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Biomedical subjects

R E Sampliner

Publications and source records attributed to R E Sampliner.

At least 109 records · Page 6Linked to original sources

NSAID effect on sporadic colon polyps.

UNLABELLED: In this study, our objective was to determine whether 6 months of open-label therapy with sulindac 400 mg/daily or piroxicam 20 mg/daily promote regression of adenomatous colonic polyps left in situ. Left-sided colonic polyps (size 3-12 mm) detected at colonoscopy were measured and left without being biopsied. The bowel wall opposite to the polyps was marked with India ink submucosally. Patients were assigned to drug therapy, and compliance was determined by pill count. Polyps were measured during sigmoidoscopy after 3 and 6 months of treatment; polyps were removed at the 6-month examination. Examiners were not blinded to drug therapy or previous polyp measurements. Seven patients completed 6 months of therapy (five sulindac and two piroxicam). Two additional patients treated with piroxicam were withdrawn secondary to adverse events (bleeding gastric ulcer and rash). In one patient treated with sulindac, a 6-mm polyp disappeared, and two other polyps seemed to regress partially. One polyp regressed partially in a piroxicam-treated patient. All other polyps remained unchanged. CONCLUSIONS: We did not observe dramatic regression of sporadic colon adenomatous polyps to either sulindac or piroxicam after 6 months of therapy in this small uncontrolled pilot study.

Adenomatous Polyps↗

Partial regression of Barrett's esophagus--an inadequate endpoint.

A patient with Barrett's esophagus and high grade dysplasia is presented. He underwent a fundoplication and, subsequently, nearly three years of high-dose proton pump inhibition therapy. At the time of esophagogastrectomy, extensive squamous re-epithelialization was observed along with two histologic foci of intramucosal adenocarcinoma. Despite partial regression of Barrett's esophagus, high grade dysplasia present for more than 4 years had progressed to adenocarcinoma. Partial squamous repopulation of Barrett's esophagus is an inadequate endpoint of therapy. Complete regression is necessary to eliminate the risk of cancer.

Adenocarcinoma↗

Are endoscopic measurements of colonic polyps reliable?

Many clinical studies of colorectal adenomatous polyps rely on endoscopic estimation of polyp size. To examine the reliability of such measurements, we conducted a study using artificial polyps in an endoscopy teaching model. Eight experienced endoscopists estimated the size of 13 polyps in two separate sessions 2 wk apart. Endoscopic estimates of polyp size tended to be significantly lower than the true polyp size for all polyps and all endoscopists at both sessions. We also found a statistically significant difference in the magnitude of the underestimation between the first and second session (p < 0.0001). At the first session, polyps tended to be estimated at 64% of their true size, and at the second session, the estimates tended to be at 77% of the actual polyp size. We estimate the magnitude of the variation in polyp measurements due to individual polyps, endoscopist, and examination session, and discuss the impact these sources of variation have in planning of clinical trials.

Colonic Neoplasms↗

The natural history of community-acquired hepatitis C in the United States. The Sentinel Counties Chronic non-A, non-B Hepatitis Study Team.

BACKGROUND: Chronic liver disease develops in more than half of patients with post-transfusion hepatitis C, but little is known about the natural history of community-acquired hepatitis C. METHODS: In 1985 and 1986 we identified adults with acute non-A, non-B hepatitis in four counties in the United States and followed them prospectively. We used three markers to detect hepatitis C virus (HCV) infection in stored samples of serum: antibody to HCV (anti-HCV) detected by second-generation serologic assays; HCV RNA detected by polymerase-chain-reaction assay; and antibody to HCV antigen (anti-HCVAg) detected by fluorescent-antibody-blocking assay. RESULTS: Of 130 patients with non-A, non-B hepatitis, 106 (82 percent) had HCV infection, 93 were positive for anti-HCV, and 13 were positive only for HCV RNA or anti-HCVAg. Chronic hepatitis developed in 60 (62 percent) of 97 HCV-infected patients followed for 9 to 48 months, with no relation to the risk factors for infection. Ten of the 30 patients who had liver biopsies had chronic active hepatitis. In samples collected 42 to 48 months after the onset of hepatitis, HCV RNA was detected in 12 of 13 tested patients with chronic hepatitis and in all 15 tested patients with hepatitis that had resolved. Anti-HCV persisted in all but two of the initially positive patients, for a rate of antibody loss of 0.6 per 100 person-years. CONCLUSIONS: Patients with community-acquired hepatitis C have a high rate of chronic hepatitis. HCV may be a major cause of chronic liver disease in the United States, and in most patients HCV infection seems to persist for at least several years, even in the absence of active liver disease.

Adolescent↗

Ornithine decarboxylase assay in human colorectal mucosa. Methodologic issues of importance to quality control.

Ornithine decarboxylase may be a useful biomarker for risk of neoplasia in colorectal tissues. Investigators have reported enzyme activities varying by as much as 10- to 20-fold using variations of the usual 14CO2 release assay. We have examined the effect of different methodologic factors on calculated ornithine decarboxylase activity. Major effects on the assay result (greater than 20% change) were produced by: (1) use of Tris vs. phosphate buffer, the former yielding 1.5- to 4-fold greater activity; (2) protein content of the reaction mixture with significant error if less than 50 micrograms; (3) use of alpha-difluoro-methylornithine-inhibited blank versus buffer-only blank. Other changes in assay conditions, including addition of sucrose, detergent, protease inhibitors, specific activity of 14C-ornithine, the nature of the trapping agent used, and incorporation of a sonication step, did not have a significant effect on ODC quantification (less than or equal to 20%). Thus, seemingly minor variations in assay conditions can greatly affect the results, which may provide a partial explanation for the variability of ODC activities reported in the literature. Strict quality control measures are mandatory in the interpretation of clinical observations utilizing this marker as an endpoint.

Biomarkers, Tumor↗

Tissue culture of epithelial cells from esophageal specialized columnar epithelium (Barrett's esophagus).

A procedure is described for the tissue culture of epithelial cells from Barrett's specialized columnar epithelium. The method employs use of nonenzymatic disaggregation techniques and use of a specialized growth medium, M-19. Successful growth can be achieved in 60-70% of cases. Characteristics of four cultures are presented including PAS, Alcian blue, and cytokeratin staining properties. Ultrastructural studies showed the presence of distended rough endoplasmic reticulum, abundant Golgi apparatus, glycogen granules, and cell-cell junctional complexes. Colony formation in anchorage-independent growth in soft agar was not observed in any culture. The cultured cells were not capable of indefinite growth. Thus, they do not behave as fully transformed cells. Availability of this culture system should be of use to the study of the biology of this metaplastic premalignant lesion.

Barrett Esophagus↗

Preventing hypoxemia during colonoscopy. A randomized controlled trial of supplemental oxygen.

Hypoxia as measured by pulse oximetry is well recognized in patients undergoing colonoscopy. A single trial of supplemental oxygen therapy has been shown to diminish the observed desaturation during colonoscopy. We further defined the role of supplemental oxygen during colonoscopy in a randomized controlled trial. Ninety-four patients undergoing routine colonoscopy were randomized to oxygen (2 L by nasal prongs) or placebo (nasal prongs only) arms. The physician and patients were blinded to which arm they were in. Sixty-four percent of patients in the placebo arm desaturated (less than 90% saturation) versus 29% in the treatment arm (p less than 0.001). There were no complications observed in either arm. We conclude that supplemental oxygen will decrease but not prevent the incidence of arterial desaturation observed during colonoscopy.

Aged↗

Histopathology of community acquired chronic hepatitis C. The Sentinel Counties Chronic Non-A, Non-B Hepatitis Study Team.

As part of a study of community-acquired non-A, non-B hepatitis, liver biopsy specimens of 29 anti-HCV positive and four anti-HCV negative patients were evaluated in order to characterize the histopathologic changes of chronic hepatitis C. Liver biopsies were performed 6 to 46 mo after onset of the disease and repeat biopsies were obtained in 10 anti-HCV positive patients. The histologic diagnoses were chronic persistent hepatitis (45%), chronic active hepatitis (35%), and chronic lobular hepatitis (21%). Irrespective of the tissue diagnosis, the majority of the patients showed characteristic histologic abnormalities in the liver, particularly damage of the small and medium-sized bile ducts (76%), lymphoid aggregates in portal tracts (45%), enlarged macrophages (48%), and steatosis (31%). In 59% of the patients, two or more of these histologic abnormalities were combined. Similar histologic changes have previously been observed in non-A, non-B hepatitis, but only uncommonly in hepatitis A or hepatitis B. We conclude that the histopathologic findings in chronic hepatitis C are highly characteristic, although not pathognomonic.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

Effectiveness of India ink as a long-term colonic mucosal marker.

We prospectively studied the use of India ink as a long-term or "permanent" mucosal marker as part of a study investigating the natural history of diminutive distal colorectal polyps. Twenty-six patients had 32 India ink tatoos implanted. The tatoo sites of the 19 patients who were followed at least 6 months continued to display intensely stained mucosa at the original sites. No side effects or complications were encountered. India ink appears to be a safe and effective long-term marker for colonic mucosal lesions.

Carbon↗

Chemopreventive studies in Barrett's esophagus: a model premalignant lesion for esophageal adenocarcinoma.

Barrett's esophagus is a premalignant lesion in which the lower esophagus is lined with metaplastic columnar epithelium rather than the normal stratified squamous epithelium. It is a precursor lesion for adenocarcinoma of the esophagus. We are studying Barrett's esophagus as a model premalignant lesion for adenocarcinoma from the standpoint of identifying biologic markers of increased cancer risk as well as therapeutic strategies for eradicating the lesion. Ornithine decarboxylase (ODC) activity in Barrett's mucosa was significantly higher than in normal adjacent mucosa from the same patient. However, polyamine content was not significantly altered, suggesting dysregulation of the polyamine pathway. Flow cytometry is being used to assess the presence of aneuploidy and its significance in a premalignant lesion. Initial results have demonstrated that aneuploidy and dysplasia can be discordant. Cytogenetic analysis using short-term epithelial cultures established from endoscopic biopsies of the lesion has demonstrated the presence of clonal karyotypic abnormalities. The clinical significance of aneuploidy and abnormal karyotype, however, remains to be proved. Chemopreventive intervention trials have included use of 13-cis-retinoic acid. Considerable toxicity was encountered, and the lesion showed no change in extent in 11 evaluable patients. A subsequent clinical trial with a biologic endpoint used alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ODC, to test whether a low dose could produce changes in polyamine content in gastrointestinal mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

The effects of 13-cis-retinoic acid and beta-carotene on cellular immunity in humans.

Deficiency of vitamin A and/or its precursors has been associated with increased cancer risk in animals and humans. Therapeutic trials of vitamin A and related compounds have demonstrated activity in several cancerous and precancerous conditions. The authors measured the effects of a retinoid, 13-cis-retinoic acid, and a carotenoid, beta-carotene, on the human immune system in vivo in conjunction with their use in ongoing clinical trials. Immune cell subpopulations were analyzed by quantifying the expression of markers using flow cytometric study. Both compounds produced significant effects on immune cell populations. 13-cis-Retinoic acid resulted in an increase in the percentage of peripheral blood lymphoid cells expressing surface markers for T-helper cells with only minimal effect on natural killer cell marker expression. In contrast, beta-carotene produced an increase in the percentage of cells expressing natural killer cell markers with smaller effect on T-helper markers. Modest increases in the percentage of cells expressing Ia antigen, transferrin, and interleukin-2 receptors were produced by both drugs. These results suggest that retinoids and carotenoids can produce major changes in immune cellular marker expression in vivo in humans at doses relevant to their potential clinical use.

Adult↗

Prospective study of the frequency and size distribution of polyps missed by colonoscopy.

An important determinant in interpreting the results of colorectal polyp chemoprevention trials is the rate of polyps missed during colonscopic examination. We prospectively examined 90 patients by tandem colonoscopy performed by two alternating examiners. In 69 (76.7%) patients, 221 neoplastic lesions were documented histologically. Of a total of 58 lesions detected in 31 patients, no neoplastic lesion greater than or equal to 10 mm in size was missed; 16% of diminutive (less than or equal to 5 mm) neoplastic polyps and 12.3% of medium-sized (6-9 mm) neoplastic polyps were missed by the first examiner. We conclude that an experienced colonoscopist will miss about 15% of colorectal neoplastic polyps less than 10 mm in size in the setting of adequate bowel preparation. Large (greater than or equal to 10 mm) polyps were rarely missed, however, with the "miss" rate in our study equal to 0, with a 95% confidence limit of 4.64%.

Adult↗