Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytokine tumor necrosis factor alpha (TNF(alpha)) may act within the neural circuitry of the medullary dorsal vagal complex (DVC) to affect changes in gastric function such as gastric stasis, loss of appetite, nausea, and vomiting. The definitive demonstration that endogenously generated TNF(alpha) is acting within the DVC circuitry to affect these changes has been impeded by the lack of an antagonist for TNF(alpha). The present studies used localized central nervous system microinjections of the TNF-adsorbant construct (TNFR:Fc) to specifically neutralize the ability of endogenously produced TNF(alpha) to activate NST neurons. Our studies reveal that TNFR:Fc suppresses induction of cFos normally evoked by TNF(alpha). These results validate our hypothesis that circulating TNF(alpha) may act directly within the DVC to affect gastric function in a variety of pathophysiological states.
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PMID:TNFalpha-stimulation of cFos-activation of neurons in the solitary nucleus is suppressed by TNFR:Fc adsorbant construct in the dorsal vagal complex. 1276 23

Diabetic gastroparesis is a common and debilitating condition affecting millions of patients with diabetes mellitus worldwide. Although gastroparesis in diabetes has been known clinically for more than 50 years, treatment options remain very limited. Until recently, the scientific literature has offered few clues regarding the precise aetiology of gastric dysfunction in diabetes.Up to 50% of patients with diabetes may experience postprandial abdominal pain, nausea, vomiting and bloating secondary to gastric dysfunction. There is no clear association between length of disease and the onset of delayed gastric emptying. Gastroparesis affects both type 1 (insulin dependent) and type 2 (non- insulin dependent) forms of diabetes. Diagnosis requires identifying the proper symptom complex, while excluding other entities (peptic ulcer disease, rheumatological diseases, medication effects). The diagnosis of gastroparesis may be confirmed by demonstrating gastric emptying delay during a 4-hour scintigraphic study. Treatment options are limited and rely on dietary modifications, judicious use of available pharmacological agents, and occasionally surgical or endoscopic placement of gastrostomies or jejunostomies. Gastric pacing offers promise for patients with medically refractory gastroparesis but awaits further investigation. Current pharmacological agents for treating gastroparesis include metoclopramide, erythromycin, cisapride (only available via a company-sponsored programme) and domperidone (not US FDA approved). All of these drugs act as promotility agents that increase the number or the intensity of gastric contractions. These medications are not uniformly effective and all have adverse effects that limit their use. Cisapride has been removed from the open market as a result of over 200 reported cases of cardiac toxicity attributed to its use. Unfortunately, there is a paucity of clinical studies that clearly define the efficacy of these agents in diabetic gastroparesis and there are no studies that compare these drugs to each other. The molecular pathophysiology of diabetic gastroparesis is unknown, limiting the development of rational therapies. New studies, primarily in animals, point to a defect in the enteric nervous system as a major molecular cause of abnormal gastric motility in diabetes. This defect is characterised by a loss of nitric oxide signals from nerves to muscles in the gut resulting in delayed gastric emptying. Novel therapies designed to augment nitric oxide signalling are being studied.
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PMID:Current concepts in diabetic gastroparesis. 1282 60

The management of both diabetic and idiopathic gastroparesis often represents a substantial clinical challenge. In formulating recommendations for therapy, it should be recognized that these are based on less than optimal evidence; in particular, there are substantial deficiencies in current knowledge relating to the pathophysiology of gastroparesis, as well as the natural history of gastrointestinal symptoms, and the majority of pharmacologic trials have been short term and associated with methodologic limitations. Although the etiologic factors differ, the overall management principles are similar in the two conditions. Maintenance of adequate nutrition is pivotal, and parenteral nutrition may be required in severe cases associated with malnutrition. In patients with diabetes, rigorous attempts should be made to optimize glycemic control--hyperglycemia slows gastric emptying and may exacerbate symptoms and attenuate the effects of prokinetic drugs. Despite the relatively poor predictive value of symptoms, it is reasonable to suggest a trial of prokinetic therapy for about 4 weeks, rather than initially establishing the diagnosis by measurement of gastric emptying. However, it should be recognized that there is a substantial placebo response, a lack of evidence to support the cost effectiveness of such an approach, and that most patients will require prolonged therapy. In type 1 diabetic patients, prokinetic therapy may potentially benefit glycemic control, and this forms an additional rationale (albeit not established) for therapy. Some patients with diabetes and idiopathic gastroparesis with severe vomiting are unable to tolerate oral medication; in such cases subcutaneous metoclopramide may prove useful. Patients with intractable symptoms should be hospitalized and given intravenous erythromycin. The repertoire of prokinetic agents available in the United States is limited and includes metoclopramide, erythromycin, and cisapride (available by special program from its manufacturer); all of these drugs are associated with side effects. The use of metoclopramide may represent the first choice for chronic oral therapy, although it has been studied less comprehensively than cisapride. Combination therapy may be potentially more efficacious than the use of single agents. Dehydration and metabolic derangements should be corrected. The choice of chronic medical therapy should be individualized, taking factors such as age, presence of diabetes, concurrent medications, and comorbidities into account. In a small number of patients in whom medical treatment fails, surgery should be considered, and, if performed, done in a specialized center. A number of novel therapies, including gastric electrical stimulation, are currently being evaluated.
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PMID:Idiopathic and Diabetic Gastroparesis. 1284 39

Gastric neuromuscular disorders encompass a spectrum of dysfunction in nerve and smooth muscle that includes gastric visceral hypersensitivity, gastric dysrhythmias, fundic dysfunction, antral hypomotility, and gastroparesis. Patients with each disorder may present with such vague dyspepsia symptoms as early satiety, upper abdominal discomfort, bloating, or nausea with or without vomiting. A careful history and physical examination may suggest a gastric neuromuscular disorder, but symptoms are nonspecific. Gastroparesis is the most severe form of neuromuscular dysfunction. Such reversible causes of gastroparesis as mechanical obstruction of the stomach and chronic mesenteric ischemia must be excluded. Gastroparesis, gastric dysrhythmias, and hypersensitivity may follow viral infection or be due to degenerative processes that affect the gastric enteric neurons, smooth muscle, or interstitial cells of Cajal. Commonly, the cause of these gastric neuromuscular disorders is unknown. An approach to the diagnosis and treatment of gastric neuromuscular disorders is reviewed, including dietary counseling, drugs, and medical devices.
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PMID:Diagnosis and treatment of neuromuscular disorders of the stomach. 1286 63

Cholangiocarcinoma most commonly presents as painless progressive jaundice. We report a case occurring in a 56-year-old Chinese woman with an unusual presentation of progressive dysphagia and vomiting. Oesophageal manometric and barium studies were indicative of achalasia, and computed tomography confirmed the presence of cholangiocarcinoma extending to the gastroesophageal junction and proximal lesser curve of the stomach. In this case, a constricting tumour at the gastroesophageal junction with probable invasion of the vagus nerves led to features of achalasia and gastroparesis.
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PMID:Cholangiocarcinoma presenting as pseudoachalasia and gastroparesis. 1290 20

Dopamine2 (D2)-like receptor antagonists are widely used for the treatment of gastroparesis and vomiting. Metoclopramide (MCP), a peripheral and central D2-like receptor antagonist, stimulates the sympathetic nervous system and may alter autonomic modulation, but the net effect of MCP to the heart is not known. The aim of our study was to investigate the effects of MCP on cardiac autonomic modulation, using power spectral analysis of heart rate variability. We evaluated the effect of MCP on cardiac autonomic modulation during prolonged supine and standing positions in 9 healthy men. We intravenously administered 10 mg MCP and placebo in a double blind and crossover manner to all participants during continuous electrocardiography recording. Placebo or MCP was administered after 15 minutes in supine position (REST phase), where participants remained for an additional 50 minutes (PSUP phase) and then stood up for 10 minutes (STA phase). Five-minute intervals were selected for power spectral analysis, and average values were calculated for low frequency (LF), normalized unit of LF (LFnu), high frequency (HF), normalized unit of HF (HFnu) components of the power spectrum, and for LF/HF ratio.Heart rate alterations were statistically significant during placebo administration (Friedman's p < 0.0001). These changes were related to the decrease in PSUP phase and increase in STA phase in post hoc analyses. There was a trend toward lower LFnu in PSUP phase (Friedman's p = 0.050), but LF/HF ratio changes did not reach a statistically significant level during placebo administration. MCP administration prevented the decrease in heart rate and LFnu component was seen with placebo in PSUP phase. Heart rate alterations also reached a significant level during MCP administration (Friedman's p = 0.002), and post hoc analyses showed that these changes were mainly related to the increase in STA phase. In contrast to placebo, MCP administration resulted in significant alterations in LFnu and LF/HF ratio (Friedman's p = 0.004 and p = 0.003, respectively). Two-way ANOVA model for LF/HF ratio changes showed that MCP induced a significant upward shift in LF/HF ratio than placebo during each phase of the study (F = 5.570; p = 0.031). We concluded that the net effect of MCP on sympathovagal balance is an increased sympathetic drive to the heart. MCP prevented the decrease in sympathetic drive to the heart during prolonged supine position and augmented sympathetic drive to the heart during mild sympathetic stimulation such as induced by standing up.
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PMID:The effect of dopamine type-2 receptor blockade on autonomic modulation. 1295 47

A causal relation between gastric stasis and gastric ulceration is suggested by the literature reviewed. In obstructive duodenal ulcer disease it is important to know that a concomitant gastric ulcer may be present and causing the symptoms. In combined ulcers, symptoms are more severe and treatment is more difficult.A clinical study of 60 cases of stasis gastric ulcer associated with chronic duodenal ulcer disease is presented. Twenty-six of these patients with gastric ulcers were bleeding at the time of their admission. The mortality rate was at least twice that for solitary ulcer. Early warning symptoms of stasis were fatigue, anorexia, fullness and weight loss; vomiting was a late manifestation. X-ray findings were often inaccurate; evidence of retention was reported in only 21. Gastric residue measurements were particularly useful in showing gastric retention.Since the basic disease in combined ulcers is the duodenal lesion, surgical treatment is primarily that for duodenal ulcer.
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PMID:STASIS GASTRIC ULCER: A COMPLICATION OF DUODENAL ULCER. 1413 88

Gastroparesis is characterized by delayed gastric emptying in the absence of obstruction. Common symptoms include nausea, vomiting, and abdominal pain. Severe gastroparesis might result in recurrent hospitalizations, malnutrition, and significant mortality. Patients failing medical therapy are often considered for a variety of surgical interventions, the efficacy of which is not well studied. This review summarizes available literature on surgical interventions in gastroparesis. A MEDLINE search for the period from 1966 to 2002 was performed to identify all English language literature regarding surgical interventions in gastroparesis. Therapies reviewed were gastrostomy, jejunostomy, gastric pacing/stimulation, and gastrectomy or surgical drainage procedures. Candidate studies involved human subjects and included surgical series or trials. The search was conducted independently by two authors and discrepancies resolved by consensus opinion. Seventeen articles met inclusion criteria. These included series reporting on gastrostomy (2), jejunostomy (3), gastric stimulation (2), and gastrectomy for postsurgical (6), diabetic (3), and idiopathic (1) gastroparesis. All trials were unblinded, uncontrolled case series or retrospective reviews. Methodologic differences did not allow for pooled analysis. Completion gastrectomy seems to provide symptom relief in postsurgical gastroparesis. Benefits of gastric surgery for other forms of gastroparesis are not adequately studied. Gastrostomy might provide symptom improvement, but only 26 subjects in two trials were evaluable. Jejunostomy improved symptoms and nutrition in 32 evaluable subjects in three trials but had significant complications. Gastric neurostimulation improves symptoms of nausea and vomiting, but therapeutic gain beyond placebo has not been demonstrated. Limited data exist concerning surgical therapies of gastroparesis. Completion gastrectomy seems effective for postsurgical gastroparesis, but a cautious approach is warranted before surgical therapies in diabetic or idiopathic gastroparesis are used.
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PMID:A systematic review of surgical therapy for gastroparesis. 1457 55

Antidopaminergic gastrointestinal prokinetics (bromopride, clebopride, domperidone, levosulpiride and metoclopramide) have been exploited clinically for the management of motor disorders of the upper gastrointestinal tract, including functional dyspepsia, gastric stasis of various origins and emesis. The prokinetic effect of these drugs is mediated through the blockade of enteric (neuronal and muscular) inhibitory D2 receptors. The pharmacological profiles of the marketed compounds differ in terms of their molecular structure, affinity at D2 receptors, ability to interact with other receptor systems [5-hydroxytryptamine-3 (5-HT3) and 5-HT4 receptors for metoclopramide; 5-HT4 receptors for levosulpiride) and ability to permeate the blood-brain barrier (compared with the other compounds, domperidone does not easily cross the barrier). It has been suggested that the serotonergic (5-HT4) component of some antidopaminergic prokinetics may enhance their therapeutic efficacy in gastrointestinal disorders, such as functional dyspepsia and diabetic gastroparesis. The antagonism of central D2 receptors may lead to both therapeutic (e.g. anti-emetic effect due to D2 receptor blockade in the area postrema) and adverse (including hyperprolactinaemia and extrapyramidal dystonic reactions) effects. As the pituitary (as well as the area postrema) is outside the blood-brain barrier, hyperprolactinaemia is a side-effect occurring with all antidopaminergic prokinetics, although to different extents. Extrapyramidal reactions are most commonly observed with compounds crossing the blood-brain barrier, although with some differences amongst the various agents. Prokinetics with a high dissociation constant compared with that of dopamine at the D2 receptor (i.e. compounds that bind loosely to D2 receptors in the nigrostriatal pathway) elicit fewer extrapyramidal signs and symptoms. A knowledge of central and peripheral D2 receptor pharmacology can help the clinician to choose between the antidopaminergic prokinetics to obtain a more favourable risk/benefit ratio.
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PMID:Review article: clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics. 1487 Dec 77

In veterinary patients, postgastric feeding is indicated for uncontrollable gastric vomiting, gastroparesis, biliary tract disease, pancreatitis, and for patients at increased risk for aspirating secondary to decreased mentation, prolonged recumbency, or an unprotected airway. Postgastric feeding may be implemented via the placement of a jejunal feeding tube. These tubes can be placed surgically (jejunostomy tubes) or with fluoroscopic or endoscopic guidance. This article will focus on methods of jejunal feeding-tube placement, advantages and disadvantages of the methods described, and complications associated with jejunal feeding.
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PMID:Placement of jejunal feeding tubes for post-gastric feeding. 1502 95


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