Pelvic Pain in Coloproctology
Treatment of irritable bowel syndrome.
Hadley SK, Gaarder SM
Am Fam Physician. 2005 Dec 15;72(12):2501-6.
Irritable bowel syndrome affects 10 to 15 percent of the U.S. population to some degree. This condition is defined as abdominal pain and discomfort with altered bowel habits in the absence of any other mechanical, inflammatory, or biochemical explanation for these symptoms. Irritable bowel syndrome is more likely to affect women than men and is most common in patients 30 to 50 years of age. Symptoms are improved equally by diets supplemented with fiber or hydrolyzed guar gum, but more patients prefer hydrolyzed guar gum. Antispasmodic agents may be used as needed, but anticholinergic and other side effects limit their use in some patients. Loperamide is an option for treatment of moderately severe diarrhea. Antidepressants have been shown to relieve pain and may be effective in low doses. Trials using alosetron showed a clinically significant, although modest, gain over placebo, but it is indicated only for women with severe diarrhea-predominant symptoms or for those in whom conventional treatment has failed. Tegaserod has an advantage over placebo in constipation-predominant irritable bowel syndrome; it is indicated for up to 12 weeks of treatment in women. However, postmarketing reports of severe diarrhea and ischemic colitis further limit its use. Herbal therapies such as peppermint oil also may be effective in the treatment of irritable bowel syndrome. Therapies should focus on specific gastrointestinal dysfunctions (e.g., constipation, diarrhea, pain), and medications only should be used when nonprescription remedies do not work or when symptoms are severe.
Detection of inflammatory markers in stools from patients with irritable bowel syndrome and collagenous colitis.
Lettesjo H, Hansson T, Peterson C, Ung KA, Ringstrom G, Abrahamsson H, Simren M
Scand J Gastroenterol. 2006 Jan;41(1):54-9.
Objective. Irritable bowel syndrome (IBS) and collagenous colitis (CC) share chronically recurring symptoms of altered bowel habits associated with abdominal pain or discomfort. The aims of the present study were to investigate whether inflammatory markers could be detected in faeces from patients with IBS and CC, and to elucidate whether such analyses could be used as non-invasive tools to distinguish between these disorders. Material and methods. Stool samples were obtained from 18 patients with CC, 46 patients with IBS and 20 healthy controls (HC). Eosinophil protein X (EPX), myeloperoxidase (MPO), tryptase, interleukin-1 beta (IL-1beta) and tumour necrosis factor alpha (TNFalpha) were measured in supernatants from processed faeces using immunoassays. Results. EPX levels were enhanced in faeces from CC patients (median 3.8 microg/g (0.47-16.2)) compared to patients with IBS (0.44 microg/g (0.25-1.8)), p<0.001, and HC (0.46 microg/g (0.21-1.3)), p<0.001. In addition, MPO was increased in CC patients (11.7 microg/g (2.0-124)) compared to IBS patients (1.7 microg/g (0.81-5.2)), p<0.01, and HC (2.5 microg/g (1.1-6.3)), p<0.05. Tryptase was found in 9/18 patients with CC, 6/46 with IBS and 1/19 HC. IL-1beta was only enhanced in 2/11 CC patients and TNFalpha was not detected in any sample. Conclusions. Increased levels of EPX, MPO and tryptase were observed in stools from collagenous colitis patients, whereas the levels in IBS patients did not differ from healthy controls. Our data suggest that faecal markers could be used as part of the clinical work-up to determine which patients should be biopsied and evaluated for collagenous colitis.
Gender issues in the management of irritable bowel syndrome.
Kane S
Int J Fertil Womens Med. 2005 Mar-Apr;50(2):79-82.
Irritable Bowel Syndrome is a prevalent condition that affects more women than men. Theories as to its underlying pathophysiology are still evolving, but what appears clear is that women pose specific challenges to the management of this condition. Indeed, some issues specific to women are not necessarily part of routine care. Certain gender-related issues such as menses, fertility, pregnancy and menopause are often overlooked and mismanaged. Women have different psychological concerns as compared to men with regard to their self-image and impact of disease. Healthcare providers, regardless of their primary focus, should be aware of these differences and be familiar with general information.
Inhibitory effects of Lactobacillus reuteri on visceral pain induced by colorectal distension in Sprague Dawley rats.
Kamiya T, Wang L, Forsythe P, Goettsche G, Mao Y, Wang Y, Tougas G, Bienenstock J
Gut. 2005 Dec 16;.
BACKGROUND AND AIMS: Probiotic bacteria are being investigated as possible treatments for many intestinal disorders. The present study aimed to explore the effects of live, heat-killed or gamma irradiated Lactobacillus reuteri on cardio-autonomic response and single fiber unit discharge in dorsal root ganglia to colorectal distension in healthy Sprague Dawley rats housed under conventional conditions. The effects of this treatment on somatic pain were also examined. METHODS: 1 X 10(9) bacteria were given by gavage for 9 days. Colorectal distension occurred under anesthesia. Heart rate was measured through continuous electrocardiography. Single fiber unit discharge was recorded from the 6th left lumbar dorsal root ganglion. Somatic pain was evaluated by the tail flick and paw pressure tests. RESULTS: Colorectal distension caused a pressure- dependent bradycardia in the control (native medium) group. Treatment with live, heat-killed or gamma irradiated bacteria as well as their products (conditioned medium) prevented the pain response even during the maximum distension pressure (80mmHg). Both viable and non-viable bacteria significantly decreased dorsal root ganglion single unit activity to distension. No effects on somatic pain were seen with any treatment. CONCLUSIONS: Oral administration of live, killed probiotic bacteria or conditioned medium inhibited the constitutive cardio-autonomic response to colorectal distension in rats through effects on enteric nerves. These data may provide a novel explanation for beneficial probiotic effects on visceral pain.
The role of fiber in the treatment of irritable bowel syndrome: therapeutic recommendations.
Zuckerman MJ
J Clin Gastroenterol. 2006 Feb;40(2):104-8.
Irritable bowel syndrome is a common clinical condition that often presents a therapeutic challenge. There is no standard therapy and a multilevel approach is recommended. A high-fiber diet is often one of these components. Many investigators have studied the effectiveness of either fiber supplementation or bulking agents in patients with irritable bowel syndrome. The purpose of this review is to summarize the current literature on the use of fiber in irritable bowel syndrome and to provide some specific recommendations. Systematic reviews of these trials have generally not found fiber to be significantly more effective than placebo at relieving global irritable bowel syndrome symptoms. There may be differences between results obtained with soluble and insoluble fiber. Adverse effects of fiber use may include abdominal discomfort and bloating. Although dietary fiber or bulking agents do not appear to be useful as sole treatment of irritable bowel syndrome, they may have a limited role in empiric therapy depending upon the patient's symptom complex, especially if constipation is the most significant symptom. The basic principles for using fiber therapy are to start with a low dose and increase slowly, to give an adequate trial and to evaluate the results early and periodically.
Rectal afferent hypersensitivity and compliance in irritable bowel syndrome: differences between diarrhoea-predominant and constipation-predominant subgroups.
Zar S, Benson MJ, Kumar D
Eur J Gastroenterol Hepatol. 2006 Feb;18(2):151-158.
OBJECTIVES: To evaluate the differences in rectal compliance and sensory thresholds for the urge to defecate and discomfort between irritable bowel syndrome (IBS) subgroups and controls, and to correlate these parameters with rectal symptoms. METHODS: A total of 38 IBS patients [Rome II criteria; 19 diarrhoea-predominant IBS (D-IBS), 16 constipation-predominant IBS (C-IBS), three with alternating diarrhoea and constipation IBS (Alt-IBS)] and 10 controls were studied. A barostat was used to measure rectal compliance and sensory thresholds, in the 'unprepared' rectum. The thresholds for the urge to defecate and discomfort were determined using phasic rectal balloon distension in a double random staircase sequence. RESULTS: D-IBS had significantly lower rectal compliance and threshold for the urge to defecate compared with controls [4 ml/mmHg interquartile range (IQR) 3.99 versus 8.4 ml/mmHg IQR 5.69; P=0.001; 8 mmHg IQR 6 versus 20 mmHg IQR 4; P=0.003]. D-IBS also had significantly lower rectal compliance and threshold for the urge to defecate compared with the C-IBS group (5.8 ml/mmHg IQR 4.61; P=0.027; 16 mmHg IQR 12; P=0.003). The volume at the threshold for discomfort was significantly lower in D-IBS compared with controls (163 ml IQR 99.5 versus 212 ml IQR 147.25; P=0.016). The severity of abdominal pain and rectal symptoms showed a significantly negative correlation with rectal sensory thresholds. CONCLUSION: This study shows that the sensory threshold for the urge to defecate and rectal compliance is significantly lower in D-IBS compared with C-IBS and controls. The consequent inability to tolerate rectal faecal loading may account for the symptoms of the passage of frequent, small-volume stools in D-IBS patients.
Is a negative colonoscopy associated with reassurance or improved health-related quality of life in irritable bowel syndrome?
Spiegel BM, Gralnek IM, Bolus R, Chang L, Dulai GS, Naliboff B, Mayer EA
Gastrointest Endosc 2005 Dec;62(6):892-899.
BACKGROUND: Although colonoscopy is rarely of clinical use in irritable bowel syndrome (IBS), it is, nonetheless, frequently performed in IBS. Proponents contend that a normal colonoscopy provides reassurance and improves health-related quality of life (HRQOL). However, no previous data have measured these effects. We sought to measure the association of a normal colonoscopy with reassurance and HRQOL in patients with IBS aged <50 years. METHODS: We retrospectively evaluated 458 patients with IBS, aged 18 to 49 years. Subjects completed a symptom questionnaire, the Symptom Checklist 90 (SCL-90) psychometric checklist, and the Short Form 36 (SF-36) Health Survey. The main outcomes were HRQOL as measured by the mental component score (MCS) and the physical component score (PCS) of the SF-36 and reassurance as operationalized by a negative response to the question: "Do you think there is something seriously wrong with your body?" The independent variable was presence or absence of a previous normal colonoscopy. We performed regression analysis to control for potential confounders, including timing of colonoscopy. RESULTS: The unadjusted mean SF-36 PCS was 42 +/- 10 (0-100 scale: 0, worst) in patients with recent colonoscopy (<12 months), 45 +/- 11 in patients with distant colonoscopy (>12 months), and 45 +/- 10 in patients without colonoscopy (p = 0.78). The mean SF-36 MCS in the 3 groups were 42 +/- 13, 44 +/- 11, and 43 +/- 11 (p = 0.57). Colonoscopy did not impact the proportion reassured (69.3%, 67.2%, 66.6%; p = 0.85). There were no significant differences between groups for any outcomes when adjusting for potential confounders. CONCLUSIONS: We found no independent association between a negative colonoscopy and reassurance or improved HRQOL in IBS patients aged <50 years. These results suggest that the role of colonoscopy in IBS may be limited but require confirmation in prospective trials.
New criteria for irritable bowel syndrome based on prospective symptom evaluation.
Walter SA, Ragnarsson G, Bodemar G
Am J Gastroenterol 2005 Nov;100(11):2598-9.
Dysregulation of peripheral cytokine production in irritable bowel syndrome.
Collins SM
Am J Gastroenterol 2005 Nov;100(11):2517-8.
Combining physostigmine with meperidine for sedation and analgesia during colonoscopy.
Yardeni IZ, Melzer E, Smolyarenko V, Zeidel A, Chervinsky A, Binder Y, Beilin B
Endoscopy 2005 Dec;37(12):1205-10.
BACKGROUND AND STUDY AIM: Opiate or benzodiazepine drugs are often used during colonoscopy, but they are associated with respiratory depression and prolonged recovery. Physostigmine, a tertiary anticholinesterase agent, is known to enhance analgesia and to reverse the central nervous system depressant effects of these drugs. This study compared the effect of giving meperidine alone with the effect of giving meperidine in combination with physostigmine in patients who were undergoing complete colonoscopy. PATIENTS AND METHODS: A total of 44 outpatients undergoing elective colonoscopy were randomly assigned to receive analgesia with either meperidine 0.5 mg/kg intravenously (group 1, n = 24) or physostigmine 10 micrograms/kg intravenously, followed 5 minutes later by meperidine 0.5 mg/kg intravenously (group 2; n = 20). The patients were assessed with regard to oxygen saturation, hemodynamic changes, pain perception and sedation scores, readiness to go home, and adverse effects. RESULTS: The group 1 patients' oxygen saturations consistently fell, both during the procedure and in the recovery period; in group 2, oxygen saturations remained stable throughout the procedure and recovery period (95.88 % +/- 0.99 vs. 98.15 +/- 0.99, P < 0.001). Patients in group 2 reported lower pain perception scores during the procedure (measured using a visual analog scale) than patients in group 1 (1.46 +/- 0.31 vs. 1.75 +/- 0.41; F(1,42) = 6.484, P < 0.015) and were less sedated during recovery ( F(1,41) = 6.56, P < 0.015). No significant differences were found between the two groups with regard to heart rate or arterial blood pressure. All patients in group 2 were ready to go home after 25 minutes in the recovery area; three patients in group 1 were not ready to leave at 25 minutes and left the facility after 60 minutes. Four patients suffered from minor side effects of physostigmine (sweating and nausea). CONCLUSIONS: Combining physostigmine with meperidine as preparatory treatment for patients undergoing colonoscopy prevents respiratory depression, improves analgesia, and shortens recovery time, with only mild side effects.
Herbal medicine with curcuma and fumitory in the treatment of irritable bowel syndrome: a randomized, placebo-controlled, double-blind clinical trial.
Brinkhaus B, Hentschel C, Von Keudell C, Schindler G, Lindner M, Stutzer H, Kohnen R, Willich SN, Lehmacher W, Hahn EG
Scand J Gastroenterol 2005 Aug;40(8):936-43.
OBJECTIVE: Irritable bowel syndrome (IBS) is a common functional disorder for which there is no reliable medical treatment. The aim of this study was to determine the efficacy of two herbal remedies used in the treatment of IBS. MATERIAL AND METHODS: In a randomized, double-blind, placebo-controlled trial, IBS patients were randomly assigned to one of three treatment groups: 1) Curcuma xanthorriza 60 mg daily (curcuma group) (n=24), 2) Fumaria officinalis 1500 mg daily (fumitory group) (n=24) and 3) placebo (n=58). The study treatment was applied three times a day for 18 weeks. The main outcome parameters were changes in global patient ratings of IBS-related pain and distension on a visual analogue scale (0-50 mm) between baseline and at the end of treatment. Additional outcome parameters included global assessments of changes in IBS symptoms and psychosocial stress caused by IBS. RESULTS: A total of 106 patients (mean age 48+/-12 years, 63% F) were included in the intention-to-treat group. IBS-related pain decreased by -0.9+/-11.5 (mm+/-SD) in the fumitory group, -0.3+/-9.9 in the placebo group and increased by 2.0+/-9.5 in the curcuma group (p=0.81). IBS-related distension decreased by -1.4+/-12.5 in the curcuma group, -2.1+/-9.2 in the placebo group and increased by 0.3+/-9.3 in the fumitory group (p=0.48). Additionally, the global assessment of changes in IBS symptoms and psychological stress due to IBS did not differ significantly among the three treatment groups. CONCLUSIONS: Neither fumitory nor curcuma showed any therapeutic benefit over placebo in patients with IBS. Therefore, the use of these herbs for the treatment of IBS cannot be recommended
Acupuncture treatment in irritable bowel syndrome.
Schneider A, Enck P, Streitberger K, Weiland C, Bagheri S, Witte S, Friederich HC, Herzog W, Zipfel S
Gut 2005 Sep 22;.
BACKGROUND AND AIMS: Despite occasional positive reports on the efficacy of acupuncture on functions of the gastrointestinal tract, there is no conclusive evidence that acupuncture (AC) is effective in the treatment of irritable bowel syndrome (IBS). PATIENTS AND METHODS: 43 patients with IBS according to Rome II criteria were randomly assigned to receive either acupuncture (n=22) or sham acupuncture (n=21) (SAC) using the so-called "Streitberger needle". Treatment duration was 10 sessions with an average of 2 acupuncture sessions per week, and primary endpoint was improvement of quality of life (QOL) using the Functional Digestive Diseases Quality of Life Questionnaire (FDDQL) and a general Quality of Life Questionnaire (SF-36), compared to baseline assessment. QOL measurement was repeated three months after treatment. RESULTS: Both the AC as well as the SAC group improved significantly in global QOL by the FDDQL at the end of treatment (p=0.022), with no differences between both groups. The SF36 was insensitive to these changes (except for pain). This effect was partially reversed three months later. Post-hoc comparison of responders and non-responders in both groups combined revealed a significant prediction of the placebo response by two subscales of the FDDQL (sleep, coping) (F=6.746, p=0.003) in a stepwise regression model. CONCLUSIONS: Acupuncture in IBS is primarily a placebo response. Based on the small differences found between AC and SAC, a study including 566 patients would be necessary to prove efficacy of AC over SAC. The placebo response may be predicted by high coping capacity and low sleep quality in individual patients.
A Randomized, Prospective, Double-Blind, Placebo-Controlled Trial of the Effect of a Calcium Channel Blocker Ointment on Pain After Hemorrhoidectomy.
Silverman R, Bendick PJ, Wasvary HJ
Dis Colon Rectum 2005 Sep 2;.
PURPOSE: Spasm of the internal sphincter plays a role in hemorrhoidal disease and may be a source of anal pain after hemorrhoid surgery. We have evaluated the effects of topical diltiazem, a calcium channel blocker, in reducing pain after hemorrhoidectomy. METHODS: After hemorrhoidectomy, 18 patients were randomly assigned to receive 2 percent diltiazem ointment (n = 9) or a placebo ointment (n = 9). Ointments were applied to the perianal region three times daily for seven days. Patients were prescribed hydrocodone bitartrate (Vicodin ((R))) to take as needed. The type and number of prescribed or nonprescribed medications taken during the postoperative period were recorded. Patients maintained a log to measure postoperative pain daily and perceived benefit of the ointment, using a Visual Analog Scale ranging from 0 to 10. Any postoperative morbidity noted during the follow-up period was recorded. RESULTS: Patients using the diltiazem ointment had significantly less pain and greater benefit than those in the placebo group throughout the first postoperative week. Postoperative pain scores in the placebo group averaged 8.8 +/- 1.2 early and diminished to 5.2 +/- 1.7 at the end of one week, compared to the diltiazem group of 5.2 +/- 2.4 early and 2.3 +/- 1.2 at the end of one week (P < 0.001, both time periods). Perceived benefit in the placebo group averaged 2.7 +/- 1.2 vs. 5.6 +/- 1.4 in the diltiazem group (P < 0.001). Total and daily narcotic use was higher in the placebo group, but this was not statistically significant (P = 0.13). No differences in the frequency of use of nonsteroidal anti-inflammatory drugs and acetaminophen were seen between the two groups, and there were no differences in morbidity between the two groups. CONCLUSIONS: Perianal application of 2 percent diltiazem ointment after hemorrhoidectomy significantly reduces postoperative pain and is perceived as beneficial, with no increase in associated morbidity. Patients using a placebo ointment tend to take more prescription narcotics for pain relief postoperatively, with a similar usage of nonsteroidal anti-inflammatory drugs and acetaminophen, although differences were not significant.
The impact of somatization on the use of gastrointestinal health-care resources in patients with irritable bowel syndrome.
Spiegel BM, Kanwal F, Naliboff B, Mayer E
Am J Gastroenterol 2005 Oct;100(10):2262-73.
BACKGROUND: It is unclear why patients with irritable bowel syndrome (IBS) consume a disproportionate amount of health-care resources versus matched controls. One possibility is the presence of comorbid somatization-a process marked by multiple unexplained somatic complaints that is highly prevalent in IBS. We sought to determine whether higher levels of somatization are associated with higher levels of gastrointestinal (GI) resource utilization in IBS. METHODS: A total of 1,410 patients >18 yr with IBS were evaluated at a university-based clinic. Subjects completed a symptom questionnaire, the SCL-90R psychometric checklist, and the SF-36 Health Survey. We measured two outcomes: (1) a 1-yr direct GI health-care costs and (2) a 1-yr number of GI physician visits. Our primary regressor was somatization as measured by the somatization subscale of the SCL-90R. We performed regression analyses to measure the adjusted influence of somatization on GI resource utilization. RESULTS: In the full sample of patients, there were no differences in the likelihood of expending versus not expending previous GI health-care costs among groups with varying levels of somatization. Similarly, there were no differences in either the likelihood of visiting a GI physician or the number of overall physician visits among patients with varying levels of somatization. However, in the subset of patients expending at least $1.00 in GI costs in the previous year (53% of cohort), there was a significantly higher cost of care for subjects with high versus low levels of somatization. CONCLUSIONS: IBS patients with high levels of somatization are not more likely to seek GI care compared to patients with low levels of somatization. However, once they are evaluated for care, patients with high somatization expend significantly more GI health-care costs. This suggests that somatization is positively associated with health-care costs in IBS, and that the association may be driven more by physicians than patients. (Am J Gastroenterol 2005;100:1-12).
A randomized controlled trial of a probiotic combination VSL# 3 and placebo in irritable bowel syndrome with bloating.
Kim HJ, Vazquez Roque MI, Camilleri M, Stephens D, Burton DD, Baxter K, Thomforde G, Zinsmeister AR
Neurogastroenterol Motil 2005 Oct;17(5):687-96.
Aim: To evaluate the effects of a combination probiotic on symptoms and colonic transit in patients with irritable bowel syndrome (IBS) and significant bloating. Methods: Forty-eight patients with Rome II IBS were randomized in a parallel group, double-blind design to placebo or VSL# 3 twice daily (31 patients received 4 weeks and 17 patients 8 weeks of treatment). Pre- and post-treatment colonic transit measurements were performed using scintigraphy with (111)In charcoal. Symptoms were summarized as an average daily score for the entire period of treatment and separately for the first 4 weeks of treatment. Weekly satisfactory relief of abdominal bloating was assessed. Results: Treatment with VSL# 3 was associated with reduced flatulence over the entire treatment period (placebo 39.5 +/- 2.6 vs VSL# 3 29.7 +/- 2.6, P = 0.011); similarly, during the first 4 weeks of treatment, flatulence scores were reduced (placebo 40.1 +/- 2.5 vs VSL# 3 30.8 +/- 2.5, P = 0.014). Proportions of responders for satisfactory relief of bloating, stool-related symptoms, abdominal pain and bloating scores were not different. Colonic transit was retarded with VSL# 3 relative to placebo (colon geometric center 2.27 +/- 0.20 vs 2.83 +/- 0.19, P = 0.05 respectively). Conclusion: VSL# 3 reduces flatulence scores and retards colonic transit without altering bowel function in patients with IBS and bloating.
Treatment of Functional Gastrointestinal Disorders Associated with Abdominal Pain.
Hyams JS
J Pediatr Gastroenterol Nutr 2005 Sep;41 Suppl 1:S47-S48.
Abdominal Pain: Is It in the Gut Or in the Head?
Di Lorenzo C
J Pediatr Gastroenterol Nutr 2005 Sep;41 Suppl 1:S44-S46.
Intrarectal lidocaine is an effective treatment for abdominal pain associated with diarrhea-predominant irritable bowel syndrome.
Verne GN, Sen A, Price DD
J Pain 2005 Aug;6(8):493-6.
Irritable bowel syndrome (IBS) is one of the most common disorders seen by gastroenterologists. Visceral hypersensitivity is now well recognized as a clinical marker for the disease. Intrarectal lidocaine has been previously shown to decrease pain report from rectal distension in patients with IBS without any significant serum lidocaine levels. We conducted a prospective, double-blind, crossover trial on 10 patients with IBS to evaluate the effects of 300 mg intrarectal lidocaine jelly on abdominal pain. Ten Caucasian premenopausal women who met the Rome II criteria for diarrhea-predominant IBS were recruited into the study. All of the patients that participated had intermittent left lower quadrant pain and diarrhea. Each patient participated in 2 sessions in which saline jelly (placebo) and lidocaine jelly was administered on a double-blind, crossover basis. Patients participated in these sessions at a time when their ongoing pain was at least 3 on a 0 to 10 visual analogue scale. In comparison to placebo saline jelly, lidocaine jelly significantly decreased abdominal pain (P < .02) for at least 4 hours. None of the patients experienced any side effects. Intrarectal lidocaine may be a potentially useful treatment for chronic abdominal pain in IBS. PERSPECTIVE: The possible presence of abnormal sodium channels in the rectal and or colonic visceral afferents of patients with IBS might serve as a clue as to the effectiveness of rectal lidocaine. The dose of lidocaine used in this study may be of sufficient strength to normalize aberrant sodium channels that may be present in the colon of patients with IBS without affecting normal sodium channels of either IBS or control subjects.
Food-specific IgG4 antibody-guided exclusion diet improves symptoms and rectal compliance in irritable bowel syndrome.
Zar S, Mincher L, Benson MJ, Kumar D
Scand J Gastroenterol 2005 Jul;40(7):800-7.
OBJECTIVE: Dietary modification improves symptoms in irritable bowel syndrome (IBS). Identification of offending foods by dietary elimination/re-challenge is cumbersome. IgG4 antibodies to common food antigens are elevated in IBS. The aim of this article was to evaluate the effect of exclusion diet based on IgG4 titres on IBS symptoms and rectal sensitivity and compliance. MATERIALS AND METHODS: The study comprised 25 patients with IBS (3 M, 22 F, mean age 43 years, Rome II criteria). IgG4 titres to 16 foods (milk, eggs, cheese, wheat, rice, potatoes, chicken, beef, pork, lamb, soya bean, fish, shrimps, yeast, tomatoes and peanuts) were measured. Foods with titres >250 microg/l were excluded for 6 months. Symptom severity was assessed with a previously validated questionnaire at baseline, at 3 months and at 6 months. Rectal compliance and sensitivity were measured in 12 patients at baseline and at 6 months. RESULTS: IgG4 antibodies to milk, eggs, wheat, beef, pork and lamb were commonly elevated. Significant improvement was reported in pain severity (p < 0.001), pain frequency (p = 0.034), bloating severity (p = 0.001), satisfaction with bowel habits (p = 0.004) and effect of IBS on life in general (p = 0.008) at 3 months. Symptom improvement was maintained at 6 months. Rectal compliance was significantly increased (p = 0.011) at 6 months but the thresholds for urge to defecate/discomfort were unchanged. CONCLUSIONS: Food-specific IgG4 antibody-guided exclusion diet improves symptoms in IBS and is associated with an improvement in rectal compliance.
Is the prevalence of small bowel bacterial overgrowth in patients with irritable bowel syndrome increased? The question remains unanswered.
Draganov P, Toskes P
Dig Dis Sci 2005 Aug;50(8):1461.
Increased beta-adrenergic sensitivity correlates with visceral hypersensitivity in patients with constipation-predominant irritable bowel syndrome.
Park JH, Rhee PL, Kim HS, Lee JH, Kim YH, Kim JJ, Rhee JC, Kang EH, Yu BH
Dig Dis Sci 2005 Aug;50(8):1454-60.
Autonomic imbalance has been proposed to be a pathophysiological factor for irritable bowel syndrome (IBS). The aim of this study was to assess beta-adrenergic abnormalities in IBS and to evaluate their relationship to visceral hypersensitivity and other symptoms of IBS patients. Sixteen IBS patients and 16 control subjects were recruited into this study. Participants were asked to complete a questionnaire regarding bowel symptoms, and in order to study beta-adrenergic sensitivity, isoproterenol stimulation tests were performed and visceral hypersensitivity was evaluated by barostat test. Results showed that beta-adrenergic activity and rectal sensitivity were more pronounced in IBS patients than in normal control patients (P < 0.01). Although both IBS subgroups also exhibited more pronounced beta-adrenergic sensitivity than did the controls (P < 0.05), a significant correlation between beta-adrenergic activity and maximally tolerable pressures on the barostat test was found only in IBS-C patients (P = 0.03, R = 0.855). In addition, patients with "hard or lumpy" stools exhibited a higher degree of beta-adrenergic activity (P = 0.00). We conclude that increased beta-adrenergic activity significantly correlated with visceral hypersensitivity in constipation-predominant IBS and symptoms of hard or lumpy stools in IBS patients.
Cognitive behaviour therapy in addition to antispasmodic treatment for irritable bowel syndrome in primary care: randomised controlled trial.
Kennedy T, Jones R, Darnley S, Seed P, Wessely S, Chalder T
BMJ 2005 Aug 20;331(7514):435. Epub 2005 Aug 10.
OBJECTIVE: To assess the efficacy of cognitive behaviour therapy delivered in primary care for treating irritable bowel syndrome. DESIGN: Randomised controlled trial. SETTING: 10 general practices in London. PARTICIPANTS: 149 patients with moderate or severe irritable bowel syndrome resistant to the antispasmodic mebeverine. INTERVENTIONS: Cognitive behaviour therapy delivered by trained primary care nurses plus 270 mg mebeverine taken thrice daily compared with mebeverine treatment alone. MAIN OUTCOME MEASURES: Primary measures were patients' scores on the irritable bowel syndrome symptom severity scale. Secondary measures were scores on the work and social adjustment scale and the hospital anxiety and depression scale. RESULTS: Of 334 referred patients, 72 were randomised to mebeverine plus cognitive behaviour therapy and 77 to mebeverine alone. Cognitive behaviour therapy had considerable initial benefit on symptom severity compared with mebeverine alone, with a mean reduction in score of 68 points (95% confidence interval 103 to 33), with the benefit persisting at three months and six months after therapy (mean reductions 71 points (109 to 32) and 11 points (20 to 3)) but not later. Cognitive behaviour therapy also showed significant benefit on the work and social adjustment scale that was still present 12 months after therapy (mean reduction 2.8 points (5.2 to 0.4)), but had an inconsistent effect on the hospital anxiety and depression scale. CONCLUSION: Cognitive behaviour therapy delivered by primary care nurses offered additional benefit over mebeverine alone up to six months, although the effect had waned by 12 months. Such therapy may be useful for certain patients with irritable bowel syndrome in primary care.
The natural history of childhood abdominal pain and its association with adult irritable bowel syndrome: birth-cohort study.
Howell S, Poulton R, Talley NJ
Am J Gastroenterol 2005 Sep;100(9):2071-8.
INTRODUCTION: The natural history of childhood abdominal pain (CAP) and its association with adult irritable bowel syndrome (IBS) remain poorly described. We aim to investigate the characteristics of CAP over the first 11 yr of life and evaluate the association of CAP to IBS at age 26 yr. METHOD: The data were collected from a 1972 birth cohort (Dunedin, NZ) who were re-assessed at ages 3, 5, 7, 9, 11, 13, 15, 18, 21, and 26 yr. IBS was classified according to Manning Criteria, as assessed using symptom data collected at age 26 yr. A history of CAP was established by scrutinizing data for all assessments completed from birth to age 11 yr. Three measures were described: medical service encounters for CAP, parental (mainly maternal) report of stomach pain (frequency over the past year), and a composite measure which included both medical encounters and parent report: three childhood time frames were evaluated-ages 0-7, 7-9, and 9-11 yr. RESULTS: A history of CAP was reported by 18.1% of children. This was typically characterized by CAP on one assessment; complaints over two or more assessment were rare. CAP was slightly more common in females and appeared to peak at age 7-9 yr. IBS at age 26 yr was significantly more common among individuals with a history of CAP between ages 7 and 9 yr compared to those with no such history, as assessed by any history (OR = 1.85; p= 0.02), parental report (OR = 1.82; p= 0.03), and medical service encounters (OR = 3.75; p= 0.03). The association between CAP at age 7-9 yr and adult IBS was not altered by adjustment for sex, socio-economic status, psychiatric disorder at age 26 yr, childhood emotional distress, or mother's score on the Malaise Inventory. CONCLUSIONS: CAP is a common complaint, which can progress to adult IBS in some children. (Am J Gastroenterol 2005;100:2071-2078).
The Use of Lactobacillus GG in Irritable Bowel Syndrome in Children: A Double-blind Randomized Control Trial.
Bausserman M, Michail S
J Pediatr 2005 Aug;147(2):197-201.
To determine whether oral administration of the probiotic Lactobacillus GG under randomized, double-blinded, placebo-controlled conditions would improve symptoms of irritable bowel syndrome (IBS) in children. STUDY DESIGN: Fifty children fulfilling the Rome II criteria for IBS were given Lactobacillus GG or placebo for 6 weeks. Response to therapy was recorded and collected on a weekly basis using the Gastrointestinal Symptom Rating Scale (GSRS). RESULTS: Lactobacillus GG was not superior to placebo in relieving abdominal pain (40.0% response rate in the placebo group vs 44.0% in the Lactobacillus GG group; P=.774). There was no difference in the other gastrointestinal symptoms, except for a lower incidence of perceived abdominal distention (P=.02 favoring Lactobacillus GG). CONCLUSIONS: Lactobacillus GG was not superior to placebo in the treatment of abdominal pain in children with IBS but may help relieve such symptoms as perceived abdominal distention.
Hypnotherapy for irritable bowel syndrome: a role in pediatric practice?
Agrawal A, Whorwell PJ
J Pediatr Gastroenterol Nutr 2005 Sep;41 Suppl 1:S49-50.
Subjective and objective sleep indices in women with irritable bowel syndrome.
Heitkemper M, Jarrett M, Burr R, Cain KC, Landis C, Lentz M, Poppe A
Neurogastroenterol Motil 2005 Aug;17(4):523-30.
Abstract Patients with irritable bowel syndrome (IBS) commonly report sleep disturbances. This study examined self-report (Pittsburgh Sleep Quality Inventory) sleep quality and polysomnography (PSG) sleep variables in 18 women with mild-to-moderate IBS, 18 with severe IBS and 38 with age- and gender-matched controls. All women were studied on two consecutive nights in a sleep research laboratory where PSG data were collected. Retrospective and daily measures were obtained of self-reported sleep quality, psychological distress and gastrointestinal symptoms across one menstrual cycle. Self-report measures of psychological distress and sleep quality were significantly worse in the IBS-severe (IBS-S) group compared with controls. Rapid eye movement (REM) latency was higher in the two IBS groups on Night 1 than the control group (P = 0.06). Percentage time in REM was highest in the IBS-S on Night 2. All groups demonstrated greater sleep disruption on Night 1 (adaptation) when compared with Night 2. These results highlight the importance of considering the 'first-night effect' in those with IBS and the lack of concordance between self-report and objective indices of sleep in women with IBS.
Central cholecystokinin activity in irritable bowel syndrome, panic disorder, and healthy controls.
Koszycki D, Torres S, Swain JE, Bradwejn J
Psychosom Med 2005 Jul-Aug;67(4):590-5.
OBJECTIVE: Irritable bowel syndrome (IBS) and panic disorder (PD) coexist with a high frequency. However, the nature of this relationship remains obscure. We have proposed that PD and IBS may share a common dysfunction of the central cholecystokinin (CCK) system. To test this hypothesis, we assessed whether the enhanced panicogenic response to CCK-tetrapeptide (CCK-4) observed in PD is also present in IBS. METHODS: Eight psychiatrically healthy IBS patients, 8 PD patients with no history of IBS, and 12 normal controls received a bolus injection of CCK-4 and placebo on two separate days in a double-blind, randomized fashion. RESULTS: Consistent with previous findings, panicogenic sensitivity to CCK-4 was enhanced in PD patients relative to controls. In contrast, IBS patients exhibited a response that was comparable to controls. Interestingly, CCK-4-induced nausea and abdominal distress were decreased in IBS patients relative to the other groups. No diagnostic difference was noted for cardiovascular response to CCK-4. CONCLUSION: These data indicate that IBS patients with no lifetime psychiatric history do not share the CCK-2 receptor dysfunction implicated in the pathophysiology of PD and that this dysfunction may not be a common mechanism for both CNS and enteric nervous system disorders. Nevertheless, the results suggest that a dysfunction of the CCK system may be involved in the pathophysiology of some enteric symptoms associated with IBS.
Response to intestinal provocation monitored by transabdominal ultrasound in patients with food hypersensitivity.
Arslan G, Gilja OH, Lind R, Florvaag E, Berstad A
Scand J Gastroenterol 2005 Apr;40(4):386-94.
OBJECTIVE: Owing to lack of objective measures, the diagnosis of food hypersensitivity may be difficult. The aim of this study was to investigate whether the intestinal response to direct provocation in patients with food hypersensitivity could be recognized by ultrasound. MATERIAL AND METHODS: Thirty-two patients with chronic abdominal complaints, self-attributed to food hypersensitivity/allergy were included in the study. Via a nasoduodenal tube, the duodenal mucosa was challenged with the suspected food item dissolved in 10 ml water or saline. Using external ultrasound, the sonographic features (wall thickness and diameter of the duodenal bulb and jejunum, peristalsis activity and luminal fluid) were recorded before and during one hour after challenge. RESULTS: Sonographic changes were observed after challenge in 14 (44%) of the 32 patients. A positive sonographic response (increased wall thickness, diameter, peristalsis and/or luminal fluid) was significantly related to a positive skin prick test (p = 0.008) and a positive double-blind placebo-controlled food challenge (p = 0.03). A significant correlation was found between provocation-induced symptoms and wall thickness of the duodenal bulb (r = 0.50, p = 0.004) or the jejunum (r = 0.42, p = 0.02). Intra- and interobserver variation of the tracing procedure showed low values. CONCLUSIONS: Responses of the proximal small intestines to direct provocation (swelling of the wall and exudation of fluid into the lumen) could be visualized by transabdominal ultrasound. This new provocation test could be helpful in the evaluation of patients with food hypersensitivity.
Irritable bowel syndrome: the possible benefits of probiotics.
Isselbacher KJ
Postgrad Med 2005 May;117(5):7.
IgG-Mediated Food Intolerance in Irritable Bowel Syndrome: A Real Phenomenon or an Epiphenomenom?
Shanahan F, J Whorwell P
Am J Gastroenterol 2005 Jul;100(7):1558-9.
Abnormal reactions to food probably contribute to the complex pathophysiology of irritable bowel syndrome, but the mechanisms involved remain unclear. Following the recent identification of subtle mucosal inflammation in at least some patients with the disorder, perhaps now is the time to revisit some of the immunological reactions to dietary antigens that, in the past, have been dismissed as irrelevant. (Am J Gastroenterol 2005;100:1558-1559).
Food-Specific Serum IgG4 and IgE Titers to Common Food Antigens in Irritable Bowel Syndrome.
Zar S, Benson MJ, Kumar D
Am J Gastroenterol 2005 Jul;100(7):1550-7.
INTRODUCTION: Food hypersensitivity is a common perception among irritable bowel syndrome (IBS) patients. Data from dietary elimination and food challenge studies support an etiopathological role of diet in IBS, but there are no well-established tests to identify food hypersensitivity. AIM: To compare IgG4 and IgE titers to common food antigens in IBS and controls. METHOD: One hundred and eight IBS [52 diarrhea-predominant (D-IBS); 32 constipation-predominant (C-IBS); 24 alternating (Alt-IBS)], and 43 controls were included in the study. IgG4 and IgE titers and skin prick testing (SPT) to 16 common foods including milk, eggs, cheese, wheat, rice, potatoes, chicken, beef, pork, lamb, fish, shrimps, soya bean, yeast, tomatoes, and peanuts were measured. RESULTS: IBS had significantly higher IgG4 titers (mug/L) to wheat (395 IQR +/- 1,011 vs 0 IQR +/- 285, p < 0.001), beef (1,079 IQR +/- 930 vs 617 IQR +/- 435, p < 0.001), pork (481 IQR +/- 379 vs 258 IQR +/- 496, p < 0.001), and lamb (241 IQR +/- 460 vs 167 IQR +/- 232, p= 0.009) compared to controls. These differences were maintained across all three subgroups. The antibody titers to potatoes, rice, fish, chicken, yeast, tomato, and shrimps were not significantly different. No significant difference in IgE titers was observed between IBS and controls. SPT was positive for only a single antigen in 5 of 56 patients tested with the same panel of foods. No correlation was seen between the pattern of elevated IgG4 antibody titers and patients' symptoms. CONCLUSION: Serum IgG4 antibodies to common foods like wheat, beef, pork, and lamb are elevated in IBS patients. In keeping with the observation in other atopic conditions, this finding suggests the possibility of a similar pathophysiological role for IgG4 antibodies in IBS. (Am J Gastroenterol 2005;100:1-8).
Treatment effects of partially hydrolyzed guar gum on symptoms and quality of life of patients with irritable bowel syndrome. A multicenter randomized open trial.
Parisi G, Bottona E, Carrara M, Cardin F, Faedo A, Goldin D, Marino M, Pantalena M, Tafner G, Verdianelli G, Zilli M, Leandro G
Dig Dis Sci 2005 Jun;50(6):1107-12.
The effects of partially hydrolyzed guar gum (PHGG) were compared in patients with irritable bowel syndrome, at 10 g/day (N = 40) and 5 g/day (N = 46) for 12 weeks. Gastrointestinal symptoms (GSRS), quality of life (SF-36), and psychological symptoms (HADS) were evaluated at baseline, during treatment (months 1 and 3), and at follow-up (month 6). In both groups symptoms and quality of life improved significantly after the first month of administration until follow-up compared to those at baseline. However, the improvement was significantly reduced at follow-up compared to the end of treatment. PHGG was effective for improving somatic (gastrointestinal symptoms) and psychological (quality of life and psychological distress) symptoms over the short term. Since the improvement tended to decrease after the end of the treatment period, further studies should evaluate the benefits of PHGG at a maintenance dosage.
Attenuation of the colorectal reflex in female patients with irritable bowel syndrome.
Ng C, Danta M, Kellow J, Badcock CA, Hansen R, Malcolm A.
Am J Physiol Gastrointest Liver Physiol 2005 May 19;.
Background & Aims Alterations in normal intestino-intestinal reflexes may be important contributors to the pathophysiology of irritable bowel syndrome (IBS). Aim: To compare the rectal tonic responses to colonic distension in female IBS patients with predominant constipation (IBS-C) and with predominant diarrhea (IBS-D) to those in healthy females, fasting and postprandially. Methods Design: Using a dual barostat assembly, two-minute colonic phasic distensions were performed during fasting and postprandially. Rectal tone was recorded before, during and after the phasic distension. Colonic compliance, and colonic sensitivity in response to the distension, were also evaluated fasting and postprandially. Participants: 8 IBS-C patients, 8 IBS-D patients and 8 age and sex-matched healthy subjects (N). Results The fasting increments in rectal tone in response to colonic distension in both IBS-C (rectal balloon volume change -4.6+/-6.1 ml) and IBS-D (-7.9+/-4.9 ml) were significantly reduced when compared to N (-34+/-9.7 ml, p=0.01). Similar findings were observed postprandially (p=0.02). When adjusted for the colonic compliance of individual subjects, the degree of attenuation in the rectal tonic response in IBS compared to N was maintained (fasting p=0.007; postprandial p=0.03). When adjusted for colonic sensitivity there was a trend for the attenuation in the rectal tonic response in IBS compared to N to be maintained (fasting p=0.07, postprandial p=0.0 Conclusion IBS patients display a definite attenuation of the normal increase in rectal tone in response to colonic distension ('colorectal reflex'), fasting and postprandially. Alterations in colonic compliance and sensitivity in IBS are not likely to contribute to such attenuation.
Irritable bowel syndrome and endometriosis.
Ferrero S, Abbamonte LH, Remorgida V, Ragni N.
Eur J Gastroenterol Hepatol 2005 Jun;17(6):687.
Differences in brain responses to visceral pain between patients with irritable bowel syndrome and ulcerative colitis.
Mayer EA, Berman S, Suyenobu B, Labus J, Mandelkern MA, Naliboff BD, Chang L.
Pain 2005 Jun;115(3):398-409.
Patients with mild chronic inflammation of the rectum or ileum have reduced perceptual responses to rectosigmoid distension compared to patients with irritable bowel syndrome (IBS). The current study sought to identify differences in regional cerebral blood flow (rCBF) during rectal distension, which might correspond to these perceptual differences. In 8 male ulcerative colitis (UC) patients with quiescent disease, 7 male IBS patients and 7 healthy male controls, rCBF was assessed using (15)O-water positron emission tomography at baseline and during actual and anticipated but undelivered rectal distensions. No group differences were seen in anterior insula and dorsal anterior cingulate cortex (dACC), two regions consistently activated by painful intestinal stimuli. However, IBS patients showed greater activation of the amygdala, rostroventral ACC, and dorsomedial frontal cortical regions. In contrast, no significant differences were observed between UC and controls. When these two non-IBS groups were combined, functional connectivity analyses showed that right lateral frontal cortex (RLFC) activation positively correlated with activation of the dorsal pons/periaqueductal gray, a key region involved in endogenous pain inhibition. According to the connectivity analysis, this effect was mediated by inhibition of medial frontal cortex by the RLFC. Chronic colonic inflammation is not necessarily associated with increased visceral afferent input to the brain during rectal distension. In the sample studied, the primary difference between functional and quiescent inflammatory disease of the colon was in terms of greater activation of limbic/paralimbic circuits in IBS, and inhibition of these circuits in UC and controls by the RLFC.
Increased placebo analgesia over time in irritable bowel syndrome (IBS) patients is associated with desire and expectation but not endogenous opioid mechanisms.
Vase L, Robinson ME, Verne GN, Price DD.
Pain 2005 Jun;115(3):338-47.
A study was conducted to determine whether changes in expected pain levels, desire for pain relief, or anxiety contribute to an increase in placebo analgesia over time as well as to determine whether placebo analgesic effects of IBS patients are related to endogenous opioid mechanisms. Twenty-six women with IBS were exposed to rectal stimulation (35 or 55mmHg for 30s) and tested under natural history (NH), rectal placebo (RP) and rectal lidocaine (RL) conditions. During all conditions, 16 patients were given saline intravenously (to test for a placebo effect) and 10 patients were given naloxone intravenously (to test naloxone antagonism of the placebo effect) on a double blind basis. Patients rated expected pain level, desire for pain relief and anxiety at 2 and 22min after the onset of NH, RP, and RL conditions and they rated actual pain intensity at 5-min intervals for 40min. There was a large and significant placebo effect (P<0.001) that increased over time. Ratings of expected pain levels, desire for pain relief and anxiety decreased over time and contributed to more variance in placebo and lidocaine responses during the last half of the session. These changes suggest that a reduction in negative emotions may be central to placebo effects. There was no significant difference between psychological mediators (desire, expectation, anxiety) or the placebo effect in the saline and naloxone groups, indicating that neither the psychological mediators nor the placebo analgesic effect were associated with endogenous opioids in this clinically related paradigm.
The placebo effect in irritable bowel syndrome trials: a meta-analysis.
Patel SM, Stason WB, Legedza A, Ock SM, Kaptchuk TJ, Conboy L, Canenguez K, Park JK, Kelly E, Jacobson E, Kerr CE, Lembo AJ. Neurogastroenterol Motil 2005 Jun;17(3):332-40.
BACKGROUND: Despite the apparent high placebo response rate in randomized placebo-controlled trials (RCT) of patients with irritable bowel syndrome (IBS), little is known about the variability and predictors of this response. OBJECTIVES: To describe the magnitude of response in placebo arms of IBS clinical trials and to identify which factors predict the variability of the placebo response. METHODS: We performed a meta-analysis of published, English language, RCT with 20 or more IBS patients who were treated for at least 2 weeks. This analysis is limited to studies that assessed global response (improvement in overall symptoms). The variables considered as potential placebo modifiers were study design, study duration, use of a run-in phase, Jadad score, entry criteria, number of office visits, number of office visits/study duration, use of diagnostic testing, gender, age and type of medication studied. FINDINGS: Forty-five placebo-controlled RCTs met the inclusion criteria. The placebo response ranged from 16.0 to 71.4% with a population-weighted average of 40.2%, 95% CI (35.9-44.4). Significant associations with lower placebo response rates were fulfillment of the Rome criteria for study entry (P=0.049) and an increased number of office visits (P=0.026). CONCLUSIONS: Placebo effects in IBS clinical trials measuring a global outcome are highly variable. Entry criteria and number of office visits are significant predictors of the placebo response. More stringent entry criteria and an increased number of office visits appear to independently decrease the placebo response.
The placebo response in functional bowel disorders: perspectives and putative mechanisms.
Enck P, Klosterhalfen S.
Neurogastroenterol Motil 2005 Jun;17(3):325-31.
The nature and determinants of the placebo response are widely unknown, as are the underlying psychological and biological mechanisms. High placebo response rates in functional bowel disorders (functional dyspepsia, irritable bowel syndrome) are similar to those in non-intestinal diseases (depression, pain, Parkinson's disease) and not too dissimilar to other organic gastrointestinal diseases (duodenal ulcer, inflammatory bowel diseases). Methodological reasons (regression to the mean, shift in signal detection through manipulation of expectations) and psycho-biological mechanisms (Pavlovian conditioning of biological processes) are proposed to explain a large component of the response variance in clinical trials. Psychobiological mechanisms of the placebo response in functional and organic diseases can also be identified in brain function studies (such as imaging).
Irritable bowel syndrome in developing countries--a disorder of civilization or colonization?
Gwee KA.
Neurogastroenterol Motil 2005 Jun;17(3):317-24.
While irritable bowel syndrome (IBS) is common in the West, early studies suggest that the prevalence is low in developing countries. However, recent studies point to increasing prevalence in newly developed Asian economies. The presentation appears to differ from the West, with a lack of female predominance, a greater frequency of upper abdominal pain and defecatory symptoms perceived as being less bothersome. This difference, together with the preoccupation with organic disease, could explain why we may be missing IBS in Asia and also why excess surgery has been observed in some Asian countries. While a recent study from China, consistent with western studies, support an important role for infection and inflammation, early studies from India reporting no association between amoebic infection and IBS appear to dispute this observation. To reconcile these seemingly contradictory observations, an hygiene hypothesis model is proposed. Exposure to a variety of microorganisms early in life could result in the colonization of the intestine with microflora that can respond more efficiently to an episode of gastroenteritis. Together with the changes with evolution of Asian economies such as westernization of the diet and increased psychosocial stress, it is proposed that loss of this internal protective effect, could give rise to a more uniform worldwide prevalence of IBS.
Mechanisms in IBS: something old, something new, something borrowed.
Camilleri M.
Neurogastroenterol Motil 2005 Jun;17(3):311-6.
Are cardiac syndrome X, irritable bowel syndrome and reflex sympathetic dystrophy examples of lateral medullary ischaemic syndromes? Syme P. Med Hypotheses 2005;65(1):145-8.
Altered pain appreciation and autonomic function are hallmarks of Cardiac syndrome X, Irritable bowel syndrome and Reflex sympathetic dystrophy. Both pain appreciation and autonomic function are controlled by the lateral medulla. This hypothesis proposes that lateral medullary ischaemia at a microvascular level is responsible for these syndromes and could also be linked to other conditions where autonomic dysfunction is a major feature such as late-onset asthma, type 2 diabetes and essential hypertension. Autonomic function is controlled by the nucleus tractus solitarius, which acts as the main viscero-afferent nucleus in the brain stem regulating vagal tone. It is particularly susceptible to ischaemia since it is highly metabolically active and lies in a medullary arterial watershed zone. The anatomical route of the vertebral artery through cervical vertebra makes it vulnerable to injury from whiplash with or without any genetic predisposition to atheroma formation. This could make microvascular occlusion commonplace and a plausible explanation for the above syndromes. Ischaemia rather than infarction occurs because of the excellent collateral blood supply in the brainstem. In support of this hypothesis, a new Transcranial doppler ultrasonography arterial signal has been described called small vessel knock, the ultrasound signal of small vessel occlusion. Recent evidence has shown that ultrasound targeting of this signal in the vertebral artery improves clinical symptoms in these syndromes which supports this hypothesis. Two such cases are discussed.
Will corticosteroids and other anti-inflammatory agents be effective for diarrhea-predominant irritable bowel syndrome?
Crentsil V.
Med Hypotheses 2005;65(1):97-102.
Irritable bowel syndrome (IBS) is one of several functional gastrointestinal disorders commonly encountered in both the clinical setting and the general population. The biopsychosocial model is currently believed to be a more complete explanatory mechanism of IBS symptom genesis and propagation. Gut inflammation and immune activation is one of the biological mechanisms for which evidence is emerging. Experimental parasitic infection of mice bowel resulted in elevated substance P levels and increased expression of cyclooxygenase 2 (COX 2) enzyme, prostaglandin E(2), IL-4, IL-5, and IL-13. In IBS patients, increased cellularity and proximity of the inflammatory or immune cells to the nerve trunks of the bowel, elevated interleukin-1beta mRNA expression in mucosal biopsies, and increased inducible nitric oxide synthase and nitrotyrosine elaboration (indicative of lymphocyte activation) were observed. Corticosteroids given after the elimination of an experimentally applied parasite from the bowel of mice resulted in the reversal of persistent gut muscle dysfunction. Selective COX-2 inhibitors attenuated the increased bowel smooth muscle contractility resulting from parasite infection of mice gut. In humans, it has been observed that the relative risk of developing IBS in asthma patients was reduced by 60% by the use of oral steroids. Despite such preclinical and human evidence for the role of inflammation and immune activation in IBS, the efficacy of anti-inflammatory and immunomodulatory agents has not been adequately investigated. Budesonide, a corticosteroid with a high mucosal activity and a low bioavailability, is an anti-inflammatory agent that may be worth investigating for its utility in diarrhea-predominant IBS.
Genetic influences in irritable bowel syndrome: a twin study.
Mohammed I, Cherkas LF, Riley SA, Spector TD, Trudgill NJ.
Am J Gastroenterol 2005 Jun;100(6):1340-4.
BACKGROUND: Aggregation of symptoms of abdominal pain or bowel disturbance has been described in the families of patients with irritable bowel syndrome (IBS). This may be due to environmental factors, including learned responses to abdominal symptoms or a genetic contribution to the etiology of IBS. OBJECTIVES: To determine the relative contribution of genetic factors to IBS by evaluating IBS symptoms in monozygotic (MZ) and dizygotic (DZ) twins. METHODS: A total of 4,480 unselected twin pairs identified from a national volunteer twin register were asked to complete a validated questionnaire. IBS was defined by the Rome II criteria. RESULTS: A total of 5,032 subjects replied (56% response rate). One thousand eight hundred seventy complete twin pairs were evaluable; 888 MZ pairs (82 male pairs, mean age 51, SD 13 (range 19-81) yr) and 982 DZ pairs (69 male pairs, age 52, SD 13 (20-82) yr). The prevalence of IBS was 17% in MZ and 16% in DZ twins. There was no significant difference in casewise concordance rates between the MZ and DZ twins (28%vs 27%, p= NS). Logistic regression analysis revealed that decreasing age and increasing psychosomatic score were independently associated with IBS. Multifactorial liability threshold modeling suggested that a combination of unique and shared environmental factors provided the best model for IBS. In contrast, somatization was shown to be moderately heritable. CONCLUSION: Genetic factors are of little or no influence on IBS where the predominant influences appear to be environmental. (
Rectal aberrant crypt foci identified using high-magnification-chromoscopic colonoscopy: biomarkers for flat and depressed neoplasia.
Hurlstone DP, Karajeh M, Sanders DS, Drew SK, Cross SS.
Am J Gastroenterol 2005 Jun;100(6):1283-9.
Aberrant crypt foci may represent preneoplastic lesions in the human colon. The prevalence of aberrant crypt foci detected using
magnification chromoscopic colonoscopy is known to follow a stepwise progression from normal subjects to those with exophytic adenomas and colon cancer. No studies have addressed the prevalence of rectal aberrant crypt foci in patients with flat and depressed colonic lesions that cluster within the right hemi-colon and may undergo de novo neoplastic transformation. ...The number of aberrant crypt foci in normal patients, patients with flat adenoma, and flat cancer follow a stepwise incremental change as previously observed for exophytic adenomas and cancer. Detection of aberrant crypt foci in the rectum may be a useful biomarker for proximal colonic flat neoplasia and could be used at index flexible sigmoidoscopic screening to stratify risk of proximal colonic neoplasia. Patients with dysplastic aberrant crypt foci of high density should receive total colonoscopy.
Digestion, diet, and disease: irritable bowel syndrome and gastrointestinal function.
Saad R, Chey WD.
Gastroenterology 2005 Jun;128(7):2175.
Functional GI Disorders: What's in a Name?
Drossman DA.
Gastroenterology 2005 Jun;128(7):1771-2.
Sex-specific alterations in autonomic function among patients with irritable bowel syndrome.
Tillisch K, Mayer EA, Labus JS, Stains J, Chang L, Naliboff BD.
Gut 2005 May 28;.
BACKGROUND: Irritable bowel syndrome (IBS) is associated with increased psychological symptoms, early life stressors, and
alterations in visceral perception and brain responses to noxious visceral stimuli. The autonomic nervous system (ANS) is a likely mediator for these brain-gut interactions. The few studies directly examining ANS measures have been suggestive of alterations in some IBS patients, but no studies to date have examined the potentially critical variables of sex differences or response to visceral stimulation. AIMS: 1. To test differences in ANS function during rest and during a visceral stressor (rectosigmoid balloon distension) between IBS patients and healthy control subjects. 2. To examine the role of sex on the autonomic responses of IBS patients. METHODS: Baseline autonomic measures were evaluated from 130 Rome I positive IBS patients and 55 healthy control subjects. Data was also collected from a subset of 46 IBS patients and 16 healthy control subjects during a sigmoid balloon distension study. Heart rate variability measures of peak power ratio (PPR) and peak power high frequency (PPHF) were analysed to assess sympathetic balance and parasympathetic response respectively. Peripheral sympathetic response was measured by skin conductance. RESULTS: IBS patients show greater skin conductance response to visceral distension than controls. IBS patients had higher PPR and lower PPHF across conditions. Male IBS patients had higher skin conductance and PPR than females and lower PPHF. CONCLUSIONS: IBS patients have altered autonomic responsiveness to a visceral stressor, with increased sympathetic and decreased parasympathetic activity. These differences are predominantly seen in males.
Intestinal gas dynamics: mechanisms and clinical relevance.
Azpiroz F.
Gut 2005 Jul;54(7):893-895.
Patients with functional gut disorders, irritable bowel disease, and related syndromes frequently attribute their symptoms to intestinal gas. While patients are usually convinced of their interpretation, the doctor has few arguments to confirm or refute it, and in this context intestinal gas has become a myth. Studies of intestinal gas dynamics have demonstrated subtle dysfunctions in intestinal motility. Hopefully, extension of these studies may help both in the classification of patients complaining of gas symptoms based on pathophysiological mechanisms, and in identification of objective markers to test mechanistically oriented treatment options.
Body mass index and chronic unexplained gastrointestinal symptoms: an adult endoscopic population-based study.
Aro P, Ronkainen J, Talley NJ, Storskrubb T, Bolling-Sternevald E, Agreus L.
Gut 2005 May 25;.
We aimed to determine whether obese subjects experience more gastroesophageal reflux (GERS) symptoms than normals, and further to determine if this association was explained by esophagitis or medications that lower oesophageal sphincter pressure (LES). METHODS: In a representative Swedish population, a random sample (n=1,001, mean age 53.5 years, 51% women) had upper endoscopy. GERS was defined as any bothersome heartburn or acid regurgitation. RESULTS: The prevalence of obesity (body mass index >/=30 was 16%; esophagitis was significantly more prevalent in obesity (26.5%) than in normals (9.3%). There were associations between obesity and GERS (OR=2.05, 95% CI 1.39,3.01), epigastric pain (OR=1.63, 95% CI 1.05, 2.55), irritable bowel symptoms (OR=1.58, 95% CI 1.05, 2.38), any abdominal pain (OR=1.59, 95% CI 1.08, 2.35), vomiting (OR=3.11, 95% CI 1.18, 8.20), retching (OR=1.74, 95% CI 1.1.3, 2.67), diarrhea (OR=2.2, 95% CI 1.38, 3.46), any stool urgency (OR=1.60, 95% CI 1.04, 2.47), nocturnal urgency (OR=2.57, 95% CI 1.33, 4.98) and incomplete rectal evacuation (OR=1.64, 95% CI 1.09, 2.47), adjusting for age, sex and education. When subjects with esophagitis and peptic ulcer were excluded, only diarrhea, incomplete evacuation and vomiting were significantly associated with obesity. The association between GERS and obesity remained significant adjusting for medication use (OR=1.9, 95% CI 1.3, 3.0). CONCLUSIONS: GERS is associated with obesity; this appears to be explained by increased upper endoscopy findings in obesity or medication use.
Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: a randomised double blind placebo controlled study.
Song GH, Leng PH, Gwee KA, Moochhala SM, Ho KY.
Gut 2005 May 24;.
BACKGROUND AND AIMS: Melatonin, a sleep-promoting agent, is involved in the regulation of gastrointestinal motility and sensation. We aimed to determine if melatonin was effective in improving bowel symptoms and sleep disturbances in irritable bowel syndrome (IBS) patients with sleep disturbance. METHODS: Forty IBS patients (aged 20-64 years; 24 female) with sleep disturbances were randomly assigned to receive either melatonin 3mg nocte (n=20) or matching placebo nocte (n=20) for two weeks. Immediately before and after the treatment, the subjects completed bowel, sleep and psychological questionnaires, and underwent rectal manometry and overnight polysomnography. RESULTS: Compared with placebo, melatonin taken for two weeks significantly decreased mean abdominal pain score (2.35 vs 0.70, p<0.001), and increased mean rectal pain threshold (24.8 vs 33.7 mmHg, p<0.01). Bloating, stool type, stool frequency, anxiety and depression scores did not significantly differ after treatment in both groups. Data from sleep questionnaire and polysomnography showed the 2-week course of melatonin did not influence sleep parameters including total sleep time, sleep latency, sleep efficiency, sleep onset latency, arousals, duration of stage 1-4, REM sleep and REM onset latency. CONCLUSIONS: Administration of melatonin 3mg nocte for two weeks significantly attenuated abdominal pain and reduced rectal pain sensitivity without improvements in sleep disturbance and psychological distress. The findings suggested that the beneficial effects of melatonin on abdominal pain in IBS patients with sleep disturbance were independent of its action on sleep disturbances and psychological profile.
Bowel habit subtypes and temporal patterns in irritable bowel syndrome: systematic review.
Guilera M, Balboa A, Mearin F
Am J Gastroenterol 2005 May;100(5):1174-84.
Irritable bowel syndrome (IBS) is a heterogeneous condition characterized by the presence of abdominal discomfort or pain and bowel habit alterations: constipation (C-IBS), diarrhea (D-IBS), or alternating C and D (A-IBS). Its clinical course is poorly known. OBJECTIVES: (i) To compare bowel habit subtypes distribution in IBS according to sample origin and diagnosis criteria; (ii) To evaluate IBS temporal patterns based on follow-up studies. METHODS: A literature search (1966-2003) was conducted in the MEDLINE and EMBASE databases. A total of 72 studies were found and 22 were finally selected. RESULTS: Population-based studies from the United States (Manning) found similar distribution among C-IBS, D-IBS, and A-IBS, while European studies (Rome I, Rome II, or self-reporting) showed either C-IBS or A-IBS as the most prevalent subtypes. Primary care office-based studies (Rome I or Rome II) showed A-IBS as the most prevalent group. Gastroenterology specialized office-based studies found either C-IBS or D-IBS as the most frequently reported subtype. Prospective follow-up investigations showed that the most frequent IBS temporal pattern profile consists of mild to moderate symptoms appearing in cluster in an intermittent way, about once a week, and lasting 2-5 days on average. CONCLUSION: IBS clinical subtypes distribution differs depending on the population evaluated, the geographical location, and the criteria employed to define IBS and bowel habit subtypes. In most cases, clinical course is characterized by the presence of mild-to-moderate symptoms appearing sequentially. Prospective studies, using clear and stable diagnostic criteria and subtype definitions, and based on daily data collection should further characterize IBS clinical course. (Am J Gastroenterol 2005;100:1174-1184).
Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome.
Morgan V, Pickens D, Gautam S, Kessler R, Mertz H
Gut 2005 May;54(5):601-7.
BACKGROUND AND AIMS: Irritable bowel syndrome (IBS) is a disorder of intestinal hypersensitivity and altered motility, exacerbated by stress. Functional magnetic resonance imaging (fMRI) during painful rectal distension in IBS has demonstrated greater activation of the anterior cingulate cortex (ACC), an area relevant to pain and emotions. Tricyclic antidepressants are effective for IBS. The aim of this study was to determine if low dose amitriptyline reduces ACC activation during painful rectal distension in IBS to confer clinical benefits. Secondary aims were to identify other brain regions altered by amitriptyline, and to determine if reductions in cerebral activation are greater during mental stress. METHODS: Nineteen women with painful IBS were randomised to amitriptyline 50 mg or placebo for one month and then crossed over to the alternate treatment after washout. Cerebral activation during rectal distension was compared between placebo and amitriptyline groups by fMRI. Distensions were performed alternately during auditory stress and relaxing music. RESULTS: Rectal pain induced significant activation of the perigenual ACC, right insula, and right prefrontal cortex. Amitriptyline was associated with reduced pain related cerebral activations in the perigenual ACC and the left posterior parietal cortex, but only during stress. CONCLUSIONS: The tricyclic antidepressant amitriptyline reduces brain activation during pain in the perigenual (limbic) anterior cingulated cortex and parietal association cortex. These reductions are only seen during stress. Amitriptyline is likely to work in the central nervous system rather than peripherally to blunt pain and other symptoms exacerbated by stress in IBS.
Brain imaging and its implications for studying centrally targeted treatments in irritable bowel syndrome: a primer for gastroenterologists.
Drossman DA
Gut 2005 May;54(5):569-73.
Research into brain-gut interactions, and the use of brain imaging, as potential investigative tools for functional gastrointestinal disorders, such as irritable bowel syndrome, is a promising new area. Studies are beginning to identify the structure and function of regions of the brain and their relationships to pain perception, stress, and other psychosocial variables. These imaging modalities may also have diagnostic potential, and perhaps even therapeutic applications, particularly with regard to understanding the benefit of centrally targeted modalities such as antidepressants and psychological treatments.
What does the future hold for irritable bowel syndrome and the functional gastrointestinal disorders?
Drossman DA
J Clin Gastroenterol 2005 May-Jun;39(5 Suppl):S251-6.
Our understanding of irritable bowel syndrome and the functional GI disorders has grown considerably over the last 15 years. In part this relates changes in their classification and definition from being due solely to motility disturbances, to being symptom based (eg, Rome criteria). This opened the door to the study of many other factors that contribute to the clinical expression of these disorders, including visceral hypersensitivity, sensitization, altered mucosal immunity, and dysfunction in brain-gut regulatory processes. New knowledge has been gained in areas of genetics, central nervous system and enteric nervous system neurotransmitters of motility, sensitivity and secretion, the effect of altered mucosal inflammation on cytokine and paracrine activation, and neural sensitization, postinfectious disorders, the influence of psychologic stress on gut functioning via alterations in regulatory pathways (eg, hypothalamic-pituitary adrenal axis, or pain regulatory system like the cingulate cortex), improved accuracy of diagnosis using Rome II criteria plus "red flags" the institution of behavioral treatments, and the use of new pharmacologic treatments both at the gut and brain level. Future research will improve upon this new knowledge via basic and translational studies of neuropeptide signaling with new neurotransmitters, new knowledge on the mechanisms for central nervous system-enteric nervous system communication and dysfunction, and more advanced clinical research on education, communication skills and their effects on outcome, genetics, pharmacogenetics and genetic epidemiology, better understanding as to how certain psychosocial domains (eg, catastrophizing, abuse) affect symptom behavior and outcome, newer pharmacologic treatments, and the use of combined pharmacologic and behavioral treatment packages. I am pleased to have the opportunity to provide a personal perspective on what the future will be for irritable bowel syndrome and the other functional GI disorders. Having been involved in this field for almost 30 years, I have been fortunate to witness tremendous changes. The focus of this presentation is to address the advances that have recently occurred that set the stage for proposing future research to help move the field along and ultimately to help our patients.
Use of diet and probiotic therapy in the irritable bowel syndrome: analysis of the literature.
Floch MH
J Clin Gastroenterol 2005 May-Jun;39(5 Suppl):S243-6.
GOAL: The goal of this report is to review the use of dietary intake and probiotics in patients with irritable bowel syndrome (IBS) in published reports. BACKGROUND: Dietary factors can be important in inducing symptoms that occur in patients with the IBS. Dietary intolerances, dietary allergies, specific food metabolites, and regular diet contents all may act as triggers and aggravate the symptoms of IBS; but when any of these mechanisms can be proven to cause the symptoms, then their elimination results in the resolution of that patient's IBS. METHODS: Our previous review was updated. In addition, a careful Medline search was made for the years from 1975 to 2004 to evaluate human research reports on diet and probiotics in the IBS. Forty-six manuscripts were reviewed on diet and six were available on probiotic use in IBS. The most common dietary factor evaluated in the literature was bran, and the most common probiotic used was Lactobacillus plantarum. CONCLUSIONS: Although investigations have shown that bran may be helpful in some patients, a complete review of the literature does not reveal conclusive evidence that diet therapy is effective in IBS. From the limited reports on probiotics, there appears to be a trend to decreasing symptoms. It is clear that much more prospective research is needed to study both dietary factors and probiotics in these areas.
Irritable bowel syndrome: a syndrome in evolution.
Lacy BE, Lee RD
J Clin Gastroenterol 2005 May-Jun;39(5 Suppl):S230-42.
As a group, functional gastrointestinal disorders are the most common gastrointestinal disorder seen by both generalists and specialists. These disorders can be frustrating to both patients and physicians as they are usually chronic in nature and difficult to treat. These disorders are associated with frequent healthcare visits, the scheduling of multiple, expensive diagnostic tests, and the use of both over-the-counter and prescription medications. All of these factors lead to a significant economic burden to society. In addition, functional gastrointestinal disorders are associated with a reduction in quality of life for the patient. Irritable bowel syndrome (IBS) is the most common of the functional gastrointestinal disorders. This syndrome has been the focus of a large number of research studies over the past two decades. These studies have resulted in a number of significant changes in our definition of IBS. In addition, these research studies have produced considerable changes in our understanding of the etiology and pathogenesis of IBS. In this section, we will review some of the evolutionary changes that have occurred in IBS. We will discuss how the definition of IBS has changed, consider our evolving strategies to evaluate and diagnose IBS, and finally, provide a brief overview of treatment options for this common disorder.
Nerves, reflexes, and the enteric nervous system: pathogenesis of the irritable bowel syndrome.
Gershon MD
J Clin Gastroenterol 2005 May-Jun;39(5 Suppl):S184-93.
The bowel exhibits reflexes in the absence of CNS input. To do so, epithelial sensory transducers, such as enterochromaffin (EC) cells, activate the mucosal processes of intrinsic (IPANs) and extrinsic primary afferent (sensory) neurons. EC cells secrete serotonin (5-HT) in response to mucosal stimuli. Submucosal IPANs, which secrete acetylcholine and calcitonin gene-related peptide, initiate peristaltic and secretory reflexes and are activated via "5-HT1P" receptors. Release of neurotransmitters is enhanced by 5-HT4 receptors, which are presynaptic and strengthen neurotransmission in prokinetic pathways. 5-HT3 receptors mediate signaling to the CNS and thus ameliorate cancer chemotherapy-associated nausea and the visceral hypersensitivity of diarrhea-predominant irritable bowel syndrome (IBS-D); however, because 5-HT3 receptors also mediate fast ENS neurotransmission and activate myenteric IPANs, they may be constipating. 5-HT4 agonists are prokinetic and relieve discomfort and constipation in IBS-C and chronic constipation. 5-HT4 agonists do not initiate peristaltic and secretory reflexes but strengthen pathways that are naturally activated. Serotonergic signaling in the mucosa and the ENS is terminated by a transmembrane 5-HT transporter, SERT. Mucosal SERT and tryptophan hydroxylase-1 expression are decreased in experimental inflammation, IBS-C, IBS-D, and ulcerative colitis. Potentiation of 5-HT due to the SERT decrease could account for the discomfort and diarrhea of IBS-D, while receptor desensitization may cause constipation. Similar symptoms are seen in transgenic mice that lack SERT. The loss of mucosal SERT may thus contribute to IBS pathogenesis.
Do interventions which reduce colonic bacterial fermentation improve symptoms of irritable bowel syndrome?
Dear KL, Elia M, Hunter JO
Dig Dis Sci 2005 Apr;50(4):758-66.
Abnormal fermentation may be an important factor in irritable bowel syndrome (IBS). Gastroenteritis or antibiotic therapy may damage the colonic microflora, leading to increased fermentation and the accumulation of gas. Gas excretion may be measured by whole-body calorimetry but there has only been one such study on IBS to date. We aimed to assess the relationship between IBS symptoms and fermentation rates in IBS. A purpose-built, 1.4-m3, whole-body calorimeter was used to assess excretion of H2 and CH4 in IBS subjects while consuming a standard diet and, again, after open randomization on either the standard diet together with the antibiotic metronidazole or a fiber-free diet to reduce fermentation. Metronidazole significantly reduced the 24-hr excretion of hydrogen (median value compared to the control group, 397 vs 230 ml/24 hr) and total gas (H2 + CH4; 671 vs 422 ml/min) and the maximum rate of gas excretion (1.6 vs 0.8 ml/min), as did a no-fiber polymeric diet (hydrogen, 418 vs 176 ml/min; total gas, 564 vs 205 ml/min; maximum rate of gas excretion, 1.35 vs 0.45 ml/min), with a significant improvement in abdominal symptoms. IBS may be associated with rapid excretion of gaseous products of fermentation, whose reduction may improve symptoms.
Brain Responses to Visceral and Somatic Stimuli in Irritable Bowel Syndrome: a Central Nervous System Disorder?
Chang L
Gastroenterol Clin North Am 2005 Jun;34(2):271-279.
Definition and classification of irritable bowel syndrome: current consensus and controversies.
Longstreth GF
Gastroenterol Clin North Am 2005 Jun;34(2):173-87.
Irritable bowel syndrome.
Talley NJ
Gastroenterol Clin North Am 2005 Jun;34(2):xi-xii.
The pathogenesis of bloating and visible distension in irritable bowel syndrome.
Azpiroz F, Malagelada JR
Gastroenterol Clin North Am 2005 Jun;34(2):257-69.
The role of food intolerance in irritable bowel syndrome.
Lea R, Whorwell PJ
Gastroenterol Clin North Am 2005 Jun;34(2):247-55.
Is irritable bowel syndrome a low-grade inflammatory bowel disease?
Bercik P, Verdu EF, Collins SM
Gastroenterol Clin North Am 2005 Jun;34(2):235-45.
Disturbances of motility and visceral hypersensitivity in irritable bowel syndrome: biological markers or epiphenomenon.
Quigley EM
Gastroenterol Clin North Am 2005 Jun;34(2):221-33.
Diagnosis of irritable bowel syndrome.
Cash BD, Chey WD
Gastroenterol Clin North Am 2005 Jun;34(2):205-20.
Irritable bowel syndrome: epidemiology, natural history, health care seeking and emerging risk factors.
Cremonini F, Talley NJ
Gastroenterol Clin North Am 2005 Jun;34(2):189-204.
Potential future therapies for Irritable Bowel Syndrome: Will Disease Modifying Therapy as Opposed to Symptomatic Control Become a Reality?
Spiller RC
Gastroenterol Clin North Am 2005 Jun;34(2):337-54.
Efficacy of current drug therapies in irritable bowel syndrome: what works and does not work.
Schoenfeld P
Gastroenterol Clin North Am 2005 Jun;34(2):319-35.
Genetics and genotypes in irritable bowel syndrome: implications for diagnosis and treatment.
Park MI, Camilleri M
Gastroenterol Clin North Am 2005 Jun;34(2):305-17.
Temporal changes in the management of diverticulitis.
Salem L, Anaya DA, Flum DR
J Surg Res 2005 Apr;124(2):318-23.
PURPOSE: This study was designed to evaluate temporal trends in the use and type of operative and non-operative interventions in the management of diverticulitis. METHODS: A retrospective cohort using a statewide administrative database was used to identify all patients hospitalized for diverticulitis in the state of Washington (1987-2001). Poisson and logistic regression were used to calculate changes in the frequency of hospitalization, operative and percutaneous interventions, and colostomy over time. RESULTS: Of the 25,058 patients hospitalized non-electively with diverticulitis (mean age 69 +/- 16, 60% female) there were only minimal changes in the frequency of admissions over time (0.006% increase per year-IRR 1.00006 95% CI 1.00004, 1.00008). The odds of an emergency colectomy at initial hospitalization decreased by 2% each year (OR 0.98 95% CI 0.98, 0.99) whereas the odds of percutaneous abscess drainage increased 7% per year (OR 1.07 95% CI 1.05, 1.1). Among patients undergoing percutaneous drainage, the odds of operative interventions decreased by 9% compared to patients who did not have a percutaneous intervention (OR 0.91 95% CI 0.87, 0.94). The proportion of patients undergoing colostomy during emergency operations remained essentially stable over time (range 49-61%), as did the proportion of patients undergoing prophylactic colectomy after initial non-surgical management (approximately 10%). CONCLUSIONS: There was a minimal increase in the frequency of diverticulitis admissions over time. A rise in percutaneous drainage procedures was associated with a decrease in emergency operative interventions. The proportion of patients undergoing colostomy remained stable, and there does not seem to be a significant increase in the use of one-stage procedures for diverticulitis.
Hypersensitivity to cutaneous thermal nociceptive stimuli in irritable bowel syndrome.
Rodrigues AC, Nicholas Verne G, Schmidt S, Mauderli AP
Pain 2005 May;115(1-2):5-11.
Irritable bowel syndrome (IBS) is a common intestinal ailment of which the pathophysiological mechanisms are not well understood. Most IBS patients demonstrate enhanced perception, visceral hypersensitivity, in response to distension of the gut lumen but there are conflicting results about changes in somatic sensitivity. This study focused on the possible contribution of abnormal pain sensitization due to positive feedback (vicious pain cycle) that affects somatic tissues due to viscero-somatic convergence. The specific objectives were to measure cutaneous thermal pain sensitivity along the segmental axis, including in dermatomes that are remote from the visceral pain focus. Pain sensitivity was probed with cutaneous thermal stimulation to the lower and upper extremities and the face in nine diarrhea-predominant IBS patients (diagnosed with ROME II criteria) and 12 healthy female controls. The stimuli were administered with a contact thermode, assuring that size of the stimulated area and stimulus duration were clearly defined and identical in all locations. Sensitization of IBS patients was not limited to symptomatic dermatomes (calf) but extended evenly across the body, including to the face (no sensitization gradient from foot to face). Also, the difference between IBS and control groups did not depend on the evoked pain intensity level, i.e. the degree of sensitization of IBS patients was similar near threshold (10% on the visual analog scale) and at higher intensities. Lastly, no correlation was found between IBS subjects' pain sensitivity of any of the three test sites and their ratings of spontaneous pain.
Comparison between partial agonist (ME3412) and antagonist (alosetron) of 5-hydroxytryptamine 3 receptor on gastrointestinal function.
Kawano K, Mori T, Fu L, Ito T, Niisato T, Yoshida S, Shiokawa S, Sato Y, Murakami H, Shishikura T
Neurogastroenterol Motil 2005 Apr;17(2):290-301.
Therapeutic use of 5-hydroxytryptamine 3 (5-HT(3)) receptor antagonists for diarrhoea-predominant irritable bowel syndrome may be accompanied by constipation. We hypothesized that ME3412, 5-chloro-2-(1,4-diazacycloheptan-1-yl)-7-methylbenzoxazole, a novel partial agonist of the 5-HT(3) receptor, would minimize constipation without reducing antidiarrhoeal activity. Receptor binding studies showed that ME3412 is highly selective for the human 5-HT(3) receptor (K(i) = 1.51 nmol L(-1)). A 5-HT(3) receptor agonist, 2-methyl-5-HT, caused contractile response in the isolated guinea-pig ileum and accelerated secretion in the guinea-pig colonic mucosal preparation. ME3412 and 5-HT(3) receptor antagonist, alosetron, antagonized the 2-methyl-5-HT-induced responses with similar potency in insurmountable and surmountable manner, respectively. ME3412 caused weak agonism in isolated ileum strips and also in the colonic mucosa with intrinsic activity of 0.09 and 0.59, respectively. In conscious dogs, alosetron (3 microg kg(-1) i.v.) suppressed the migrating motor complex (MMC), whereas a relatively high dose (300 microg kg(-1)) of ME3412 was required for inhibition of MMC. ME3412 and alosetron suppressed 5-HT induced-diarrhoea in mice. In contrast, ME3412 did not significantly affect colonic propulsion compared with alosetron. These results imply that the partial agonist may relieve diarrhoea with low risk of inducing constipation.
Pathogenesis of irritable bowel syndrome: the mast cell connection.
Santos J, Guilarte M, Alonso C, Malagelada JR
Scand J Gastroenterol 2005 Feb;40(2):129-40.
Characterization of the alternating bowel habit subtype in patients with irritable bowel syndrome.
Tillisch K, Labus JS, Naliboff BD, Bolus R, Shetzline M, Mayer EA, Chang L
Am J Gastroenterol 2005 Apr;100(4):896-904.
BACKGROUND: Due to a wide range of symptom patterns, patients with irritable bowel syndrome (IBS) are often subgrouped by bowel habit. However, the IBS subgroup with alternating bowel habits (IBS-A) has been poorly characterized. OBJECTIVES: (i) To determine a set of bowel habit symptom criteria, which most specifically identifies IBS patients with an alternating bowel habit, (ii) to describe IBS-A bowel symptom patterns, and (iii) to compare clinical characteristics among IBS-A, constipation-predominant (IBS-C), and diarrhea-predominant IBS (IBS-D). METHODS: One thousand one hundred and two Rome I positive IBS patients were analyzed. Three sets of potential criteria for IBS-A were developed and compared by multirater Kappa test. Gastrointestinal, psychological, extraintestinal symptoms, and health-related quality of life were compared in IBS-A, IBS-C, and IBS-D using chi(2) test and analysis of variance (ANOVA). RESULTS: Stool consistency was determined to be the most specific criteria for alternating bowel habits. IBS-A patients reported rapid fluctuations in bowel habits with short symptom flares and remissions. There was a greater prevalence of psychological and extraintestinal symptoms in the IBS-A subgroup compared to IBS-C and IBS-D. No differences were seen between bowel habit subtypes in health-related quality of life. CONCLUSIONS: IBS-A patients have rapidly fluctuating symptoms and increased psychological comorbidity, which should be taken into account for clinical practice and clinical trials. (Am J Gastroenterol 2005;100:1-9).
What does the future hold for irritable bowel syndrome and the functional gastrointestinal disorders?
Drossman DA
J Clin Gastroenterol 2005 May-Jun;39(4):S251-6.
Our understanding of irritable bowel syndrome and the functional GI disorders has grown considerably over the last 15 years. In part this relates changes in their classification and definition from being due solely to motility disturbances, to being symptom based (eg, Rome criteria). This opened the door to the study of many other factors that contribute to the clinical expression of these disorders, including visceral hypersensitivity, sensitization, altered mucosal immunity, and dysfunction in brain-gut regulatory processes. New knowledge has been gained in areas of genetics, central nervous system and enteric nervous system neurotransmitters of motility, sensitivity and secretion, the effect of altered mucosal inflammation on cytokine and paracrine activation, and neural sensitization, postinfectious disorders, the influence of psychologic stress on gut functioning via alterations in regulatory pathways (eg, hypothalamic-pituitary adrenal axis, or pain regulatory system like the cingulate cortex), improved accuracy of diagnosis using Rome II criteria plus "red flags" the institution of behavioral treatments, and the use of new pharmacologic treatments both at the gut and brain level. Future research will improve upon this new knowledge via basic and translational studies of neuropeptide signaling with new neurotransmitters, new knowledge on the mechanisms for central nervous system-enteric nervous system communication and dysfunction, and more advanced clinical research on education, communication skills and their effects on outcome, genetics, pharmacogenetics and genetic epidemiology, better understanding as to how certain psychosocial domains (eg, catastrophizing, abuse) affect symptom behavior and outcome, newer pharmacologic treatments, and the use of combined pharmacologic and behavioral treatment packages. I am pleased to have the opportunity to provide a personal perspective on what the future will be for irritable bowel syndrome and the other functional GI disorders. Having been involved in this field for almost 30 years, I have been fortunate to witness tremendous changes. The focus of this presentation is to address the advances that have recently occurred that set the stage for proposing future research to help move the field along and ultimately to help our patients.
Use of diet and probiotic therapy in the irritable bowel syndrome: analysis of the literature.
Floch MH
J Clin Gastroenterol 2005 May-Jun;39(4):S243-6.
GOAL: The goal of this report is to review the use of dietary intake and probiotics in patients with irritable bowel syndrome (IBS) in published reports. BACKGROUND: Dietary factors can be important in inducing symptoms that occur in patients with the IBS. Dietary intolerances, dietary allergies, specific food metabolites, and regular diet contents all may act as triggers and aggravate the symptoms of IBS; but when any of these mechanisms can be proven to cause the symptoms, then their elimination results in the resolution of that patient's IBS. METHODS: Our previous review was updated. In addition, a careful Medline search was made for the years from 1975 to 2004 to evaluate human research reports on diet and probiotics in the IBS. Forty-six manuscripts were reviewed on diet and six were available on probiotic use in IBS. The most common dietary factor evaluated in the literature was bran, and the most common probiotic used was Lactobacillus plantarum. CONCLUSIONS: Although investigations have shown that bran may be helpful in some patients, a complete review of the literature does not reveal conclusive evidence that diet therapy is effective in IBS. From the limited reports on probiotics, there appears to be a trend to decreasing symptoms. It is clear that much more prospective research is needed to study both dietary factors and probiotics in these areas.
Irritable bowel syndrome: a syndrome in evolution.
Lacy BE, Lee RD
J Clin Gastroenterol 2005 May-Jun;39(4):S230-42.
As a group, functional gastrointestinal disorders are the most common gastrointestinal disorder seen by both generalists and specialists. These disorders can be frustrating to both patients and physicians as they are usually chronic in nature and difficult to treat. These disorders are associated with frequent healthcare visits, the scheduling of multiple, expensive diagnostic tests, and the use of both over-the-counter and prescription medications. All of these factors lead to a significant economic burden to society. In addition, functional gastrointestinal disorders are associated with a reduction in quality of life for the patient. Irritable bowel syndrome (IBS) is the most common of the functional gastrointestinal disorders. This syndrome has been the focus of a large number of research studies over the past two decades. These studies have resulted in a number of significant changes in our definition of IBS. In addition, these research studies have produced considerable changes in our understanding of the etiology and pathogenesis of IBS. In this section, we will review some of the evolutionary changes that have occurred in IBS. We will discuss how the definition of IBS has changed, consider our evolving strategies to evaluate and diagnose IBS, and finally, provide a brief overview of treatment options for this common disorder.
Nerves, reflexes, and the enteric nervous system: pathogenesis of the irritable bowel syndrome.
Gershon MD
J Clin Gastroenterol 2005 May-Jun;39(4):S184-93.
The bowel exhibits reflexes in the absence of CNS input. To do so, epithelial sensory transducers, such as enterochromaffin (EC) cells, activate the mucosal processes of intrinsic (IPANs) and extrinsic primary afferent (sensory) neurons. EC cells secrete serotonin (5-HT) in response to mucosal stimuli. Submucosal IPANs, which secrete acetylcholine and calcitonin gene-related peptide, initiate peristaltic and secretory reflexes and are activated via "5-HT1P" receptors. Release of neurotransmitters is enhanced by 5-HT4 receptors, which are presynaptic and strengthen neurotransmission in prokinetic pathways. 5-HT3 receptors mediate signaling to the CNS and thus ameliorate cancer chemotherapy-associated nausea and the visceral hypersensitivity of diarrhea-predominant irritable bowel syndrome (IBS-D); however, because 5-HT3 receptors also mediate fast ENS neurotransmission and activate myenteric IPANs, they may be constipating. 5-HT4 agonists are prokinetic and relieve discomfort and constipation in IBS-C and chronic constipation. 5-HT4 agonists do not initiate peristaltic and secretory reflexes but strengthen pathways that are naturally activated. Serotonergic signaling in the mucosa and the ENS is terminated by a transmembrane 5-HT transporter, SERT. Mucosal SERT and tryptophan hydroxylase-1 expression are decreased in experimental inflammation, IBS-C, IBS-D, and ulcerative colitis. Potentiation of 5-HT due to the SERT decrease could account for the discomfort and diarrhea of IBS-D, while receptor desensitization may cause constipation. Similar symptoms are seen in transgenic mice that lack SERT. The loss of mucosal SERT may thus contribute to IBS pathogenesis.
Is there a relation between irritable Bowel syndrome and urinary stone disease?
Erdem E, Akbay E, Sezgin O, Doruk E, Canpolat B, Cayan S
Dig Dis Sci 2005 Mar;50(3):605-8.
Our aim was to investigate the role of renal colic, a clinical condition characterized by excruciating pain, in the etiopathogenesis of irritable bowel syndrome (IBS). Two groups of patients were enrolled in the study. Group I consisted of 59 patients (33 male and 26 female) with a median age of 41.9 (18 to 58) years. The patients in group I were admitted to our clinic with urinary stone disease and with a medical history of acute renal colic. Group II consisted of 55 patients (25 male and 30 female) with a median age of 40.1 (18 to 56) years, complaining of urologic abnormalities other than stone disease. IBS was diagnosed using Rome criteria. Metabolic analysis for stone disease was performed on patients in group I. The incidence of five metabolic abnormalities--low urine volume, hypercalciuria, hyperoxaluria, hyperuricosuria and hypocitraturia--in patients with and without irritable bowel disease was investigated. IBS was found in 16 of the 59 patients (27.1%) in group I and in 6 of the 55 patients (10.9%) in group II. The difference was statistically significant (P < 0.05). Relative risk of developing IBS was 2.48 times higher in patients with urinary stone disease than in those without stone disease. There was no statistically significant difference in the metabolic analysis of patients with and without IBS in group I. IBS causes great suffering. Urinary stone disease should be considered as an etiological factor during management of IBS patients. In the presence of gastrointestinal symptoms, a patient with a medical history of acute renal colic might be referred to a gastroenterologist.
Tegaserod is safe, well tolerated and effective in the treatment of patients with non-diarrhoea irritable bowel syndrome.
Fried M, Beglinger C, Bobalj NG, Minor N, Coello N, Michetti P
Eur J Gastroenterol Hepatol 2005 Apr;17(4):421-427.
OBJECTIVE: To evaluate the safety/tolerability and efficacy of tegaserod, a 5-HT4 receptor partial agonist, in the treatment of patients with non-diarrhoea irritable bowel syndrome (non-D-IBS) in Switzerland. METHODS: This was an 8-week, open-label, prospective, multicentre study. Patients (>/=18 years old) met the Rome II diagnostic criteria for IBS, excluding those with diarrhoea for >/=14 days in the previous 3 months. Details of IBS symptoms experienced in the preceding week were recorded at visit 1 (day 1). Eligible patients received 6 mg tegaserod twice daily for 8 weeks. Adverse events (AEs) and serious AEs were recorded, along with detailed assessment of diarrhoeal episodes. Efficacy assessments included the overall number and percentage of responders after 8 weeks' treatment. RESULTS: A total of 850 patients (72% women; mean age, 51.4 years) were enrolled, and 843 received at least one dose of tegaserod. AEs were reported in 38% of patients, of which 13% were drug-related. Diarrhoea occurred early during treatment (13% in the first week, 7% thereafter), was mild to moderate in severity, was transient and was resolved with continued treatment. In total, 208 patients left the study early, primarily due to AEs. Diarrhoea accounted for 68 of these discontinuations. Nine serious AEs were reported but these were not related to tegaserod treatment. Sixty-six percent of patients responded to tegaserod on the Subject's Global Assessment of relief after 8 weeks. Benefits were also seen across individual IBS symptoms. CONCLUSION: Tegaserod (6 mg twice daily) appears to be safe, well-tolerated and effective in the treatment of non-D-IBS over 8 weeks.
Impact of irritable bowel syndrome on patients' lives: development and psychometric documentation of a disease-specific measure for use in clinical trials.
Longstreth GF, Bolus R, Naliboff B, Chang L, Kulich KR, Carlsson J, Mayer EA, Naesdal J, Wiklund IK
Eur J Gastroenterol Hepatol 2005 Apr;17(4):411-420.
OBJECTIVE: To develop a disease-specific questionnaire to capture the impact of irritable bowel syndrome (IBS) and its treatment on patients' lives, the Irritable Bowel Syndrome Impact Scale (IBS-IS). PATIENTS AND METHODS: One hundred and fifty-five IBS patients participated (126 (81%) female; age (mean+/-SD) 45.5+/-12.4 years). We developed the initial 39 items from the literature, available IBS-specific instruments and input from physicians, nurses and patients. We deleted IBS-IS items with a high ceiling effect, items that measured a different construct and items showing a high correlation (r>0.90) with another item and with Rasch analysis, leaving 26 items. We then applied exploratory factor analysis to examine domain groupings. Subjects completed the IBS-IS instrument, the Gastrointestinal Symptom Rating Scale for IBS (GSRS-IBS), Short Form-36 (SF-36), Visceral Sensitivity Index (VSI), and Hospital Anxiety and Depression (HAD) scale. Internal consistency, construct validity and discriminate validity were assessed. RESULTS: The 26 items represented five domains: fatigue, impact on daily activities, sleep disturbance, emotional distress and eating habits. The internal consistency reliability for the domains was 0.87 to 0.96. Most associations between similar constructs in the IBS-IS, GSRS-IBS, SF-36, VSI, and HAD were >0.40. Each IBS-IS domain score decreased with increasing IBS symptom severity (P<0.05), and the patients scored >5 score units lower than a US general population scored on all eight SF-36 dimensions. CONCLUSION: The IBS-IS is a short, user-friendly instrument with excellent psychometric properties that has potential usefulness for clinical trials.
The effects of the 5-HT3 antagonist, alosetron, on brain serotonin synthesis in patients with irritable bowel syndrome.
Nakai A, Diksic M, Kumakura Y, D'Souza D, Kersey K
Neurogastroenterol Motil 2005 Apr;17(2):212-21.
Serotonin (5-HT) plays an important role in the pathophysiology of irritable bowel syndrome (IBS). Using alpha-[(11)C]methyl-L-tryptophan-positron emission tomography (PET), it was demonstrated that brain 5-HT synthesis is increased in patients with IBS, in a gender-specific manner. The aims of the study were to evaluate the effects of alosetron on brain 5-HT synthesis in patients with IBS. Six male and five female non-constipation-predominant IBS patients were enrolled. The subjects received alosetron or a placebo for 14 days, separated by a 2-week washout period. On day 14, rectal distensions commenced just prior to the PET scan (which was performed for 80 min), and continued for 20-min periods. The functional images were analysed with SPM99. Alosetron vs placebo treatments, in a randomized, double-blinded, crossover manner, were studied. 5-HT synthesis was greater in several regions in the males than in the females during the alosetron treatment, whereas there was no region in which the females had greater synthesis. There were significant gender-treatment interactions of synthesis in the cingulate gyrus, caudate nucleus, globus pallidus, and cerebellum. The gender differences in the effect of alosetron on brain 5-HT synthesis may be related to the gender differences in the efficacy of alosetron.
Overlapping conditions in women with irritable bowel syndrome.
Heitkemper M, Jarrett M
Urol Nurs 2005 Feb;25(1):25-30; quiz 31.
Irritable bowel syndrome is a common and often unpredictable disorder with an increased incidence among women. It is characterized by abdominal pain associated with constipation-diarrhea. Recent research, current theories about etiology and pathophysiology, diagnosis, management, and overlapping conditions such as interstitial cystitis and chronic pelvic pain are discussed.
A prospective assessment of bowel habit in irritable bowel syndrome in women: defining an alternator.
Drossman DA, Morris CB, Hu Y, Toner BB, Diamant N, Leserman J, Shetzline M, Dalton C, Bangdiwala SI
Gastroenterology 2005 Mar;128(3):580-9.
BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is subtyped as IBS with diarrhea (IBS-D) or IBS with constipation (IBS-C) based on Rome II guidelines. The remaining group is considered as having mixed IBS (IBS-M). There is no standard definition of an alternator (IBS-A), in which bowel habit changes over time. Our aim was to use Rome II criteria to prospectively assess change in bowel habit for more than 1 year to understand IBS-A. METHODS: Female patients (n=317) with IBS entering a National Institutes of Health treatment trial were studied at baseline with questionnaires and 2-week daily diary cards of pain and stool frequency and consistency. Studies were repeated at the end of treatment (3 months) and at four 3-month intervals for one more year. Algorithms to classify subjects into IBS-D, IBS-C, and IBS-M groups used diary card information and modified Rome II definitions. Changes in bowel habit at 3-month intervals were then assessed using these surrogate diary card measures. RESULTS: At baseline, 36% had IBS-D, 31% IBS-M, and 34% IBS-C. Except for stool frequency, there were no differences between groups. While the proportion of subjects in each subgroup remained the same over the year, most individuals (more than 75%) changed to either of the other 2 subtypes at least once. IBS-M was the least stable (50% changed out by 12 weeks). Patients were more likely to transition between IBS-M and IBS-C than between IBS-D and IBS-M. Notably, only 29% switched between the IBS-D and IBS-C subtypes over the year. CONCLUSIONS: While the proportion of subjects in each of the IBS subtypes stays the same, individuals commonly transition between subtypes, particularly between IBS-M and IBS-C. We recommend that IBS-A be defined as at least one change between IBS-D and IBS-C by Rome II criteria over a 1-year period.
Origin of gas retention and symptoms in patients with bloating.
Salvioli B, Serra J, Azpiroz F, Lorenzo C, Aguade S, Castell J, Malagelada JR
Gastroenterology 2005 Mar;128(3):574-9.
BACKGROUND & AIMS: Patients reporting abdominal bloating exhibit impaired tolerance to intestinal gas loads. The aim of this study was to identify the gut compartment responsible for gas retention. METHODS: In 30 patients predominantly reporting abdominal bloating (24 with irritable bowel syndrome and 6 with functional bloating) and 22 healthy subjects, gas (nitrogen, carbon dioxide, and oxygen) was infused into the intestine for 2 hours while measuring rectal gas outflow. First, in 12 patients and 10 healthy subjects, gas transit (24 mL/min jejunal infusion labeled with 74 MBq bolus of 133 Xe) was measured by scintigraphy. Second, in groups of patients and healthy subjects, the effects of gas infusion (12 mL/min) in the jejunum versus ileum, jejunum versus cecum, and jejunum versus sham infusion (n=6 each) were compared by paired tests. RESULTS: In patients, total gut transit of gas was delayed (50% clearance time, 33 +/- 4 min vs 23 +/- 4 min in healthy subjects; P <.05) owing to impaired small bowel transit (50% clearance time, 20 +/- 2 min vs 12 +/- 3 min in healthy subjects; P <.05), whereas colonic transit was normal (50% clearance time, 13 +/- 2 min vs 11 +/- 2 min in healthy subjects; not significant). Furthermore, jejunal gas infusion in patients was associated with gas retention (329 +/- 81 mL vs 88 +/- 79 mL in healthy subjects; P <.05), whereas direct ileal or colonic infusion was not (61 +/- 103 mL and -143 +/- 87 mL retention, respectively). CONCLUSIONS: In patients reporting bloating, the small bowel is the gut region responsible for ineffective gas propulsion.
Effect of CCK-1 Antagonist, Dexloxiglumide, in Female Patients with Irritable Bowel Syndrome: A Pharmacodynamic and Pharmacogenomic Study.
Cremonini F, Camilleri M, McKinzie S, Carlson P, Camilleri CE, Burton D, Thomforde G, Urrutia R, Zinsmeister AR
Am J Gastroenterol 2005 Mar;100(3):652-63.
BACKGROUND: Cholecystokinin (CCK) is involved in gastrointestinal motor response to meals. The potential role of CCK receptor antagonists in functional gastrointestinal disorders is unclear. AIMS: To evaluate the effects of dexloxiglumide, a CCK-1 receptor antagonist, on gastrointestinal transit (GIT) and symptoms in patients with constipation-predominant IBS (C-IBS); and to explore the influence of CCK-1 receptor polymorphisms on gut transit and the pharmacodynamic response to therapy. METHODS: A total of 36 patients with C-IBS and normal to slow baseline colonic transit (CT) were randomized (double-blind, parallel design) to 7 days of dexloxiglumide 200 mg or placebo t.i.d. Daily bowel habits diaries and weekly relief of IBS symptoms were recorded. At the end of treatment, GIT and CT were measured. Peripheral blood DNA was examined for polymorphisms in genes controlling CCK: four related to CCK-1, one to the CCK gene promoter, and one related to CCK-2. The distributions of allelic variants and association with gastric emptying in response to dexloxiglumide and placebo were assessed. RESULTS: Dexloxiglumide was associated with accelerated gastric emptying t(1/2) (p= 0.004), and slower ascending colon emptying t(1/2) (p < 0.01), with no significant effect on overall CT or satisfactory relief of IBS. There was an association between CCK 779T > C polymorphism and slower rate of gastric emptying (p= 0.04). CONCLUSIONS: Dexloxiglumide accelerates gastric emptying and delays proximal but not overall CT in patients with C-IBS. Dexloxiglumide does not accelerate transit in C-IBS. The role of CCK-1 gene polymorphisms in delaying gastric emptying and in determining response to therapy deserves further study. (Am J Gastroenterol 2005;100:652-663).
Recognition and treatment of irritable bowel syndrome among women with chronic pelvic pain.
Williams RE, Hartmann KE, Sandler RS, Miller WC, Savitz LA, Steege JF
Am J Obstet Gynecol 2005 Mar;192(3):761-7.
Objective We sought to describe irritable bowel syndrome (IBS) treatment among women with chronic pelvic pain. Study design We performed a cross-sectional study of new chronic pelvic pain patients between 1993 and 2000 (n = 987). IBS was defined by Rome I criteria. IBS treatment was defined as lower gastrointestinal drugs or referral. Analyses were descriptive and multivariable. Results IBS occurred in 35% of patients. In the highest quartile of pain, women with IBS were not more likely to have IBS treatment initiated. In the lowest three quarters of pain, women with IBS were 5.08 times more likely to have IBS treatment initiated. IBS was not diagnosed 40% of the time. IBS treatments were not recommended to 67% of patients with IBS. More than 35% of patients were prescribed narcotics. Conclusion IBS is not consistently diagnosed and treated even in a pelvic pain clinic. Yet, treatment of IBS may reduce the overall abdominal pain of these patients.
Post-infectious irritable bowel syndrome in patients with Shigella infection.
Ji S, Park H, Lee D, Song YK, Choi JP, Lee SI
J Gastroenterol Hepatol 2005 Mar;20(3):381-6.
Abstract Background and Aims: Bacterial gastroenteritis has been known as a risk factor of irritable bowel syndrome (IBS). Several risk factors of post-infectious IBS (PI-IBS) have been documented. The aims of this study were to verify the role of bacterial gastroenteritis in the development of IBS and the risk factors for the development of PI-IBS. The clinical course of PI-IBS was also investigated. Methods: We recruited 143 patients with shigellosis during its outbreak and 113 controls. Both groups were followed up for 12 months. Bowel symptoms were evaluated by use of questionnaires at 3, 6 and 12 months after the initial recruitment. Results: Complete data were obtained from 101 patients (70.6%) and 102 healthy controls (90.3%). At 12 months, 15 patients and six controls had IBS (adjusted OR; 2.9, 95% CI; 1.1-7.9). Of the 15 patients, five had IBS symptoms consistently for 12 months, three did not have IBS symptoms initially and seven had fluctuating bowel symptoms. The duration of diarrhea was an independent risk factor of PI-IBS. Conclusions: Bacterial gastroenteritis is a risk factor of IBS and the duration of diarrhea as the index of severity of initial illness is an independent risk factor of PI-IBS. The clinical course of PI-IBS is variable over the 1 year of follow-up.
Treatment of irritable bowel syndrome.
Farthing MJ
BMJ 2005 Feb 26;330(7489):429-30.
Impaired reflex control of intestinal gas transit in patients with abdominal bloating.
Passos MC, Serra J, Azpiroz F, Tremolaterra F, Malagelada JR
Gut 2005 Mar;54(3):344-8.
BACKGROUND: Patients with abdominal bloating and distension exhibit impaired transit of intestinal gas which may lead to excessive gas retention and symptoms. Furthermore, we have previously shown that intestinal gas transit is normally accelerated by rectal distension. We hypothesise that in patients with functional bloating this modulatory mechanism fails and impairs gas transit. METHODS: In 12 healthy subjects and eight patients with abdominal bloating we compared, by paired studies, the effect of rectal versus sham distension on intestinal gas transit. Gas was infused into the jejunum (12 ml/min) for three hours with simultaneous perfusion of lipids into the duodenum (Intralipid 1 kcal/min) while measuring evacuation of gas per rectum. RESULTS: In healthy subjects, duodenal lipid infusion produced gas retention (409 (68) ml) which was prevented by rectal distension (90 (90) ml; p<0.05 v sham distension). In contrast, rectal distension in patients with abdominal bloating failed to reduce lipid induced gas retention (771 (217) ml retention during rectal distension v 730 (183) ml during sham distension; NS; p<0.05 v healthy controls for both). CONCLUSION: Failure of distension related reflexes impairs intestinal gas propulsion and clearance in patients with abdominal bloating.
Is health care seeking for irritable bowel syndrome and functional dyspepsia a socially learned response to illness?
Koloski NA, Boyce PM, Talley NJ
Dig Dis Sci 2005 Jan;50(1):153-62.
In a population-based study of 207 subjects with irritable bowel syndrome (IBS) or functional dyspepsia (FD) and controls (n = 100), we aimed to determine whether dimensions of abnormal illness behavior from the Abnormal Illness Behaviour Questionnaire and aspects of social learning of illness behavior from the Social Learning of Illness Behaviour scale were independent predictors of health care seeking for IBS and FD. Results showed that dimensions of abnormal illness behavior and aspects of social learning of illness behavior (encouragement, reinforcement, and modeling) did not significantly differentiate between consulters and nonconsulters with IBS and/or FD. The Disease Conviction scale (OR = 1.55; 95% CI, 1.15-2.09) of the Abnormal Illness Behaviour Questionnaire was an independent predictor of having a diagnosis of IBS and/or FD, independent of age and gender, psychiatric diagnoses, and symptom severity. We conclude that a belief in the presence of serious pathology characterizes community subjects with IBS and FD, but not health care seeking.
High interdigestive and postprandial motilin levels in patients with the irritable bowel syndrome.
Simren M, Bjornsson ES, Abrahamsson H
Neurogastroenterol Motil 2005 Feb;17(1):51-7.
Abstract Motilin shows cyclic variation with the different phases of the migrating motor complex (MMC). Altered motilin levels have been found in irritable bowel syndrome (IBS) patients, but in these studies motilin levels were analysed without the knowledge of the phases of MMC. We included 13 healthy controls (HC) and 24 patients with IBS [12 diarrhoea-predominant (IBS-D) and 12 constipation-predominant (IBS-C)]. We performed interdigestive and postprandial antroduodenojejunal manometry and blood samples for analysis of motilin were drawn. Group differences in plasma levels of motilin were analysed during mid-phase II, just before the start of phase III (pre-III), during phase I, immediately before the meal and 30 and 60 min after the 500 kcal mixed meal. Higher motilin levels were observed in IBS vs HC in both the interdigestive and postprandial periods (P < 0.05). No significant differences between IBS-C and IBS-D were observed. The cyclic variation of motilin during MMC and the meal response was similar in IBS and controls. IBS patients, irrespective of the predominant bowel habit, demonstrate higher motilin levels than HCs in all phases of the MMC and also after a meal. These findings may bear some pathophysiological importance in IBS and relate to the gastrointestinal dysmotility often seen in these patients.
Proctalgia fugax: caused by pudendal neuropathy?
Takano M
Dis Colon Rectum 2005 Jan;48(1):114-20.
There is a strange disease called proctalgia fugax in which rather uncomfortable pain appears suddenly mostly at night without any particular warning and disappears completely without any objective traces. It also is categorized as a functional anorectal pain under the Rome II (diagnostic criteria for the functional gastrointestinal disorders). For the causes, many theories have been advocated but not decisive and therefore were not linked to the definite treatment. The author experienced 68 patients with proctalgia fugax, among which 55 patients had tenderness along the pudendal nerve. The location, character, and degree of pain caused by digital examination were confirmed by all of them to be similar to that which they experience at times of paroxysm. After administration of a nerve block, symptoms disappeared completely in 65 percent of the patients and decreased in 25 percent. These data suggest that the pathogenesis of proctalgia fugax is neuralgia of the pudendal nerves.
A dose-ranging, phase II study of the efficacy and safety of alosetron in men with diarrhea-predominant IBS.
Chang L, Ameen VZ, Dukes GE, McSorley DJ, Carter EG, Mayer EA
Am J Gastroenterol 2005 Jan;100(1):115-23.
BACKGROUND: A randomized, double blind, placebo-controlled dose-ranging study was conducted to assess the efficacy of alosetron in men with diarrhea-predominant irritable bowel syndrome (IBS). METHODS: Six hundred and sixty-two men were randomized to treatment with alosetron 0.5, 1.0, 2.0, 4.0 mg, or placebo twice daily for 12 wk, followed by a 4-wk posttreatment period. Adequate relief of IBS pain and discomfort during week 5-12 of the treatment phase was the primary endpoint; secondary endpoints included bowel urgency, stool frequency, and consistency, incomplete evacuation, bloating, and abdominal pain or discomfort. RESULTS: Subjects ranked urgency and abdominal pain as their most bothersome IBS symptoms. The average rate of adequate relief during week 5-12 was significantly higher in the alosetron 1.0 mg twice-daily group compared to placebo (53%vs 40%, p= 0.04), and all doses of alosetron significantly reduced stool consistency scores (p < 0.001) indicating firmer stools. No significant effects of alosetron were seen with regard to urgency, number of bowel movements, bloating, and incomplete evacuation. Constipation was the most common adverse event and occurred in a dose-related manner among subjects receiving alosetron, 9% (0.5 mg twice daily), 15% (1.0 mg twice daily), 11% (2.0 mg twice daily), and 21% (4.0 mg twice daily). No serious adverse events of constipation were reported. One subject in the 0.5 mg twice-daily group had an episode of rectal bleeding suggestive of a possible diagnosis of ischemic colitis. CONCLUSIONS: Alosetron 1 mg twice daily provided adequate relief of IBS pain and discomfort, and improved stool consistency in men with diarrhea-predominant IBS.
Visceral Sensitivity and Symptoms in Patients with Constipation- or Diarrhea-predominant Irritable Bowel Syndrome (IBS): Effect of a Low-Fat Intraduodenal Infusion.
Caldarella MP, Milano A, Laterza F, Sacco F, Balatsinou C, Lapenna D, Pierdomenico SD, Cuccurullo F, Neri M
Am J Gastroenterol 2005 Feb;100(2):383-9.
BACKGROUND: Visceral hypersensitivity is common in Irritable Bowel Syndrome (IBS) patients, and symptoms exacerbate postprandially. Yet the effects of nutrients on visceral sensitivity and symptoms in these patients have not been fully explored. AIMS: To evaluate the differences of visceral sensitivity and symptoms in healthy subjects and IBS patients during fasting and intraduodenal lipids infusion. METHODS: Graded rectal distensions at fixed tension levels were performed in 16 IBS patients (8 IBS-C and 8 IBS-D) and 6 healthy subjects before and during intraduodenal lipids infusion at 0.5 kcal/min. Tension levels were increased in 4 gr increments up to 64 gr or discomfort during both conditions. At each step, perception and symptoms were measured by means of a validated questionnaire. RESULTS: In basal conditions, perception thresholds in IBS patients and health were, respectively, 8 +/- 2 gr versus 32 +/- 9 gr (p < 0.001) with no changes during lipids. Intraduodenal lipids infusion significantly lowered threshold of discomfort in IBS patients in comparison to fasting (24 +/- 6 gr vs 34 +/- 4 gr; p < 0.05), while health tolerated all distension without discomfort. No differences of compliance, perception, or discomfort were observed between the two subgroups of patients at each tension step. The predominant symptom elicited in patients with IBS-C was abdominal pain (54%), while patients with IBS-D exhibited urgency (63%, p < 0.005); this pattern was maintained during lipids. CONCLUSIONS: Intraduodenal lipids increase visceral sensitivity in both IBS-C and IBS-D; symptoms specificity in response to rectal distension is maintained in the postprandial period. Lipids may be responsible for the postprandial symptoms exacerbation in IBS. (Am J Gastroenterol 2005;100:383-389).
Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCR.
Malinen E, Rinttila T, Kajander K, Matto J, Kassinen A, Krogius L, Saarela M, Korpela R, Palva A
Am J Gastroenterol 2005 Feb;100(2):373-82.
OBJECTIVE: The gut microbiota may contribute to the onset and maintenance of irritable bowel syndrome (IBS). In this study, the microbiotas of patients suffering from IBS were compared with a control group devoid of gastrointestinal (GI) symptoms. MATHODS: Fecal microbiota of patients (n = 27) fulfilling the Rome II criteria for IBS was compared with age- and gender-matched control subjects (n = 22). Fecal samples were obtained at 3 months intervals. Total bacterial DNA was analyzed by 20 quantitative real-time PCR assays covering approximately 300 bacterial species. RESULTS: Extensive individual variation was observed in the GI microbiota among both the IBS- and control groups. Sorting of the IBS patients according to the symptom subtypes (diarrhea, constipation, and alternating predominant type) revealed that lower amounts of Lactobacillus spp. were present in the samples of diarrhea predominant IBS patients wheras constipation predominant IBS patients carried increased amounts of Veillonella spp. Average results from three fecal samples suggested differences in the Clostridium coccoides subgroup and Bifidobacterium catenulatum group between IBS patients (n = 21) and controls (n = 15). Of the intestinal pathogens earlier associated with IBS, no indications of Helicobacter spp. or Clostridium difficile were found whereas one case of Campylobacter jejuni was identified by sequencing. CONCLUSIONS: With these real-time PCR assays, quantitative alterations in the GI microbiota of IBS patients were found. Increasing microbial DNA sequence information will further allow designing of new real-time PCR assays for a more extensive analysis of intestinal microbes in IBS. (Am J Gastroenterol 2005;100:1-10).
Yeast metabolic products, yeast antigens and yeasts as possible triggers for irritable bowel syndrome.
Santelmann H, Howard JM
Eur J Gastroenterol Hepatol 2005 Jan;17(1):21-6.
Many patients with irritable bowel syndrome (IBS) are disillusioned by the lack of efficacy of treatments and suffer from numerous symptoms not covered by the Rome criteria for IBS, as the current empirical treatment regimens fail to address these persistent debilitating 'IBS associated symptoms'. These symptoms are similar to other symptom complexes like chronic fatigue and the so-called 'candida syndrome', and many seek help from alternative medicine. The possible role of Candida and yeasts in non-immune compromised individuals is disputed and is the subject of this review. Even if the involvement of yeasts in the aetiology of IBS still remains unclear, there is increasing evidence for yeasts being able to cause IBS-symptoms in sensitized patients via Candida products, antigens and cross-antigens. But more research is needed before antifungal treatment can be recommended as a first line treatment for IBS.
Hypnotherapy in the treatment of irritable bowel syndrome.
Gonsalkorale WM, Whorwell PJ
Eur J Gastroenterol Hepatol 2005 Jan;17(1):15-20.
There is accumulating and compelling evidence that hypnotherapy is an effective treatment for irritable bowel syndrome. Recently, studies have shown that hypnotherapy has beneficial effects that are long lasting, with most patients maintaining improvement, and with decreased consultation and medication needs in the long term. The particular gut directed approach used, which is aimed at normalizing and controlling gut function, is also described. While the mechanisms of how hypnotherapy brings about its therapeutic effect are not fully known, changes in colonic motility and rectal sensitivity have been demonstrated, although changes in central processing and psychological effects may also play a role.
Cognitive behaviour therapy for irritable bowel syndrome.
Hutton J
Eur J Gastroenterol Hepatol 2005 Jan;17(1):11-4.
The UK Department of Health states that there is suggestive, although not conclusive, evidence for the efficacy of cognitive behavioural therapy (CBT) in irritable bowel syndrome (IBS) and that CBT should be considered as a treatment option for the syndrome. This paper provides a general introduction to CBT, the principles which underlie it and how they can be applied to IBS. The components of CBT for IBS are described in some detail. Guidelines for gastroenterologists are provided on how these principles can be used to inform their practice and the existing outcome data are reviewed.
Intestinal infection and irritable bowel syndrome.
Parry S, Forgacs I
Eur J Gastroenterol Hepatol 2005 Jan;17(1):5-9.
The observation that the symptoms of irritable bowel syndrome (IBS) in some patients might follow an episode of acute gastroenteritis came from epidemiological studies. Both retrospective and prospective studies suggest that between 4% and 26% of patients develop IBS for the first time after gastroenteritis. The diagnosis of post-infectious IBS is typically made from the history. In addition, as with the diagnosis of IBS more generally, it is important to exclude other clinical causes for persistent bowel dysfunction. There is little, if any, evidence to support the widely-held view that patients with post-infectious IBS carry a better prognosis than IBS patients more generally. The management of patients with post-infectious IBS is the standard approach that might be applied to all patients with IBS. Post-infectious IBS patients may differ from IBS patients in general in having a low-level of intestinal inflammation. Work in animal models, and detection of low-grade inflammation in intestinal biopsies combined with markers of intestinal inflammation such as faecal calprotectin all indicate a strong possibility that persisting inflammation after the acute infection may be important in the pathogenesis of post-infectious IBS.
Unorthodox treatment for irritable bowel syndrome?
Bjarnason I, Bjarnason A
Eur J Gastroenterol Hepatol 2005 Jan;17(1):1-3.
Renal tubular proteinuria in patients with irritable bowel syndrome.
O'Brien AJ, Lamb EJ, Muller AF
Eur J Gastroenterol Hepatol 2005 Jan;17(1):69-72.
OBJECTIVE: Irritable bowel syndrome (IBS) is a common condition that is poorly understood. We have previously demonstrated tubular protinuria in patients with inflammatory bowel disease. This study examined whether tubular proteinuria was a feature of IBS. METHODS: Eighty control subjects (male:female, 28:52; age range 20-65 years) and 21 patients with IBS (male:female, 9:12; age range 16-64 years) (not significant) were recruited. Patients with known renal disease, hypertension, diabetes or microbiological evidence of urinary infection were excluded. The IBS patients all fulfilled the ROME II criteria. None had preceding gastroenteritis. Urinary alpha1-microglobulin (alpha1-M) was measured in a second-voided morning urine sample and corrected for urinary concentration by measurement of creatine. Blood samples were analysed for haematochemical indices including C-reactive protein. Statistical analysis was by unpaired t test. RESULTS: None of the IBS patients were reclassified with inflammatory bowel disease over a 5-year follow up period. All had normal haematochemical parameters. Mean +/- standard deviation urinary alpha1-M concentrations were significantly higher in IBS patients than controls (IBS patients, 1.17 +/- 0.65 mg/mmol; controls, 0.75 +/- 0.36 mg/mmol; P < 0.01) and exceeded 1.5 mg/mmol (the upper reference limit) in seven patients. There was no difference in urinary alpha1-M concentrations in the diarrhoea-predominant and constipation-predominant groups (mean +/- standard deviation, 1.342 +/- 0.65 versus 0.76 +/- 0.48 mg/mmol; P = 0.062). CONCLUSIONS: Urinary alpha1-M concentration is commonly increased in IBS, suggesting the presence of renal proximal tubular injury.
Overlap of gastrointestional symptom complexes in a US community.
Locke GR 3rd, Zinsmeister AR, Fett SL, Melton LJ 3rd, Talley NJ
Neurogastroenterol Motil 2005 Feb;17(1):29-34.
Abstract Background: Although the Rome criteria define a number of individual functional gastrointestinal disorders, people may have symptoms of multiple disorders at the same time. In addition, therapies may be effective in subsets of people with specific disorders, yet at the same time help people with multiple disorders. Aim: To estimate the prevalence of combinations of gastrointestional (GI) symptom complexes. Methods: A valid self report questionnaire which records GI symptoms was mailed to an age- and gender-stratified random sample of Olmsted County, MN residents aged 30-64 years. Standard definitions were used to identify people with gastro-oesophageal reflux, dyspepsia, irritable bowel syndrome (IBS), constipation and diarrhoea. The prevalence of people meeting multiple symptom complexes was estimated. Specifically, combinations of dyspepsia, IBS and constipation were compared to dyspepsia, IBS and diarrhoea. Results: A total of 657 (69%) of 943 eligible subjects responded; 643 provided data for each of the necessary symptom questions. Each two-way combination of symptom group was present in between 4 and 9% of the population; each three-way combination was present in 1-4% of the population. The overlap between dyspepsia, IBS and constipation was similar to dyspepsia, IBS and diarrhoea, except body mass index was higher in the diarrhoea overlap group (P = 0.03). Conclusion: Symptom complex overlap is common in the community; for each condition, the majority of sufferers reported an additional symptom complex. This overlap of symptoms challenges the current paradigm that functional GI disorders represent multiple discreet entities.
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