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1.  Complementary and alternative medicine for treatment of irritable bowel syndrome 
Canadian Family Physician  2009;55(2):143-148.
Abstract
OBJECTIVE
To review the evidence supporting selected complementary and alternative medicine approaches used in the treatment of irritable bowel syndrome (IBS).
QUALITY OF EVIDENCE
MEDLINE (from January 1966), EMBASE (from January 1980), and the Cochrane Database of Systematic Reviews were searched until March 2008, combining the terms irritable bowel syndrome or irritable colon with complementary therapies, alternative medicine, acupuncture, fiber, peppermint oil, herbal, traditional, yoga, massage, meditation, mind, relaxation, probiotic, hypnotherapy, psychotherapy, cognitive therapy, or behavior therapy. Results were screened to include only clinical trials, systematic reviews, and meta-analyses. Level I evidence was available for most interventions.
MAIN MESSAGE
Soluble fibre improves constipation and global IBS symptoms. Peppermint oil alleviates IBS symptoms, including abdominal pain. Probiotic trials show overall benefit for IBS but there is little evidence supporting the use of any specific strain. Hypnotherapy and cognitive-behavioural therapy are also effective therapeutic options for appropriate patients. Certain herbal formulas are supported by limited evidence, but safety is a potential concern. All interventions are supported by systematic reviews or meta-analyses.
CONCLUSION
Several complementary and alternative therapies can be recommended as part of an evidence-based approach to the treatment of IBS; these might provide patients with satisfactory relief and improve the therapeutic alliance.
PMCID: PMC2642499  PMID: 19221071
2.  Pharmacologic and Complementary and Alternative Medicine Therapies for Irritable Bowel Syndrome 
Gut and Liver  2011;5(3):253-266.
Irritable bowel syndrome (IBS) is a chronic functional gastrointestinal disorder characterized by episodic abdominal pain or discomfort in association with altered bowel habits (diarrhea and/or constipation). Other gastrointestinal symptoms, such as bloating and flatulence, are also common. A variety of factors are believed to play a role in the development of IBS symptoms, including altered bowel motility, visceral hypersensitivity, psychosocial stressors, altered brain-gut interactions, immune activation/low grade inflammation, alterations in the gut microbiome, and genetic factors. In the absence of biomarkers that can distinguish between IBS subgroups on the basis of pathophysiology, treatment of this condition is predicated upon a patient's most bothersome symptoms. In clinical trials, effective therapies have only offered a therapeutic gain over placebos of 7-15%. Evidence based therapies for the global symptoms of constipation predominant IBS (IBS-C) include lubiprostone and tegaserod; evidence based therapies for the global symptoms of diarrhea predominant IBS (IBS-D) include the probiotic Bifidobacter infantis, the nonabsorbable antibiotic rifaximin, and alosetron. Additionally, there is persuasive evidence to suggest that selected antispasmodics and antidepressants are of benefit for the treatment of abdominal pain in IBS patients. Finally, several emerging therapies with novel mechanisms of action are in development. Complementary and alternative medicine therapies including probiotics, herbal therapies and acupuncture are gaining popularity among IBS sufferers, although concerns regarding manufacturing standards and the paucity of high quality efficacy and safety data remain.
doi:10.5009/gnl.2011.5.3.253
PMCID: PMC3166664  PMID: 21927652
Serotonin; Chloride secretogogues; Antibiotics; Antidepressants; Probiotics
3.  P05.03. Integrative Primary Care Approach to Irritable Bowel Syndrome 
Focus Area: Integrative Approaches to Care
Irritable bowel syndrome (IBS) is thought to affect 5% to 10% of the population and is likely a constellation of disorders resulting in abdominal pain, diarrhea, and/or constipation. This presentation will review the scientific evidence for common integrative treatments. A comprehensive integrative history often elucidates underlying factors contributing to symptoms. Assessment of the foundations of health, as with most conditions, is important for IBS. In addition to nutrition, physical activity, sleep, stress management, and mental/spiritual health will be reviewed. There will be a specific mention of mind-body pain syndrome and its manifestations of abdominal pain. A review of available testing will discuss utility in pursuing laboratory confirmation of food allergy/intolerances. Dietary interventions address food intolerances and poor dietary choices. Elimination diets, including specific approaches such as the FODMAP diet, can result in dramatic symptom relief. Soluble fiber has been shown to be helpful; in contrast, adding insoluble fiber can exacerbate symptoms in some individuals. Probiotics have been studied widely and are recommended to help re-establish favorable gut flora. Strains, dosing, and duration will be addressed. Peppermint oil can address bloating. Other common supplements and botanicals for IBS will be reviewed. Treatments of stress reduction, cognitive behavioral therapy, and hypnosis have been evaluated for this condition and will be discussed.
doi:10.7453/gahmj.2013.097CP.P05.03
PMCID: PMC3875059
4.  A randomized trial of yoga for adolescents with irritable bowel syndrome 
BACKGROUND:
Adolescents with irritable bowel syndrome (IBS) frequently experience interference with everyday activities. Mind-body approaches such as yoga have been recommended as interventions for patients with IBS. Despite promising results among adult samples, there have been limited studies exploring the efficacy of yoga with pediatric patients.
OBJECTIVE:
To conduct a preliminary randomized study of yoga as treatment for adolescents with IBS.
METHODS:
Twenty-five adolescents aged 11 to 18 years with IBS were randomly assigned to either a yoga or wait list control group. Before the intervention, both groups completed questionnaires assessing gastrointestinal symptoms, pain, functional disability, coping, anxiety and depression. The yoga intervention consisted of a 1 h instructional session, demonstration and practice, followed by four weeks of daily home practice guided by a video. After four weeks, adolescents repeated the baseline questionnaires. The wait list control group then received the yoga intervention and four weeks later completed an additional set of questionnaires.
RESULTS:
Adolescents in the yoga group reported lower levels of functional disability, less use of emotion-focused avoidance and lower anxiety following the intervention than adolescents in the control group. When the pre- and postintervention data for the two groups were combined, adolescents had significantly lower scores for gastrointestinal symptoms and emotion-focused avoidance following the yoga intervention. Adolescents found the yoga to be helpful and indicated they would continue to use it to manage their IBS.
CONCLUSIONS:
Yoga holds promise as an intervention for adolescents with IBS.
PMCID: PMC2673138  PMID: 17149454
Adolescents; Irritable bowel syndrome (IBS); Mind-body; Recurrent abdominal pain; Yoga
5.  Towards positive diagnosis of the irritable bowel. 
British Medical Journal  1978;2(6138):653-654.
A questionnaire to establish the presence of 15 symptoms thought to be typical of the irritable bowel syndrome (IBS) was given to 109 unselected patients referred to gastroenterology or surgery clinics with abdominal pain or a change in bowel habit or both. Review of case records 17--26 months later established a definite diagnosis of IBS in 32 patients and of organic disease in 33. Four symptoms were significantly more common among patients with IBS--namely, distension, relief of pain with bowel movement, and looser and more frequent bowel movements with the onset of pain. Mucus and a sensation of incomplete evacuation were also common in these patients. The more of these symptoms that were present the more likely was it that the patient's pain or altered bowel habit, or both, was due to IBS. We conclude that a careful history can increase diagnostic confidence and reduce the amount of investigation in many patients with chronic abdominal pain.
PMCID: PMC1607467  PMID: 698649
6.  Optimizing outcomes with alosetron hydrochloride in severe diarrhea-predominant irritable bowel syndrome 
Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder that causes a range of symptoms. Currently, alosetron hydrochloride (Lotronex®), a selective serotonin type 3 receptor antagonist, is the only medication approved for the treatment of severe diarrhea-predominant irritable bowel syndrome (IBS-D) in women who have inadequately responded to conventional therapy. Alosetron has demonstrated efficacy compared with placebo in clinical trials and has been shown to improve overall health-related quality of life (HRQoL). However, rare instances of ischemic colitis and severe complications of constipation have been reported. As a result, in 2000 alosetron was voluntarily withdrawn from the market but was reintroduced in 2002 with a more restricted indication and a requirement that clinicians and patients follow a prescribing program. Although the efficacy and benefit of alosetron has been clearly demonstrated, it has been used sparingly since its reintroduction. This brief review describes the history of alosetron, efficacy of alosetron in the treatment of IBS, the impact of severe IBS on HRQoL, safety considerations, the risk evaluation and mitigation strategy program under which alosetron is now prescribed, and an update on postmarketing surveillance data.
doi:10.1177/1756283X10362277
PMCID: PMC3002579  PMID: 21180598
Irritable bowel syndrome; diarrhea; 5-HT3 antagonist; alosetron
7.  Autonomic nervous system activity in constipation-predominant irritable bowel syndrome patients 
Summary
Background
The main mechanism underlying irritable bowel syndrome is currently believed to be a dysfunction of the brain-gut axis. Autonomic nervous system dysfunction can contribute to development of irritable bowel syndrome symptoms by disturbing visceral sensations.
Material/Methods
Thirty patients with a diagnosis of constipation-predominant irritable bowel syndrome and 30 healthy volunteers were included in the study. Resting and functional autonomic nervous system tests and percutaneous electrogastrography were performed. Plasma adrenalin, noradrenalin, insulin, ghrelin and cholecystokinin activity was analyzed.
Results
Increased sympathetic activation with disturbed parasympathetic function was demonstrated. Patients had substantially higher plasma catecholamine concentration, which confirms sympathetic overbalance. Hyperinsulinemia may explain sympathetic predominance followed by gastric and intestinal motility deceleration. Abnormal, reduced ghrelin and cholecystokinin titre may disturb brain-gut axis functioning and may be responsible for gastric motility deceleration. In electrogastrography, distinctly lower values of fasting normogastria percentage and dominant power were observed. Patients had substantially lower slow wave coupling percentage both in fasting and postprandial periods, which negatively correlated with plasma catecholamines level. Gastric myoelectrical activity disturbances may result from lack of sympatho-parasympathetic equilibrium.
Conclusions
Central sympathetic influence within the brain-gut axis is most probably responsible for myoelectrical activity disturbances in irritable bowel syndrome patients.
doi:10.12659/MSM.883269
PMCID: PMC3560712  PMID: 22847198
irritable bowel syndrome; autonomic nervous system activity; heart rate variability; gastric myoelectric activity; electrogastrography
8.  Partial Agonism of 5-HT3 Receptors: A Novel Approach to the Symptomatic Treatment of IBS-D 
ACS Chemical Neuroscience  2012;4(1):43-47.
Irritable bowel syndrome (IBS) is a functional bowel disorder characterized by abdominal pain, discomfort, and altered bowel habits, which have a significant impact on quality of life for approximately 10–20% of the population. IBS can be divided into three main types IBS-D (diarrhea predominant), IBS-C (constipation predominant), and mixed or alternating IBS. 5-HT3 receptor antagonism has proved to be an efficacious treatment option for IBS-D. For example, alosetron displays efficacy in the treatment of multiple symptoms, including abdominal pain, discomfort, urgency, stool frequency and consistency. However, significant constipation occurred in approximately 25% of patients, leading to withdrawal of up to 10% of patients in clinical trials. Targeting compounds with partial agonist activity at the 5-HT3 receptor represents a mechanistic departure from the classic 5-HT3 receptor antagonist approach and should result in agents that are applicable to a broader array of IBS patient populations. Attenuation of the activity of the ion channel without completely abolishing its function may control or normalize bowel function without leading to a total block associated with severe constipation. We have identified a new class of selective, orally active 5-HT3 receptor ligands with high 5-HT3 receptor affinity and low partial agonist activity currently in preclinical development that should offer a significant advantage over existing therapies.
doi:10.1021/cn300166c
PMCID: PMC3548414  PMID: 23342199
5-HT3 receptor; partial agonist; irritable bowel syndrome; IBS
9.  Presacral schwannoma treated as irritable bowel syndrome 
BMJ Case Reports  2010;2010:bcr0520102972.
Presacral tumours represent a heterogeneous group of predominantly benign and occasionally malignant neoplasms. These tumours, though rare, frequently present either incidentally or with vague symptoms. Schwannomas of the presacral region are one variant described as benign tumours of neurogenic origin. The case of a large presacral schwannoma in a 26-year-old man, who was treated for irritable bowel syndrome for 4 years, is presented. The patient presented with intermittent constipation, a feeling of incomplete evacuation of the bowel and vague abdominal discomfort relieved by defecation. The symptomatology worsened and constipation became frequent, and the patient experienced increased urinary frequency. Baseline investigations were normal and ultrasonography of the abdomen revealed a pelvic mass, which on CT scanning was revealed to be a large retrorectal mass. The tumour was resected and histology revealed it to be a schwannoma. This unique case is presented to emphasise that irritable bowel syndrome must be a diagnosis of exclusion, especially if atypical symptoms are present.
doi:10.1136/bcr.05.2010.2972
PMCID: PMC3038043  PMID: 22791578
10.  Constipation-Predominant Irritable Bowel Syndrome Associated to Hyperprolactinemia 
Case Reports in Gastroenterology  2011;5(3):523-527.
Irritable bowel syndrome (IBS) is considered to be a physical disorder that mainly affects the bowel and is clinically characterized by lower abdominal pain or discomfort, diarrhea, constipation (or alternating diarrhea/constipation), gas, bloating, and nausea. According to recent studies, it appears that there is an association with increased prolactin levels in patients suffering from IBS. We report a rare case of regression of IBS symptoms (constipation type) in a 16-year-old female adolescent after receiving cabergoline for treating hyperprolactinemia due to pituitary macroadenoma. Our hypothesis is that increased prolactin levels, for instance due to a pituitary adenoma, may suppress prolactin-releasing peptide release and lead to a reverse feedback interaction, consequently resulting in oversecretion of cholecystokinin, inducing the development of IBS.
doi:10.1159/000331806
PMCID: PMC3214685  PMID: 22087083
Prolactin; Cholecystokinin; Irritable bowel syndrome; Constipation
11.  Irritable bowel syndrome in the general population. 
BMJ : British Medical Journal  1992;304(6819):87-90.
OBJECTIVE--To determine the prevalence of symptoms compatible with a clinical diagnosis of irritable bowel syndrome in the general population. DESIGN--Validated postal questionnaire sent to 2280 subjects randomly selected in 10 year age bands from the lists of eight general practitioners. The Manning criteria were used to define irritable bowel syndrome. SETTING--Urban population in Southampton and mixed urban-rural population in Andover, Hampshire. RESULTS--A response of 71% yielded 1620 questionnaires for analysis, of which 412 (25%) reported more than six episodes of abdominal pain in the preceding year, with 350 (22%) reporting symptoms consistent with the diagnosis of irritable bowel syndrome. The male: female ratio was 1:1.38. More subjects with irritable bowel syndrome had constipation and diarrhoea and 35% with the syndrome reported rectal bleeding compared with an overall prevalence of 20%. Other symptoms and conditions including heartburn, dyspepsia, flushing, palpitations, migraine, and urinary symptoms were significantly more common in the group with irritable bowel syndrome. Abdominal pain in childhood was more common in the subjects with irritable bowel syndrome (12%) than without (3%). One third of the group with irritable bowel syndrome had sought medical advice during the study period (male:female ratio 1:1.21); consultation behaviour was influenced by age and the presence of associated symptoms, varied considerably among patients registered with different general practitioners, and was poorly correlated with symptom severity. CONCLUSION--Symptoms consistent with a diagnosis of irritable bowel syndrome are present in almost one quarter of the general population and tend to be associated with a number of other complaints and conditions, some of which may reflect smooth muscle dysfunction.
PMCID: PMC1880997  PMID: 1737146
12.  Hyperimmune egg powder for the treatment of irritable bowel syndrome: A case series 
Abstract
Objective
To demonstrate the benefits of a hyperimmune egg powder supplement for treating irritable bowel syndrome in 2 patients.
Clinical Features
The first patient, not under chiropractic care, had been diagnosed with irritable bowel syndrome by her primary care physician. She sought care due to failure of several other alternative therapies. Her primary care physician ordered specific dietary modifications, yet this regimen did not appear to improve her symptoms. The second patient, also diagnosed with irritable bowel syndrome by her primary care physician, decided to seek care because the attending physician was concurrently treating her for idiopathic scoliosis, and both treatments could be administered at 1 office visit. Her primary reason for seeking this treatment was her longstanding episodic intestinal cramping and diarrhea. She overheard another patient in the same clinic discussing how the hyperimmune egg powder had alleviated her digestive complaints and decided to undergo a 2-week trial of the hyperimmune egg powder.
Intervention and Outcome
The first subject was given a 31- day supply of the hyperimmune egg powder. She reported significant subjective improvement in frequency of defecation and stool consistency after 48 hours. She kept a daily journal to monitor her bowel habits during the trial period. The second subject was provided a 15-day supply of hyperimmune egg powder and instructed to keep the same daily journal to monitor her bowel habits. During the second week of the trial, she noticed less frequent bowel habits and a more solid stool consistency. However, shortly after she stopped taking the hyperimmune egg powder, the pre-trial symptoms returned. Because of this, she was put back on the hyperimmune egg powder, and the symptoms improved thereafter.
Conclusion
The addition of hyperimmune egg powder into an ordinary daily diet may have improved bowel function in 2 subjects, at least subjectively. However, it is unclear whether the subjective improvements are due to the hyperimmune egg powder or any psychosomatic effect created by physician contact, regardless of treatment type. This study should be repeated on a larger scale with a control group before any conclusions are made.
doi:10.1016/S0899-3467(07)60061-5
PMCID: PMC2646983  PMID: 19674619
MeSH: Irritable Bowel Syndrome; Immunization, Passive Immunity; Non-MeSH: Hyperimmune Egg
13.  A Role for Corticotropin-releasing Factor in Functional Gastrointestinal Disorders 
Current Gastroenterology Reports  2009;11(4):270-277.
Functional gastrointestinal disorders (FGIDs), which include irritable bowel syndrome (IBS), encompass a heterogeneous group of diseases identified by chronic or recurrent symptom-based diagnostic criteria. Psychosocial factors are key components in the outcome of clinical manifestations of IBS symptoms. Anxiogenic and endocrine responses to stress are mediated by the corticotropin-releasing factor (CRF)–CRF1 receptor pathway. Preclinical studies show that activation of the CRF1 receptor by exogenous CRF or stress recapitulates many functional symptoms of IBS diarrhea-predominant patients as related to anxiogenic/hypervigilant behavior, autonomic nervous system alterations, induction of diarrhea, visceral hyperalgesia, enhanced colonic motility, mucus secretion, increased permeability, bacterial translocation, and mast cell activation, which are all alleviated by selective CRF1 receptor antagonists. Clinical studies also support that CRF administration can induce IBS-like symptoms in healthy subjects and heighten colonic sensitivity in IBS patients. Yet to be ascertained is whether CRF1 receptor antagonists hold promise as a new therapy in IBS treatment.
PMCID: PMC3295847  PMID: 19615302
14.  Brain networks underlying perceptual habituation to repeated aversive visceral stimuli in patients with irritable bowel syndrome 
Neuroimage  2009;47(3):952-960.
Patients with irritable bowel syndrome (IBS) show decreased discomfort and pain thresholds to visceral stimuli, as well hypervigilance to gastrointestinal sensations, symptoms, and the context in which these visceral sensations and symptoms occur. Previous research demonstrated normalization of visceral hypersensitivity following repeated exposure to experimental rectal stimuli over a 12 month period that was associated with reduction in cortical regions functionally associated with attention and arousal. Building upon these functional analyses, multivariate functional and effective connectivity analyses were applied to [15O] water positron emission tomography (PET) data from 12 IBS patients (male=4) participating in a PET study before and after 4 visceral sensory testing sessions involving rectal balloon distensions over a 1 year period. First, behavioral partial least squares was applied to test for networks related to reduced subjective ratings observed following repeated application of an aversive rectal stimulus. Next, path analysis within a structural equation modeling framework tested the hypothesis that perceptual habituation to the repeated visceral stimuli resulted in part from the reduced connectivity within a selective attention to threat network over time. Two independent, perception-related networks comprised of interoceptive, attentional and arousal regions were engaged differentially during expectation and distension. In addition, changes in the effective connectivity of an attentional network as well as modulatory amygdala influence suggested that perceptual habituation associated with repeated stimulus delivery results both in an increase in top down modulation of attentional circuits, as well as in a reduction of amygdala-related interference with attentional mechanisms.
doi:10.1016/j.neuroimage.2009.05.078
PMCID: PMC3399695  PMID: 19501173
15.  Efficacy and mode of action of mesalazine in the treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D): study protocol for a randomised controlled trial 
Trials  2013;14:10.
Background
Irritable bowel syndrome (IBS) is reported by one in ten of the population accounting for up to 40% of new referrals to gastroenterology outpatients. Patients characteristically have abdominal discomfort and disturbed bowel habit. Diarrhoea-predominant IBS is characterised by frequent loose stools with associated urgency and abdominal cramps. Current symptomatic treatments can reduce bowel frequency but often fail to reduce discomfort.
Mesalazine is an anti-inflammatory drug used to treat patients with inflammatory bowel disease. There is one pilot study suggesting it may be beneficial to patients who have diarrhoea-predominant IBS but these findings need to be confirmed in a larger trial. The current study aims to test the effectiveness of mesalazine to reduce symptoms in diarrhoea-predominant IBS patients. The study will also investigate the mode of action of the drug, especially its impact on mast cell activation.
Methods/design
This is a multicentre randomised, double-blind, placebo-controlled trial using a parallel group design. At least 108 participants with diarrhoea-predominant IBS will be recruited through at least six hospitals. The intervention is a 12-week course of 2g mesalazine granules taken up to twice a day. The comparator is a blinded placebo granule formulation.
Outcome measures include stool diaries, symptom questionnaires, stool and blood samples together with rectal mucosal biopsies. The daily stool diary will record stool frequency and form, urgency, bloating, abdominal pain and a global satisfaction with control of IBS scored each week. The questionnaires will assess bowel symptoms, while the samples and biopsies will be used to analyse underlying mechanisms of any response.
Primary outcome will be the average stool frequency during weeks 11 and 12 of the treatment period and will be compared between treatment arms using an analysis of covariance in the form of a general linear model incorporating baseline characteristics that are thought a priori to strongly predict outcome. The primary efficacy parameter will be the difference in mean frequency between treatment arms.
Discussion
This report describes a randomised controlled trial that will provide evidence of any benefit of treating diarrhoea-predominant IBS patients with mesalazine. The results will be available toward the end of 2013.
Trial registration
ISRCTN76612274
doi:10.1186/1745-6215-14-10
PMCID: PMC3551830  PMID: 23302220
Irritable bowel syndrome; Diarrhoea-predominant; Mesalazine
16.  Impact and Outcomes of an Iyengar Yoga Program in a Cancer Centre 
Current Oncology  2008;15(Suppl 2):s109.es72-s109.es78.
Background
Individuals have increasingly sought complementary therapies to enhance health and well-being during cancer, although little evidence of their effect is available.
Objectives
We investigated how an Iyengar yoga program affects the self-identified worst symptom in a group of participants. whether quality of life, spiritual well-being, and mood disturbance change over the Iyengar yoga program and at 6 weeks after the program. how, from a participant’s perspective, the Iyengar yoga program complements conventional cancer treatment.
Patients and Methods
This pre–post instrumental collective case study used a mixed methods design and was conducted at a private Iyengar yoga studio. The sample consisted of 24 volunteers (23 women, 1 man; 88% Caucasian; mean age: 49 years) who were currently on treatment or who had been treated for cancer within the previous 6 months, and who participated in ten 90-minute weekly Iyengar yoga classes.
The main outcome measures were most-bothersome symptom (Measure Your Medical Outcome Profile 2 instrument), quality of life and spiritual well-being (Functional Assessment of Chronic Illness Therapy–General subscale and Spiritual subscale), and mood disturbance (Profile of Mood States–Short Form). Participant perspectives were obtained in qualitative interviews.
Results
Statistically significant improvements were reported in most-bothersome symptom (t(23) = 5.242; p < 0.001), quality of life (F(2,46) = 14.5; p < 0.001), spiritual well-being (F(2,46) = 14.4; p < 0.001), and mood disturbance (F(2,46) = 10.8; p < 0.001) during the program. At follow-up, quality of life (t(21) = −3.7; p = 0.001) and mood disturbance (t(21) = 2.4; p = 0.025) significantly improved over time. Categorical aggregation of the interview data showed that participants felt the program provided them with various benefits not included on the outcomes questionnaires.
Conclusions
Over the course of the Iyengar Yoga for Cancer program, participants reported an improvement in overall well-being. The program was also found to present participants with a holistic approach to care and to provide tools to effectively manage the demands of living with cancer and its treatment.
PMCID: PMC2528557  PMID: 18769575
Iyengar yoga; cancer; complementary and alternative medicine; integrative oncology; mixed methodology
17.  Alpha 2 Delta (α2δ) Ligands, Gabapentin and Pregabalin: What is the Evidence for Potential Use of These Ligands in Irritable Bowel Syndrome 
Irritable bowel syndrome (IBS) is a complex disorder that is characterized by abdominal pain and altered bowel habit, and often associates with other gastrointestinal symptoms such as feelings of incomplete bowel movement and abdominal bloating, and extra-intestinal symptoms such as headache, dyspareunia, heartburn, muscle pain, and back pain. It also frequently coexists with conditions that may also involve central sensitization processes, such as fibromyalgia, irritable bladder disorder, and chronic cough. This review examines the evidence to date on gabapentin and pregabalin which may support further and continued research and development of the α2δ ligands in disorders characterized by visceral hypersensitivity, such as IBS. The distribution of the α2δ subunit of the voltage-gated calcium channel, possible mechanisms of action, pre-clinical data which supports an effect on motor–sensory mechanisms and clinical evidence that points to potential benefits in patients with IBS will be discussed.
doi:10.3389/fphar.2011.00028
PMCID: PMC3114047  PMID: 21713059
α2δdelta ligands; gabapentin; pregabalin; irritable bowel syndrome; visceral sensitivity; central sensitization; peripheral sensitization; motility
18.  Complementary and alternative medicines in irritable bowel syndrome: An integrative view 
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder with a high incidence in the general population. The diagnosis of IBS is mainly based on exclusion of other intestinal conditions through the absence of inflammatory markers and specific antigens. The current pharmacological treatment approaches available focus on reducing symptom severity while often limiting quality of life because of significant side effects. This has led to an effectiveness gap for IBS patients that seek further relief to increase their quality of life. Complementary and alternative medicines (CAM) have been associated with a higher degree of symptom management and quality of life in IBS patients. Over the past decade, a number of important clinical trials have shown that specific herbal therapies (peppermint oil and Iberogast®), hypnotherapy, cognitive behavior therapy, acupuncture, and yoga present with improved treatment outcomes in IBS patients. We propose an integrative approach to treating the diverse symptoms of IBS by combining the benefits of and need for pharmacotherapy with known CAM therapies to provide IBS patients with the best treatment outcome achievable. Initial steps in this direction are already being considered with an increasing number of practitioners recommending CAM therapies to their patients if pharmacotherapy alone does not alleviate symptoms sufficiently.
doi:10.3748/wjg.v20.i2.346
PMCID: PMC3923011  PMID: 24574705
Irritable bowel syndrome; Complementary and alternative medicine; Hypnotherapy; Cognitive behavioral therapy; Herbal therapy; Peppermint
19.  Psychopharmacological Treatment and Psychological Interventions in Irritable Bowel Syndrome 
Irritable bowel syndrome (IBS) accounts for 25% of gastroenterology output practice, making it one of the most common disorders in this practice. Psychological and social factors may affect the development of this chronic disorder. Furthermore, psychiatric symptoms and psychiatric diseases are highly prevalent in this condition, but the approach to treating these is not always straightforward. As emphasized in the biopsychosocial model of IBS, with regard to the modulatory role of stress-related brain-gut interactions and association of the disease with psychological factors and emotional state, it proves useful to encourage psychopharmacological treatments and psychosocial therapies, both aiming at reducing stress perception. The aim of this paper is to analyze the effectiveness of psychopharmacological treatment and psychological interventions on irritable bowel syndrome.
doi:10.1155/2012/486067
PMCID: PMC3432371  PMID: 22956940
20.  Tegaserod in the treatment of irritable bowel syndrome (IBS) with constipation as the prime symptom 
Irritable bowel syndrome with constipation (IBS-C) as the predominant bowel symptom is a prevalent disorder, characterized by recurring abdominal pain/discomfort, bloating, and constipation, and imposes a significant socio-economic burden. Traditional treatments generally address just one of the multiple IBS symptoms. The efficacy and safety profile of tegaserod, a serotonin 5-HT4 receptor agonist, has been demonstrated in several randomized, placebo-controlled, and open-label trials. This review discusses the major clinical trials of tegaserod, which have involved 8948 IBS patients. Overall, data reveal that tegaserod is an effective treatment for IBS-C, providing statistically significant relief of overall and multiple individual IBS-C symptoms (abdominal pain/discomfort, bloating, and constipation) in both placebo-controlled and “real-life” open-label settings. Repeat treatments with tegaserod were also shown to be effective, which is noteworthy given the chronic and episodic nature of IBS. Moreover, tegaserod was associated with improvements in patients’ quality of life and work productivity. Data also indicate that tegaserod is well tolerated over the short-term (4 weeks), long-term (12 months), and repeated treatments. Diarrhea is the only adverse event consistently associated with tegaserod and was generally mild and transient. Overall, tegaserod has been demonstrated to offer effective and well-tolerated treatment of IBS-C, providing patients with meaningful symptom relief.
PMCID: PMC1936292  PMID: 18360619
efficacy; IBS; safety; serotonin; tegaserod; Zelnorm
21.  Irritable Bowel Syndrome, Gut Microbiota and Probiotics 
Irritable bowel syndrome (IBS) is a complex disorder characterized by abdominal symptoms including chronic abdominal pain or discomfort and altered bowel habits. The etiology of IBS is multifactorial, as abnormal gut motility, visceral hypersensitivity, disturbed neural function of the brain-gut axis and an abnormal autonomic nervous system are all implicated in disease progression. Based on recent experimental and clinical studies, it has been suggested that additional etiological factors including low-grade inflammation, altered gut microbiota and alteration in the gut immune system play important roles in the pathogenesis of IBS. Therefore, therapeutic restoration of altered intestinal microbiota may be an ideal treatment for IBS. Probiotics are live organisms that are believed to cause no harm and result in health benefits for the host. Clinical efficacy of probiotics has been shown in the treatment or prevention of some gastrointestinal inflammation-associated disorders including traveler's diarrhea, antibiotics-associated diarrhea, pouchitis of the restorative ileal pouch and necrotizing enterocolitis. The molecular mechanisms, as cause of IBS pathogenesis, affected by altered gut microbiota and gut inflammation-immunity are reviewed. The effect of probiotics on the gut inflammation-immune systems and the results from clinical trials of probiotics for the treatment of IBS are also summarized.
doi:10.5056/jnm.2011.17.3.252
PMCID: PMC3155061  PMID: 21860817
Immunity; Inflammation; Irritable bowel syndrome; Microbiota; Probiotics
22.  Diagnostic value of the Manning criteria in irritable bowel syndrome. 
Gut  1990;31(1):77-81.
Because unexplained 'functional symptoms' are a major cause of referral to gastroenterologists, the efficiency of the medical history to lead to a positive diagnosis of irritable bowel syndrome, without resorting to the use of expensive tests, remains a key question. Whilst the six criteria of Manning et al are widely used, data on their validity in discriminating irritable bowel syndrome from healthy controls, irritable bowel syndrome from non-ulcer dyspepsia and especially among irritable bowel syndrome subgroups, are not available. To evaluate this, we studied 361 outpatients who completed a bowel disease questionnaire, which objectively measured Manning's (and other) criteria. The group included 82 patients with irritable bowel syndrome, 33 with non-ulcer dyspepsia, 101 with organic gastrointestinal disease, and 145 healthy controls. Diagnoses were based on a full and independent clinical evaluation, not on responses to the bowel disease questionnaire. Reliability was assessed by a test-retest procedure. All six of the individual Manning criteria were found to be reliable (median kappa = 0.79). Based on a logistic regression analysis of the discriminatory value of Manning's criteria, as the number of positive criteria increased, so did the predicted probability of irritable bowel syndrome. This predictive value was highest in younger patients and in females. The Manning criteria discriminated irritable bowel syndrome from organic gastrointestinal disease and from all non-irritable bowel syndrome gastrointestinal disease with a sensitivity of 58% and 42%, and a specificity of 74% and 85%, respectively. Stools that were often loose and watery provided an additional independent criterion for distinguishing irritable bowel syndrome from non-irritable bowel syndrome. Thus, symptoms can be used to diagnose irritable bowel syndrome positively, but Manning's criteria are not highly sensitive.
PMCID: PMC1378344  PMID: 2318433
23.  Evaluation of Psychological Aspects Among Subtypes of Irritable Bowel Syndrome 
Context:
While some studies have found disparities between subtypes of irritable bowel syndrome (IBS), others did not found such differences.
Aim:
This study aimed to investigate whether there are differences in psychological features between the subtypes of IBS.
Settings and Design:
A cross-sectional study was performed on all consecutive outpatients IBS diagnosed (from Oct. 2010 to Oct. 2011) in Taleghani Hospital gastroenterology clinic, Tehran, Iran.
Materials and Methods:
A total of 153 consecutively diagnosed IBS patients (using Rome III criteria); including 80 constipation-predominant (IBS-C), 22 diarrhea-predominant (IBS-D), and 51 mixed IBS (IBS-M) were asked to complete the Symptom Checklist 90 Revised (SCL-90-R).
Statistical Analysis:
Pearson's chi-square test was used to compare nominal variables. One-way ANOVA was used to compare continuous variables.
Results:
Although IBS-C patients were more suffered from psychiatric disorders, there were no statistical differences between mean score of IBS-C, IBS-D, and IBS-M patients regarding to all of SCL-90-R subscales and three global indices including Global Severity Index (GSI), Positive Symptom Distress Index (PSDI) and Positive Symptom Total (PST) (P<0.05).
Conclusion:
Our finding showed that there are no different symptomatic profiles between IBS subtypes.
doi:10.4103/0253-7176.101780
PMCID: PMC3498777  PMID: 23162190
Irritable bowel syndrome; psychiatric aspects; Rome III criteria; symptom checklist-90-revised
24.  Gastro-oesophageal reflux in the irritable bowel syndrome. 
Gut  1986;27(10):1127-1131.
Symptomatic assessment and oesophageal investigations were done in 25 consecutive patients with the irritable bowel syndrome attending a gastroenterological clinic. Symptoms of gastro-oesophageal reflux, dysphagia, and a globus sensation were significantly commoner than in a control group of fracture clinic patients. Ambulatory oesophageal pH monitoring showed clearly abnormal reflux in 11 of 22 patients (50%). Nine patients had macroscopic endoscopic changes and a further 11 biopsy changes alone, of oesophagitis which was thus present in 80% overall. Lower oesophageal sphincter pressure was significantly less in irritable bowel patients than in age and sex matched controls, but upper oesophageal sphincter pressure was comparable in the two groups and disordered peristalsis was not found. Oesophageal symptoms in the irritable bowel syndrome are mainly caused by gastro-oesophageal reflux predisposed to by a subnormal lower oesophageal sphincter pressure, rather than by oesophageal spasm.
PMCID: PMC1433888  PMID: 3781323
25.  Gynaecological consultation in patients with the irritable bowel syndrome. 
Gut  1989;30(7):996-998.
A 12 month follow up study to assess the impact of symptoms suggestive of irritable bowel syndrome in women presenting to gynaecology clinics with pelvic pain is reported. Of 71 women 37 (52%) had symptoms suggestive of irritable bowel syndrome at presentation. A firm gynaecological diagnosis was reached in only three (8%) women positive for irritable bowel syndrome compared with 15 (44%) without (p = 0.002). After 12 months 24 (65%) women with irritable bowel syndrome were still symptomatic compared with 11 (32%) without (p = 0.01). This study shows that women with irritable bowel syndrome frequently attend gynaecological clinics but rarely have gynaecological pathology and the prognosis is poor in terms of resolution of their pain.
PMCID: PMC1434306  PMID: 2759494

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