis has suggested that chromosomal region 17p13.3 may harbour genes influencing left ventricular mass (LVM) in man. To date, the genetic factors accounting for LVM variability remain largely unknown but a non-coding RNA gene within this region, micro-RNA 22 (miR-22), has been implicated in cardiac hypertrophy and heart failure in animal models.
View Article and Find Full Text PDFJ Bone Joint Surg Am
September 2012
Background: Unicompartmental knee arthroplasty has been associated with consistently worse implant survival rates than total knee arthroplasty in worldwide arthroplasty registers. The rate of revision and the proportion of revisions performed for unexplained knee pain after either a unicompartmental or total knee arthroplasty were studied to assess if there is evidence to support the hypothesis that the numbers of revisions performed for unexplained knee pain differ between these two implant types.
Methods: Using data from the National Joint Registry (NJR) of England and Wales, we identified 402,714 primary knee arthroplasties (366,965 total knee arthroplasties and 35,749 unicompartmental knee arthroplasties) that were consecutively entered from April 2003 to December 2010.
Objectives: There is growing emphasis on minimizing surgical delay for neck of femur fractures. Surgery within 36 h of diagnosis by the emergency department (ED) is classed as a key performance indicator. We aimed to determine the influence of the effect of time of presentation to the ED on surgical delay and 90-day mortality.
View Article and Find Full Text PDFAlthough genetic and environmental factors explain approximately half of the interindividual variability in warfarin dose requirement in adults, there is limited information available in children. In a cross-sectional study of anticoagulated children from 5 tertiary care centers, 120 children with a stable warfarin dose were genotyped for VKORC1 (-1639G > A; rs9923231), CYP2C9 (*2 and *3 alleles; rs1799853 and rs1057910), and CYP4F2 (V433M; rs2108622) polymorphisms. Clinical and demographic features were recorded.
View Article and Find Full Text PDFThis study addresses the epidemiology of knee injuries in adolescent males. Data were collected prospectively from 41 Premiership soccer academies over a 5 year period from July 2000 to June 2005. A total of 12,306 player seasons were registered in the U9 to the U16 age categories with a total of 1750 recordable injuries specific to the knee joint.
View Article and Find Full Text PDFObjective: The combined thickness of the intima and media of the carotid artery (carotid intima-medial thickness, CIMT) is associated with cardiovascular disease and stroke. Previous studies indicate that carotid intima-medial thickness is a significantly heritable phenotype, but the responsible genes are largely unknown. Hexose-6 phosphate dehydrogenase (H6PDH) is a microsomal enzyme whose activity regulates corticosteroid metabolism in the liver and adipose tissue; variability in measures of corticosteroid metabolism within the normal range have been associated with risk factors for cardiovascular disease.
View Article and Find Full Text PDFBackground: Polymorphisms in 11-β hydroxysteroid dehydrogenase type 1 (11β-HSD1, encoded by HSD11B1) have been reported to be associated with obesity-related cardiovascular risk factors, such as type II diabetes and hypertension. Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular death associated with these factors but has significant additional heritability, the cause of which is undetermined. The 11β-HSD1 is believed to maintain tonic inhibition of the mineralocorticoid receptor in cardiomyocytes, and mineralocorticoid receptor activation is involved in the pathophysiology of LVH.
View Article and Find Full Text PDFAims: Genetic variation in the fatty acid translocase (CD36) gene has been shown in animal models to affect several risk factors for the development of left-ventricular hypertrophy, but this phenotype has not, thus far, been investigated in humans. We examined the relationship between common genetic polymorphisms in the CD36 gene and left-ventricular mass.
Methods And Results: We studied a cohort of 255 families comprising 1425 individuals ascertained via a hypertensive proband.
Background: Blood pressure (BP) has significant heritability, but the genes responsible remain largely unknown. Single nucleotide polymorphisms (SNPs) at the STK39 locus were recently associated with hypertension by genome-wide association in an Amish population; in vitro data from transient transfection experiments using reporter constructs suggested that altered STK39 expression might mediate the effect. However, other large studies have not implicated STK39 in hypertension.
View Article and Find Full Text PDFThe P2X receptor gene family encodes a series of proteins that function as ATP-gated nonselective ion channels. P2X receptor channels are involved in transducing aldosterone-mediated signaling in the distal renal tubule and are potential candidate genes for blood pressure regulation. We performed a family based quantitative genetic association study in 248 families ascertained through a proband with hypertension to investigate the relationship between common genetic variation in the P2X4, P2X6, and P2X7 genes and ambulatory blood pressure.
View Article and Find Full Text PDFAims: To localize chromosomal regions (or quantitative trait loci) that harbour genetic variants influencing the variability of electrocardiographic (ECG) and echocardiographic left ventricular hypertrophy (LVH).
Methods And Results: We evaluated genetic linkage to ECG Sokolow-Lyon voltage, ECG Cornell voltage product, ECG left ventricular (LV) mass, and to echocardiographic septal wall thickness, LV cavity size, and LV mass in 868 members of 224 white British families. A genome-wide scan was performed with microsatellite markers that covered the genome at 10-cM intervals and linkage was assessed by variance components analysis.
Am J Physiol Regul Integr Comp Physiol
March 2008
Plasma potassium is a moderately heritable phenotype, but no robust associations between common single nucleotide polymorphisms (SNPs) and plasma potassium have previously been described. Genetic influences on renal potassium handling could be important in the etiology of hypertension. We have tested whether common genetic variation in the gene encoding the beta-subunit of the epithelial sodium channel (SCNN1B) affects plasma potassium and blood pressure level in a study of 1,425 members of 248 families ascertained on a proband with hypertension.
View Article and Find Full Text PDFAims: The ADIPOQ gene encodes the protein adiponectin, and decreased circulating adiponectin levels have been observed in cardiovascular disease. We investigated the role of the ADIPOQ gene single-nucleotide polymorphisms (SNPs) A-11426G, G-11391A, C-11377G, and T45G with plasma adiponectin levels and common carotid artery intima media thickness (IMT) in a cohort of healthy subjects participating in the RISC (Relationship between Insulin Sensitivity and Cardiovascular disease) study.
Methods And Results: Anthropometric and metabolic assessment and B-mode ultrasound of the carotid IMT were measured in 1306 subjects [589 men; 717 women, mean +/- SD age 43.
Background: Many previous studies have investigated whether there is an association between genotypes at the angiotensinogen (AGT) gene and hypertensive status, but few have incorporated quantitative data. Although meta-analyses support a possible effect of AGT variants on blood pressure (BP), substantial unexplained between-study heterogeneity has been observed. We hypothesized that a primary effect of AGT variants on arterial stiffness (and thus pulse pressure) might explain such heterogeneity, and tested for such an effect in a family study.
View Article and Find Full Text PDFBackground: Obesity is a major public health problem. Body mass index (BMI) is a highly heritable phenotype but robust associations of genetic polymorphisms to BMI or other obesity-related phenotypes have been difficult to establish. Recently a large genetic association study showed evidence for association of the single nucleotide polymorphism (SNP) rs7566605, which lies 10 Kb 5' to the first exon of the insulin-induced gene 2 (INSIG-2), with obesity in several cohorts.
View Article and Find Full Text PDFContext: Variation in the region of chromosome 8 including the genes steroid 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) influences mineralocorticoid and glucocorticoid metabolism. However, the relative importance of polymorphisms in CYP11B1 and CYP11B2 in determining these phenotypes is unknown.
Objective: Our objective was to investigate genetic influences of the CYP11B1 and CYP11B2 genes on mineralocorticoid metabolism.
Background And Purpose: Studies in unrelated individuals have produced conflicting findings concerning the putative association between the interleukin-6 (IL-6) -174G/C polymorphism and carotid intimal-medial thickness (IMT). We have used a family-based genetic association design to assess the heritability of carotid IMT and to investigate the hypothesized association of carotid IMT with the IL-6 to -174G/C polymorphism.
Methods: We studied 854 members of 224 white British families.
Rare mutations in the proopiomelanocortin (POMC) gene cause severe early-onset childhood obesity. However, it is unknown whether common variants in POMC are responsible for variation in body weight or fat distribution within the commonly observed range in the population. We tested for association between three polymorphisms spanning the POMC gene and obesity phenotypes in 1,428 members of 248 families.
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