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Biomedical subjects

R E Sampliner

Publications and source records attributed to R E Sampliner.

At least 91 records · Page 5Linked to original sources
PubMed1994

Evaluation of hepatic injury arising during fluconazole therapy.

Previous reports have described hepatotoxicity associated with ketoconazole therapy. There is also concern that therapy with fluconazole might cause the same side effect as ketoconazole. We describe two patients who developed unexplained liver test abnormalities after beginning fluconazole therapy. To determine whether fluconazole might have been responsible, liver biopsies were performed. Specimens from both patients demonstrated an absence of hepatocyte necrosis, which, if present, would have necessitated discontinuation of fluconazole therapy. A critical review of other case reports of fluconazole-associated hepatitis also failed to produce a consistent picture. Our experience indicates that a liver biopsy may be useful in selected patients to exclude clinically relevant hepatotoxicity due to fluconazole therapy and to allow its continued use.

Adult↗
PubMed1994

The effect of hepatic disease on the disposition of moricizine in humans.

The pharmacokinetics of moricizine and two of its metabolites, moricizine sulfoxide and phenothiazine-2-carbamic acid ethyl ester sulfoxide, were studied in healthy control subjects and in patients with chronic liver disease (cirrhosis). Moricizine disposition was significantly altered by hepatic cirrhosis. Compared to healthy subjects, the hepatic disease patients had an increased Cmax (59%), an increased t1/2 (141%), and a reduced plasma clearance (71%). Additionally, small but statistically significant increases were observed for tmax and the fraction of moricizine not bound to plasma proteins in patients with hepatic disease. The elimination of both moricizine metabolites was also altered by hepatic dysfunction as indicated by significantly prolonged terminal half-lives. Furthermore, there was a reduction in the conversion of moricizine to moricizine sulfoxide. Both hepatic blood flow and hepatic metabolizing capacity were assessed in all subjects and patients by administration of indocyanine green and antipyrine, respectively. Indocyanine green and antipyrine plasma clearances were decreased by 38 and 51%, respectively, indicating that both functions were diminished by hepatic cirrhosis. We conclude that the moricizine dose required for arrhythmia patients with hepatic disease should be lower, and perhaps, the dosing frequency should be less than in patients with normal liver function.

Administration, Oral↗
PubMed1994

Nonsteroidal antiinflammatory agents in chemoprevention of colorectal cancer. At what cost?

The objective was to provide a comparison of the known toxicities of nonsteroidal antiinflammatory drugs (NSAIDS) and the likelihood of benefit from colorectal cancer (CRC) chemoprevention attributed to them. Chemoprevention trials require large numbers of subjects followed over many years and are therefore very expensive and difficult. Hence, it is important that agents tested in these trails have a realistic expectation of actual use in the population. Data sources were published literature on the toxicity and CRC chemopreventive activity of NSAIDS. Presently available NSAIDS, used at their usual therapeutic doses, have a serious toxicity rate that quickly exceeds any benefit from CRC prevention. In contrast, low-dose aspirin is worth evaluating, especially because of the potential for simultaneous cardiovascular risk reduction. Possibly, low doses of other NSAIDS may have benefit, but this remains unproven. Synthesis of other NSAIDS, with less toxicity, is another approach towards making the toxicity-benefit ratio more favorable for the use of these agents for CRC prevention.

Animals↗
PubMed1994

24-hour pH monitoring in symptomatic patients without erosive esophagitis who did not respond to antireflux treatment.

Twenty symptomatic patients without erosive esophagitis underwent 24-h esophageal pH monitoring after failing standard medical antireflux treatment. Sixty-five percent had abnormal esophageal acid exposure, and the majority of these improved on proton pump inhibitor therapy. However, 35% had a normal 24-h pH test. One patient had coronary artery disease, one had diffuse esophageal spasm, and two had a negative work-up and no improvement with omeprazole. Consequently, we suggest that patients like these have an omeprazole trial. If symptoms persist, 24-h esophageal pH monitoring can appropriately define more rational management. Patients with abnormal esophageal acid exposure will require more aggressive acid-control therapy, whereas those with normal esophageal acid exposure will need further work-up to assess the cause of their symptoms.

Adult↗
PubMed1994

Diagnostic inconsistencies in Barrett's esophagus. Department of Veterans Affairs Gastroesophageal Reflux Study Group.

BACKGROUND/AIMS: Few studies have compared the precision of various diagnostic tests used to determine the presence of Barrett's esophagus. The aim of this study was to compare the results of histological, endoscopic, and manometric tests for patients with Barrett's esophagus in two closely spaced examinations. METHODS: In a Veterans Administration Cooperative Study, 192 patients with complicated gastroesophageal reflux disease had esophageal manometry and endoscopy performed at baseline and after 6 weeks. At each examination, the endoscopist localized the most proximal level of Barrett's epithelium and the lower esophageal sphincter and obtained esophageal biopsy specimens. RESULTS: One hundred sixteen patients met the criteria for Barrett's esophagus on at least one of the two endoscopic examinations. Among patients with specialized columnar epithelium, 20% had specialized columnar epithelium found on only one of the two examinations. Although the mean lower esophageal sphincter level did not change, approximately 10% of patients had a change > or = 4 cm on endoscopy and manometry between examinations. This led to an apparent change in the diagnosis in 18% of patients with Barrett's esophagus. CONCLUSIONS: From one endoscopic examination to another, inconsistencies in the ability to detect specialized columnar epithelium are common. This may lead to substantial problems in establishing an accurate diagnosis of Barrett's esophagus.

Barrett Esophagus↗
PubMed1994

Effect of up to 3 years of high-dose lansoprazole on Barrett's esophagus.

OBJECTIVE: Barrett's esophagus is a metaplastic condition resulting from gastroesophageal reflux disease. Previous medical and surgical therapies have failed to predictably eradicate Barrett's. The objective of this study was to assess the impact of long-term, high-dose lansoprazole, a proton pump inhibitor, on Barrett's esophagus. METHODS: Patients with Barrett's esophagus at least 3 cm long and with specialized columnar epithelium were treated with 60 mg of lansoprazole each morning. Every 6 months, patients had standardized symptomatic, laboratory, and endoscopic assessment. The length of Barrett's esophagus was measured, photo-documented, and biopsied. RESULTS: Twenty-seven patients with Barrett's esophagus have been treated an average of 2.9 yr. Symptoms improved (70%, 19 patients), and erosive esophagitis healed (100%, 13 patients), but there was no significant reduction in the length of Barrett's epithelium (mean length at baseline 5.7 cm, final visit 5.3 cm). However, by the final visit, 20 of 26 patients (77%) had squamous islands: two unchanged in size, six with increased surface area, and 12 newly developed on therapy. Initially, mean fasting gastrin levels rose significantly but then plateaued after 1 month of therapy. Of 10 patients with gastrin levels for 18 months or longer, only one had a level > or = 400 pg/ml. CONCLUSIONS: Lansoprazole 60 mg for up to 3 yr was safe and effective in controlling symptoms and esophagitis. The impact on the extent of Barrett's esophagus over this time interval was manifested by the extension and development of squamous islands.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1994

Endoscopic evaluation of Barrett's esophagus.

Barrett's esophagus is a premalignant condition, the recognition of which is increasing because of widespread utilization of upper endoscopy. Awareness and identification of the squamocolumnar junction are key to endoscopic recognition of Barrett's esophagus. Biopsy is essential to document Barrett's esophagus and to detect dysplasia. Specific mucosal abnormalities need to be targeted. In addition, systematic biopsies need to be taken for dysplasia/carcinoma surveillance. Experimental endoscopic application of energy to Barrett's esophagus offers the potential for elimination of this lesion. Endoscopic recognition and diagnosis remain the key to clinical management of Barrett's esophagus.

Barrett Esophagus↗
PubMed1994

A normal initial colonoscopy after age 50 does not predict a polyp-free status for life.

OBJECTIVES: The prevalence of colon polyps increases with age in the general population. It is unknown whether a lack of adenomatous polyps determined at one time point after the age of 50 is predictive of a subsequent low risk of polyp development. METHODS: Twenty-nine patients between ages 50 and 70 who had no prior history of polyps and had a normal colonoscopy at least 5 yr previously were recruited for follow-up colonoscopy to evaluate the incidence of neoplastic disease in this presumably low-risk group. RESULTS: The incidence of adenomatous polyps after a mean of 5.74 yr was 41.4% (95% confidence interval: 23.5-61.1%). A total of 20 adenomatous polyps were found in 12 patients. Seven polyps were 5 mm or more in size. CONCLUSIONS: We conclude that in patients with no history of colonic neoplasia who are 50 yr old, or older, the finding of a normal colonoscopy does not predict diminished risk of neoplasia.

Adenomatous Polyps↗
PubMed1994

Gastrointestinal tissue polyamine contents of patients with Barrett's esophagus treated with alpha-difluoromethylornithine.

alpha-Difluoromethylornithine (DFMO), an investigational chemopreventive agent, suppresses polyamine contents and decreases epithelial carcinogenesis in experimental models. The ability of this drug to decrease polyamine contents in human esophageal tissues has not yet been determined. Eight patients with Barrett's esophagus were treated with DFMO at a dose of 1.5 g/m2/day for 12 weeks. Four sites (Barrett's lesion, adjacent normal squamous esophagus, gastric tissue, and small bowel) were biopsied in each patient before, during, and after DFMO treatment in order to assess the effects of this drug on tissue polyamine levels. Ornithine decarboxylase activities and polyamine contents varied in each site analyzed. The rank orders were Barrett's > small bowel congruent to normal esophagus > gastric tissue for ODC activities, and small bowel > or = Barrett's congruent to normal esophagus > gastric tissue for putrescine contents. Spermidine, but not spermine, contents in the Barrett's lesions and normal squamous esophageal tissue were suppressed by systemic DFMO treatment and recovered to untreated control values when DFMO therapy was discontinued. Systemic DFMO treatment did not affect the levels of either of these two amines in gastric tissue and small bowel. Since DFMO can suppress polyamine contents in several gastrointestinal tissues, including Barrett's mucosa, we conclude that it is an effective agent with which to test the hypothesis that depletion of spermidine contents may prevent the development of adenocarcinoma of the esophagus in this specific patient group.

Aged↗
PubMed1994

Two-year incidence of colon adenomas developing after tandem colonoscopy.

OBJECTIVES: We attempted to determine an accurate frequency of new polyp growth in a cohort of veteran male patients who were initially cleared of polyps by tandem colonoscopy. METHODS: Followup colonoscopy was performed 2 yr after tandem colonoscopy. A polyp was categorized as "new" if it was not located in a segment of the colon or rectum that had harbored a neoplastic polyp of the same histology at tandem colonoscopy, in contradistinction to lesions designated as "same-segment" polyps. RESULTS: Fifty-eight of 90 patients who had tandem colonoscopy as a part of a previous study were available for follow-up colonoscopy for 2 yr. Ninety-one percent had a history of benign neoplastic polyps or cancer. Neoplastic polyps were documented in 52% (95% CI, 45-74%) of patients at followup, and 38% (95% CI, 26-52%) were found to have a total of 31 "new" lesions. All new lesions were tubular adenomas. The largest number of new polyps in an individual patient was four, and the largest new lesion was 20 mm in size with a flat, linear configuration. Most (25/31) new polyps were < or = 5 mm, and the number of neoplastic polyps per patient at follow-up was less than at tandem colonoscopy. CONCLUSIONS: Approximately one-half of older, male patients with a history of neoplastic polyps will demonstrate neoplastic polyps at 2 yr. In at least one-third of patients, these appear to be new lesions. In some patients, de novo neoplastic polyps can grow to > or = 1 cm within 2 yr.

Adenoma↗
PubMed1993

Significance of isolated hepatitis B core antibody in blood donors.

BACKGROUND: About 25% of blood donors who test positive for antibody to hepatitis B core antigen (anti-HBc) have no other positive hepatitis B serologic results. Because of the potential importance and diagnostic uncertainty of this test result, we studied its significance by assessing the serologic response to hepatitis B vaccine in donors with an isolated anti-HBc pattern. METHODS: Specimens from 300 blood donors that were positive for anti-HBc by enzyme immunoassay were tested for anti-HBc by radioimmunoassay and for antibody to hepatitis B surface antigen (anti-HBs). A subgroup of 37 were further studied after administration of hepatitis B vaccine and compared with 34 similarly vaccinated age- and sex-matched seronegative controls. Measurements of anti-HBs were made at vaccination and 1, 2, 4, 8, 25, and 30 weeks after initial vaccination. RESULTS: Among 300 donors who tested positive for anti-HBc by enzyme immunoassay, the radioimmunoassay for anti-HBc was negative in 76 (25.3%) and the test for anti-HBs was negative in 104 (34.7%). Significant differences were observed for radioimmunoassay anti-HBc and anti-HBs titers, alanine aminotransferase, and male-female ratios between four distinct serogroups (A through D) defined by the combination (positive/negative) of radioimmunoassay anti-HBc and anti-HBs results. No significant differences between the study and control groups were observed in the magnitude of anti-HBs responses at any of the six postvaccine testing periods. CONCLUSIONS: Isolated anti-HBc in US blood donors is usually a false-positive result, regardless of the titer.

Adult↗
PubMed1993

Increased mortality with gallstone disease: results of a 20-year population-based survey in Pima Indians.

OBJECTIVE: To determine if gallstone disease is associated with an increased risk for malignancy and higher total mortality in Pima Indians. DESIGN: Inception cohort. SETTING: American Indian community. PARTICIPANTS: Age- and sex-stratified random population-based sample. MEASUREMENTS: Between 1966 and 1969, an age- and sex-stratified random sample of Pima Indians from the Gila River Indian Community in Arizona was examined to identify evidence of gallstone disease defined as either gallstones (oral cholecystography) or previous cholecystectomy. During 20 years of follow-up, deaths were recorded and underlying causes of death, according to death certificates, were determined. RESULTS: Among 383 persons with known gallbladder status, 186 (49%) died: 133 among the 222 persons with gallstone disease and 53 among the 161 without. The overall death rate was higher in persons with gallstone disease than in those with normal gallbladders. The age- and sex-adjusted death rate ratio was 1.9 (95% Cl, 1.3 to 2.7). Furthermore, the death rate attributed to malignancies was 6.6 times (Cl, 1.3 to 33.1) as high in persons with gallstone disease as in those with normal gallbladders. Of the 20 fatal malignancies in persons with gallstone disease, 11 occurred in the digestive tract, of which six involved the gallbladder or bile ducts. CONCLUSIONS: Increased cancer mortality and total mortality were found in Pima Indians with gallstone disease. Although plausible explanations exist for the increased cancer mortality, the increased death rates due to other causes are unexplained. Whether cholecystectomy would change this risk is unknown.

Adolescent↗
PubMed1993

Age- and gender-related differences in 24-hour esophageal pH monitoring of normal subjects.

Twenty-four-hour esophageal pH monitoring is currently the most sensitive test for diagnosing gastroesophageal reflux. Little is known, however, about the effect of aging and gender on esophageal acid exposure in asymptomatic individuals. Thirty asymptomatic volunteers underwent 24-hr esophageal pH monitoring. Fifteen were < 65 years (eight female, seven male) and 15 were > or = 65 years (seven female, eight male). In this asymptomatic group no significant difference was seen by age, while males were found to have significantly more esophageal acid exposure than females. The need for sex-specific normal 24-hr pH monitoring values is suggested. Thirty percent of these asymptomatic subjects were abnormal by conventional 24-pH criteria. The clinical importance of these "silent refluxers" is unknown.

Adult↗
PubMed1993

Regression of Barrett's esophagus by laser ablation in an anacid environment.

Consistent regression of intestinal metaplasia in Barrett's esophagus has not been achieved with medical or surgical interventions. In this case report, a patient with Barrett's esophagus of stable length had half the circumference of the Barrett's epithelium ablated with laser therapy while on a high-dose proton-pump inhibitor. In the absence of esophageal acid exposure and after laser ablation, the intestinal metaplasia was documented to reepithelialize with normal squamous mucosa, which has persisted.

Aged↗
PubMed1993

Review article: Barrett's oesophagus--cancer risk, biology and therapeutic management.

Barrett's oesophagus is receiving increasing scrutiny as the rates of adenocarcinoma of the oesophagus rise. Because clinical features are not predictive of the presence of Barrett's oesophagus and most individuals with Barrett's oesophagus go undetected, a case can be made for surveillance endoscopy in patients with chronic reflux. Once Barrett's oesophagus is diagnosed patients should be entered into a surveillance programme despite lack of proof of efficacy. Scientific study of putative biological markers of increased risk has added dramatically to the understanding of the biology of the lesion, but currently the finding of high grade dysplasia remains the best marker predicting the presence of greatly increased risk of developing cancer. It is likely that newer molecular biology techniques will become clinically applicable biological markers in the future. Currently there is no effective medical nor surgical therapy to cause regression of the metaplastic Barrett's epithelium, however the application of novel de-differentiating agents or ablation of the metaplastic epithelium while controlling oesophageal acid exposure and other environmental abnormalities offer hope that effective treatment of Barrett's oesophagus may someday be reality.

Adenocarcinoma↗
PubMed1993

Treatment of reflux esophagitis resistant to H2-receptor antagonists with lansoprazole, a new H+/K(+)-ATPase inhibitor: a controlled, double-blind study. Lansoprazole Study Group.

This multicenter, randomized, double-blind, 8-wk study compared the new H+/K(+)-ATPase inhibitor, lansoprazole, 30 mg daily, to ranitidine 150 mg bid for treatment of erosive reflux esophagitis resistant to histamine-2 receptor antagonists (H2RA). Patients were evaluated after 2, 4, 6, and 8 wk of treatment by symptom assessment and endoscopy. Healing rates for lansoprazole were 71%, 80%, 88%, and 89% at 2, 4, 6, and 8 wk, respectively, compared to 21%, 33%, 45%, and 38% for ranitidine (p < 0.001 at all points). Lansoprazole was significantly more effective than ranitidine for relief of heartburn and reduction of antacid tablet use. Increases in serum gastrin concentrations between the baseline and the 8-wk visit were greater in lansoprazole-treated than in ranitidine-treated patients. Lansoprazole was safe and well tolerated. In patients with erosive reflux esophagitis resistant to standard doses of H2RA, lansoprazole 30 mg/day is more effective than continuation of an H2RA (ranitidine 150 mg bid) for healing of esophagitis and improvement of symptoms.

2-Pyridinylmethylsulfinylbenzimidazoles↗