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Biomedical subjects

M A Kamm

Publications and source records attributed to M A Kamm.

At least 19 recordsLinked to original sources
PubMed2006

Efficacy and safety of bisacodyl in the acute treatment of constipation: a double-blind, randomized, placebo-controlled study.

BACKGROUND: Although laxatives are a first-line treatment for constipation, there are few randomized placebo-controlled trials assessing their efficacy. AIM: To determine the effect and safety of oral bisacodyl on stool frequency and consistency in patients with idiopathic constipation. METHODS: 55 patients (age 19-89 years) with idiopathic constipation were recruited from eight primary care practices and randomized to receive bisacodyl, 10 mg once daily, or placebo, on three successive days following a 3-day run-in period. Patients recorded stool frequency and consistency and adverse events. RESULTS; In each treatment group, 27 patients were evaluable for efficacy. The mean number of stools per day was significantly greater in the bisacodyl-treated group (1.8/day) compared with placebo (0.95/day) over the treatment phase (P=0.0061). Mean stool consistency score improved from 'hard' (run-in) to between 'soft' and 'well-formed' during bisacodyl treatment, remaining between 'moderately hard' and 'hard' for placebo treatment (P<0.0001). The investigator's global efficacy score was superior for the bisacodyl group compared with placebo. Both treatments were well tolerated. Serum electrolyte levels and incidence of adverse events were comparable between treatment groups. CONCLUSIONS: Bisacodyl is effective and safe in improving stool frequency and consistency in acute treatment of idiopathic constipation.

Acute Disease↗
PubMed2006

Bacterial and fungal microbiota in relation to probiotic therapy (VSL#3) in pouchitis.

BACKGROUND: The intestinal microbiota plays a critical role in the pathophysiology of pouchitis, a major complication after ileal pouch anal anastomosis in patients with ulcerative colitis. Recently, controlled trials have demonstrated that probiotics are effective in maintenance of remission in pouchitis patients. However, the mechanism by which therapy with probiotics works remains elusive. This study explores the role of the bacterial and fungal flora in a controlled trial for maintenance of remission in pouchitis patients with the probiotic VSL#3 compound. METHODS: The mucosa associated pouch microbiota was investigated before and after therapy with VSL#3 by analysis of endoscopic biopsies using ribosomal DNA/RNA based community fingerprint analysis, clone libraries, real time polymerase chain reaction (PCR), and fluorescence in situ hybridisation. Patients were recruited from a placebo controlled remission maintenance trial with VSL#3. RESULTS: Patients who developed pouchitis while treated with placebo had low bacterial and high fungal diversity. Bacterial diversity was increased and fungal diversity was reduced in patients in remission maintained with VSL#3 (p = 0.001). Real time PCR experiments demonstrated that VSL#3 increased the total number of bacterial cells (p = 0.002) and modified the spectrum of bacteria towards anaerobic species. Taxa specific clone libraries for Lactobacilli and Bifidobacteria showed that the richness and spectrum of these bacteria were altered under probiotic therapy. CONCLUSIONS: Probiotic therapy with VSL#3 increases the total number of intestinal bacterial cells as well as the richness and diversity of the bacterial microbiota, especially the anaerobic flora. The diversity of the fungal flora is repressed. Restoration of the integrity of a "protective" intestinal mucosa related microbiota could therefore be a potential mechanism of probiotic bacteria in inflammatory barrier diseases of the lower gastrointestinal tract.

Adult↗
PubMed2006

Review article: biological drugs in Crohn's disease.

Biological drugs have opened new therapeutic horizons for treating Crohn's disease (CD), but have also brought with them issues related to immunogenicity, long-term efficacy, safety and cost. At present, inhibitors tumour necrosis factor and adhesion molecules are the most advanced in use and development. When treating luminal disease with infliximab, two-thirds of patients respond initially. The ACCENT 1 study demonstrated that 28% of initial responders are in remission for 1 year. Infliximab has also had a major impact on the management of Crohn's anorectal fistulas. The ACCENT 2 study demonstrated initial response in two-thirds of patients. One-fifth of all treated patients were healed at 1 year. Infliximab diminished the need for further surgery. Magnetic resonance imaging scanning allows the extent of deep healing to be assessed and may influence the duration of treatment. The Mayo Clinic experience in 500 patients demonstrated 6% serious adverse events related to infliximab. The TREAT registry will provide long-term safety data on a larger group of patients. Concurrent immunosuppressive drugs and pre-infusion steroids can decrease antibody formation to infliximab. Screening for tuberculosis (TB) diminishes the rate of TB activation. Biological drugs can offer great therapeutic benefit, but their use must be considered in context.

Antibodies, Monoclonal↗
PubMed2006

Ghrelin augments afferent response to distension in rat isolated jejunum.

Ghrelin has been shown to decrease firing of gastric vagal afferents at doses comparable with circulating levels in the fasted state. This raises the possibility that ghrelin may have a hormonal action on other vagal afferent populations. The aim of this study was to determine the effects of ghrelin on jejunal afferent activity; including responses to distension, 2-methyl-5-hydroxytryptamine (2-methyl-5-HT) and cholecystokinin (CCK) in both naïve and vagotomized rats. Ghrelin significantly augmented the afferent response to distension. No effect was observed on baseline afferent discharge, or the response to 2-methyl-5-HT and CCK. The effect of ghrelin was more pronounced at lower ramp distending pressures (0-30 mmHg). Similarly, ghrelin augmented the jejunal afferent responses to phasic distension at 10-30 mmHg, but had no effect at higher pressures. Chronic subdiaphragmatic vagotomy and administration of the growth hormone secretagogue receptor (GHS-R) antagonist [D-Lys3]-GHRP-6 prevented the augmentation of the afferent responses to distension indicating ghrelin is acting through the GHS-R on vagal afferent fibres. Ghrelin augments the mechanosensation of jejunal vagal afferents and hence may lead to increased perception of hunger contractions.

Animals↗
PubMed2005

Clinical, microbiological, and immunological effects of fructo-oligosaccharide in patients with Crohn's disease.

BACKGROUND AND AIMS: The intestinal microbiota play a pivotal role in the inflammation associated with Crohn's disease through their interaction with the mucosal immune system. Some bifidobacteria species are immunoregulatory and induce increased dendritic cell interleukin 10 (IL-10) release in vitro. Fructo-oligosaccharides (FOS) increase faecal and mucosal bifidobacteria in healthy volunteers. The aim of this study was to assess the effect of FOS administration on disease activity, bifidobacteria concentrations, and mucosal dendritic cell function in patients with moderately active Crohn's disease. PATIENTS AND METHODS: Ten patients with active ileocolonic Crohn's disease received 15 g of FOS for three weeks. Disease activity was measured using the Harvey Bradshaw index. Faecal and mucosal bifidobacteria were quantified by fluorescence in situ hybridisation, and mucosal dendritic cell IL-10 and Toll-like receptor (TLR) expression were assessed by flow cytometry of dissociated rectal biopsies. RESULTS: FOS induced a significant reduction in the Harvey Bradshaw index from 9.8 (SD 3.1) to 6.9 (3.4) (p<0.01). There was a significant increase in faecal bifidobacteria concentration from 8.8 (0.9) log(10) to 9.4 (0.9) log(10) cells/g dry faeces (p<0.001). The percentage of IL-10 positive dendritic cells increased from 30 (12)% to 53 (10)% (p=0.06). Finally, the percentage of dendritic cells expressing TLR2 and TLR4 increased from 1.7 (1.7)% to 36.8 (15.9)% (p=0.08) and from 3.6 (3.6)% to 75.4 (3.4)% (p<0.001), respectively. CONCLUSIONS: FOS supplementation increases faecal bifidobacteria concentrations and modifies mucosal dendritic cell function. This novel therapeutic strategy appears to decrease Crohn's disease activity in a small open label trial and therefore warrants further investigation.

Adult↗
PubMed2005

Ghrelin enhances gastric emptying in diabetic gastroparesis: a double blind, placebo controlled, crossover study.

BACKGROUND: Diabetic gastroparesis is a disabling condition with no consistently effective treatment. In animals, ghrelin increases gastric emptying and reverses postoperative ileus. We present the results of a double blind, placebo controlled, crossover study of ghrelin in gastric emptying in patients with diabetic gastroparesis. METHODS: Ten insulin requiring diabetic patients (five men, six type I) referred with symptoms indicative of gastroparesis received a two hour infusion of either ghrelin (5 pmol/kg/min) or saline on two occasions. Blood glucose was controlled by euglycaemic clamp. Gastric emptying rate (GER) was calculated by real time ultrasound following a test meal. Blood was sampled for ghrelin, growth hormone (GH), and pancreatic polypeptide (PP) levels. Cardiovagal neuropathy was assessed using the Mayo Clinic composite autonomic severity score (range 0 (normal)-3). RESULTS: Baseline ghrelin levels were mean 445 (SEM 36) pmol/l. Ghrelin infusion achieved a peak plasma level of 2786 (188) pmol/l at 90 minutes, corresponding to a peak GH of 70.9 (19.8) pmol/l. Ghrelin increased gastric emptying in seven of 10 patients (30 (6)% to 43 (5)%; p = 0.04). Impaired cardiovagal tone correlated inversely with peak postprandial PP values (p < 0.05) but did not correlate with GER. CONCLUSIONS: Ghrelin increases gastric emptying in patients with diabetic gastroparesis. This is independent of vagal tone. We propose that analogues of ghrelin may represent a new class of prokinetic agents.

Adult↗
PubMed2005

Sacral nerve stimulation for faecal incontinence in patients with previous partial spinal injury including disc prolapse.

BACKGROUND: This study examined the use of sacral nerve stimulation (SNS) to treat faecal incontinence in patients with partial spinal injury. METHODS: Patients selected for SNS had experienced more than one episode of faecal incontinence per week to liquid or solid stool for more than 1 year and had failed maximal conservative treatment. All patients had an intact external anal sphincter. RESULTS: Temporary SNS was performed in 13 patients (median age 58.5 (range 39-73) years). The spinal insults were disc prolapse (six), trauma (four), spinal stenosis (one) or occurred during neurosurgery (two). Twelve patients (eight women and four men) had successful temporary stimulation and proceeded to permanent implantation. The median follow-up time was 12 (range 6-24) months. The mean(s.d.) number of episodes of incontinence decreased from 9.33(7.64) per week at baseline to 2.39(3.69) at last follow-up (P = 0.012). The number of days per week with incontinence and staining decreased significantly (both P < 0.001). Ability to defer defaecation improved from a median of not being able to defer (range 0-1 min) to being able to defer for 5-15 (range 0 to over 15) min (P = 0.022). CONCLUSION: SNS can benefit patients with faecal incontinence following partial spinal injury.

Adult↗
PubMed2005

Injectable bulking agents for treating faecal incontinence.

BACKGROUND: Reports of the use of injectable bulking agents for faecal incontinence are currently confined to a small number of pilot studies. However, the use of these agents is rapidly becoming widespread based on this limited knowledge. METHODS: This review provides an overview of the products available and the methods of delivery based on the pilot studies, selected articles reporting experience of these agents in urology, plastic surgery and laryngology, and some animal studies. RESULTS AND CONCLUSIONS: Although bulking agents have been used to treat urinary incontinence for over four decades, their use in faecal incontinence has so far been limited. The large choice of products now available and the lack of a defined injection strategy will hamper efforts to produce meaningful prospective randomized trials.

Biocompatible Materials↗
PubMed2005

Recent developments in CT colonography.

CT colonography allows reliable, non-invasive, rapid, high resolution imaging of the whole large bowel. Recent advances in technology such as computer-aided detection (CAD), scanning with or without bowel preparation, and low radiation are continually developing to improve the efficacy of this technique. This review will update the reader as to ongoing developments while presenting current thinking from the gastroenterological perspective.

Adenoma↗
PubMed2005

Review article: Population screening for colorectal cancer.

Colorectal cancer is a common cancer and common cause of death. The mortality rate from colorectal cancer can be reduced by identification and removal of cancer precursors, adenomas, or by detection of cancer at an earlier stage. Pilot screening programmes have demonstrated decreased colorectal cancer mortality; as a result many countries are developing colorectal cancer screening programmes. The most common modalities being evaluated are faecal occult blood testing, flexible sigmoidoscopy and colonoscopy. Implementation of screening tests has been hampered by cost, invasiveness, availability of resources and patient acceptance. New technologies such at computed tomographic colonography and stool screening for molecular markers of neoplasia are in development as potential minimally invasive tools. This review considers who should be screened, which test to use and how often to screen.

Colorectal Neoplasms↗
PubMed2005

Production of interleukin (IL)-10 and IL-12 by murine colonic dendritic cells in response to microbial stimuli.

Intestinal dendritic cells (DC) are likely to regulate immunity to gut microflora, but little is known about their responses to bacterial antigens. Therefore, DC from normal murine colon were characterized and their cytokine responses to components of Gram-negative and/or Gram-positive bacteria assessed. Cells were obtained by digestion of colonic tissue and contained DC that were identified by flow cytometry as CD11c(+) major histocompatibility complex (MHC) class II(+) cells. Purified DC were obtained by immunomagnetic separation plus cell sorting. DC had the morphology of immature myeloid cells, were endocytically active, expressed low levels of co-stimulatory molecules and stimulated a weak allogeneic mixed leucocyte reaction. Analysis of flow cytometry data by a sensitive subtraction method allowed measurement of production of interleukin (IL)-12 and IL-10 by small numbers of gut DC by intracellular staining. Fewer than 5% of unstimulated DC produced either IL-10 or IL-12. IL-10 production was significantly up-regulated following stimulation with Bifidobacteria longum, but not after exposure to lipopolysaccharide (LPS) or Streptococcus faecium. In contrast, colonic DC produced IL-12 in response to both LPS and B.longum. Thus, colonic DC can produce both IL-12 and IL-10 following bacterial stimulation. Cell wall components from different bacteria stimulate distinct responses and may direct immune responses differentially in the gut.

Animals↗
PubMed2005

Effect of sacral neuromodulation for faecal incontinence on sexual activity.

INTRODUCTION: Faecal incontinence affects a percentage of the population and can have a significant effect on their ability to establish and maintain sexual relations. PATIENTS AND METHODS: Sixteen consecutive patients with permanent sacral neuromodulation (SNM) for faecal incontinence completed a 'Sex Life Questionnaire' at their follow up visit to ascertain whether there was any improvement in this aspect of their life. RESULTS: Nine of the sixteen patients was sexually active. These nine patients (median age 56 (35-61) years) had a significant reduction in faecal incontinence episodes per week from a median of 12 (1-55) to 1.5 (0-8.5) (P = 0.008). All nine patients reported that their sex life had been affected by feacal incontinence prior to SNM and seven had felt benefit from implantation. The median improvement in their sex life was 40% (1-100) and the percentage improvement was inversely correlated to age (r = -0.834, P = 0.005). CONCLUSION: SNM improves the quality of sexual activity in 78% of patients. More improvement seems to be gained the younger the patients.

Adult↗
PubMed2004

Azathioprine dose escalation in inflammatory bowel disease.

BACKGROUND: Forty per cent of patients with inflammatory bowel disease fail to respond to standard dose azathioprine (2 mg/kg/day). AIMS: To evaluate the efficacy and safety of increasing the azathioprine dose according to a fixed schedule and guided by clinical response and adverse effects. METHODS: We reviewed the records of all patients with inflammatory bowel disease treated by a single clinician over 6 years, unresponsive to at least 3 months treatment with standard dose azathioprine, and whose dose was subsequently increased. RESULTS: Forty patients (27 male; 24 Crohn's, 16 ulcerative colitis) with chronic active disease or recurrent flares despite standard dose azathioprine for a median 8 months (range 3-114) increased their dose from a median 2.02 (1.61-3.19) mg/kg/day to 2.72 (2.37-3.99) mg/kg/day in one to four increments of 0.5 mg/kg/day, and were followed over a median 6 (0.5-54) months. Eleven of the 40 patients (seven Crohn's, four ulcerative colitis) responded or had reduced frequency of flare-ups at the end of follow-up, while 17 of the 40 patients had no benefit. Response was more likely for maximum doses < or =2.5 mg/kg/day (six of 11 patients) than for doses >2.5 mg/kg/day (five of 29 patients) (P = 0.042). Twelve patients (11 of whom received maximum doses >2.5 mg/kg/day) were unable to maintain an increased azathioprine dose because of leukopenia in eight, nausea in three, and raised liver enzymes in one (all transient and reversible). CONCLUSIONS: Increasing the azathioprine dose up to 2.5 mg/kg/day appears beneficial in patients who have not responded to 2 mg/kg/day. Further increase above 2.5 mg/kg/day is less likely to be efficacious, and is associated with a substantial risk of adverse reactions.

Adult↗
PubMed2004

Erythromycin for the treatment of chronic intestinal pseudo-obstruction: description of six cases with a positive response.

BACKGROUND: Chronic intestinal pseudo-obstruction, due to intestinal myopathy or neuropathy, is characterized by the signs and symptoms of intestinal obstruction in the absence of true obstruction. Episodes are resistant to medical therapy. AIM: To determine the value of erythromycin treatment in chronic intestinal pseudo-obstruction. METHODS: All patients with proven chronic intestinal pseudo-obstruction treated with erythromycin were reviewed. Patients with symptomatic benefit are described in detail. Responders were compared with non-responders to identify the factors associated with benefit. RESULTS: Fifteen consecutive patients (nine females; median age, 37 years; median follow-up, 41 months) were treated with oral erythromycin, 1.5-2.0 g/day. Six patients (three primary visceral myopathy, two normal histology on light microscopy, one visceral myopathy secondary to scleroderma) responded, with decreased pain and vomiting, normalized bowel dysfunction and decreased episodes of ileus. Five of the six patients (83%) who responded to erythromycin were male, compared with two of the nine non-responders (22%) (P = 0.04). Four of the six responders (67%) had histological or immunohistological visceral myopathy, compared with three of the nine patients (33%) who failed to respond. Responders were less likely than non-responders to be taking long-term opiates. CONCLUSIONS: Erythromycin is effective for acute episodes of ileus and chronic symptoms in some patients with chronic intestinal pseudo-obstruction.

Adult↗
PubMed2004

Sacral nerve stimulation for faecal incontinence in the UK.

BACKGROUND: Sacral nerve stimulation (SNS) is an effective therapy for faecal incontinence. Published studies derive largely from single centres and there is a need to determine the broader applicability of this procedure. METHODS: Prospective data were collected for all patients undergoing SNS in the UK. Records were reviewed to determine the outcome of treatment. RESULTS: In three UK centres 59 patients underwent peripheral nerve evaluation, with 46 (78 per cent) proceeding to permanent implantation. Of these 46 patients (40 women) all but two had improved continence at a median of 12 (range 1-72) months. Faecal incontinence improved from a median (range) of 7.5 (1-78) to 1 (0-39) episodes per week (P < 0.001). Urgency improved in all but five of 39 patients in whom ability to defer defaecation was determined, improving from a median of 1 (range 0-5) to 10 (range from 1 to more than 15) min (P < 0.001). Maximum anal squeeze pressure and sensory function to rectal distension changed significantly. Significant improvement occurred in general health (P = 0.024), mental health (P = 0.008), emotional role (P = 0.034), social function (P = 0.013) and vitality (P = 0.009) subscales of the Short Form 36 health survey questionnaire. There were no major complications. One implant was removed. CONCLUSION: SNS is a safe and effective treatment, in the medium to long term, for faecal incontinence when conservative treatment has failed.

Adult↗
PubMed2004

Systematic review of sacral nerve stimulation for faecal incontinence and constipation.

BACKGROUND AND METHOD: This systematic review assesses the efficacy and safety of sacral nerve stimulation (SNS) for faecal incontinence and constipation. Electronic databases and selected websites were searched for studies evaluating SNS in the treatment of faecal incontinence or constipation. Primary outcome measures included episodes of faecal incontinence per week (faecal incontinence studies) and number of evacuations per week (constipation studies). RESULTS: From 106 potentially relevant reports, six patient series and one crossover study of SNS for faecal incontinence, and four patient series and one crossover study of SNS for constipation, were included. After implantation, 41-75 per cent of patients achieved complete faecal continence and 75-100 per cent experienced improvement in episodes of incontinence. There were 19 adverse events among 149 patients. The small crossover study reported increased episodes of faecal incontinence when the implanted pulse generator was switched off. Case series of SNS for constipation reported an increased frequency of evacuation. There were four adverse events among the 20 patients with a permanent implant. The small crossover study reported a reduced number of evacuations when the pulse generator was switched off. CONCLUSION: SNS results in significant improvement in faecal incontinence in patients resistant to conservative treatment. Early data also suggest benefit in the treatment of constipation.

Constipation↗
PubMed2004

Prospective evaluation of intestinal homing memory T cells in ulcerative colitis.

BACKGROUND: Intestinal homing (beta7+) memory T cells reflect the mucosal environment in which they were primed. We hypothesized that prospective assessment of cytokine production by intestinal homing (beta7+) memory T cells in ulcerative colitis patients followed from remission to early relapse may elucidate shifts in cytokine production relevant to the mucosal environment associated with the early phase of inflammation. METHODS: Twelve patients with frequently relapsing ulcerative colitis (> or = 2 relapses in the previous 12 months) were recruited in remission and followed prospectively until relapse. Antibody labeling of whole blood and flow cytometry were used to identify beta7+ cells and beta7- populations within CD3+CD45RA- leukocytes. Production of cytokines (IFN-gamma, TNF-alpha, IL-2, IL-10, TGF-beta, and IL-4) was determined by intracellular labeling. RESULTS: Early relapse of ulcerative colitis was associated with a shift of T cells from the naive to the memory T cell pool, and further the ratio of beta7+:beta7- memory T cells was significantly reduced at relapse (p < 0.01). A greater proportion of intestinal homing beta7+ memory T cells produced IL-4 (p < 0.02) and TNF-alpha (p < 0.05) at disease relapse compared with remission. Non-intestinal homing beta7- memory T cells also showed a tendency toward an increased production of TH1 and TH2 cytokines. CONCLUSIONS: The earliest phase of intestinal inflammation in ulcerative colitis patients is associated with an increase in both TH1 (TNF-alpha and TH2 (IL-4) cytokines by intestinal homing beta7+ memory T cells. These data support the principles of targeting lymphocyte trafficking as therapies in ulcerative colitis.

Adult↗