Colorectal Disease (Colorectal Dis )

Publisher: Association of Coloproctology of Great Britain and Ireland, Blackwell Publishing


Colorectal Disease is a new journal publishing original research in any discipline relating to colorectal pathology. The journal will further education and inter-professional development by including regular review articles, discussions of current controversies, occasional highly selected case reports, and question and answer features.Colorectal Disease is the official organ of the Association of Coloproctology of Great Britain and Ireland. The journal will report news of the Association and take a major interest in coloproctological matters across Europe as a whole.

  • Impact factor
  • 5-year impact
  • Cited half-life
  • Immediacy index
  • Eigenfactor
  • Article influence
  • Website
    Colorectal Disease website
  • Other titles
    Colorectal disease (Online)
  • ISSN
  • OCLC
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Blackwell Publishing

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • Some journals impose embargoes typically of 6 or 12 months, occasionally of 24 months
    • no listing of affected journals available as yet
  • Conditions
    • See Wiley-Blackwell entry for articles after February 2007
    • Publisher version cannot be used
    • On author or institutional or subject-based server
    • Server must be non-commercial
    • Publisher copyright and source must be acknowledged with set statement ("The definitive version is available at ")
    • Articles in some journals can be made Open Access on payment of additional charge
    • 'Blackwell Publishing' is an imprint of 'Wiley-Blackwell'
  • Classification
    ​ yellow

Publications in this journal

  • [show abstract] [hide abstract]
    ABSTRACT: AIM: Posterior tibial nerve stimulation (PTNS) has emerged in recent years as a therapy for faecal incontinence. Its long-term effectiveness is yet to be established, along with what the form of retreatment should be in the event of loss of effectiveness. The present study aimed to establish the mid-term results to identify the proportion of patients who may need further treatment, and if so when. METHOD: A prospective study including 30 patients was conducted at an academic hospital. The patients underwent 12 weekly outpatient treatment sessions, each lasting 30 min (first PTNS phase). Neuromodulation was discontinued in those patients who did not have a 40% decrease in their pretreatment Wexner score. Patients having a better than 40% response were offered another 12-week course of complete treatment (second PTNS phase), following which they received no further PTNS treatment (phase without PTNS) but were assessed at 6 months and 2 years. RESULTS: All patients finished the first phase and 22/30 patients continued to the second phase. During this phase 11 patients showed an improved Wexner score (baseline/first phase/second phase: 14.3 ± 4.2 vs 9.9 ± 5.4 vs 6.8 ± 5.4). After a 6-month period without any treatment, the score was still improved in 11/30 patients (9.1 ± 6.2). At 2 years there was improvement in 16/30 patients (8.8 ± 7.1). There was a significant improvement in three variables of the quality of life questionnaire: lifestyle, coping behaviour and embarrassment. CONCLUSION: The response to first and second phase PTNS was maintained for up to 2 years. Retreatment was not required in about half of patients, even when they had finished the treatment 6 months or 2 years previously.
    Colorectal Disease 04/2014; 16:304-10.
  • Colorectal Disease 04/2014; 16(4).
  • Colorectal Disease 04/2014; 16(4):233-4.
  • [show abstract] [hide abstract]
    ABSTRACT: Limited data are available on the relationship between the histological features of the resected specimens in patients with ulcerative colitis (UC) or indeterminate colitis (IC) and the outcome of restorative proctocoectmy. The aim of our study was to determine if the histological features of the resected specimen in patients with UC and IC can predict ileal pouch-related outcome. A review of all patients who had a restorative proctocoectmy created following completion proctectomy or proctocolectomy for UC and IC was performed. Between 1992 and 2011, 142 patients (132 with UC and 10 with IC) were reviewed. After a median follow up of 36 (3 - 149) months, 51 (35.9%) developed a pouch-related complication. Forty-two (29.7%) developed pouchitis while three (2.1%) developed a pouch-cutaneous fistula. Four (2.8%) had pouch failure, while stricture of the anastomosis was seen in three (2.1%) patients. The presence of extension of the inflammation into the muscularis propria of the resected specimen was associated with an increased risk of pouch-related complications (p = 0.01). The presence of submucosal oedema was also a significant risk factor (p = 0.03). Both these factors were the only variables that remained statistically significant on multivariate analysis for the development of pouch-related complications (Table 4) CONCLUSION: The extension of inflammation into the muscularis propria appears to predict pouch-related complications following restorative proctocoectmy for ulcerative colitis or indeterminate colitis. This article is protected by copyright. All rights reserved.
    Colorectal Disease 03/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Nitric oxide donors, such as isosorbide dinitrate ointment (ISDN), are considered as first choice agents in the treatment of chronic anal fissure. Injection with botulinum toxin A in the internal anal sphincter is often used as second-line therapy, although it may give better results and fewer side effects than nitric oxide donors. The aim of this randomized clinical trial was to investigate whether botulinum toxin A (Dysport(®) ) is more effective than ISDN in the primary treatment of chronic anal fissure. In the period April 2005 until October 2009, 60 patients (32 male) with a median age of 42 (25-82) years were randomized to receive either ISDN 10 mg/mL (1%) (n=33) or injection with 60 units Dysport(®) (n=27). The primary endpoint was the percentage complete fissure healing after 8 weeks. After a median of 9 weeks complete fissure healing was noted in 18 of 27 patients in the Dysport(®) group and in 11 of 33 patients in the ISDN group (p=0.010). Absolute improvement of pain scores after 9 weeks was similar in both groups (p=0.733). Patients treated with Dysport(®) had fewer side effects than patients treated with ISDN (p=0.028). Of the patients with a healed fissure, 28% of the Dysport(®) group and 50% of the ISDN group had a recurrence within one year (p=0.286; HR 2.08; 95% CI=0.54-7.97). Dysport(®) is more effective with fewer side effects than ISDN ointment in the primary treatment of chronic anal fissure. The recurrence rates within one year in both treatment groups is high. This article is protected by copyright. All rights reserved.
    Colorectal Disease 03/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: Solitary rectal ulcer syndrome (SRUS) is uncommon and its management is controversial. The aim of this study was to evaluate the outcome of patients with SRUS who underwent laparoscopic ventral rectopexy (LVR). A review was performed of a prospective database at the Oxford Pelvic Floor Centre to identify patients between 2004 and 2012 with a histological diagnosis of SRUS. All were initially treated conservatively and surgical treatment was indicated only for patients with significant symptoms after failed conservative management. The primary end-point was healing of the ulcer. Secondary end-points included changes in the Wexner Constipation Score and Faecal Incontinence Severity Index (FISI). Thirty-six patients with SRUS were identified (31 women), with a median age of 44 (15–81) years. The commonest symptoms were rectal bleeding (75%) and obstructed defaecation (64%). The underlying anatomical diagnosis was internal rectal prolapse (n = 20), external rectal prolapse (n = 14) or anismus (n = 2). Twenty-nine patients underwent LVR and one a stapled transanal rectal resection (STARR) procedure. Nine (30%) required a further operation, six required posterior STARR for persistent SRUS and two a per-anal stricturoplasty for a narrowing at the healed SRUS site. Healing of the SRU was seen in 27 (90%) of the 30 patients and was associated with significant improvements in Wexner and FISI scores at a 3-year follow-up. Almost all cases of SRUS in the present series were associated with rectal prolapse. LVR resulted in successful healing of the SRUS with good function in almost all patients, but a significant number will require further surgery such as STARR for persistent obstructed defaecation.
    Colorectal Disease 03/2014; 16(3):O112-6.
  • [show abstract] [hide abstract]
    ABSTRACT: AimColorectal resection in women with endometriosis involving the low and mid rectum may result in poorer outcome than conservative procedures. In this technical note we present a new technique for transanal full thickness disc excision of endometriosis nodules involving the rectum. Method The procedure is performed by combined laparoscopic and transanal routes. The former involves paring the area of the rectum infiltrated by the nodule, which is then made amenable to endoluminal removal using the Contour Transtar stapler to carry out a large disc excision. ResultsThe technique can remove a specimen as large as 80 mm in diameter and can applied to patients with infiltrating rectal endometrial nodules up to 10 cm from the anal margin and 50-60% of the rectal circumference. The procedure is probably less likely to lead to rectal stenosis and denervation compared to colorectal resection. Conclusion This technique of transanal rectal disc excision using the contour stapler is suitable in patients with infiltrating endometrial nodules of the lower and mid-rectum. It avoids a low rectal resection with its potential for complications and unfavorable function.This article is protected by copyright. All rights reserved.
    Colorectal Disease 03/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: AimThe NHS Cancer Plan describes initiatives to improve patient care in the UK, including the Two Week Rule (TWR) Cancer Referral Pathway. To meet this target a Straight to Test (STT) endoscopy service was devised to expedite diagnosis of suspected colorectal cancer. Our novel study aimed to determine patient satisfaction with this new approach to rapid access investigation.Method An anonymised questionnaire was posted to 300 patients who had undergone STT endoscopy in our unit between January and June 2010. It assessed satisfaction with the service overall, time from referral to investigation, pre-test information, bowel preparation instructions and time to results as well as preference for a traditional pre-test or post-test outpatient appointment and awareness that the referral was for suspected bowel cancer.Results174 questionnaires obtained (58% yield; mean age 68·8; 44·8% male). 82·2% of patients were “very satisfied” with the service overall, 82·8% with time from referral to test, 75·2% with time from test to results, 73% with endoscopy information and 69·5% with bowel preparation instructions. Eight per cent would rather have seen a specialist prior to endoscopy, 31·6% would have preferred a post-test appointment and 68·4% of patients were aware that referral was for suspected bowel cancer.ConclusionSTT is popular with patients. It offers a fast and cost effective service in the diagnosis of colorectal cancer and meets national targets whilst reducing the volume burden on outpatient clinics. However, its success heavily relies on accurate communication between GP, patient and secondary care.This article is protected by copyright. All rights reserved.
    Colorectal Disease 03/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: AimThe study was designed to evaluate a new completely diverted tube ileostomy (CDTI) with a reversible single row stapled occlusion of the distal limb to defunction a low colorectal anastomoses, and to compare it with a loop ileostomy (LI). Method From September 2010 to August 2012, 95 rectal cancer patients who underwent elective low anterior resections were recruited into the study. They received either a CDTI or LI. Demographics, clinical features, and operative data were recorded. ResultsFifty-four patients (56%) had a CDTI and 41 (44%) an LI. There were no significant differences in patient demographics and clinical characteristics. Anastomotic dehiscence occurred in 3 (5.6%) and 2 (4.9%) of patients in each group (not signficant [NS}).and no patient developed faecal peritonitis. In the CDTI group, the distal ileum recanalised from the stapler occlusion spontaneously with an average anastomosis exclusion time of 27.9 (14-70) days. The CDTI tube was removed on day 33 (20-75) and the interval to closure of the LI was 12.3 (6-30) days. Conclusion The CDTI procedure is a safe and effective technique for defunctioning an elective low colorectal anastomosis and avoids a formal stoma.This article is protected by copyright. All rights reserved.
    Colorectal Disease 03/2014;
  • Colorectal Disease 03/2014; 16(3):155.
  • [show abstract] [hide abstract]
    ABSTRACT: Faecal incontinence is common and significantly affects quality of life. Its treatment involves dietary manipulation, medical treatments, perineal rehabilitation or surgery. In this paper, the French National Society of Coloproctology offers recommendations based on the data in the current literature, including those on recently developed treatments. There is a lack of high quality data and most of the recommendations are therefore based either on grade of recommendation B or expert recommendation (Level 4). However, the literature supports the construction of an algorithm based on the available scientific evidence and expert recommendation which may be useful in clinical practice. The French National Society of Coloproctology proposes a decision-making algorithm that includes recent developments of treatment. The current recommendations support sacral nerve modulation as the key treatment for faecal incontinence. They do not support the use of sphincter substitutions except in certain circumstances. Transanal irrigation is a novel often successful treatment of faecal incontinence due to neurological disorders.
    Colorectal Disease 03/2014; 16(3):159-66.
  • [show abstract] [hide abstract]
    ABSTRACT: AimColorectal anastomotic leakage is a serious complication. Despite extensive research, no consensus on the most important preoperative risk factors exists. The aim of this systematic review and meta-analysis was to evaluate risk factors for anastomotic leakage in patients operated with colorectal resection.Method The databases Medline, Embase and Cinahl were searched for prospective observational studies on preoperative risk factors for anastomotic leakage. Meta-analyses were performed on outcomes based on odds ratios (OR) from multivariate regression analyses. The Newcastle-Ottawa scale was used for bias assessment within studies and the GRADE approach was used for quality assessment of evidence on outcome levels.ResultsThis review included 23 studies evaluating 110,272 patients undergoing colorectal resection for cancer. The meta-analyses found that a low rectal anastomosis (OR 3.26 [2.31, 4.62]), male gender (OR 1.48 [1.37, 1.60]) and preoperative radiotherapy (OR 1.65 [1.06, 2.56]) may be risk factors for anastomotic leakage. Primarily due to observational design, the quality of evidence was regarded moderate or low for these risk factors by the GRADE approach.Conclusion Based on the best available evidence important preoperative risk factors for colorectal anastomotic leakage have been identified. Knowledge on risk factors may influence treatment and procedure related decisions, and possibly reduce the leakage rate.This article is protected by copyright. All rights reserved.
    Colorectal Disease 03/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: The application of α-adrenoceptor agonists can improve faecal incontinence symptoms. The aim of this study was to investigate the pharmacokinetic and systemic effects of NRL001 administered as different strengths in 1 or 2 g suppositories. This randomised, double-blind, placebo controlled study included 48 healthy subjects. Group 1 consisted of two cohorts of 12 subjects administered either four single doses of 1 or 2 g rectal suppository with either 5, 7.5 or 10 mg NRL001, or matching placebo. Group 2 consisted of two cohorts of 12 subjects administered either four single doses of 1 or 2 g rectal suppository with either 10, 12.5 or 15 mg NRL001, or matching placebo. Doses were given in an escalating manner with placebo at a random position within the sequence. Tmax was at ~4.5 h post-dose for all NRL001 doses. Median AUC0-tz , AUC0-∞ and Cmax increased with increasing dose for both suppository sizes. The estimate of ratios of geometric means comparing 2 g with 1 g suppository, and regression analysis for dose proportionality, was close to 1 for the variables AUC0-tz , AUC0-∞ and Cmax (P > 0.05). For both suppository sizes, 20-min mean pulse rate was significantly decreased compared with placebo with all doses (P < 0.05). Blood pressure decreased overall. There were 144 adverse events (AEs) and no serious AEs reported during the study. All AEs were mild in severity. The regression analysis concluded that the doses were dose proportional.
    Colorectal Disease 03/2014; 16 Suppl 1:16-26.
  • [show abstract] [hide abstract]
    ABSTRACT: AimLocal excision of early rectal cancer is a less morbid alternative to major abdominal. This review evaluates the role of local excision with neoadjuvant or adjuvant chemoradiotherapy to identify a select group of patients where local excision is appropriate without significantly compromising the oncologic outcome. Method Medline, Pubmed and Cochrane Central Register of Controlled Trials databases were searched to identify relevant articles investigating the role of local excision with adjuvant or neoadjuvant chemoradiotherapy in patients with T1/T2N0M0 disease. 11 studies comprising of 455 patients were selected. Oncologic end points included overall survival, disease-free and disease-specific survival, recurrence rates as well as peri-operative morbidity and mortality. ResultsAt a range of 30.5 – 115.2 months, median overall survival, disease-specific and disease-free survival were 75% (66 – 80.6%), 89% (75 – 93.3%) and 74% (64 – 85.2%). Median local, distant and overall recurrence rates were 10% (4.8 – 25%), 4.7% (4 – 11.8%) and 13.1% (10.7 – 23.5%). Mortality was 0% in all studies except one (2.9%). Most reported complications were minor and treated conservatively. Conclusion This systematic review provides data suggesting that selected patients with T1/T2N0M0 rectal cancer may undergo local excision without compromising the oncologic outcome otherwise conferred by total mesorectal excision. It may be a particularly useful option in patients in whom radical surgery is contraindicated. Randomised trials comparing both management strategies to consolidate this finding may lead to a paradigm change in the management of early rectal cancer.This article is protected by copyright. All rights reserved.
    Colorectal Disease 03/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: This study aimed to assess the dose and volume effects of suppository preparations and safety of NRL001 (one of four possible stereoisomers of methoxamine hydrochloride) on anal sphincter tone using rectal suppositories in healthy adult volunteers. This was a Phase I, single-centre, randomised, double-blind, three-way crossover study during which subjects received three single doses of 1 g rectal suppositories (containing 5 or 10 mg NRL001 or matching placebo) or 2 g rectal suppositories (containing 10 or 15 mg NRL001 or matching placebo) on three separate dosing days. The outcome measures were mean anal resting pressure (MARP) variables (monitored continuously for 20-30 min before and up to 6 h after dosing), pharmacokinetics (PK) and safety assessments. Twenty-six subjects were dosed with study medication. Two subjects were withdrawn prematurely and were not included in the main analysis. There was a dose-dependent increase in anal sphincter tone (MARP) when comparing the 5 and 10 mg doses of NRL001; however, the 15 mg dose did not have a significantly greater effect than the 10 mg dose. Suppository size (1 or 2 g) did not appear to have an effect on sphincter tone. There was no evidence against dose proportionality for the PK variables, but the mean maximum plasma concentration (Cmax ) for the 1 g suppository group was higher than for the 2 g group. Twenty-one adverse events were reported in 8 (30.8%) subjects. A dose dependent decrease in heart rate was noted; however, there were no adverse events reported that were related to this reduction in heart rate. The increase in anal sphincter tone supports the potential therapeutic use of NRL001 in treating faecal incontinence, with further studies in patients required. NRL001 was well tolerated in single doses of up to 15 mg.
    Colorectal Disease 03/2014; 16 Suppl 1:5-15.
  • [show abstract] [hide abstract]
    ABSTRACT: NRL001 is a highly specific α1 -adrenoceptor agonist currently under evaluation for the treatment of faecal incontinence caused by a weak internal anal sphincter. The aim of this meta-analysis was to quantify the effect of NRL001 on cardiovascular parameters including heart rate, blood pressure and QT interval. Data from the four Phase I healthy volunteer studies SUM (NCT00857467), SURD (NCT01099670), SUSD (NCT00850590) and SAGE (NCT01099683) were pooled and analyses were performed on individual subject data. Mixed effects regression analysis was used to determine the effect of NRL001 on heart rate, blood pressure and QT intervals. A multivariate statistical model was used to determine the effect of covariates on heart rate. Subjects given NRL001 experienced a dose related decrease in heart rate of up to 9.48 bpm compared with subjects in the placebo arms. No statistically significant evidence for a threshold effect was found. There was no clear evidence of dose effect of NRL001 on blood pressure. QT interval increased in all NRL001 subject as expected; QTC F also showed a statistically significant increase. However, QTC B was shortened with no significant treatment effect. NRL001 was found to have a dose-dependent effect on heart rate; however clinically-relevant bradycardia was not reported, indicating the decrease in heart rate was not of clinical significance. Furthermore, no clinically-significant drug effect on blood pressure or mean arterial pressure was observed. QT intervals were affected by changes in heart rate. However, trends were dependant on the correction factor used. No consistent QT effect was observed, but a thorough QTC study will be required to confirm the effects of rectally applied NRL001.
    Colorectal Disease 03/2014; 16 Suppl 1:51-8.
  • [show abstract] [hide abstract]
    ABSTRACT: Enterocutaneous fistula (ECF) presents a complex management problem with significant mortality and morbidity. The aim of this study was to assess the outcome of patients undergoing surgical cure for ECF and to predict factors that might relate to increased postoperative morbidity. Medical records of all patients who underwent definitive surgery for cure of an ECF within our colorectal surgery unit between 2000 and 2010 were reviewed. Forty-one patients (18 male) were identified, in whom 44 definitive procedures were performed. The median age was 54 (17-81) years. The median postoperative length of stay in hospital was 14 (2-213) days. Half (50%) of the ECFs occurred as a postoperative complication followed by spontaneous fistulation in Crohn's disease (36%). The interval to definitive surgery was influenced by the aetiology of the fistula. The median time to surgery after formation of postoperative fistula was 240 days (7.9 months). There was no 30-day postoperative mortality. There were two (4.5%) recurrences at 3 months. Thirty-eight (86%) patients suffered postoperative morbidity as defined by the Clavien-Dindo classification. High-grade morbidity occurred in 32% of patients. On univariate analysis, factors identified as being significantly associated with high-grade morbidity included a fistula output of > 500 ml/day (P = 0.004) in patients with postoperative ECF, malnutrition at presentation (P = 0.04) and a serum albumin value of < 30 g/l (P = 0.02) in patients with spontaneous ECF due to Crohn's disease. The majority of persistent complex ECFs can be cured surgically with low mortality and recurrence in a multidisciplinary setting. Postoperative morbidity, however, remains a significant burden.
    Colorectal Disease 03/2014; 16(3):209-18.
  • [show abstract] [hide abstract]
    ABSTRACT: AimComplete mesocolic excision (CME) and extended lymphadenectomy (EL) have been proposed to safely improve colon cancer survival outcomes The aim of this study was to evaluate the evidence regarding oncological outcomes, morbidity and mortality after such techniques for colon cancer.MethodA systematic review of the literature was conducted to evaluate evidence regarding oncological outcomes, morbidity and mortality after CME or EL. Three major databases (PubMed, MEDLINE and the Cochrane Library) were searched. The review included original articles reporting outcomes after CME or EL from January 1950 to July 2012.Results21 predominately retrospective studies involving 5246 patients were included (mean age 68·2 years, 56.5 percent male). Reporting of outcomes was inconsistent. Median follow up was 60 months. The operative mortality rate was 3.2 per cent and the cumulative morbidity rate 21.5 per cent. The weighted mean local recurrence rate, 5-year overall and disease-free survival rates were 4.5%, 58.1% and 77·4 per cent respectively.Conclusion The available data for CME and EL has numerous fundamental limitations which prohibit adoption. Contemporary controlled studies are required prior to universal recommendation.This article is protected by copyright. All rights reserved.
    Colorectal Disease 03/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: AimSignificant variation in colorectal surgery outcomes exist between different countries. Better understanding of the sources of variable outcomes using administrative data requires alignment of differing clinical coding systems. We aimed to map similar diagnoses and procedures across administrative coding systems used in different countries.Method Administrative data were collected in a central database as part of The Global Comparators (GC) Project. In order to unify these data, a systematic translation of diagnostic and procedural codes was undertaken. Codes for colorectal diagnoses, resections, operative complications and reoperative interventions were mapped across the respective national healthcare administrative coding systems. Discharge data from January 2006 to June 2011 for patients who had undergone colorectal surgical resections were analysed to generate risk-adjusted models for mortality, length of stay, readmissions and reoperations.Results52544 case records were collated from 31 institutions in five countries. Mapping of all the coding systems was achieved so that diagnosis and procedures from the participant countries could be compared. Using the aligned coding systems to develop risk adjusted models, the 30-day mortality rate for colorectal surgery was 3.95% (95% confidence int4erval [CI] 0.86-7.54), the 30-day readmission rate was 11.05% (5.67-17.61), the 28-day reoperation rate was 6.13% (3.68-9.66) and the mean length of stay was 14 (7.65-46.76) days.Conclusion The linkage of international hospital administrative data that we developed enabled comparison of documented surgical outcomes between countries. This methodology may facilitate international benchmarking.This article is protected by copyright. All rights reserved.
    Colorectal Disease 03/2014;
  • [show abstract] [hide abstract]
    ABSTRACT: The 1R,2S stereoisomer of methoxamine hydrochloride, NRL001, is a highly selective α1-adrenoceptor agonist being developed for the local treatment of non-structural faecal incontinence caused by weak internal anal sphincter tone. This study investigated the steady state pharmacokinetics (PK) and safety of 2 g rectal suppositories containing NRL001 in different strengths (7.5, 10, 12.5 or 15 mg). Healthy volunteers aged 18-45 years received 14 daily doses of NRL001 2 g suppositories or matching placebo. In each dose group nine participants received NRL001 and three received placebo. Blood samples to determine NRL001 concentrations were taken on Days 1, 7 and 14. Cardiovascular parameters were collected via electrocardiograms, Holter monitoring (three lead Holter monitor) and vital signs. Forty-eight volunteers were enrolled; 43 completed the study and were included in the PK analysis population. AUC and Cmax broadly increased with increasing dose, Tmax generally occurred between 4.0 and 5.0 h. Although the data did not appear strongly dose proportional, dose proportionality analysis did not provide evidence against dose proportionality as the log(dose) coefficients were not significantly < 1. NRL001 did not accumulate over time for any dose. Increasing NRL001 concentrations were related to changes in vital sign variables, most notably decreased heart rate. The most commonly reported adverse events (AEs) in the active treatment groups were paraesthesia and piloerection. Treatment with NRL001 was generally well tolerated over 14 days once daily dosing and plasma NRL001 did not accumulate over time. Treatment was associated with changes in vital sign variables, most notably decreased heart rate. AEs commonly reported with NRL001 treatment were events indicative of a systemic α-adrenergic effect.
    Colorectal Disease 03/2014; 16 Suppl 1:36-50.

Related Journals