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J W Freston

Publications and source records attributed to J W Freston.

At least 19 recordsLinked to original sources
PubMed2001

Attributable risk of H. pylori in peptic ulcer disease: does declining prevalence of infection in general population explain increasing frequency of non-H. pylori ulcers?

Recent reports in the United States have found that fewer peptic ulcers are due to Helicobacter pylori than previously believed. The aim of this study is to determine if the declining prevalence of H. pylori infection in the general population can account for the apparent increase in the frequency of non-H. pylori ulcers. A total of 396 patients with peptic ulcer or ulcer scar were enrolled in this study. The pre-1950 population consisted of 149 patients with gastric ulcers and with 44 duodenal ulcers. The post-1950 population consisted of 96 patients with gastric ulcers and 107 with duodenal ulcers. The frequency of H. pylori-negative gastric ulcers was 5.4% in patients born before 1950 and 4.2% in patients born after 1950, and the frequency of H. pylori-negative duodenal ulcers was 0% and 1.9%, respectively. There are no statistical differences between the two populations in gastric and duodenal ulcers. H. pylori seropositivity was 74.9% in asymptomatic volunteers born before 1950 and 20.7% in those born after 1950 (P < 0.01) in the general population. The attributable risk of H. pylori infection in peptic ulcer diseases was not affected by the prevalence of H. pylori infection in the general population in Japan. This suggests that the apparent increase in frequency of non-H. pylori ulcers in the United States is not simply due to the declining prevalence of infection. Other explanations for non-H. pylori ulcers should be sought.

Adult↗
PubMed2000

Management of peptic ulcers: emerging issues.

Most peptic ulcers are caused by Helicobacter pylori infection. The infection is best diagnosed by a radiolabeled carbon urea breath test, which also can prove that eradication therapy was successful. Serologic testing is useful for establishing prior or present infection but not to determine if the infection has been eradicated. Endoscopic tests usually are not needed to establish a diagnosis. Modern ulcer treatment consists of H. pylori eradication in infected patients. A combination of a proton pump inhibitor plus clarithromycin and amoxicillin or a proton pump inhibitor plus bismuth, metronidazole, and tetracycline are the most effective regimens. Reinfection is less than 2% per year in developed countries. Evidence suggests that H. pylori eradication may foster the development of erosive esophagitis, but confirmatory studies are needed. Studies also suggest an interaction between H. pylori infection and peptic ulcers related to the use of nonsteroidal antiinflammatory drugs (NSAIDs). However, the studies are conflicting: One shows that H. pylori eradication protects against NSAID-related ulcers; another suggests protection afforded by the infection. Non-H. pylori peptic ulcers remain a challenge, especially in the United States, where one study showed that 42% of peptic ulcers were not due to the infection. Some non-H. pylori ulcers are refractory to usual doses of antisecretory drugs.

Anti-Bacterial Agents↗
PubMed2000

Helicobacter pylori-negative peptic ulcers: frequency and implications for management.

Most patients with peptic ulcers are infected with Helicobacter pylori, but the infection may not be responsible for the ulcer. It is increasingly recognized that different causes of ulcers coexist in a given patient, confounding determination of the exact cause of the ulcer. For example, in infected patients with ulcers who also are using nonsteroidal anti-inflammatory drugs (NSAIDs), it is not possible to establish the ulcer's cause. Moreover, recent studies in the United States in infected patients with duodenal ulcers who were treated with various regimens to prove their efficacy in eradicating H. pylori and preventing ulcer recurrence found that approximately 20% of patients suffered an ulcer recurrence despite successful H. pylori eradication. The infection clearly did not cause their ulcers but was originally thought to have done so. Thus, as many as one-fifth of patients with ulcers may have the cause falsely attributed to H. pylori infection. When this number is added to that of ulcer patients who are H. pylori-negative upon original presentation--at least 20% in other recent U.S. studies--it is evident that the proportion of non-H. pylori ulcer patients is larger than originally believed. This proportion is likely to increase with the declining incidence of H. pylori infection. Other causes of ulcers include the use of aspirin and NSAIDs (which may be surreptitious), hypersecretory states, Crohn's disease, and patients with "idiopathic" ulcers. Patients with "idiopathic" ulcers are characterized by postprandial hypersecretion of acid and hypergastrinemia with accelerated gastric emptying. H. pylori ulcers may be difficult to manage because antisecretory drugs are less effective in inhibiting gastric acidity in the absence of H. pylori infection.

Anti-Ulcer Agents↗
PubMed1999

Rationalizing cyclooxygenase (COX) inhibition for maximal efficacy and minimal adverse events.

New information indicates that cyclooxygenase-2 (COX-2) is constitutively expressed in several tissues, including brain, lung, pancreas, kidney, and ovary, and plays an important role in renal and gastrointestinal function. Selective COX-2 inhibition has been associated in animal studies with impairment of ulcer healing and renal function and inhibition of prostacyclin, an effect that inhibits vasodilation without inhibiting platelet aggregation. The clinical consequences, if any, of these effects remain to be determined in long-term studies in humans. The premise that selective COX-2 inhibitors will cause less gastrointestinal toxicity than nonsteroidal antiinflammatory drugs that inhibit both COX isoforms needs to take into account the low toxicity of nabumetone. The gastrointestinal safety profile of this nonacidic, dual COX inhibitor that does not undergo enterohepatic circulation has been evaluated in extensive clinical trials. The data submitted to the US Food and Drug Administration in the New Drug Application for nabumetone (Relafen), the comparative trials subsequently completed, the published databases of the comparative gastrointestinal toxicity of various nonsteroidal anti-inflammatory drugs (NSAIDs), and the meta-analysis published in this issue of The American Journal of Medicine (Schoenfeld, page 48S) indicate that nabumetone has the lowest incidence of gastrointestinal toxicity among the extensively studied NSAIDs. Overall, the incidence is approximately 10-fold less than with comparator drugs. This rate is an appropriate current reference against which the gastrointestinal toxicity of COX-2 inhibitors can be compared.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1999

Safety profile of Lansoprazole: the US clinical trial experience.

OBJECTIVE: Lansoprazole has undergone extensive clinical evaluation for the treatment of acid-peptic diseases. The aim of this study was to define the safety profile of lansoprazole and compare it to that of other therapeutic agents evaluated in the same controlled trials. METHODS: The clinical safety profile of lansoprazole and comparative agents (placebo, ranitidine and omeprazole) was reviewed for 3281 patients who participated in short term (up to 8 weeks) and long term (up to 56 months) clinical trials conducted in the US. Adverse events, laboratory value changes and gastric biopsy changes that occurred during treatment were compared statistically for differences between treatments. RESULTS: The incidence of adverse events and number of patients discontinuing treatment because of adverse events was similar for lansoprazole and comparative agents. Other than elevated serum gastrin levels, a known effect of proton pump inhibitors, no trends in laboratory changes were observed. Median values for gastrin levels remained within the normal range; about 2% of patients had gastrin levels >400 pg/ml at any time, while <1% had 2 or more gastrin values >500 pg/ml. Values returned to baseline levels after therapy was discontinued. No significant changes in gastric endocrine cell growth from baseline to final visit were observed, nor was there evidence of dysplasia or neoplasia. CONCLUSION: Lansoprazole is well tolerated for both short and long term treatment of acid-related disease. The tolerability of lansoprazole is comparable to that of ranitidine, omeprazole and placebo in the treatment of these diseases.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1997

Pharmacoeconomic comparison of treatments for the eradication of Helicobacter pylori.

BACKGROUND: Patients with Helicobacter pylori-induced duodenal ulcer should have their infection eradicated. The optimal choice of antibiotic therapy, however, is less clear. OBJECTIVE: To evaluate costs and outcomes of treatment with 8 antibiotic regimens with documented activity against H pylori vs maintenance therapy with histamine2-receptor antagonists (H2RA). METHODS: A meta-analysis for 119 studies enrolling 6416 patients to determine aggregate eradication rates. The complexity of each regimen was used to determine the anticipated compliance rate and actual effectiveness. A decision analytic model with Monte Carlo simulation determined annual costs and health outcomes. RESULTS: Average annual total costs of testing for H pylori infection and antibiotic treatment ranged from $223 to $410 and prevented ulcer recurrence in 70% to 86% of patients. The H2RA maintenance therapy cost $425 and prevented recurrence in 72% of patients. The lowest costs and recurrence rates were achieved by 3 regimens: standard triple therapy (a combination of bismuth subsalicylate, metronidazole, and tetracycline hydrochloride) for 14 days ($223, with 18% recurrence); a combination of clarithromycin, metronidazole, and a proton pump inhibitor for 7 days ($235, with 15% recurrence); and standard triple therapy with a proton pump inhibitor for 7 days ($236, with 14% recurrence). CONCLUSION: Treatment with any regimen resulted in lower costs compared with H2RA maintenance therapy. Three antibiotic regimens had consistently lower costs and better outcomes: standard triple therapy for 14 days, metronidazole, clarithromycin, and a proton pump inhibitor for 7 days, and standard triple therapy plus a proton pump inhibitor for 7 days.

Anti-Bacterial Agents↗
PubMed1997

Review and analysis of the effects of olestra, a dietary fat substitute, on gastrointestinal function and symptoms.

Olestra, a dietary fat substitute, was recently made available to consumers in savory snacks in three cities. Early reports of gastrointestinal complaints attributed to olestra attracted media coverage and fostered confusion among physicians and consumers about the nature of olestra and its effects on the digestive system. We reviewed all published studies of olestra's gastrointestinal effects and all relevant unpublished studies submitted to the Food and Drug Administration. Each study was analyzed by a group of expert gastroenterologists and epidemiologists. The symptoms reported with olestra ingestion are similar to those reported with ingestion of fiber and sorbitol, although the mechanisms involved in changing stool characteristics differ among these food additives. Olestra's effects on stool habit and characteristics are due to its presence in the stool. Large amounts are more likely to induce gastrointestinal symptoms than small amounts. There is no evidence that olestra induces pathological change in bowel function: there is no increased fluid or electrolyte nor is there altered gastrointestinal motility or microflora. Olestra and triglyceride ingestion resulted in a similar frequency of symptoms in normal adults and children and in people with chronic inflammatory bowel disease in remission. Olestra traverses the digestive tract intact to become a stool additive. Some subjects develop a change in bowel habit and stool characteristics due to the presence of more olestra in the stool. These changes resemble those associated with ingestion of sorbitol and fiber.

Controlled Clinical Trials as Topic↗
PubMed1997

What remaining questions regarding Helicobacter pylori and associated diseases should be addressed by future research? View from North America.

Several areas regarding Helicobacter pylori that need improvement or clarification in the United States include treatment of dyspepsia, physician education on disease associations with H. pylori, and evidence from U.S. studies that 7-day H. pylori eradication regimens are more effective than current regimens. Dyspepsia, a ubiquitous condition in the United States, is routinely managed on the basis of a positive H. pylori serology without other investigations. This approach has been fostered by cost-effectiveness studies of various approaches to duodenal ulcer and dyspeptic patients. Serology-directed therapy was the most cost-effective option vs. endoscopy-directed management. The option of not obtaining endoscopy had broad appeal to primary care physicians. In addition, a recent survey suggests that even gastroenterologists routinely attempt H. pylori eradication in infected patients with nonulcer dyspepsia, despite a number of negative efficacy studies. Finally, the option of not eradicating a World Health Organization-defined carcinogen in the litigious United States is unappealing to clinicians. Eradication of H. pylori in patients with dyspepsia despite more negative trials is likely to continue. There is evidence that U.S. physician awareness of the H. pylori-disease associations and the best therapies are improving rapidly, but further improvement is needed. Discrepancy of awareness of H. pylori between gastroenterologists and family physicians exists. In a recent survey, 94% and 72% of gastroenterologists regarded H. pylori as a causative agent in duodenal and gastric ulcer, respectively, vs. 68% and 68% of family physicians, and only 9% of family physicians believed there was a definite relationship between H. pylori infection and gastric cancer vs. 21% of gastroenterologists. One hundred three different H. pylori regimens were being used; 31% of family physicians and 11% of gastroenterologists used ineffective regimens or regimens of unknown effectiveness. Although 1-week proton pump inhibitor triple therapy is promising, there is skepticism that U.S. studies will yield the optimistic results that have characterized the European studies. Unlike in Europe, the U.S. standard is to use double diagnostics to prove eradication rather than just the urea breath test and to use intent-to-treat rather than assessable patient analyses. Both approaches reduce apparent eradication rates.

Dyspepsia↗
PubMed1997

Long-term acid control and proton pump inhibitors: interactions and safety issues in perspective.

Concerns have been raised regarding the safety of proton pump inhibitors in the long-term management of acid-related peptic disease, especially with regard to the physiological effects of prolonged hypochlorhydria. Of special consideration is the potential for development of enterochromaffin-like cell hyperplasia and gastric carcinoids, colorectal adenocarcinoma and polyps, and bacterial overgrowth as a result of achlorhydria. However, the magnitude of hypergastrinemia associated with the administration of proton pump inhibitors is comparable to that observed after vagotomy and is 3- to 6-fold lower than that observed with pernicious anemia. Only minimal morphological changes in gastric endocrine cells have been observed after the long-term daily administration of proton pump inhibitors, and these changes appear to be self-limiting, nondysplastic, and nonneoplastic. All current evidence suggests that the hypergastrinemia observed during proton pump inhibitor therapy has little clinical significance. However, longer-term results are necessary so that one can appreciate the full implications of acid suppression by proton pump inhibitors.

Antacids↗
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↗