Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although biofeedback has been applied to many gastrointestinal disorders, including reflux esophagitis, peptic ulcer disease, and irritable bowel syndrome, the limited number of reports precludes conclusions concerning its safety or efficacy in these disorders. Most studies have used biofeedback in the treatment of fecal incontinence. Uncontrolled trials have shown this procedure can reduce substantially the frequency of incontinence in 70% to 83% of patients at up to 1 to 2 years of follow-up. Biofeedback has been most successful in patients with a surgical cause for fecal incontinence, but recent data suggest the procedure may also be useful in diabetics. The few number of sessions required, its apparent safety, physiological appeal, and apparent success suggest biofeedback is a promising therapy for this disorder, but it remains inadequately tested.
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PMID:Biofeedback for gastrointestinal disorders: a review of the literature. 389 57

Colonic motility disorders can be treated by changing the diet, modifying the patient's daily behaviour, giving drugs to enhance or inhibit colonic contraction, or by performing surgery. Therapy in constipation mainly relies on the use of bulk-forming agents, in addition to a change in behaviour. Dietary fibre, particularly bran, appears to be effective in diverticular disease. Bowel atony is largely caused by increased sympathetic activity, and thus frequently responds to sympatholysis. In the irritable bowel syndrome, amelioration is achieved by taking bran and omitting badly tolerated food; antispasmodics and psychotherapy are also probably beneficial. Diarrhoea and incontinence may be treated by opioids, such as loperamide. Recent progress has been mainly in the understanding of the pathophysiology of these disorders, but rapid therapeutic advances are now taking place.
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PMID:Therapeutic possibilities in colonic motility disorders. 638 75

Interstitial cystitis, a sterile bladder condition, is characterized by urinary frequency, urgency, burning and suprapubic pain. Increasing evidence indicates that interstitial cystitis is a heterogeneous syndrome that reflects an immune response to a variety of triggers. More than 50% of the patients have allergies, 30% have the irritable bowel syndrome and almost 20% suffer from migraine headaches. Increased numbers of mast cells have been reported in interstitial cystitis. Mast cell activation, which is critical if these cells were to be implicated in this syndrome, has been investigated by electron microscopy, which definitively shows mast cell secretion. Recently, methylhistamine, the major metabolite of histamine, and the specific mast cell marker, tryptase, were shown to be significantly elevated in urine of interstitial cystitis patients. Bladder biopsies from 53 patients were analyzed blindly for the number and degree of activation of mast cells using 4 different stains for light microscopy, as well as electron microscopy. Controls included 16 patients with incontinence and chronic bacterial cystitis. Mast cells in controls were less than 10/mm.2 and were all nearly intact. Surprisingly, mast cells from 11 cancer patients averaged 50/mm.2 but almost all were intact. In contrast, mast cells from 26 interstitial cystitis patients averaged 40/mm.2 and more than 90% were activated to various degrees. Therefore, bladder mast cell activation is a characteristic pathological finding in at least a subset of patients with interstitial cystitis.
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PMID:Activation of bladder mast cells in interstitial cystitis: a light and electron microscopic study. 786 1

Classic treatment of high anal fistulas by the laying open technique requires total or subtotal section of the sphincter muscles and results in anal incontinence. This study assesses the efficacy of the flap advancement technique in these cases. It entails the resection of the crypt at the origin of the fistula, the area being covered by a mucomuscular flap of the rectal wall. From 1977 to early 1992, 18 patients (13 female and 5 male patients; mean age: 40 years) presenting with a deep anal fistula underwent such an operation. There were 16 suprasphincteric and 2 high transsphincteric tracts. Associated IBD was noted in 7 cases (5 Crohn's colitis, 2 UC). Five fistulas were of obstetrical origin. In 8 cases, patients had undergone previous surgical treatments without success. All patients had a flap advancement. In 2 cases, a colostomy had been previously carried out. Two more diverting stomies were performed (combined abdominal procedures). No mortality or morbidity was encountered. Mean postoperative stay was 8 days. Current status could be established in all patients. Three immediate failures were observed (1 case of Crohn's disease, two recurring cases). All the other patients did well with persistent healing of the fistula after a mean follow-up of 61 months (range, 6-150). Three stomies were closed; one patient delayed the procedure. Functional results were excellent. In the "success" group, all the evaluable patients (14/15) had normal fecal continence. Two female patients are still complaining of mild flatus incontinence. In the failure group, the preoperative anorectal function was maintained.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Treatment of deep anal fistulas using a flap from the rectal wall]. 819 10

Our objective was to obtain national data of the estimated prevalence, sociodemographic relationships, and health impact of persons with functional gastrointestinal disorders. We surveyed a stratified probability random sample of U.S. householders selected from a data base of a national market firm (National Family Opinion, Inc.). Questions were asked about bowel symptoms, sociodemographic associations, work absenteeism, and physician visits. The sampling frame was constructed to be demographically similar to the U.S. householder population based on geographic region, age of householder, population density, household income, and household size. Of 8250 mailings, 5430 were returned suitable for analysis (66% response). The survey assessed the prevalence of 20 functional gastrointestinal syndromes based on fulfillment of multinational diagnostic (Rome) criteria. Additional variables studied included: demographic status, work absenteeism, health care use, employment status, family income, geographic area of residence, population density, and number of persons in household. For this sample, 69% reported having at least one of 20 functional gastrointestinal syndromes in the previous three months. The symptoms were attributed to four major anatomic regions: esophageal (42%), gastroduodenal (26%), bowel (44%), and anorectal (26%), with considerable overlap. Females reported greater frequencies of globus, functional dysphagia, irritable bowel syndrome, functional constipation, functional abdominal pain, functional biliary pain and dyschezia; males reported greater frequencies of aerophagia and functional bloating. Symptom reporting, except for incontinence, declines with age, and low income is associated with greater symptom reporting. The rate of work/school absenteeism and physician visits is increased for those having a functional gastrointestinal disorder. Furthermore, the greatest rates are associated with those having gross fecal incontinence and certain more painful functional gastrointestinal disorders such as chronic abdominal pain, biliary pain, functional dyspepsia and IBS. Preliminary information on the prevalence, socio-demographic features and health impact is provided for persons who fulfill diagnostic criteria for functional gastrointestinal disorders.
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PMID:U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact. 835 66

Anorectal tests need to be tailored to the presentation of the individual patient. Clearly the tests are most useful when they identify anatomic or physiologic abnormalities for which there are successful treatments. For the incontinent patient, anal manometry is the most useful test. Sphincter injuries should be repaired, whereas neurogenic incontinence is best treated initially with biofeedback. Three tests are more useful for the constipated patient: colonic transit time, degree of pelvic floor descent on straining, and balloon expulsion. Colonic inertia responds to total colectomy and pelvic floor dysfunction to biofeedback. Meanwhile, patients with irritable bowel syndrome require rereferral back to their physicians.
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PMID:Anorectal and pelvic floor function. Relevance of continence, incontinence, and constipation. 868 71

The 5-HT4 receptor is a member of the seven transmembrane spanning G-protein-coupled family of receptors. The receptor is positively coupled to adenylate cyclase and exists in two isoforms (5-HT4S and 5-HT4L) that differ in the length and sequence of their carboxy termini. The 5-HT4 receptor is pharmacologically defined by selective agonists such as SC 53116 and RS 67506, and selective antagonists such as GR 113808, SB 204070, and RS 39604. The receptor is widely distributed in the central nervous system and peripheral tissues. In the periphery, the receptor plays an important role in the function of several organ responses including the alimentary tract, urinary bladder, heart and adrenal gland. In the alimentary tract, stimulation of 5-HT4 receptors has a pronounced effect on smooth muscle tone, mucosal electrolyte secretion, and the peristaltic reflex. In the urinary bladder, activation of 5-HT4 receptors modulates cholinergic/purinergic transmission. In the heart, stimulation of atrial 5-HT4 receptors produces positive inotropy and tachycardia that can precipitate arrhythmias. In the adrenal gland, agonism of 5-HT4 receptors stimulates release of cortisol, corticosterone, and aldosterone. Since its discovery in 1988, significant advances have been made in our understanding of the physiology and pharmacology of the 5-HT4 receptor. These advances have led to the development of several selective 5-HT4 receptor agonists and antagonists that may have therapeutic utility in the treatment of peripheral disorders such as irritable bowel syndrome, gastroparesis, urinary incontinence and cardiac arrhythmias.
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PMID:Peripheral 5-HT4 receptors. 890 10

Compounds with high affinity for muscarinic M3 receptors have been used for many years to treat conditions associated with altered smooth muscle tone or contractility such as urinary urge incontinence, irritable bowel syndrome or chronic obstructive airways disease. M3 selective antagonists have the potential for improved toleration when compared with non-selective compounds. Darifenacin has high affinity (pKi 9.12) and selectivity (9 to 74-fold) for the human cloned muscarinic M3 receptor. Consistent with this profile, the compound potently inhibited M3 receptor mediated responses of smooth muscle preparations (guinea pig ileum, trachea and bladder, pA2 8.66 to 9.4) with selectivity over responses mediated through the M1 (pA2 7.9) and M2 receptors (pA2 7.48). Interestingly, darifenacin also exhibited functional tissue selectivity for intestinal smooth muscle over the salivary gland. The M3 over M1 and M2 selectivity of darifenacin was confirmed in a range of animal models. In particular, in the conscious dog darifenacin inhibited intestinal motility at doses lower than those which inhibit gastric acid secretion (M1 response), increase heart rate (M2 response) or inhibit salivary secretion. Clinical studies are ongoing to determine if darifenacin has improved efficacy and or toleration when compared with non-selective agents.
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PMID:Muscarinic antagonists in development for disorders of smooth muscle function. 1006 2

Muscarinic M3 receptor antagonists have therapeutic potential for the treatment of disorders associated with altered smooth muscle contractility or tone. These include irritable bowel syndrome (IBS), chronic obstructive airways disease (COAD) and urinary incontinence. Zamifenacin is a potent muscarinic receptor antagonist on the guinea pig ileum (pA2 value 9.27) with selectivity over M2 receptors in the atria (135-fold) and M1/M4 receptors in the rabbit vas deferens (78-fold). In addition, zamifenacin had lower affinity for the M3 receptor in the salivary gland (pKi 7.97). In animals, zamifenacin potently inhibited gut motility in the absence of cardiovascular effects and with selectivity over inhibition of salivary secretion. In healthy volunteers, zamifenacin inhibited small and large bowel motility and increased the rate of gastric emptying over a dose range which was associated with minimal anticholinergic side effects. These data show that zamifenacin, a selective muscarinic M3 receptor antagonist, was well tolerated in man and was efficacious as an inhibitor of gut motility. Further studies in patients are required with muscarinic M3 receptor antagonists to confirm efficacy against symptoms in diseases associated with altered smooth muscle contractility.
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PMID:Pre-clinical and clinical pharmacology of selective muscarinic M3 receptor antagonists. 1018 86

Abbott and Takeda are developing TAK-637, an orally active NK1 antagonist, for the potential treatment of urinary incontinence, depression, irritable bowel syndrome and pollakiuria. By November 1999, it was in phase II trials in Europe and phase I in Japan and the US for urinary incontinence [348496], [350686]. By October 2000, phase II trials had been initiated in the US for urinary incontinence, depression and IBS [381167], [386950], [419868], and in May 2001, these were scheduled to finish in 2002 [412024].
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PMID:TAK-637. Takeda. 1189 Mar 61


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