Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0013395 (dyspepsia)
 4,879 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastrointestinal prokinetics promote or increase the coordination of the gut wall contractions leading to enhancement of propulsive motility and, consequently, caudal displacement of luminal contents. Currently, they are considered drugs of choice for the treatment of upper gastrointestinal tract functional motor disorders such as those associated with gastrooesophageal reflux disease, chronic dyspepsia, gastroparesis (idiopathic or secondary to other diseases) and acute or chronic idiopathic intestinal pseudo-obstruction. The aim of the present review is to give an outline of the pharmacology of currently available prokinetics and of novel drugs endowed with gastrointestinal prokinetic action that require further pharmacological and/or clinical testing. The novel drugs include recent generations of benzamide and non-benzamide 5-HT4 receptor agonists, motilin receptor agonists, and inhibitors of nitric oxide synthase. Furthermore, based on our improved knowledge of the role of 5-HT in emesis and gastrointestinal motility, the therapeutic potential of potent mixed 5-HT4 agonists--5-HT3 antagonists in the control of cytotoxic-drug-induced emesis and associated gut motor disturbances will be discussed. Lastly, a section of this review deals with the colon as a possible target for the action of prokinetics.
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PMID:Recent advances in the pharmacology of gastrointestinal prokinetics. 893 12

Gastrointestinal involvement occurs in most patients with systemic sclerosis and is subclinical in about one third. Early pathology is characterized by vasculopathy, resulting in tissue ischemia and progressive dysfunction. Noninvasive esophageal studies using semisolid bolus scintigraphy are sensitive but lack specificity. Long-term treatment of reflux with high-dose proton pump inhibitors appears safe and effective for symptom relief and may prevent recurrence of esophagitis and stricture. Dyspepsia may result from gastroparesis and antral distension. Gastric antral vascular ectasia is a vascular manifestation, and bleeding may be controlled endoscopically. Prokinetic agents effective in pseudoobstruction include metoclopramide, domperidone, cisapride, octreotide, and erythromycin. Patients with intestinal neuropathy or response to bolus octreotide are more probable long-term responders. The combination of octreotide and erythromycin may be particularly effective in systemic sclerosis. The combination of cisapride and erythromycin may cause serious cardiac arrhythmia and is contraindicated. Omeprazole may predispose to small intestinal bacterial overgrowth. Malabsorption not responding to antibiotic therapy should be investigated with small-bowel biopsy to rule out more unusual causes. Pneumatosis cystoides intestinalis may be due to excessive hydrogen production by intestinal bacteria altering the partial pressure of nitrogen in the intestinal wall. In selected cases, surgery for intestinal failure is an option with resection or bypass of affected segments or placement of enterostomy tubes for feeding or decompression. Careful preoperative characterization of intestinal segments is required.
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PMID:Gastrointestinal features of scleroderma. 901 61

Efficacy of one-week triple antimicrobial therapy (bismuth, tinidazole, amoxicillin) as compared to the same drug combination given for 4 weeks was assessed in children with Helicobacter pylori (H. pylori) gastritis and non-ulcer dyspepsia. Twenty-six patients (group A) and 30 (group B) had one-week and four-week schedule, respectively. Eradication (absence of organism at endoscopy at least 1 month after ending treatment) was achieved in 84.6% of group A (22) and 83.3% of group B (25), with marked reduction of histological gastritis score in both groups. Among patients with eradicated H. pylori, symptoms improved significantly in 14 and 16 patients of group A and B, respectively, but were still present in 17 (8 group A, 9 group B). The latter showed gastroparesis and abnormal gastro-oesophageal reflux at a subsequent diagnostic work-up and improved with prokinetic therapy. In 3 patients of group A and 3 of group B, symptoms improved despite persistence of bacterium into the stomach. Finally, in 3 cases (1 group A, 2 group B) both symptoms and H. pylori infection were unchanged. At 6 month follow-up, symptoms were present in 7 patients (3 group A, 4 group B): 6 of them (3 group A, 3 group B) showed H. pylori gastritis at endoscopy. We conclude that in children with dyspepsia and H. pylori gastritis one-week triple antimicrobial schedule is effective in eradicating bacterium; however, detection of H. pylori gastritis in dyspeptic children does not invariably indicate a pathogenic role of the organism in these patients.
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PMID:Helicobacter pylori gastritis and non-ulcer dyspepsia in childhood. Efficacy of one-week triple antimicrobial therapy in eradicating the organism. 903 84

Assessment of gastric emptying time by ultrasonography is increasingly used to evaluate gastroparesis. At first normal values have to be defined. In 20 healthy volunteers the upper value of half emptying time after a semisolid meal was 50 min. A good correlation of gastric emptying time evaluated by scintigraphy was found. Diabetics with autonomous neuropathy had a remarkable delay in gastric emptying, not seen in patients with functional dyspepsia. In dyspeptic patients pathologic width of the antrum (measured by planimetry after overnight fasting) decreased during therapy with cisapride in correlation to the improvement of symptoms.
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PMID:[Possibilities of ultrasonography of gastric emptying]. 912 48

Dyspepsia is a vague term for the nonspecific symptoms of upper abdominal discomfort, prolonged postprandial fullness or early satiety, nausea, vomiting, and upper abdominal bloating. Many common and accepted diseases and disorders such as gastroesophageal reflux and irritable bowel syndrome cause dyspepsia symptoms; these disorders should be identified and treated. However, many patients with dyspepsia symptoms have normal radiographic and endoscopic evaluations; in these patients, neuromuscular of functional disorders of the stomach ranging from gastric dysrhythmias to gastroparesis may be the cause of dyspepsia symptoms. A practical approach to the evaluation and treatment of dyspepsia symptoms attributed to gastric neuromuscular dysfunction of unknown origin is described.
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PMID:Dyspepsia of unknown origin: pathophysiology, diagnosis, and treatment. 943 96

Helicobacter pylori infection is a common infection in Singapore affecting about 31% of the population. The seroprevalence of H. pylori infection increases with age from 3% in children below 5 years to 71% in adults above 65 years. Amongst the races, Chinese and Indians had similar rates of seropositivity (34.3% and 33.6%) while in Malays it was significantly lower (13.7%; P < 0.05). H. pylori infection is associated with peptic ulcer disease (both duodenal and gastric ulcer) as well as gastric cancer [adenocarcinoma, early gastric cancer and mucosa-associated lymphoma of T cell type (MALT) lymphoma]. Its role in non-ulcer dyspepsia is controversial. H. pylori was found in 31% of non-ulcer dyspepsia patients in Singapore compared with 28% in normal healthy controls. Gastric emptying test using indigestible solids shows that gastroparesis per se, H. pylori in the presence of gastroparesis (but not H. pylori alone) are related to dyspeptic symptom. H. pylori plays a synergistic role with non-steroidal anti-inflammatory drugs (NSAIDs) in causing bleeding in gastric ulcer but not in duodenal ulcer. Invasive and non-invasive methods are available for diagnosis of H. pylori and should be used to establish the aetiology of gastro-duodenal disease. Currently two groups of therapeutic regimes with eradication rates of 90% are available: bismuth containing regimes and proton-pump inhibitors based regimes. Triple therapy for one week (using three drugs effective against H. pylori) is currently the treatment of choice.
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PMID:Helicobacter pylori infection--current status in Singapore. 949 71

Patients with gastroparesis frequently present challenging clinical, diagnostic, and therapeutic problems. Data from 146 gastroparesis patients seen over six years were analyzed. Patients were evaluated at the time of initial diagnosis and at the most recent follow-up in terms of gastric emptying and gastrointestinal symptomatology. The psychological status and physical and sexual abuse history in female idiopathic gastroparesis patients were ascertained and an association between those factors and gastrointestinal symptomatology was sought. Eighty-two percent of patients were females (mean age: 45 years old). The mean age for onset of gastroparesis was 33.7 years. The etiologies in 146 patients are: 36% idiopathic, 29% diabetic, 13% postgastric surgery, 7.5% Parkinson's disease, 4.8% collagen vascular disorders, 4.1% intestinal pseudoobstruction, and 6% miscellaneous causes. Subgroups were identified within the idiopathic group: 12 patients (23%) had a presentation consistent with a viral etiology, 48% had very prominent abdominal pain. Other subgroups were gastroesophageal reflux disease and nonulcer dyspepsia (19%), depression (23%), and onset of symptoms immediately after cholecystectomy (8%). Sixty-two percent of women with idiopathic gastroparesis reported a history of physical or sexual abuse, and physical abuse was significantly associated with abdominal pain, somatization, depression, and lifetime surgeries. At the end of the follow-up period, 74% required continuous prokinetic therapy, 22% were able to stop prokinetics, 5% had undergone gastrectomy, 6.2% went onto gastric electrical stimulation (pacing), and 7% had died. At some point 21% had required nutrition support with a feeding jejunostomy tube or periods of parenteral nutrition. A good response to pharmacological agents can be expected in the viral and dyspeptic subgroups of idiopathics, Parkinson's disease, and the majority of diabetics, whereas a poorer outcome to prokinetics can be expected in postgastrectomy patients, those with connective tissue disease, a subgroup of diabetics, and the subset of idiopathic gastroparesis dominated by abdominal pain and history of physical and sexual abuse. Appreciation of the different etiologies and psychological status of the patients may help predict response to prokinetic therapy.
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PMID:Demography, clinical characteristics, psychological and abuse profiles, treatment, and long-term follow-up of patients with gastroparesis. 982 25

Gastric function is finely modulated by a series of neurological mechanisms, so that gastric digestion is normally not perceived. Alteration of these control mechanisms may lead to different situations, which are frequently associated with symptoms. An impaired tonic contraction of the proximal stomach, that is, an impaired gastric tone, results in gastroparesis. Patients with functional dyspepsia, and also patients with achalasia, have impaired meal accommodation of the stomach. Interestingly, patients with functional dyspepsia may also have a sensory dysfunction, and both dysfunctions could play a synergistic role. However, the sensory dysfunction in dyspepsia, particularly the types of afferent fibres affected, and the mechanisms of impaired accommodation, still remain to be characterized. Evaluation of gastric function has been approached using the barostat. However, the barostat has limitations and potential technical pitfalls that require proper attention. Meal ingestion induces a variety of reflexes and the net result is a relaxation of the stomach. However, gastric reflexes can be best evaluated with the stomach empty, when the stimuli are applied at a different site. Nevertheless, altered reflex responses may be difficult to interpret. For instance, absent or decreased relaxatory responses may equally correspond to a gastroparetic stomach without tone or to a dyspeptic stomach unable to relax. In this context, it may be important to measure basal tone. Distension of the stomach by means of the barostat has been also used to test gastric sensitivity. However, recent studies have shown that perception of gastric distension relays on stimulation of tension receptors; since wall tension depends on both pressure and volume, distension with the barostat may be difficult to standardize. Hopefully, a battery of tests may become available in the near future for a complete neuromuscular evaluation of the gut.
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PMID:Gastric neurology: evolving concepts and techniques. 983 Dec 67

Several serotonin (5-HT) receptor subtypes have been defined by pharmacological responses to selective agonists and antagonists and by pathways of receptor-effector coupling. Using molecular techniques, additional receptor subtypes have been described. 5-HT receptors are prevalent in the central nervous system and gut and participate in induction of emesis. 5-HT3 antagonists are used to prevent emesis from cancer chemotherapy and also demonstrate efficacy in radiation-induced nausea, postoperative nausea, hyperemesis gravidarum, and nausea and vomiting with the acquired immunodeficiency syndrome. 5-HT4 agonists exhibit prokinetic properties in nauseated patients with gastroparesis and functional dyspepsia. Conversely, 5-HT4 antagonists have antiemetic activity in some experimental models. The 5-HT1D receptor agonist sumatriptan reduces emesis with migraine headaches and in cyclic vomiting syndrome, most likely via action on central nervous system sites. In other models, 5-HT1A and 5-HT2A/5-HT2C agonists exhibit antiemetic properties. The utility of 5-HT receptor ligands in treating emesis is the subject of active investigation.
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PMID:Serotonin receptor physiology: relation to emesis. 1049 49

Dysphagia and chest pain are the two commonest symptoms of abnormalities of oesophageal motility. Dysphagia is to be distinguished into high or oropharyngeal and low or oesophageal dysphagia. Oropharyngeal dysphagia pertains to dysfunction of the pars cricopharyngea of the M. constrictor pharyngis inferior (M. cricopharyngeus), which is frequently associated with a Zenker diverticulum. Treatment consists of endoscopical or surgical myotomy and diverticulectomy. In achalasia there is incomplete relaxation of the lower esophageal sphincter with aperistalsis. The main treatment modalities are endoscopic pneumodilation and surgical myotomy of this sphincter. In dysphagia or non-cardiac chest pain spastic or hypocontractile abnormalities of the oesophageal motility can be involved, these are often difficult to treat. Disorders of gastric motility are mainly gastroparesis and functional dyspepsia. In diabetic gastroparesis, adequate monitoring of the blood sugar level is also necessary. New insights into the pathophysiology of functional dyspepsia concern abnormal visceral sensitivity and reduced adaptive relaxation of the stomach during intake of food.
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PMID:[Gastrointestinal surgery and gastroenterology. VII. Proximal motility disorders in the digestive tract]. 1074 45


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