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N J McC Mortensen

Publications and source records attributed to N J McC Mortensen.

16 recordsLinked to original sources
PubMed2004

Mechanism of action of botulinum toxin on the internal anal sphincter.

BACKGROUND: Botulinum toxin is an effective treatment for anal fissure. Manometric studies support an apparent action of botulinum toxin on the internal anal sphincter (IAS). This aim of this study was to establish the underlying mechanism. METHODS: Porcine IAS strips were suspended in a superfusion organ bath and allowed to equilibrate. Electrical field stimulation (EFS) was applied with parameters that induced nitrergic relaxation followed by noradrenaline-mediated contraction. These responses were compared before and after addition of botulinum toxin. RESULTS: All strips developed myogenic tone, which was slightly increased following the addition of botulinum toxin. EFS-induced nitrergic relaxation was unaffected by toxin treatment. However, EFS-induced contraction was significantly reduced by toxin treatment. 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), a nicotinic agonist, caused muscle strip contraction, which was blocked by guanethidine, implying the presence of sympathetic ganglia within the IAS. Botulinum toxin significantly attenuated DMPP-induced contraction. CONCLUSION: In the treatment of anal fissure the major effect of botulinum toxin on the IAS is blockade of sympathetic (noradrenaline mediated) neural output. This is probably a postganglionic action, involving a reduction in noradrenaline release at the neuromuscular junction. Botulinum toxin has no significant effect on nitrergic transmission, which is probably not vesicular in nature.

Anal Canal↗
PubMed2004

Chronic anal fissure.

BACKGROUND: The treatment of chronic anal fissure has shifted in recent years from surgical to medical. METHODS: A Medline search of studies relevant to modern management of chronic anal fissure was undertaken. RESULTS: Traditional surgery that permanently weakens the internal sphincter is associated with a risk of incontinence. Medical therapies temporarily relax the internal sphincter and pose no such danger, but their limited efficacy has led to displacement rather than replacement of traditional surgery. Emerging medical therapies promise continued improvement and new sphincter-sparing surgery may render traditional surgery redundant. CONCLUSION: First-line use of medical therapy cures most chronic anal fissures cheaply and conveniently. The few non-responders can be targeted for sphincter assessment before traditional surgery. If the initial good results of new sphincter-sparing surgery are confirmed, it may be possible to avoid any risk of incontinence, while achieving high rates of fissure healing.

Anal Canal↗
PubMed2004

Perianal Crohn's disease.

BACKGROUND: The management of perianal Crohn's disease is difficult. A wide variety of treatment options exist although few are evidence based. METHODS: A search was conducted using the National Library of Medicine for articles on perianal Crohn's disease and its incidence, classification, assessment and management. RESULTS AND CONCLUSION: Perianal Crohn's disease can manifest as skin tags, ulcers, fissures, abscesses, fistulas or stenoses. Improved radiological imaging with endoanal anal ultrasonography and magnetic resonance imaging has improved its assessment and may be used to predict outcome after surgery. Many treatment options exist. During acute complications they are generally aimed at resolving the immediate problem and limiting damage to anal and perianal tissues; this may be a 'bridge' to definitive treatment. The likelihood of success of definitive treatment must be weighed against the risk of complications, especially faecal incontinence.

Aminosalicylic Acids↗
PubMed2003

L-Erythro-methoxamine is more potent than phenylephrine in effecting contraction of internal anal sphincter in vitro.

BACKGROUND: Topical phenylephrine has been shown to increase resting anal canal pressure in normal and incontinent individuals. However, high concentrations of gel (10-40 per cent) are required that may cause local side-effects. The aim of this study was to determine whether methoxamine, another alpha-1-adrenoceptor agonist, might be a more potent alternative to phenylephrine. METHODS: Porcine internal anal sphincter (IAS) tissue was cut into strips, suspended in a superfusion organ bath and allowed to equilibrate. Strips were subjected to each drug under test for 20 s, sufficient to obtain stable tone. Phenylephrine, methoxamine (1 : 1 : 1 : 1 ratio of its four isomers) and each of the individual isomers of methoxamine were evaluated in turn. RESULTS: In vitro, methoxamine racemate and phenylephrine were similarly potent in causing contraction of IAS strips (mean(s.e.m.) dose giving half maximal effect (EC(50)) at 74.7(16.5) versus 58.3(13.4) micro M respectively; P = 0.443). However, one of the methoxamine isomers, L-erythro-methoxamine (EC(50) 17.6(3.7) micro M), was significantly more potent than the other three isomers, methoxamine racemate and phenylephrine (P = 0.002). CONCLUSION: L-Erythro-methoxamine is four times more potent than phenylephrine and is a possible treatment for incontinence. Trials are under way to examine the efficacy of L-erythro-methoxamine in vivo.

Adrenergic alpha-Agonists↗
PubMed2003

Options for sphincter preservation in surgery for low rectal cancer.

BACKGROUND: Abdominoperineal excision of the rectum with a permanent end-sigmoid colostomy was the classical operation for cancer of the distal third of the rectum. A number of factors have recently led to a more conservative approach, allowing sphincter preservation when excising tumours that are not invading the anal sphincter. METHODS: The review is based on the published literature of the treatment of low rectal cancers accessed by searching Medline and other online databases. It includes a description of all the surgical options currently available for low rectal tumours, and a discussion of the advantages and disadvantages of the types of anastomosis and reconstruction. RESULTS AND CONCLUSION: It is now technically possible to remove rectal cancer that is extending into the anal canal with preservation of the anal sphincter mechanism and with a satisfactory oncological outcome. Ultra-low colorectal and coloanal anastomosis, together with a colonic pouch or coloplasty, produces acceptable function in many patients. However, there is still controversy about the risk of tumour implantation, the place of downsizing neoadjuvant therapy, and true long-term functional outcome. Despite these concerns, surgeons should strive to perform rectal resection with sphincter preservation for low-lying rectal cancer whenever possible.

Anal Canal↗
PubMed2002

Quantification of histologic regression of rectal cancer after irradiation: a proposal for a modified staging system.

PURPOSE: Long-course preoperative radiotherapy has been recommended for rectal carcinoma when there is concern about the ability to perform a curative resection, for example, in larger tethered tumors or those sited anteriorly or near the anal sphincter. "Downstaging" of the tumor may occur, and this is of importance when estimating the prognosis and selecting postoperative therapy for patients. We studied the effects of preoperative chemoradiotherapy on the pathology of rectal cancer, and we propose a simplified measurement of tumor regression, the Rectal Cancer Regression Grade. METHODS: We have reviewed those patients who received preoperative chemoradiotherapy followed by surgical resection for carcinomas of the mid or distal third of the rectum found to be Stage T3/4 on transrectal ultrasound or CT between January 1995 and December 1998. Patients received 45 to 50 Gy irradiation and an infusion of 5-fluorouracil. The surgical specimens were examined by one pathologist, and the Rectal Cancer Regression Grade was quantified. RESULTS: Forty-two patients, mean age 60 (range, 42-86) years, underwent chemoradiotherapy before surgery for rectal carcinoma. There were 28 anterior resections (67 percent; 9 with a colonic pouch), 12 abdominoperineal resections (27 percent), and 2 Hartmann's procedures (5 percent). Comparison of preoperative and pathologic staging revealed that the depth of invasion was downstaged in 17 patients (38 percent), and the status of involved lymph nodes was downstaged in 13 (50 percent) of 26 patients. Tumor regression was more than 50 percent (Rectal Cancer Regression Grades 1 and 2) in 36 patients (86 percent), with 7 patients (17 percent) having complete regression with absence of residual cancer cells. CONCLUSION: Significant tumor regression was seen in 86 percent of cases after chemoradiotherapy, with 19 patients showing a "good" responsiveness. We propose a modified pathologic staging system for irradiated rectal cancer, the Rectal Cancer Regression Grade, which includes a measurement of tumor regression. The utility of the proposed Rectal Cancer Regression Grade must be tested against long-term outcomes before its value in predicting prognosis and survival can be determined.

Adult↗
PubMed2002

Evidence for separate disease phenotypes in intestinal Crohn's disease.

BACKGROUND: This study investigated the hypothesis that separate phenotypes of Crohn's disease exist which display differing patterns of recurrence with a tendency to preservation of phenotype between serial operations. METHODS: Some 483 abdominal operations (278 patients) were identified from a prospectively compiled database. Patterns of recurrence (reoperation) were analysed by Kaplan-Meier plots and log rank tests according to disease phenotype (perforated, stenosed or ulcerated). Serial operations were analysed by agreement of phenotype and microscopic features of disease using kappa statistics and correlation coefficients. RESULTS: There was no significant difference in recurrence according to disease phenotype (median reoperation-free survival time 43.0, 50.2 and 47.9 months for perforated, stenosed and ulcerated types respectively; log rank chi(2) = 3.5, P = 0.18). There was poor agreement in phenotype between serial operations (kappa = 0.22 for first/second operation and kappa= 0.15 for second/third operation) and no significant correlation between pathological features was identified (r between -0.19 and 0.48). CONCLUSION: No evidence was found for the existence of separate disease phenotypes with differing natural histories or underlying pathological characteristics.

Crohn Disease↗
PubMed2002

An insight into the genetic pathway of adenocarcinoma of the small intestine.

BACKGROUND: Although the adenoma to carcinoma pathway in colorectal cancer is well described, the mechanisms of carcinogenesis in the small intestine remain unclear. AIMS: The aim of this study was to investigate candidate genes in the genetic pathway of adenocarcinoma of the small intestine. SUBJECTS AND METHODS: A total of 21 non-familial, non-ampullary adenocarcinomas of the small intestine were analysed. DNA was extracted from formalin fixed paraffin wax embedded tissue using standard techniques. The replication error (RER) status was determined by amplification of BAT26. The mutation cluster region (MCR) of the adenomatous polyposis coli (APC) gene was screened using polymerase chain reaction single strand conformational polymorphism and direct sequencing. Immunohistochemistry was performed on formalin fixed paraffin wax embedded tissue using monoclonal antibodies for hMLH1, hMSH2, beta-catenin, E-cadherin, and p53. RESULTS: Fourteen male and seven female patients with a median age of 64 years (range 21-85) presented with adenocarcinoma of the duodenum (10), jejunum (7), and ileum (4). One cancer (5%) was found to be RER+, and all tumours stained positive for hMLH1 and hMSH2. No mutations were detected in the MCR of the APC gene. beta-Catenin showed increased nuclear expression with loss of membranous staining in 10 cancers (48%). Absent or decreased membrane expression of E-cadherin was found in eight cancers (38%). Strong staining of p53 was found in the nucleus of five cancers (24%). CONCLUSION: We did not detect mutations in the MCR of the APC gene, and this suggests that adenocarcinoma of the small intestine may follow a different genetic pathway to colorectal cancer. Abnormal expression of E-cadherin and beta-catenin was common and reflects an early alternative to APC in this pathway in which mutations may be found in adenocarcinoma of the small intestine.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Oral nifedipine reduces resting anal pressure and heals chronic anal fissure.

BACKGROUND: Topical preparations have been used in the treatment of anal fissure. However, they are not universally successful and there is confusion over the site and dose of application. This study assessed the effectiveness of oral nifedipine in reducing resting anal pressure and on fissure healing. METHODS: Anal manometry was performed on eight healthy volunteers and 15 patients with chronic anal fissure before and after oral administration of nifedipine 20 mg. Nifedipine was taken twice daily. Fissure healing was assessed over an 8-week period and pain scores were monitored. RESULTS: Oral nifedipine produced an initial reduction in maximum resting anal pressure (MRP) of 35 per cent (P < 0.001) and of 28 per cent after 5 days (P < 0.001) in healthy volunteers. A reduction in MRP of 36 per cent (P < 0.001) was observed in patients with fissure. Pain scores were significantly reduced during the treatment period. Healing was complete in nine patients after 8 weeks and a further three were asymptomatic. Ten patients experience flushing and four had mild headaches. There were no episodes of postural hypotension or incontinence. CONCLUSION: Oral nifedipine reduces resting anal pressure. It is well tolerated and offers an alternative treatment for chronic anal fissure.

Administration, Oral↗
PubMed1989

Use of a modified N-nitrosoproline test to show intragastric nitrosation in patients at risk of gastric cancer.

Intragastric nitrosation has been implicated in the pathogenesis of gastric cancer and in precancerous conditions such as pernicious anaemia and the post-gastrectomy state. Intragastric nitrosation was assessed in at-risk patients by N-nitrosoproline (NPRO) excretion using both a conventional and a modified test. Twenty-four hour urinary excretion of NPRO was measured after oral administration of sodium nitrate (300 mg) and L-proline (500 mg) as an indirect indicator of intragastric nitrosation. In the conventional test no differences in intragastric nitrosation were found between at-risk patients and controls. In the modified test the loading dose of sodium nitrate was omitted and urinary NPRO levels were found to be significantly increased in Polya partial gastrectomy patients (P = 0.003) and post-vagotomy patients (P = 0.03) compared to controls. In pernicious anaemia patients NPRO levels were also higher than in controls but just failed to reach statistical significance. This study has confirmed that hypochlorhydria results in increased intragastric nitrosation, thus facilitating the formation of potentially carcinogenic N-nitroso compounds.

Adult↗
PubMed1988

Intra-operative air testing: an audit on rectal anastomosis.

Thirty three patients having an anastomosis to the rectum were studied prospectively to determine the usefulness of intra-operative air testing. The pelvis was filled with saline and the anastomosis was distended with air. Any leaks demonstrated were oversewn. A Gastrografin enema was performed on all the patients on the eighth postoperative day. Overall, there were 4 (12%) clinical leaks and 10 (30%) radiological leaks. In six patients with air leaks demonstrated at operation, two had a radiological leak, one of which presented clinically as well. We believe that in the other four patients a potential leak was probably avoided as a result of intra-operative air testing. This technique is simple, safe and effective and probably helps reduce leakage after colorectal anastomosis.

Aged↗
PubMedDate not supplied

Reconstructive rectal surgery.

Rectal cancer causes approximately 6000 deaths in the UK each year. The role of the surgeon in rectal cancer is to control local disease and minimise the risk of recurrence. Reconstructive rectal surgery for cancer aims to combine a safe oncological procedure with the maximum quality of life possible. An improved understanding of rectal cancer pathology allied to modern surgical techniques such as intestinal stapling guns, endoanal anastomoses and the colonic pouch has led to an increased number of sphincter saving operations being performed. We have reviewed the background, technical advances and looked at the future of reconstructive rectal surgery for rectal cancer. Firstly we discuss the work which led to low anterior resection being accepted as an oncologically safe operation. followed by an overview of surgical techniques that have facilitated low anterior resection for rectal cancer with good functional results for the patient. Lastly, we look at the role of radiotherapy and the neosphincter in reducing the need for a permanent stoma.

Anal Canal↗