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Biomedical subjects

J W Freston

Publications and source records attributed to J W Freston.

At least 19 recordsLinked to original sources
PubMed1995

The rationale for continuous maintenance treatment of reflux esophagitis.

Reflux esophagitis is a chronic process associated with frequent episodes of relapse in many patients. In addition, the disease may be progressive in at least some patients. Erosion of the esophageal mucosa precedes the development of some of the complications of the condition. There is accumulating evidence that continuous treatment of patients with erosive esophagitis effectively maintains symptomatic remission and absence of esophageal erosions. Whether such treatment will prevent the development of complications has not yet been demonstrated. We investigated a number of questions concerning the natural history and complications of erosive esophagitis and the need for maintenance treatment for patients with severe manifestations of disease as well as the impact of continuous maintenance treatment on the natural history of reflux esophagitis and its complications.

Chronic Disease↗
PubMed1995

Effects of hypochlorhydria and hypergastrinemia on structure and function of gastrointestinal cells. A review and analysis.

Since hypochlorhydria can induce hypergastrinemia, and gastrin has a trophic effect on some gastrointestinal cells, states that cause elevated plasma gastrin levels are of interest in terms of effects on cell growth and function. This article reviews the relationship between gastric mucosal cells during periods of acid stimulation and inhibition and analyses the effects of hypochlorhydria and hypergastrinemia on gastric and colonic cells and tumors. Hypochlorhydria releases the inhibitory effect of antral gastrin cells, inducing them to release gastrin in the presence of peptides or amino acids in the gastric lumen or in response to antral distension. Gastrin stimulates the oxyntic mucosa, which may lead to hyperplasia of enterochromaffin-like cells, resulting in enterochromaffin-like carcinoid tumors in aged rats and, rarely, in patients with chronic atrophic gastritis or gastrinomas. In addition to hypergastrinemia, other factors appear to be required for the progression of enterochromaffin-like hyperplasia to carcinoids; genetic factors may be involved. Gastrin elevations due to antisecretory drug therapy are indirectly proportional to the degree of acid inhibition and are reversible upon cessation of therapy. The gastrin levels during omeprazole therapy are similar to those caused by gastric vagotomy. Available evidence does not support a relationship between hypergastrinemia and the occurrence or growth of gastric carcinoma or colonic tumors.

Achlorhydria↗
PubMed1995

Critical issues in the management of gastroesophageal reflux disease.

AIM: To discuss some of the critical issues in the management of gastroesophageal reflux disease (GERD). OPINION: GERD is a chronic relapsing disease characterized by pathological exposure of the distal esophagus to gastric acid. Diagnosis of the condition can often be made on the basis of symptomatology alone. Endoscopy can help in assessing the degree of esophageal damage, influencing the choice of therapy, and should be performed at least once during a symptomatic patient's lifetime to exclude a diagnosis of Barrett's esophagus. However, endoscopy is mandatory at diagnosis if alarm symptoms are present. Treatment should aim to provide the lowest degree of acid suppression needed for the control of symptoms. Proton pump inhibitors (PPIs) represent the most cost-effective treatment option for the short- and long-term management of GERD. Compared with standard- and high-dose H2-receptor antagonists, PPIs result in superior and faster healing and symptom relief across all grades of esophagitis and are more effective at maintaining patients in symptomatic and endoscopic remission. Treatment with PPIs has also been shown to reduce the rate of recurrent stricture after initial dilatation. PPIs are generally well tolerated, and to date there have been no reports of gastric dysplasia resulting from their long-term use. Anti-reflux surgery should be reserved for patients who are unresponsive to continuous PPI therapy or perhaps for young patients. It will be several years before the impact of laparoscopic fundoplication as a cost-beneficial therapy for GERD can be assessed. CONCLUSION: The superior clinical efficacy of PPIs when compared with any other drug regimen for GERD make them the treatment of choice for the short- and long-term management of this troublesome condition.

Anti-Ulcer Agents↗
PubMed1994

Emerging strategies for managing peptic ulcer disease.

The relationship between the inhibition of intragastric acidity and healing has been determined for both duodenal and gastric ulcers, with a stronger correlation being evident in duodenal ulcer. Omeprazole is clearly more effective than H2-receptor antagonists in healing duodenal ulcers and in the resolution of attendant symptoms. As the recommended treatment periods are shorter with omeprazole (e.g. 2-4 weeks) than with H2-receptor antagonists (4-8 weeks), omeprazole has also been shown to be more cost-effective. Long-term management strategies for peptic ulcer are evolving rapidly in the light of evidence that Helicobacter pylori eradication reduces or eliminates ulcer relapse. Regimens, such as omeprazole in combination with amoxycillin or clarithromycin, that both eradicate H. pylori and heal ulcers rapidly are appealing because they are simple, well tolerated, convenient and efficient in both healing ulcers and preventing relapse. This comprehensive approach appears to be evolving as the dominant strategy for the future treatment of peptic ulcer diseases. Gastric ulcer disease is also treated more effectively with omeprazole than with H2-receptor antagonists, both in terms of speed and reliability of healing, and in terms of symptom resolution. At 4 weeks, symptom resolution has been specifically examined in six comparative trials; in three of these, omeprazole was superior to the H2-receptor antagonist, and in the other three was at least as good as the H2-receptor antagonist. Omeprazole, 40 mg once daily, effectively heals non-steroidal anti-inflammatory drug (NSAID)-induced ulcers in about 90% of cases, even if NSAID therapy is continued, and is probably the treatment of choice for patients with ulcers requiring continued NSAID therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Amoxicillin↗
PubMed1993

Future prospects for proton pump inhibitors.

Future prospects for proton pump inhibitors depend on their efficacy and safety relative to H2-receptor antagonists, the therapeutic standard for acid peptic disorders. As safety concerns diminish, efficacy considerations become more important as these may pertain to cost effectiveness. Comparative, controlled trials show that omeprazole and lansoprazole are somewhat more effective than H2-blockers in healing duodenal and gastric ulcers, providing faster relief of symptoms. Relapse after cessation of therapy is similar between the two classes. The proton pump inhibitors are substantially more effective in healing lesions and relieving symptoms in patients with reflux oesophagitis, and are particularly effective in cases that have failed to heal after 12 weeks of treatment with H2-blockers. Relapse rates of oesophagitis are significantly less with prolonged treatment with omeprazole than ranitidine. A proton pump inhibitor combined with amoxicillin is less effective than triple therapy with antibiotics and bismuth in eradicating Helicobacter pylori infections, but is more convenient and associated with fewer side-effects. Efficacy might be improved by more optimal dosing regimens. Prospects for reversible proton pump inhibitors depend on the balance between their theoretical advantages and their acid inhibition profile which, at present, closely resembles that of H2-blockers.

Anti-Ulcer Agents↗
PubMed1992

Clinical significance of hypergastrinaemia: relevance to gastrin monitoring during omeprazole therapy.

During the early experience with omeprazole, it was recommended that plasma gastrin levels be monitored to identify patients with 4-5-fold increases above baseline. Such patients were thought to be at an increased risk of developing gastric carcinoid tumours. Studies have established that plasma gastrin levels usually rise 2-4-fold during omeprazole therapy, there being considerable inter- and intra-individual variation. Approximately 3.3% of patients have plasma gastrin levels above 400 pg/ml when treated continuously for 1 year. In clinical practice, it is not cost-effective to screen all patients to detect such a small percentage, particularly given the paucity of realistic treatment options in such patients, and the growing evidence that hypergastrinaemia during omeprazole treatment is of little, if any, clinical significance.

Colonic Neoplasms↗
PubMed1990

Overview of medical therapy of peptic ulcer disease.

Medical management of peptic ulcer disease continues to evolve with the recent introduction of new H2-receptor antagonists, prostaglandin analogs, and a proton pump inhibitor, and clarification of the relationship between suppression of gastric acidity and ulcer healing. Nizatidine and roxatidine acetate, the new H2 blockers, are safe and effective but do not appear to have new properties of clinical importance. The modes of action of omeprazole and the prostaglandins have been clarified. Omeprazole is a prodrug that is protonated and secured in the secretary canaliculus of the parietal cell where the active derivative covalently binds sulfhydryl groups of H+/K(+)-ATPase, thereby irreversibly and profoundly blocking acid secretion. Prostaglandins bind a receptor on the basolateral membrane of the parietal cell, releasing a protein that inhibits cyclic AMP, the second messenger of histamine-stimulated acid secretion. The ulcer-healing properties of prostaglandins can be attributed largely if not entirely to their inhibition of acid secretion. Antacids, on the other hand, may heal ulcers by effects other than acid neutralization, as the low-dose regimens that heal ulcers only weakly neutralize acid. The way in which sucralfate and colloidal bismuth heal ulcers remains unclear; they may do so through multiple effects including, in the case of bismuth, eradication of C. pylori. H2-receptor antagonists continue as first-line treatment for acute DU and GU and the prevention of recurrence. The antacid and sucralfate regimens are less convenient but safe and effective. Misoprostol has a disadvantageous safety profile relative to available agents but is effective in preventing NSAID-induced gastric ulcers. The efficacy of omeprazole in acid-peptic disease is established but the way in which it should be used is still unclear because of long-term safety concerns.

Anti-Ulcer Agents↗
PubMed1990

Peptic ulcers in the elderly: unique features and management.

Contrary to the general trend, peptic ulcers are on the rise in the elderly in terms of frequency, complications, and mortality, possibly due to the use of and complications from nonsteroidal anti-inflammatory drugs (NSAIDs). Unfortunately, the infrequency of abdominal pain and the frequent presence of serious concomitant diseases complicate both the diagnosis and management of peptic ulcers in the elderly. Ulcers heal equally when treated with H2-receptor antagonists, antacids, or sucralfate. Patients with a history of silent, complicated ulcers and patients with serious concomitant diseases require low-dose maintenance H2-blockers to prevent ulcer recurrence. The frequency of NSAID-related ulcers may be reduced in selected patients with misoprostol in the case of gastric ulcers, or misoprostol or H2-blockers in the case of duodenal ulcers. NSAID-related ulcers heal when treated with H2-blockers.

Age Factors↗
PubMed1989

Mechanisms of relapse in peptic ulcer disease.

Although modern medicine therapy reliably heals peptic ulcers, relapse is the rule and remains a major challenge to investigators and practitioners alike. Several factors associated with ulcer recurrence have been identified but pathogenetic mechanisms are obscure. Some recent studies suggest that the type of treatment used to heal the initial ulcer influences the propensity to recurrence. Although there is circumstantial evidence that relapse may be accelerated after initial treatment with H2-receptor antagonists, overall it appears that differences in recurrence rates are more likely due to the influence of colloidal bismuth subcitrate in reducing recurrence rates. Several mucosal abnormalities have been identified in patients with peptic ulcer disease in remission. These include defective gastric mucus, reduced duodenal bicarbonate secretion and altered synthesis of certain prostaglandins, particularly of the E series. Decreased salivary secretion of epidermal growth factor and gastric Campylobacter pylori infections have also received much attention recently. It is postulated that the cause of recurrent ulceration, like that of initial ulceration, is multifactorial, and that local factors caused by the initial ulcer may contribute to the propensity of recurrence.

Bicarbonates↗
PubMed1988

The pathophysiological and pharmacological basis of peptic ulcer therapy.

Both genetic and nongenetic factors predispose to ulcer diathesis. At the mucosal level ulcers result from an imbalance between aggressive factors and mucosal defense. Ulcer therapy reduces aggressive forces, bolsters defense, or both. Gastric acid, the major aggressive factor, may have its secretion inhibited or it may be partially neutralized by antacids. H2 receptor antagonists competitively block histamine occupancy of H2 receptors on parietal cells, thereby preventing stimulation of adenylate cyclase, cAMP rises, and activation of protein kinase and H+/K+ATPase. Prostaglandins inhibit acid secretion largely by preventing histamine-induced cAMP rises. Proton pump inhibitors bind H+/K+ATPase. Antimuscarinics inhibit acetylcholine receptors on the parietal cell, thereby blocking Ca2+ entry and subsequent activation of protein kinase and the proton pump. Mucosal defense is enhanced by certain prostaglandins, colloidal bismuth subcitrate and sucralfate. Prostaglandins stimulate secretion of bicarbonate and mucus, among other effects. Colloidal bismuth and sucralfate bind to proteins in the ulcer base and stimulate bicarbonate and mucus secretion, partially, in the case of sucralfate, by increasing endogenous prostanoid synthesis. Sucralfate also binds pepsin and bile acids. Colloidal bismuth temporarily eradicates mucosal colonization by Campylobacter pylori, another putative agent in ulcer diathesis.

Antacids↗
PubMed1987

Safety perspectives on parenteral H2-receptor antagonists.

Much controversy has been associated with the similarities and differences among the histamine (H2)-receptor antagonists with respect to safety. The safety issues, including those recently identified with the use of parenteral H2-receptor antagonists, are analyzed here with the intent of placing these data into proper perspective. The focus of the analysis is on a few of the more important issues: central nervous system effects and clinically significant drug interactions. A review of the voluminous safety literature on these agents indicates that, as a class, they have enviable safety records. When individual agents are compared, some small differences in safety profiles emerge, but, on the whole, similarities are more striking.

Drug Interactions↗