Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0017168 (gastroesophageal reflux disease)
 11,783 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lansoprazole, a proton pump inhibitor, inactivates the H(+)/K(+)-ATPase pump in parietal cells, thereby suppressing basal and stimulated gastric acid secretion and increasing intragastric pH. After 8-12 weeks' treatment with lansoprazole, all children (n = 27) with esophagitis at baseline were healed (confirmed by endoscopy) and 76% of 62 evaluable children experienced improvements in overall gastroesophageal reflux disease (GERD) symptoms. In this noncomparative trial, 66 children (aged 1-11 years) with GERD with or without esophagitis received oral lansoprazole 15 or 30 mg once daily dependent on their weight. The drug is generally well tolerated in children with GERD. In the largest study, the most common treatment-related adverse events occurring during therapy were constipation and headache.
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PMID:Lansoprazole: in the management of gastroesophageal reflux disease in children. 1251 6

Gastrointestinal food allergies are a spectrum of disorders that result from adverse immune responses to dietary antigens. The named disorders include immediate gastrointestinal hypersensitivity (anaphylaxis), oral allergy syndrome, allergic eosinophilic esophagitis, gastritis, and gastroenterocolitis; dietary protein enterocolitis, proctitis, and enteropathy; and celiac disease. Additional disorders sometimes attributed to food allergy include colic, gastroesophageal reflux, and constipation. The pediatrician faces several challenges in dealing with these disorders because diagnosis requires differentiating allergic disorders from many other causes of similar symptoms, and therapy requires identification of causal foods, application of therapeutic diets and/or medications, and monitoring for resolution of these disorders. This review catalogs the spectrum of gastrointestinal food allergies that affect children and provides a framework for a rational approach to diagnosis and management.
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PMID:Clinical aspects of gastrointestinal food allergy in childhood. 1277

Novartis has developed and launched tegaserod, an aminoguanidine indole 5-HT(4) receptor partial agonist, for the potential treatment of constipation-predominant irritable bowel syndrome (IBS) [286804], [311514] and other functional GI disorders, such as gastroesophageal reflux disease (GERD), chronic constipation and functional dyspepsia [342937], [362853]. It was launched in Mexico for IBS in July 2001 [416879] and in the Czech Republic, Venezuela and Colombia by October 2001. By this time, the product had also been approved in Switzerland [427419]. In September 2001, launch of the product for GERD, chronic constipation and functional dyspepsia was expected after 2003 [422828]; later in October 2001, the launch dates for the latter two indications were anticipated for 2004 [427419], [431614]. In December 2000, Merrill Lynch predicted sales of SFr 150 million in 2001, rising to SFr 612 million in 2004, larger than the September 2000 predictions of SFr 120 million in 2001 rising to SFr 378 million in 2004 [394812], [383742]. Later in February 2001, Merrill Lynch predicted sales of SFr 150 million in 2001 rising to SFr 785 million per annum in 2005, assuming a US launch during the third quarter of 2001 [411704]. Following the withdrawal of the MAA and then the rejection of tegaserod's NDA by the FDA, in June 2001, Merrill Lynch progressively revised its 2005 sales forecasts from SFr 1.1 billion to SFr 950 million and then to SFr 375 million [422783]. In June 2001, Merrill Lynch also suggested that there was a significant possibility that tegaserod would never reach the market. In August 2001, Deutsche Bank estimated sales of SFr 200 million in 2004 and SFr 550 million in 2005 [422674]. Analysts at Credit Suisse predicted in October 2001, that there was only a three in ten chance that tegaserod would ever reach a major market following the issuance of a 'non-approvable' letter by the FDA in June 2001. They predicted sales of SFr 5 million in 2001, rising to SFr 325 million in 2005 [426409].
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PMID:Tegaserod (Novartis). 1286 78

Cough is an important defensive reflex of the airway and a common symptom of respiratory disease. After an upper respiratory tract virus infection, cough is transient, but is more persistent with conditions such as asthma, rhinosinusitis, gastroesophageal reflux, chronic obstructive pulmonary disease (COPD) and lung cancer. Treatment directed at these conditions may improve cough, but there remains a need to control cough directly. The most effective antitussives are opioids, such as morphine, codeine or pholcodeine, but they produce side effects including drowsiness, nausea, constipation and physical dependence. Opioids such as k- and d-opioid receptor agonists, non-opioids such as nociceptin, neurokinin and bradykinin receptor antagonists, vanilloid receptor VR(1) antagonists, blockers of sodium-dependent channels, and maxi-K calcium-dependent channel activators of afferent nerves may all represent novel antitussives and this needs to be confirmed in clinical trials.
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PMID:Current and future prospects for drugs to suppress cough. 1291 74

To evaluate a pre-thickened formula (Enfamil AR) for regurgitant gastroesophageal reflux, 104 infants were enrolled in a 5-week, multicenter, double-blind, randomized, placebo-controlled parallel group trial. The Enfamil AR group showed greater symptom reduction by the end of the first week: percent feedings with any regurgitation (p = 0.045), total regurgitation volume score (p = 0.035), and percent feedings with choke-gag-cough (p = 0.004). The most symptomatic infants at baseline had a reduction in trouble sleeping significantly with Enfamil AR by the end of the study (p = 0.030). This formula flows through a standard nipple, reduces regurgitation and choking-gagging-coughing within a week, and improves sleep in the most symptomatic babies by 5 weeks, without causing constipation.
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PMID:Efficacy of a pre-thickened infant formula: a multicenter, double-blind, randomized, placebo-controlled parallel group trial in 104 infants with symptomatic gastroesophageal reflux. 1292 49

Information on the utility of solid-phase gastric emptying studies (SPGES) in the evaluation of children with symptoms of upper gastrointestinal (GI) motor dysfunction is limited. This study was conducted to evaluate the impact of SPGES in the clinical management and outcome of children with upper GI symptoms suggestive of gastroparesis. The records of 45 children who underwent SPGES (31F; 3-17 years) were reviewed. All patients had GI symptoms suggesting gastroparesis. Patients were fed with Tc-99m-sulfur colloid-labeled chicken liver. Adult normal half-life (T1/2) values (F 103 +/- 14 minutes; M 66 +/- 13.6 minutes) were used. The relationships among symptoms, treatment, and outcome were evaluated. Of the 45 patients 9 had delayed, 16 had rapid, and 20 had normal gastric emptying. Six of 9 patients with delayed gastric emptying responded to cisapride. Four of 16 patients with rapid emptying were diagnosed with the dumping syndrome. Of the children with rapid gastric emptying, 87% were females. Twenty patients with normal emptying were diagnosed with gastroesophageal reflux (8), nonulcer dyspepsia (5), irritable bowel syndrome (2), Helicobacter pylori (1), lactose intolerance (1), eosinophilic gastroenteritis (1), duodenitis (1), and constipation (1). In patients who had SPGES for possible gastroparesis, 20% had gastroparesis, 36% had rapid gastric emptying, and 44% had normal gastric emptying. The high number of females in the rapid gastric emptying group might be secondary to normal adult female T1/2 values that were used. The practice of using adult normal T1/2 values in prepubertal girls may need to be revised. Patients with delayed gastric emptying responded to cisapride.
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PMID:The impact of solid-phase gastric emptying studies in the management of children with dyspepsia. 1455 21

Gastro-oesophageal reflux disease (GORD) is a chronic disorder characterised by an increased exposure of the oesophagus to intragastric contents. Currently, GORD symptoms are maintained under control with antisecretory agents, mainly gastric proton pump inhibitors (PPIs). Although impaired oesophageal motility may partly underlie the pathophysiology of GORD, the use of prokinetic agents has been found to be unsatisfactory. To date, novel pharmacological approaches for GORD are mainly related to the control of transient lower oesophageal sphincter (LOS) relaxations (TLOSRs). The majority of patients with GORD have reflux episodes during TLOSRs, which are evoked by gastric distension, mainly occurring after ingestion of a meal. Patients with reflux disease with normal peristalsis and without or with mild erosive disease could potentially benefit from anti-TLOSR therapy. This therapy might also be of value to treat some severe forms of esophagitis in combination with PPIs. GABA-B-receptor agonists are the most promising class of agents identified so far for TLOSR control. The GABA-B-receptor agonist, baclofen, is the most effective compound in inhibiting TLOSRs in humans. Since baclofen has several CNS adverse effects, novel orally available GABA-B agonists are needed for effective and well tolerated treatment of GORD. Endogenous or exogenous cholecystokinin (CCK) causes a reduction in LOS pressure, an increase in TLOSR frequency and a reduction in gastric emptying. In healthy volunteers and patients with GORD, loxiglumide, a selective CCK1-receptor antagonist, was found to reduce the rate of TLOSRs, although its effect on postprandial acid reflux may be modest. Orally effective CCK antagonists are not marketed to date. The anticholinergic agent atropine, given to healthy volunteers and patients with GORD, markedly reduced the rate of TLOSRs. Because of severe gastrointestinal (and other) adverse effects of anticholinergics, including worsening of supine acid clearance and constipation, it is unlikely that this class of drugs will have a future as anti-TLOSR agents on a routine basis. In spite of their effectiveness in reducing TLOSR rate, untoward adverse effects, such as addiction and severe constipation, currently limit the use of morphine and other opioid mu-receptor agonists. The same applies to nitric oxide synthase inhibitors, which are associated with marked gastrointestinal, cardiovascular, urinary and respiratory adverse effects. Animal studies provide promising evidence for the use of cannabinoid receptor 1 agonists, by showing potent inhibition of TLOSRs in the dog, thus opening a new route for clinical investigation in humans. A better understanding of TLOSR pathophysiology is a necessary step for the further development of novel drugs effective for anti-reflux therapy.
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PMID:Progress with novel pharmacological strategies for gastro-oesophageal reflux disease. 1496 71

This study was conducted in order to analyze the clinical manifestations, the endoscopic findings, the histology of the gastrointestinal mucosa, the treatments and the clinical course in infants who had hematemesis induced by cow milk allergy. The medical records were reviewed retrospectively. The criteria for the diagnosis of CMA included elimination of cow milk formula resulting in improvement of symptoms, specific endoscopic and histologic findings as well as the exclusion of other causes. Twenty-three infants with a diagnosis of hematemesis were analyzed, which included 20 infants with CMA and 3 infants with gastroesophageal reflux disease (GERD). In the CMA group were 12 girls and 8 boys whose ages were 4.3 +/- 1.4 months. The onset of vomiting after starting cow milk formulas was 70.6 +/- 48.9 days. Gastroduodenoscopy was performed on 15 patients showing erythema, erosion and friability of the gastric mucosa in all patients and lymphoid hyperplasia in the duodenal bulb in 7 patients. Eight patients had mild to moderate eosinophilic infiltration and 5 patients had eosinophilia. Cow milk formulas were changed to other formulas: two children were initially given extensively hydrolyzed casein formulas and later followed by a soy formula, 14 were given a soy formula and 4 were given partially whey hydrolyzed formulas. All patients showed clinical signs of improvement a few days later. Patients that were able to tolerate cow milk were 1.5 +/- 0.9 years old. During the follow-up period (2.6 +/- 1.8 years after treatment) 4 patients were diagnosed with asthma, 4 patients with chronic respiratory symptoms, 4 patients with constipation and 2 others with food allergies. CMA induced gastritis in infancy may not be classified as eosinophilic gastritis because of the low level of eosinophilic infiltration. The elimination of cow milk and subsequent substitution with a soy formula is the proper management.
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PMID:Hematemesis in infants induced by cow milk allergy. 1519 38

Over a 2-year period, 34 children were referred to the division of pediatric gastroenterology at the University of Virginia with chronic upper gastrointestinal symptoms whose symptoms rapidly and completely resolved when their unrecognized constipation was treated. The average age at presentation was 8.24 (SD 0.78) years and average duration of upper intestinal symptoms was 15.6 (SD 3.5) months. Twenty-six of 34 had experienced recurrent vomiting, 6 complained of chronic nausea, 17 had chronic symptoms of gastroesophageal reflux, and 20 complained of chronic or recurrent abdominal pain, most often in the epigastric region. Smaller numbers had experienced early satiety, choking, gagging, dysphagia, or intermittent diarrhea. Given the prevalence of constipation in childhood, it seems likely that many children who experience chronic upper intestinal symptoms may be suffering from chronic unrecognized constipation as the cause of their upper intestinal symptoms.
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PMID:Recurrent vomiting and persistent gastroesophageal reflux caused by unrecognized constipation. 1520 51

Acute abdominal pain in children occurs often and requires rapid clarification. Hints as to the condition are often given by the first impression and the case history of the patient. When the clinical examination and laboratory results do not lead to a clear finding, imaging methods such as a sonography can clarify the case. The most common cause for abdominal pain in infants is acute enteritis, mostly brought about by rotaviruses. Additional diagnoses are abdominal hernia, malrotation, hypertrophic pyloric stenosis, invagination or gastroesophageal reflux. In school-age children, the classic finding is "appendicitis". This should be differentiated from constipation, gastritis, pancreatitis, sigmoid volvulus, bowel and intestinal obstruction or, perhaps, gallstone trouble.
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PMID:[Acute abdominal pain in childhood]. 1536 66


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