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Biomedical subjects

D Y Graham

Publications and source records attributed to D Y Graham.

At least 505 records · Page 28Linked to original sources
PubMed1985

Controlled comparison of topical anesthetic agents in flexible upper gastrointestinal endoscopy.

Topical anesthetics are generally part of the premedication associated with upper gastrointestinal endoscopy. Selection is not usually based on objective criteria. We performed a randomized study comparing six anesthetic agents: three sprays (Cetacaine, Hurricaine, and 10% Xylocaine spray) and three gargles (2% lidocaine, and two combinations of 2% lidocaine diluted 1:1 with mouthwash). Normal subjects, experienced in undergoing gastroscopy, underwent repeated upper gastrointestinal endoscopic examinations with a 34 F Pentax fiberscope. Topical anesthetic was the only premedication used. The parameters evaluated by the subjects were taste, effectiveness of anesthesia, and ease of scope passage. At the end of the trial each subject ranked the agents in order of preference. Although subjects differed in their preference for the different anesthetic agents (sometimes significantly), there was no single parameter such as taste, degree of anesthesia, or ease of passage of the endoscope that could be correlated with overall preference. All agents gave acceptable levels of local anesthesia, although there was a distinct subjective preference for spray forms. We recommend that if a local anesthetic is used, it should be one of the spray formulations. This recommendation is based on safety, the relative ease of application, and the lack of profound differences between agents.

Adult↗
PubMed1985

Nonsteroidal anti-inflammatory effect of sulindac sulfoxide and sulfide on gastric mucosa.

Gastric injury resulting from nonsteroidal anti-inflammatory drugs is thought to require direct contact of the drug with the gastric mucosa. An inactive form of a drug (as a prodrug) should protect against mucosal damage. Because sulindac sulfoxide has little effect on prostaglandin synthesis until it is reduced to sulindac sulfide after absorption, we performed a double-blind, crossover endoscopic study in 15 normal subjects to compare the prodrug sulindac sulfoxide (200 mg b.i.d.), the active sulfide metabolite sulindac sulfide (100 mg b.i.d., which yields similar sulfide blood concentrations), a positive control (aspirin, 650 mg q.i.d.), and a negative control (placebo). Each drug was taken for 1 week and gastric mucosa were endoscopically assessed before and after 2, 5, and 7 days of dosing. Aspirin predictably damaged the gastric mucosa, whereas the effects of sulindac sulfoxide and sulindac sulfide could not be distinguished from those of the placebo. We conclude that sulindac sulfoxide as a prodrug is not directly responsible for the reduced severity of gastric mucosal lesions. Both sulindac sulfoxide and sulindac sulfide are poorly soluble in acid gastric contents and the reduced damage may relate to the inability of high concentrations of the drug to enter gastric mucosal cells.

Administration, Oral↗
PubMed1985

Biotin-avidin amplified ELISA for quantitation of human IgA.

A biotin-avidin amplified enzyme-linked immunosorbent assay (ELISA) for the measurement of human IgA in serum, colostrum, gastric juice, and supernatants of in vitro mitogen-stimulated human peripheral blood mononuclear cells is described. The ELISA reproducibly detects as little as one nanogram of IgA in a fifty microliter sample (20 ng/ml).

Avidin↗
PubMed1985

Detection of rotaviruses by nucleic acid hybridization with cloned DNA of simian rotavirus SA11 genes.

We developed a dot-blot hybridization assay to detect rotaviral RNA sequences in tissue culture or in clinical samples. 32P-labeled cloned cDNA probes of the simian rotavirus SA11 specifically detected rotaviral RNA sequences and were more sensitive for detecting SA11 than was the commercial enzyme-linked immunosorbent assay Rotazyme test. A full-length probe of SA11 gene 6 detected 2.5 X 10(5) SA11 particles or approximately 0.27 ng of purified SA11 dsRNA. Combined probes from genes 6 and 9 detected 0.135 ng of purified SA11 dsRNA. The assay detected group A rotaviruses from different subgroups and serotypes, but the sensitivity of RNA detection varied from 0.5 to 31 ng when RNA from heterologous strains of virus was analyzed. An analysis of coded stool samples correctly identified 31 (91%) of 34 samples positive for rotavirus by electron microscopy and 100% of 26 samples negative for rotavirus by electron microscopy. Preliminary experiments also showed the assay has potential to directly characterize (subgroup and serotype) rotaviral isolates.

Cloning, Molecular↗
PubMed1985

Preparation for barium enema: comparison of a commercial formula diet and low-residue, clear-liquid diets in inpatients.

The barium enema examination is the most frequently done initial diagnostic evaluation for disease of the lower gastrointestinal tract. Adequate preparation of the colon is essential because inadequate preparation necessitates repetition, with patient discomfort, decreased caloric intake, and increased cost. A formula diet (Ensure) has been reported as superior to the usual low-residue, clear-liquid diet for bowel preparation. We evaluated the feasibility of using this formula diet in a general medical inpatient population. We found no significant difference in the quality of preparation (72% and 76% optimal or adequate preparation, respectively) for our inpatient population. The formula diet has several theoretical advantages, including a greater number of calories, lower cost, and better patient acceptance.

Barium Sulfate↗
PubMed1985

Healing of benign gastric ulcer: comparison of cimetidine and placebo in the United States.

Recently the Food and Drug Administration approved cimetidine for the treatment of benign gastric ulcer. Approval was based in part on the results of our large multicenter trial involving 172 patients with benign gastric ulcer between 0.5 and 2.5 cm in diameter: 87 were randomly assigned to receive cimetidine (300 mg four times daily) and 85 to receive placebo. Cimetidine treatment resulted in significantly more rapid healing than placebo; after 2 and 6 weeks of therapy, 10.0% and 44.8% of patients receiving placebo were healed, as compared to 22.6% and 65.1% receiving cimetidine. The results of our study were compared with the time-response curve previously published (0, 4, and 8 weeks of therapy). The combined data yielded linear healing rates for the first 8 weeks of therapy (r greater than 0.99 for both cimetidine and placebo). These studies can be used to define expectations for healing of benign gastric ulcer, and we recommend follow-up intervals of 8 and, if unhealed, 16 weeks.

Adult↗
PubMed1984

Cimetidine, cigarette smoking, and recurrence of duodenal ulcer.

Three hundred seventy patients with recently healed duodenal ulcer entered into a one-year, double-blind, randomized multicenter trial comparing placebo with three different dose schedules of cimetidine (200 mg twice a day, 300 mg twice a day, and 400 mg at bedtime) for the prevention of recurrent duodenal ulcer. By the end of one year, the cumulative symptomatic recurrence rate as demonstrated by endoscopy was similar for the patients receiving the three dosages of cimetidine (19 per cent, 15 per cent, and 13 per cent, respectively; not significant), whereas the placebo-treated group had a 34.7 per cent symptomatic recurrence rate (P less than 0.01 as compared with each cimetidine group). Cigarette smoking was found to be an important variable; among the placebo recipients ulcer recurrence was significantly more likely in smokers (72 per cent) than in nonsmokers (21 per cent, P less than 0.001). The frequency of ulcer recurrence in smokers was significantly reduced by treatment with cimetidine (from 72 per cent to 34 per cent, P less than 0.). Smokers who received cimetidine were at least as likely to have a recurrence as were nonsmokers who received placebo (34 per cent vs. 21 per cent, not significant). Thus, smoking appears to be a major factor in recurrence of duodenal ulcer, and in smokers, giving up smoking may be more important in the prevention of ulcer recurrences than administration of cimetidine.

Cimetidine↗
PubMed1984

In vitro adsorption of bile salts and aspirin to sucralfate.

Sucralfate, an aluminum salt of sulfated sucrose, is a new drug designed for the treatment of peptic ulcer. Sucralfate has been reported to be useful in a variety of situations including prevention of aspirin-induced gastric mucosal damage. We investigated the in vitro adsorption of bile salts or aspirin to sucralfate in environments simulating the stomach (pH 1.5), small intestine (pH 7), and colon (pH 7.8). Bile salts were incubated with sucralfate, and the quantity of bile salt adsorbed was calculated by subtraction from the amount remaining in solution after centrifugation at 12,500g for 30 min. Adsorption experiments were performed in bile salt solutions at pH 1.5 and 7.0 with 0-10 g/dl sucralfate using glycocholate, glycochenodeoxycholate, taurocholate, taurodeoxycholate, or taurochenodeoxycholate. The dihydroxy-unconjugated bile salts, deoxycholic, and chenodeoxycholic salts were tested at pH 7.8. Binding capacity (micromoles per gram sucralfate) was calculated from the linear regression of micromoles bound vs grams sucralfate incubated. Sucralfate adsorbed all bile salts tested (except taurocholic acid at pH 1.5) but was less effective than cholestyramine. Sucralfate does not adsorb sufficient bile salts at neutral pH to cause bile salt depletion. Aspirin was minimally adsorbed by sucralfate [7.5 mumol (1.4 mg)/g sucralfate, pH 1.5], and thus adsorption of aspirin does not explain the protective effect of sucralfate against aspirin injury.

Adsorption↗
PubMed1984

Pathogenesis of rotavirus-induced diarrhea. Preliminary studies in miniature swine piglet.

The pathogenesis of diarrhea caused by rotavirus infection was studied in miniature swine piglets. The animals were inoculated orally with 2 X 10(7) plaque-forming units of porcine rotavirus (OSU strain). During the height of diarrhea, intestinal function was investigated by in vivo perfusion of a 30-cm segment of proximal jejunum and a 30-cm segment of distal ileum. Absorption of Na+ and water decreased and 3-O-methylglucose transport was markedly reduced, P less than 0.01 compared to control animals. Mucosal lactase and sucrase levels were depressed in both the jejunum and ileum, P less than 0.001. Na+,K+-ATPase activity was significantly depressed only in the ileum, P less than 0.001. These changes were associated with a marked reduction in villous height, suggesting that the diarrhea could be an osmotic diarrhea due to nutrient (carbohydrate) malabsorption. Fresh stool samples were obtained and analyzed immediately for NA+,K+, osmolarity, glucose, and lactose; the osmotic gap was also determined. Stool osmolarity continually increased from 248 +/- 20 mosm/liter prior to inoculation to 348 +/- 20 mosm/liter at 75 +/- 1 hr postinoculation (P less than 0.005); the majority of the fecal osmotic gap could be accounted for by the amount of lactose present in the stools. Stool sodium increased from 34 +/- 6 mM prior to inoculation to a maximum of 65 +/- 4 mM at 53 +/- 1 hr postinoculation, P less than 0.001. There was no significant change in potassium concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Ultrastructural localization of rotavirus antigens using colloidal gold.

Colloidal gold was used to localize six of the ten known proteins of the simian rotavirus SA11 within infected cells by ultrastructural immunocytochemistry. Monospecific or monoclonal antibodies to selected structural and nonstructural proteins were the primary antisera. The major outer capsid glycoprotein, VP7, was associated with nonenveloped particles, with particles de-enveloped by Triton X-100 and with both nuclear and cytoplasmic inclusions. The protease-sensitive outer capsid protein, VP3, was also found on nonenveloped and de-enveloped particles. The major inner capsid protein, VP6, was accessible to antibodies on some of the nonenveloped particles (presumably single-shelled particles) and on the de-enveloped particles. A monospecific antibody to the gene 11 product, believed to be a precursor to a minor structural protein, VP9, reacted strongly with viroplasmic inclusions. Virus particles were weakly labeled by this antibody. NS35, a nonstructural SA11 protein, was found only in the viroplasms. NS29, a nonstructural glycoprotein, was localized to the cytoplasmic side of the endoplasmic reticulum membrane and to the inside of enveloped virus particles. These data support the hypothesis that NS29 facilitates budding of the virus particles and acquisition of the outer capsid layer.

Animals↗
PubMed1984

Search for evidence of a viral aetiology for inflammatory bowel disease.

The aetiology of the inflammatory bowel diseases. Crohn's disease, and ulcerative colitis, is still obscure. A viral aetiology has been proposed, based in part on reports that filtrates prepared from tissues of patients with inflammatory bowel disease induce cytopathic effects in tissue culture cells. Our attempts to culture viruses in many cell lines from filtrates prepared from the tissue of 95 patients have been negative, except for one case in which cytomegalovirus was isolated from the tissue of a Crohn's disease patient. Our studies confirm previous reports that intestinal tissue filtrates induce cytopathic effects in inoculated cell cultures, but the effect we observed is non-specific; cytopathic effects were induced in most cell lines tested and with similar frequency irrespective of whether the intestinal filtrates were prepared from Crohn's disease patients, ulcerative colitis patients, or non-inflammatory bowel disease controls. Electron microscopy studies of tissue culture cells exhibiting cytopathic effects have not revealed virus particles. Characterisation of the cytopathic effect inducing factor showed that it was incapable of serial passage in tissue culture, too small to be a conventional virus, resistant to inactivation by ultraviolet light, and heat stable. Our results suggest that the observed cytopathic effect was caused by a non-replicating cytotoxic factor, or factors, released from intestinal tissues of both inflammatory bowel disease and non-inflammatory bowel disease patients.

Animals↗
PubMed1984

RNA electropherotypes of human rotaviruses from North and South America.

Between April 1979 and December 1982, viral agents were found in 231 of 695 children admitted to the Texas Children's Hospital with gastroenteritis. Electron microscopic analysis showed that rotaviruses were the most common viral agents, and a seasonal pattern of rotavirus disease was observed. The migration patterns of the RNA segments of these rotaviruses on electrophoresis in polyacrylamide gels were compared with those of rotaviruses collected from other areas of the United States of America and from Argentina, Colombia and Mexico. A number of different RNA electropherotypes were found, including some patterns not previously reported.

Child↗
PubMed1984

Administration of purified colonization factor antigens (CFA/I, CFA/II) of enterotoxigenic Escherichia coli to volunteers. Response to challenge with virulent enterotoxigenic Escherichia coli.

Colonization factor antigens (CFAs) were administered orally to volunteers, and the mucosal immune response was assessed by measuring secretory immunoglobulin A (IgA) in saliva and intestinal secretions and by challenge with virulent enterotoxigenic Escherichia coli (ETEC). A combination of CFA/I and CFA/II (8 mg each) administered orally in four doses in milk failed to induce a mucosal IgA response and also failed to protect against challenge with CFA-positive ETEC. When CFA was administered orally (1.5 mg divided into three doses with bicarbonate) to volunteers without preexisting serum anti-CFA levels, it failed to elicit a serum IgG or intestinal secretory IgA response or to protect against challenge with virulent ETEC. The CFA is destroyed by acid gastric contents but it induced significant antibody titer rises in 8 of 11 (73%) volunteers with preexisting serum anti-CFA IgG levels after oral administration of 1 mg of CFA/I with sodium bicarbonate. Subcutaneous priming (50 micrograms CFA/I) did not induce a serum IgG response but, when followed by oral boosting (1 mg CFA/I in two divided doses with sodium bicarbonate), induced intestinal anti-CFA secretory IgA in 4 of 8 volunteers and protected against challenge with CFA/I-positive ETEC. These results, although preliminary, are encouraging and demonstrate that it may be possible to develop an effective oral vaccine based on soluble nonreplicating antigens such as purified CFAs.

Administration, Oral↗
PubMed1984

The Hemo-matic Analyzer: a new occult blood testing device.

It is now recognized that screening for fecal occult blood is useful to alert the clinician to possible colon cancer in an early stage. The guaiac impregnated card is not widely used because patients must maintain strict diets omitting red meat, peroxidase-containing foods, iron supplements, and ascorbic acid. The Hemo-matic Analyzer uses a special filter to adsorb fecal Hb which is then automatically washed free of interfering substances and quantitatively identified. The filter electrostatically binds Hb and not pepsinized blood or substances that interfere with occult blood testing. We evaluated the sensitivity of this device and compared it to the Hemoccult II test in vivo and in vitro. It was approximately six times more sensitive than Hemoccult II and was not influenced by the presence of ascorbic acid, plant peroxidase, or ingestion of a large quantity of rare red meat. In addition, the samples remained positive more than 10 wk after preparation. The Hemo-matic Analyzer is a useful new device that offers many advantages over Hemoccult card testing for screening for colon cancer.

Adult↗