Esophageal manometry and 24-hour pH testing in the management of gastroesophageal reflux patients.

BACKGROUND: With rising interest in gastroesophageal reflux disease, an evaluation of the importance of manometry (M) and 24-hour pH testing (pH) for decisions regarding these patients is appropriate. METHODS: Two gastroenterologists and two surgeons were presented with history and physical examination, endoscopy, histology, and esophagram data ("DATA") from 100 patients and asked to make a treatment decision. After some time, either pH or M was added to DATA, and a further decision requested. Finally, DATA plus pH plus M was presented, and a decision was requested. Decisions were evaluated for changes in medical therapy, changes between medical and surgical therapy, and changes in type of surgery offered. RESULTS: Overall, 43% (173 of 400) of decisions were altered by the addition of both M and pH to DATA, with 28.5% (114 of 400) of decisions changed from medical therapy to surgery or vice versa by the addition of both tests to DATA. The addition of M alone changed decisions more often than pH alone especially with regard to the type of surgery offered (P <0.05). CONCLUSIONS: Together, M and pH alter clinical decisions and often alter the decision regarding surgery. Both tests appear important, but M more frequently alters overall management decisions and the type of surgery offered. Despite the need for cost containment, these clinical tools are essential to important decisions regarding the care of patients with gastroesophageal reflux disease.

Interrelationship between cellular calcium homeostasis and free radical generation in myocardial reperfusion injury.

This review describes the interrelationship between two important biological factors, intracellular calcium overloading and oxygen-derived free radicals, which play a crucial role in the pathogenesis of myocardial ischemic reperfusion injury. Free radicals are generated during the reperfusion of ischemic myocardium, and polyunsaturated fatty acids in the membrane phospholipids are the likely targets of the free radical attack. On the other hand, activation of phospholipases can provoke the breakdown of membrane phospholipids which results in the activation of arachidonate cascade leading to the generation of prostaglandins, and oxygen free radicals can be produced during the interconversion of the prostaglandins. In conclusion, it has been emphasized that the two seemingly different causative factors of reperfusion injury, intracellular calcium overloading and free radical generation are, in fact, highly interrelated.

Reflux esophagitis in humans is a free radical event.

UNLABELLED: In this study, we investigated the implication of oxygen-derived free radicals in reflux esophagitis of humans. For this purpose we assessed oxidative stress in distal esophageal biopsies of controls, patients with various grades of esophagitis, Barrett's esophagus with and without severe associated esophagitis and patients following Nissen fundoplication. The total amount of oxygen-derived free radicals was measured by chemiluminescence. Membrane damage caused by free radicals was assessed by analysis of lipid peroxidation. In addition, we measured esophageal mucosal tissue levels of the free radical scavenger superoxide dismutase. RESULTS: Chemiluminescence and lipid peroxidation increased with the grade of esophagitis and were highest in patients with Barrett's esophagus. Findings following Nissen fundoplication were similar to controls. Superoxide dismutase decreased as the grade of esophagitis increased being lowest in Barrett's patients with severe associated esophagitis. High superoxide dismutase levels were found in Barrett's mucosa with mild associated esophagitis. CONCLUSIONS: Reflux esophagitis is mediated by free radicals. Barrett's is a severe form of oxidative damage. Antireflux surgery prevents oxidative damage of the esophageal mucosa. Superoxide dismutase is consumed by esophageal damage. In some patients with Barrett's, high superoxide dismutase levels of the esophageal mucosa may prevent severe esophagitis.

The hypertensive lower esophageal sphincter.

BACKGROUND: This study defines the entity of the hypertensive lower esophageal sphincter (HLES) and its treatment, including surgical implications. METHODS: Esophageal manometry was performed on 1,300 patients. Of these, 53 (4%) had HLES with resting pressure > 26.5 mm Hg, defined as the upper limit of normal resting LES pressure. Thirty-two of these patients had 24-hour esophageal pH studies. The response to treatment was assessed. RESULTS: Fourteen patients (26%) with HLES had achalasia. Of the remaining 39 (74%), 25 had an isolated HLES with normal esophageal body motility, 5 had a nonspecific esophageal motility disorders (NEMD), 4 were post-Nissen fundoplication, 3 had a nutcracker esophagus, and 2 had diffuse esophageal spasm (DES). Nineteen percent of HLES patients had gastroesophageal reflux on pH studies. Eighty-two percent of HLES patients responded well to symptom-directed medical therapy. Two patients with esophageal body dysmotility responded well to an esophageal myotomy with a partial fundoplication. CONCLUSIONS: Patients with the HLES form a heterogeneous group. Gastroesophageal reflux in HLES patients is not uncommon. Patients with HLES respond well to medical therapy. Carefully selected patients require surgery.

Reflux esophagitis in humans is mediated by oxygen-derived free radicals.

BACKGROUND: Oxidative stress in reflux esophagitis was investigated before and after antireflux surgery. PATIENTS AND METHODS: Oxidative stress was studied in the distal and proximal esophagus of control patients (without esophagitis, but with other gastrointestinal disorders), of patients with various grades of esophagitis (including Barrett's esophagus), and in patients who had a Nissen fundoplication. Oxidative stress was assessed by chemiluminescence, lipid peroxidation (LP), and by measuring superoxide dismutase (SOD). RESULTS: Chemiluminescence and LP increased with the degree of esophagitis and was highest in patients with Barrett's esophagus; SOD decreased with damage, except in cases of Barrett's esophagus associated with mild esophagitis. Chemiluminescence and LP in reflux patients were higher in the distal than in the proximal esophagus, and SOD was lower, whereas no such difference was found in controls. Findings after Nissen fundoplication were similar to those of controls. CONCLUSIONS: Reflux esophagitis is mediated by free radicals depleting SOD. Barrett's esophagus is a severe form of oxidative damage; in some patients, high SOD levels may prevent severe esophagitis. Antireflux surgery prevents oxidative damage.

Free radical scavengers prevent reflux esophagitis in rats.

Free radical damage in reflux esophagitis of rats induced by 24-hr duodenojejunal ligation was studied. Oxygen free radicals were selectively blocked. Groups were: sham operation, reflux, reflux + superoxide dismutase (SOD), catalase, dimethylthiourea, allopurinol, and inactivated SOD or inactivated catalase alone or in the combination SOD + catalase or SOD + catalase + dimethylthiourea + allopurinol. Macroscopic esophagitis was inhibited only by SOD, alone or in combination with other agents. Esophageal mucosal lipid peroxidation was 10-fold increased in the reflux group compared to the sham group (P < 0.05). This response was damped by SOD > catalase (P < 0.05) but not by the inactivated enzymes, dimethylthiourea or allopurinol. SOD + catalase showed no significant improvement on SOD alone. Total inhibition of lipid peroxidation was achieved by combining all scavengers. Total glutathione (GSH) in the esophageal mucosa was stimulated by reflux. This response was inhibited by scavengers equivalent to their efficacy in preventing lipid peroxidation. It is concluded that reflux esophagitis is associated with free radical release with O2- being the main source. Free radicals appear to stimulate GSH production in this prolonged oxidative stress.

Free radical production in nicotine treated pancreatic tissue.

The ability of nicotine to induce oxidative stress in the pancreatic tissue of rats was investigated. Homogenized pancreatic tissue of Sprague-Dawley rats was incubated with nicotine in a dose of 200 ng/mg protein/ml for 15, 30, 45, and 60 min or was incubated for 30 min with nicotine in a dose of 50, 100, 200, 400, and 800 ng/mg protein/ml. Pancreatic tissue was also incubated with 200 ng/mg protein/ml nicotine with or without the scavengers superoxide dismutase (SOD), catalase, SOD+catalase, inactivated SOD, inactivated catalase, or albumin. Incubation with 0.9% NaCl served as control. There was a positive correlation between the duration of nicotine incubation and chemiluminescence (r = 0.6) or lipid peroxidation (r = 0.71) and also between the nicotine dose and chemiluminescence (r = 0.54) or lipid peroxidation (r = 0.66). Thirty minutes incubation of pancreatic tissue with nicotine in a dose of 200 ng/mg protein/ml increased chemiluminescence 5 fold and lipid peroxidation 2.5 fold. This response was dampened by SOD or catalase and abolished by SOD+catalase. Inactivated enzymes or albumin had no scavenging effect. These results demonstrate that nicotine causes oxidative stress to the pancreatic tissue of rats.

In vitro free radical production in rat esophageal mucosa induced by nicotine.

Oxidative stress induced by nicotine was investigated in the esophageal mucosa of rats. The homogenized mucosa was incubated for 30 min with 50, 100, 200, 400, and 800 ng/mg protein/ml nicotine or with 200 ng/mg protein/ml nicotine for 15, 30, 45, and 60 min. Esophageal mucosa was also incubated for 30 min with 200 ng/mg protein/ml nicotine with or without the scavengers superoxide dismutase (SOD), catalase, SOD+catalase, inactivated SOD, inactivated catalase, or albumin. Incubation with 0.9% NaCl served as control. There was a strong correlation between chemiluminescence and the nicotine dose (r = 0.75) or the nicotine incubation time (r = 0.77). Thirty-minute incubation of the esophageal mucosa with 200 ng/mg protein/ml nicotine increased chemiluminescence 5.5-fold and lipid peroxidation 3.3-fold. This response was dampened by SOD or catalase and abolished by SOD+catalase. Inactivated enzymes or albumin had no scavenging effect. These results demonstrate that nicotine causes oxidative stress to the esophageal mucosa.