Charles H Knowles

Queen Mary, University of London, Londinium, England, United Kingdom

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Publications (168)1140.57 Total impact

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    ABSTRACT: AimSacral nerve stimulation (SNS) may be offered to patients with constipation who have failed to improve with conservative treatment. The response to SNS is variable with a significant loss of efficacy in some patients. An increased frequency of stimulation may improve the efficacy of SNS for faecal incontinence. This study aimed to see if alteration of the pulse width or frequency improved the outcome for those with constipation.Method Eleven patients with constipation currently being treated by SNS were recruited from three centres. They were randomised to five different protocols of stimulation each applied for five weeks. Group 1 used standard settings (pulse width 210 μsec, frequency 14 Hz) and in the other four (Groups 2-5), the pulse width and/or frequency were halved or doubled. Patients and investigators were blinded to the group allocation.ResultsThe Cleveland Clinic constipation score varied significantly between the five groups. Group 1 achieved the lowest score mean (±SD) 13.4 (±4.4) [p=0.03]. The number of digitations per defecation was the lowest in Group 4, 90 μsec and 14Hz (p<0.01). No other variable changed significantly. Standard settings were the most preferred by the recruited patients.Conclusion Alteration of pulse width or frequency of stimulation had no significant effect on the outcome of SNS for constipation.This article is protected by copyright. All rights reserved.
    Colorectal Disease 04/2015; DOI:10.1111/codi.12982 · 2.02 Impact Factor
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    ABSTRACT: Background The overlap of unexplained gastrointestinal (GI) and somatic symptoms is well established in patients with functional gastrointestinal disorders (FGID). Joint hypermobility syndrome (JHS) is a non-inflammatory connective tissue disorder associated with GI and somatic symptoms. We aimed to determine whether there is an association between diagnosis of JHS and FGID and the impact of this association on comorbidities and quality of life (QOL).Methods Prospective case–control study in secondary care GI clinics over 2 years. JHS was assessed by the first author prior to consultation in 641 consecutive new patients. Diagnosis of FGID (cases, n = 336) or organic disorders (controls, n = 305) was established blind to JHS status. JHS prevalence was compared in cases (FGID patients) and controls (organic disorders patients). Extra-intestinal comorbidity and QOL were compared in FGID patients with and without JHS.Key ResultsJHS prevalence was higher in FGID compared to organic GI disorders (39.0% vs 27.5%, ORadj: 1.51, CI: 1.07–2.12, p = 0.02), and particularly associated with functional gastroduodenal disorders (44.1%, ORadj: 2.08, CI: 1.25–3.46, p = 0.005), specifically postprandial distress syndrome (51%, ORadj: 1.99, CI: 1.06–3.76, p = 0.03). FGID patients with JHS had increased chronic pain (23.2% vs 11.9%, p = 0.01), fibromyalgia (10.5% vs 3.1%, p = 0.01), somatization scores (13 vs 10, p < 0.001), urinary autonomic scores (30.5 vs 20.7, p = 0.03), and worse pain-related QOL scores (45.0 vs 63.5, p = 0.004).Conclusions & InferencesJHS is significantly associated with FGID, and this subgroup of patients have increased comorbidity and decreased QOL. Further research is required to understand the pathophysiological basis of this association.
    Neurogastroenterology and Motility 04/2015; 27(4). DOI:10.1111/nmo.12535 · 3.42 Impact Factor
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    ABSTRACT: The enzyme guanosine triphosphate-cyclohydrolase-1 (GCH-1) is a rate limiting step in the de novo synthesis of tetrahydrobiopterin (BH4) a co-factor in monoamine synthesis and nitric oxide production. GCH-1 is strongly implicated in chronic pain based on data generated using the selective GCH-1 inhibitor 2,4-diamino-6-hydroxypyrimidine (DAHP), and studies which have identified a pain protective GCH-1 haplotype associated with lower BH4 production and reduced pain. To investigate the role for GCH-1 in visceral pain we examined the effects of DAHP on pain behaviors elicited by colorectal injection of mustard oil in rats, and the pain protective GCH-1 haplotype in healthy volunteers characterized by esophageal pain sensitivity before and after acid injury, and assessed using depression and anxiety questionnaires. In rodents pretreatment with DAHP produced a substantial dose related inhibition of pain behaviors from 10 to 180 mg/kg i.p. (p < 0.01 to 0.001). In healthy volunteers, no association was seen between the pain protective GCH-1 haplotype and the development of hypersensitivity following injury. However, a substantial increase in baseline pain thresholds was seen between first and second visits (26.6 ± 6.2 mA) in subjects who sensitized to esophageal injury and possessed the pain protective GCH-1 haplotype compared with all other groups (p < 0.05). Furthermore the same subjects who sensitized to acid and possessed the haplotype, also had significantly lower depression scores (p < 0.05). The data generated indicate that GCH-1 plays a role in visceral pain processing that requires more detailed investigation. © 2015 John Wiley & Sons Ltd.
    Neurogastroenterology and Motility 03/2015; DOI:10.1111/nmo.12538 · 3.42 Impact Factor
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    ABSTRACT: The diagnostic accuracy of anorectal manometry (AM), which is necessary to diagnose functional defecatory disorders (FDD), is unknown. Using blinded analysis and standardised reporting of diagnostic accuracy, we evaluated whether AM could discriminate between asymptomatic controls and patients with functional constipation (FC). Derived line plots of anorectal pressure profiles during simulated defecation were independently analysed in random order by three expert observers blinded to health status in 85 women with FC and 85 age-matched asymptomatic healthy volunteers (HV). Using accepted criteria, these pressure profiles were characterised as normal (ie, increased rectal pressure coordinated with anal relaxation) or types I-IV dyssynergia. Interobserver agreement and diagnostic accuracy were determined. Blinded consensus-based assessment disclosed a normal pattern in 16/170 (9%) of all participants and only 11/85 (13%) HV. The combined frequency of dyssynergic patterns (I-IV) was very similar in FC (80/85 (94%)) and HV (74/85 (87%)). Type I dyssynergia ('paradoxical' contraction) was less prevalent in FC (17/85 (20%) than in HV (31/85 (36.5%), p=0.03). After statistical correction, only type IV dyssynergia was moderately useful for discriminating between FC (39/85 (46%)) and HV (17/85 (20%)) (p=0.001, positive predictive value=70.0%, positive likelihood ratio=2.3). Interobserver agreement was substantial or moderate for identifying a normal pattern, dyssynergia types I and IV, and FDD, and fair for types II and III. While the interpretation of AM patterns is reproducible, nearly 90% of HV have a pattern that is currently regarded as 'abnormal' by AM. Hence, AM is of limited utility for distinguishing between FC and HV. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    Gut 03/2015; DOI:10.1136/gutjnl-2014-308835 · 13.32 Impact Factor
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    ABSTRACT: Background Sacral nerve stimulation (SNS) has proven short- to medium-term effectiveness for the treatment of faecal incontinence (FI); fewer long-term outcomes have been presented and usually in small series. Here, the long-term effectiveness of SNS was evaluated in a large European cohort of patients with a minimum of 5 years' follow-up.Methods Prospectively registered data from patients with FI who had received SNS for at least 5 years from ten European centres were collated by survey. Daily stool diaries, and Cleveland Clinic and St Mark's incontinence scores were evaluated at baseline, after implantation and at the last follow-up. SNS was considered successful when at least 50 per cent symptom improvement was maintained at last follow-up.ResultsA total of 407 patients underwent temporary stimulation, of whom 272 (66·8 per cent) had an impulse generator implanted; 228 (56·0 per cent) were available for long-term follow-up at a median of 84 (i.q.r. 70–113) months. Significant reductions in the number of FI episodes per week (from median 7 to 0·25) and summative symptom scores (median Cleveland Clinic score from 16 to 7, St Mark's score from 19 to 6) were recorded after implantation (all P < 0·001) and maintained in long-term follow-up. In per-protocol analysis, long-term success was maintained in 71·3 per cent of patients and full continence was achieved in 50·0 per cent; respective values based on intention-to-treat analysis were 47·7 and 33·4 per cent. Predictive analyses determined no significant association between pretreatment variables and successful outcomes. Risk of long-term failure correlated with minor symptom score improvement during the temporary test phase.ConclusionSNS remains an effective treatment for FI in the long term for approximately half of the patients starting therapy.
    British Journal of Surgery 02/2015; 102(4). DOI:10.1002/bjs.9740 · 5.21 Impact Factor
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    ABSTRACT: Background Sacral nerve stimulation (SNS) is a well established therapy for faecal incontinence (FI). Percutaneous tibial nerve stimulation (PTNS) is a newer, less invasive, treatment. The effectiveness and acceptability of these treatments have not been compared systematically.Methods An investigator-blinded randomized pilot trial of PTNS versus SNS with a parallel qualitative study was performed. Quantitative clinical outcomes and qualitative data from patient interviews were collected for both interventions.ResultsForty patients (39 women; mean age 59 years) met the eligibility criteria; 23 were randomized to receive SNS and 17 to PTNS. Fifteen patients progressed to permanent SNS implantation and 16 received a full course of PTNS. Within-group effect sizes were marginally greater for SNS than for PTNS on available-case analysis. Mean(s.d.) FI episodes per week at baseline, and 3 and 6 months of follow-up were: 11·4(12·0), 4·0(4·0) and 4·9(6·9) respectively for SNS compared with 10·6(11·2), 5·8(6·9) and 6·3(6·9) for PTNS. Mean(s.d.) Cleveland Clinic Incontinence Score values at baseline, and 3 and 6 months were: 16·2(3·0), 11·1(5·2) and 10·4(5·6) for SNS versus 15·1(2·7), 11·7(4·4) and 12·1(5·2) for PTNS. Improvement of at least 50 per cent in FI episodes per week at 6 months was seen in 11 of 18 patients in the SNS group compared with seven of 15 in the PTNS group. Effect estimates for SNS with chronic implanted stimulation were larger (10 of 15 patients at 6 months). Disease-specific and generic quality-of-life improvements complemented clinical outcome data. Qualitative analysis of interview data suggested that both treatments had high acceptability amongst patients.Conclusion In the short term, both SNS and PTNS provide some clinical benefit to patients with FI. Registration numbers: 2010-018728-15 and 10479 (
    British Journal of Surgery 01/2015; 102(4). DOI:10.1002/bjs.9695 · 5.21 Impact Factor
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    Annals of surgery 09/2014; 261(1). DOI:10.1097/SLA.0000000000000887 · 7.19 Impact Factor
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    ABSTRACT: Background Sacral nerve stimulation (SNS) is now well established as a treatment for fecal incontinence (FI) resistant to conservative measures and may also have utility in the management of chronic constipation; however, mechanism of action is not fully understood. End organ effects of SNS have been studied in both clinical and experimental settings, but interpretation is difficult due to the multitude of techniques used and heterogeneity of reported findings. The aim of this study was to systematically review available evidence on the mechanisms of SNS in the treatment of FI and constipation.Methods Two systematic reviews of the literature (performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses framework) were performed to identify manuscripts pertaining to (a) clinical and (b) physiological effects of SNS during the management of hindgut dysfunction.Key ResultsThe clinical literature search revealed 161 articles, of which 53 were deemed suitable for analysis. The experimental literature search revealed 43 articles, of which nine were deemed suitable for analysis. These studies reported results of investigative techniques examining changes in cortical, gastrointestinal, colonic, rectal, and anal function.Conclusions & InferencesThe initial hypothesis that the mechanism of SNS was primarily peripheral motor neurostimulation is not supported by the majority of recent studies. Due to the large body of evidence demonstrating effects outside of the anorectum, it appears likely that the influence of SNS on anorectal function occurs at a pelvic afferent or central level.
    Neurogastroenterology and Motility 09/2014; 26(9). DOI:10.1111/nmo.12388 · 3.42 Impact Factor
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    Neurogastroenterology and Motility 09/2014; 26(9). DOI:10.1111/nmo.12364 · 3.42 Impact Factor
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    ABSTRACT: IntroductionAlthough sacral neuromodulation (SNM) is an established treatment for faecal incontinence, stimulation parameters have been derived empirically and only one frequency (14 Hz) is employed clinically. The aim of this study was to test a range of stimulation frequencies to establish an optimal frequency of SNM for maximum augmentation of anal canal cortical evoked potentials (EPs) in an animal model.Methods In female Wistar rats, anal canal EPs were recorded over the primary somatosensory cortex using a flexible multielectrode array, and the effect of SNM was studied. SNM was applied at 0·1–100 Hz and a frequency response curve plotted. The data were fitted to a quadratic equation.ResultsThe magnitude of potentiation of anal canal EPs caused by SNM depended significantly on stimulation frequency (P < 0·001). The frequency–potentiation relationship was parabolic in form, with a clear optimum at 2 Hz. The SNM must be applied for at least 3 min. The theoretical maximal potentiation predicted by the model was not found to be statistically different to actual data recorded (P = 0·514–0·814). The response depended on stimulation amplitude in an ‘all-or-nothing’ fashion. EPs were augmented when the SNM intensity was 0·5 times the motor threshold to tail twitch or greater, but values below this intensity failed to affect the EPs.Conclusion The effect of SNM in this animal model is governed principally by frequency, with an optimum of 2 Hz. If animal data can be translated to humans, optimization of SNM frequency may offer a clinically relevant improvement in the efficacy of SNM.Surgical relevanceSacral neuromodulation (SNM) for faecal incontinence currently employs stimulation parameters that have been derived empirically and may not be optimal. This study used an animal model of SNM and focused on its acute effect on anal canal cortical evoked potentials (EPs). It was found that SNM potentiated EPs, with a clear optimum at a frequency of 2 Hz. If this finding is applicable to the mechanism of action of human SNM, this suggests that there may be a clinically relevant improvement by reducing stimulus frequency from its typical value of 14 Hz to 2 Hz.
    British Journal of Surgery 09/2014; 101(10). DOI:10.1002/bjs.9587 · 5.21 Impact Factor
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    ABSTRACT: Chronic visceral pain affects millions of individuals worldwide and remains poorly understood, with current therapeutic options constrained by gastrointestinal (GI) side effects. Visceral pain is strongly associated with inflammation and distension of the gut. Here we report that the voltage-gated sodium channel subtype NaV1.9 is expressed in half of gut-projecting rodent dorsal root ganglia sensory neurons. We show that NaV1.9 is required for normal mechanosensation, for direct excitation and for sensitisation of mouse colonic afferents by mediators from inflammatory bowel disease tissues, and by noxious inflammatory mediators individually. Excitatory responses to ATP or PGE2 were substantially reduced in NaV1.9-/- mice. Deletion of NaV1.9 substantially attenuates excitation, and subsequent mechanical hypersensitivity, following application of inflammatory soup (bradykinin, ATP, histamine, PGE2 and 5HT) to visceral nociceptors located in the serosa and mesentery. Responses to mechanical stimulation of mesenteric afferents were also reduced by loss of NaV1.9 and there was a rightward shift in stimulus-response function to ramp colonic distension. By contrast, responses to rapid, high-intensity phasic distension of the colon are initially unaffected; however run-down of responses to repeat phasic distension were exacerbated in NaV1.9-/- afferents. Finally colonic afferent activation by supernatants derived from inflamed human tissue was greatly reduced in NaV1.9-/- mice. These results demonstrate that NaV1.9 is required for persistence of responses to intense mechanical stimulation, contributes to inflammatory mechanical hypersensitivity and is essential for activation by noxious inflammatory mediators including those from diseased human bowel. These observations indicate that NaV1.9 represents a high-value target for development of visceral analgesics.
    Pain 06/2014; 155(10). DOI:10.1016/j.pain.2014.06.015 · 5.84 Impact Factor
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    ABSTRACT: The Joint hypermobility syndrome (JHS) is a non-inflammatory connective tissue disorder with a prevalence of 20%. It is characterised by joint hypermobility,chronic pain, fibromyalgia (FM) and dysautonomia. Gastrointestinal (GI) symptoms e.g., dyspepsia, reflux, bloating and constipation are present in up to 80% of affected individuals. Small studies suggest that FGID are common in these patients yet no controlled studies have systematically investigated if JHS is associated with particular GI diagnoses nor explored the effect of JHS on non-GI symptom presentation and quality of life (QOL).
    Gut 06/2014; 63(Suppl 1):A194-A195. DOI:10.1136/gutjnl-2014-307263.420 · 13.32 Impact Factor
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    ABSTRACT: Autonomic nervous system dysfunction has been implicated in visceral hypersensitivity. However, the specific contribution of the parasympathetic nervous system (PNS) is unclear. We aimed to determine whether physiological and pharmacological manipulation of parasympathetic tone influences the development of hypersensitivity in a validated model of acid-induced oesophageal pain.
    Gut 05/2014; DOI:10.1136/gutjnl-2013-306698 · 13.32 Impact Factor
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    ABSTRACT: Current diagnostic methods for gastro-oesophageal reflux disease (GORD) have moderate sensitivity/specificity and can be invasive and expensive. Pepsin detection in saliva has been proposed as an 'office-based' method for GORD diagnosis. The aims of this study were to establish normal values of salivary pepsin in healthy asymptomatic subjects and to determine its value to discriminate patients with reflux-related symptoms (GORD, hypersensitive oesophagus (HO)) from functional heartburn (FH). 100 asymptomatic controls and 111 patients with heartburn underwent MII-pH monitoring and simultaneous salivary pepsin determination on waking, after lunch and dinner. Cut-off value for pepsin positivity was 16 ng/mL. Patients were divided into GORD (increased acid exposure time (AET), n=58); HO (normal AET and + Symptom Association Probability (SAP), n=26) and FH (normal AET and-SAP, n=27). 1/3 of asymptomatic subjects had pepsin in saliva at low concentration (0(0-59)ng/mL). Patients with GORD and HO had higher prevalence and pepsin concentration than controls (HO, 237(52-311)ng/mL and GORD, 121(29-252)ng/mL)(p<0.05). Patients with FH had low prevalence and concentration of pepsin in saliva (0(0-40) ng/mL). A positive test had 77.6% sensitivity and 63.2% specificity for diagnosis of GORD+HO (likelihood ratio: 2.2). However, one positive sample with >210 ng/mL pepsin suggested presence of GORD+HO with 96% specificity (likelihood ratio: 24.4). Only 18/84 (21.4%) of GORD+HO patients had 3 negative samples. In patients with symptoms suggestive of GORD, salivary pepsin testing may complement questionnaires to assist office-based diagnosis. This may lessen the use of unnecessary antireflux therapy and the need for further invasive and expensive diagnostic methods.
    Gut 05/2014; 64(3). DOI:10.1136/gutjnl-2014-307049 · 13.32 Impact Factor
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    ABSTRACT: Background: Nitric oxide (NO) is elaborated in huge amounts in acute illness and exacerbations of inflammatory bowel disease. NO acts as an inhibitory neurotransmitter by relaxation of smooth muscle cells and suggested to be of major importance in acute colonic dilatation in ulcerative colitis. The migrating motor complex (MMC) is a cyclic motility pattern aiding absorption of nutrients and propulsion of intestinal contents. When MMC is dysregulated, it constitutes a cornerstone in the diagnosis of enteric dysmotility, which can promote development of small intestinal bacterial overgrowth. Little is known on how NO works in conjunction with other neurotransmitters to regulate the motor activity of the MMC during fasting. Methods: Twenty-one healthy volunteers (22-38 years) underwent antroduodenojejunal manometry recordings for 4h after a bolus injection of either saline or the NO synthase inhibitor NG-monomethyl-L-arginine (L-NMMA, 10 mg/kg IV) with or without atropine (1mg) or ondansetron (8mg). Effects on the MMC pattern and the subsequent MMC were determined. Exhaled and rectal NO was monitored throughout the experiments. Peptide hormones ghrelin, motilin and somatostatin with known effects of the MMC were measured. Supplementary in vitro studies were done on human small bowel muscle strips with bethanechol (10-5M) in the presence of L-NMMA (10-4M) and tetrodotoxin (TTX, 10-6M). Results: L-NMMA elicited pre-mature duodeno-jejunal phase III in all subjects but one, irrespective of atropine or ondansetron. L-NMMA also shortened the MMC cycle length and shifted motility towards phase II with strong suppression of phase I of the subsequent MMC. This effect was not seen after pretreatment with atropine or ondansetron. Instead, atropine extended phase II activity of the MMC, whereas ondansetron had no effect. After administration of L-NMMA no increase of gut hormones was found. L-NMMA reduced exhaled NO levels in all subjects, whereas only 12 of 17 had reduced rectal NO. Systemic blood pressure was consistently elevated for two hours after L-NMMA. In vitro, L-NMMA enhanced bethanechol-induced contractions that were insensitive to TTX. Conclusions: NO exerts an inhibitory action on the MMC by suppressing the phase III activity independently of muscarinic and 5-HT3 receptor blockade. Furthermore, the motility intensity over the different phases of the MMC seems to be under influence of NO. Phase I of the MMC seems strongly dependent on NO, being counter-regulated by cholinergic and serotonergic mechanisms, whereas phase II is dependent on atropine-sensitive mechanisms for transition into the next phase III of MMC. The sensitization of motility by inhibition of NO is due to a direct effect on the smooth muscle cells, as neither gut peptide hormone release, nor neuronal mechanisms are related to the increased motor activity.
    Digestive Disease Week, USA; 05/2014
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    ABSTRACT: RPMC) in the distal colon. The 5-HT3 agonist m-CPBG and 5-HT exerted strong inhibitory effects, suggesting that the 5-HT3 antagonists have effects in addition to blocking effects of endogenous 5-HT. The fact that antagonists and agonists are all inhibitory to the most prominent propulsive activity of the colon, the neurogenic LDC, suggests a complicated receptor repertoire on inhibitory and excitatory neurons making the pharmacological applica-tion of 5-HT related compounds affecting all receptors within the whole colon difficult to interpret. Pancolonic Long Distance Contractions (LDCs; left) are inhibited and Rhythmic Propulsive Motor Complexes (RPMCs; bottom right) markedly increased in the distal colon by addition of the 5HT3 antagonist palonosetron. A similar effect is seen with 5HT4 receptor stimulation. Chronic constipation is associated with advanced age. The causes are not always clear, but reductions in human enteric nerve density with age have been observed [1]. Due to extensive enteric nerve reserve the functional significance of this observation is unknown. We report the largest recorded functional study of neuromuscular activities in human isolated colon over a wide range of ages, and compare with similar studies in mice. Macroscopically-normal colon was obtained at surgery for bowel cancer, following informed consent. Mucosa-free strips were cut parallel to circular muscles and suspended in Krebs solution for isometric recording. Electrical field stimulation (EFS) was applied at 5Hz for 10s every 1min as previously described [2]. Colonic loops (3mm wide) were prepared from female C57BL/6 mice (3 & 24 months) with 5Hz EFS applied for 30s every 2min. N=patients/mice. Tissue was obtained from 132 patients (1118 strips; 30-90 years). Strips contracted (787 strips, 70%) or relaxed during EFS (331; 30%), and a contraction on termination of EFS often followed (899 strips, 80%). Responses were abolished by tetrodotoxin 1μM (n=12). Contrac-tions during EFS were abolished (n=16), and after-contractions decreased (by 48±5%; n= 18) by atropine 1μM. These were decreased further by NK1-3 receptor antagonists (31±7%; n=11). Relaxations were abolished by the NO synthase inhibitor L-NAME 300μM (n=53). The contractions during EFS decreased with age (by 57±22 mg/g tissue/year; P=0.013; r 2 = 0.13; n=47). Similarly the % of strips which relaxed in response to EFS (≥3 strips/patient) increased with age (P=0.004; r 2 =0.08; n=132), e.g. 40% of strips >79 years of age relaxed. When separated for region and gender, the latter change was statistically significant only in the ascending colon of females (P=0.003; r 2 =0.28; n=30), although a similar trend was observed in males (P=0.06; r 2 =0.19; n=19). There were no changes in the contractions to carbachol 10μM with age (P=0.08; r 2 =0.07; n=47). In mice, EFS induced relaxations followed by after-contractions (50 proximal, 32 distal loops; n=10 3 months; n=11 24 months). In proximal colon, 5Hz EFS evoked larger responses in 3 month than 24 month old mice (31±8 g/g tissue and 16±3 g/g tissue; P<0.05; 2-way ANOVA; Bonferroni post-test; n=10, 11). This age-related effect is seen only in proximal and not distal colon. Responses to carbachol 10μM (n=10, 11) were unchanged with age in both regions. We have demonstrated that advanced age is associated with changes in the neuromuscular function of human colon. This change was only detected in the ascending colon, was more prominent in females, and is supported by findings in mice. Further studies are now required to investigate age-related structural changes. 1. Bernard CE et al.
    DDW- Digestive disease week, USA; 05/2014
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    ABSTRACT: Two types of neuromodulation are currently practised for the treatment of fecal incontinence (FI): sacral nerve stimulation (SNS) and percutaneous tibial nerve stimulation (PTNS). This study compares these therapies, as no data exist to prospectively assess their relative efficacy and costs. The subjects of this study were two distinct cohorts undergoing SNS (between 2003 and 2008) or PTNS (2008-onwards) for FI. Clinical outcomes assessed at 3 months included incontinence scores and the number of weekly incontinence episodes. The direct medical costs for each procedure were calculated from the audited expenditure of our unit. Thirty-seven patients (94.6 % women) underwent permanent SNS and 146 (87.7 % women) underwent PTNS. The mean pre-treatment incontinence score (±SD) was greater in the SNS cohort (14 ± 4 vs. 12 ± 4) and the mean post-treatment incontinence scores were similar for the two therapies (9 ± 5 vs. 10 ± 4), with a greater effect size evident in the SNS patients. In a 'pseudo case-control' analysis with 37 "matched" patients, the effect of both treatments was similar. The cost of treating a patient for 1 year was £11 374 ($18 223) for permanent SNS vs. £1740 ($2784) for PTNS. Given the lesser cost and invasive nature of PTNS, where both techniques are available, a trial of PTNS could be considered for all patients.
    Surgery Today 05/2014; 44(11). DOI:10.1007/s00595-014-0898-0 · 1.21 Impact Factor
  • Gastroenterology 05/2014; 146(5):S-722. DOI:10.1016/S0016-5085(14)62619-6 · 13.93 Impact Factor
  • Gastroenterology 05/2014; 146(5):S-714. DOI:10.1016/S0016-5085(14)62593-2 · 13.93 Impact Factor
  • Rebecca Burgell, Charles H. Knowles, S. Mark Scot
    Gastroenterology 05/2014; 146(5):S-355. DOI:10.1016/S0016-5085(14)61283-X · 13.93 Impact Factor

Publication Stats

2k Citations
1,140.57 Total Impact Points


  • 1997–2015
    • Queen Mary, University of London
      • • Barts and The London School of Medicine and Dentistry
      • • The Blizard Institute of Cell and Molecular Science
      Londinium, England, United Kingdom
  • 2006–2014
    • Barts Health NHS Trust
      Londinium, England, United Kingdom
  • 2013
    • The University of Manchester
      Manchester, England, United Kingdom
  • 2008–2013
    • University of London
      • The London School of Medicine and Dentistry
      Londinium, England, United Kingdom
  • 2008–2010
    • Homerton University Hospital NHS Foundation Trust
      Londinium, England, United Kingdom
  • 2009
    • The Peninsula College of Medicine and Dentistry
      Plymouth, England, United Kingdom
  • 2002
    • University of Milan
      Milano, Lombardy, Italy
  • 2000
    • Royal College of Surgeons of England
      Londinium, England, United Kingdom