Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Encopresis is often the result of chronic constipation in the majority of paediatric patients. In clinical practice, however, encopresis is also seen without constipation and it is unknown whether these two clinical variants are based on similar or different pathophysiological mechanisms, requiring different therapeutic approaches. We analysed clinical symptoms, colonic transit time (CTT), orocaecal transit time (OCTT), anorectal manometric profiles, and behavioural scores. Patients were divided into two groups, one consisted of 111 children with paediatric constipation, and another group of 50 children with encopresis and/or soiling without constipation. Significant clinical differences in children with encopresis/soiling existed compared with children with paediatric constipation regarding: bowel movements per week, the number of daytime soiling episodes, the presence of night time soiling, the presence and number of encopresis episodes, normal stools, pain during defecation, abdominal pain, and good appetite. Total and segmental CTT were significantly prolonged in paediatric constipation compared with encopresis/soiling, 62.4 (3.6-384) and 40.2 (10.8-104.4) hours, respectively. No significant differences were found in OCTT. Among the two groups, all manometric parameters were comparable, except for a significantly higher threshold of sensation in children with paediatric constipation. The defecation dynamics were abnormal in 59% and 46% in paediatric constipation and encopresis/soiling, respectively, and were significantly different from controls. Using the child behaviour checklist no significant differences were found when comparing children with paediatric constipation and encopresis/soiling, while both patient groups differed significantly from controls. In conclusion, our findings support the concept of the existence of encopresis as a distinct entity in children with defecation disorders. Identification of such children is based on clinical symptoms, that is, normal defecation frequency, absence of abdominal or rectal palpable mass, in combination with normal marker studies and normal anal manometric threshold of sensation, Thus, encopresis is not always the result of constipation and can be the only clinical presentation of a defecation disorder.
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PMID:Is encopresis always the result of constipation? 797 89

The aim of this study was to estimate the effectiveness of DUPHALAC preparation, produced by Solvay-Pharma, in treatment of functional chronic constipation. 112 children, aged 10 months-15.5 years were examined. DUPHALAC appeared to be very effective, were examined. Only two patients did not accept its taste. Rapidly (approximately after 2.5 weeks) improvement was achieved such as of restoration normal peristalsis and of previously disturbed defecation rhythm, softening of a stool, regression of pain and/or dyspeptic ailments, encopresis and improvement of appetite. In no case undesirable side effects were observed.
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PMID:[Duphalac (lactulose) in the treatment of chronic constipation in children]. 963 15

The solitary rectal ulcer (SRU) is a benign lesion of adults of either sex, which presents with chronic constipation, peculiar defecatory disorders, rectal prolapse and smaller psychological abnormalities. The characteristic appearance of this disease is a "neither being always ulcerate, nor always solitary" lesion, but often with polypoid or granular feature, typically localized in anterior rectal wall, a few inches from anal channel. Distinctive histopathological specimens are localized mucosal distortion, hypertrophic proliferation of muscularis mucosae and obliteration of lamina propria by fibroblasts and muscle fibres from the muscularis mucosae. Very few intermittent or recurrent symptoms are rectal bleeding and mucous discharge with defecations, difficulty of a complete ampullar evacuation and sometimes pelvic or rectoperineal pain. Clinical picture and endoscopic biopsies led to diagnosis. Barium enema, defecography, transrectal ultrasound, manometry and electromyography have an additional role. Medical treatment is performed by high-fiber diet, but biofeedback training is very helpful. Surgical management is as an excisional surgery, as a rectopexy if there is prolapse. Fecal diversion and rectocolic resection are considered only for patients with obstinate and severe symptoms. Even in patients who seem to advocate a surgical approach it is important to heal a dyskinetic puborectalis muscle.
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PMID:[The solitary rectal ulcer today. A review of the literature]. 997 95

Although it is unclear to what extent irritable bowel syndrome (IBS) symptoms represent a normal perception of abnormal function or an abnormal perception of normal function, many believe that IBS constitutes the clinical expression of an underlying motility disorder, affecting primarily the mid- and lower gut. Indeed, transit and contractile abnormalities have been demonstrated with sophisticated techniques in a subset of patients with IBS. As a consequence, drugs affecting gastrointestinal (GI) motility have been widely employed with the aim of correcting the major IBS manifestations, ie, pain and altered bowel function. Unfortunately, no single drug has proven to be effective in treating IBS symptom complex. In addition, the use of some medications has often been associated with unpleasant side effects. Therefore, the search for a truly effective and safe drug to control motility disturbances in IBS continues. Several classes of drugs look promising and are under evaluation. Among the motor-inhibiting drugs, gut selective muscarinic antagonists (such as zamifenacin and darifenacin), neurokinin2 antagonists (such as MEN-10627 and MEN-11420), beta3-adrenoreceptor agonists (eg, SR-58611A) and GI-selective calcium channel blockers (eg, pinaverium bromide and octylonium) are able to decrease painful contractile activity in the gut (antispasmodic effect), without significantly affecting other body functions. Novel mechanisms to stimulate GI motility and transit include blockade of cholecystokinin (CCK)A receptors and stimulation of motilin receptors. Loxiglumide (and its dextroisomer, dexloxiglumide) is the only CCKA receptor antagonist that is being evaluated clinically. This drug accelerates gastric emptying and colonic transit, thereby increasing the number of bowel movements in patients with chronic constipation. It is also able to reduce visceral perception. Erythromycin and related 14-member macrolide compounds inhibit the binding of motilin to its receptors on GI smooth muscle and, therefore, act as motilin agonists. This antibiotic accelerates gastric emptying and shortens orocecal transit time. In the large bowel a significant decrease in transit is observed only in the right colon, which suggests a shift in fecal distribution. Several 'motilinomimetics' have been synthesized. Their development depends on the lack of antimicrobial activity and the absence of fading of the prokinetic effect during prolonged administration. 5-hydroxytryptamine (5-HT)4 agonists with significant pharmacological effects on the mid- and distal gut (such as prucalopride and tegaserod) are available for human use. These 'enterokinetic' compounds are useful for treating constipation-predominant IBS patients. 5-HT3 receptor antagonists also possess a number of interesting pharmacological properties that may make them suitable for treatment of IBS. Besides decreasing colonic sensitivity to distension, these drugs prolong intestinal transit and may be particularly useful in diarrhea-predominant IBS. Finally, when administered in small pulsed doses, octreotide, besides reducing the perception of rectal distension, accelerates intestinal transit, although other evidence disputes such an effect.
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PMID:Management of irritable bowel syndrome: novel approaches to the pharmacology of gut motility. 1020 10

We report a case of ruptured stercoral ulceration due to chronic constipation which is caused by rectal carcinoma. This case suffered from difficulty of stool passage for 5 months. Periumbilical pain and current-jelly stool were experienced before his admission. Physical examination revealed diffuse abdominal rebounding pain and laboratory data showed leukocytosis. Computed tomography demonstrated marked dilatation of the sigmoid colon with stool impaction due to neoplastic growth in the rectosigmoid junction. Thickening and edematous change of the colonic wall were noted. There was amorphous material with gas in the mesocolon, which indicated fecal peritonitis. Emergent operation with Hartman's procedure and left colostomy was performed. Diffuse pressure gangrene of the sigmoid colon wall with a perforating hole was identified. Pathologically, the resected colon specimen showed non-specific-acute and chronic inflammatory change. The perforating hole was surrounded by a necrotic border of ulcerative mucosa. After the operation, pelvic drainage was undertaken for 1 month and then the patient was discharged uneventfully.
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PMID:Rectal carcinoma with stercoral ulcer perforation. 1102 Aug 68

Existing pharmacotherapeutic options for the treatment of patients with irritable bowel syndrome (IBS) are limited in treating the multiple symptoms associated with the disorder. There is much interest in the use of serotonin agents as new therapeutics. Acting primarily through 5-HT3 and 5-HT4 receptors, serotonin elicits changes in motor function and possibly visceral sensation. Two serotonin agents were developed specifically for IBS: tegaserod, a 5-HT4 receptor partial agonist, and alosetron, a 5-HT3 receptor antagonist (which is no longer available). Phase III clinical trial data show that during a 12-week treatment period with tegaserod, IBS patients with abdominal pain and discomfort, bloating, and constipation experienced significant global relief (i.e., improvement in overall well-being, abdominal pain, and bowel habit) compared with placebo. Improvement in bowel movement frequency and consistency was achieved and pain was relieved by 1 week. During 12 weeks of treatment, alosetron was shown to elicit significant relief of abdominal pain and discomfort compared with placebo or mebeverine in female IBS patients with diarrhea. Alosetron slowed colonic transit and treatment efficacy was apparent after a week of treatment. Another 5-HT4 receptor agonist, prucalopride, which is being developed for chronic constipation, accelerates colonic transit and increases stool frequency. Therefore, this agent may be of benefit in IBS patients with constipation.
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PMID:Drug therapy options for patients with irritable bowel syndrome. 1147 11

We examined the effects of YM-31636 (2-(1H-imidazol-4-ylmethyl)-8H-indeno[1,2-d]thiazole monofumarate), a novel 5-HT3 receptor agonist, on gastrointestinal functions including visceral pain reflex in rats. Injection of YM-31636 increased the number of fecal pellets. This effect was completely inhibited by ramosetron, a 5-HT3 receptor antagonist. YM-31636 also increased the intracolonic pressure measured in both conscious and anesthetized rats. In isolated distal colon, YM-31636 increased the short-circuit current response. This effect was abolished by ramosetron. Both the maximal response and the potency of YM-31636 were weaker than those of other 5-HT3 receptor agonists. In two visceral pain reflex models, YM-31636 neither changed the magnitude of pressor response to colonic distension in anesthetized rats nor affected the visceromotor threshold to colorectal distension in conscious rats. In conclusion, YM-31636 facilitated defecation without increasing visceral pain. Consequently, 5-HT3 receptor agonists like YM-31636 would be promising in the treatment of chronic constipation.
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PMID:A novel 5-HT3 receptor agonist, YM-31636, increases gastrointestinal motility without increasing abdominal pain. 1171 40

The entity of an occult tight filum terminale syndrome, characterized by clinical findings consistent with a tethered cord syndrome, but with the conus ending in a normal position, has been recognized recently. The indications for sectioning the filum terminale in this situation are not well characterized and are controversial. We report a retrospective review of a consecutive series of 60 children (ages 3-18 years) with a diagnosis of occult tight filum terminale syndrome who underwent section of the filum and were followed for more than 6 months (mean 13.9 months). The criteria for surgical intervention were (1) spina bifida occulta, (2) progressive bladder instability unresponsive to conservative measures, (3) urological/nephrological evaluation to confirm or rule out nonneurogenic etiology, and (4) two or more of the following: (a) bowel involvement (fecal incontinence or chronic constipation), (b) lower extremity weakness, (c) gait changes, (d) reflex/tone abnormalities, (e) sensory disturbances, (f) back/leg pain, (g) orthopedic abnormalities/limb length discrepancy, (h) scoliosis/lordosis, (i) recurrent urinary tract infections, (j) abnormal voiding cystourethrogram/ultrasound, (k) syringomyelia, and (l) neurocutaneous stigmata. Postoperatively, urinary incontinence/retention showed complete resolution in 52%, marked improvement (>95% resolution) in 35%, moderate improvement (>75%) in 6%, minimal improvement (> 50%) in 6%, and no improvement (<50%) in 2%. Fecal incontinence completely resolved in 56%, improved in 41%, and was unchanged in 3%. Weakness, sensory abnormalities, and pain improved or resolved in all patients.
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PMID:Occult tight filum terminale syndrome: results of surgical untethering. 1588 17

The epidemiology and health-related quality of life associated with functional gastrointestinal disorders are reviewed, with particular emphasis on irritable bowel syndrome and functional dyspepsia. The literature supports the significant world-wide prevalence of functional gastrointestinal disorders, including irritable bowel syndrome (IBS), functional dyspepsia and chronic constipation. An increased female prevalence has been demonstrated in most studies in patients with IBS and chronic constipation, but not functional dyspepsia. The female to male ratio appears to be greater in the health care-seeking population than in community populations. However, some differences in the reported general prevalence and gender-related prevalence of functional gastrointestinal disorders may be due to cultural factors and study methodology. A significant health care burden is associated with IBS, with increased out-patient services, abdominal and pelvic surgeries, and gastrointestinal- and non-gastrointestinal-related physician visits and health care costs. Health-related quality of life is impacted significantly in patients with functional gastrointestinal disorders, such as functional dyspepsia and IBS, compared with the general healthy population, as well as patients with other chronic medical conditions, such as gastro-oesophageal reflux disease and asthma. Impaired health-related quality of life has been demonstrated, in particular, in patients with moderate to severe disease seen in referral settings. The health-related quality of life appears to improve in treatment responders, or correlates with symptom improvement, with at least some treatment modalities studied in functional gastrointestinal disorders, but further studies are needed. Predictors of health-related quality of life in patients with functional gastrointestinal disorders include psychosocial factors, such as early adverse life events, and symptoms related to visceral perception, e.g. pain and chronic stress. The presence of extra-intestinal symptoms appears to have a major if not greater impact on health care visits, excess health care costs and health-related quality of life in patients with functional gastrointestinal disorders.
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PMID:Review article: epidemiology and quality of life in functional gastrointestinal disorders. 1552 53

Lubiprostone [RU 0211, SPI 0211] is a bicyclic fatty acid that acts as a chloride channel opener, increasing intestinal water secretion. Lubiprostone, an orally-administered formulation, is one of a series of functional fatty acid compounds discovered by Dr Ryuji Ueno, and is currently undergoing development for the treatment of constipation, constipation-predominant irritable bowel syndrome (IBS-C) and postoperative ileus with Sucampo Pharmaceutical's. Lubiprostone activates a specific chloride channel (CLC2) on cells lining the gut, thereby naturally increasing intestinal fluid secretion. The increased fluid level softens the stool, promotes spontaneous bowel movements, and reduces abdominal discomfort/pain and bloating. The chloride channel is a protein that controls cell membrane transport of chloride ion. Lubiprostone acts on the ClC-2 chloride channel, which is located in the apical intestinal membrane. In November 2004, Takeda Pharmaceuticals entered into a collaboration and licensing agreement for Lubiprostone with Sucampo Pharmaceuticals for the treatment of chronic constipation and constipation-predominant Irritable Bowel Syndrome (c-IBS). Under the terms of the agreement, Takeda received the right to market the product in the US and Canada, while Sucampo reserved the co-promotion rights for these countries. Takeda's wholly-owned US subsidiary, Takeda Pharmaceuticals North America Inc., will sell lubiprostone once the product is approved by the US FDA. Takeda will also receive an option for marketing rights in other territories, including Japan and Europe. Takeda and Sucampo agreed on the exclusive manufacturing and supply of Lubiprostone by R-Tech Ueno, Ltd, a member of the Sucampo Group. Sucampo has the potential to receive up to dollar US 210 million in initial and milestone payments, some of which are contingent upon the successful achievement of several milestones. Takeda will fund a major part of development costs not only for chronic constipation and c-IBS, but also for other indications in the gastroenterology field. Takeda will make royalty payments to Sucampo after the product is launched. In May 2005, Sucampo received dollar US 20 million from Takeda Pharmaceutical as payment for achieving a development milestone of initiating a phase III clinical trial of lubiprostone to treat patients with constipation-predominant irritable bowel syndrome. Sucampo Pharmaceuticals submitted a new drug application (NDA) for lubiprostone to the FDA on 31 March 2005 for approval in the treatment of chronic idiopathic constipation (CIC) and associated symptoms in adults. Sucampo completed three long-term, open-label safety studies, which will support the NDA for lubiprostone, in treating constipation. Results from its second open-label safety study with lubiprostone were announced in February 2004, with the first two studies demonstrating long-term safety and sustained effectiveness in constipated subjects. In the US, the final phase III study for chronic constipation was completed in the fourth quarter of 2004. In November 2004, Sucampo announced completing a phase II safety and efficacy study of lubiprostone for the treatment of IBS-C. This study, which was initiated in April 2003, randomised 195 patients with documented IBS into four treatment groups (three doses of SPI 0211 and placebo) from 19 locations throughout the US.
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PMID:Lubiprostone: RU 0211, SPI 0211. 1599 86


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