Biomedical subjects

B DeYoung

Publications and source records attributed to B DeYoung.

6 recordsLinked to original sources

PubMed2000

Phase I trial of exisulind (sulindac sulfone, FGN-1) as a chemopreventive agent in patients with familial adenomatous polyposis.

Exisulind (sulindac sulfone; FGN-1), a metabolite of sulindac without known effects on prostaglandin synthesis, can promote apoptosis and inhibit tumorigenesis in preclinical systems. We performed a Phase I trial of this compound in patients with familial adenomatous polyposis (FAP) to examine the tolerability and safety of this drug in the cancer chemoprevention setting. Six patients each were treated with exisulind at doses of 200, 300, and 400 mg p.o. twice a day. Reversible hepatic dysfunction was noted in four of six patients treated at the 400-mg p.o., twice-a-day dose level, but in only one to two of six patients treated at each of the lower dose levels. The serum half-life of exisulind was 6-9 h; little drug accumulation was noted over time. A nonsignificant trend toward increased apoptosis in polyps was noted at the maximum tolerated dose, but no decrease in polyp numbers or significant effects on cellular proliferation was noted. After treatment, polyps tended to display a "halo" appearance grossly and mucinous differentiation histologically. The maximum safe dose of exisulind is 300 mg p.o. twice a day in patients with subtotal colectomies. Reversible hepatic dysfunction limits further dose escalation. A decrease in polyp numbers could not be demonstrated, but the trend toward increased apoptosis at the MTD and the observation of mucinous change histologically suggest that further investigation of drugs of this class might be warranted.

Adenomatous Polyposis Coli↗

PubMed1999

Sulindac sulfone induced regression of rectal polyps in patients with familial adenomatous polyposis.

Sulindac sulfone (Exisulind), a metabolite of the non-steroidal anti-inflammatory drug, sulindac, was evalauted for its effects on the development of rectal polyps in patients with familial adenomatous polyposis. Three cohorts of 6 patients each were given doses of 200, 300, or 400 mg Exisulind twice daily. Hepatotoxicity, shown by elevation in blood transaminase levels, was the dose-limiting toxicity and occurred at the 400 mg bid dose. Due to this toxicity, all patients treated with the 400 mg dose were subsequently reduced to the 200 mg dose level. Subsequently, 2 of the 6 patients were dose-escalated to 400 mg bid dose. The patients were treated with Exisulind for a period of six months. Sixteen of 18 patients had regression of small polyps (> or = 6 mm in diameter) characterized by a flattening of the polyps and a macular "halo" appearance. Histopathologic examination of the polyp biopsy specimens showed a marked increase in the proportion of mucin producing cells in the glands after treatment with Exisulind at all dose levels. Ki-67 staining, a measure of cell proliferation, was higher in the polyps than in normal mucosa. There was no significant change in the proliferation index between baseline and six month values in any of the groups treated with Exisulind or in normal tissues. The median apoptotic labeling index, as determined by the TUNEL technique, was higher in the polyps than in normal-appearing mucosa. Overall, there was no significant change in the apoptotic labeling index between base-line and 6 months in normal-appearing mucosa however, the index in polyps was increased. These results suggest that treatment of FAP patients with Exisulind for a period of six months may lead to regression of small polyps, and that the mechanisms of Exisulind--induced regression appear to be through stimulation of mucus differentiation and apoptosis in glandular epithelium.

Adenomatous Polyposis Coli↗

PubMed1997

Assessment of disseminated pancreatic cancer: a comparison of traditional exploratory laparotomy and radioimmunoguided surgery.

BACKGROUND: After curative resection for pancreatic cancer, only 10% of patients survive disease for 5 years. These dismal results suggest the presence of occult tumor at the time of initial operation. This phase I/II study was conducted to compare traditional exploratory laparotomy with radioimmunoguided surgery (RIGS) in the assessment of disseminated pancreatic cancer. METHODS: Ten patients with the diagnosis of adenocarcinoma of the pancreas were injected intravenously with 1 mg CC49 monoclonal antibody radiolabeled with 2 mCi iodine 125. All patients were evaluated by a standard abdominal exploration followed by RIGS. Tumor identified by each technique was documented and categorized as neoplasm disseminated to viscera or lymphatics. RESULTS: There were 25 visceral sites of disease that were traditionally discovered at the time of exploration including pancreas, omentum, small bowel, pelvis, liver, and other. All 25 sites of disease were positive by RIGS plus an additional four sites of visceral tumor for a total of 29 RIGS positive sites of disease. Six lymphatic sites of disease were discovered by traditional examination; however, 44 sites of lymphatic sites were documented by RIGS (p < 0.001). In addition, nine traditionally and pathologically negative/RIGS positive nodes were subjected to cytokeratin and MOC 31 immunohistochemistry. Six of nine nodes were positive by cytokeratin immunohistochemistry, and five of the six cytokeratin positive nodes were MOC 31 positive. CONCLUSIONS: These data suggest that the RIGS technique detected significantly more foci of visceral spread of tumor than traditional exploratory laparotomy and significantly more sites of lymphatic dissemination were identified by RIGS than by standard exploration.

Adenocarcinoma↗

PubMed1997

Generating autotetraploid sporophytes and their use in analyzing mutations affecting gametophyte development in the fern Ceratopteris.

The haploid gametophytes of the fern Ceratopteris richardii are autotrophic and develop independently of the diploid sporophyte plant. While haploid genetics is useful for screening and characterizing mutations affecting gametophyte development in Ceratopteris, it is difficult to assess whether a gametophytic mutation is dominant or recessive or to determine allelism by complementation analysis in a haploid organism. This report describes how apospory can be used to produce genetically marked polyploid sporophytes whose gametophyte progeny are heterozygous for mutations affecting sex determination in the gametophyte and a known recessive mutation affecting the phenotype of both the gametophyte and sporophyte. The segregation ratios of wild-type to mutant phenotypes in the gametophyte progeny of polyploid sporophyte plants indicate that all of the mutations examined are recessive. The presence of many multivalents and few univalents in meiotic chromosome preparations of spore mother cells confirm that the sporophyte plants assayed are polyploid. The DNA content of the sperm of their progeny gametophytes was also found to be approximately twice that of sperm from wild-type haploid gametophytes.

Alleles↗

PubMed1986

Pulmonary function in dogs with mitral valve regurgitation.

Mitral valve regurgitation was created in 2 groups of dogs. Groups were selected on absence (group 1) or presence (group 2) of clinical signs of congestive left ventricular failure. Group-2 dogs, in which mean left atrial pressures were greater than 30 mm of Hg, had increases in heart rate, pulmonary arterial mean pressure, left atrial diameter, and left ventricular diastolic diameter. These changes were associated with decreased arterial O2 tension, decreased static and dynamic compliance, reduced lung volumes, and increased pulmonary resistance. Group-1 dogs, in which mean left atrial pressure was less than 30 mm of Hg, had moderate changes in hemodynamics, but no changes in pulmonary function, except during exercise when arterial O2 tension decreased.

Animals↗

PubMed1979

Aortic interruption in a dog.

A 3-month-old English Bulldog was found to have a discontinuity between the ascending and descending aorta. There were no signs of illness associated with the interruption. The descending aorta was supplied with blood by collateral circulation. An aortic graft of woven synthetic material was surgically implanted to connect the ascending and descending aorta. Without any restrictions on the dog's activity, the dog has lived for over 1 year and continues to do well.

Animals↗