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Biomedical subjects

T E Bynum

Publications and source records attributed to T E Bynum.

At least 19 recordsLinked to original sources
PubMed1992

Clinical aspects of gastroduodenal ulcer recurrence: an overview.

Duodenal ulcer is a disease characterized by very high rates of recurrence: up to 80% at 1 year, 95% at 2 years. Maintenance therapy will reduce relapse rates. However, when therapy directed against gastric acid is stopped, the slope of the recurrence curve is identical whether therapy is stopped after 6 weeks, 8 weeks, 3 months, 6 months, 1 year, or 2 years. This suggests that therapy directed against acid does nothing to change the natural history of ulcer disease. Cytoprotective therapy is equally successful as H2-blockers at healing ulcer or reducing relapse rates, but the time to recurrence is significantly prolonged after either acute or maintenance cytoprotective therapy is stopped. This suggests that cytoprotective therapy has a beneficial effect that does improve the natural history of ulcer disease. The mechanism by which maintenance therapy reduces ulcer relapse could be masking symptoms (analgesic), accelerated healing, or true prevention of ulcer recurrence. By using frequent endoscopic assessment combined with complex statistical evaluation (calculating traditional ulcer prevalence, point prevalence, and maximal ulcer prevalence), we showed that sucralfate cytoprotection genuinely prevents ulcer recurrence. The incidence of asymptomatic ulcer recurrence after sucralfate is 10% but is up to 40% after H2-blocker therapy.

Histamine H2 Antagonists↗
PubMed1991

Maintenance therapy with sucralfate in duodenal ulcer: genuine prevention or accelerated healing of ulcer recurrence?

We sought to compare the efficacy of sucralfate to placebo for the prevention of duodenal ulcer recurrence and to determine that the efficacy of sucralfate was due to a true reduction in ulcer prevalence and not due to secondary effects such as analgesic activity or accelerated healing. This was a double-blind, randomized, placebo-controlled, parallel groups, multicenter clinical study with 254 patients. All patients had a past history of at least two duodenal ulcers with at least one ulcer diagnosed by endoscopic examination 3 months or less before the start of the study. Complete ulcer healing without erosions was required to enter the study. Sucralfate or placebo were dosed as a 1-g tablet twice a day for 4 months, or until ulcer recurrence. Endoscopic examinations once a month and when symptoms developed determined the presence or absence of duodenal ulcers. If a patient developed an ulcer between monthly scheduled visits, the patient was dosed with a 1-g sucralfate tablet twice a day until the next scheduled visit. Statistical analyses of the results determined the efficacy of sucralfate compared with placebo for preventing duodenal ulcer recurrence. Comparisons of therapeutic agents for preventing duodenal ulcers have usually been made by testing for statistical differences in the cumulative rates for all ulcers developed during a follow-up period, regardless of the time of detection. Statistical experts at the United States Food and Drug Administration (FDA) and on the FDA Advisory Panel expressed doubts about clinical study results based on this type of analysis. They suggested three possible mechanisms for reducing the number of observed ulcers: (a) analgesic effects, (b) accelerated healing, and (c) true ulcer prevention. Traditional ulcer analysis could miss recurring ulcers due to an analgesic effect or accelerated healing. Point-prevalence analysis could miss recurring ulcers due to accelerated healing between endoscopic examinations. Maximum ulcer analyses, a novel statistical method, eliminated analgesic effects by regularly scheduled endoscopies and accelerated healing of recurring ulcers by frequent endoscopies and an open-label phase. Maximum ulcer analysis reflects true ulcer recurrence and prevention. Sucralfate was significantly superior to placebo in reducing ulcer prevalence by all analyses. Significance (p less than 0.05) was found at months 3 and 4 for all analyses. All months were significant in the traditional analysis, months 2-4 in point-prevalence analysis, and months 3-4 in the maximal ulcer prevalence analysis. Sucralfate was shown to be effective for the prevention of duodenal ulcer recurrence by a true reduction in new ulcer development.

Double-Blind Method↗
PubMed1991

Practice patterns and costs of hospitalization for upper gastrointestinal hemorrhage.

We conducted an observational study at three hospitals in Boston to examine the patterns of practice and the costs involved in the medical management of noncirrhotic, upper gastrointestinal bleeding. A total of 111 patients were identified and studied: 42 from hospital 1, 38 from hospital 2, and 31 from hospital 3. There were no significant differences in the management of the patients, except for the more frequent use of upper gastrointestinal radiography at hospital 3 and the more frequent use of cimetidine at hospital 2. Only a small percentage (3-7%) of patients required surgery, and overall mortality (0-8%) was low. The average cost of hospitalization, determined by using the New England Medical Center cost model, was calculated for direct costs ($3,180). The majority of costs incurred were for hospital bed or intensive care unit stay (63%) and transfusion of blood products (14%), with costs for physicians' services (9%), endoscopy (2%), and upper gastrointestinal radiography (1%) accounting for only a small percentage. This study demonstrates remarkable similarity in practice patterns and resource utilization at three different hospitals and provides data on the actual costs involved in hospitalization for noncirrhotic, upper gastrointestinal hemorrhage.

Acute Disease↗
PubMed1991

Non-acid mechanisms of gastric and duodenal ulcer formation.

The pathophysiology of gastric and duodenal ulcer disease has two sides: the aggressive attack, principally by the highly corrosive gastric acid; and the defending forces of mucus, mucosal resistance, and other protective substances and functions. This report reviews the roles of both the attacking and defending forces in the pathophysiology of ulcer disease. It also discusses how an early notion of ulcer formation (e.g., the Schwarz dictum of "no acid, no ulcer," first published in 1910) became the slogan by which ulcer disease was understood and from which therapy took its cue. Subsequent work has since found that the Schwarz dictum holds for duodenal ulcer, but not for gastric ulcer. Non-acid mechanisms of ulcer formation--i.e., impairment of at least one of the defending or protective forces--are also described, as are treatment approaches to ulcer disease. Although suppression of acid secretion is a mainstay of treatment, agents that safely and effectively strengthen the defense are being used more frequently. There are signs that the safe limits for acid-suppressing therapy have been reached or passed. On the other hand, the search for therapy that strengthens the defensive factors has only begun.

Animals↗
PubMed1989

Sucralfate tablets 1 g twice a day for the prevention of duodenal ulcer recurrence.

Sucralfate 1 g twice daily was found to be significantly better than placebo for the prevention of duodenal ulcer recurrence. This was a double-blind, randomized, placebo-controlled, parallel groups study. A total of 254 patients with a history of two or more duodenal ulcers, the most recent event diagnosed within three months of study entry, were entered into the trial after healing was documented. Patients received sucralfate 1 g twice daily or placebo for four months, or until recurrence. Endoscopies and symptom assessments were scheduled monthly and at investigator discretion upon symptom development. Treatment groups were comparable with regard to number of patients, age, sex, smoking status, and ulcer history. Traditional ulcer prevalence and point prevalence analyses were performed. Traditional ulcer prevalence included all ulcers found at scheduled visits and interim recurrences. Point prevalence included only ulcers found at scheduled visits. In the traditional analysis, sucralfate was significantly better than placebo in reducing ulcer recurrence for all months of the study. The life table estimate of the cumulative percent with ulcer at four months was 42 percent for the sucralfate group and 63 percent for the placebo group (p = 0.002). At four months, there were 49 recurrences among 122 patients in the sucralfate group and 71 among 117 patients for the placebo group. In the point prevalence analysis, sucralfate was significantly better than placebo in reducing ulcer recurrence at Months 2 through 4. The life table estimate of the cumulative percent with ulcer at four months was 36 percent for the sucralfate group and 55 percent for the placebo group (p = 0.005). At four months, there were 38 recurrences among 114 patients in the sucralfate group and 54 among 104 patients for the placebo group. Both analyses demonstrated that sucralfate 1 g twice daily was significantly better than placebo for the prevention of duodenal ulcer recurrence. Symptom development was associated with recurrence in both treatment groups. Smoking was associated with a greater tendency to recur in placebo-treated patients only.

Clinical Trials as Topic↗
PubMed1989

Hemobilia in a patient with multiple hepatic artery aneurysms: a case report and review of the literature.

Hepatic artery aneurysm is a rare vascular lesion that accounts for nearly 10% of hemobilia cases. Its etiology is most often atherosclerosis, trauma, or infection. Autoaggressive disorders are rarely associated with hepatic artery aneurysm as is thyroid dysfunction. Presented here is a case of hemobilia secondary to a rupture of one of multiple aneurysms of both right and left hepatic arteries in a women with a history of rheumatoid arthritis, hypothyroidism, and hypertension. Surgical intervention has been the rule in the past. Selective transcatheter embolization has gained clinical application in recent years, especially in the treatment of intrahepatic aneurysms. Its efficacy and safety are demonstrated by this case.

Aged↗
PubMed1988

Cure of hemophilia A by orthotopic liver transplantation.

A patient with hemophilia A and transfusion-associated end-stage chronic liver disease underwent orthotopic liver transplantation. He had no requirement for exogenous factor VIII replacement during the 27 mo he survived. Although his hemophilia was cured, he had antibodies to the human immunodeficiency virus; ultimately he died of complications arising from acquired immunodeficiency syndrome. Liver transplantation for cirrhotic hemophiliacs can free them of the need for antihemophilic-factor therapy; however, application of this approach may be limited by the high prevalence of human immunodeficiency virus infection in multitransfused hemophiliacs.

Adult↗
PubMed1988

Alternatives to the acid-oriented approach to ulcer disease: does 'cytoprotection' exist in man? A new classification of antiulcer agents.

This review summarizes the historical contradictions and inconsistencies that form the labile arguments advocating neutralization or inhibition of secretion of gastric acid for the prevention or treatment of gastroduodenal ulcers. Re-evaluation of old concepts is needed in the wake of recognition that even the most potent antisecretory agents do not change the natural history of ulcer disease; that is, the recurrence is high after termination of treatment. New biochemical, functional, and structural targets are listed for pharmacologic intervention in ulcer disease. As a supplement or alternative to the antisecretory agents, we should now consider prosecretory agents (for example, for bicarbonate and mucus secretion) and antioxidants (for example, free radical scavengers). Gastroduodenal motility, smooth muscle, the vascular endothelial cell, and the basement membrane seem to represent additional pharmacologic targets toward which new gastroprotective drugs can be directed even though the biochemical mechanism of action of these new agents may not be fully understood. New results suggest that these elements have a role in the pathogenesis of ulcer disease, and their modulations seem to exert a beneficial effect without inhibiting gastric secretion in rodents. In man, the acid antisecretory and cytoprotective doses seem to overlap, but arguments are presented to shift defining gastric 'cytoprotection' by the dose of drugs to the characterization of the phenomenon (for example, events such as the ethanol-induced hemorrhagic erosions which cannot be decreased by antisecretory agents). Furthermore, non-prostaglandin and non-H2-receptor antagonist drugs are available that exert acid-independent gastroprotection both in animals and humans. The future is thus bright for the development of new antiulcer agents.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1987

Clinical interpretation of recurrence data.

High rates of recurrence of peptic ulcer disease have been demonstrated in numerous studies. Maintenance drug therapy can successfully reduce the rate of recurrence and probably should be given during the first year after healing, when complications are more likely to be serious. After the first year, serious complications such as perforation, bleeding, and death are not likely. The most appropriate candidates for maintenance therapy are patients older than age 50 and those who are at high risk for relapse (e.g., those who smoke, have a family history of ulcer disease, or a history of ulcer relapse). The currently available cytoprotective agent sucralfate may be the most appropriate agent to use for maintenance therapy because it is locally acting and low in toxicity, as well as effective.

Humans↗
PubMed1985

Diet and other risk factors for cancer of the pancreas.

The findings of a case - control study of cancer of the pancreas, which was conducted in the Baltimore metropolitan area, are reported. Two hundred one patients with pancreatic cancer were matched on age (+/- 5 years), race, and sex to hospital and non-hospital controls, the latter selected by random-digit-dialing (RDD). All subjects were interviewed regarding diet, beverage consumption, occupational and environmental exposures, and medical and surgical history. Significantly decreased risks were associated with consumption of raw fruits and vegetables and diet soda, and significantly increased risks were associated with consumption of white bread when cases were compared with hospital and RDD controls. A significantly reduced risk was associated with consumption of wine when cases were compared to RDD controls. Risk ratios for consumption of coffee were not significantly different from one, although there appeared to be a dose - response relationship in women. A moderate but statistically nonsignificant increase in relative odds was found for cigarette smoking, and cessation of smoking was associated with a marked reduction in risk. No significant associations were found with particular occupational exposures. Tonsillectomy was associated with a significantly reduced risk, a finding that has been observed for other cancers as well. The current evidence indicates that pancreatic cancer is likely to result from a complex interaction of factors and suggests that the study of its etiology requires a multidisciplinary approach involving both laboratory and epidemiologic components.

Aged↗
PubMed1979

Gastric aspiration in localization of gastrointestinal hemorrhage.

We compared the findings from gastric aspiration for blood with the site of gastrointestinal (GI) hemorrhage ultimately identified by endoscopy or angiography in 1,190 patients whose cases were analyzed retrospectively and prospectively during a six-year period. Gastric aspirates were positive for blood in 837 patients. An upper GI site proximal to Treitz' ligament was identified in 93%, and none had a lower GI site. A negative aspirate was found in 353 patients; a lower GI site was identified in 60%, and 1% (three patients) had an upper GI site. In these three patients, hemorrhage occurred in clinical settings suggesting ulcer disease, and bleeding duodenal ulcers were found in all three. All of the other 180 patients with a bleeding duodenal ulcer had a positive gastric aspirate.

Aged↗
PubMed1979

Ischemic hepatitis.

Seven patients with cardiovascular disease had clinical episodes and marked transaminase elevations that suggested viral hepatitis, but all had morphologic evidence (from liver biopsy or autopsy specimens) that documented centrilobular necrosis (ischemic hepatitis) with no evidence of viral or drug injury. Several also had moderate or marked passive congestion of the liver so the liver biopsies of 15 additional patients were retrospectively reviewed. In this latter group congestion alone was associated with normal or minimal elevation in transaminases while all patients with notable (greater than 5 times normal) transaminase elevations had centrilobular necrosis. Congestion alone, no matter how severe or prolonged, seems to do little if any damage to the liver. Centrilobular necrosis, or ischemic hepatitis, correlates with significant hypertransaminasemia, appears to result from failure of hepatic perfusion (with or without preceding hypotension), and presents with clinical and laboratory manifestations that suggest viral hepatitis.

Adolescent↗
PubMed1979

Mesenteric vascular effects of prostaglandins F2 alpha and B2. Possible advantages over vasopressin in control of gastrointestinal bleeding.

Mesenteric vascular effects of prostaglandins B2 and F2 alpha were studied and compared to those of vasopressin in the dog, cat and baboon. Vasopressin reduced superior mesenteric blood flow (SMBF) 80-100%, and significantly increased hepatic arterial blood flow and systemic arterial pressure. Prostaglandin B2 produced vasodilatation at low doses and biphasic vasodilatation/vasoconstriction at high doses. Prostaglandin F2 alpha elicited only vasoconstriction, reducing SMBF, left gastric, and inferior mesenteric blood flow 80-100%. Systemic arterial pressure was not significantly changed. Thus, vasopressin and prostaglandin F2 alpha are equally effective mesenteric vasoconstrictors. Because of reduced systemic effects, prostaglandin F2 alpha has excellent potential as a mesenteric vasoconstrictor to control gastrointestinal hemorrhage.

Animals↗