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Biomedical subjects

A Forbes

Publications and source records attributed to A Forbes.

At least 55 records · Page 3Linked to original sources
PubMed2004

Human lymphocyte stimulation with pouchitis flora is greater than with flora from a healthy pouch but is suppressed by metronidazole.

BACKGROUND/AIMS: The gut flora may play an important role in the pathogenesis of inflammatory bowel disease. An ileal reservoir or pouch can be created to replace the excised rectum after proctocolectomy. In patients with ulcerative colitis this is subject to inflammation and termed pouchitis. Using bacteria from patients the authors sought evidence for the presence rather than the identity of a pathogenic species in pouchitis, and for its absence in healthy pouches by the differential effect on lymphocyte proliferation. METHODS: An ex vivo cell culture assay was used in which peripheral blood mononuclear cells or lamina propria mononuclear cells were cultured with sterile sonicates of gut flora from patients with or without pouchitis in the presence of antigen presenting cells. RESULTS: Sonicated pouchitis flora produced a consistent and intense proliferation of the mononuclear cells but that produced by sonicates from healthy pouches was minimal (p = 0.012 or 0.018, peripheral blood or lamina propria mononuclear cells). Preparation of the sonicates with the antibiotic metronidazole abolished their stimulatory ability (p = 0.005, peripheral blood mononuclear cells). In separate assays neither direct addition of metronidazole nor of its hydroxy metabolite affected the mononuclear cells' proliferation with alternative stimuli. CONCLUSIONS: These results strongly support a bacterial aetiology for pouchitis.

Adolescent↗
PubMed2004

Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk.

BACKGROUND AND AIMS: The risk of colorectal cancer is increased in ulcerative colitis (UC). Patients with UC have diverse colonoscopic appearances. Determining colonoscopic markers for cancer risk could allow patient risk stratification. PATIENTS AND METHODS: Following on from an earlier study which demonstrated a correlation between inflammation severity and neoplasia risk, a case control study was performed to look for colonoscopic markers of colorectal neoplasia risk in UC. Each patient with neoplasia detected between 1988 and 2002 was matched with two non-dysplastic colitic controls. Data were collected on post-inflammatory polyps, scarring, strictures, backwash ileitis, a shortened, tubular, or featureless colon, severe inflammation, and normal looking surveillance colonoscopies. RESULTS: Cases (n = 68) and controls (n = 136) were well matched. On univariate analysis, cases were significantly more likely to have post-inflammatory polyps (odds ratio (OR) 2.14 (95% confidence interval 1.24-3.70)), strictures (OR 4.22; 1.08-15.54), shortened colons (OR 10.0; 1.17-85.6), tubular colons (OR 2.03; 1.00-4.08), or segments of severe inflammation (OR 3.38; 1.41-10.13), and less likely to have had a macroscopically normal looking colonoscopy (OR 0.40; 0.21-0.74). After multivariate analysis, a macroscopically normal looking colonoscopy (OR 0.38; 0.19-0.73), post-inflammatory polyps (2.29; 1.28-4.11), and strictures (4.62; 1.03-20.8) remained significant. The five year risk of colorectal cancer following a normal looking colonoscopy was no different from that of matched general population controls. CONCLUSIONS: Macroscopic colonoscopic features help predict neoplasia risk in UC. Features of previous/ongoing inflammation signify an increased risk. A macroscopically normal looking colonoscopy returns the cancer risk to that of the general population: it should be possible to reduce surveillance frequency to five years in this cohort.

Adolescent↗
PubMed2003

Review article: Oral, modified-release mesalazine formulations--proprietary versus generic.

Products containing mesalazine have been used in the treatment of inflammatory bowel disease for many years. Many of the oral, modified-release products are reaching the point of patent expiration, and it is expected that several new 'generic' versions will be developed. As mesalazine acts topically, the drug needs to be available at the site of inflammation to be effective. For this reason, the currently available products have been developed with individual formulations so that physicians have a choice when matching the different release profiles to the site and extent of disease. As such, the current guidelines state that oral, delayed-release mesalazine formulations are not interchangeable and should be prescribed by their proprietary (brand) name. The standard regulatory assessment process for generic or 'copy' products, using systemic bioequivalence data, does not appear to be sufficient when evaluating topically acting, oral, modified-release products. We therefore recommend that the regulatory bodies should require that new, oral mesalazine products should be assessed by a combination of dissolution, bioequivalence and (a minimum of one) adequately powered, comparative trial to determine therapeutic equivalence. Of most importance here is that the assessment of new modified-release products is sufficiently rigorous to allow patients and physicians to be confident in their use.

Administration, Oral↗
PubMed2003

Quantitative trait loci for low aflatoxin production in two related maize populations.

Aflatoxin B(1) formed by Aspergillus flavus Fr:Link has been associated with animal disease and liver cancer in humans. We performed genetic studies in progenies derived from maize inbred Tex6, associated with relatively low levels of aflatoxin production, crossed with the historically important inbred B73. (Tex6 x B73) x B73 BC(1)S(1) and Tex6 x B73 F(2:3) mapping populations were produced and evaluated in 1996 and 1997 in Champaign, Ill. Ears were inoculated 20 to 24 days after midsilk using a pinboard method and a mixture of conidia of A. flavus Link:Fr. isolates. Aflatoxin B(1) levels in harvested ears were determined using an indirect competitive ELISA. Molecular markers were assayed on the populations and used to generate maps. Molecular marker - QTL associations for lower levels of aflatoxin production were determined using multiple regression (MR) and composite interval analysis with multiple regression (CIM MR). MR revealed sets of markers associated with lower aflatoxin production in 1996 and 1997, and CIM MR detected a smaller subset of loci significant in 1997. QTLs for lower aflatoxin were attributed to both Tex6 and B73 parental sources. Environment strongly influenced the detection of QTLs for lower aflatoxin production in different years. There were very few chromosome regions associated with QTLs in more than 1 year or population with MR analysis, and none with CIM MR analysis. In 1997, QTLs for lower aflatoxin were detected with CIM MR in bins 5.01-2 and 5.04-5 in the BC(1)S(1) population, and in bins 3.05-6, 4.07-8 and 10.05-10.07 in the F(2:3) population. These QTL associations appear the most promising for further study.

Aflatoxins↗
PubMed2003

Comparison of tibial cartilage volume and radiologic grade of the tibiofemoral joint.

OBJECTIVE: To compare tibial cartilage volume as measured by magnetic resonance imaging (MRI) with radiologic assessment of the tibiofemoral joint. METHODS: The MRI-determined tibial cartilage volume was compared with the radiologic grade of individual features of osteoarthritis (osteophytes and joint space narrowing [JSN]) in 252 subjects (mean +/- SD age 60.2 +/- 10 years, 62% female) who were participating in studies of knee cartilage. RESULTS: JSN seen on both medial and lateral radiographs of the tibiofemoral joint was inversely associated with the respective tibial cartilage volume. This inverse relationship was strengthened with adjustment for age, sex, body mass index (BMI), and bone size. After adjustment for these confounders, for every increase in JSN grade (0-3), the medial tibial cartilage volume was reduced by 257 mm(3) (95% confidence interval [95% CI] 193-321) and the lateral tibial cartilage volume by 396 mm(3) (95% CI 283-509). The relationship between mean cartilage volume and radiologic grade of JSN was linear. Based on results in the subgroup of subjects with normal radiographic findings, we have proposed a model to estimate average "normal" cartilage volume in men and women for a given age, BMI, and bone size. CONCLUSION: The results of this study demonstrate a strong negative, linear association between medial and lateral tibial cartilage volume and increasing grade of JSN. Using data from radiographically normal subjects, we have proposed a simple model for estimating "normal" cartilage volume. However, larger studies will be needed to confirm these findings and to determine whether they are valid in younger subjects.

Aged↗
PubMed2003

Genetic variation in the IGSF6 gene and lack of association with inflammatory bowel disease.

The immunoglobulin superfamily 6 gene (IGSF6) on chromosome 16p11-p12 has been investigated as a positional and functional candidate for inflammatory bowel disease (IBD) susceptibility. Screening of the six exons of IGSF6 for single nucleotide polymorphisms (SNPs) detected four novel SNPs, and validated three of six SNPs listed in the international SNP database (dbSNP). The seven SNPs in IGSF6 formed five distinct linkage disequilibrium groups. There was no evidence for association of the common SNPs with disease in a large cohort of patients with IBD. The novel SNPs and the linkage disequilibrium map will be a useful resource for the analysis of IGSF6 in other immune disorders.

CD8 Antigens↗
PubMed2003

Genetic variation at the chromosome 16 chemokine gene cluster: development of a strategy for association studies in complex disease.

The chemokine gene cluster [CCL22, CX3CL1, CCL17] (previously known as [SCYA22, SCYD1, SCYA17]) is a candidate locus for one of the susceptibility genes for inflammatory bowel disease that are located in the peri-centromeric region of chromosome 16. Screening for sequence variation at this locus led to the detection of 14 single nucleotide polymorphisms (SNPs). An efficient experimental and computational approach was developed to estimate allele frequencies and pairwise linkage disequilibrium relationships between SNPs at this locus, and to test them for association with inflammatory bowel disease. The 12 common SNPs were assigned to 5 distinct linkage disequilibrium groups. Genotyping of one SNP from each linkage disequilibrium group in a large cohort of families with inflammatory bowel disease did not provide convincing evidence of association with either Crohn's disease or ulcerative colitis. We describe an efficient experimental design from SNP screening to association testing. This strategy can be used to test candidate genes for involvement in susceptibility to complex disease.

Chemokines↗
PubMed2003

Infliximab in moderately severe glucocorticoid resistant ulcerative colitis: a randomised controlled trial.

BACKGROUND: Tumour necrosis factor production is increased in the mucosa of patients with active ulcerative colitis. The benefits of infliximab in Crohn's disease are established. We investigated its efficacy in ulcerative colitis. METHODS: We conducted a randomised placebo controlled trial of infliximab (5 mg/kg) in the treatment of glucocorticoid resistant ulcerative colitis. Infusions were given at weeks 0 and 2. Disease activity and quality of life were recorded over eight weeks of follow up. Remission was defined as an ulcerative colitis symptom score (UCSS) of < or =2 and/or Baron score of 0 at week 6. Patients not in remission were offered open label infliximab 10 mg/kg and reviewed two weeks later. RESULTS: After two weeks, there was no statistically significant difference between the infliximab and placebo groups in the proportion of patients with a Baron score of 0 (13% (3/23) v 5% (1/19) (95% confidence interval (CI) -9% to 24%); p=0.74). After six weeks, remission (UCSS < or =2) rates were 39% (9/23) versus 30% (6/20) (95% CI -19 to 34%; p=0.76). The median improvement in UCSS was 3 for the infliximab group and 2.5 for the placebo group (p=0.82, Mann-Whitney U test). A Baron score of 0 was likely in either group (26% (6/23) v 30% (6/20) (95% CI -30% to 23%); p=0.96). Improvement in the IBDQ and EuroQol was not significantly different between the groups (p=0.22 and 0.3, respectively, Mann-Whitney U test). Twenty eligible patients were given open labelled infusions. Remission was achieved in 3/11 (27%) patients initially treated with infliximab and in 1/9 (11%) patients treated with placebo. CONCLUSION: These data do not support the use of infliximab in the management of moderately active glucocorticoid resistant ulcerative colitis.

Adult↗
PubMed2002

Systematic review for non-surgical interventions for the management of late radiation proctitis.

Chronic radiation proctitis produces a range of clinical symptoms for which there is currently no recommended standard management. The aim of this review was to identify the various non-surgical treatment options for the management of late chronic radiation proctitis and evaluate the evidence for their efficacy. Synonyms for radiation therapy and for the spectrum of lower gastrointestinal radiation toxicity were combined in an extensive search strategy and applied to a range of databases. The included studies were those that involved interventions for the non-surgical management of late radiation proctitis. Sixty-three studies were identified that met the inclusion criteria, including six randomised controlled trials that described the effects of anti-inflammatory agents in combination, rectal steroids alone, rectal sucralfate, short chain fatty acid enemas and different types of thermal therapy. However, these studies could not be compared. If the management of late radiation proctitis is to become evidence based, then, in view of its episodic and variable nature, placebo controlled studies need to be conducted to clarify which therapeutic options should be recommended. From the current data, although certain interventions look promising and may be effective, one small or modest sized study, even if well-conducted, is insufficient to implement changes in practice. In order to increase recruitment to trials, a national register of cases with established late radiation toxicity would facilitate multi-centre trials with specific entry criteria, formal baseline and therapeutic assessments providing standardised outcome data.

Administration, Rectal↗
PubMed2002

Non surgical interventions for late radiation proctitis in patients who have received radical radiotherapy to the pelvis.

BACKGROUND: Chronic radiation proctitis (inflammation of the rectum) may develop after the completion of pelvic radiotherapy. Presently there is no recommended standard management. OBJECTIVES: To assess the effects of various non-surgical treatment options for the management of late chronic radiation proctitis. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register, issue 1, 2001, MEDLINE 1966 to 2001, EMBASE 1980 to 2001, CANCERCD 1980 to 2001, Science Citation Index 1991 to 2001, CINAHL 1982 to 2001, as well as sources of grey literature. We also hand searched relevant textbooks and contacted experts in the field. SELECTION CRITERIA: Studies (preferentially randomised controlled trials) of interventions for the non-surgical management of late radiation proctitis in patients who have undergone pelvic radiotherapy as part of their cancer treatment. DATA COLLECTION AND ANALYSIS: The inclusion criteria were independently applied by two of the reviewers (AD and EJM) and where there was disagreement this was resolved by involving a third reviewer to form a consensus. MAIN RESULTS: Six randomised controlled trials were included. None of the trials compared anti-inflammatories with placebo. However rectal sucralfate showed greater clinical improvement for proctitis than anti-inflammatories (odds ratio 14.00, 95% confidence interval 1.46 to 134.26; n=1 study), though no difference was seen for endoscopic improvement (odds ratio 2.74, 95% confidence interval 0.64 to 11.76, n=1 study). The addition of metronidazole to the anti-inflammatory regime also appeared to improve the response rate, as measured by the reduction in rectal bleeding, diarrhoea, erythema and ulceration (n=1 study). Similarly rectal hydrocortisone appeared to be more effective than rectal betamethasone for clinical improvement although no difference was seen in endoscopic improvement (n=1 study). Short chain fatty acid enemas did not appear to be effective compared to placebo (n=2 studies). In the comparison of the heater probe and bipolar electrocautery (n=1 study), there was no discernible difference for severe bleeding after one year, but the heater probe demonstrated a greater increase in the haematocrit and reduced transfusion requirements. REVIEWER'S CONCLUSIONS: Late radiation complications are a relatively rare manifestation, with many potential carers and poor diagnostic criteria. Although certain interventions look promising and may be effective (such as rectal sucralfate, adding metronidazole to the anti-inflammatory regime and heater probes), single small studies (even if well conducted) provide insufficient evidence. The episodic and variable nature of late radiation proctitis also requires placebo controlled studies to establish whether particular treatments are effective. Regional or centralised registers of radiation toxicity should be established so that interventions can be administered in the setting of multi-centre trials with specific entry criteria, formal baseline and therapeutic assessments providing standardised outcome data including quality of life evaluations.

Anti-Inflammatory Agents↗
PubMed2002

Review article: Crohn's disease--the role of nutritional therapy.

Maintenance of adequate nutrition is of obvious importance in the management of patients with Crohn's disease. Exclusive parenteral nutrition can achieve high rates of remission, but this is not usually necessary since exclusive elemental and polymeric enteral regimes can yield similarly good results. Comparison of exclusive enteral formula feeding with steroid treatment favours steroids only because compliance is less complete for the restrictive nutritional regimes, and formula feeds should always be the first choice in the growing child with active Crohn's disease. It is probable that the nature of the lipid provided in Crohn's diets is clinically important, and there is some evidence that the n-3 fatty acids are beneficial. Continuation of nutritional supplements once remission has been obtained appears valuable even when malnutrition is not a major consideration.

Child↗
PubMed2002

Mouldy houses influence symptoms of asthma among atopic individuals.

BACKGROUND: The influence of current levels of indoor fungi on asthma is a controversial issue that needs to be resolved in order to advise patients appropriately. OBJECTIVE: To assess the seasonal variation in indoor fungal levels and the impact of these levels on asthma among mould-sensitized individuals. METHODS: Thirty-five young adults with current asthma and sensitization to fungi were visited four times over 1 year. At each home visit a questionnaire was administered and samples of dust and air were collected. Participants also recorded information on symptoms, peak expiratory flows (PEF) and medication use. Dust samples were analysed for house dust mite allergen (Der p 1) and total fungal biomass (ergosterol). Total and genus-specific fungal propagules were identified in air samples. Seasonal variation in allergen levels and significant independent effects of fungal levels on peak flow variability (PFV) were identified by repeated measures analysis of variance. RESULTS: Significant seasonal variations were observed in viable airborne fungi, ergosterol levels in the floor dust and PFV. PFV correlated significantly with symptom scores and the dose of reliever medication. PFV was also significantly associated with smoking and visible mould. The association between visible mould and PFV was independent of season, smoking and the dose of reliever medication. However, there was no association between total fungi, specific fungi or ergosterol and PFV. Der p 1 levels had no significant influence on asthma, even in HDM-sensitized individuals. CONCLUSIONS: Mouldy homes adversely influence asthma in asthmatics sensitized to fungi.

Air Pollution, Indoor↗
PubMed2002

Differential expression of cell adhesion molecules within inflamed ileal pouch mucosa: relationship to recruited cell subtypes.

INTRODUCTION: Endothelial-bound cell adhesion molecules are important in recruiting inflammatory cells to the mucosa in inflammatory bowel disease (IBD). Little is known of the expression of these molecules in relation to the recruitment of particular cell subtypes in the early course of mucosal inflammation. We therefore studied the expression of several adhesion molecules to examine their potential correlation with the cellular infiltrate in the inflamed ileal pouch, a possible disease model for ulcerative colitis. METHODS: Eleven patients (group 1) with familial adenomatous polyposis (FAP) with no evidence of ileal pouch inflammation and 14 patients (group 2) with ileal pouch inflammation (all with a prior diagnosis of ulcerative colitis) underwent pouch endoscopy with biopsy. Cryostat sections of biopsies were immunostained using a three-stage immunoperoxidase method for the adhesion molecules intercellular adhesion molecule (ICAM-1), vascular cellular adhesion molecule (VCAM-1), E-selectin and mucosal addressin cell adhesion molecule 1 (MAdCAM-1). These results were correlated with immunostaining for the cell markers CD3, CD4, CD8, CD45RO, CD14 and CD15, which were quantified by computer image analysis. RESULTS: MAdCAM-1, ICAM-1 and VCAM-1 were expressed to similar degrees on the endothelia of groups 1 and 2. In contrast, E-selectin was significantly increased in group 2 (P = 0.003) and correlated with immunostaining for CD15 (r = 0.72), CD4 (r = 0.55) and CD14 (r = 0.53). MAdCAM-1 expression did not correlate with any cell subset. CD15 was the only cell marker to be altered significantly, being increased in group 2 (P = 0.002). CONCLUSIONS: The inflammatory process seen in ileal pouch inflammation is characterized by up-regulation of E-selectin and recruitment of CD15-positive cells, emphasizing the role of neutrophil recruitment and migration to the epithelium in the pathogenesis of this condition.

Adenomatous Polyposis Coli↗
PubMed2002

How reliably do rheumatologists measure shoulder movement?

OBJECTIVE: To assess the intrarater and interrater reliability among rheumatologists of a standardised protocol for measurement of shoulder movements using a gravity inclinometer. METHODS: After instruction, six rheumatologists independently assessed eight movements of the shoulder, including total and glenohumeral flexion, total and glenohumeral abduction, external rotation in neutral and in abduction, internal rotation in abduction and hand behind back, in random order in six patients with shoulder pain and stiffness according to a 6x6 Latin square design using a standardised protocol. These assessments were then repeated. Analysis of variance was used to partition total variability into components of variance in order to calculate intraclass correlation coefficients (ICCs). RESULTS: The intrarater and interrater reliability of different shoulder movements varied widely. The movement of hand behind back and total shoulder flexion yielded the highest ICC scores for both intrarater reliability (0.91 and 0.83, respectively) and interrater reliability (0.80 and 0.72, respectively). Low ICC scores were found for the movements of glenohumeral abduction, external rotation in abduction, and internal rotation in abduction (intrarater ICCs 0.35, 0.43, and 0.32, respectively), and external rotation in neutral, external rotation in abduction, and internal rotation in abduction (interrater ICCs 0.29, 0.11, and 0.06, respectively). CONCLUSIONS: The measurement of shoulder movements using a standardised protocol by rheumatologists produced variable intrarater and interrater reliability. Reasonable reliability was obtained only for the movement of hand behind back and total shoulder flexion.

Aged↗
PubMed2002

The Parkinson's disease sleep scale: a new instrument for assessing sleep and nocturnal disability in Parkinson's disease.

BACKGROUND: No formal instruments are available for quantifying sleep problems in Parkinson's disease. OBJECTIVE: To develop a new sleep scale to quantify the various aspects of nocturnal sleep problems in Parkinson's disease, which may occur in up to 96% of affected individuals. METHODS: Employing a multidisciplinary team approach, a visual analogue scale was devised addressing 15 commonly reported symptoms associated with sleep disturbance in Parkinson's disease-the Parkinson's disease sleep scale (PDSS). In all, 143 patients with Parkinson's disease completed the PDSS, covering the entire spectrum of disease from newly diagnosed to advanced stage. As controls, 137 age healthy matched subjects also completed the scale. Test-retest reliability was assessed in a subgroup of subjects. The Epworth sleepiness scale was also satisfactorily completed by 103 of the patients with Parkinson's disease. RESULTS: PDSS scores in the Parkinson group were significantly different from the healthy controls. Patients with advanced Parkinson's disease had impaired scores compared with early/moderate disease. Individual items of the scale showed good discriminatory power between Parkinson's disease and healthy controls. Relevant items of the PDSS correlated with excessive daytime sleepiness. The scale showed robust test-retest reliability. CONCLUSIONS: This appears to be the first description of a simple bedside screening instrument for evaluation of sleep disturbances in Parkinson's disease. A combination of subitems may help identify specific aspects of sleep disturbance, which in turn may help target treatment.

Adult↗