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Biomedical subjects

Yehuda Ringel

Publications and source records attributed to Yehuda Ringel.

16 recordsLinked to original sources
PubMed2006

Low-dose naltreoxone for the treatment of irritable bowel syndrome: a pilot study.

Preclinical studies have shown that a very low dose of naltreoxone hydrochloride (NTX), an opiate antagonist, can block excitatory opioid receptors without affecting inhibitory opioid receptors, resulting in analgesic potency without side effects. The present study assessed the efficacy and safety of PTI-901 (low-dose NTX) treatment in Irritable bowel syndrome (IBS) patients. Forty-two IBS patients participated in an open-label study. Participants received 0.5 mg PTI-901/day for 4 weeks and were evaluated during baseline, during treatment, and at 4-week follow-up. Patients recorded degree of abdominal pain, stool urgency, consistency, and frequency. Primary outcomes were number of pain-free days and overall symptom relief, evaluated by a global assessment score. Data were analyzed per protocol. Global assessment improved in 76% of 42 patients. During treatment, the mean weekly number of pain-free days increased from 0.5+/-1 to 1.25+/-2.14 (P=0.011). There were no significant adverse reactions. PTI-901 improves pain and overall feeling, and is well tolerated by IBS patients. A large, randomized, double-blind, placebo-controlled study is justified.

Abdominal Pain↗
PubMed2006

The burden of gastrointestinal and liver diseases, 2006.

BACKGROUND: Digestive and liver diseases are a source of significant morbidity, mortality, and health-care costs for the U.S. population. An annual report of the toll of these diseases could be helpful to clinicians, policymakers, and researchers. AIM: To describe the epidemiology of gastrointestinal and liver diseases in the United States using data from privately and publicly held databases. METHODS: We collected data from the National Center for Health Statistics, the National Ambulatory Medical Care Survey, the National Inpatient Sample, the Centers for Disease Control and Prevention, and the National Cancer Institute, as well as proprietary pharmaceutical databases to construct a report on the impact of gastrointestinal and liver diseases on the U.S. population. We compiled information on causes of death, hospitalization, clinic visits, cancer incidence, and mortality and infectious disease incidence from these databases, and extracted data specific to gastrointestinal diseases. Because of the high costs associated with medications used to treat gastrointestinal diseases, we also include in this year's report a special section on pharmacoepidemiology and pharmacoeconomics. RESULTS: Colorectal cancer continues to be the leading cause of GI-related death, although the data indicate a downward trend in deaths. Abdominal pain, diarrhea, vomiting, and nausea are the most common GI symptoms precipitating a visit to the physician, and GERD is the most common GI-related diagnosis given in office visits. Chest pain not specified to be cardiac in origin is the most common cause of inpatient admission possibly related to GI disease, with cholelithiasis and pancreatitis following. Americans spend in excess of US dollars 10 billion/yr on proton pump inhibitors (PPIs), and two of the top five selling drugs in the United States are PPIs. Trends in PPI use demonstrate turbulent changes, likely reflecting both new drug entries into the field, as well as drug marketing. The number of PPI prescriptions/yr in the United States has doubled since 1999. Twenty-three drugs used for gastrointestinal diseases are among the top 200 generic drugs used in the United States. CONCLUSIONS: Gastrointestinal and liver diseases are significant contributors to the morbidity, mortality, and health-care expenditures of the U.S. population.

Female↗
PubMed2006

Treatment of functional diarrhea.

Functional diarrhea (FD), one of the functional gastrointestinal disorders, is characterized by chronic or recurrent diarrhea not explained by structural or biochemical abnormalities. The treatment of FD is intimately associated with establishing the correct diagnosis. First, FD needs to be distinguished from diarrhea-predominant irritable bowel syndrome (IBS), in which, unlike in FD, abdominal pain is a primary diagnostic criterion. Next, FD must be differentiated from the myriad organic causes of chronic diarrhea. Unlike IBS, in which a positive diagnosis can be made with an acceptable level of confidence using symptom-based criteria and minimal testing, the diagnosis of FD is still primarily a diagnosis of exclusion. Thus, the onus is on the physician to eliminate potential underlying causes, both common and uncommon, in the proper clinical setting. Once the diagnosis has been established, the clinician and patient should first focus on identifying, eliminating, and/or treating aggravating factors. These may include physiologic factors (eg, small bowel bacterial overgrowth), psychological factors (eg, stress and anxiety), and dietary factors (eg, carbohydrate malabsorption). Thereafter, appropriate treatment for functional diarrhea may be instituted. Treatment options include dietary and lifestyle modification, pharmacologic therapies, and alternative modalities. Although many of these strategies have been studied in IBS, almost none of them has been examined specifically in FD. Furthermore, given the poorly understood pathophysiologic basis of FD, these treatments primarily target a patient's symptoms and presumed altered physiology rather than underlying etiologic mechanisms. Therefore, we stress that treatment must be approached in an individualized manner and that dietary and pharmacologic therapies should be part of a comprehensive therapeutic approach in which education and reassurance form the foundation. In general, we attempt to remove dietary triggers and recommend increased fiber intake. We then add anticholinergic, antispasmodic, antimotility, and antidiarrheal agents as the first line of pharmacotherapy. Should a patient not respond to these, and for patients who have a significant degree of psychological dysfunction, central acting agents, including antidepressants and/or anxiolytics, may be beneficial. During the treatment period, we also recommend that physicians keep an open mind. If signs or symptoms that suggest an ongoing or previously unrecognized organic process develop, then a re-evaluation of the clinical picture is indicated.

Journal Article↗
PubMed2006

New directions in brain imaging research in functional gastrointestinal disorders.

Functional brain imaging has greatly enhanced the ability to investigate brain-gut interactions and to assess the central nervous system role on visceral pain perception. The results of studies using brain imaging in irritable bowel syndrome (IBS) have demonstrated differences in brain activation between patients with IBS and healthy controls. In addition, the more recent studies are starting to shed light on pathophysiological mechanisms that underlie the generation of functional gastrointestinal (GI) symptoms as well as the response to treatment. These studies highlight the potential of functional brain imaging to become an important and exciting investigative tool in research of functional GI disorders. However, the multifactorial, multideterminant nature of these disorders, the current limitations in the understanding of the pathophysiology of the disorders, and the heterogeneous patient population make brain imaging research in this field difficult and require caution in the interpretation of the data. The continued development of brain imaging techniques provides not only exciting opportunities but also significant challenges to the field. This article focuses on brain imaging research in functional GI disorders. It describes some of the recent developments in the use of brain imaging in research of the brain-gut axis and provides an overview of the current data.

Biomedical Research↗
PubMed2005

Selected topics in probiotics and prebiotics: meeting report for the 2004 international scientific association for probiotics and prebiotics.

On August 29-31, 2004, 84 academic and industry scientists from 16 countries gathered in Copper Mountain, Colorado USA to discuss certain issues at the forefront of the science of probiotics and prebiotics. The format for this invitation only meeting included six featured lectures: engineering human vaginal lactobacilli to express HIV-inhibitory molecules (Peter Lee, Stanford University), programming the gut for health (Thaddeus Stappenbeck, Washington University School of Medicine), immune modulation by intestinal helminthes (Joel Weinstock, University of Iowa Hospitals and Clinics), hygiene as a cause of autoimmune disorders (G. A. Rook, University College London), prebiotics and bone health (Connie Weaver, Purdue University) and prebiotics and colorectal cancer risk (Ian Rowland, Northern Ireland Centre for Food and Health). In addition, all participants were included in one of eight discussion groups on the topics of engineered probiotics, host-commensal bacteria communication, 'omics' technologies, hygiene and immune regulation, biomarkers for healthy people, prebiotic and probiotic applications to companion animals, development of a probiotic dossier, and physiological relevance of prebiotic activity. Brief conclusions from these discussion groups are summarized in this paper.

Animals↗
PubMed2004

Digestive and liver diseases statistics, 2004.

BACKGROUND & AIMS: Digestive and liver diseases are associated with substantial morbidity and mortality in the United States. Statistics about the incidence, prevalence, mortality, and resource utilization of digestive and liver diseases in the United States may be cumbersome to obtain because they are scattered in multiple sources. These data may be useful for policy makers, grant applicants, and authors. METHODS: Data on the most common gastrointestinal and liver diseases were collected from large publicly available national databases. Information was collected on inpatient and outpatient gastrointestinal complaints and diagnoses, gastrointestinal cancers, and deaths from common liver diseases. RESULTS: The leading gastrointestinal complaint prompting an outpatient visit is abdominal pain, with 12.2 million annual visits, followed by diarrhea, nausea, and vomiting. Abdominal pain is the leading outpatient gastrointestinal diagnosis, accounting for 5.2 million visits annually, followed by gastroesophageal reflux disease, with 4.5 million visits. Gallstone disease is the most common inpatient diagnosis, with 262,411 hospitalizations and a median inpatient charge of USD$11,584. Colorectal cancer is the most common gastrointestinal cause of death and is the most common gastrointestinal cancer, with an incidence of 54 per 100,000. Among gastrointestinal cancers, primary liver cancer had the highest increase in incidence from 1992 to 2000. CONCLUSIONS: Gastrointestinal and liver diseases are associated with significant outpatient and inpatient healthcare utilization. Following trends in utilization is important for determining allocation of resources for health care and research.

Biliary Tract Diseases↗
PubMed2003

Regional brain activation in response to rectal distension in patients with irritable bowel syndrome and the effect of a history of abuse.

Previous studies have demonstrated alterations in brain response to rectal distension in patients with irritable bowel syndrome (IBS) compared to controls. Our aim was to compare regional brain activity in response to rectal balloon distension in patients with IBS and healthy controls. We studied six patients with IBS and six healthy controls. Positron emission tomography scans were obtained during rectal balloon distensions. Statistical parametric mapping and region of interest analysis were performed to identify and compare differences in regional cerebral blood flow (CBF) for each distension pressure within and between the groups of interest. In post-hoc analyses, patients with a history of sexual or physical abuse were compared to patients without abuse. In response to rectal distension, controls exhibit a greater increase in anterior cingulate cortex (ACC) activity compared to the IBS group (Z = 3.2, P = 0.001). Thalamic activity was higher in the IBS patients relative to the control group (Z = 3.3, P < 0.001). Increased ACC activity was observed in IBS patients with no history of abuse (Z = 5.2, P < 0.001) similar to controls, whereas no such increased activity was noticed in the abused group. In conclusion, this study replicates previous findings showing alterations in brain response to rectal distension in patients with IBS. The observations on the effect of abuse suggest a possible modulating role of abuse history on this brain response.

Adolescent↗
PubMed2003

Alterations of brain activity associated with resolution of emotional distress and pain in a case of severe irritable bowel syndrome.

BACKGROUND & AIMS: The association of psychosocial disturbances with more severe irritable bowel syndrome (IBS) is well recognized. However, there is no evidence as to how these associations might be mediated. Functional magnetic resonance imaging (fMRI) offers an opportunity to study whether activation of the cingulate cortex, an area involved with the affective and pain intensity coding might be linked to poorer clinical status with IBS. In this case report, we found an association between the severity of a patient's clinical symptoms and psychosocial state, with activation of the cingulate cortex. We also found that clinical and psychosocial improvement was associated with reduced cingulate activation. METHODS: Observational case report of a young woman observed for 16 years with a history of sexual abuse, psychosocial distress, and functional GI complaints. Psychosocial, clinical, and fMRI assessment was performed when the patient experienced severe symptoms and again 8 months later when clinically improved. RESULTS: During severe illness, the patient had major psychosocial impairment, high life stress, a low visceral pain threshold, and activation of the midcingulate cortex (MCC), prefrontal area 6/44, and the somatosensory cortex, areas associated with pain intensity encoding. When clinically improved, there was resolution in activation of these 3 areas, and this was associated with psychosocial improvement and an increased threshold to rectal distention. CONCLUSIONS: Activation of the MCC and related areas involved with visceral pain encoding are associated with poor clinical status in patients with severe IBS and psychosocial distress and appear to be responsive to clinical improvement.

Affective Symptoms↗
PubMed2002

Flexible sigmoidoscopy: the patients' perception.

BACKGROUND: Anxiety, discomfort, and high levels of concern can affect patient attitude toward endoscopic procedures as well as compliance and adherence to current recommendations for the examination. This study evaluated how patients perceive flexible sigmoidoscopy. METHODS: A prospective study was conducted at two sites of 764 patients presenting for GI endoscopy (flexible sigmoidoscopy 175, colonoscopy 384, EGD 205). Before these procedures, patients rated their anticipated (preprocedure) difficulty and degree of concern for each of 30 specific concerns. After the procedure, the patients rated their actual (postprocedure) difficulty. Patients' levels of concerns and difficulty were compared before and after the procedure and among the 3 procedure types. RESULTS: Before the procedure, patients who were to undergo flexible sigmoidoscopy had fewer concerns and lower scores for the severity of the concerns than did patients having colonoscopy or EGD. After the procedure, patients who had flexible sigmoidoscopy rated it as more difficult than patients who had colonoscopy or EGD. Patients who had colonoscopy and EGD graded their actual difficulty as less than their anticipated difficulty. However, patients who had flexible sigmoidoscopy rated the actual difficulty the same as the anticipated difficulty. CONCLUSIONS: Although patients have fewer concerns regarding flexible sigmoidoscopy than for the other endoscopic procedures, after the procedure they rate sigmoidoscopy as more difficult compared with postprocedure ratings by patients who underwent colonoscopy or EGD. This suggests that it may be necessary to change the perception of flexible sigmoidoscopy as being the best tolerated of the endoscopic procedures.

Adolescent↗
PubMed2002

Irritable bowel syndrome: classification and conceptualization.

The irritable bowel syndrome is one of a group of functional gastrointestinal disorders within the Rome classification system that is characterized by abdominal discomfort or pain associated with a change in stool habit. It is a multidetermined biopsychosocial disorder in which physiological, psychological, behavioral, and environmental factors may contribute to the clinical expression of the disorder. These can include: (1) early life (e.g., genetic or environmental) factors; (2) physiological factors including increased motor reactivity, visceral hypersensitivity, which may be enabled by postinfectious events, and dysregulation of brain-gut communication (e.g., altered central pain control mechanisms). In addition, psychosocial factors including psychiatric co-morbidity, major trauma (e.g., abuse history), and maladaptive coping may amplify the clinical expression of the disorder and its outcome. Currently, clinical outcome has become understood in terms of global symptom relief and health-related quality of life.

Colonic Diseases, Functional↗
PubMed2002

Brain research in functional gastrointestinal disorders.

The current understanding is that functional gastrointestinal disorders (FGIDs) result from dysregulation of the bidirectional communication between the gut and the brain (i.e., the brain-gut axis), modulated by various psychosocial and environmental factors (i.e., the biopsychosocial model). This concept has led to a growing interest in the research of brain function in relation to gut motor and sensory function. Brain research on the mechanisms that are involved in the generation of gastrointestinal symptoms includes studies of the gut response to brain stimulation with technique such as transcranial magnetic stimulation or studies of the brain response to gut stimulation by cortical evoked potentials, positron emission tomography, and functional magnetic resonance imaging. Studies using these techniques have shown that visceral/gut sensation involves activation of several brain regions that are associated with various brain functions, including sensation, cognition, and affect. The complexity of the brain response to visceral stimulation and the multidetermined nature of FGIDs make studies of brain function in FGID patients difficult and demands great caution in interpreting their results. Nevertheless, brain research in FGIDs is an emerging field and suggests that patients with irritable bowel syndrome differ from healthy subjects in the way that their brain response to visceral (e.g., rectal) distention. These studies emphasize the role of the central nervous system in conducting and processing visceral signals and suggest that alteration in brain processes involving perception and affective responses might be key factors in the pathogenesis of functional gastrointestinal symptoms.

Autonomic Nervous System↗