Methylene blue but not indigo carmine causes DNA damage to colonocytes in vitro and in vivo at concentrations used in clinical chromoendoscopy.
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Cells, Cultured↗
Biomedical subjects
D Burke
Publications and source records attributed to D Burke.
Angiopoietins in malignancy.
BACKGROUND: Tumour growth is dependant upon the development of an adequate blood supply. This, in turn, is thought to depend upon a switch by the tumour, from a dormant to angiogenic state. Recent data suggest that this switch may occur when the balance of pro- and anti-angiogenic agents alters to promote angiogenesis. Angiopoietins may be involved in this balance. METHODS: An electronic literature search was performed with respect to angiopoietins from 1996 to the present. Published data from in-vitro and in-vivo studies were critically analysed. A specific focus was made of studies relating to tumour growth and vasculature. RESULTS: Since angiopoietin-1 was first described in 1996, three more angiopoietins have been described. All family members bind to the Tie-2 receptor. There is now a considerable accumulation of data that suggests they play a pivotal role in the development and stabilisation of tumour vasculature. angiopoietin-2 appears to be pro-angiogenic whilst angiopoietin-1 appears to be a stabilising factor. CONCLUSIONS: Recent trials of anti-angiogenic agents show promise in the treatment of solid human cancers. The angiopoietins are a new family of proteins that appear to be influential in the development of the tumour vasculature. Manipulation of the angiopoietin balance may provide a potential therapeutic target in human cancer.
Angiopoietins↗
Intra-anal collagen injection for the treatment of faecal incontinence.
BACKGROUND: Intra-anal injectable agents have been used to treat faecal incontinence. The aim of this study was to report the experience of a cohort of patients who underwent intra-anal injection of collagen and to determine which patients benefited from the technique. METHODS: Data, including age, sex, incontinence score, classification of incontinence, baseline resting pressure and vector volume, were collected prospectively for 73 consecutive patients (59 women) undergoing intra-anal collagen injection. Patients were reviewed after treatment and incontinence scores documented. A proportion of patients also underwent repeat anorectal physiological testing 8 weeks after the procedure. RESULTS: At a median follow-up of 12 months after the intra-anal injection, 63 per cent of patients had an improved incontinence score and 73 per cent reported an overall improvement in symptoms. Logistic regression showed that older age and idiopathic faecal incontinence were predictors of a successful outcome (P = 0.042 and P = 0.048 respectively). CONCLUSION: Intra-anal collagen injection appears to have a role in the treatment of faecal incontinence. The majority of patients can expect both objective and subjective improvement. The best results are achieved in older patients and in those with idiopathic incontinence.
Administration, Rectal↗
Letter 1: randomized clinical trial of bowel preparation with a single phosphate enema or polyethylene glycol before elective colorectal surgery (Br J Surg 2006; 93: 427-433).
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Anastomosis, Surgical↗
Dysbiosis and pouchitis.
BACKGROUND AND METHODS: The exact aetiology of pouchitis is unknown, but an association with dysbiosis has been suggested. This is a retrospective review of 17 studies published between 1985 and 2005, identified by a search of the Medline, Pubmed and Embase databases. RESULTS: The methodology of the studies varied widely. Many were performed at a time when the distinction between a healthy and an inflamed pouch was vague; misclassification of patients makes the analysis of data difficult and conclusions uncertain. CONCLUSION: The evidence that dysbiosis is a cause of pouchitis is poor. Nevertheless, available data allow the construction of an algorithm to aid management and suggest a structured approach for future research.
Algorithms↗
Measurement of the anal cushions by transvaginal ultrasonography.
PURPOSE: The anal cushions are believed to contribute to the anal continence mechanism. Transvaginal ultrasound previously has been used to visualize the anal sphincters. Using this method, visualization of the anal cushions has been described but no quantitation of the cushions has been undertaken. Because impairment of the anal cushion function may lead to anal incontinence, this study was designed to evaluate the use of transvaginal ultrasound to measure the anal cushions. METHODS: Patients attending a gynecologic ultrasound list were recruited into the study. By measuring cross-sectional areas, a cushion:canal ratio was calculated. RESULTS: Fifty females were studied. Results showed that the area enclosed within the internal anal sphincter had a median of 2.37 cm(2) (interquartile range, 1.76-2.61). The cushion:canal ratio was 0.66 (interquartile range, 0.57-0.7). Interobserver error was 0.98 and intraobserver error 0.99. CONCLUSIONS: In this pilot study, we conclude that transvaginal ultrasonography is a reliable method of measuring the anal cushions in healthy control subjects. A narrow normal range can be established. This may be compared later with anal cushion size in patients who have symptoms of incontinence and may be used to assess changes in the size of the cushions in response to recently described anal cushion bulking agents.
Anal Canal↗
How do clinical features help identify paediatric patients with fractures following blunt wrist trauma?
OBJECTIVE: Wrist injuries are a common presentation to the emergency department (ED). There are no validated decision rules to help clinicians evaluate paediatric wrist trauma. This study aimed to identify which clinical features are diagnostically useful in deciding the need for a wrist radiograph, and then to develop a clinical decision rule. METHODS: This prospective cohort study was carried out in the ED of Sheffield Children's Hospital. Eligible patients were recruited if presenting within 72 hours following blunt wrist trauma. A standardised data collection form was completed for all patients. The outcome measure was the presence or absence of a fracture. Univariate analysis was performed with the chi2 test. Associated variables (p<0.2) were entered into a multivariate model. Classification and regression tree (CART) analysis was used to derive the clinical decision rule. RESULTS: In total, 227 patients were recruited and 106 children were diagnosed with fractures (47%). Of 10 clinical features analysed, six were found by univariate analysis to be associated with a fracture. CART analysis identified the presence of radial tenderness, focal swelling, or an abnormal supination/pronation as the best discriminatory features. Cross fold validation of this decision rule had a sensitivity of 99.1% (95% confidence interval 94.8% to 100%) and a specificity of 24.0% (17.2% to 32.3%). The radiography rate would be 87%. CONCLUSIONS: Radial tenderness, focal swelling, and abnormal supination/pronation are associated with wrist fractures in children. The clinical decision rule derived from these features had a high sensitivity, but low specificity, and would not substantially alter our current radiography rate. The potential for a clinical decision rule for paediatric wrist trauma appears limited.
Adolescent↗
Direct measurements of Ab and Ac using vertex and kaon charge tags at the SLAC detector.
Exploiting the manipulation of the SLAC Linear Collider electron-beam polarization, we present precise direct measurements of the parity-violation parameters A(c) and A(b) in the Z-boson-c-quark and Z-boson-b-quark coupling. Quark-antiquark discrimination is accomplished via a unique algorithm that takes advantage of the precise SLAC Large Detector charge coupled device vertex detector, employing the net charge of displaced vertices as well as the charge of kaons that emanate from those vertices. From the 1996-1998 sample of 400 000 Z decays, produced with an average beam polarization of 73.4%, we find A(c)=0.673+/-0.029(stat)+/-0.023(syst) and A(b)=0.919+/-0.018(stat)+/-0.017(syst).
Journal Article↗
Infliximab in the surgical management of complex fistulating anal Crohn's disease.
OBJECTIVES: To assess prospectively the efficacy and safety of treatment of perianal Crohn's disease by means of a combination of surgical management and a standardized protocol for the intravenous infusion of infliximab. METHODS: A consecutive series of patients who presented with complex perianal Crohn's fistulae between November 1999 and March 2003 were included in the study. Perianal sepsis was eradicated with drainage of collections and insertion of setons. Infliximab was infused at 5 mg/kg at 0, 2, and 6 weeks. Setons were removed after the second infliximab infusion. Endpoints were defined as either complete, partial or no response as noted at subsequent outpatient follow up. Adverse reactions were recorded. RESULTS: Twenty-one patients had a median of three fistulae per patient (range 1-9). All patients tolerated the initial protocol, receiving a median of five infusions of infliximab (range 3-19); median follow up 20 months (range 12-52). Eleven patients (53%) were continued on maintenance therapy with 12 weekly infusions of infliximab for either a perceived clinical need for treatment or after a relapse of their symptoms. Ten (47%) patients experienced a complete response to treatment and the remaining 11 (53%) experienced a partial response. No patient failed to respond to treatment. Four adverse reactions were noted (2 mild allergies, 1 rash and 1 patient experienced joint pains). All adverse reactions settled with cessation of the drug infusion. CONCLUSIONS: The combination of seton drainage and infusion of infliximab completely healed the perineum of 47% patients with complex fistulating perianal Crohn's disease. Partial response was seen in the remainder of patients. No serious adverse reactions reported.
Adult↗
MRI assessment of the bony pelvis may help predict resectability of rectal cancer.
OBJECTIVE: The outcome after surgical treatment of rectal cancer may be influenced by the technical difficulty of the operation, which is thought to be affected by pelvic size. The aim of this study was to examine the association between bony pelvic dimensions and CRM involvement. PATIENTS AND METHODS: All patients with primary rectal cancer between December 1999 and January 2002 were studied. Staging was performed by pelvic MRI. Nine pelvic dimensions were measured from the MR images on a workstation. Pathology reports were obtained for all patients and the mesorectal specimen was examined. Technical difficulty was assessed by circumferential resection margin (CRM) involvement. RESULTS: Of 126 patients with primary rectal cancer, 88 had staging MRI and rectal excision; there were significant differences between the sexes in all 9 pelvic dimensions (P < 0.05). In females, the interspinous diameter was significantly shorter in patients with CRM involvement compared with patients with a negative CRM. In female patients predicted to have a negative CRM, the anteroposterior diameter of the inlet, the anteroposterior diameter of the midplane and the transverse diameter of the midplane (interspinous distance) were significantly shorter in patients who actually had a positive CRM compared with those in whom the CRM was negative. In male patients, there was no correlation between pelvic dimensions and CRM status. CONCLUSIONS: In certain patients with rectal cancer, CRM positivity may be predicted from pre-operative MRI pelvic measurements. This may influence the choice of adjuvant therapy.
Aged↗
A clinical trial of creatine in ALS.
BACKGROUND: Mitochondrial dysfunction occurs early in the course of ALS, and the mitochondria may be an important site for therapeutic intervention. Creatine stabilizes the mitochondrial transition pore, and is important in mitochondrial ATP production. In a transgenic mouse model of ALS, administration of creatine prolongs survival and preserves motor function and motor neurons. METHODS: The authors conducted a randomized double-blind, placebo controlled trial on 104 patients with ALS from 14 sites to evaluate the efficacy of creatine supplementation in ALS. The primary outcome measure was maximum voluntary isometric contraction of eight upper extremity muscles, with secondary outcomes including grip strength, ALS Functional Rating Scale-Revised, and motor unit number estimates. Patients were treated for 6 months, and evaluated monthly. RESULTS: Creatine was tolerated well, but no benefit of creatine could be demonstrated in any outcome measure. CI analysis showed that the study, although powered to detect a 50% or greater change in rate of decline of muscle strength, actually made an effect size of greater than 23% unlikely. It was also demonstrated that motor unit number estimation was performed with acceptable reproducibility and tolerability, and may be a useful outcome measure in future clinical trials. CONCLUSION: Any beneficial effect of creatine at 5 g per day in ALS must be small. Other agents should be considered in future studies of therapeutic agents to address mitochondrial dysfunction in ALS. In addition, motor unit number estimation may be a useful outcome measure for future clinical trials in ALS.
Adolescent↗
Pattern recognition approach to the detection of single-trial event-related functional magnetic resonance images.
Functional magnetic resonance imaging (FMRI) is an imaging technique for determining which regions of the brain are activated in response to a stimulus or event. Early FMRI experiment paradigms were based upon those used in positron emission tomography (PET), i.e. employing a block design consisting of extended periods of 'on' against 'off' activations. More recent experiments were based on event-related FMRI, harnessing the fact that very short stimuli trains or single events can generate robust responses. FMRI data suffer from low signal-to-noise ratios, and typical event-related experiment paradigms employ selective averaging over many trials before using statistical methods for determining active brain regions. The paper reports a pattern recognition approach to the detection of single-trial FMRI responses without recourse to averaging and at modest field strengths (1.5T). Linear discriminant analysis (LDA) was applied in conjunction with different feature extraction techniques. Use of the unprocessed data samples as features resulted in single-trial events being classified with an accuracy of 61.0 +/- 9.5% over five subjects. To improve classification accuracy, knowledge of the ideal template haemodynamic response was used in the feature extraction stage. A novel application of parametric modelling yielded an accuracy of 69.8 +/- 6.3%, and a matched filtering approach yielded an accuracy of 71.9 +/- 5.4%. Single-trial detection of event-related FMRI may yield new ways of examining the brain by facilitating new adaptive experiment designs and enabling tight integration with other single-trial electrophysiological methods.
Brain↗
Improved direct measurement of the parity-violation parameter Ab using a mass tag and momentum-weighted track charge.
We present an improved direct measurement of the parity-violation parameter A(b) in the Z boson-b-quark coupling using a self-calibrating track-charge technique applied to a sample enriched in Z-->bb events via the topological reconstruction of the B hadron mass. Manipulation of the Stanford Linear Collider electron-beam polarization permits the measurement of A(b) to be made independently of other Z-pole coupling parameters. From the 1996-1998 sample of 400,000 hadronic Z decays, produced with an average beam polarization of 73.4%, we find A(b)=0.906+/-0.022(stat)+/-0.023(syst).
Journal Article↗
Does the need to self-digitate or the presence of a large or nonemptying rectocoele on proctography influence the outcome of transanal rectocoele repair?
INTRODUCTION: Transanal repair of anterior rectocoele is a well described technique with variable success rate. In our department we offer repair to patients who fit the following criteria; the need to self digitate (transvaginal or perineal); a large rectocoele; a nonemptying rectocoele. Using these selection criteria previous authors have shown excellent results. The aim of our study was to review our results using this selective approach and also to determine whether the need to self digitate, the presence of a large rectocoele and the degree of emptying could predict which patients would achieve a successful result. METHODS: Fifty-five patients underwent repair over a three-year period. The main presenting symptom was noted for each patient and also whether self-digitation was required in order to achieve successful evacuation. Dynamic evacuation proctography was performed on all patients. Size of rectocoele, percentage of paste expelled and other proctographic abnormalities were noted for each patient. Follow up was at 6 weeks and 6 months at which point patients were asked whether their symptoms had resolved, improved, remained the same or had worsened. RESULTS: Complete data were available for 48 of the patients (median age 52 years, IQR 43-63). The presenting complaint was constipation in 22 patients, obstructive defaecation in 15, incomplete evacuation in 5, postdefaecation soiling in 4 and dyspareunia in 2. Thirty-eight patients noted the need to self-digitate, 10 did not. Proctography revealed a large rectocoele (> 4 cm) in 22 patients and a medium or small rectocoele (< 4 cm) in 26 patients. There was a rectocoele alone in 34 patients, in combination with perineal descent in 11 and with intussusception in 3. Median percentage of paste expelled was 70% (range 20-95). At 6 weeks postoperatively, 43 patients had complete resolution of their symptoms whilst 5 reported only some or no improvement. At 6 months, 37 patients sustained complete resolution of their symptoms and 11 did not. Pre-operative factors were compared for these two groups of patients. There was no difference in age (P > 0.05, Mann-Whitney U-test) between the two groups There was also no difference in size of rectocoele, degree of emptying, the presence of another proctographic abnormality and the need to self-digitate between the two groups (P > 0.05, Fisher's exact test). DISCUSSION: No factors were seen to distinguish between the successful and unsuccessful groups of patients following rectocoele repair, however, an overall success rate of 75% was achieved using our selection criteria. This figure is in keeping with reported success rates in the literature.
Adult↗
Comparison of ropivacaine 0.5% (in glucose 5%) with bupivacaine 0.5% (in glucose 8%) for spinal anaesthesia for elective surgery.
BACKGROUND: Hyperbaric solutions of ropivacaine have been used successfully to provide spinal anaesthesia. This study was designed to compare the clinical efficacy of hyperbaric ropivacaine with that of the commercially available hyperbaric preparation of bupivacaine. METHODS: Forty ASA grade I-II patients undergoing lower-abdominal, perineal or lower-limb surgery under spinal anaesthesia were recruited and randomized to receive ropivacaine 5 mg ml(-1) (with glucose 50 mg ml(-1)), 3 ml or bupivacaine 5 mg ml(-1) (with glucose 80 mg ml(-1)), 3 ml. The level and duration of sensory block, intensity and duration of motor block, and time to mobilize and micturate were recorded. Patients were interviewed at 24 h and at 1 week to identify any residual problems. RESULTS: All blocks were adequate for the proposed surgery, but there were significant differences between the two groups in mean time to onset of sensory block at T10 (ropivacaine 5 min; bupivacaine 2 min; P<0.005), median maximum extent (ropivacaine T7; bupivacaine T5; P<0.005) and mean duration of sensory block at T10 (ropivacaine 56.5 min; bupivacaine 118 min; P=0.001). Patients receiving ropivacaine mobilized sooner (ropivacaine mean 253.5 min; bupivacaine 331 min; P=0.002) and passed urine sooner (ropivacaine mean 276 min; bupivacaine 340.5 min; P=0.01) than those receiving bupivacaine. More patients in the bupivacaine group required treatment for hypotension (>30% decrease in systolic pressure; P=0.001). CONCLUSIONS: Ropivacaine 15 mg in glucose 50 mg ml(-1) provides reliable spinal anaesthesia of shorter duration and with less hypotension than bupivacaine. The recovery profile for ropivacaine may be of interest given that more surgery is being performed in the day-case setting.
Amides↗
Prehospital use of paracetamol among children attending the accident and emergency department.
OBJECTIVES: To identify patterns of prehospital administration of paracetamol to children who were perceived to be feverish by their carers. METHODS: A prospective cohort study of carers of children attending a paediatric accident and emergency (A&E) department. Carers of children completed a questionnaire to identify domestic patterns of paracetamol use. Data were collected on temperature of the child in the A&E department, administration of antipyretics in the A&E department, diagnosis, and disposal from the A&E department. RESULTS: Seventy five adults attending the A&E department consented to involvement. Sixty five of the children were feverish on arrival in the A&E department. Twenty one children (32.3%) had not received paracetamol before attending. There was a significant relation between knowledge of the antipyretic properties of paracetamol and administration (chi(2)=5.0, p<0.05). There was a significant correlation between fever and administration of paracetamol in the A&E department (chi(2)=23.7, p<0.01), however, 15 feverish patients (24.6%) were not treated. CONCLUSIONS: Most carers administer paracetamol appropriately in the prehospital setting. Administration correlates significantly with knowledge of its benefits. There is scope for education of carers and A&E department staff in the in the appropriate use of antipyretics such as paracetamol.
Acetaminophen↗
Sanfilippo syndrome type D: identification of the first mutation in the N-acetylglucosamine-6-sulphatase gene.
Mucopolysaccharidosis type IIID is the least common of the four subtypes of Sanfilippo syndrome. It is caused by a deficiency of N-acetylglucosamine-6-sulphatase, which is one of the enzymes involved in the catabolism of heparan sulphate. We present the clinical, biochemical, and, for the first time, the molecular diagnosis of a patient with Sanfilippo D disease. The patient was found to be homozygous for a single base pair deletion (c1169delA), which will cause a frameshift and premature termination of the protein. Accurate carrier detection is now available for other members of this consanguineous family.
Base Sequence↗
Nitrogen removal using a vertically moving biofilm system.
The aim of this laboratory study was to establish the efficacy of a new experimental biofilm system for the removal of nitrogen from synthetic wastewater. The system consisted of six reactors in series: one anaerobic, one anoxic and four aerobic reactors. In both the anaerobic and anoxic reactors, a plastic cuboid module was repeatedly moved up and down in the wastewater, while being totally submerged at all times. In each of the aerobic reactors, an identical module to that used in the anaerobic and anoxic reactors was intermittently and repeatedly immersed in and lifted out of the wastewater. All the individual reactors had a bulk fluid volume of 28.2 litres and the average temperature of the wastewater was about 10 degrees C. Each module consisted of crossflow corrugated plastic sheets with a surface area of 1.824 m2. The nitrate recycle flow from the fourth aerobic tank to the anoxic tank was twice the inflow to that tank. In the anoxic reactor, filtered COD was removed at an average rate of 2.22 kg COD/m3 x d and nitrate-nitrogen was denitrified at a rate of 0.42 kg NO3-N/m3 x d. The average nitrification rate in the second aerobic reactor was 0.12 kg NH4-N/m3 x d. The new biofilm system was simple to construct and operate.
Bacteria, Aerobic↗