Disease relevance of Heartburn

• CONTEXT: Cisapride, an oral prokinetic drug indicated for the symptomatic treatment of nocturnal heartburn due to gastroesophageal reflux disease, was approved by the US Food and Drug Administration in July 1993 [1].
• Zollinger-Ellison syndrome patients without heartburn had a higher mean sphincter pressure than did patients with heartburn (who had a mean sphincter pressure similar to that of controls but greater than that in patients with idiopathic gastroesophageal reflux) [2].
• At follow-up of these 37 patients, (31) 84% had no or only occasional mild heartburn, (33) 89% were free from erosive esophagitis, and (2) 5% were taking H2 antagonists or omeprazole [3].
• Symptoms including fatigue, exhaustion, weakness, polydipsia, polyuria, nocturia, joint pain, bone pain, constipation, depression, anorexia, nausea, heartburn, and associated conditions, including nephrolithiasis, and hematuria occurred more often in patients with primary hyperparathyroidism than in the thyroid control patients (p < 0.05) [4].
• The combination of cimetidine and sucralfate suspension was superior to cimetidine alone in improving daytime heartburn symptoms (p less than 0.05) but not nighttime heartburn, dysphagia, or regurgitation [5].

High impact information on Heartburn

• These studies suggest that LES dysfunction and gastroesophageal reflux, rather than gastric hypersection, are responsible for the heartburn caused by coffee in certain susceptible persons [6].
• Cimetidine, but not placebo, reduced acid secretion and heartburn in response to coffee, suggesting that acid was required for the development of symptoms [6].
• RESULTS: Four patients were dropped from the study (sulindac group) due to urosepsis (1 patient), heartburn (2 patients), and anemia (1 patient) [7].
• Complete relief of nighttime heartburn was noted by 79.5% of patients in the 20-mg omeprazole group, 85.1% in the 40-mg omeprazole group, and 34.9% in the placebo group (P less than or equal to 0.05) [8].
• Metoclopramide significantly suppressed the subjective signs of nausea (7 of 8 cases) and heartburn (all cases) [9].

Chemical compound and disease context of Heartburn

• Clinical effectiveness of antacids and bethanechol in therapy of heartburn is supported by controlled treatment trials [10].
• Epigastric pain and/or heartburn were significantly less frequent in patients receiving omeprazole (P =.00124) or ranitidine (P =.038) than in those receiving placebo [11].
• CONCLUSION: Lansoprazole, at a daily dose of 15 mg or 30 mg, is significantly better than placebo in reducing symptoms of persistent or recurrent upper abdominal discomfort accompanied by at least some symptoms of heartburn [12].
• Compared with baseline, significant increases in time to heartburn was found with famotidine at weeks 4 (383 (102), p < 0.01) and 5 (344 (92), p < 0.01) but not week 8 (336 (90) seconds) [13].
• A double-blind, placebo-controlled study of the effectiveness and safety of nizatidine in the prevention of postprandial heartburn [14].

Biological context of Heartburn

• However, 2 patients with normal emptying studies had symptomatic heartburn, and 2 patients with delay of both solid and liquid gastric emptying gave no history of gastroesophageal reflux [15].
• In an effort to piece together the complex puzzle, investigators from all disciplines have gathered their patients with wheezing and heartburn and studied the epidemiology, the possible cause or effect mechanisms and the therapeutic response to GER treatment [16].
• Significant adverse effects of aspirin were noted with respect to the side effects of stomach pain, heartburn and vomiting, elevation of systolic blood pressure to greater than 160 mm Hg, and elevation of serum urea nitrogen and serum uric acid levels to the abnormal range [17].

Anatomical context of Heartburn

• Future studies in patients with symptomatic GER disease (GERD) should be able to determine whether typical symptoms such as heartburn, as well as atypical symptoms such as chest pain, are related to the GER-related distention of the esophagus [18].
• The purpose of this study was to compare the safety profile and efficacy of famotidine oral dosing regimens, 40 mg nocte and 20 mg b.d. with placebo in the relief of symptoms in patients suffering from frequent heartburn found to have endoscopically normal oesophageal mucosa or mild non-erosive oesophagitis [19].
• Risedronate-treated patients with active heartburn, esophagitis, other esophageal disorders, or peptic ulcer disease at study entry did not experience worsening of their underlying conditions or an increased frequency of upper GI tract adverse events overall [20].
• Both ranitidine and omeprazole significantly reduced gastric acid output (P less than 0.001) and gastric volume output (P less than 0.001) compared to a basal evaluation and resulted in complete disappearance of pyrosis [21].
• Since diurnal and episodic release of steroid and peptide hormones occur, it is postulated that heartburn and other digestive dysfunction during pregnancy are associated with elevated steroid and peptide (beta-endorphin, NPY) hormone interaction with innate biological rhythms controlling the gastrointestinal tract [22].

Gene context of Heartburn

• Heartburn correlated positively with the mean somatostatin level [23].
• Of 68 patients with CF greater than or equal to 5 years of age, 20.6% experienced regurgitation and 26.5% had heartburn [24].
• Increased TRPV1 expression in the inflamed oesophagus may mediate the heartburn in oesophagitis, and TRPV1 blockers may provide novel treatment [25].
• METHODS: A total of 247 patients with dyspeptic symptoms (166 women, mean age 44 (SEM 1) year), with a negative upper gastrointestinal endoscopy and without dominant symptoms of heartburn participated in the study [26].
• CONCLUSION: Proton pump inhibitor treatment provides more consistent heartburn relief than an H2-receptor antagonist, or "step-up" or "step-down" therapy [27].

Analytical, diagnostic and therapeutic context of Heartburn

• Oesophageal perfusion with 10 mM HCl did not cause symptoms (nausea and heartburn), but tripled the oesophageal HCO3- output from a baseline of 51 mumol/10 cm/10 min (p = 0.021), while doubling the rate of salivary HCO3- secretion from a median basal value of 140 mumol/10 min (p = 0.021) [28].
• However, the 89 evaluable ranitidine-treated patients with normal endoscopy also experienced a marked and rapid reduction in heartburn at the end of 1 wk [29].
• OBJECTIVE: This randomized, double-blind, multicenter study was conducted to confirm a previous finding that lansoprazole relieves heartburn faster than omeprazole in patients with erosive esophagitis [30].
• This prospective, randomized, double-blind study compared omeprazole and cimetidine in the treatment of GERD-associated heartburn both in patients with symptomatic non-ulcerative oesophagitis and in those with heartburn but without oesophagitis [31].
• Physicians are reluctant to perform esophagogastroduodenoscopy (EGD) during pregnancy for pyrosis to reliably differentiate gastroesophageal reflux from peptic ulcer disease [32].

References