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Biomedical subjects

H W Boyce

Publications and source records attributed to H W Boyce.

At least 19 recordsLinked to original sources

Effect of 5-fluorouracil on methotrexate transport and cytotoxicity in HT29 colon adenocarcinoma cells.

Exposure of the human colon adenocarcinoma HT29 cells to different concentrations of 5-fluorouracil (5FU) for 24 h resulted in a dose-dependent increase in the cellular glutathione (GSH) level which remained elevated up to 72 h following 5FU treatment. Pretreatment of HT29 cells with 5FU was found to enhance the uptake of methotrexate (MTX) as compared to control cells. Administration of MTX 24 h after 5FU was found to be synergistic, whereas administration of MTX 24 h before 5FU or together with 5FU was not found to be synergistic. The results of this study suggest that the increase in cellular GSH level as a result of 5FU pretreatment may play a role in the enhancement of MTX uptake and the cytotoxicity of both drugs in HT29 cells.

Adenocarcinoma

Cruciferous vegetables and glutathione: their effects on colon mucosal glutathione level and colon tumor development in rats induced by DMH.

The effect of a diet containing 10-40% lyophilized cabbage or broccoli as cruciferous vegetable or 10-40% lyophilized potato as noncruciferous vegetable fed for 14 days on the colon mucosal glutathione (GSH) level was studied in male rats. The GSH levels of the duodenum mucosa and the liver were also measured. Cabbage and broccoli enhanced the colon and duodenum mucosal GSH levels in a dose-related manner; potato had no effect. All three vegetables had no effect on the liver GSH level. The effect of GSH on colon tumorigenesis induced by 1,2-dimethylhydrazine (DMH) was also examined in rats. Male Sprague-Dawley rats were injected with DMH (20 mg/kg body wt) weekly for 20 weeks. DMH lowered the colon mucosal GSH level. GSH (100 mg/day/rat) dissolved in the drinking water and given to rats during and after DMH injections had little or no effect on tumor incidence and total number of colon tumors. Tumors were larger in rats that received GSH than in those that received water. This study shows that the colon mucosal GSH level can be enhanced by feeding rats a diet high in cabbage or broccoli and that GSH added to the drinking water did not affect DMH-induced colon tumorigenesis under the experimental conditions used.

1,2-Dimethylhydrazine

The effect of endotoxin on 1,2-dimethylhydrazine-induced colonic tumors in rats.

The effect of endotoxin on colon tumors was studied in male Sprague-Dawley rats. Colon tumors were induced in weanling rats by the administration of 20 weekly subcutaneous injections of 1,2-dimethylhydrazine (DMH). When colon tumors were detected by colonoscopy in 80% of the rats around week 24 after DMH injection, the animals were divided randomly into two groups. One group served as the control. The other group received six endotoxin (Escherichia coli) treatments every fifth day. The first dose was 50 micrograms/100 g (intraperitoneally); the remaining doses were 100 micrograms/100 g (subcutaneously). Rats were killed 2 weeks after the last endotoxin injection. Endotoxin treatments resulted in larger colon tumors. The median tumor size was 71 mm2 for endotoxin-treated and 31 mm2 for untreated rats (P less than 0.02). Endotoxin treatments also resulted in a significantly higher incidence (P less than 0.05) of ulcer development in the small intestine, that is 47% in the endotoxin-treated versus 23% in the untreated rats. After a single subcutaneous injection of endotoxin (100 micrograms/100 g), the colon mucosal reduced glutathione (GSH) level was raised by 21% at 16 hours, reached a peak on day 2, then decreased to baseline by day 4. The increased GSH level in the colon mucosa was maintained up to the third endotoxin injection. By the fifth injection, no increase in the GSH level was observed. These results suggest that the growth of colon tumors in rats induced by DMH could be enhanced by endotoxin treatments. The enhanced tumor growth may be due to an increase in the colon GSH level and/or other mediators released by macrophages as a result of endotoxin treatments.

1,2-Dimethylhydrazine

Effect of DL-buthionine-S,R-sulfoximine on 1,2-dimethyl-hydrazine-induced colonic tumors in rats.

The effect of DL-buthionine-S,R-sulfoximine (BSO), a specific inhibitor of glutathione biosynthesis, on colon tumor development was studied in rats. Weanling male Sprague-Dawley rats were randomly assigned to one of three groups following a week of adaptation. Group 1 rats received BSO (4.5 mM) daily in the drinking water one week before 1,2-dimethylhydrazine (DMH) injections and continued to receive BSO daily until sacrificed; group 2 rats received BSO (4.5 mM) after the last DMH injection, and continued to receive BSO daily until sacrificed; group 3 rats did not receive BSO. All experimental rats received 20 weekly subcutaneous injections of DMH (20 mg/kg body wt.) for colon tumor induction. The tumor incidence was lower in group 1 (54%) than in group 2 (97%) or group 3 (96%). The median tumor size is significantly smaller in group 1 (11 mm2) than group 3 (46 mm2). The group 2 had the largest median tumor size (65 mm2).

1,2-Dimethylhydrazine

Effect of ascorbic acid on plasma alcohol clearance.

The effects of short-term and long-term ascorbic acid supplements on plasma alcohol clearance were studied in 13 clinically healthy male subjects. Two dose levels of alcohol, 0.5 and 0.8 g/kg body weight, were used. Blood samples were taken at zero time, 0.5 hours, then hourly up to 6 hours after alcohol consumption for the measurement of plasma alcohol and ascorbic acid levels, red-cell reduced glutathione level, and plasma alanine aminotransferase activity. At both dosages of alcohol, short-term as well as long-term pretreatment with ascorbic acid significantly enhanced the clearance of plasma alcohol. Although long-term ascorbic acid pretreatment resulted in better alcohol clearance, no significant difference in alcohol clearance was found between short-term and long-term ascorbic acid pretreatment. The two dose levels of alcohol had no significant effect on the red-cell reduced glutathione concentration or plasma alanine aminotransferase activity.

Adult

Incomplete intestinal metaplasia in the diagnosis of columnar lined esophagus (Barrett's esophagus).

To investigate the distribution and specificity of intestinal metaplasia (IM) in columnar lined esophagus (CLE), the authors reviewed biopsies of the hiatal hernia pouch (HHP) and esophagus from 17 patients with CLE (84 biopsies) and 10 controls (25 biopsies). The proximal margin of the gastric folds was used as an endoscopic landmark, corresponding to the gastroesophageal muscular junction (GEMJ). No biopsies obtained above the GEMJ in control patients showed columnar mucosa. No goblet cell metaplasia was seen in 21 biopsies of the HHP from patients with CLE or in 13 corresponding biopsies from controls. In contrast, alcian blue (AB) stains showed diffuse acid mucins in 3 of 21 biopsies of the HHP from patients with CLE and in 10 of 13 corresponding biopsies from controls, demonstrating that goblet cell metaplasia clearly distinguishes biopsies of CLE from the HHP (P less than 0.01), whereas small amounts of diffuse acid mucin on AB stains do not. IM evidenced by goblet cell metaplasia was frequently seen in biopsies only 2-3 cm above the GEMJ, and CLE was limited to that area in three patients, suggesting that the distal esophagus cannot be dismissed as a site for metaplastic and possibly premalignant mucosa. Adenocarcinoma was diagnosed during the course of the study in one patient with only 5 cm of columnar mucosa above the GEMJ.

Adult

A new objective measurement of esophageal lumen patency.

This study was performed to develop a system to measure dysphagia in an objective fashion, test its correlation with subjective estimates of dysphagia, and encourage the use of a standardized measure of esophageal stenosis. Thirty-five patients with mechanical dysphagia underwent subjective estimates of dysphagia using a dysphagia scale graded from 0 to 5, as well as a diet scale. Lumen diameter was measured endoscopically, using the open or closed biopsy forceps as a measuring guide. Patients were then given barium capsules or tablets of increasing diameter under fluoroscopy, in the upright position. Pills were given sequentially until a pill failed to traverse the esophagus in less than 20 s. The diameter of the pill failing to traverse the esophagus within 20 s correlated strongly with the endoscopically measured diameter by Spearmans rank correlation (Rs = 0.85). The weakest correlation was between endoscopically measured diameter and the dysphagia scale (Rs = 0.48). The diameter of the pill failing to traverse the esophagus within 20 s is an excellent estimate of esophageal lumen diameter. Pill size correlates much better with esophageal lumen diameter than dysphagia or diet scales. This new dysphagia assessment system should simplify standardization of the grading of dysphagia.

Barium Sulfate

Effect of endotoxin on the rat colon glutathione level.

The effect of endotoxin on the colon glutathione level was studied in male rats. Endotoxin (Escherichia coli) from 25 ug to 100 ug/100g body weight was administered intravenously. The Glutathione level was measured 16 hours after endotoxin was given. Results showed that endotoxin significantly enhanced the colon glutathione concentration as measured by 5,5'-dithiobis (2-nitrobenzoic acid). The increase which ranged from 11% to 50% was dose dependent. At an endotoxin dose of 1000 ug/100g body weight, colon glutathione level was found to be enhanced from 2 hours up to 48 hours. In contrast, the duodenum and jejunum glutathione levels were found to be significantly reduced. The increase in the colon glutathione level may have a protective effect against oxidative damage to the colon.

Animals

Treatment of pharyngoesophageal stenosis by polyvinyl prosthesis.

Many authors have objected to the use of esophageal stents in the palliative management of lesions obstructing the cervical esophagus, especially when the prosthesis must lie within 2 cm of the cricopharyngeus muscle (CPM). Ten patients with stenosis of the cervical esophagus by lesions within 2 cm of or involving the CPM were considered for prosthesis placement. The prosthesis was successfully placed in eight patients, five of whom had a tracheoesophageal fistula (TEF). A prosthesis could not be placed in two patients, and two patients complained of a minimal but tolerable foreign body sensation. Six prostheses were custom-made. The necessity to place a prosthesis within 2 cm of or even immediately proximal to the CPM should not be considered an absolute contraindication to esophageal prosthesis placement in selected patients. Foreign body sensation may be absent or minimal, and stent migration is common.

Aged

Comparative evaluation of gastrointestinal intolerance produced by plain and tri-buffered aspirin tablets.

Two multi-investigator, double-blind, randomized, placebo-controlled, crossover trials were conducted to determine whether tri-buffered formulations of both regular strength aspirin and extra strength aspirin would be less likely than plain aspirin to provoke subjective gastrointestinal (GI) intolerance. Each trial was divided into two phases, a qualification phase and a test phase. During the qualification phase, subjects with a history of gastrointestinal intolerance to aspirin were randomized to a double-blind crossover treatment with aspirin and placebo (325 mg aspirin per tablet in study 1 and 500 mg aspirin per tablet in study 2), two tablets four times a day for 3 days or until the occurrence of stomach upset. Subjects who reported gastrointestinal symptoms with aspirin and not with placebo qualified to participate in the test phase of the study. They were rerandomized to participate in a three-way crossover study of plain aspirin, tri-buffered aspirin, and placebo in the test phase. Tri-buffered aspirin was associated with an appreciable reduction in the incidence of gastrointestinal upset relative to plain aspirin, 34 percentage points in study 1 (p less than 0.001) and 33 percentage points in study 2 (p less than 0.001). Similar results were obtained in the evaluation of the reduction of the severity of gastrointestinal symptoms.

Adult

Early diagnosis of columnar-lined esophagus: a new endoscopic diagnostic criterion.

The relationship between the proximal margins of the gastric mucosal folds and the squamocolumnar mucosal junction (SCMJ) in normal subjects and in patients with columnar-lined esophagus (CLE) was studied. Results indicate that in the normal esophagus, the SCMJ is located within 2 cm of the proximal margin of the gastric folds. The proximal margin of the gastric folds in a hiatal hernia pouch provide a fixed, reproducible, anatomic landmark at endoscopy, which designates the junction of the muscular wall of the esophagus and stomach and permits one to predict the expected normal location of the SCMJ. The diagnosis of CLE should be considered at endoscopy when either the SCMJ is located or columnar epithelium is obtained by biopsy at a site greater than 2 cm above the proximal margin of the gastric folds located within a hiatal hernia pouch. This study provides an endoscopic criterion to permit a more accurate diagnosis of CLE in its earliest stages and may permit a better assessment of its prevalence.

Barrett Esophagus

Longitudinal follow-up of chronic hemodialysis patients without vitamin supplementation.

Vitamin supplementation for dialysis patients is still controversial. In our study, we followed longitudinally over a period of a year, 15 patients on chronic hemodialysis who were deprived of vitamin supplementation. Microbiological assays were used to determine the levels of five vitamins of the B group (folate, niacin, B12, B6, and thiamine). Vitamin C was measured chemically. During the observation period when vitamins were not supplemented, a marked drop of many of these vitamins in blood levels were encountered. For vitamins B12 and C, the plasma levels remained within the normal range in all the subjects studied. For the other vitamins, the blood levels were found to be low in a few patients. Our data suggest that vitamin supplementation is probably not needed in most stable hemodialysis patients as it is recommended now, and that perhaps, if supplementation is indicated, less should be given than is presently prescribed. Further research is needed in this area.

Adult