Pelvic Pain in Coloproctology

Diagnostic criteria for patients with irritable bowel syndrome.
Cayley WE Jr
Am Fam Physician. 2006 Aug 15;74(4):557.

Public Speaking Stress-Induced Neuroendocrine Responses and Circulating Immune Cell Redistribution in Irritable Bowel Syndrome.
Elsenbruch S, Lucas A, Holtmann G, Haag S, Gerken G, Riemenschneider N, Langhorst J, Kavelaars A, Heijnen CJ, Schedlowski M
Am J Gastroenterol. 2006 Sep 4;.

OBJECTIVES: Augmented neuroendocrine stress responses and altered immune functions may play a role in the manifestation of functional gastrointestinal (GI) disorders. We tested the hypothesis that IBS patients would demonstrate enhanced psychological and endocrine responses, as well as altered stress-induced redistribution of circulating leukocytes and lymphocytes, in response to an acute psychosocial stressor when compared with healthy controls. METHODS: Responses to public speaking stress were analyzed in N = 17 IBS patients without concurrent psychiatric conditions and N = 12 healthy controls. At baseline, immediately following public speaking, and after a recovery period, state anxiety, acute GI symptoms, cardiovascular responses, serum cortisol and plasma adrenocorticotropic hormone (ACTH) were measured, and numbers of circulating leukocytes and lymphocyte subpopulations were analyzed by flow cytometry. RESULTS: Public speaking led to significant cardiovascular activation, a significant increase in ACTH, and a redistribution of circulating leukocytes and lymphocyte subpopulations, including significant increases in natural killer cells and cytotoxic/suppressor T cells. IBS patients demonstrated significantly greater state anxiety both at baseline and following public speaking. However, cardiovascular and endocrine responses, as well as the redistribution of circulating leukocytes and lymphocyte subpopulations after public speaking stress, did not differ for IBS patients compared with controls. CONCLUSIONS: In IBS patients without psychiatric comorbidity, the endocrine response as well as the circulation pattern of leukocyte subpopulations to acute psychosocial stress do not differ from healthy controls in spite of enhanced emotional responses. Future studies should discern the role of psychopathology in psychological and biological stress responses in IBS.

Postinfectious irritable bowel syndrome--a meta-analysis.
Halvorson HA, Schlett CD, Riddle MS
Am J Gastroenterol. 2006 Aug;101(8):1894-9; quiz 1942.

OBJECTIVES: Irritable bowel syndrome (IBS) is a heterogeneous disorder affecting 12% of the population worldwide. Several studies identify IBS as a sequela of infectious gastroenteritis (IGE) with reported prevalence ranging from 4% to 31% and relative risk from 2.5 to 11.9. This meta-analysis was conducted to explore the differences between reported rates and provide a pooled estimate of risk for postinfectious irritable bowel syndrome (PI-IBS). DATA SOURCES: Electronic databases (MEDLINE, OLDMEDLINE, EMBASE, Cochrane database of clinical trials) and pertinent reference lists (including other review articles). REVIEW METHODS: Data were abstracted from included studies by two independent investigators; study quality, heterogeneity, and publication bias were assessed; sensitivity analysis was performed; and a summative effect estimate was calculated for risk of PI-IBS. RESULTS: Eight studies were included for analysis and all reported elevated risk of IBS following IGE. Median prevalence of IBS in the IGE groups was 9.8% (IQR 4.0-13.3) and 1.2% in control groups (IQR 0.4-1.8) (sign-rank test, p= 0.01). The pooled odds ratio was 7.3 (95% CI, 4.7-11.1) without significant heterogeneity (chi2 heterogeneity statistic, p= 0.41). Subgroup analysis revealed an association between PI-IBS risk and IGE definition used. CONCLUSIONS: This study provides supporting evidence for PI-IBS as a sequela of IGE and a pooled risk estimate revealing a sevenfold increase in the odds of developing IBS following IGE. The results suggest that the long-term benefit of reduced PI-IBS may be gained from primary prevention of IGE.

Commentary on peripheral and central contributions to hyperalgesia in irritable bowel syndrome.
Mayer EA
J Pain. 2006 Aug;7(8):539-41; discussion 542-3.

Peripheral and central contributions to hyperalgesia in irritable bowel syndrome.
Price DD, Zhou Q, Moshiree B, Robinson ME, Nicholas Verne G
J Pain. 2006 Aug;7(8):529-35.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder seen by gastroenterologists. We discuss some recent evidence for potential neural mechanisms that could contribute to somatic and visceral hyperalgesia in IBS patients. The combination of research studies of human IBS patients and studies of rats with delayed rectal hypersensitivity after recovery from experimentally induced neonatal colitis strongly suggests a mechanism wherein both primary visceral hyperalgesia and secondary widespread cutaneous hyperalgesia are dynamically maintained by tonic impulse input from the noninflamed colon and/or rectum. The secondary hyperalgesia is likely to be at least partly related to sensitization of spinal cord dorsal horn neurons and in this respect might be similar to other persistent pain conditions such as fibromyalgia and complex regional pain syndrome. PERSPECTIVE: Pain in irritable bowel syndrome is likely to be at least partly maintained by peripheral impulse input from the colon/rectum and central sensitization, yet it is also highly modifiable by psychological factors such as nocebo and placebo effects. A synergistic interaction might occur between psychological factors and abnormal afferent processing.

July

Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome.
Whorwell PJ, Altringer L, Morel J, Bond Y, Charbonneau D, O'Mahony L, Kiely B, Shanahan F, Quigley EM
Am J Gastroenterol. 2006 Jul;101(7):1581-90.

BACKGROUND: Probiotic bacteria exhibit a variety of properties, including immunomodulatory activity, which are unique to a particular strain. Thus, not all species will necessarily have the same therapeutic potential in a particular condition. We have preliminary evidence that Bifidobacterium infantis 35624 may have utility in irritable bowel syndrome (IBS). OBJECTIVES: This study was designed to confirm the efficacy of the probiotic bacteria B. infantis 35624 in a large-scale, multicenter, clinical trial of women with IBS. A second objective of the study was to determine the optimal dosage of probiotic for administration in an encapsulated formulation. METHODS: After a 2-wk baseline, 362 primary care IBS patients, with any bowel habit subtype, were randomized to either placebo or freeze-dried, encapsulated B. infantis at a dose of 1 x 10(6), 1 x 10(8), or 1 x 10(10), cfu/mL for 4 wk. IBS symptoms were monitored daily and scored on to a 6-point Likert scale with the primary outcome variable being abdominal pain or discomfort. A composite symptom score, the subject's global assessment of IBS symptom relief, and measures of quality of life (using the IBS-QOL instrument) were also recorded. RESULTS: B. infantis 35624 at a dose of 1 x 10(8) cfu was significantly superior to placebo and all other bifidobacterium doses for the primary efficacy variable of abdominal pain as well as the composite score and scores for bloating, bowel dysfunction, incomplete evacuation, straining, and the passage of gas at the end of the 4-wk study. The improvement in global symptom assessment exceeded placebo by more than 20% (p < 0.02). Two other doses of probiotic (1 x 10(6) and 1 x 10(10)) were not significantly different from placebo; of these, the 1 x 10(10) dose was associated with significant formulation problems. No significant adverse events were recorded. CONCLUSIONS: B. infantis 35624 is a probiotic that specifically relieves many of the symptoms of IBS. At a dosage level of 1 x 10(8) cfu, it can be delivered by a capsule making it stable, convenient to administer, and amenable to widespread use. The lack of benefits observed with the other dosage levels of the probiotic highlight the need for clinical data in the final dosage form and dose of probiotic before these products should be used in practice.

Treatment of diarrhea-predominant irritable bowel syndrome with traditional Chinese herbal medicine: a randomized placebo-controlled trial.
Leung WK, Wu JC, Liang SM, Chan LS, Chan FK, Xie H, Fung SS, Hui AJ, Wong VW, Che CT, Sung JJ
Am J Gastroenterol. 2006 Jul;101(7):1574-80.

BACKGROUND: As there is no effective treatment for irritable bowel syndrome (IBS), many patients turn to traditional Chinese medicine (TCM) for possible cure. We investigated the therapeutic efficacy of an ancient herbal Chinese formula in patients with diarrhea-predominant IBS. METHODS: This was a randomized double-blinded placebo-controlled trial. Chinese IBS patients with predominant diarrhea symptoms that fulfilled Rome II criteria were recruited. The diagnosis was verified by a TCM herbalist using TCM criteria. Eligible patients were randomized to receive a standard preparation of TCM extracts that contained 11 herbs or placebo with similar appearance and taste for 8 wk after a 2-wk run-in period. Patients were followed up for an additional 8 wk post-treatment. Primary outcome was patient's global symptom assessment. Other outcome measures included individual IBS symptom scores and health-related quality of life (short form 36). RESULTS: One hundred nineteen patients were randomized: 60 to receive TCM and 59 to receive placebo. There was no significant difference in the proportion of patients with global symptom improvement between the TCM and placebo groups at week 8 (35% vs 44.1%, p = 0.38) and at week 16 (31.7% vs 33.9%, p = 0.62). Moreover, there was no difference in individual symptom scores and the quality-of-life assessment between the two groups at all time points. BACKGROUND: The use of this herbal formulation for diarrhea-predominant IBS did not lead to global symptom improvement. Further controlled clinical studies may be necessary to characterize the role of TCM in the management of IBS.

Chronic abdominal pain: not always irritable bowel syndrome.
Wildi SM, Gubler C, Fried M, Bauerfeind P, Hahnloser D
Dig Dis Sci. 2006 Jun;51(6):1049-51.

Sex differences in irritable bowel syndrome in Japanese university students.
Shiotani A, Miyanishi T, Takahashi T
J Gastroenterol. 2006 Jun;41(6):562-8.

BACKGROUND: Epidemiological studies of irritable bowel syndrome (IBS) among young adults are few, especially in Asian countries. Our aim was to examine the prevalence of IBS, whether there was a sex difference, and whether allergic diseases were important risk factors for IBS in young adults. METHODS: Newly enrolled university students completed health survey questionnaires regarding general health. Those with gastrointestinal symptoms completed the Gastrointestinal Symptom Rating Scale (GSRS) and an additional questionnaire covering the presence of allergic manifestations. IBS was diagnosed based on the Rome II criteria. RESULTS: IBS was diagnosed in 268 of 2495 students [10.7%; constipation-predominant type (IBS-C), 128; diarrhea-predominant type (IBS-D), 117; unclassified, 23]. IBS-C was associated with female sex (odds ratio, 6.4; 95% confidence interval, 4.1-9.7; P < 0.001), whereas there was no sex difference in IBS-D. The proportions of subjects with food sensitivity were significantly different among the three groups (4.0%, subjects without IBS; 8.6%, IBS-C group; and 15.4%, IBS-D group) (P < 0.001). The median GSRS scores for pain (1.67 vs 1, P = 0.001), indigestion (1.75 vs 1.5, P < 0.001), and constipation (2.0 vs 1.33, P < 0.001) were higher, and the median diarrhea score was lower (1.33 vs 1.67) (P < 0.001), in women than in men. The median score for diarrhea (2.33 vs 1.67, P = 0.001) was significantly higher in subjects with food sensitivity than in those without. CONCLUSIONS: There was a strong relationship between IBS-C and female sex, and food sensitivity seemed to be an exacerbating factor for IBS-D.

Therapeutic strategies for functional dyspepsia and the introduction of the Rome III classification.
Suzuki H, Nishizawa T, Hibi T
J Gastroenterol. 2006 Jun;41(6):513-23.

Although placebo response rates in clinical trials for functional dyspepsia (FD) are more than 30%, a recent meta-analysis based on randomized controlled trials (RCTs) showed that antisecretory drugs were more or less superior to placebos. On the other hand, large-scale RCTs on the efficacy of treatment with prokinetics on FD are still needed. Indications for antibiotic eradication therapy for Helicobacter pylori-positive FD are still controversial, but there seems to be a small but significant therapeutic gain achieved with H. pylori eradication. Since preprandial and postprandial symptomatic disturbances are very important targets for FD treatment, ghrelin, a novel appetite-promoting gastrointestinal peptide that also promotes gastric motility or basal acid secretion can be expected to be a therapeutic target. In the recently published Rome III classification, FD is redefined for patients with symptoms thought to originate from the gastroduodenal region, specifically epigastric pain or burning, postprandial fullness, or early satiation, and it is divided into the subcategories postprandial distress syndrome and epigastric pain syndrome. These new criteria are of value in clinical practice, for epidemiological, pathophysiological, and clinical research, and for the development of new therapeutic strategies.

June

Physicians' attitudes and practices in the evaluation and treatment of irritable bowel syndrome.
Lacy BE, Rosemore J, Robertson D, Corbin DA, Grau M, Crowell MD
Scand J Gastroenterol. 2006 Aug;41(8):892-902.

Objective. Irritable bowel syndrome (IBS) is a common disorder characterized by abdominal discomfort and disordered bowel habits. Despite the high prevalence of IBS, little is known about how physicians perceive this condition. The aims of our study were to measure physicians' understanding of IBS, to assess their attitudes towards patients with IBS, and to determine whether there are differences in the way Internal Medicine physicians (IM), Family Practice physicians (FP), and Gastroenterology physicians (GI) evaluate and treat IBS patients. Material and methods. A survey was sent to 3000 physicians nationwide, 1000 each to IM, FP, and GI. The survey contained 35 questions assessing demographics, the etiology and pathophysiology of IBS, the use of diagnostic tests, and practice patterns and attitudes. Results. Of the deliverable questionnaires, 501 were returned completed; 472 of the respondents interviewed only adult patients, representing the cohort for this analysis. The mean age of all respondents was 47; most were men (80%). IM and FP made a new diagnosis of IBS 1.3-1.6 times each week, while GI made a new diagnosis 5.4 times each week (p<0.0001). Compared with the perceptions of FP and IM, GI felt that IBS patients were less sick than other patients (p<0.001), although they required more time per visit. More GI compared with FP and IM stated that prior infection and a history of abuse were the causes of IBS (p<0.01), while FP were more likely to believe that diet was a cause of IBS (p<0.01). GI felt a new diagnosis of IBS could be made without further testing 42% of the time. FP and IM felt that one-third of IBS patients needed referral to a GI. Conclusions. The attitudes and practice patterns of physicians towards patients with IBS differ depending on practice specialty. This may be due to differences in training, the ability to perform specialized tests, and/or differences in referral patterns. Further training may improve the ability of physicians in all specialties confidently to diagnose and treat patients with IBS.

Enteroendocrine cell counts correlate with visceral hypersensitivity in patients with diarrhoea-predominant irritable bowel syndrome.
Park JH, Rhee PL, Kim G, Lee JH, Kim YH, Kim JJ, Rhee JC, Song SY
Neurogastroenterol Motil. 2006 Jul;18(7):539-46.

The objective of this study was to determine whether or not the number of enteroendocrine cells (ECs) in the gut is related to visceral hypersensitivity in patients with diarrhoea-predominant irritable bowel syndrome (D-IBS). Twenty-five subjects with D-IBS (mean, 43.1 years; 16 women, nine men) were recruited into our study, along with 13 healthy controls (mean, 40.7 years; nine women, four men). Maximally tolerable pressures were evaluated via barostat testing, and the levels of ECs were immunohistochemically identified and quantified via image analysis. The numbers of ECs between the D-IBS subjects and the controls were not significantly different in the terminal ileum, ascending colon and rectum. However, the maximally tolerable pressures determined in the D-IBS subjects were significantly lower than those of the control subjects (P < 0.01), and we detected a significant relationship between the maximally tolerable pressures and the numbers of ECs in the rectum (r = -0.37, P < 0.01). Rectal sensitivity was enhanced to a greater degree in D-IBS patients exhibiting an elevated level of rectal ECs. This study provides some evidence to suggest that ECs play an important role in visceral hypersensitivity.

Novel smooth muscle markers reveal abnormalities of the intestinal musculature in severe colorectal motility disorders.
Wedel T, Van Eys GJ, Waltregny D, Glenisson W, Castronovo V, Vanderwinden JM
Neurogastr oenterol Motil. 2006 Jul;18(7):526-38.

Histopathological studies of gastrointestinal motility disorders have mainly focused on enteric nerves and interstitial cells of Cajal, but rarely considered the enteric musculature. Here we used both classical and novel smooth muscle markers and transmission electron microscopy (TEM) to investigate muscular alterations in severe colorectal motility disorders. Full-thickness specimens from Hirschsprung's disease, idiopathic megacolon, slow-transit constipation and controls were stained with haematoxylin/eosin (HE) and Masson's trichrome (MT), incubated with antibodies against smooth muscle alpha-actin (alpha-SMA), smooth muscle myosin heavy chain (SMMHC), smoothelin (SM) and histone deacetylase 8 (HDAC8) and processed for TEM. Control specimens exhibited homogeneous immunoreactivity for all antibodies. Diseased specimens showed normal smooth muscle morphology by HE and MT. While anti-alpha-SMA staining was generally normal, immunoreactivity for SMMHC, HDAC8 and/or SM was either absent or focally lacking in Hirschsprung's disease (80%), idiopathic megacolon (75%) and slow-transit constipation (70%). Ultrastructurally, clusters of myocytes with noticeably decreased myofilaments were observed in all diseases. SMMHC and the novel smooth muscle markers SM and HDAC8 often display striking abnormalities linked to the smooth muscle contractile apparatus unnoticed by both routine stainings and alpha-SMA, suggesting specific defects of smooth muscle cells involved in the pathogenesis of gastrointestinal motility disorders.

Management of patients with chronic abdominal pain in clinical practice.
Camilleri M
Neurogastroenterol Motil. 2006 Jul;18(7):499-506.

A practical approach to the management of chronic abdominal pain is needed, given the high prevalence and impact of this problem. This article describes an approach that has evolved based on clinical experience and review of the literature: identifying predominant bloaters and abdominal wall pain; exclusion of organic disease, including consideration of laparoscopy for diagnosis; consideration of chronic functional abdominal pain and the first and second line pharmacotherapies; and seeking specialist care in a pain clinic, psychiatry, or behavioural therapy.

Neuroimmune signalling in the gut - mediators linked to disorders?
Vergnolle N
Neurogastroenterol Motil. 2006 Jul;18(7):497-8.

Mucosal barrier defects in irritable bowel syndrome. Who left the door open?
Barbara G
Am J Gastroenterol. 2006 Jun;101(6):1295-8.

There has been recent interest into the potential role of cellular and molecular mechanisms in the pathophysiology of irritable bowel syndrome (IBS). Although the intestinal mucosa of IBS patients is endoscopically and histologically "normal," it contains an increased number of activated T lymphocytes and mast cells, along with evidence of an increased release of mediators known to signal to epithelial, neuronal, and muscle cells leading to intestinal dysfunction. In this issue, Dunlop et al. provide evidence of increased intestinal permeability in patients with diarrhea predominant IBS. There is now consistent evidence indicating that mucosal barrier defects allow the passage of an increased load of luminal antigens of dietary and bacterial origin which, in turn, elicit the activation of mucosal immune responses involved in the generation of diarrhea. Further work has now to be done to better understand the interplay among luminal factors, epithelial cells, and mucosal immunocytes in the pathogenesis of IBS.

Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes.
Dunlop SP, Hebden J, Campbell E, Naesdal J, Olbe L, Perkins AC, Spiller RC
Am J Gastroenterol. 2006 Jun;101(6):1288-94.

OBJECTIVES: Irritable bowel syndrome (IBS) is a heterogeneous condition and defined according to symptoms. Low-grade inflammation has been associated with IBS, particularly that following infection, but whether altered intestinal permeability profiles relate to irritable bowel subtype or onset is uncertain. Our aim was to compare small and large intestinal permeability in various subtypes of IBS to healthy controls. METHODS: Intestinal permeability was measured using 1.8 MBq of 51Cr-EDTA and collecting urine over 24 h; Study 1: patients with diarrhea-predominant postinfectious IBS (N=15), constipation-predominant IBS (N=15), and healthy controls (N=15); Study 2: two groups of diarrhea-predominant IBS (D-IBS), one with a history of onset after acute gastroenteritis (postinfectious) (N=15) and the other without such a history (nonpostinfectious) (N=15) both compared with healthy controls (N=12). RESULTS: Permeability expressed as percentage of total dose excreted in urine (median [inter-quartile range]). Study 1: Proximal small intestinal permeability was increased in postinfectious IBS (0.19 [0.12-0.23]) in contrast to constipated IBS (0.085 [0.043-0.13]) and controls (0.07 [0.035-0.19]) (p=0.02). IBS patients with eczema, asthma, or hayfever had increased proximal small intestinal permeability compared with IBS patients without atopy (p=0.02). Study 2: Small intestinal permeability was greater in nonpostinfectious diarrhea-predominant IBS (0.84 [0.69-1.49]) compared with postinfectious IBS (0.43 [0.29-0.63], p=0.028) or controls (0.27 [0.2-0.39]), p=0.001). CONCLUSIONS: Small intestinal permeability is frequently abnormal in diarrhea-predominant IBS. Those without a history of infectious onset appear to have a more severe defect.

Relationship of Underlying Abnormalities in Rectal Sensitivity and Compliance to Distension with Symptoms in Irritable Bowel Syndrome.
Lee KJ, Kim JH, Cho SW
Digestion. 2006 Jun 22;73(2-3):133-141.

Background/Aims: Abnormalities in rectal physiology play an important role in the genesis of symptoms in irritable bowel syndrome (IBS). However, their relationship to symptoms is unclear. Our aim was to investigate the association of abnormalities in rectal sensitivity and compliance to specific symptoms in IBS. Methods: Fifty-six IBS patients and 14 healthy controls participated in this study. The intensities of individual IBS symptoms in the past 4 weeks were scored on a graded 5-point Likert scale. Using a barostat, isobaric rectal distensions were performed before and after a meal. Results: Rectal hypersensitivity and hypocompliance in the fasting state were observed in 68 and 52% of IBS patients, respectively. Postprandial hypersensitivity of the rectum was significantly more prevalent in the diarrhea-predominant IBS (D-IBS) group compared to the constipation-predominant IBS (C-IBS) group. The D-IBS group showed a significant postprandial decrease in rectal compliance, but the C-IBS group did not. A significant correlation was observed between a sense of incomplete evacuation and increased bowel movements with postprandial rectal hypersensitivity or hypocompliance. Conclusion: A sense of incomplete evacuation and increased bowel movements are related to postprandial abnormalities in rectal sensitivity and compliance to distension. The other IBS symptoms do not seem to predict such abnormalities.

Acupuncture for functional gastrointestinal disorders.
Takahashi T
J Gastroenterol. 2006 May;41(5):408-17.

Functional gastrointestinal (GI) symptoms are common in the general population. Especially, motor dysfunction of the GI tract and visceral hypersensitivity are important. Acupuncture has been used to treat GI symptoms in China for thousands of years. It is conceivable that acupuncture may be effective in patients with functional GI disorders because it has been shown to alter acid secretion, GI motility, and visceral pain. Acupuncture at the lower limbs (ST-36) causes muscle contractions via the somatoparasympathetic pathway, while at the upper abdomen (CV-12) it causes muscle relaxation via the somatosympathetic pathway. In some patients with gastroesophageal reflux disease (GERD) and functional dyspepsia (FD), peristalsis and gastric motility are impaired. The stimulatory effects of acupuncture at ST-36 on GI motility may be beneficial to patients with GERD or FD, as well as to those with constipation-predominant irritable bowel syndrome (IBS), who show delayed colonic transit. In contrast, the inhibitory effects of acupuncture at CV-12 on GI motility may be beneficial to patients with diarrhea-predominant IBS, because enhanced colonic motility and accelerated colonic transit are reported in such patients. Acupuncture at CV-12 may inhibit gastric acid secretion via the somatosympathetic pathway. Thus, acupuncture may be beneficial to GERD patients. The antiemetic effects of acupuncture at PC-6 (wrist) may be beneficial to patients with FD, whereas the antinociceptive effects of acupuncture at PC-6 and ST-36 may be beneficial to patients with visceral hypersensitivity. In the future, it is expected that acupuncture will be used in the treatment of patients with functional GI disorders.

May

Prevalence, comorbidity and impact of irritable bowel syndrome in Norway.
Vandvik PO, Lydersen S, Farup PG
Scand J Gastroenterol. 2006 Jun;41(6):650-6.

Objective. To study the prevalence of irritable bowel syndrome (IBS) and its comorbidity in a Norwegian adult population.Material and methods. In 2001, 11,078 inhabitants (aged 30-75 years) in Oppland County were invited to take part in a public health survey. A total of 4622 subjects (42%) completed the questionnaires on symptoms of IBS (Rome II criteria), comorbidity, health-care visits and medications. The impact of comorbidity on global health, working disability and use of health-care resources in subjects with IBS was explored by stepwise logistic regression.Results. The population prevalence of IBS was 388/4622 (8.4% (95% CI: 7.6-9.4%)) with a female predominance and an age-dependent decrease. The proportion who had consulted for IBS ranged from 51% among 30-year-olds to 79% in 75-year-olds (p=0.05). IBS was associated with musculoskeletal complaints (OR = 2.4-3.4 for six different items), fibromyalgia (OR = 3.6 [2.7-4.8]), mood disorder (OR = 3.3 (2.6-4.3)), reduced global health (OR = 2.6 (2.1-3.2)), working disability (OR = 1.6 (1.2-2.1)), more frequent health-care visits and use of medications (OR 1.7-2.3). When controlling for comorbidity, reduced global health (OR = 1.5 (1.1-2.0)) and use of alternative health care (OR = 1.7 (1.3-2.4)) remained associated with IBS. Severity of abdominal pain/discomfort was a predictor of having to seek a physician for IBS (OR = 1.3 (1.2-1.5)).Conclusions. Symptoms of IBS were reported by 8% of Norwegian adults and had resulted in consultations with physicians for the majority in the long run. Subjects with IBS in the community were characterized by frequent somatic and psychiatric comorbidity. Their observed reduced health, working disability and increased use of health resources were largely explained by comorbid symptoms and disorders.

Randomised double-blind placebo-controlled trial of aloe vera for irritable bowel syndrome.
Davis K, Philpott S, Kumar D, Mendall M
Int J Clin Pract. 2006 Jun 2;.

Aloe vera (AV) is suggested to be beneficial in treating irritable bowel syndrome (IBS) symptoms, but no scientific trials exist to confirm this. We aim to assess the efficacy of AV on IBS in refractory secondary care patients. Patients with IBS were randomised to receive AV or matching placebo for a month. Symptoms were assessed at baseline, 1 and 3 months. Fifty-eight patients randomised, 49 completed the protocol to 1 month and 41 to 3 months. Eleven of thirty-one (35%) AV patients, and 6 of 27 (22%) placebo patients responded at 1 month (p = 0.763). Diarrhoea predominant patients showed a trend towards a response to treatment at 1 month (10/23 V 2/14, p = 0.07). There was no evidence that AV benefits patients with IBS. However, we could not rule out the possibility that improvement occurred in patients with diarrhoea or alternating IBS whilst taking AV. Further investigations are warranted in patients with diarrhoea predominant IBS, in a less complex group of patients.

The Incidence of Irritable Bowel Syndrome Among Community Subjects With Previous Acute Enteric Infection.
Borgaonkar MR, Ford DC, Marshall JK, Churchill E, Collins SM
Dig Dis Sci. 2006 Jun 7;.

The purpose of this study was to determine the incidence of postinfectious irritable bowel syndrome (IBS) among community subjects with positive stool studies. This was a prospective cohort study whereby all individuals with stool-positive acute enteric infection (AEI) were recruited from 3 health regions in Ontario, Canada. Each person completed questionnaires regarding preinfectious bowel habit and their bowel habit 3 months postinfection. Manning and Rome I criteria were used to diagnose irritable bowel syndrome. Two hundred thirty-one patients participated. Forty had preexisting IBS and were excluded. Of the remaining 191 patients, 7 developed irritable bowel syndrome, for an incidence of 3.7% (95% confidence interval: 1.0-6.3%). Fever during AEI was the only identifiable risk factor for developing postinfectious IBS (odds ratio, 11.96; P = .02). The incidence of postinfectious IBS in community subjects is 3.7%. Fever during the AEI may be an important risk factor for this condition.

Quality of Life and Chronic Pain Four Years After Gastrointestinal Surgery.
Bruce J, Krukowski ZH
Dis Colon Rectum. 2006 Jun 2;.

PURPOSE: Little is known about the prevalence of chronic postsurgical pain after gastrointestinal surgery. This study was designed to assess the prevalence of chronic pain andquality of life in a cohort of patients who underwent surgery for benign and malignant gastrointestinal disease. METHODS: A prospective cohort design was used to assess quality of life and morbidity at four years postoperatively in435 patients who had upper, hepatopancreaticobiliary, small-bowel, and/or colorectal anastomotic surgery in 1999 at one regional center in Northeast Scotland. Chronic pain and quality of life were assessed by postal survey using the European Organization for Research and Treatment of Cancer Quality of Life-C30 questionnaire and McGill Pain Questionnaire. RESULTS: Of the 435 patients recruited in 1999, 135 (31 percent) had died by censor date in 2003. There was a 74 percent (n = 202) response rate from surviving patients eligible for follow-up. Prevalence of chronic pain at four years postoperatively was 18 percent (95 percent confidence interval, 13-23 percent). Pain was predominantly neuropathic in character; a subgroup reported moderate-to-severe pain. Risk factors for chronic postsurgical pain included female gender, younger age, and surgery for benign disease. Compared with those who were pain-free at follow-up, patients with chronic pain had poorer functioning, poorer global quality of life, and more severe symptoms, independent of age, gender, and cancer status. CONCLUSIONS: The prevalence of chronic pain after laparotomy for gastrointestinal malignancy and nonmalignant conditions at four years after surgery was 18 percent. These patients had significantly poorer quality of life scores independent of age, gender, and cancer status.

Repetitive rectal painful distention induces rectal hypersensitivity in patients with irritable bowel syndrome.
Nozu T, Kudaira M, Kitamori S, Uehara A
J Gastroenterol. 2006 Mar;41(3):217-22.

BACKGROUND: A reduced rectal perceptual threshold has been reported in patients with irritable bowel syndrome (IBS), but this phenomenon may be induced by a comorbid psychological state. We evaluated the rectal pain threshold at baseline and after conditioning (repetitive rectal painful distention: RRD) in patients with IBS or functional abdominal pain syndrome (FAPS), which is an abdominal pain disorder, and in healthy controls, and determined whether rectal hypersensitivity is a reliable marker for IBS. METHODS: The rectal sensory threshold was assessed by a barostat. First, a ramp distention of 40 ml/min was induced, and the threshold of pain and the maximum tolerable pressure (mmHg) were measured. Next, RRD (phasic distentions of 60-s duration separated by 30-s intervals) was given with a tracking method until the subjects had complained of pain six times. Finally, ramp distention was induced again, and the same parameters were measured. The normal value was defined by calculating the 95% confidence intervals of controls. RESULTS: Five or six of the seven IBS patients showed a reduced rectal pain threshold or maximum tolerable pressure, respectively, at baseline. In all patients with IBS, both thresholds were reduced after RRD load, but they were reduced in none of the patients with FAPS. RRD significantly reduced both thresholds in the IBS group (P < 0.05), but it had no effect in the control or FAPS groups. CONCLUSIONS: Rectal hypersensitivity induced by RRD may be a reliable marker for IBS. Conditioning-induced visceral hypersensitivity may play a pathophysiologic role in IBS.

The role of neurokinin 1 receptors in the maintenance of visceral hyperalgesia induced by repeated stress in rats.
Bradesi S, Kokkotou E, Simeonidis S, Patierno S, Ennes HS, Mittal Y, McRoberts JA, Ohning G, McLean P, Marvizon JC, Sternini C, Pothoulakis C, Mayer EA
Gastroenterology. 2006 May;130(6):1729-42.

BACKGROUND & AIMS: The neurokinin 1 receptors (NK(1)Rs) and substance P (SP) have been implicated in the stress and/or pain pathways involved in chronic pain conditions. Here we examined the participation of NK(1)Rs in sustained visceral hyperalgesia observed in rats exposed to chronic psychological stress. METHODS: Male Wistar rats were exposed to daily 1-hour water avoidance stress (WA) or sham WA for 10 consecutive days. We tested intraperitoneal or intrathecal injection of the NK(1)R antagonist SR140333 on the visceromotor reflex to colorectal distention in both groups at day 11. Real-time reverse-transcription polymerase chain reaction, Western blot, and immunohistochemistry were used to assess the expression of NK(1)Rs and/or SP in samples of colon, spinal cord, and dorsal root ganglia. RESULTS: Both intraperitoneal and intrathecal SR140333 injection diminished the enhanced visceromotor reflex to colorectal distention at day 11 in stressed rats but did not affect the response in control animals. Real-time polymerase chain reaction and Western blotting demonstrated stress-induced up-regulation of spinal NK(1)Rs. Immunohistochemistry showed an increased number of NK(1)R-expressing neurons in the laminae I of the dorsal horn in stressed rats. The expression of NK(1)Rs was decreased in colon from stressed rats compared with control. The expression of SP gene precursor in dorsal root ganglia was unchanged in stressed rats compared with controls. CONCLUSIONS: Stress-induced increased NK(1)R expression on spinal neurons and the inhibitory effect of intrathecal NK(1)R antagonist on visceral hyperalgesia support the key contribution of spinal NK(1)Rs in the molecular pathways involved in the maintenance of visceral hyperalgesia observed after chronic WA.

April

A Survey of Irritable Bowel Syndrome in Vietnam Using the Rome Criteria.
Zuckerman MJ, Nguyen G, Ho H, Nguyen L, Gregory GG
Dig Dis Sci. 2006 May 3;.

Prevalence estimates for irritable bowel syndrome from surveys in Western countries are 4.4% to 22%, generally higher in women than men, and only a minority seek health care. There are few studies of bowel patterns in Asian countries. We conducted a survey of a nonpatient population in Ho Chi Minh City, Vietnam, to determine bowel patterns and the prevalence of bowel dysfunction. A forced-choice, self-report questionnaire was distributed to 738 predominantly health care workers, as well as patient relatives, at Cho Ray Hospital in Ho Chi Minh City and returned by 411 (response rate of 55.7%). Results were analyzed for men and women using Student's t-test for continuous variables and chi-square test for categorical variables. Subjects were 53.6% female, with a mean age of 27.7+/-6.9 years. Overall perception of health was excellent/very good in 13.6%, good in 54.2%, and fair/poor in 32.1% (males, 17.1%, 51.3%, and 31.5%, vs. females, 10.6%, 56.7%, and 32.7%; P=NS). The mean number of stools reported per week was 6.5 (males, 6.6, vs. females, 6.4; P=NS) and ranged between 3 and 21 stools per week in 95.5%. The frequency of irritable bowel syndrome symptoms (using Rome I criteria) was 7.2% (95% CI=4.8-10.1), with males at 4.8% (95% CI=2.2-8.9) vs. females at 9.2% (95% CI=5.7-13.9) (P=0.08). Of the subjects with irritable bowel syndrome symptoms, 6 of 29 (20.7%) had seen a physician for bowel symptoms. There were no gender differences in reported infrequent stool (12.0%), frequent stool (11.3%), hard stool (17.5%), loose stool (6.5%), straining (14.5%), incomplete emptying (16.2%), bloating (15.0%), urgency (10.0%), or mucus (2.7%). In conclusion, this survey of a nonpatient population in Vietnam showed that irritable bowel syndrome symptoms as defined by Rome criteria were common and that there were no significant differences between sexes in either stool frequency or prevalence of irritable bowel syndrome, unlike previous studies from the United States. The prevalence of irritable bowel syndrome in Vietnam in this study was in the lower range of reported data from Western countries, possibly in part related to the use of the Rome criteria. Only a minority of subjects with irritable bowel syndrome symptoms reported seeking health care for these symptoms.

Visceral hypersensitivity in irritable bowel syndrome: a summary review.
Stacher G, Christensen J
Dig Dis Sci. 2006 Mar;51(3):440-5.

We examined published reports from 1970 to the present to evaluate the theory that abnormal visceral sensitivity characterizes the irritable bowel syndrome. Evidence to support claims that abnormal visceral sensitivity defines the irritable bowel syndrome falls short because of cognitive deficits in gastrointestinal neurobiology, limitations in experimental design and execution, and the interpretation of results.

Prevalence of irritable bowel syndrome and depression in fibromyalgia.
Kurland JE, Coyle WJ, Winkler A, Zable E
Dig Dis Sci. 2006 Mar;51(3):454-60.

The purpose of this study was to determine the point prevalence of depressive symptoms, using the PRIME-MD questionnaire, and irritable bowel syndrome (IBS), while comparing the Rome II to the Rome I criteria, in patients with fibromyalgia (FM) and rheumatologic controls in an outpatient setting. The prevalence of IBS in FM patients (n = 105) was 63% by Rome I and 81% by Rome II criteria. The prevalence of IBS in controls (n = 62) was 15% by Rome I and 24% by Rome II criteria (FM vs. control; P < 0.001). Depressive symptoms were met in 40% of FM patients and 8% of controls (P < 0.001). The coexistence of IBS and depressive symptoms in the FM patients was 31% (Rome I) and 34% (Rome II). The prevalence of IBS and depressive symptoms was higher in FM patients compared to the control population. Identification of IBS and depressive symptoms in FM patients might enable clinicians to better meet the needs of this patient population.

Prevalence, sociodemography, and quality of life of older versus younger patients with irritable bowel syndrome: a population-based study.
Minocha A, Johnson WD, Abell TL, Wigington WC
Dig Dis Sci. 2006 Mar;51(3):446-53.

We studied the prevalence as well as the sociodemographic characteristics and QOL of older adults (> 50 years) with irritable bowel syndrome (IBS) among the population at large and compared it to their younger counterparts'. We hypothesized that IBS is less prevalent among older persons and they suffer poorer QOL compared to younger IBS patients. A total of 1000 adults from nine sites, including a medical center, churches, and a blood bank in our metropolitan area (670 African Americans, 320 Caucasians, and 10 others), completed self-administered questionnaires providing sociodemographic information and details regarding bowel habits and associated symptoms for diagnosing the IBS based on Rome II criteria. QOL was assessed by the SF-12 questionnaire. The study database was divided into two groups, younger (< 50 years) and older (> or = 50 years). The two age groups were similar with respect to gender and household income. Ninety-five of the 1000 participants had IBS, giving a total sample prevalence of 9.5% (< 50 years, 9.9%, vs > or = 50 years, 7.6%). The prevalence of IBS was similar in the two groups irrespective of race, sex, marital status, size of household, location of residence (rural versus urban), level of educational status, and household income. Compared to the older group, there was a trend toward a higher prevalence of IBS among divorced subjects (12.7% vs 0%; P = 0.1) and those below poverty level of income (15.3% vs 7.5%; P = 0.09) in the younger subjects. In contrast, older IBS patients were more likely to attend church regularly (32.5% vs 58.8%; P < 0.05). There were no differences in history of traveler's diarrhea, food intolerance, and drug allergies between the two groups. Health care utilization was similar between the two IBS groups in terms of number of physician visits, use of prescription and alternative medications, and being disabled due to IBS. There was no difference in the overall QOL score means (27.8 vs 29.5; P = NS) or in its general health and physical functioning components. However, older IBS patients had better social functioning (9.1 vs 9.8; P < 0.05). Although in our study IBS occurred less frequently among older adults than among younger patients, the difference is not statistically significant. While IBS affects QOL at all ages, social functioning was actually better on average among older compared to younger IBS patients.

Recommendations for probiotic use.
Floch MH, Madsen KK, Jenkins DJ, Guandalini S, Katz JA, Onderdonk A, Walker WA, Fedorak RN, Camilleri M
J Clin Gastroenterol. 2006 Mar;40(3):275 -8.

Probiotics are live microbial organisms that are administrated as supplements or in foods to benefit the host. It is the recommendation that they may be helpful in the prevention and treatment of acute diarrhea in adults and children, the prevention of antibiotic-associated diarrhea in adults and children, and the maintenance of remission and prevention of pouchitis. Although early results indicate that probiotics may also be useful in immunologic modulation to prevent atopy, treatment of radiation intestinal disease, vaginosis, ulcerative colitis, and the irritable bowel syndrome, the studies available are not sufficient to say they are definitely helpful. Even fewer data are available to recommend probiotics for the treatment of H pylori and Crohn disease and for the prevention of cardiovascular risk factors or other degenerative diseases. Clearly, larger and better-designed studies of probiotics are necessary, including comparative and dose-ranging trials.

Probiotics and chronic disease.
Broekaert IJ, Walker WA
J Clin Gastroenterol. 2006 Mar;40(3):270-4.

In today's climate, changed lifestyles and the increased use of antibiotics are significant factors that affect the preservation of a healthy intestinal microflora. The concept of probiotics is to restore and maintain a microflora advantageous to the human body. Probiotics are found in a number of fermented dairy products, infant formula, and dietary supplements. Basic research on probiotics has suggested several modes of action beneficial for the human body and clinical research has proven its preventive and curative features in different intestinal and extraintestinal diseases. Chronic diseases cause considerable disablement in patients and represent a substantial economic burden on healthcare resources. Research has demonstrated a crucial role of nutrition in the prevention of chronic disease. Thus, positive, strain-specific effects of probiotics have been shown in diarrheal diseases, inflammatory bowel diseases, irritable bowel syndrome, and Helicobacter pylori-induced gastritis, and in atopic diseases and in the prevention of cancer. As the majority of probiotics naturally inhabit the human intestinal microflora, their use has been regarded as very safe. However, in view of the range of potential benefits on health that might be achieved by the use of some probiotic bacteria, major and thorough evaluation is still necessary. In conclusion, probiotics act as an adjuvant in the prevention and treatment of a wide variety of chronic diseases.

Probiotics and irritable bowel syndrome: rationale, putative mechanisms, and evidence of clinical efficacy.
Camilleri M
J Clin Gastroenterol. 2006 Mar;40(3):264-9.

The irritable bowel syndrome (IBS) follows an acute, presumably infectious diarrheal illness in approximately 15% of patients. There may be a persistent, mild inflammatory state with changes in mucosal function or structure. Changes in the colonic bacterial flora reported in IBS seem related to predominant bowel. Colonic bacteria normally metabolize nutrients with the formation of gas and short chain fatty acids. The latter may induce propulsive contractions and accelerate colonic transit or they may enhance fluid and sodium absorption in the colon. This review addresses the mechanisms, rationale and current evidence for the efficacy of probiotics, including Lactobacilli, Bifidobacteria, and VSL#3, in the treatment of IBS. The mechanisms influenced by probiotics include immune function, motility, and the intraluminal milieu. Probiotics may suppress the low-grade inflammation associated with IBS or restore normal local immune function. Lactobacilli and Bifidobacteria subspecies are able to deconjugate and absorb bile acids, potentially reducing the colonic mucosal secretion of mucin and fluids that may contribute to functional diarrhea or IBS with diarrhea. Therapeutic trials show the potential benefit of Bifidobacteria or Lactobacilli species alone or in the specific probiotic combination, VSL#3, on symptoms in IBS. Colonic transit was retarded in IBS patients treated with VSL#3 without induction of significant changes in bowel function. In summary, probiotics are promising therapies in IBS.

Probiotics in the treatment of inflammatory bowel disease.
Rioux KP, Fedorak RN
J Clin Gastroenterol. 2006 Mar;40(3):260-3.

The demonstration that immune and epithelial cells can discriminate between different microbial species has extended our understanding of the actions of probiotics beyond simple antimicrobial concepts. Several probiotic mechanisms of action, relative to inflammatory bowel disease, have been elucidated: (1) competitive exclusion, whereby probiotics compete with microbial pathogens; (2) immunomodulation and/or stimulation of an immune response; (3) antimicrobial activity and suppression of pathogen growth; (4) enhancement of barrier activity; and (5) induction of T cell apoptosis. The unraveling of these mechanisms of action has led to new support for the use of probiotics in the management of clinical inflammatory bowel disease. While level 1 evidence now supports the therapeutic use of some probiotics in the maintenance treatment of pouchitis, only level 2 and 3 evidence are currently available in support of the use of probiotics in the treatment of ulcerative colitis and Crohn's disease. Nevertheless, one significant and consistent finding has emerged over the course of research in the past year: not all probiotic bacteria have similar therapeutic effects. Rigorously designed, controlled clinical trials, to investigate the unresolved issues related to efficacy, dose, duration of use, single or multistrain formulation, and the concomitant use of prebiotics, synbiotics or antibiotics, are vital.

Probiotics for the prevention of antibiotic-associated diarrhea and Clostridium difficile diarrhea.
Katz JA
J Clin Gastroenterol. 2006 Mar;40(3):249-55.

Antibiotic-associated diarrhea is a common clinical problem occurring in up to 25% of patients, with diarrhea owing to Clostridium difficile accounting for up to a quarter of cases. The clinical and economic costs of antibiotic-associated diarrhea are significant and better treatments are needed. Probiotics may offer potential effective therapy for antibiotic-associated diarrhea by restoring intestinal microbial balance. A number of different probiotics have been evaluated in the prevention and treatment of antibiotic-associated diarrhea in adults and children, including the nonpathogenic yeast Saccharomyces boulardii and multiple lactic-acid fermenting bacteria such as Lactobacillus rhamnosus GG (LGG). A careful review of the literature supports the efficacy of S. boulardii in the prevention of antibiotic-associated diarrhea recurrent C. difficile infection in adults, whereas LGG is useful in the treatment of antibiotic-associated diarrhea in children. Not enough data exist to currently support the use of other probiotic preparations in these conditions. Although generally safe and well tolerated, both S. boulardii and LGG should be used cautiously in immunocompromised patients. Further study of probiotics, including large, well-designed, randomized controlled dose-ranging trials, comparative trials, and cost-benefit analyses are necessary.

Design of Treatment Trials for Functional Gastrointestinal Disorders.
Irvine EJ, Whitehead WE, Chey WD, Matsueda K, Shaw M, Talley NJ, Veldhuyzen van Zanten SJ
Gastroenterology. 2006 May;130(5):1538-1551.

This document addresses the design of trials to assess the efficacy of new treatments for functional gastrointestinal disorders (FGID), emphasizing trials in irritable bowel syndrome and dyspepsia, because most research has been undertaken in these conditions. The double-blind, randomized, placebo-controlled, parallel group trial remains the preferred design. Randomized withdrawal designs, although encouraged by the European Agency for the Evaluation of Medicinal Products, have the same potential disadvantages as a crossover design, including carryover effects, unmasking (unblinding), and overestimation of the potential benefit for clinical practice. Innovative trial designs that evaluate intermittent (on demand) treatment are likely to become more common in the future. Investigators should include as broad a spectrum of patients as possible and should report recruitment strategies, inclusion/exclusion criteria, and attrition data. The primary analysis should be based on the proportion of patients in each treatment arm who satisfy an a priori treatment responder definition, or a prespecified clinically meaningful change in a patient-reported symptom improvement measure. Such measures of improvement are psychometrically validated subjective global assessments or a change from baseline in a validated symptom severity questionnaire. It is unethical to change the responder definition after a trial begins. Data analysis should address all patients enrolled, using an intention-to-treat principle. Reporting of results should follow the Consolidated Standards for Reporting Trials guidelines and include an analysis of harms data and secondary outcome measures to support or explain the primary outcome. Trials should be registered in a public location, prior to initiation, and should be published even if the results are negative or inconclusive.

Childhood functional gastrointestinal disorders: child/adolescent.
Rasquin A, Di Lorenzo C, Forbes D, Guiraldes E, Hyams JS, Staiano A, Walker LS
Gastroenterology. 2006 May;130(5):1527-37.

The Rome II pediatric criteria for functional gastrointestinal disorders (FGIDs) were defined in 1999 to be used as diagnostic tools and to advance empirical research. In this document, the Rome III Committee aimed to update and revise the pediatric criteria. The decision-making process to define Rome III criteria for children aged 4-18 years consisted of arriving at a consensus based on clinical experience and review of the literature. Whenever possible, changes in the criteria were evidence based. Otherwise, clinical experience was used when deemed necessary. Few publications addressing Rome II criteria were available to guide the committee. The clinical entities addressed include (1) cyclic vomiting syndrome, rumination, and aerophagia; 2) abdominal pain-related FGIDs including functional dyspepsia, irritable bowel syndrome, abdominal migraine, and functional abdominal pain; and (3) functional constipation and non-retentive fecal incontinence. Adolescent rumination and functional constipation are newly defined for this age group, and the previously designated functional fecal retention is now included in functional constipation. Other notable changes from Rome II to Rome III criteria include the decrease from 3 to 2 months in required symptom duration for noncyclic disorders and the modification of the criteria for functional abdominal pain. The Rome III child and adolescent criteria represent an evolution from Rome II and should prove useful for both clinicians and researchers dealing with childhood FGIDs. The future availability of additional evidence-based data will likely continue to modify pediatric criteria for FGIDs.

Childhood functional gastrointestinal disorders: neonate/toddler.
Hyman PE, Milla PJ, Benninga MA, Davidson GP, Fleisher DF, Taminiau J
Gastroenterology. 2006 May;130(5):1519-26.

Recognizing the importance of childhood functional gastrointestinal disorders in understanding adult functional gastrointestinal disorders, and encouraging clinical and research interest, the Rome Coordinating Committee added a pediatric working team to Rome II in 1999. For Rome III, there was an increase from 1 to 2 pediatric working teams. This report summarizes the current consensus concerning functional disorders in infants and toddlers. Another report covers disorders diagnosed more often in school-aged children and adolescents. The symptoms from functional gastrointestinal disorders in children younger than 5 years depend on maturational factors in anatomy, gastrointestinal physiology, and intellectual and affective functioning. There has been little or no change for infant regurgitation, infant rumination syndrome, or infant dyschezia. Cyclic vomiting syndrome may be diagnosed after 2 rather than 3 episodes. The description of infant colic has been expanded, although there was consensus that infant colic does not reflect gastrointestinal malfunction. The greatest change was in functional constipation. Functional constipation and functional fecal retention in the 1999 report were merged into a single entity: functional constipation. Data-driven changes in diagnostic criteria for functional constipation appear to be less rigid and more inclusive than previous criteria.

Functional anorectal disorders.
Bharucha AE, Wald A, Enck P, Rao S
Gastroenterology. 2006 May;130(5) :1510-8.

This report defines criteria for diagnosing functional anorectal disorders (ie, fecal incontinence, anorectal pain, and disorders of defecation). Functional fecal incontinence is defined as the uncontrolled passage of fecal material recurring for >/=3 months in an individual with a developmental age of >/=4 years that is associated with: (1) abnormal functioning of normally innervated and structurally intact muscles, and/or (2) no or minor abnormalities of sphincter structure and/or innervation insufficient to explain fecal incontinence, and/or (3) normal or disordered bowel habits (ie, fecal retention or diarrhea), and/or (4) psychological causes. However, conditions wherein structural and/or neurogenic abnormalities explain the symptom, or are part of a generalized process (eg, diabetic neuropathy) are not included within functional fecal incontinence. Functional fecal incontinence is a common, but underrecognized symptom, which is equally prevalent in men and women, and can often cause considerable distress. The clinical features are useful for guiding diagnostic testing and therapy. Functional anorectal pain syndromes include proctalgia fugax (fleeting pain) and chronic proctalgia; chronic proctalgia may be subdivided into levator ani syndrome and unspecified anorectal pain, which are defined by arbitrary clinical criteria. Functional defecation disorders are characterized by 2 or more symptoms of constipation, with >/=2 of the following features during defecation: impaired evacuation, inappropriate contraction of the pelvic floor muscles, and inadequate propulsive forces. Functional disorders of defecation may be amenable to pelvic floor retraining by biofeedback therapy (such as dyssynergic defecation).

Functional abdominal pain syndrome.
Clouse RE, Mayer EA, Aziz Q, Drossman DA, Dumitrascu DL, Monnikes H, Naliboff BD
Gastroenterology. 2006 May;130(5):1492- 7.

Functional abdominal pain syndrome (FAPS) differs from the other functional bowel disorders; it is less common, symptoms largely are unrelated to food intake and defecation, and it has higher comorbidity with psychiatric disorders. The etiology and pathophysiology are incompletely understood. Because FAPS likely represents a heterogenous group of disorders, peripheral neuropathic pain mechanisms, alterations in endogenous pain modulation systems, or both may be involved in any one patient. The diagnosis of FAPS is made on the basis of positive symptom criteria and a longstanding history of symptoms; in the absence of alarm symptoms, an extensive diagnostic evaluation is not required. Management is based on a therapeutic physician-patient relationship and empirical treatment algorithms using various classes of centrally acting drugs, including antidepressants and anticonvulsants. The choice, dose, and combination of drugs are influenced by psychiatric comorbidities. Psychological treatment options include psychotherapy, relaxation techniques, and hypnosis. Refractory FAPS patients may benefit from a multidisciplinary pain clinic approach.

Functional bowel disorders.
Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC
Gastroenterology. 2006 May;13 0(5):1480-91.

Employing a consensus approach, our working team critically considered the available evidence and multinational expert criticism, revised the Rome II diagnostic criteria for the functional bowel disorders, and updated diagnosis and treatment recommendations. Diagnosis of a functional bowel disorder (FBD) requires characteristic symptoms during the last 3 months and onset >/=6 months ago. Alarm symptoms suggest the possibility of structural disease, but do not necessarily negate a diagnosis of an FBD. Irritable bowel syndrome (IBS), functional bloating, functional constipation, and functional diarrhea are best identified by symptom-based approaches. Subtyping of IBS is controversial, and we suggest it be based on stool form, which can be aided by use of the Bristol Stool Form Scale. Diagnostic testing should be guided by the patient's age, primary symptom characteristics, and other clinical and laboratory features. Treatment of FBDs is based on an individualized evaluation, explanation, and reassurance. Alterations in diet, drug treatment aimed at predominant symptoms, and psychotherapy may be beneficial.

Functional gastroduodenal disorders.
Tack J, Talley NJ, Camilleri M, Holtmann G, Hu P, Malagelada JR, Stanghellini V
Gastroenterology. 2006 May;130(5):1466-79.

Functional esophageal disorders.
Galmiche JP, Clouse RE, Balint A, Cook IJ, Kahrilas PJ, Paterson WG, Smout AJ
Gastroenterology. 2006 May;130(5):1459-65.

Gender, Age, Society, Culture, and the Patient's Perspective in the Functional Gastrointestinal Disorders.
Chang L, Toner BB, Fukudo S, Guthrie E, Locke GR, Norton NJ, Sperber AD
Gastroenterology. 2006 May;130(5):1435-1446.

Patients with functional gastrointestinal disorders (FGID) often experience emotional distress, a perceived lack of validation, and an unsatisfactory experience with health care providers. A health care provider can provide the patient with a framework in which to understand and legitimize their symptoms, remove self-doubt or blame, and identify factors that contribute to symptoms that the patient can influence or control. This framework can be strengthened with the consideration of various important factors that impact FGID but are often overlooked. These include gender, age, society, culture, and the patient's perspective. There is evidence for sex- and gender-related differences in FGID, particularly irritable bowel syndrome (IBS). Whereas the majority of FGID, including IBS, bloating, constipation, chronic functional abdominal pain, and pelvic floor dysfunction, are more prevalent in women than men, functional esophageal and gastroduodenal disorders do not appear to vary by gender. Limited studies suggest that sex differences in visceral perception, cardioautonomic responses, gastrointestinal motility, and brain activation patterns to visceral stimuli exist in IBS. Gender differences in social factors, psychological symptoms, and response to psychological treatments have not been adequately studied. However, there appears to be a greater clinical response to serotonergic agents developed for IBS in women compared to men. The impact of social and cultural factors on the meaning, expression, and course of FGID are important. The prevalence of IBS appears to be lower in non-Western than Western countries. Although further studies are needed, the existing literature suggests that they are important to consider from both research and clinical perspectives.

Pharmacological and pharmacokinetic aspects of functional gastrointestinal disorders.
Camilleri M, Bueno L, de Ponti F, Fioramonti J, Lydiard RB, Tack J
Gastroenterology. 2006 May;130(5):1421-34.

Medications are commonly used for the treatment of patients with functional gastrointestinal disorders. The general goal of this report is to review the pharmacokinetics and pharmacology of medications used in functional gastrointestinal disorders. Methods included literature review, consensus evaluation of the evidence for each topic assigned originally to 1 or 2 authors, and broader review at a harmonization session as part of the Rome III process. This report reviews the animal models that have been validated for the study of effects of pharmacologic agents on sensation and motility; the preclinical pharmacology, pharmacokinetics, and toxicology usually required for introduction of novel therapeutic agents; the biomarkers validated for studies of sensation and motility end points with experimental medications in humans; the pharmacogenomics applied to these medications and disorders; and the pharmacology of agents that are applied or have potential for treatment of functional gastrointestinal disorders, including psychopharmacologic agents. Clinician and basic investigators involved in the treatment or investigation of functional gastrointestinal disorders or disease models need to have a comprehensive understanding of a vast range of medications. It is anticipated that the interaction between investigators of basic science, basic and applied pharmacology, and clinical trials will lead to better treatment of these disorders.

Probiotics prevent bacterial translocation and improve intestinal barrier function in rats following chronic psychological stress.
Zareie M, Johnson-Henry KC, Jury J, Yang PC, Ngan BY, McKay DM, Soderholm JD, Perdue MH, Sherman PM
Gut. 2006 Apr 25;.

Chronic psychological stress, including water avoidance stress (WAS), induces intestinal mucosal barrier dysfunction and impairs mucosal defenses against luminal bacteria. The aim of this study was to determine the ability of a defined probiotic regimen to prevent WAS- induced intestinal pathophysiology. Male rats were submitted to either WAS or sham stress for 1 h/day on 10 consecutive days. Additional animals received 7 days of Lactobacillus acidophilus and L. rhamnosus in the drinking water prior to stress and remained on these probiotics for the duration of the study. Rats were then sacrificed, intestinal segments assessed in Ussing chambers, and mesenteric lymph nodes cultured to determine bacterial translocation. All animals remained healthy for the duration of the study. Chronic WAS induced excess ion secretion (elevated baseline short- circuit current) and barrier dysfunction (increased conductance) in both the ileum and colon, associated with increased bacterial adhesion and penetration into surface epithelial cells. Approximately 70% of rats subjected to WAS had bacterial translocation to mesenteric lymph nodes, while there was no bacterial translocation in controls. Probiotic pretreatment alone had no effect on intestinal barrier function. However, WAS-induced increased ileal short circuit current was reduced with probiotics, whereas there was no impact on altered conductance. Pretreatment of animals with probiotics also completely abrogated WAS-induced bacterial adhesion and prevented translocation of bacteria to mesenteric lymph nodes. These findings indicate that probiotics can prevent chronic stress-induced intestinal abnormalities and, thereby, exert beneficial effects in the intestinal tract.

The Functional Gastrointestinal Disorders and the Rome III Process.
Drossman DA
Gastroenterology. 2006 May;130(5):1377-90.

The road to Rome.
Thompson WG
Gastroenterology. 2006 May;130(5):1552-6.

Digestive Disease Week and the 107th Annual Meeting of the American Gastroenterological Association Institute, May 20-25, 2006, Los Angeles, California, USA. Abstracts.
Gastroenterology. 2006 Apr;130(4 Suppl 2):A1-911.

March

Measuring health-related quality of life in patients with irritable bowel syndrome: can less be more?
Lackner JM, Gudleski GD, Zack MM, Katz LA, Powell C, Krasner S, Holmes E, Dorscheimer K
Psychosom Med. 2006 Mar-Apr;68(2):312-20.

OBJECTIVE: This study assessed the ability of a brief, well-validated generic health-related quality of life (HRQOL) measure to characterize the symptom burden of patients with irritable bowel syndrome (IBS) with reference to a large survey of U.S. community-living adults. METHODS: One hundred four Rome II diagnosed patients with IBS completed measures of pain, psychological dysfunction (neuroticism, somatization, distress, abuse), and HRQOL (SF-36, IBS-QOL, CDC HRQOL-4) during baseline assessment of a National Institutes of Health-funded clinical trial. The four-item CDC HRQOL-4 assesses global health and the number of days in the past 30 days resulting from poor physical health, poor mental health, and activity limitation. RESULTS: Patients with IBS averaged 15 of 30 days with poor physical or mental health. These average overall unhealthy days exceeded those of respondents with arthritis, diabetes, heart disease/stroke, cancer, and class III obesity (body mass index > or =40 kg/m2) from the U.S. survey. Fifteen percent of patients identified musculoskeletal disorders, not IBS symptoms, as the major cause of their activity limitation. Overall unhealthy days among patients with IBS varied directly with IBS symptom severity, abuse, pain, and psychological distress. Controlling for personality variables that influence perception and reporting HRQOL did not diminish the statistical significance of associations between the CDC HRQOL-4 and other study measures. CONCLUSIONS: The CDC HRQOL-4 is a psychometrically sound, rapid, and efficient instrument whose HRQOL profile reflects the symptom burden of moderate-to-severe IBS, is sensitive to treatment effects associated with cognitive behavior therapy, and is not a proxy for personality variables identified as potential confounders of HRQOL. HRQOL is related to but not redundant with psychological distress.

Quality of life of patients with irritable bowel syndrome is low compared to others with chronic diseases.
Ten Berg MJ, Goettsch WG, van den Boom G, Smout AJ, Herings RM
Eur J Gastroenterol Hepatol. 2006 May;18(5):475-81.

BACKGROUND: Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal dysmotility disorder. This study aimed to estimate the burden of illness of a Dutch population of community dwelling patients suffering from IBS. METHODS: Patients identified at community pharmacies, using mebeverine as a proxy for IBS, were administered a questionnaire regarding (1) the Rome II criteria for IBS, (2) predominant type of stool during complaints, (3) severity of symptoms (abdominal pain and discomfort), (4) generic and disease-specific quality of life, (5) current health status (utilities), and (6) loss of productivity. RESULTS: Three hundred and seventy-five users of mebeverine were identified of which 169 patients met the Rome II criteria for IBS, and were included in the study. More than half (58%) of the IBS patients reported severe abdominal pain and complaints. Generic and disease-specific quality of life outcomes showed impairment on all dimensions. Current health status in IBS patients, calculated on the basis of the EQ-5D VAS, was perceived on 62% of full health (95% CI, 60-66%). A calculation of health status in these patients based on the SF-6D algorithm showed a comparable score of 0.67 (1 is full health; 95% CI, 0.65-0.68). The loss in productivity of IBS patients was 1.8 days (95% CI, 1.1-2.5) per month. CONCLUSIONS: This study confirmed that the burden of illness of IBS in the Netherlands is substantial. IBS patients treated with mebeverine experienced low quality of life and suffered from severe pain. Based on these results, more attention for the diagnosis and treatment of IBS seems to be justified.

February

Perception of Electrocutaneous Stimuli in Irritable Bowel Syndrome.
Iovino P, Tremolaterra F, Consalvo D, Sabbatini F, Mazzacca G, Ciacci C
Am J Gastroenterol. 2006 Feb 8;.

BACKGROUND AND AIM: Irritable bowel syndrome (IBS) and fibromyalgia syndrome (FMS) are common conditions with some similarities, but different perceptual responses to somatic and visceral stimuli. The purpose of this study was to assess in a large group of IBS patients the somatic perception by transcutaneous electrical nerve stimulation (TENS) and its relation to the level of severity and presence of FMS. METHODS: In 99 patients grouped by the validated functional bowel disorder severity index (FBDSI) in mild, moderate, and severe IBS and in 33 healthy controls (HC), we studied discomfort thresholds and perception of somatic stimuli at control (hands and elbows) and active (trapezius) sites by TENS and by using a specific questionnaire. RESULTS: The use of TENS showed that IBS showed significant higher thresholds and lower perception cumulative score compared to HC. The severity of IBS is significantly associated with age and mean control site values for discomfort and borderline associated with gender in the ordinal model constructed for the ascending series protocol. The severity of IBS is also significantly associated with the active cumulative perception score in the long stimulus protocol. Due to limited sample size of IBS men with FMS, analyses of discomfort thresholds and cumulative perception score by FMS were done only for women. IBS women without FMS had significantly higher mean control site values for discomfort and significantly lower active cumulative perception score than HC. IBS women with FMS had significantly lower mean active site values for discomfort thresholds than IBS women without FMS (Dunn's test p < 0.05). CONCLUSIONS: IBS patients showed somatic hypoalgesia to electrical stimuli. The severity of IBS and the presence of FMS influence the perception of somatic stimuli induced by TENS.

Proximal and distal gut hormone secretion in irritable bowel syndrome.
Van Der Veek PP, Biemond I, Masclee AA
Scand J Gastroenterol. 2006 Feb;41(2):170-7.

OBJECTIVE: Sensory and motor dysfunctions of the gut are both important characteristics of irritable bowel syndrome (IBS). Several gut peptides contribute to the regulation of gastrointestinal function but little is known about gut hormone secretion in IBS. MATERIAL AND METHODS: We evaluated perceptual thresholds and fasting and postprandial plasma levels of proximal (cholecystokinin (CCK), motilin) and distal (peptide YY) gut peptides up to 1 h after ingestion of a high caloric meal in 99 IBS patients and 40 age- and gender-matched healthy controls. RESULTS: Fasting plasma CCK levels were significantly elevated in patients (1.2+/-0.8 pM) compared with those in controls (0.8+/-0.7 pM, p=0.006), as was the incremental postprandial CCK response (72+/-73 versus 40+/-42 pM.60 min, respectively; p=0.003). No differences in fasting and postprandial motilin or PYY levels were found. The postprandial PYY response was significantly increased in hypersensitive compared to normosensitive patients (215+/-135 versus 162+/-169 pM, p=0.048). Patients with a diarrhoea predominant bowel habit had higher fasting motilin levels compared to constipated patients or alternating type IBS patients (82.1+/-36.5 versus 60.8+/-25.1 versus 57.5+/-23.9 pM, one-way ANOVA p=0.003). CONCLUSIONS: IBS patients have increased fasting and postprandial plasma levels of CCK. Changes in plasma levels of motilin and PYY may contribute to the clinical expression of IBS, such as the presence of visceral hypersensitivity or a predominant bowel habit.

Women and irritable bowel syndrome: Is the gain in pain mainly in the brain?
Gangula PR, Pasricha PJ
J Gastroenterol Hepatol. 2006 Feb;21(2):343-4.

Gender-related differences in visceral perception in health and irritable bowel syndrome.
Kim HS, Rhee PL, Park J, Lee JH, Kim YH, Kim JJ, Rhee JC
J Gastroenterol Hepatol. 2006 Feb;21(2):468-73.

Background: Irritable bowel syndrome (IBS) is more common in female subjects, and IBS patients generally exhibit reduced pain thresholds to rectal distension. The aim of the present paper was to determine gender-related differences in rectal perception in both healthy controls and IBS patients. Methods: Fifty-nine IBS patients (age 20-65 years; mean, 39.2 years; 31 women, 28 men) with symptoms that fulfilled Rome-II criteria and 21 healthy controls (age 25-58 years; mean, 37.8 years; 11 women, 10 men) were recruited. Participants completed a questionnaire regarding bowel symptoms and psychological distress, and maximal tolerable pressures were evaluated via barostat tests. Results: Although healthy women appear to have lower perception thresholds than men, significant gender differences in pain sensitivity were not detected (P > 0.05). In addition, female patients with IBS also exhibited no enhanced colorectal perception, as compared with male IBS patients (P > 0.05). Conclusions: No gender differences in visceral perception were determined to exist between the healthy controls and the IBS patients. Therefore, the increased prevalence of IBS in women may be related to another set of pathophysiological factors, and not to gender-related differences in visceroperception.

Pharmacological treatment of the irritable bowel syndrome and other functional bowel disorders.
Mearin F
Digestion. 2006;73 Suppl 1:28-37. Epub 2006 Feb 8.

Functional digestive disorders constitute one of the main causes of consultation in gastroenterology and primary health care. Is still unclear whether therapy has to be aimed to the gut, to the neural pathways controlling bowel motility and perception, or to the processing mechanisms of symptoms and disease behaviour. It is conceivable that in the next future better understanding of functional bowel disorders pathophysiology will help us to tailor treatment for different patients. At the moment, subclassification of the diverse patterns of symptomatology allows to adjust new treatments for irritable bowel syndrome (IBS) according to the clinical predominance for each patient. The knowledge of motor and sensorial response to different stimuli in IBS patients and the pathways to the central nervous system is an important source of information for the development of new molecules. Fiber-enriched diet is frequently given for constipation-predominant IBS. Loperamide, antispasmodic drugs and tricyclic antidepressants are nowadays the basis for pharmacological treatment of diarrhea- predominant IBS. The scientific evidence supporting this therapeutical approach is however limited. Visceral analgesics and serotonin agonists and antagonists may play an important therapeutical role in the near future. However, it is not likely that one single treatment will help every functional bowel disorder patient and many of them will need a more complex approach with a multidisciplinary therapy (diet, psychotherapy, medications).

Treatment of functional bowel disorders: is there room for antibiotics?
Corazza GR, Di Stefano M, Scarpignato C
Digestion. 2006;73 Suppl 1:38-46. Epub 2006 Feb 8.

Small bowel bacterial overgrowth is a syndrome associated with a broad range of predisposing conditions, characterized by the presence of pathological amounts or types of bacteria at the level of the small bowel, clinically evident with a spectrum of symptoms such as diarrhea, flatulence, abdominal pain and bloating. Some of these symptoms are very common complaints in patients suffering from functional bowel disorders (FBDs). Although the pathophysiological mechanisms responsible for FBDs are certainly multifactorial and not yet completely understood, several pieces of evidence suggest that an increased metabolic activity of intestinal bacteria is responsible for gas-related intestinal symptoms in a large subgroup of patients. In addition, byproducts of colonic fermentation might be able to trigger symptoms in those patients displaying visceral hypersensitivity. Targeting enteric bacteria with antibiotics therefore represents a logical approach to FBDs. Although systemic antimicrobials have been mostly used in the past, the availability of poorly absorbed antibiotics like rifaximin, being safe and effective, has represented a step forward in the treatment of this challenging clinical condition.

January

Brain imaging in IBS: drawing the line between cognitive and non-cognitive processes.
Naliboff BD, Mayer EA
Gastroenterology. 2006 Jan;130(1):267-70.

Altered 5-hydroxytryptamine signaling in patients with constipation- and diarrhea-predominant irritable bowel syndrome.
Atkinson W, Lockhart S, Whorwell PJ, Keevil B, Houghton LA
Gastroenterology. 2006 Jan;130(1):34-43.

BACKGROUND & AIMS: Evidence suggests that postprandial platelet-depleted plasma 5-hydroxytryptamine (5-HT) concentrations may be abnormal in irritable bowel syndrome (IBS). However, interpretation of the data has been hampered by the variable methodology and rather small numbers used in previous studies. Therefore, the aim of this study was to measure concentrations of platelet-depleted plasma 5-HT and its metabolite 5-HIAA under fasting and fed conditions in a large group of patients with diarrhea-predominant (d-) and constipation-predominant (c-) IBS, compared with controls. The ratio of plasma 5-HIAA:5-HT and platelet stores was also assessed. METHODS: Twenty-nine c-IBS patients (aged, 19-53 years), 55 d-IBS patients (aged, 19-52 years), and 35 healthy volunteers (aged, 18-46 years) had platelet-depleted plasma 5-HT/5-HIAA concentrations measured using reverse-phase, high-performance liquid chromatography with fluorimetric detection before and after a standard meal. RESULTS: d-IBS patients had raised platelet-depleted plasma 5-HT concentrations under fasting and fed conditions (P < .05). However, the postprandial relative to fasting concentration was similar to controls. In contrast, c-IBS patients failed to show an increase in platelet-depleted plasma 5-HT concentration with meal ingestion compared with controls (P < .01). c-IBS was associated with decreased 5-HIAA (P < .01) but normal 5-HIAA:5-HT ratio and d-IBS with normal 5-HIAA concentrations but reduced 5-HIAA:5-HT ratio (P < .005). C-IBS but not d-IBS patients had increased platelet 5-HT. CONCLUSIONS: These results support the concept that d-IBS is characterized by reduced 5-HT reuptake, whereas impaired release may be a feature of c-IBS. These results also provide a rational basis for current pharmacologic approaches involving modulation of different 5-HT receptors in c- and d-IBS.

Novel evidence for hypersensitivity of visceral sensory neural circuitry in irritable bowel syndrome patients.
Lawal A, Kern M, Sidhu H, Hofmann C, Shaker R
Gastroenterology. 2006 Jan;130(1):26-33.

BACKGROUND & AIMS: Visceral hypersensitivity in irritable bowel syndrome (IBS) patients has been documented by evaluation of perceived stimulations that can reflect abnormalities of both sensory neurocircuitry and cognitive processes. The presence of actual neurohypersensitivity in human beings has not been documented separately. Because subliminal stimulations are free from the influence of stimulus-related cognitive processes, functional magnetic resonance imaging (fMRI) cortical response to these stimuli can be considered a measure of activity of the neural circuitry alone. The aim of this study was to compare quantitatively the cerebral cortical fMRI activity response to equal subliminal stimulations between IBS patients and age-matched controls. METHODS: We studied 10 IBS patients and 10 healthy controls using a computerized barostat-controlled rectal distention device. fMRI activity volume and percent maximum signal intensity change for equal subliminal distention pressures were compared between controls and patients. RESULTS: Three levels of subliminal distention pressures (eg, 10, 15, and 20 mm Hg), were represented in both controls and patients and were analyzed for fMRI response. In all 3 distention levels the fMRI activity volume in IBS patients was significantly larger than age- and sex-matched controls (P < .05). The percent maximum signal intensity change was similar between IBS patients and controls. CONCLUSIONS: The volume of cerebral cortical activity response to equal subliminal distention pressures in IBS patients is significantly larger than in controls, documenting the existence of hypersensitivity of the neural circuitry in this patient group irrespective of stimulus-related cognitive processes.

A randomized double-blind placebo-controlled trial of rifaximin in patients with abdominal bloating and flatulence.
Sharara AI, Aoun E, Abdul-Baki H, Mounzer R, Sidani S, Elhajj I
Am J Gastroenterol. 2006 Feb;101(2):326-33.

AIMS: To study the efficacy of rifaximin, a nonabsorbable antibiotic, in relieving chronic functional symptoms of bloating and flatulence. METHODS: Randomized double-blind placebo-controlled trial consisting of three 10-day phases: baseline (phase 1), treatment with rifaximin 400 mg b.i.d. or placebo (phase 2), and post-treatment period (phase 3). Primary efficacy variable was subjective global symptom relief at the end of each phase. A symptom score was calculated from a symptom diary. Lactulose H(2)-breath test (LHBT) was performed at baseline and end of study. RESULTS: One hundred and twenty-four patients were enrolled (63 rifaximin and 61 placebo). Baseline characteristics were comparable and none had an abnormal baseline LHBT. Rome II criteria were met in 58.7% and 54.1%, respectively. At the end of phase 2, there was a significant difference in global symptom relief with rifaximin versus placebo (41.3%vs 22.9%, p= 0.03). This improvement was maintained at the end of phase 3 (28.6%vs 11.5%, p= 0.02). Mean cumulative and bloating-specific scores dropped significantly in the rifaximin group (p <0.05). Among patients with IBS, a favorable response to rifaximin was noted (40.5%vs 18.2%; p= 0.04) persisting by the end of phase 3 (27%vs 9.1%; p= 0.05). H(2)-breath excretion dropped significantly among rifaximin responders and correlated with improvement in bloating and overall symptom scores (p= 0.01). No adverse events were reported. CONCLUSIONS: Rifaximin is a safe and effective treatment for abdominal bloating and flatulence, including in IBS patients. Symptom improvement correlates with reduction in H(2)-breath excretion. Future trials are needed to examine the efficacy of long-term or cyclic rifaximin in functional colonic disorders.

Contribution of IBD5 Locus to Clinical Features of IBD Patients.
Latiano A, Palmieri O, Valvano RM, D'Inca R, Vecchi M, Ferraris A, Sturniolo GC, Spina L, Lombardi G, Dallapiccola B, Andriulli A, Devoto M, Annese V
Am J Gastroenterol. 2006 Feb;101(2):318-25.

AIM: The aim of this study was to investigate the influence of the IBD5 locus on clinical features of inflammatory bowel disease (IBD) patients, and its possible interaction with the CARD15 gene. PATIENTS AND METHODS: A cohort of 1,199 IBD patients (570 with CD and 629 with ulcerative colitis [UC]), and 357 healthy subjects were investigated. Information on clinical features was fully available for 855 IBD patients. Two SNPs in the IBD5 locus (IGR2198a_1 and IGR2096a_1) and the three major variants of CARD15 gene were genotyped in patients and controls. RESULTS: Homozygous carriers of risk alleles were significantly more frequent in CD (22.6% for IGR2198a_1, OR = 1.6, p= 0.015; 21.9% for IGR2096a_1, OR = 1.6, p= 0.012) compared to controls (16.8% and 15.7%, respectively). The homozygote frequency was also increased in UC patients, but not significantly. No significant gene-gene interaction was detected between IBD5 and CARD15. A univariate analysis detected association between IBD5 and steno/fistulizing behavior in CD patients (OR = 1.9; p= 0.004), and presence of more extensive colitis in UC patients (OR = 1.7; p= 0.01). Results from multiple logistic regression, after correction for covariates, showed that the influence of IBD5 on clinical outcome of CD was completely masked by that of CARD15, while the influence on more extensive colitis in UC patients was confirmed. CONCLUSIONS: Our study shows that presence of the IBD5 risk alleles, particularly in the homozygous state, is associated with IBD and especially with CD, without a significant epistasis with CARD15. The contribution of CARD15 risk alleles to CD clinical features is prominent on that of IBD5.

Abdominal pain impacts quality of life in women with irritable bowel syndrome.
Cain KC, Headstrom P, Jarrett ME, Motzer SA, Park H, Burr RL, Surawicz CM, Heitkemper MM
Am J Gastroenterol. 2006 Jan;101(1):124-32.

OBJECTIVES: Patients with irritable bowel syndrome (IBS) report lower health-related quality of life (QoL) as compared to healthy controls. The aims of this analysis were to describe which IBS symptoms were rated on a daily diary as most distressing/severe by IBS women, and determine which IBS symptoms were most predictive of lower QoL and have the greatest impact on daily life. METHODS: This report is a secondary analysis of prospective and retrospective symptom severity and impact data, collected on 242 women with IBS, aged 18-48, who were studied between 1997 and 2004. RESULTS: On the daily diary, intestinal gas was the most frequent IBS symptom with subjects reporting at least minimal intestinal gas on 74% of days and moderate or worse severity on 27% of days. Abdominal pain occurred at least minimally on 62% of days. Diarrhea was the least common. Across women, abdominal pain was most strongly related to life impact variables and QoL, followed by intestinal gas and bloating. Analysis of day-to-day variation within women showed that abdominal pain was most strongly correlated with daily life impact variables and constipation had the weakest correlation. While diarrhea had a lower correlation with life impact, this was due to the low prevalence of diarrhea. When it occurs, diarrhea has a large impact. Partial correlation analysis showed that the impact of diarrhea is independent of abdominal pain. CONCLUSION: Abdominal pain is the most disruptive IBS symptom. Diarrhea also has an independent and significant impact when it occurs, especially in those with diarrhea-predominant IBS. (Am J Gastroenterol 2006;101:124-132).

Racial differences in epidemiology of irritable bowel syndrome alone, un-investigated dyspepsia alone, and "overlap syndrome" among african americans compared to Caucasians: a population-based study.
Minocha A, Chad W, Do W, Johnson WD
Dig Dis Sci. 2006 Jan;51(1):218-26.

There is A paucity of data on racial differences in epidemiology of irritable bowel syndrome (IBS) alone and un-investigated dyspepsia (UD) alone compared to "overlap syndrome" (OS). We conducted a random survey (n = 990). Subjects completed a questionnaire which included Rome II criteria for IBS and functional dyspepsia (FD). Among African Americans, the prevalence of IBS alone, UD alone, and OS was 0.6%, 17%, and 7.3%, respectively. It was 0%, 13%, and 13% among Caucasian Americans. All but four patients with IBS had UD. Among patients with UD, OS was seen in 30% of African Americans, compared to 50% among Caucasian Americans. Among African Americans, UD patients were younger compared to OS patients. African Americans with UD were more likely than OS patients to have children. Marital status, education, and household income were not a factor among Caucasians. African Americans patients below poverty level were more likely to have UD than OS (22% vs 10%). Considering patients with UD alone, race, age, sex, marital status, number of children, education, and income level were not different between African Americans and Caucasians. Compared to African Americans, Caucasians with OS were likely to be married and live in an urban area. There was a higher prevalence of OS among Caucasians with lower education. OS is 2.5 times more likely to occur among Caucasians compared to African Americans. We conclude that OS is more common among Caucasians than African Americans. IBS and OS are virtually synonymous.

Recurrent abdominal pain: what determines medical consulting behavior?
Venepalli NK, Van Tilburg MA, Whitehead WE
Dig Dis Sci. 2006 Jan;51(1):192-201.

Recurrent abdominal pain (RAP) is associated with increased health care visits and school absences. In adults suffering from functional pain, psychosocial factors determine illness behavior and we aimed to investigate its role among children. A community sample of 40 RAP consulters, 41 RAP nonconsulters, and 36 pain-free controls and their mothers completed questionnaires on GI and non-GI symptoms, school absences, psychological symptoms, coping, self-esteem, and behavioral and cognitive responses to RAP. T-tests showed significant differences between RAP and controls in (1) GI and non-GI symptoms and school absences, (2) child distress and passive coping, and (3) mother's IBS severity, somatization, and fears about RAP. RAP consulters reported the same levels of GI symptoms and psychological distress as nonconsulters but missed significantly more school and their mothers reported more fears about RAP. Severity of symptoms and psychological distress did not predict consulting behavior. Only maternal fears about abdominal symptoms differentiated consulters from nonconsulters.

The incidence of abdominal and pelvic surgery among patients with irritable bowel syndrome.
Cole JA, Yeaw JM, Cutone JA, Kuo B, Huang Z, Earnest DL, Walker AM
Dig Dis Sci. 2005 Dec;50(12):2268-75.

Rates of abdominopelvic surgery, with a particular focus on gallbladder procedures, were measured in patients with irritable bowel syndrome (IBS) (n = 108,936) and compared with those in a general population sample (n = 223,082). The patient sample was selected from persons who were members of a managed care organization during the years 1995-2000. Medical records from a randomly selected subset of IBS patients were reviewed to confirm the diagnosis. Crude and standardized rates and adjusted rate ratios for surgery were calculated. The incidence of abdominopelvic surgery, excluding gallbladder procedures, was 87% higher in patients with IBS than that for the general population. The incidence of gallbladder surgery was threefold higher in IBS patients than the general population. Patients with IBS have an increased risk for abdominopelvic and gallbladder surgery and, thus, an associated risk for experiencing morbidity and mortality associated with these surgical procedures.

A controlled cross-over study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome.
Tack J, Broekaert D, Fischler B, Van Oudenhove L, Gevers A, Janssens J
Gut. 2006 Jan 9;.

INTRODUCTION: Selective Serotonin Reuptake Inhibitors (SSRIs) are frequently used in the treatment of irritable bowel syndrome (IBS), although evidence of their efficacy is scarce. AIM: Twenty three non-depressed IBS patients were recruited from a tertiary care center and included in a crossover trial comparing 6 weeks treatment with the SSRI citalopram (3 weeks 20 mg, 3 weeks 40 mg) with placebo. IBS symptom severity was the primary outcome measure, and depression and anxiety scores were also measured. The effect of acute administration of citalopram on colonic sensitivity and on colonic response to feeding was investigated as a putative predictor of symptomatic response to the drug. RESULTS: After 3 and 6 weeks treatment, citalopram significantly improved abdominal pain, bloating, impact of symptoms on daily life and overall well-being, compared to placebo. There was only a modest effect on stool pattern. Changes in depression or anxiety scores were not related to symptom improvement. The effect of acute administration of citalopram during a colonic barostat study did not predict clinical outcome. Analysis of the first treatment period as a double-blind parallel- arm study confirmed the benefit of citalopram over placebo. CONCLUSIONS: The SSRI citalopram significantly improves IBS symptoms including abdominal pain, compared to placebo. The therapeutic effect is independent of effects on anxiety, depression and colonic sensorimotor funciton.

Local anesthesia in anal surgery: a simple, safe procedure.
Argov S, Levandovsky O
Am J Surg. 2006 Jan;191(1):111-3.

A symptom-based approach to making a positive diagnosis of irritable bowel syndrome with constipation.
Malagelada JR
Int J Clin Pract. 2006 Jan;60(1):57-63.

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder. Characterised by abdominal pain or discomfort, bloating and altered bowel habit, IBS is a chronic recurring condition, typically affecting up to 15% of the Western population, IBS can be subclassified into IBS with constipation (IBS-C), IBS with diarrhoea (IBS-D), or IBS with alternating constipation or diarrhoea symptoms (IBS-A). Conventional clinical diagnosis focuses on excluding all potential organic causes of patient symptoms. However, a positive diagnosis of IBS may be established using published criteria such as the Manning and/or Rome criteria. While these methods are useful to identify patients with IBS who are suitable for enrollment into clinical trials, the criteria are relatively complex and not readily applicable to general practice. In this review we present an 'identify, eliminate, probe' algorithm that may be appropriate to establish a positive diagnosis of patients with IBS-C, as symptoms characteristic of patients in this IBS subgroup are least likely to be confused with symptoms reflecting serious organic disease.

Possible role of nitric oxide in visceral hypersensitivity in patients with irritable bowel syndrome.
Kuiken SD, Klooker TK, Tytgat GN, Lei A, Boeckxstaens GE
Neurogastroenterol Motil. 2006 Feb;18(2):115-22.

Background: Visceral hypersensitivity is a consistent finding in a considerable proportion of patients with irritable bowel syndrome (IBS), and may provide a physiological basis for the development of IBS symptoms. In this study, we aimed to confirm the hypothesis that nitric oxide (NO) is involved in maintaining visceral hypersensitivity in IBS. Ten healthy volunteers (HV) and 12 IBS patients with documented hypersensitivity to rectal distension underwent a rectal barostat study. The effect of placebo and the specific NO synthase inhibitor N(G)-monomethyl-l-arginine (l-NMMA) on resting volume, rectal sensitivity to distension and rectal compliance was evaluated in a double-blind, randomized, cross-over fashion. N(G)-monomethyl-l-arginine did not alter resting volumes in HV or IBS patients. In HV, l-NMMA did not alter rectal sensory thresholds compared to placebo (45 +/- 3 and 46 +/- 3 mmHg, respectively). In contrast, l-NMMA significantly increased the threshold for discomfort/pain in IBS patients (placebo: 18 +/- 2, l-NMMA: 21 +/- 3 mmHg, P < 0.05). Rectal compliance was not affected by l-NMMA. Although NO does not seem to play a major role in normal rectal sensation or tone, we provide evidence that NO may be involved in the pathophysiology of visceral hypersensitivity in IBS.

Ultrasound examination of the sigmoid colon: possible new diagnostic tool for irritable bowel syndrome.
Crade M, Pham V
Ultrasound Obstet Gynecol. 2006 Feb;27(2):206-9.

BJECTIVE: Irritable bowel syndrome (IBS) affects about 10% of the population, and is primarily a disease of women. It may cause chronic pelvic pain. As yet there is no imaging test to aid in diagnosis, which relies upon history. We aimed to determine whether transvaginal sonographic investigation of the sigmoid colon could aid in the diagnosis of IBS. METHOD: Transvaginal ultrasound was used in 175 female patients undergoing pelvic ultrasound studies for a variety of reasons, none specifically for bowel complaints. We measured the wall of the sigmoid colon and then obtained the history of positive or negative for IBS. RESULTS: The majority of those 27 reporting a history of IBS had thickening of the wall of the sigmoid colon. A cut-off of 3.0 mm gave a sensitivity for this group of patients of 70%, specificity of 95%, positive predictive value of 73% and negative predictive value of 95%. CONCLUSION: Transvaginal ultrasound may be useful in identifying patients at risk for IBS. Consideration of colon wall measurement during pelvic ultrasound should be studied, as IBS may be a cause of chronic pelvic pain. Copyright (c) 2006 ISUOG. Published by John Wiley & Sons, Ltd.

Assessment of visceral pain-related pseudo-affective responses to colorectal distension in mice by intracolonic manometric recordings.
Arvidsson S, Larsson M, Larsson H, Lindstrom E, Martinez V
J Pain. 2006 Feb;7(2):108-18.

Recently, a new manometric method has been proposed to quantify visceromotor responses (VMR) to colorectal distension (CRD) in rats. This method is based on monitoring pressure changes within the distending balloon during CRD. This study assesses the applicability of such a technique to the quantification of VMRs to CRD in mice. Electrical activity of the abdominal muscles and pressure changes within the distending balloon (mechanical response) were simultaneously recorded in conscious mice during CRD (phasic ascending, 10-80 mm Hg, or repetitive, 55 mm Hg). There was a clear stimulus-response relationship with a strong correlation between electrical and mechanical responses during the ascending (r(2) = 0.899, n = 7) or repetitive phasic CRD (r(2) = 0.926, n = 8). Repetitive phasic distensions (55 mm Hg) increased the mechanical and electrical responses by 71 +/- 20% and 42 +/- 16%, respectively (pulses 10-12 vs. 1-3; n = 8, both P < .01). Atropine (0.5 or 1 mg/kg, subcutaneously) did not affect the mechanical response to CRD. The mu-opioid agonist, fentanyl (0.05 mg/kg, subcutaneously), completely prevented the sensitizing response associated to repetitive distensions. These results show that noninvasive, surgery-free manometry of intracolonic pressure is a reliable method to assess VMRs to CRD in mice. The analgesic effect of compounds could be determined, indicating that the method can be used in pharmacologic studies. PERSPECTIVE: The model presented to assess visceral pain in mice allows a broad use of this species in pharmacological studies and will be of use in the characterization of potential targets and new drugs for the treatment of human pathologies with visceral pain arising from the gut as a significant component.

Role of partially hydrolyzed guar gum in the treatment of irritable bowel syndrome.
Giannini EG, Mansi C, Dulbecco P, Savarino V
Nutrition. 2006 Jan 12;.

Irritable bowel syndrome (IBS) is the world's most common gastrointestinal functional disorder and is associated with a several social and economic costs. Health-related quality of life is often impaired in patients with IBS. The pathophysiologic mechanisms underlying IBS remain poorly defined. The therapeutic approach to patients with IBS is based on symptoms, and fibers may play an important role in treatment. Among the various types of fiber, water-soluble, non-gelling fibers seem to be a promising option for treatment of IBS. Partially hydrolyzed guar gum (PHGG) is a water-soluble, non-gelling fiber that has provided therapeutic benefits. In clinical trials, PHGG decreased symptoms in constipation-predominant and diarrhea-predominant forms of IBS and decreased abdominal pain. Further, an improvement in quality of life was observed in patients with IBS during and after treatment with PHGG. Moreover, PHGG seems to have prebiotic properties because it increases the colonic contents of short-chain fatty acids, Lactobacilli, and Bifidobacteria.

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