Issue 38, Spring 2007 Deb Geno Executive Director Los Angeles, CA Lin Chang,MD Secretary/Treasurer Los Angeles, CA Emeran Mayer, MD Vice President Rochester, MN G. RichardLocke,MD President President Richard Locke,MD promote andadvancemultidisciplinaryresearcheducationinthebasic The missionoftheFunctionalBrain-GutResearchGroupistosupport, Functional science, clinicalandbehavioralaspectsofbrain-gutinteractions. its By in ourfield. represent our future and we hope they continue to be interested They winners. were attendees 20 All syndrome”. bowel ritable T circulating of properties homing “Gut Milwaukee,WI Nancy Norton Boston, MA Tony Lembo,MD Manchester, UK Lesley Houghton,PhD Tucson, AZ Ronnie Fass,MD Columbus, OH Carlo DiLorenzo,MD Council to and mice” in hyperalgesia visceral post-inflammatory controls 6 top prize for this presentation “G protein-coupled receptor kinase Niels disorders. GI functional in underway rently cur research of breadth the reflected presentations The globe. We eventsuchasuccess. for alloftheireffort inmaking thisyear’s Quigley,organizer, our to and Parkman Henry and Fried, Joyce Carlo DiLorenzo, to our faculty, Lin Chang, Ray Clouse, Eamonn and Chey Bill chairs, our to year.Thanks every grown has and Olden Kevin by initiated was event FBG This California. Diego, San near 2007 25, to 23 March held conference Investigators Greetings! Message fromthePresident Motility the American of effort joint a is This Neurogastroenterology and Motility will be for the host Society organization. European The Switzerland. Lucerne, in 2008, 6-9, neurogastroenterology Please with theIFFGD.We arepleasedtobeinvolved. 12-15 2007. The FBG has benefitted greatly from our interaction Birgit 7 the had th Eijkelkamp International time Research mark Adam 20 you I enthusiastic have (ad-hoc member) your receive from from Symposium calendars just Adelaide, Utrecht, this and returned young newsletter, motility John Herr Newsletter Design Kirsten Nyrop Newsletter Managing Editor Douglas A. Drossman, MD Newsletter Editor 2004 -2006—GeorgeF. Longstreth,MD 2002 2000 1998 1996 1994 1989 Past-Presidents Brain-Gut the for in Australia,

investigators ------Milwaukee,

from the 2004 2002 2000 1998 1996 1994 Netherlands, meeting second the —KevinOlden,MD —W. Grant Thompson, MD —NicholasJ. Talley, MD,PhD —KennethL.Koch,MD —WilliamE.Whitehead,PhD —Douglas A. Drossman,MD the ir- with patients in cells IFFGD Group who Fifth to the (AMS), Society to Congratulations Wisconsin, be international joint who from won will held Annual was have around a November prize awarded on Young hosted April the for - Founded 1989 www.fbgweb.org E mail:[email protected] Fax: 507-266-9081 Phone: 507-538-0367 USA Rochester, MN55904 1820 SpruceMeadowsDrive be The FBG annual meeting and reception will May 22 FBG Annual Meeting Annual meeting: Reception: 5:30-6:30pm B-C-D Ballroom. 22, at the Grand Hyatt Hotel, Independence Office FBG News Announcements Special Reports MeetingSchedule DDW IFFGD Spring2007Update Edition gastrointestinal disorders,Third Rome III:Thefunctional Book Review Guest Column Cross-Cultural Column Rona L.Levy, MSW, PhD,MPH Member Spotlight Editor’s Column Message from thePresident Table ofContents held at DDW in 6:30-7:30pm. Washington DC, May 12 10 29 26 19 15 14 8 7 3 1  Message from the President

European Society for Neurogastroenterology and Motility (ESNM), Of course, the person most involved with the FBG is our executive the International Group for the Study of Neurogastroenterology director Deb Geno. One special initiative she has underway is our and Motility, and the FBG. Doug Drossman and Carlo DiLorenzo web site, www.fbgweb.org. We hope to have a new version ready attended the program planning meeting on behalf of the FBG and for display at our annual meeting. we are excited about the results. This meeting should be of great interest to all of our members. The FBG annual meeting will be at DDW in Washington DC, Tuesday May 22, in the Grand Hyatt Hotel, Independence B-C-D Due to the success of the inaugural meeting in Boston, the deci- Ballroom. The reception is 5:30-6:30pm and the annual meeting is sion has been made to have this joint meeting annually, beginning 6:30- 7:30pm.. I hope to see you all there. Thanks. in 2008. I am pleased to announce that the FBG will be the host of the 2009 meeting. We now have a lot of work to do! We are pleased that the IFFGD has joined us in planning this meeting. We will have details to discuss at our annual membership meeting at DDW. We will need help! I am hoping that we will have several FBG members involved.

Speaking of involvement, I am pleased to announce our new coun- cilors, Ronnie Fass and Tony Lembo. I want to thank our “retiring” councilors, Brian Lacy, Fermin Mearin, and Max Schmulson for their energy and effort. Of note, Max was elected president of the newly formed, Latin-American Society for Neurogastroenterology. I also want to thank all the candidates for council who were brave enough to have their names on the ballot, and I am hoping you all will be willing to run again.

Dear FBG member,

Mark your calendar’s for the Functional Brain-Gut Research Group’s Annual Meeting And Reception!

The Independence, B-C-D ballrooms The Grand Hyatt Washington, DC

Tuesday, May 22, 2007 Reception 5:30-6:30 pm Annual Meeting 6:30-7:30 pm

Hope to see you there!

Deb Geno Executive Director

Functional Brain Gut Functional Brain Gut Research Group Research Group Editor’s Column 

Gastroenterology for These historical data then need to be refined with a physical examination and diagnostic studies: when to do the blood tests Functional GI Disorders or an endoscopy, whether to order the CT scan or MRI, or even in the 21st Century do any testing at all. Once all this information is obtained, the gastroenterologist must put it all together and determine a reasonable diagnostic approach and plan of care. Thus, the science involves integrating the evident data on gastrointestinal pathology and physiology within the context of the person.

The art of gastroenterology is the interaction with the patient; it is not what you do but how you do it. It involves understanding Douglas A. Drossman, MD and participating in the patient’s inner world as related to his or Editor her illness: to use good interview skills to validate the previous medical information and obtain new meaningful data directly from the patient, and to put the more personal psychosocial influences The field of gastroenterology is changing. In this article, I reflect on into proper context. It also involves understanding the patient’s the practice of gastroenterology as well as the changing pattern “illness schema” or perception of what is wrong, and what his or of care being provided particularly for patients with functional GI her concerns or expectations are from the doctor. This information disorders. It has been abstracted and modified from a chapter is integrated into an effective diagnostic and treatment plan. in an upcoming book “Inside the Minds: Gastroenterology Best Finally, the physician must convey this information in a manner Practices” by Aspatore Press, 2007. that is acceptable to the patient, and work toward reaching mutual agreement as to how to move forward. In effect, all of this involves The Science and Art of Gastroenterology establishing a trusting relationship with good communication and shared decision making between the clinician and the patient. Gastroenterology is, I believe, unique among the medical subspecialties: a blend of science and art. For example, with These skills are not learned through technology or textbooks. cardiology, pulmonary disease and nephrology, clinicians can rely Instead, it requires that gastroenterologists be mentored from on cardiac catheterization, lung physiology, or kidney function knowledgeable teachers. In fact, the AGA has recommended that tests to understand how well a specific organ is functioning and for training in functional GI and motility, the fellow must receive this closely relates to how ill the patient is. But, understanding supervised clinic time with a senior physician skilled in this gastroenterological illnesses is more complex because there are particular area(1). In addition, clinicians must learn from their own no numbers or calculations of organ function to explain why the experience with patients and possess a genuine desire to help patient has abdominal pain or nausea. We need to look at the the patient. Typically, doctors prefer patients who get better and person and his or her symptoms (e.g., pain, nausea, or diarrhea) thank them for their effort. But, with the most prevalent chronic GI within the context of daily functioning, life stress, quality of life, disorders (e.g., chronic liver disease, inflammatory bowel disease, and coping style. It is all of these in combination that determines functional GI and motility disorders, chronic pancreatitis, intestinal the challenge and excitement of working with gastrointestinal malabsorption), this is not always the case. So, physicians need to disorders. value the process of their care with patients. This means building the relationship to help patients help themselves, expecting only The science of gastroenterology starts at the sub-microscopic level, occasionally to make a rare diagnosis or to cure. What patients understanding how neurotransmitters and hormones in the bowel, with chronic illness truly want is a sense of hope, and to have a such as serotonin or cholecystokinin (CCK), affect gastrointestinal doctor who cares and won’t abandon them. Studies show that an function. Stress can produce these and other neurotransmitters effective physician-patient relationship not only improves patient in the brain and they can then work “downstream” to affect satisfaction, adherence to treatment and avoids litigation, but it intestinal motility, inflammation of the bowel, or the secretion of also leads to better clinical results (2). these organs. All GI symptoms are intimately connected to and regulated by the brain; that is why understanding psychosocial Diagnosis and Treatment issues is so paramount. Sometimes the process of developing a diagnosis and treatment So, the gastroenterologist needs to understand the science in plan is straightforward. If, for instance, a patient reports blood in relation to possible disease and dysfunction of organ systems that the stool or has heartburn or becomes jaundiced, it does not take produce symptoms and often consider how it may be modified more than ten or fifteen minutes to get the history and decide on by the individual’s life context. Thus, nausea may occur from a a plan: endoscopy for bleeding or heartburn, or blood studies and disease in the liver, or from gallstones, a stomach ulcer, poorly diagnostic imaging to evaluate the liver. The rest follows without functioning intestinal movements (motility), medication side difficulty effects, a recent infection, an early pregnancy, a recollection of early traumatic experience, or even having an argument with But, what is more challenging in GI practice is seeing patients with one’s spouse. Similarly, a patient with inflammatory bowel disease chronic unexplained conditions like the functional GI and motility (IBD) may be doing well and then suddenly experience pain and disorders that require a more comprehensive biopsychosocial diarrhea; the disease itself may or may not have worsened, but perspective (3). Diagnosis first involves reviewing extensive other factors – such as a super-imposed infection, stress, dietary records, often in advance of the patient’s visit, to see what studies change, or any combination – may also be the cause. have and have not already been done. Once the background

Functional Brain Gut Functional Brain Gut Research Group Research Group  Editor’s Column

information is obtained, instead of asking the same questions those with acute problems and those with chronic conditions. or redoing the tests, the physician tries to go where others have Researchers found that patients with chronic conditions had not: to consider diagnoses that may have been overlooked and to more procedures done, more medications prescribed, and more find out about the illness within the life context of the patient. For exploratory laparotomies performed even when the doctors example, did the symptoms begin at Christmas dinner on the first believed they probably were not indicated. Why would they go anniversary of the parent’s death? Or, has there been a history against their better judgment? Furor Medicus depends on two of emotional trauma or physical or sexual abuse?(4). At tertiary factors: the level of uncertainty within the doctor and the level of care medical centers, half of the women seen in gastroenterology insistence by the patient to do something. Residents in training clinics report a history of abuse, and those individuals have more are likely to perform extra procedures and unneeded treatments severe symptoms and poorer quality of life (5). We are now because they do not have the experience to deal with the learning that this observation may relate to areas where encoded uncertainty of medicine. On the other hand, even experienced memories modify brain physiology, leading to amplification of the physicians may go against their own better judgment and order pain experience (6;7). It is this biopsychosocial understanding of studies and treatments when the patient insists that something be illness and disease that puts the patient’s symptoms into a clearer done now in order to achieve a quick solution. The most effective perspective and opens the door to more effective treatments. gastroenterologists are those who can step back and look at the big picture rather than simply react. In situations like this, it is best Some patients have become conditioned to respond to stress to: “Don’t just do something, stand there”. with gastrointestinal symptoms, yet are not aware of this association. This may be confusing or in the least challenging In these types of situations, the physician needs to acknowledge for gastroenterologists where the association with stress seems the patient’s frustration, make it clear that the pain is real and evident. For example, if a young child at age 5 goes to school then focus on developing a supportive relationship that helps the on the first day, he might experience a psycho-physiological patient find ways to accept the illness and learn to self-manage. response to the fear of leaving home: abdominal cramps and These are patients who have been to many doctors, and what diarrhea. If the parent singles out these symptoms as a reason to they need is someone to work with them regardless of the ultimate keep the child home, and in fact “rewards” the child by providing diagnosis or outcome. toys and allowing him to watch TV, the child’s relief in avoiding the feared situation could reinforce the recurrence of such symptoms It may take a little longer on the first visit to obtain and integrate in future distressing circumstances, even into adult life. On the the needed information and establish an effective relationship. other hand, if the parent says, “Johnny, you have a stomachache. But, the end results will pay off far more than conducting another Maybe you are feeling nervous about going to school; let’s talk endoscopy that turns out negative. The rewards for the physician about it,” then the child learns to understand his anxiety about come from working with a patient who has suffered for many years going to school and to verbalize this anxiety instead of expressing without understanding why, and helping them find the answers it through the conditioned symptoms. Our research has shown that and improve their quality of life. many patients with IBS who frequently see physicians grew up in family environments where they did not learn to communicate Is this gastroenterology? As it turns out, I have not addressed the stress verbally, although they did receive attention and were technical aspects of the discipline. Acquiring skill in endoscopy brought to physicians when they voiced physical complaints. and motility and gaining adequate knowledge of the field is a Thus, the situation may arise where the physician suspects that requirement for training. The technical areas of gastroenterology stress may be playing a role and the patient is unaware of this. are well standardized and reinforced in practice. It is challenging Conversely, patients who make the link between stress and GI and exciting and hardly needs emphasis: there is immediate symptoms seem less distressed with their symptoms and do not gratification in stopping a bleeding artery in the stomach, making go to doctors as often (8). a diagnosis of achalasia from motility testing, or taking out a gallstone during sphincterotomy. However, there is also deep I once had a patient with many years of abdominal pain and many satisfaction from gaining skills in the more cognitive aspects evaluations say to me on the first visit: “I am not leaving this chair of gastroenterology, clinical reasoning and decision making, until you agree to operate.” These are challenging situations for communication techniques, and building of the physician-patient patient and doctor. Indeed, the patient who says they know their relationship. This is where the work can be gratifying for physician pain is “real” and that there is no stress in their lives requires a and patient alike. physician with experience, patience and skill to provide a different level of understanding and support. These patients may also have Sub-Specialties within Gastroenterology been mishandled by the health care system, and they are fearful of being rejected yet choose to see many doctors trying to find an Gastroenterology is a complex field and research is constantly answer. changing the way we view GI diseases and conditions. Over the years, there has been a partitioning of the field into a variety of It is so much easier in our litigious and cost-focused health sub-specialties within the broad area of gastroenterology. When care system to perform costly tests and prescribe symptomatic I was in training in the mid 1970’s, we were responsible for all treatments without making an effort to understand what is really areas of gastroenterology and liver disease. Over time, “sub going on. Patients with complex, long-standing conditions do not sub-specialties” emerged where individuals worked solely with benefit from this approach. In the 1970’s, researchers studied a particular organ systems, such as the esophagus, pancreas and concept called “furor medicus” (9). They evaluated patients who liver, and each had their own sets of diseases and dysfunctions. came to the emergency room and divided them into two groups: In fact, over the past twenty to thirty years, probably with the

Functional Brain Gut Functional Brain Gut Research Group Research Group Editor’s Column 

emergence of transplantation, liver disease has developed into For the future, I think it will be helpful to employ gastroenterologists, the clearly defined sub-specialty of hepatology. Nowadays, physician assistants, psychologists, and motility experts to gastroenterologists often distinguish themselves as either “solid” work together to get to know the illness, the patient, and their (i.e., liver and pancreas) or “hollow” organ (e.g., esophagus psychosocial and coping resources and to find ways to break the stomach and intestines) specialists. vicious cycle. Ultimately, the task is to help patients regain their sense of control over their illness and their life. The effective health In addition to organ system specialists (e.g., esophagologists, care provider makes the effort to provide a clear physiological IBD experts, pancreatologists, and hepatologists), there are explanation as to why patients are having symptoms and offer the procedural specialists. While all gastroenterologists learn a rationale for treatment based on this understanding. A major endoscopy, some focus primarily on the technically precise effort is to focus on helping patients become “re-empowered”, so disciplines of endoscopic ultrasound or interventional endoscopy, they can feel in control enough to manage their symptoms. Since doing sphincterotomies for gallstones in the common bile duct and these are chronic GI disorders, we must communicate that “cure” stent placements for benign and malignant strictures. In recent may not occur, but patients can still regain their daily function and years, there is even growing interest in endoscopic surgery. improve their quality of life. It is not unusual after many years of illness and with proper treatment to come back feeling much Finally, there is our small but growing group of subspecialists better saying: “The symptoms are still there, but they don’t bother who focus on functional GI and motility disorders and treat the me as much”. largest group of patients (about 40%) seen in gastroenterology practice. Diagnosis is based on symptoms and at times physiology Challenges in Gastroenterology testing, since there are no findings on x-ray or endoscopy. The symptoms are understood to be caused by dysfunction of the The biggest challenge in gastroenterology is to address and nerves and muscles of the gastrointestinal system. This leads to hopefully reverse the shift over the last two decades from a focus altered motility, visceral hypersensitivity, and other physiological on the provision of quality care to that of bringing in more money dysfunctions that are amplified by stress and emotions. Many (10). Physicians are performing more and more procedures and are skilled in gastrointestinal motility of the esophagus, stomach, are seeing patients in briefer periods of time, since more income intestines and anorectum, while others focus primarily on can be generated by doing a procedure than by performing a diagnosis and management based on the symptoms that define clinic visit, talking and thinking. For example, it is not unusual these disorders. We have a responsibility to keep this discipline for a patient coming in for abdominal pain to immediately get an strong, scientifically based, and of value to patients. endoscopy and if it is negative, to be prescribed a narcotic pain killer without the physician really thinking through the diagnosis, Helping patients with functional GI disorders to help the reason for the visit, or the long term management plan. themselves Managed care has changed the way we look at patients these days: diagnostic tests have replaced clinical decision making and In our field, working with the functional GI disorders, it is important a quick fix is preferred; if it brings in more money, all the better. to focus on the interaction of the brain and gut (3). These disorders must be understood and managed in a way that integrates the Another challenge is to reverse the continued reduction of biological, psychological and social factors both for clinical care federal funding for clinical gastroenterological research. Many and research. gastroenterologists who do clinical research are being forced to move out of academic medicine and into the pharmaceutical Patients with functional GI and motility disorders who have been industry or clinical practice, because it is becoming more and to many high quality clinical practices often get referred to us in more difficult to find the needed support to do clinical research. FBG because they continue to have disabling symptoms and poor Although the National Institutes of Health (NIH) are looking to quality of life. On occasion, we come up with new diagnoses and provide more “translational” and clinical research support, their treatments; however, most often, we attend to the educational history is to prioritize basic over clinical research, and the lowest and management aspects of conditions that have already been priority is directed toward the functional GI and motility disorders. diagnosed. If a patient says “no one has told me what I have”, we Furthermore, any effort to reverse this pattern is hampered by can interpret that as a failure of communication. When they say continual budget cuts to NIH due to other federal budget priorities. “nothing has worked for me”, it becomes important to understand The general perception that basic research is a funding priority what was prescribed, for how long, whether it was taken, and how relates to the premise that finding the molecular basis for diseases much the patient was given the opportunity to become involved will lead to cures. No doubt, this has potential for many diseases. in their own care. However, the health problems in Western society have shifted from immediately treatable acute diseases to multi-determined Because functional GI disorders do not have specific findings chronic disorders that impact the patient and the family. With with laboratory studies, x-ray or endoscopy, the patients often chronic illnesses, treatment now needs to be directed toward feel that something else is being missed or that their symptoms symptom management and improved quality of life, and a cure are psychosomatic -- “in my head”. They feel “out of control” and may not be likely for quite some time. Thus, it is important to unable to manage their symptoms. A vicious cycle then ensues: find ways to allocate clinical funds for research to help patients feeling unable to understand or control a condition that has great manage chronic gastrointestinal disorders. This is a goal I hope impact on their life, the patient becomes anxious and distressed, to achieve over the next 5-10 years. which in turn leads to more symptoms and so it continues.

Functional Brain Gut Functional Brain Gut Research Group Research Group  Editor’s Column

A third challenge is to find ways to legitimize the functional GI liver and other gastrointestinal conditions on an ongoing basis, disorders because of their profound impact. For example, irritable and performing routine endoscopies as needed. The practicing bowel syndrome is considered second to the common cold as a gastroenterologist will refer the patients to GI subspecialists reason for work absenteeism, about $2 billion are spent each year when further expertise is needed in a more specialized area of treating patients with IBS and, when factoring in indirect costs gastroenterology. This is already happening. as well, the cost to society in the US is close to $20 billion (11). Yet, these disorders are not considered as important compared I am hopeful there may also be a group of gastroenterologists to cancer or heart disease. They can be overlooked, ignored, or primarily involved with functional GI and motility disorders that will considered insignificant by the media, general public, and funding have learned the communication and cognitive skills to properly agencies, despite their impact on morbidity, impaired quality of diagnose and care for these patients. This may require a shift in life and societal costs. It is not completely clear why this is the our health care economics to a more nationalized system, where case, although it may relate to societal values that minimize or proper compensation can be applied to the cognitive skills. It is make humorous attention to bodily functions like gaseousness, also likely that nurse practitioners or physician assistants as well vomiting and defecation difficulties produced by gastrointestinal as nutritionists and psychologists will be part of this health care disturbances. Furthermore, because these disorders lack team. In the end, the hope is that all patients with GI disorders will structural abnormalities detectable by x-ray or endoscopy, they are be better served. often relegated to second class status when compared to “real” disorders like ulcer disease, colon cancer or inflammatory bowel Reference List disease (12). People often believe that if the doctor cannot find a physical cause for the symptoms, then it is psychosomatic. Thus, 1. Ouyang A, Camilleri M, 7. Drossman DA. Brain Imaging there needs to be a way to communicate to patients, physicians Drossman DA, Kahrilas and its Implications for and society an understanding of the biopsychosocial model for PJ, Reynolds JC, Shaker Studying Centrally Targeted understanding GI disorders. R. Task force on training in Treatments in IBS: A Primer motility, diverticular disease, for Gastroenterologists. Gut. 2005;54:569-73. The fourth challenge as discussed, is to find the ways to teach and functional illness. physicians how to build their clinical decision and relationship Gastroenterol. 1996;110:1274- 8. Lowman BC, Drossman DA, 76. skills. The data supports improved outcomes(13). After 30 Cramer EM, McKee DC. years in practice, experience has shown that no other attribute 2. Drossman DA. The Physician- Recollection of childhood events in adults with irritable contributes as much to physician and patient satisfaction and an Patient Relationship. In: bowel syndrome. J Clin improved clinical outcome for patients with all gastrointestinal Corazziari E, ed. Approach to the Patient with Chronic Gastroenterol. 1987;9:324-30. disorders. While I believe that the advances in technology within Gastrointestinal Disorders. the field have been and will continue to take care of themselves, 9. DeVaul RA, Faillace LA. Milan: Messaggi; 1999: 133- Persistent pain and illness the greatest need is to get NIH, clinical payers and our medical 39. insistence - A medical profile schools to focus on physician training in the cognitive skills and 3. Drossman DA. Presidential of proneness to surgery. Am J the scientific evidence will show it works. Address: Gastrointestinal Surg. 1978;135:828-33. Illness and Biopsychosocial 10. Drossman DA. Medicine has The Future of Gastroenterology Model. Psychosom Med. become a business. But what 1998;60:258-67. is the cost? Gastroenterol. In the 1960’s, gastroenterologists moved away from being 4. Drossman DA, Talley NJ, Olden 2004;126:952-53. internists with special interests in the gastrointestinal tract to KW, Leserman J, Barreiro MA. 11. Sandler RS, Everhart JE, becoming “proceduralists”, performing endoscopies, interventional Sexual and physical abuse and Donowitz M, Adams E, Cronin endoscopies, and ultrasound. Now, gastroenterologists can gastrointestinal illness: Review K, Goodman C et al. The reduce the need for surgery by endoscopically removing polyps and recommendations. Ann burden of selected digestive before they turn into cancer, or draining abscesses that otherwise Intern Med. 1995;123:782-94. diseases in the United States. would require an operation or taking out gallstones. Over the next 5. Drossman DA, Li Z, Leserman Gastroenterol. 2002;122:1500- five years, we are likely to see even more emphasis on technical J, Toomey TC, Hu Y. Health 1511. procedures, such as surgical endoscopies and newer diagnostic status by gastrointestinal 12. Drossman DA. Functional GI imaging methods. Interventional endoscopy will likely move away diagnosis and abuse history. Disorders: What’s in a Name? from “mainstream” gastroenterology. The technical demands will Gastroenterol. 1996;110:999- Gastroenterol. 2005;128:1771- 1007. require additional training to maintain competence. Similarly, other 72. areas of gastroenterology will also separate out, because of their 6. Drossman DA, Ringel Y, 13. Roter DL, Hall JA. own unique features. Hepatology has already done that; possibly Vogt B, Leserman J, Lin W, Consequences of Talk: The inflammatory bowel disease (IBD) specialists and GI oncologists Smith JK et al. Alterations Relationship between Talk of brain activity associated and Outcomes. Doctors will need to affiliate at medical centers, because of the need to with resolution of emotional collaborate with surgeons and radiologists. talking to Patients / Patients distress and pain in a case talking to doctors: Improving of severe IBS. Gastroenterol. communication in medical What will be left? Routine gastroenterological care and endoscopy 2003;124:754-61. visits. 2nd ed. Westport, CT: will always be needed by patients in the community. I suspect Prager Publishing; 2007: 143- that the gastroenterologist in practice will function much like 64. the internist, serving as a “gatekeeper”, managing the common problems like GERD, functional GI disorders and milder forms of

Functional Brain Gut Functional Brain Gut Research Group Research Group Member Spotlight 

Rona L. Levy, M.S.W., Ph.D., M.P.H.

my skills in biofeedback and relaxation training, as well as pain Professor, School of Social Work management issues and techniques. During that year, Frank and I Adjunct Professor, Division of began discussions and some work on how spouses of pain patients Gastroenterology influenced pain experience. Adjunct Professor, Department of Psychology One month after I was promoted to Full Professor, I met my husband University of Washington Andrew Feld, who is a gastroenterologist. Within the first three Seattle, WA, USA years of our marriage, three wonderful children quickly followed. (They are now no longer children: one is about to graduate from high school and the other two are students at Dartmouth and Harvard.) While I stayed in academia and continued teaching, I Throughout junior and senior high school, I had always planned on must admit my research activities slowed down quite a bit until being a physician. However, in my senior year of high school, I had they all had started first grade. When I came up for air, I realized a college counselor who had always wanted to be a psychologist that a lot of the skills and knowledge I had in behavioral medicine and also realized she had counseled my father 30 years before could be useful particularly in gastroenterology. As I am/was on a me. With her excitement over this special connection, she decided hard money position, I had the flexibility to follow my interests and I should fulfill her dream and become a psychologist, and her could pursue the direction I wanted. In my early research in GI, I enthusiasm was infectious. I entered Brandeis University as a participated in studies looking at factors that influenced symptoms psychology major. I liked psychology, but to be honest, academics of women with Irritable Bowel Syndrome, and then developing were not my top priority during my undergraduate years. I wanted treatment strategies for women with IBS. At one of the first IFFGD to explore the world and my own personal growth. What followed meetings, I met Brenda Toner, also a psychologist focusing on GI was a transfer to Antioch College in Yellow Springs, Ohio, and then issues, and we have remained good friends. Brenda introduced traveling around Europe with friends in a VW minibus. Berkeley me to Doug Drossman, a colleague she described and I came to was next (Antioch, Europe, Berkeley – see the pattern? -- those know as focal in the developing recognition of the importance of were the times and I was right on theme). When I could not get psychosocial aspects of the functional GI disorders. a job in Berkeley in anything related to psychology, I applied to graduate school at the University of Michigan in a wonderful A casual conversation with William Whitehead over a conference socially-conscious program that combined training in psychology dinner about mutual interests in the influence of others on symptom with social work – which explains how I picked up my M.S.W. on expression led to a very rewarding and productive collaboration with my way to a Ph.D. (both in four years, a record for the program, him which still continues. This work began by exploring the relative I believe). My dissertation, which began a career-long interest in contributions of genetics and social learning to the development the topic of compliance, was on ways to enhance the likelihood of functional GI disorders. NIH-supported research allowed us to that patients who received counseling would follow through on investigate some of the learning mechanisms which contributed to behavioral treatment prescriptions. After completing that program, gastrointestinal problems in the children of parents with IBS. Based I was not quite ready to finish my formal education, so I enrolled in on what we learned about these mechanisms, we currently are a post-doc program at the School of Public Health, which rounded conducting ongoing studies on intervention strategies for treating out my degree acquisition with an M.P.H. However, while working children with functional GI problems, as well as IBD. toward my M.P.H., I realized Medicine was still the field I loved, so I started taking pre-med courses with the plan to enter medical Obesity research is another direction of our group in Seattle. We school in the future. I thought I would face the inevitable and take have published on the relationship between GI symptoms and my first real job, and then somehow go through medical school while obesity, and also are conducting NIH-funded studies on enhancing working. Life has a funny way of completing circles in unexpected maintenance following weight loss, improving healthy diet and ways and so, although I got caught up on other paths and never exercise among Native American families, and strategies for did enter medical school, my professional activities are not much physicians to prevent obesity in children. different than if I had! My various professional hats and honors reflect the translational For the first several years on the faculty at the University of nature of my work. I am a licensed psychologist, a Professor in the Washington, my research activities were in two areas: (1) the School of Social Work, as well as Adjunct Professor in the Division development of the single subject research methodology and of Gastroenterology and Department of Psychology. I feel very publishing one of the first books in this area and (2) treatment fortunate to have been honored by being elected to Fellow status compliance with medical regimens, especially physician in numerous professional organizations which also represent my communication styles, reminder systems, and other strategies to activities in behavioral medicine, psychology, and gastroenterology: increase adherence across several specialties, including pediatrics, Academy of Behavioral Medicine Research, American College dentistry, cardiology, etc. A number of articles and a book on patient of Gastroenterology, American Gastroenterological Association, adherence also resulted from this work, including one on adherence American Psychological Association, American Psychological issues in gastroenterology practice. I was funded by NIH to spend Society, and the Society of Behavioral Medicine. a sabbatical year at Duke University working with Richard Surwit and Frank Keefe, which also gave me the opportunity to hone

Functional Brain Gut Functional Brain Gut Research Group Research Group  Cross-cultural Column

Irritable Bowel Syndrome (IBS) in Mexico

Max Schmulson, M.D. Profesor Titular de Medicina Laboratorio de Hígado, Páncreas y Motilidad (HIPAM) Departamento de Medicina Experimental, Facultad de Medicina-Universidad Nacional Autónoma de México, Hospital General de México

This is the second in a series of commentaries edited by Mary- there is a general belief that seeing a mental health expert indicates Joan and Charles Gerson, co-chairs of the FBG Cross-Cultural severe pathology or “craziness.” Physicians have to be very Committee. Dr. Schmulson’s observations are based on careful how they refer patients to a mental health professional and questions posed by Drs. Gerson and personally surveyed from there is even high resistance in patients against taking low dose Dr. Schmulson’s colleagues (physicians who do not specialize in antidepressants for IBS symptoms as this is also seen as a marker functional GI disorders), as well as his patients and their family of mental disease. members. Are there gender differences? Background: Facts on health care behavior by IBS patients in Mexico There is general agreement that IBS occurs more frequently in women than in men. However, this difference is interpreted IBS has a 16% prevalence in Mexico (and up to 35% among differently by each sex. volunteers). 70 to 82% of those suffering from IBS seen in community and specialty clinic surveys are female. (1-2) IBS is the Women’s viewpoint. Women feel it is more frequent in women most common reason for consultation with gastroenterologists and because they speak more freely and are less embarrassed to when patients were asked why they came to a referral center, the speak about their GI symptoms. “Women enjoy speaking about the most frequently reported reason was abdominal pain/discomfort subject and sharing their knowledge about the subject.” Women (78%) followed by symptom stressfulness (60%), impairment in feel that men report their symptoms much less frequently because daily function (33%), and fear of cancer (11%). (2, 3) In Mexico, it is socially unacceptable for them to speak about those subjects IBS has a high impact on HRQOL and it has been shown that health and that is the reason IBS is not seen as frequently in men. Women worries and body image are important factors. (4) One study in the consider themselves to be “experts” on IBS. State of San Luis Potosi determined that the use of complementary medicine during the previous 12 months was 51% in IBS patients Men’s viewpoint. The men interviewed thought it was more frequent compared to 36% in functional dyspepsia and 27% in esophageal in women because they suffer more frequently from emotional reflux. (5) Herbals were most frequently used. problems that are related to their menstrual cycle, and also because “women tolerate less pain and abdominal discomfort”, not because The Survey: Feelings and Beliefs about IBS in Mexico men are ashamed to speak about the subject. However, men contradict themselves by saying it is not socially acceptable to feel How do Mexicans feel about IBS? gastrointestinal symptoms and much less to speak about them.

IBS is felt to be very common. There is general agreement that Are bowel symptoms a source of shame? IBS is a psychosomatic problem. It is also commonly believed that food may be a factor that exacerbates symptoms. Some individuals While GI symptoms are felt to be common and not a source of do not view IBS as an illness, but as symptoms brought on by shame, men are embarrassed to speak about gastrointestinal stress or emotions. While the importance of emotional factors is symptoms and women are ashamed about having abdominal recognized, there is a general resistance to psychological referral. bloating. One way that Mexicans deal with GI symptoms is by joking, Here is an example: A patient in her 40’s stated: “Stress generates much more often by men than by women. Many jokes are openly my symptoms. I’m stressed because of my husband who has made in Mexican society about GI symptoms, for example: “You are a very bad character and has fights constantly, for example in going to go in your pants”, if someone is frightened or anxious. restaurants.” Comment by Charles and Mary-Joan Gerson: In contrast to our How do Mexicans respond to a suggestion that psychological help Hong Kong report (Fall 2006 FBG newsletter), Mexicans openly would be useful? acknowledge that IBS symptoms are common and are related to emotions. Acceptance of the importance of emotions, both Unfortunately, although both Mexican men and women emphasize personal and in the family, is part of Mexican culture. Women are psychological stress as a precipitant to symptom exacerbation, much more open about their GI symptoms than men. Men tend to

Functional Brain Gut Functional Brain Gut Research Group Research Group Cross-cultural Column 

be embarrassed regarding public acknowledgment and sublimate References this by joking. Mexican male and female norms of social behavior undoubtedly contribute to these gender differences. 1. Lopez-Colombo A, Bravo-Gonzáles D, Corona-Lopez A, Perez- Lopez ME, Cervantes-Ocampo M, Romero-Ogawa , Morgan Frequent reference to family members represents a cultural D, Schmulson M. First community-based study of functional belief that the individual is part of a greater unit, the family, and gastrointestinal disorders (FGID) in Mexico using the Rome II one’s health can be affected by family relationships, consistent modular questionnaire. Gastroenterology 2006;130(Suppl.2): with research findings in IBS. In an eight country study, including A-508(T1254). Mexico, symptoms were worse if family relationship conflict was 2. Schmulson M, Ortíz O, Santiago-Lomeli M, Gutiérrez-Reyes G, high and if attributions about illness were physiological rather Gutiérrez-Ruiz MaC, Robles-Díaz G, Morgan D. Frequency of than psychological. (6) Of concern is the reluctance of patients functional bowel disorders among healthy volunteers in Mexico to benefit from psychological help. How gastroenterologists can City. Digestive Diseases (Issue on GI Motility-New Directions): present this referral recommendation so that it is better received 2006; 24;342-347. should be addressed. 3. Schmulson M, Ortiz O, Hinojosa C, Arcila D. A single session of reassurance can acutely improve the self-perception of impairment in patients with IBS. Journal of Psychosomatic Research. 2006;61:461-7. 4. Schmulson M, Ortiz O, Mejia-Arangure JM, Hu YB, Morris C, Arcila D, Gutierrez-Reyes G, Bangdiwala S, Drossman D. Further validation of the IBS-QOL: Mexican female IBS patients have poorer quality of life than females from North Carolina. Dig.Dis.Sci. (In press) 5. Carmona-Sanchez R, Tostado-Fernandez FA. [Prevalence of use of alternative and complementary medicine in patients with irritable bowel syndrome, functional dyspepsia and gastroesophageal reflux disease]. Rev Gastroenterol Mex. 2005;70:393-8. Spanish. 6. Gerson MJ, Gerson CD, Awad R, Dancey C, Poitras P, Porcelli P, Sperber A. An international study of irritable bowel syndrome: family relationships and mind-body attributions. Social Science & Medicine 2006; 62: 2838-2847.

Functional Brain Gut Functional Brain Gut Research Group Research Group 10 Guest Column

Probiotics

limitations of the culture methods employed in so many earlier Eamonn M. Quigley, MD, FRCP, studies. While additional studies are need in this area, it seems FACP, FACG, FRCPI unlikely, given the enormous size and diversity of the colonic flora, Professor of Medicine and Human that the administration of a probiotic in what will, inevitably, be Physiology; Principal Investigator, relatively tiny numbers can exert its effects by simple replacement Alimentary Pharmabiotic Centre or displacement of “bad” bacteria. National University of Ireland, Cork; Cork, IRELAND Much interest has been generated by the demonstration of a host [email protected] of immune-modulating effects for certain probiotics, including an enhancement of immunoglobulin A production and a modulation of the pattern of cytokine production by immune cells. These latter effects have been associated with an amelioration of mucosal Probiotics are currently defined as live microbial food ingredients inflammation in a variety of animal models of inflammatory bowel that alter the gastrointestinal microflora (also referred to as the disease and have even been shown to modify inflammatory microbiota) and, thereby, confer health benefit. After years of hype process distant from the gut, in the liver and in the synovium. A and inflated claims, science has of late come to bear on probiotics relatively modest body of clinical trial data from human studies and has, in many instances, confirmed valuable properties. This in inflammatory bowel disease supports the potential value progress has occurred in the context of a re-awakening of interest of probiotics as inflammatory agents (8). A significant body of in the critical role of the enteric flora in homeostasis in health and in evidence now suggests that immune activation and a low-grade disease pathogenesis when perturbed (1). Furthermore, evidence inflammatory state may be evident in, at least some, IBS patients continues to accumulate to indicate a critical role for dysfunction (9). The documentation of increased mast cells and lymphocytes in interactions between the flora and the host in the etiology of in the colo-rectal mucosa and the detection of increased levels inflammatory bowel disease and systemic inflammatory disorders. of pro-inflammatory cytokines in serum and in peripheral blood Clinical trials to demonstrate the translation of potentially beneficial mononuclear cells all support this novel, and unexpected, concept. properties, or characteristics of probiotics, into real patient benefit Indeed, in one study, elevated serum cytokines were shown to have, until recently, been less plentiful and often sub-standard correlate with an altered responsiveness of the hypothalamic- in quality; here too, not surprisingly, progress has also occurred, pituitary-adrenal (HPA) axis, suggesting an influence of mucosal of late. What is the relevance of these advances to functional inflammation on the brain-gut axis, long regarded as of fundamental gastrointestinal disorders? importance to the pathophysiology of IBS (10). While correlations between mucosal immunopathology and systemic cytokine levels A host of bacteriological experiments have clearly demonstrated have yet to be established and precise relationships between that several probiotics (lactobacilli and bifidobacteria being the these immunological findings and patient demographics and most widely studied) exert anti-pathogenic activity, not only by symptomatology remain to be defined, these observations do simple exclusion but also through the production of specific provide a rationale for the use of probiotics, and especially bacteriocins and the digestion of bacterial toxins. Several also those with known immune-modulating properties, in IBS. Indeed, possess anti-viral activity. These properties may be of special O’Mahony and colleagues have documented a correlation between relevance to post-infectious irritable bowel syndrome (IBS) (2,3) the clinical response to a particular probiotic, bifidobacterium or post-infectious functional dyspepsia (FD) (3). While the efficacy infantis 35624, and normalization of the ratio between pro- and of probiotics, in either prevention or therapy, in this context, has anti-inflammatory cytokines in peripheral blood mononuclear cells not been directly tested, the aforementioned anti-bacterial and (11). Probiotics have also been shown, again in animal models, to anti-viral properties have been harnessed to clinical benefit in the enhance gut barrier function and retard translocation of pathogens. management of clostridium difficile infection, diarrheal illnesses in This has been translated into therapeutic benefit in some critical childhood and pouchitis. The recent description of post-infectious illnesses. There is some limited evidence, again primarily in the IBS following an outbreak of viral gastroenteritis should add further post infectious scenario, for impaired intestinal barrier function momentum to this effort (4). The ability of probiotics to modify the in IBS but the impact of probiotics on this parameter of intestinal flora could be of value in IBS patients, in general. While the issue function, in IBS, has yet to be evaluated. of relationships between small intestinal bacterial overgrowth (SIBO) and IBS remain controversial, with overly sensitive tests In man, it is now been clearly established that probiotics can such as the lactulose breath hydrogen test suggesting a strong exert a beneficial impact on acute diarrhoeal illnesses, such as correlation (5) and the more rigorous approach of culturing jejunal rotavirus-associated diarrhea, and that certain organisms appear aspirates indicating none (6), probiotics could certainly play a role effective in pseudomembranous (or C difficile-associated) colitis. in the management of SIBO, if, indeed, it is a factor in IBS. On In human inflammatory bowel disease, the best evidence to date the other hand, IBS, has been associated with disturbances in for efficacy of probiotics comes from pouchitis, where a probiotic the colonic microflora and, especially with a relative deficiency of cocktail, VSL#3, has been shown to be highly effective in both bifidobacteria (7); a situation that could be remedied by probiotic primary and secondary prevention (12). Studies in ulcerative administration. It must be conceded that the interpretation of colitis and Crohn’s disease have, to date, been less impressive data in this area is rendered difficult by significant variations in (8). It should come as no surprise that, given recent interest in the methodology and patient population and well as by the intrinsic

Functional Brain Gut Functional Brain Gut Research Group Research Group Guest Column 11

potential roles of prior bacterial infection and low-grade colonic 5. Pimentel M, Chow EJ, Lin HC. Eradication of small bowel inflammation in its pathogenesis, that probiotics have also been bacterial overgrowth reduces symptoms of irritable bowel studied in irritable bowel syndrome (IBS). While many initial syndrome. Am J Gastroenterol 2000;95:3503-6. Quigley studies were underpowered and subject to criticism on the basis EM. Bacterial flora in irritable bowel syndrome: role in of study design, overall trends suggested benefit, especially, in pathophysiology, implications for management. Chin J Dig relation to what could be generally referred to as “gas-related” Dis 2007;8:2-7. symptoms (13,14). More recently, in two separate studies, we 6. Posserud I, Stotzer PO, Bjornsson E, Abrahamsson H, Simren have demonstrated clear evidence of efficacy for one specific M. Small intestinal bacterial overgrowth in patients with irritable bifidobacterium (bifidobacterium infantis 35624) in improving all bowel syndrome. Gut 2006; [Epub ahead of print]. of the cardinal symptoms of IBS. The first study compared this bifidobacterium with a lactobacillus and placebo when administered 7. Malinen E, Rinttila T, Kajander K, Matto J, Kassinen A, Krobius in a milk vehicle for eight weeks, in unselected IBS patients (11); L, Saarela M, Korpela R, Palva A. Analysis of the fecal the second included over 360 females recruited from primary microbiota of irritable bowel patients and healthy controls with care who received one of three doses of an encapsulated form real-time PCR. Am J Gastroenterol 2005;100:373-382. of the probiotic or placebo for eight weeks (15). In both studies 8. Sheil B, Shanahan F, O’mahony L. Probiotic effects on the bifidobacterium produced a significant improvement in such inflammatory bowel disease. J Nutr 2007;137:819S-24S. cardinal IBS symptoms as pain, bloating and bowel dysfunction as well as an impressive improvement in a measure of global relief. 9. Quigley EM. Irritable bowel syndrome and inflammatory bowel While encouraging, these were relatively short-term studies and disease: interrelated diseases? Chin J Dig Dis. 2005;6:122- these results need to be confirmed in the long-term. 32. 10. Dinan TG, Quigley EM, Ahmed SM, Scully P, O’Brien One considerable advantage that probiotics have over traditional S, O’Mahony L, O’Mahony S, Shanahan F, Keeling PW. pharmaceuticals is an excellent safety profile. Probiotics are well Hypothalamic-pituitary-gut axis dysregulation in irritable tolerated in IBS and there have been, to date, no well-documented bowel syndrome: plasma cytokines as a potential biomarker? instances of infections or other serious adverse events associated Gastroenterology 2006;130:304-311. with probiotic use in irritable bowel syndrome. 11. O’Mahony L. McCarthy J, Kelly P, Shanahan F, Quigley EM. Lactobacillus and bifidobacterium in irritable bowel syndrome: References symptom responses and relationship to cytokine profiles. Gastroenterology 2005; 128:541-51. 1. Quigley EM, Quera R. Small intestinal bacterial overgrowth: roles of antibiotics, prebiotics and probiotics. Gastroenterology 12. Chapman TM, Plosker GL, Figgitt DP. VSL#3 probiotic mixture: 2006;130(2Suppl 1):S78-S90. a review of its use in chronic inflammatory bowel diseases. Drugs 2006;66:1371-87. 2. Mearin F, Perez-Oliveras M, Perello A, Vinyet J, Ibanez A, Coderch J, Perona M. Dyspepsia and irritable bowel syndrome 13. Hamilton-Miller JMT. Probiotics in the Management of Irritable after a Salmonella outbreak: a one year follow-up cohort study. Bowel Syndrome: A Review of Clinical Trials. Microb Ecol Gastroenterology 2005 ;129 :98-104. Health Dis 2001;13:212-216. 3. Marshall JK, Thabane M, Garg AX, Clark WF, Salvadori M, 14. Quigley EM, Flourie B. Probiotics and irritable bowel syndrome: Collins SM; Walkerton Health Study Investigators. Incidence a rationale for their use and an assessment of the evidence to and epidemiology of irritable bowel syndrome after a large date. Neurogastroenterol Motil. 2007;19:166-72. waterborne outbreak of bacterial dysentery. Gastroenterology 15. Whorwell PJ, Altringer L, Morel J, Bond Y, Charbonneau D, 2006;131:445-50. O’Mahony L, Kiely B, Shanahan F, Quigley EM. Efficacy of 4. Marshall JK, Thabane M, Borgaonkar MR, James C. an encapsulated probiotic Bifidobacterium infantis 35624 in Postinfectious Irritable Bowel Syndrome after a Food-Borne women with irritable bowel syndrome. Am J Gastroenterol. Outbreak of Acute Gastroenteritis Attributed to a Viral 2006;101:1581-90. Pathogen. Clin Gastroenterol Hepatol. 2007; [Epub ahead of print]

Functional Brain Gut Functional Brain Gut Research Group Research Group 12 Book Review

ROME III The Functional Gastrointestinal Disorders, Third Edition, 2006

Rome III: The Functional ROME III, the Third Edition, published in September 2006, is Gastrointestinal Disorders, a 1,048 page document written by a collaborative effort of 82 Third Edition. MacLean, VA: international experts. The book consists of seventeen chapters Degnon Associates, Inc., 2006. that contain the most recent information on the epidemiology, pathophysiology, diagnosis, and treatment of FGIDs. Diagnostic Reviewed by: criteria for some of the FGIDs have been revised. “Red flag” Susan Lucak, M.D. symptoms and signs that warrant further diagnostic evaluation Columbia University Medical have been included. Suggestions for when to make a mental health Center referral have also been given. New chapters on pharmacology and pharmacokinetics, sociocultural perspectives related to gender, age, and cultural impact, and childhood FGIDs have Functional gastrointestinal disorders (FGIDs) are a group of been divided into two chapters, one for the neonate/toddler and disorders in clinical medicine that have often posed immense the other for the child/adolescent. One chapter is also devoted problems for patients to experience, for clinicians to diagnose to the development and validation of the Rome III Diagnostic and treat, and for researchers to study. The “road to Rome” Questionnaire. New appendices contain validated Rome III adult began in Rome, Italy, in 1988 during the 12th International and pediatric questionnaires and a table comparing Rome II and Congress of Gastroenterology, where a working team was set up Rome III diagnostic criteria. The most notable aspects of Rome III chaired by W. Grant Thompson, MD to create guidelines for the pertain to the following disorders: management and study of irritable bowel syndrome (IBS). Later, a group of outstanding experts under the leadership of Dr. Douglas Irritable bowel syndrome (IBS) subtyping: In Rome II, IBS with A. Drossman embarked on a mission to define, understand, constipation (IBS-C) and IBS with Diarrhea (IBS-D) subtypes study, diagnose, and treat all of the elusive FGIDs. After a 1990 were based on frequency of bowel irregularities. In Rome III, stool publication outlining the classification system, several committees consistency is emphasized. IBS-C is defined as having at least convened in Rome, Italy, throughout 1994 and began a process 25% of bowel movements (BMs) that are hard or lumpy; in IBS-D, of review and analysis of the medical literature to improve the loose or watery stools are present in at least 25% of BMs. A new methodology for studying, diagnosing and treating about 21 category, IBS with mixed bowel habit pattern (IBS-M), is defined FGID’s. The ultimate goal was to improve the lives of our patients as having both hard, lumpy and loose, watery BMs, each 25% of and their families. the time. This is not to be confused with IBS with an alternating bowel pattern, in which constipation or diarrhea will alternate for a ROME I, the First Edition published in1994, was a compilation of prolonged period of time. The recurring abdominal pain/discomfort documents previously published in Gastroenterology International in IBS has to be present for at least 3 days/month for the last 3 over a period of five years by 30 international investigators who months, with symptom onset at least 6 months prior to diagnosis. categorized the FGIDs from esophagus to anus. The most striking It is important to recognize that bowel habit pattern subtypes are result of this process was the creation of the Rome I symptom- unstable over time, with a tendency of IBS-C to become IBS-D based diagnostic criteria for FGIDs. These criteria began to and IBS-C and IBS-M sharing similar characteristics. change the diagnostic approach to FGIDs, no longer considered “diagnoses of exclusion” but rather “diagnoses of inclusion”. The Functional dyspepsia classification: Functional dyspepsia (FD) Rome criteria enabled positive diagnoses without the need for is a very difficult symptom complex to embrace. In the past, FD extensive and unnecessary diagnostic studies to “rule out organic was categorized as ulcer-like or dysmotility-like. Based on recent disease”. In addition, recommendations for the optimal design of physiologic, clinical and population studies, Rome III offers a new research protocols were included, to ensure improved uniformity way of thinking about FD. It is described as an “umbrella” term for and quality in future clinical trials and investigations. what appear to be two subsets that may overlap: (1) postprandial distress syndrome (PDS), consisting of dyspeptic symptoms ROME II, the Second Edition published in 2000, resulted from induced by a meal, and (2) epigastric pain syndrome (EPS), in the continual process of analyzing new scientific and clinical which epigastric pain is present regardless of meal ingestion. evidence in the study of FGIDs. Rome II diagnostic criteria for IBS were extended with a focus on frequency of symptoms occurring Functional disorders of the gallbladder and sphincter of Oddi: twelve weeks (not necessarily consecutive weeks) within twelve Functional biliary tract disorders have been a challenging months. For the first time, pediatric FGIDs were categorized, group of disorders to diagnose and treat. These disorders are and chapters highlighting physiology of motility, sensation, of low prevalence in comparison to other FGIDs, but they tend brain-gut interactions, and psychosocial aspects were included. to be investigated with invasive and risky studies, such as Recommendations from the Clinical Outcomes Conference held endoscopic retrograde pancreatography (ERCP) or sphincter in Vienna in 1998, a conference that initiated the collaborative of Oddi manometry, and treated with unnecessary endoscopic process of Rome committees with international expert advisors, sphincetrotomy and surgery. Rome III recommends more pharmaceutical companies and regulatory agencies, were also restrictive evaluation of these disorders. When diagnostic criteria outlined. are met, studies such as endoscopic ultrasound (EUS) and

Functional Brain Gut Functional Brain Gut Research Group Research Group 13

magnetic resonance imaging (MRI) of the abdomen should be mental health providers, the pharmaceutical industry and, most of performed first, followed by a therapeutic trial of medications all, our patients with FGIDs will greatly benefit. There is something such as nifedipine or antidepressants. If these treatments are here for everyone! The Rome process continues to be a formidable unsuccessful, it is recommended that more invasive studies and process, but it has been based on a very solid foundation. I treatments be carried out in centers specifically dedicated to these congratulate all who have participated in this “colossal” effort. disorders. This is in an effort to limit the number of unnecessary and potentially risky procedures and to identify a group of patients Drossman DA, Corazziari E, Delvaux M, Spiller RC, Talley NJ, who are more likely to benefit from these interventions. Thompson WG, Whitehead WE (Editors). Rome III: The Functional Gastrointestinal Disorders, Third Edition. McLean, VA: Degnon Rome III is the single most comprehensive and authoritative Associates, Inc., 2006. resource on the subject of FGIDs. It is readable, well organized, clearly labeled, and extensively referenced. The 82 experts who To order: $99 for soft-bound and $125 for cloth bound – see participated in the Rome III process have created an outstanding website www.romecriteria.org work from which clinicians, clinical investigators, basic scientists,

Functional Brain Gut Functional Brain Gut Research Group Research Group 14 IFFGD Spring 2007 Update

International Foundation for Functional Gastrointestinal Disorders Providing Support for 15 Years

Spring 2007 Update Nancy Norton President

It has been another busy season for the International Foundation Since September, IFFGD has exhibited during five major medical for Functional Gastrointestinal Disorders (IFFGD) as we continued meetings attended by professionals from gastroenterology, urology, our efforts to raise awareness and understanding about digestive pediatric gastroenterology, and family practice. The meetings disorders and the burden they create for individuals, families, and provided opportunities to exchange ideas with clinicians who treat society. In recent months, IFFGD has reached out to legislators, the patients with digestive disorders and distribute patient education public, and clinicians to direct attention to the quality-of-life issues literature. patients face daily and the need for improved treatment options. Our enduring goal is to improve the lives of those affected by digestive IFFGD has been a long-time proponent for increased research disorders. By working cooperatively with healthcare professionals funding at the National Institutes of Health (NIH) and regularly and patients to improve understanding of the disorders, we are provides testimony to Congress on behalf of those affected by gradually helping to bring about that change. Our thanks go out to digestive disorders. In April 2007, IFFGD Vice President, William each of you for supporting IFFGD in this mission. Norton, testified before the House Appropriations Subcommittee on Labor, Health & Human Services, Education and Related Agencies Nancy J. Norton to draw attention to the need for additional research and recommend President and Founder, IFFGD increased funding to support digestive disorders research.

November 2006 was the 9th annual GERD Awareness Week. As in previous years, media outlets published IFFGD educational messages about GERD. An article, “Is Your Holiday Meal Getting Hard to Swallow? Keep Reflux Disease out of your Celebrations” appeared in newspapers. Special kits of educational materials were available to groups interested in raising awareness about GERD.

Functional Brain Gut Functional Brain Gut Research Group Research Group 15 DDW 2007

Clinical Research Fora

Sunday, May 20th esophagitis – Xiaohong Sun E. Dukes 11:00am Evidence for familial aggregation of 9:30am Long-term mast cell stabilization Esophageal Motility and Sensation IBS in a large family case-control study – Yuri downregulates mucosal microinflammation in Chairs: Ronnie Fass, Peter J. Kahrilas A. Saito the jejunum of diarrhea-prone Irritable Bowel 8:30 – 10:00am, Room 152 Syndrome (IBS) – Laura Ramos 11:15am Prevalence of idiopathic fecal 8:30am Acid related oesophageal sensitivity, incontinence in a community sample – Alexandra 9:45am The effect of ghrelin on gut transit in not dysmotility, differentiates subgroups of Ilnyckyj man – Ylva Haglund patients with non-erosive reflux disease – Anton 11:30am Irritable Bowel Syndrome (IBS) is V. Emmanuel strongly associated with generalized anxiety Tuesday, May 22nd 8:45am Increased intrabolus pressure: a disorder (GAD): a population-based study novel pathophysiologic factor in non-obstructive – Justin Wu New insights on the treatment of functional dysphagia – Mentore Ribolsi dyspepsia 11:45am The 102 T/C polymorphism of the Chairs: Michael P. Jones, Richard J. Saad 9:00am Absence of augmentation of the 5-Ht2a receptor gene is more frequent in IBS in 10:30am – 12:00pm, Room 154 cortical swallowing network by subliminal Mexico, and more likely to be associated with IBS esophageal acid exposure in GERD patients females and IBS-C – Max Schmulson 10:30am Relationship between gastric – Krisna Chair emptying rate, symptoms, quality of life (QoL), Pathophysiology of colonic motility and response to prokinetic drugs in patients 9:15am Distension-induced pain in the disorders with postprandial distress syndrome (PDS) esophagus correlates with wall stress and strain Chairs: Anil Minocha, Henry C. Lin – Enriquez Dominguez-Munoz but not mucosal perfusion in healthy volunteers 2:15 – 3:45pm, Room 151 A – Dag Arne Hoff 10:45am Efficacy and safety of Itopride 2:15pm Sacral nerve stimulation for in functional dyspepsia: results of Phase II 9:30am High-resolution manometry (HRM) constipation: an international multi-centre study multicenter, randomized, double blind, placebo- in the detection of achalasia: computerized – Thomas C. Dudding controlled trials – Nicholas J. Talley algorithms of analysis tested on 400 consecutive 2:30pm Evidence of enteric neuronal loss, patients – John Rice 11:00am Comparative study of the effects altered chemical coding and increased oxidative of Mitemcinal (GM-611), Erythromycin, and 9:45am Investigation of esophageal sensation stress in colons from diabetic patients – Richard Cisapride on gastric emptying in Rhesus and biomechanical properties in functional chest Blatt monkeys – Kenji Yogo pain – Issam Nasr 2:45pm Abnormalities of prostaglandins and 11:15am Tegaserod significantly improves Anorectal motility, sensation and disorders COX enzymes in female patients with slow transit moderate-severe dysmotility symptoms in Chairs: Ashok K. Tuteja, Satish C. Rattan constipation – Jose Behar patients with functional dyspepsia – Nimish 10:30am – 12:00pm, Room 209 3:00pm Association of Faah gene variation in Vakil 10:30am Anorectal-cortical function is impaired metabolism of endocannobinoid and phenotype 11:30am Work productivity and daily activity in patients with dyssynergic defecation – Jose of functional gastrointestinal disorders and impairment in patients with functional dyspepsia: M. Remes-Troche gastrointestinal transit – Paula Carlson double-blind comparison of Tegaserod vs. 10:45am A novel implantable on-demand 3:15pm Role of platelet activating factor placebo – Loren Laine microstimulator can increase resting anal (PAF)-induced H2O2 production via activation of 11:45am Effect of placebo in controlled trails sphincter pressure: a pilot study in a porcine NADPH oxidases in sigmoid motor dysfunction in of patients with functional dyspepsia: a meta- model – John O. Clarke Ulcerative Colitis (UC) – Sharad Kunnath analysis – Changcheng Wang 11:00am Determining the site of origin of the 3:30pm Colonic hypomotility associated Gastric motility, sensation and disorders defecatory urge using combined impedance and with butyrate-induced non-inflammatory Chairs: William L. Hasler, Anil Minocha manometry in the human ano-rectum – Taher hypersensitivity of the colon can be restored 2:15 – 3:45pm, Room 209 Omari by estrogen substitution in ovariectomized rats – Bruno M. Balsiger 2:15pm Simultaneous use of smartpill pH and 11:15am Which factors predispose to pressure capsule, antroduodenal manometry, incontinent bowel movements in women with and gastric emptying scintigraphy to access fecal incontinence? – Adil E. Bharucha Monday, May 21st gastric emptying of digestible and nondigestible solids – Henry P. Parkman 11:30am Predictive factors for successful Pharmacotherapeutics in functional sacral nerve stimulation in the treatment of gastrointestinal and motility disorders 2:30pm The herbal medication, Iberogast®, fecal incontinence: a 10 year cohort analysis Chairs: Max Schmulson, Martin Storr relaxes the proximal stomach, stimulates antral – Thomas C. Dudding 8:30 - 10:00am, Room 144 motility, but does not affect pyloric and duodenal motility, and slows gastric emptying of liquids in 11:45am Functional constipation (FC): relation 8:30am Pharmacogenomics of Clonidine in healthy men – Christine Feinle-Bisset of the clinical and functional features to rectal Irritable Bowel Syndrome -- Irene Busciglio sensory threshold (Rst) – Belen Herreros 2:45pm Incidence and predictors of small 8:45am Td-5108, a selective 5-HT agonist intestinal bacterial overgrowth in gastroparesis Epidemiology of functional GI disorders with high intrinsic activity, shows immediate and – Savio Reddymasu Chairs: Richard Locke, John K. Marshall sustained prokinetic activity in healthy subjects 10:30am – 12:00pm, Room 147 – M.R. Goldsberg 3:00pm Acute Tryptophan depletion confirms involvement of 5-Hydroxytryptamine in the 10:30am Enhanced expression of genes 9:00am VIP: a novel class of promotility/ control of gastric sensorimotor function in man associated with visceral hypersensitivity in the prokinetic agents – Xuan-Zhend Shi small intestine of Irritable Bowel Syndrome – Brecht Geeraerts 9:15am Lack of effect of the NK3 receptor patients – Angele Kerckhoffs 3:15pm Plasma glucose-dependent gastric antagonist, Talnetant Sb223242, on symptoms slow wave uncoupling and loss of rhythmicity 10:45am Different clinical characteristics of of IBS: results of two randomized, double-blind, during graded hyperglycemic clamping in patients with non-erosive disease and reflux placebo-controlled dose ranging trials – George humans measured by multichannel mucosal Functional Brain Gut Functional Brain Gut Research Group Research Group 16DDW Meeting Schedule

recording – Radoslav Coleski Washington DC Convention Center, Room functional abdominal pain or Irritable Bowel 151 Syndrome: a randomized controlled trial – Arine 3:30pm Response of diaphragm biofeedback Chairs: Mae F. Go; William D. Chey. Vlieger on proximal gastric volume after test meal – Xiaohong Sun Lubiprostone significantly improves symptom 11:45am Impact of serotonin receptor-3 gene relief rates in asdults with irritable bowel polymorphism on Irritable Bowel Syndrome Impact of diabetes on gastrointestinal syndrome and constipation(IBS-C): Data – Lisa Aibiki motility from two, twelve-week, randomized, placebo- Chairs: Henry P. Parkman, Sean M. Ward Functional gastrointestinal disorders: controlled double-blind trials. - Douglas A. 4:00 – 5:30pm, Room 140 symptoms, diagnosis and validation Drossman, MD Chairs: David Armstrong, Mark Pimentel 4:00pm Differences in protein expression 2:15 – 3:45pm, Room 151 AB between diabetic nod mice with and without Wednesday, May 23rd delayed gastric emptying – Kyoung M. Choi 2:15pm Screening for Celiac Sprue in patients with suspected Irritable Bowel Syndrome: results 4:15pm Preliminary results of multipoint gastric Functional gastrointestinal disorders: from a prospective US multi-center trial – William electrical pacing for the treatment of patients with psychosocial and psychotherapeutic D. Chey diabetic gastroparesis – Richard McCallum Chairs: Jennifer A. Christie, Jeffrey M. Lackner 2:30pm Gastroenterologist (GE) perceptions 4:30pm Soy germ-enriched pasta containing 10:30am – 12:00pm, Room 140 of patient anxiety (Anx) and Depression (Dep): is isoflavones ameliorates gastric emptying time in poor perception misattribution? Laurie Keefer diabetic patients – Carlo Clerici 10:30am Structured patient education is superior to a self-help guidebook in Irritable 2:45pm Is intolerance of drugs an extra 4:45pm A placebo-controlled cross-over Bowel Syndrome (IBS) – a randomized controlled GI somatic manifestation of Irritable Bowel study of intrapyloric injection of botulinum toxin trial – Gisela Ringstrom Syndrome? Alexandre Gougeon in diabetic or postsurgical gastroparesis – Joris Arts 10:45am Women respond to conditioning and 3:00pm Continuous 40-hour esophageal acid men to suggestion of nausea – Paul Enck exposure in normal weight (Nw), overweight 5:00pm Double blinded randomized study of (Ow), and obese (Ob) patients with GERD temporary gastric electrical stimulation (GES): 11:00am Differential modulation of the regional symptoms – Michael D. Crowell preliminary results of the endostim study brain by hypnotic suggestion between patients (Endoscopic Stimulation Temporarily Implanted with Irritable Bowel Syndrome and healthy 3:15pm G298s mutation in Nav1.5 in a patient Mucosally) – Thomas L. Abell subjects – Takahiro Terui with Irritable Bowel Syndrome reduces sodium current density and mechanosensitivity – Peter 5:15pm The role of advanced glycation END 11:15am Gastrointestinal symptom-specific R. Strege products (AGEs) in the pathogenesis of diabetic anxiety: an important predictor of health outcome enteropathy – Pankaj J. Pasricha and symptom severity in patients with Irritable 3:30pm Cluster analysis evidence that Irritable Bowel Syndrome – Magnus Simren Bowel Syndrome is not a single disorder but a Late Breaking Absracts collection of distinct syndromes – William E. Tuesday May 22 10:30 - 12:00 PM 11:30am Hypnotherapy for children with Whitehead

Basic Research Fora

Sunday, May 20th Chairs: Million Mulegeta, Hans-Rudi 10:30am – 12:00pm, Room 103 AB Berthoud 10:30am Differential functioning of pain 10:30am – 12:00pm, Room 151A Synaptic transmission in the enteric modulatory networks in men with and without nervous system 10:30am Involvement of the anterior cingulate Irritable Bowel Syndrome: a central role of the Chairs: Tamas Ordog, Alan Lomax cortex in visceral pain: mediation by NMDA parabrachial nucleus – Kirsten Tillish 8:30 – 10:00am, Room 143C receptors and Ca2+/Calmodulin-dependent 10:45am Cortical mapping of digestive protein Kinase II dependent pathways – Zhijun 8:30am Functional and phenotypic symptoms during intracerebral electrical Cao characterization of beta-3 adrenoceptor in stimulation – Agata Mulak human enteric neurons – Nadia Hafsi 10:45am Brain processing of somatic pain 11:00am Heart rate variability as a marker of and of endogenous somatic pain modulation in 8:45am Synaptic activation of Trpc channels stress in inflammatory bowel diseases – Bruno Irritable Bowel Syndrome – Clive Wilder-Smith by metabotropic purinergic P2yl receptors in Bonaz the submucosal plexus of the guinea pig small 11:00am Attenuation of colitis by a tricyclic 11:15am Alterations of emotional modulation intestine – Sumei Liu antidepressant is mediated via the vagus nerve in Irritable Bowel Syndrome: an fMRI study – Jean-Eric Ghia 9:00am Synaptophluorin mice: a novel model – Joshua Bueller to study synaptic transmission in the enteric 11:15am Chronological assessment of 11:30am Alterations in intestinal serotonin nervous system – Pieter Vanden Berghe ultrastructural gut inflammation in a rat model of expression in Dyspepsia and Irritable Bowel persistent natural stress – Maria Vicario 9:15am Functional interaction between P2X Syndrome – Amy E. Foxx-Orenstein and nicotinic acetylcholine receptors in enteric 11:30am The role of NMDA receptors in chronic 11:45am Stress-induced cortical response neurons and in transfected Hek-293 cells – Dima visceral hyperalgesia following a neonatal and colonic mucosal CRF-1 mRNA receptor Alkawwas somatic stimulus – Adrian Miranda expression correlate with symptoms of chronic 9:30am Expression of Pkg1 in intrinsic primary 11:45am Decreased cortical activation during stress and quality of life in Irritable Bowel afferent neurons of the ENS: potential role in rectal distention in patients with functional Syndrome (IBS) – Elizabeth J. Videlock development of long-term hyperexcitability and constipation with normal rectal compliance IBS – Zhishan Li – Annie O. Chan Wednesday, May 23rd 9:45am Brain derived neurotrophic factor (BDNF) enhances enteric nervous system Monday, May 21st Infection, inflammation and immune signaling both at the pre- and postsynaptic level modulation of gut motility – Werend Boesmans Translational aspects of brain gut Chairs: Keith A. Sharkey, Aiping Zhao Brain-gut axis: basic science interactions 10:30am – 12:00pm, Room 101 Chairs: Qasim Aziz, Nicholas Verne Functional Brain Gut Functional Brain Gut Research Group Research Group DDW Meeting Schedule 17

10:30am Efficient knock-down of Rgs4 +Foxp3+Regulatory T cells in Irritable Bowel Model – Hiroto Miwa expression in colonic smooth muscle in vitro Syndrome – Tobias Liebregis 2:45pm Autonomic responses to distal and in vivo by small interfering RNA (Sirna) 11:45am Inflammation-induced changes in esophageal acidification and their relationship to – Wenhui Hu the electrical and synaptic properties of guinea sensitization in a human model of visceral pain 10:45am Citrobacter Rodentium-induced pig colonic myenteric neurons persist following hypersensitivity – Abhishek Sharma alterations in colonic function are associated recovery from inflammation – Eric Krauter 3:00pm Mice lacking the TRPV4 ion channel with upregulation of H-17 cytokines – Jennifer Upper gastrointestinal tract sensory display major deficits in spinal colonic but not A. Stiltz physiology and pathophysiology vagal gastroesophageal mechanosensory 11:00am Evidence of small bowel neuro- Chairs: Jyoti N. Sengupta, Braden Kuo function – Stuart M. Brierley muscular abnormalities in a rat model of herpes 2:15 – 3:34pm, Room 101 3:15pm Molecular and behavioral correlates simplex virus-1 (Hsv1) infection of the enteric 2:15pm Role of nitric oxide in peripheral control of chronic gastric hypersensitivity in a novel nervous system – Roberto de Giorgio of vagal afferent mechanosensitivity – Amanda model of functional dyspepsia type pain in rats 11:15am Inflammation of the guinea pig distal J. Page – John Winston colon is associated with a loss of intestinofugal 2:30pm Decreased rat voluntary movement 3:30pm Cholecystokinin induced plasticity neurons – David R. Linden as a measure of chronic visceral pain: a study of esophago-gastric vago-vagal reflexes – R. 11:30am Ctla-4 haplotypes and Cd4+Cd25 using the Rat Chronic Acid Reflux Esophagitis berto Travagli

Clinical Practice Symposium

Tuesday, May 22 9:14am Non-medical therapies for constipation: 10:30am – 12:00pm, Ballroom C biofeedback, pudendal nerve stimulation, colonic 10:30 am Screening for Celiac Sprue in IBS: pacing – Michael A. Kamm Controversies in constipation when and how? – Brennan M. Spiegel Chairs: William E. Whitehead, Lawrence R. 9:36am Colectomy: pre-op evaluation, 10:53am Prebiotics and probiotics: ready for Schiller outcomes and adverse events – Emina H. prime time in IBS? – Robin C. Spiller 8:30am – 10:00am, Ballroom C Huang 11:14am Antibiotics for IBS: should we or 8:30am Which diagnostic tests in which Inflammation and IBS: Understanding shouldn’t we? – Stephen J. Vanner patients? – Adil E. Bharucha pathogenesis and altering treatment 8:52 am Current and emerging therapies for paradigms 11:36am Is IBS an immune disorder? – Jackie constipation – William D. Chey Chairs: Philip Schoenfeld, Udi Ringel D. Wood

Clinical Symposia

Sunday, May 20th Tuesday, May 22nd Wednesday, May 23rd

Impact of visceral hyposensitivity in Outcome measures in functional Functional pain syndromes: overlap of IBS functional gastrointestinal disorders gastrointestinal disorders and co-morbid conditions Chairs: Bruce D. Naliboff, Satish S. Rao Chairs: Emeran A. Mayer, E. Jan Irvine Chairs: Douglas A. Drossman 8:30 – 10:00am, Room 209 2:15 – 3:45pm, Room 151 AB 8:30 – 10:00am, Room 143 ABC 8:30am Definitions, diagnosis, prevalence, 2:15pm What determines the symptom severity 8:30am Epidemiology of IBS and co-morbid and clinical impact of visceral hyposensitivity in functional gastrointestinal disorder patients conditions – Ami D. Sperber – Mark Scott – Brennan M. Spiegel 8:48am Psychological correlates of IBS, 9:00am Peripheral and central pathophysiologic 2:37pm The gold standard: global symptom chronic fatigue syndrome and fibromyalgia – the mechanisms of rectal hyposensitivity – Marc relief as primary endpoint – Allen Mangel role of anxiety and depression – Francis Creed Gladman 2:59pm The challenge of the gold standard 9:06am Neurobiologic alterations in IBS and 9:30am Impact of visceral hyposensitivity – William E. Whitehead fibromyalgia – Lin Chang on the management of constipation and fecal 3:21pm Do we need a new gold standard? 9:24am Infections, cognitions and behaviors incontinence – Satish S. Rao – Michael Camilleri in IBS and chronic fatigue syndrome – Rona Moss-Morris 9:42am Summary and conclusions – Douglas A. Drossman

Basic Symposium, Topic Forum

Tuesday, May 22nd 4:30pm Post-inflammatory visceral Wednesday, May 23rd hypersensitivity and pain mechanisms – Nathalie Mechanisms of persistent Vergnolle Repceptors and ion channels on visceral postinflammatory changes in gut function 5:00pm Impact of inflammation on gut function: afferents Chairs: Giovanni Barbara, Keith A. Sharkey what makes it a “memorable” response – Terez Chairs: Michael Pezzone, Michael J. Beyak 4:00 – 5:30pm, Room 152 Shea-Donohue 8:30 – 10:00am, Room 156 4:00pm Persistent post-inflammatory 8:30am Transient receptor potential Vanilloid- alterations in enteric nerve function – Gary M. 4 activation in the colon causes visceral Mawe hypersensitivity symptoms – Nicolas Cenac Functional Brain Gut Functional Brain Gut Research Group Research Group 18DDWFBG Meeting Election Schedule Results for Council

8:45am Modulation of visceral afferents by Chairs: Shin Fukudo, Million Mulugeta predicts clinically important difference in pain large conductance Kca channels – Jorgen 10:30am – 12:00pm, Room 147 and is independent of baseline pain severity Jensen in Irritable Bowl Syndrome (IBS) – Vanessa Z. 10:30am CRF1/CRF2 receptors: the Yin and Ameen 9:00am P23 and Trypsin IV, inhibitor-resistant Yang of the stress response – Rita Valentino Trypsins, induce pancreatitis and activate 11:00am Women with Irritable Bowel 11:00am CRF signaling in the periphery: nociceptive pathways in the pancreas – Eugene Syndrome: pelvic floor disorders and associated organ-specific warning systems – Charalabos P. Ceppa quality of life – Jennifer Y. Wang Pothoulakis 9:15am Electrophysiological and molecular 11:15am Accelerated small bowel transit 11:30am CRF1rs in the clinic: will they work? signatures of glucose inhibited neurons in the and contracted transverse colon in diarrhoea- – Emeran A. Mayer nodose ganglia – Gintautas Grabauskas predominant Irritable Bowel Syndrome (IBS-D): Outcomes and treatment of the Irritable novel insights from magnetic resonance imaging 9:30am Cinnamaldehyde sensitizes and Bowel Syndrome (MRI) – Robin C. Spiller activates rat vagal and spinal afferent neurons Chairs: Richard Locke, Uri Ladabaum in vitro and in vivo – Anne-Marie Coelho 11:30am Safety and efficacy of Crofelemer 10:30am – 12:00pm, Room 151 AB in patients with diarrhea predominant Irritable 9:45am Structure and function of 10:30am Is asking “How are you doing?” Bowel Syndrome (D-IBS) – Anthony J. Lembo mechanoreceptors innervating the internal anal enough to capture health related quality of life sphincter of the guinea pig – Penny Lynn 11:45am The safety profile of Alosetron since (HRQOL) and overall severity in Irritable Bowel reintroduction under the risk management The CRF signaling system: from basic Syndrome (IBS)? – Brenna M. Spiegel program – Eric Carter science to novel IBS therapy 10:45am Global measure of adequate relief

Motility and Nerve Gut Interaction Plenary Session

Monday, May 21st – Viola Andresen 4:45pm Fecal serine-protease activity: a possible pathophysiological factor and 4:15pm The Hpa-axis function and autonomic biomarker for diarrhea-predominant Irritable Chairs: James J. Galligan, Emeran A. response to stress in functional bowel disorders Bowel Syndrome – Krisztina Gecse Mayer in a population based cohort – Tamira K. 4:00 – 5:30pm, Room 101 Klooker 5:00pm History of trauma and the risk of IBS among women veterans – Hashem El-Serag 4:00pm Effects of a novel, first-in-class 4:30pm Impact of serotonin transporter gene Guanylate Cyclase-C activator, Linaclotide polymorphism on brain activation by colorectal 5:15pm Randomized controlled trial shows Acetate (Md-1100), on gastrointestinal and distention in healthy subjects and patients with biofeedback to be superior to alternative colonic transit habits in patients with constipation- Irritable Bowel Syndrome – Shin Fukudo treatments for patients with fecal incontinence predominant Irritable Bowel Syndrome (C-IBS) – Steve Heymen

Poster Sessions: all sessions are from 8:00 am to 5:00 pm, and all are in Hall E

Sunday, May 20 Tuesday, May 22 Wednesday, May 23

BASIC: Enteric nervous system modulation of CLINICAL: FGD – psychological and CLINICAL: Epidemiology of functional GI gut function psychotherapy aspects disorders COMBINED: Inflammation, infection and BASIC: Gastric motility and sensation – basic CLINICAL: FGD – symptoms and diagnosis immune modulation of gut motility science CLINICAL: Pharmacotherapeutics in GI BASIC: Oropharyngeal, esophageal motility and functional and motility disorders Monday, May 21 sensation – basic science BASIC: Basic science of the brain-gut axis COMBINED: Anorectal motility, sensation and COMBINED: Brain gut interactions, translational BASIC or COMBINED: Gastric motility and disorders aspects functional disorders COMBINED: Esophageal motility and functional COMBINED: Colonic motility disorders COMBINED: Small intestinal motility and COMBINED: Gastrointestinal sensory disorders mechanisms and visceral hypersensitivity

Business Meeting: Motility & Nerve-Gut Interaction

Monday, May 21st

5:30 – 6:30pm, Room 101 Chairs: James J. Galligan, Emeran A. Mayer

Breakfast Symposium, Tuesday, May 22nd

“The IBS Consensus: Unifying Practical Strategies “Peripheral Treatment of the Symptoms” Grand Hyatt, Washington DC for the Optimal Treatment of IBS” Independence Ballroom Eamonn M.M. Quigley, Tuesday, May 22, 2007 Douglas A. Drossman MD “Probiotics and Antibiotics” 5:55 AM to 7:45 AM Moderator Ray E. Clouse Michael Camilleri, “Central Treatment of the Symptoms” Functional Brain Gut Functional Brain Gut Research Group Research Group Special Report 19

IBS Days (Reizdarm-Tage) in Tübingen, Germany March 28 to 31, 2007 Paul Enck, MD

For the second time since his move to the Department of Doug Drossman, Chapel Hill; Sigrid Elsenbruch, Essen; Psychosomatic Medicine and Psychotherapy, University Margarete Heitkemper, Seattle; Peter Henningsen, Munich; Hospital Tübingen, Germany, Paul Enck, the department´s Bernd Löwe, Heidelberg; Ute Martens Tuebingen; Frauke director of research, and the department chair, Stephan Musial, Essen; Hubert Moennikes, Berlin; Brenda Toner, Zipfel have organized the IBS days in Tübingen, in Toronto; David Thompson, Manchester; Peter Whorwell, collaboration with the local Department of Gastroenterology Manchester and others – to discuss recent developments and the German IBS patient self-aid organisation (www. of standardization of IBS definitions and guidelines. DSM reizdarmselbsthilfe.de). This time, the 4-day event included V and ICD 11 trends were contrasted with results from the a CME-symposium for physicians in private practice, hospital Rome consensus process. It was found that attempts to bring doctors, and psychologist on Wednesday afternoon, a 2-day the subspecialties of gastroenterology and psychosomatic/ expert workshop on Irritable bowel syndrome -- a single psychiatry together would be in the interest not only of IBS gastrointestinal disease or a general somatoform disorder? patients and their clinical management but also be of profit on Thursday and Friday, and a patient information day on for future research in this challenging area. Proceedings of Saturday. All three events were well attended and perceived the workshop will be published in a future issue of the Journal by the respective audience. of Psychosomatic Research.

Highlight of the Wednesday CME symposium on new The final day (Saturday) encouraged more than 100 IBS developments in IBS management at the University Hospitals patients to attend and discuss their personal history and Tübingen was Douglas Drossman´s state-of-the-art lecture suffering with the local experts. The four days of research on “Structuring Doctor-Patient Communication in IBS” that and teaching were regarded as an overall success by all demonstrated (via videos) the well-known ability of the author and were financially supported by the German Research to teach and guide doctor-patient interaction. Council (DFG) as well as by the industry (AstraZeneca, Falk, Lundbeck, Steigerwald, Symbiopharm). The workshop on Thursday and Friday took place in the remote and romantic environment of a 1000-year old castle (www.schloss-haigerloch.de) near Tübingen that allowed 25 national and international experts – among them David Alpers, St.Louis; Qasim Aziz, London; Francis Creed, Manchester;

Functional Brain Gut Functional Brain Gut Research Group Research Group 20 Fifth Annual Young Investigators Forum

Fifth Annual Young Investigators Forum William D. Chey, MD, AGAF, FACG Associate Professor of Medicine Director - GI Physiology Laboratory University of Michigan Health System

The Fifth Annual Young Investigators Forum was recently held from March 23-25, 2007, in Del Mar, California. As in previous years, this meeting provided a showcase for the best a n d b r i g h t e s t y o u n g investigators conducting research in Functional Bowel Disease and Motility Disorders. In all, 20 young investigators and 7 faculty from 19 medical centers in the United States, Europe, and Australia participated in the meeting. The scientific presentations spanned t h e s p e c t r u m o f o u r discipline. Each and every one of the fellows did an outstanding job and should be congratulated for their scientific contributions to our field. In addition to outstanding covered included keys to a great presentation, setting up science, I was impressed by the level of preparation that went a GI physiology laboratory, funding opportunities for young into the investigator’s slides and oral presentations. It is clear investigators, manuscript and grant preparation, how to that this group is ready to present their work at Digestive effectively interact with industry, and how to get the most out Diseases Week and other important scientific meetings. of a mentoring relationship.

Each year, the faculty identifies the two most outstanding I have heard back from several fellows and faculty members research projects presented at the meeting. This year’s who universally stated that they took a great deal away from winners were Birgit Adam from the University of Adelaide, the weekend. Such feedback validates the need to continue Australia, for “Gut homing properties of circulating T cells this important FBG initiative. Perhaps as important as the in patients with IBS” and Niels Eijkelkamp from UMC outstanding science that was presented were the new Utrecht, the Netherlands, for “G protein-coupled receptor relationships that were forged during the meeting. If history kinase 6 controls post-inflammatory visceral hyperalgesia is a guide, they will last a lifetime. in mice”. Both of these impressive young investigators were able to transform the complexities of their projects into It has been an honor and a privilege to chair this year’s Young understandable concepts that made clear the timeliness and Investigator’s Meeting. The experience leaves me hopeful importance of their research. and excited about the future of these young investigators and for the continued vibrancy and longevity of our field. I wish the In addition to presenting their work, fellows received incoming chair, Carlo DiLorenzo, good wishes as he begins invaluable insights on a variety of topics through lectures to plan the next Young Investigator’s Meeting. and interactive work-shops with the faculty which included Lin Chang, Ray Clouse, Carlo DiLorenzo, G. Richard Locke, Henry Parkman, and Eamonn Quigley. Topics that were

Functional Brain Gut Functional Brain Gut Research Group Research Group 21

Birgit Adam, MD Niels Eijkelkamp, MSc University of Adelaide, U n i v e r s i t y M e d i c a l Royal Adelaide Hospital; Center Utrecht, The Adelaide, South Australia, Netherlands Australia N i e l s E i j k e l k a m p In 2002, I graduated received his MSc with in Medicine from the honor in 2003 from the University of Duisburg- university of Utrecht Essen, Germany. A (Netherlands). During the S t u d e n t R e s e a r c h finalization of his MSc, Scholarship in 2000 from he did basic research the Medical School of in the laboratory of the University Duisburg- Essen enabled me to establish an animal model of post-inflammatory visceral hyperalgesia as part of my doctorial thesis under Psychoneuroimmunology at the University Medical Center the supervision of Professor Gerald Holtmann. Prior to Utrecht (Netherlands) and Ohio State University (Columbus, graduation, I was fortunate to spend a 4-month period OH). Currently, he is in his PhD program at the Laboratory of at the University of California Los Angeles (UCLA) in the Psychoneuroimmunology at the University Medical Center laboratories of Professor Emeran A. Mayer. in Utrecht (Netherlands). The research subject of his PhD is about how a family of kinases (G protein-coupled receptor I pursued my clinical training and research career further kinases), that are involved in G protein coupled receptor in the Department of Gastroenterology and Hepatology, (GPCR) desensitisation, can influence the development of University Hospital Essen and, in 2004, I was awarded inflammatory bowel disease and in particular the persistence a Scholarship by the University of Duisburg-Essen for a of post-inflammatory visceral hyperalgesia after recovery of Research-Fellowship at the Department of Gastroenterology a colonic inflammation. and Hepatology at the Royal Adelaide Hospital, University of Adelaide, Australia. Since June 2005, I have been a fellow at During his PhD, he has been awarded twice with a Travel that department pursuing my clinical training and translational Award from the psychoneuroimmunology research society research in the field of functional gastrointestinal disorders (PNIRS). Recently, his abstract on the role of GRK6 on the under the mentorship of Professor Gerald Holtmann. Our development of post-inflammatory hyperalgesia was selected group has successfully identified an association of cellular to be presented at the FBG YOUNG INVESTIGATROS immune activation and symptoms in patients with functional FORUM and was also selected for the FBG Young gastrointestinal disorders. Besides continuing my PhD investigators Forum award. He is scheduled to complete his program, I am a part-time student in a postgraduate program program this year. to obtain a Master for Business Administration (MBA) specializing in health care management at the University of South Australia.

I am very pleased to have participated in the FBG Young Investigators Forum in Del Mar that provided a unique opportunity to closely interact with leading experts and young researchers in the area of neurogastroenterology and motility. Being the recipient of the FBG Young Investigators Forum Award this year is a great honor, and I would like to thank the FBG and organizers for an excellent meeting and their tremendous support of junior researchers.

Functional Brain Gut Functional Brain Gut Research Group Research Group 22 Special Report

Rome Foundation CD Slide Set Project Douglas Drossman, MD

As part of a two-year initiative, the Rome Foundation met The committees include: as a group in Freeport, Grand Bahamas Island, in January 2007 for a 3-day meeting to develop slides for the functional • Basic Science/Physiology/Pharmacokinetics (J. Wood GI disorders. Developed initially to provide a graphical Chair, L. Bueno, J. Kellow) representation of the Rome III book chapters, the work also • Epidemiology (P. Moayyedi Chair, G. Longstreth, N. includes new information since publication that adds to our Talley) knowledge of the FGIDs. There are six committees charged • Psychosocial, Sociocultural/Quality of Life/Brain imaging. with developing separate modules which will be made (A. Sperber Chair, E. Guthrie, R. Levy, B. Naliboff, K. available as a complete set for teaching or self-learning to Olden) gastroenterologists and primary care doctors in 2008. • Diagnosis and Criteria (A Wald Chair, B. Cash, E. Corazziari, T. Lembo, S. Spechler, J. Tack) All committees work primarily via teleconferences where the • Management and Design of Treatment Trials (W. Chey slide content and graphics are reviewed. Once each year, Chair, L. Chang, EJ Irvine, M. Schmulson, W. G. the committees meet as a group to critique the work of each Thompson). committee. At the helm of this work is Jerry Schoendorf, a graphic designer who has produced the remarkable graphics for the AGA slide sets (see Figure 1). In addition, Ms. Carlar Blackman has served as administrative coordinator of the project.

Figure 1 Example of high-quality graphics showing visceral sensory neuron

What is a Sensory Neuron? Dorsal root ganglion

Schwann cells

Cell body

Myelin Output to central processing Detection Channels / receptors (e.g.,(e.g., VR1) VR1)

Functional Brain Gut Functional Brain Gut Research Group Research Group Special Report 23

FBG Sponsored Symposium XXX Pan-American Congress of Gastroenterology Cancun, Mexico November 11-16, 2006

In the city of Cancun, Mexico, from November 11 to 16, 2006, the XXX Pan-American Congress of Gastroenterology took place and was outstandingly chaired by Dr. Enrique Wolpert. There were more than 3,500 participants from around the world. The scientific program included symposia of the AGA, Cleveland Clinic, NASPGHAN, Latin American Pancreatic Study Group, AIGE, SIED, and Spanish Society of Digestive Pathology as well as the Mexican Association of Gastroenterology, Group of Scientific Cooperation Japan- Bolivia, ASGE, WGO-OMGE, and the Functional Brain-Gut Research Group.

The FBG symposium included talks by George Longstreth, who reviewed the epidemiological aspects of FGIDs in Latin America; Fernando Azpiroz, who discussed motility Fernando Azpiroz, MD, Barcelona, Spain; George Longstreth, MD, abnormalities; Douglas Drossman explaining the new Rome San Diego, CA; Kevin Olden, MD, Little Rock, AR; Doug Drossman, MD, Chapel Hill, NC; Max Schmulson, MD, Mexico City, Mexico III criteria and the rationale for the changes; Max Schmulson presenting the results of the Latin American Consensus on Chronic Constipation; and Kevin Olden discussing new treatments. The symposium also included a Q&A session. The symposium was very successful, with large attendance that helped strengthen ties between the FBG and the region. It is important to mention that pioneering at a Pan-American Congress was a Rome Foundation booth in the exhibits section, where the Rome III book was sold for the first time ever.

The Congress was a success and, as someone interested in FGID, I am highly pleased with the amount of meetings related to all aspects of FGIDs not only during the FBG sponsored symposium but also in the postgraduate course and other symposia and research forums of the Congress.

Max Schmulson, MD Professor of Medicine, Laboratory of Liver, Pancreas and Motility (HIPAM), Department of Experimental Medicine, Hospital General de Mexico, Faculty of Medicine, Universidad Nacional Autonoma de Mexico-UNAM

Functional Brain Gut Functional Brain Gut Research Group Research Group 24 Special Report

We are always interested to highlight the Not only in my head publications of our members in areas related to the FGIDs. This is a column that appeared in the And then the editorial board received for review Health Section of Israel’s leading women’s weekly a book written by Prof. Ami Sperber, a senior magazine that reviewed Dr. Ami Sperber’s new physician in the Department of Gastroenterology of book on IBS. The writer “takes to her belly” her the Soroka Medical Center, an associate professor own experience with IBS in an interview with Dr. in the Faculty of Health Sciences of Ben-Gurion Sperber. We hope you will enjoy it. University of the Negev, and a consultant to the Editor Functional Gastrointestinal Disorders Unit of the Ichilov Tel-Aviv Medical Center. Do you take things to your belly instead of to heart?” asks Prof. Ami Sperber, a “Do you take things to your belly instead of to your senior physician in the Department of heart” asked the title, and I almost yelled out loud, Gastroenterology of the Soroka Medical Center. “Yes”. And the cover picture – hands placed on or “I sure do”, answers Tali Rozin, Managing hugging the belly – looked familiar to me. That’s Editor of the health section of Israel’s leading my position. But the surprises didn’t stop there. women’s weekly magazine (La-Esha). This On the cover, under the title, appeared another article is on Irritable Bowel Syndrome and Prof. expression: “The Sensitive Bowel Syndrome”. He Sperber’s book, which can help calm down the calls it sensitive in Hebrew. Not angry or irritable, syndrome. but sensitive. How comforting.

Yes, I take things to my belly Then a second surprise awaited me inside the book. I was there By Tali Rozin (Managing Editor, Health Section) on almost every page. Starting with the personal story of “AB” who asked to “exchange her belly for a better one” to the personal I have been taking things to my belly for ten years now. I even story of “MN” who wrote about this “angry” entity (her bowels) that remember the date when it all began: an anxiety attack in the midst always seems to show up just before an important meeting or an of a traumatic event, followed by long months of suffering. Anything important social event”. that I ate found its way out almost immediately, my stomach hurt and a vicious cycle began to develop: I was afraid to be far away from a But these personal stories were not the main point. I identified with restroom (so I stayed home most of the time), I was afraid of having those, but I learned from the book itself. For example, I learned that diarrhea (so I cut down on food), and every time that it happened 5-20% of the adult population in the world suffers from the syndrome (and it happened often) I became more and more tense. (the range is broad because of sampling problems), that much like I suffer from diarrhea others suffer from constipation, bloating, Dr. Het, a gastroenterologist that I turned to, looked into my rear flatulence, or all of the above, that two-thirds of the sufferers are end with a fiberscope and notified me “Lady, you have a nervous women, that there’s a thing called a “functional disorder”, that IBS stomach, there’s nothing wrong with you.” In order to fight this can be treated, and most important of all that “it’s not all in my “nothing” he recommended that “whenever it happens” I should head”. take a valium pill. I didn’t accept the thought that I was hysterical and turned to Chinese medicine. The initial storm subsided. Since A third surprise became clear a few days after I finished reading then, and for years, I continued (what am I saying I continued? I the book: I felt much, much, much better. Prof. Sperber, by the still continue) to be treated by acupuncture to attain some peace way, was not surprised. “In the case of health problems such as and balance. I also went for psychological therapy that helped me this one, which is shrouded with all types of superstitions and lack with many other things, but not really for this. of clarity, explanations as to what is going on, why it is happening, what can be done, what can’t be done, and what our limitations are Did my nervous stomach become calm? Not at all. Over the years - this is probably the most important part of therapy” he says. “In I learned that it’s called the “angry bowel” (in Hebrew) or “irritable my experience, people relax more after hearing a clear and simple bowel” (in English), and so did all my family and friends. At times explanation, without us promising goods that we can’t deliver”. when we were already dressed and ready to leave the house to go somewhere, I stayed in the bathroom. In the editorial offices of this “Angry” is a judgmental term magazine, for example, everyone is familiar with the mornings when I arrive at work with my hands on my belly, maybe just holding it, “Two sentences”, he says, “drive me out of my mind: ‘There’s maybe stroking it, primarily trying to strengthen it and myself. And nothing wrong with you’ and ‘It’s all in your head’ and these are the no, even though it is clean here, I do not use public restrooms. Not two sentences that are said to patients over and over.” That’s why here and not anywhere else. he wrote the book, for patients and their families, “because you can’t separate them. Many times if the patient’s surroundings are After looking into it I learned that I am not alone in this. Very few contemptuous, suspicious or not supportive, matters can become women are prepared to admit publicly that they suffer thus. much worse. However, if a significant other has information there is more chance that he/she will understand that this is a legitimate problem and not only in their partner’s or friend’s head”.

Functional Brain Gut Functional Brain Gut Research Group Research Group Special Report 25

Tali Rozin: Yet, the book is called “Do you take things to your medications that we have today for IBS, are not given for belly instead of to your heart”. In other words, something that isn’t depression. It should be understood that both depression and physical. disorders like IBS are affected by a chemical named serotonin, which can be found in the digestive tract and in the central nervous Sperber: I admit that the title misses the mark a little. This is system including the brain. 95% of serotonin is found in the nervous a statement that I started saying to my patients and by their system of the digestive tract where it is affects gastrointestinal reactions I saw how much it touched home. But there needs to be motility and participates in determining the threshold for pain; the a continuation to this comment, it can’t stand on its own because it two principal components of IBS. might give the impression that everything really is in their head. I tell my patients that the broad range of conditions for which these drugs are prescribed reminds me of aspirin. I don’t even know what In the book I try to explain that unlike a structural disease such aspirin was originally used for – joint disease, reduction of fever, as cancer, inflammation or ulceration for which the patients has prevention of stroke, or hypertension – but today it has 50,000 uses. “receipts” IBS is a functional disorder. Functional is not crazy. Similarly, the anti-depressants are used for many purposes other Functional relates to how the system functions. Unfortunately all our than depression, but the problem is the stigma that is attached examinations and tests do not assess function, only structure. to them so people are reluctant to take them. I have to explain that I prescribe them not because of depression or psychosis, but Tali Rozin: Why is it important to call IBS in Hebrew the “sensitive because they can help put order into digestive tract motility and bowel syndrome” rather than the “angry bowel syndrome” as it is improve the threshold of sensitivity. commonly called? The art of medicine Sperber: Because of the negative connotation in the term “angry”. “Angry (or the Hebrew term for irritable) seems to place all the Since IBS is a functional rather than a structural disorder and there blame on the individual. It’s a judgmental term. The expression are no blood tests, x-rays, or invasive procedures upon which the “sensitive bowel syndrome” paves the way for patient education. diagnosis can be based, doctors tend to diagnose it through a We are treating hypersensitivity, a low threshold for pain, and we process of exclusion. aim to raise this threshold. We are not trying to calm down an angry, irritated person, and as far as sensitivity goes, it’s not only “This diagnostic approach of exclusion is out-dated” Prof. Sperber the intestines that are hypersensitive. It’s a whole complexity, an says and explains that diagnosis is not only the fruit of the science of axis between the intestines and the brain. The hypersensitive medicine but also of the art of medicine. “The art of medicine starts bowel sends messages in the direction of the brain, which are with the ability to say: ‘OK we’ve done enough tests’” he says. “Many either passed through to consciousness factors affect this ability including the or blocked. It’s like a gate. If the gate doctor’s degree of confidence, the fear is open – all the information flows that they might be missing something forward. If the gate is closed – nothing else, pressure on the part of patients gets through. This gate can be open who want the doctor to find something to different degrees. If someone is real, and even counter pressure on the hypersensitive their gate is open part of the medical-economic system. wide and all the information reaches consciousness. “People come to me completely discouraged. They have usually already Tali Rozin: Is there a connection been to 30 other doctors before they between sensitivity and stress? see me. They come into my room, lay down on the bed and say: ‘Doc, right Sperber: Stress is not the cause of IBS, now, without anesthesia, I want you to but it is a modulator, and it’s important open my stomach and remove this thing to remember that we are referring to that is making my life miserable’”. chronic stress. It’s not a simple reaction to something that happened on a particular day. It’s not a one-to- “These same people, 40 minutes later, leave my room with a smile one type of association. If someone is burned out by chronic stress even though I’ve just told them that I don’t know how to cure them. – that can be due to a problem at work, an interpersonal problem, This is because I’ve listened to them and defined realistic treatment or making a living – this can create a physiological change in the goals. I didn’t tell them that they would get up tomorrow morning threshold of sensitivity. As far as we know people do not develop without IBS. I did say to them that we would work together and IBS only because of chronic stress, but if they have a propensity that over the coming months their symptoms would be reduced for IBS it may become a problem, and if someone has IBS chronic and their condition would improve. stress can definitely make it worse. “There are three things that I ask patients in the course of our first Tali Rozin: So now, after you explain to me that IBS is a functional meeting: 1) why did they come?, 2) what do they think they have and disorder and that it is not caused by stress, you suggest that I take what are their fears and concerns?, and 3) what do they expect from an anti-depressant? I’m not depressed, my stomach hurts. me? These three questions lead to an adjustment of expectations. We usually agree upon two treatment goals: improved quality of life Sperber: Anti-depressant drugs, which are among the best and reduced symptoms. And these goals can be achieved.

Functional Brain Gut Functional Brain Gut Research Group Research Group 26 Special Report & Announcements

FBG Symposium at American Psychosomatic Society Shin Fukudo, MD, PhD, Professor Department of Behavioral Medicine Tohoku University Graduate School of Medicine

Is gut-to-brain signaling the key of origin for emotion? In Paul Enck (University Hospitals Tuebingen, Germany) referred the the symposium of the 65th Annual Meeting of the American high rate of placebo responses in IBS treatments and proposed Psychosomatic Society on March 8, 2007, members of FBG two underlying mechanisms them -- Pavlovian conditioning and presented their data and discussed with neuroscientists. How nice manipulation of expectations by suggestions. He showed that to have a symposium titled Brain-Gut Interactions and Interoceptive gender differences contribute to placebo response, with women Awareness of Emotion with Rome III members including two past being more prone to conditioning and men more to suggestions. presidents (Douglas A. Drossman, University of North Carolina, Qasim Aziz (University of London, UK) demonstrated that infusion and Richard D. Lane, University of Arizona) during the APS in of hydrochloric acid into the healthy oesophagus reduces the Budapest, Hungary, the country of Hans Selye! Shin Fukudo pain threshold not only in the acid exposed region (peripheral (Tohoku University, Japan) and Lane chaired the session. sensitization) but also in the adjacent unexposed region (central sensitization). Development of acid induced oesophageal First, Drossman presented an overview and key concepts of hypersensitivity can be prevented using a prostanoid receptor 1 functional gastrointestinal disorders. A progression of brain imaging receptor antagonist which blocks the prostaglandin receptor E2 in patients with irritable bowel syndrome (IBS) with abuse history and ketamine an NMDA receptor antagonist. was elegantly demonstrated. Lane proposed a theory of Levels of Emotional Awareness. He showed that in IBS patients lower From the symposium, one could see that brain-gut interactions emotional awareness is associated with greater pain and distress, and interoception are not limited to the field of gastroenterology whereas healthy functioning is associated with awareness of but also have potential for exploring a fundamental understanding distress. A lack of top-down processing in the brain may result of emotion. Further communication between FBG members and in the amplification of IBS symptoms. Fukudo identified the more neuroscientists is warranted. activated brain regions with intense distention between placebo and corticotropin-releasing hormone (CRH) antagonist treatments. In IBS patients, the CRH antagonist seems to be more effective in modulating the right anterior insula, right prefrontal cortex, and left parahippocampal gyrus. Emeran A. Mayer (University of California, Los Angeles) emphasized the importance of connectivity of the key brain structures and cortical limbic pontine interactions at homeostatic regulation and emotion. IBS patients may have overactivity of the dorsal anterior cingulate cortex.

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Neurogastroenterology and Motility 2008 Joint International Meeting Lucerne, Switzerland 6-8 November 2008 From Mark Fox

Functional gastrointestinal diseases (FGIDs) are the most common conditions seen in gastroenterology office and hospital based practice, but remain among the most difficult to manage. Conventional investigations and treatments have not been directed at the root causes of troublesome symptoms; however, times are changing rapidly.

The Joint International Meeting for Neurogastroenterology & Motility on 6-8 November 2008 will provide a forum for scientists and clinicians to assess the tremendous progress that is being made in this field of research. The scientific committee -- comprised of two representatives each from the Functional Brain-Gut Research Group (FBG), American Motility Society (AMS), European Society of Front row (from left to right): Neurogastroenterology and Motility (ESNM), and the International Roberto Dantas (IMS; Sao Paolo, Brazil), Michael Fried Society for Motility and Neurogastroenterology (IMG) (see photo) (University Hospital Zürich, Switzerland), Doug Drossman -- met on 2-4th February in Switzerland under the direction of (FBG; Chapel Hill, USA), Gianrico Farrugia (AMS; Mayo Michael Fried, chairman of the local organizing committee at the Clinic, Rochester, USA). University Hospital Zürich. Two days of intense discussion and Second row: Carlo DiLorenzo (FBG; Columbus, debate produced an exciting and comprehensive program for USA), Michael Schemann (ESNM; Münich, Germany), the November meeting. Stand-out plenary sessions will include a Jay Pasricha (AMS; Galveston, USA). Third Row: review of ‘The Stress Response in FGID’, ‘New Movements in GI Ashley Blackshaw (IMS; Adelaide, Australia), Vincenzo Motility’, and the ‘Regulation of Feeding and Body Weight’. Each Stanghellini (ESMN; Bologna, Italy), Mark Fox and Radu session will feature basic scientists and clinicians, highlighting Tutuian (Local Organizing Team; University Hospital the exchange of ideas ‘from bench to bedside and back again’. Zürich, Switzerland). Original research presented by Young Investigators will ensure that the content is up-to-date. Invited speakers from related fields of inquiry will bring fresh insight into the causes of FGIDs and their management. In addition to the sweep of ideas offered by these sessions, the meeting will provide an opportunity to consider topics in detail and to discuss these with experts. Workshops will include ‘enteric neurobiology’, ‘visceral sensitivity and sensation’, a report from the Rome working groups, and an important focus on ‘what happens to children with FGID’.

The meeting will take place at the lakeside conference centre in Lucerne, a beautiful city in the centre of Switzerland less than one hour from the international hub of Zürich Airport. Hotels are within walking distance of the conference centre and the heart of the medieval city; arrangements that ensure conversations begun at the meeting can continue into the evening. The scientific committee Planning the 2008 Neurogastroenterology conference believes the program provides plenty of interest to all those involved in Lucerne in understanding the causes and treating the effects of FGID at every level. We look forward to meeting you there!

Functional Brain Gut Functional Brain Gut Research Group Research Group 28 Announcements

2nd International Symposium of ACG Midwest Regional Postgraduate Neurogastroenterology Course of the Romanian Society of Sheraton Chicago Hotel & Towers, Chicago, Illinois Neurogastroenterology June 29 – July 1, 2007 William Chey, MD and Ali Keshavarzian, MD, Co-Directors Cluj, Romania For more information: 4-7 October 2007 http://www.acg.gi.org/physicians/education.asp For further information: Dan Dumitrascu, MD [email protected] [email protected] Friday, June 29 phone: 00 40 722 756475 11:00am – 6:00am Registration, exhibits open fax: 00 40 264 433427 12:00pm – 4:00pm Practice Management Symposium (separate registration) Following the success of the 1st International Symposium of Neurogastroenterology organized in Brasov in September 2005, 4:00pm – 5:30pm Plenary Session: Obesity, which gathered together many specialists from Romania and East bariatric surgery and its European countries and some international leaders of opinion complications in neurogastroenterology, largely funded by the Alexander von Friday evening reception Humboldt Foundation, we have the pleasure to announce the 2nd International Symposium of Neurogastroenterology, funded Saturday, June 30 through a grant from the Romanian Ministry of Research and Technology. The symposium will be held in Cluj, Romania 8:00am – 5:00pm Registration, exhibits open between 4 and 7 October 2007. The scientific programme of 8:00am – 9:00am GI disorders in pregnant women the meeting will contain lectures given by invited speakers 9:20am – 10:20am Liver disease who are internationally recognized prominent personalities in neurogastroenterology and by national and East European 10:40am – 12:10pm Inflammatory Bowel Disease researchers with experience in this field. It will also include oral 12:15pm – 1:00pm Breakout Session 1 presentations and posters. An industrial exhibition and some nice social events will complete the programme of this symposium. 1:15pm – 2:15pm Breakout Session 2 2:30pm – 5:30pm Sedation Course Cluj, the home city of this symposium is a picturesque 2000 (separate registration) year old city located in the center of the Romanian province of Transylvania. Its diverse architectural and artistic heritage and multicultural feature, as well as charming sites in the Sunday, July 1 neighborhood, make the city very attractive for tourists. The 8:00am – 12:30pm Registration, exhibits open venue -- Casa de Cultura a Studentilor (Culture House of the 8:00am – 12:30pm Plenary Sessions Students) – is located in the downtown of the city. • Functional Bowel Disorders • Colorectal Cancer Registration fees • Celiac Disease Specialists 12:15pm Course Adjourns 30 EUR pre-regsitration, 50 EUR on-site

Residents, nurses, students 15 EUR pre-regsitration, 25 EUR on-site

Call for abstracts Abstracts of original work in the following fields of neurogastroenterology are invited: functional gastrointestinal disorders, digestive motility disorders, brain-gut interactions, psychosomatic aspects of digestive diseases, and basic research. The accepted submissions will be presented in oral or poster sessions. Please send abstracts up to 250 words in Word format to this email -- [email protected] Deadline: 30 May 2007.

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Election Results FBG Annual Meeting – May 22 Congratulations! The FBG annual meeting and reception will be held at Two new Council members have been elected and will be DDW in Washington DC, May 22, at the Grand Hyatt replacing Brain Lacy, MD and Max Schmulson, MD. Please Hotel, Independence B-C-D Ballroom. The reception is welcome Ronnie Fass, MD and Tony Lembo, MD. 5:30-6:30pm and the annual meeting is 6:30- 7:30pm.

AGA Motility and Nerve Gut Interactions Section – election results

The results of recent elections by the AGA membership:

Vice Chair Gianrico Farrugia MD Ronnie Fass Tony Lembo Tucson, AZ Boston, MA Clinical Councilors Bill Whitehead PhD Lin Chang MD Cyclic Vomiting Syndrome Basic Science Councilors Association (CVSA) Nathalie Vergnole PhD Scientific/Medical Update - April 2007 Simon Brookes PhD Kathleen Adams, President & Research Liaison - Nigel W. Bunnett PhD 2006 was another landmark year for CVS in regard to They will take office at DDW this May and will serve diagnosis and treatment for CVS in adults. CVSA now has for the next two years through DDW 2010 (Nominating more adult patients on our rolls than children. This grossly Committee: Doug Drossman MD (chair), Satish Rao MD, underserved group of adult patients will hopefully begin Keith Sharkey PhD) to find more expert care around the country as a result of the efforts of the ever-growing body of professionals that currently provide care to adults with CVS. These men and women have been doing presentations at meetings to a new audience of their peers. Special thanks goes the tireless work of CVSA advisor, Dr. Henry Parkman of Temple University, who has driven the opportunities to highlight CVS in adults. He has moved forward with the help of Drs. B.U.K. Li and Richard McCallum.

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IBS Chat: Real Life Stories and Solutions Jeffrey D. Roberts M.S.Ed.,President and Founder of the Irritable Bowel Syndrome Self Help and Support Group

Dr. Barbara Bradley Bolen Clinical Psychologist The IBS Self Help and Support Group has announced the launching IBS Chat: Real Life Stories and Solutions, published by iUniverse Inc. and receiving iUniverse’s Publisher’s Choice™ designation. IBS Chat is co-authored by Jeffrey D. Roberts, M.S.Ed., President and Founder of the Irritable Bowel Syndrome Self Help and Support Group and Dr. Barbara Bradley Bolen, Clinical Psychologist and author of the widely acclaimed Breaking the Bonds of Irritable Bowel Syndrome. It is a compilation of the best posts to the Bulletin Board of the on-line Irritable Bowel Syndrome (IBS) Self Help and Support Group, (http://www.ibsgroup.org), and offers practical strategies for managing symptoms, information about a wide variety of treatment options, and insight into the effect that IBS can have on a person’s life. Available by calling 1-800- AUTHORS and online at iUniverse.com, barnesandnoble. com, amazon.com.

NeurogastroenterologyNeurogastroenterolo & MotilityJoint International Meeting 2008 6-9 November 2008 Lucerne, Switzerland S a ve the date! &www.ngm2008.com

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New Members

Myung-Gyu Choi, MD Rinarani Sanghavi, MD Darren Brenner, MD Borko Nojkov, MD Seoul, Republic of Korea Dallas, Texas Ann Arbor, MI Ann Arbor, MI Jae Myung Park, MD Gengqing Song, MD Siva Doma, MD Martina, Puzanovova, MD Seoul, Republic of Korea Oklahoma City, OK Philadelphia, PA Nashville, TN Tim O’Neill, PhD Maria Perez, MD Niels Eijkelkamp, MD Savio Reddymasu, MD Mason, Ohio New York, NY Utrecht, The Netherlands Kansas City, KS Muhammad Nabeel Kerstin Suarez, MD April Gruddell, MD Kevin Ruff, MD Hamilton, Ontario, Canada Zurich, Switzerland Rochester, MN Rochester, MN John Clark, MD Julia Anderson, MD Kevin Halsey, MD Ron Schey, MD Baltimore, MD Nashville, TN Madison, WI Tucson, AZ Stephan Weinland, PhD Ashok Attaluri, MD Brian Hughes, MD Ann Marie Reynolds Chapel Hill, NC Iowa City, IA Little Rock, Arkansas Denver, Colorado

Alex, son of Dr. and Mrs. Jeffrey Hyams -- member-in-training for the Rome committee on infant FGIDs who appears to require minimal sleep (much to the dismay of his parents).

Functional Brain Gut Functional Brain Gut Research Group Research Group Corporate Sponsors We would like to thank our corporate sponsors:

• Novartis Pharmaceuticals • Takeda Pharmaceuticals • Proctor & Gamble Pharmaceuticals • SmartPill Pharmaceuticals • Axcan Pharmaceuticals