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Biomedical subjects

J P Delaney

Publications and source records attributed to J P Delaney.

At least 19 recordsLinked to original sources
PubMed1995

Intestinal radioprotection by vitamin E (alpha-tocopherol).

OBJECTIVES: The major objective of this study was to test vitamin E as a potential radioprotectant for the small bowel of the rat. SUMMARY BACKGROUND DATA: Vitamin E has previously been shown to provide radioprotection in animal models: increased survival after whole-body irradiation, diminished absorptive malfunction, and modest diminution in postirradiation hemolysis. The lumenal route for intestinal radioprotection has not been tested. METHODS: Rat mid-small bowel was surgically exteriorized and segmented by ties into compartments, each of which was filled with a test solution 30 minutes before 1100 cGy of x-irradiation was administered. After the rats were killed 5 days later, the various segments were evaluated for surviving crypts, mucosal height, and goblet cell preservation. Lumenal agents included alpha-tocopherol phosphate and alpha-tocopherol acetate. In a separate study, dietary supplements of alpha-tocopherol were given for 10 days before irradiation, and the same irradiation sequence was carried out. RESULTS: Small bowel crypt cell numbers, mucosal height, and goblet cell numbers were significantly protected from radiation effects by dietary alpha tocopherol pretreatment and by lumenal application of the vitamin. CONCLUSIONS: These studies indicate that vitamin E can serve as a partial protectant against acute irradiation enteritis, whether given as chronic oral systemic pretreatment or as a brief topical application.

Animals↗
PubMed1994

Radioprotection of the rat small intestine with topical WR-2721.

BACKGROUND: The classic radioprotectant WR-2721 has been shown to reduce the severity of small bowel injury when administered systemically shortly before irradiation is delivered. This study tested the possibility that WR-2721 could provide protection when applied topically to intestinal mucosa. The second question addressed was the influence of pH on the effectiveness of this agent. METHODS: The model used involved irradiation of exteriorized rat small bowel. A length of intestine was compartmentalized. The various individual segments were filled with a lumenal Tris buffer (pH 9), WR-2721, or a combination of these two, then irradiated with 1100 cGy. The animals were sacrificed 5 days later. Surviving crypt cells and mucosal height were the criteria used to quantitate mucosal injury. RESULTS: The pH 9 buffer alone provided a small (16%) but significant preservation of crypt cell numbers. WR-2721 improved crypt survival by 54% at neutral pH, 83% at pH 9. CONCLUSIONS: These data indicate that WR-2721, when applied topically to the small bowel mucosa of the rat before irradiation, provides substantial protection against radiation damage. The degree of benefit is amplified greatly when the drug is in an alkaline medium.

Administration, Topical↗
PubMed1994

Misoprostol in the intestinal lumen protects against radiation injury of the mucosa of the small bowel.

Systemically administered misoprostol, a PGE1 analog, has been shown to be an intestinal radioprotector. The purpose of this study was to determine if administration of misoprostol into the intestinal lumen can also reduce the severity of acute radiation enteritis. The rat small bowel was operatively exteriorized and segmented by means of suture ties. The remainder of the intestine and the rat were shielded in a lead box. Misoprostol was introduced into the lumen in various doses. After 30 min exposure to misoprostol, the isolated, exteriorized, segmented bowel was subjected to 11 Gy X irradiation. Five days later the animals were sacrificed and the intestines harvested for evaluation. Surviving crypt numbers per circumference and mucosal height were the criteria used for quantification of damage. Mucosa exposed to misoprostol at the time of radiation delivery showed significantly increased crypt numbers and mucosal height compared to adjacent saline-filled intestine.

Animals↗
PubMed1992

The influence of lumenal pH on the severity of acute radiation enteritis.

The severity of acute radiation injury to small bowel mucosa was studied as a function of lumenal pH at the time of irradiation. Rats were anaesthetized and 15 cm of mid small bowel was exteriorized with the rest of the animal and intestine shielded in a lead box. The target intestine was segmented into three portions, each of which was filled with Tris buffer, adjusted to pH 5, 7 and 9 respectively. Twenty minutes later the exteriorized bowel was given 1100 cGy X-irradiation. Rats were sacrificed 4, 5 and 6 days later and the intestine histologically assessed for injury. The indices of injury were surviving crypt numbers, mucosal height and mucus-containing goblet cells. To verify that pH was the critical variable an identical study was done employing three buffers chemically different from Tris: MES (pH 5.5), ADA (pH 7), and CAPSO (pH 9). These animals were sacrificed 5 days postirradiation. For all three parameters, and on each day postirradiation, the pH 9 segment showed less damage than did the segments with lumenal pH 7 or 5. We conclude that lumenal pH at the time of irradiation plays a significant role in the severity of acute mucosal injury. Alkaline pH is relatively protective.

Animals↗
PubMed1992

Intestinal radioprotection by two new agents applied topically.

The purpose of this study was to test two novel antioxidant drugs, each capable of inhibiting membrane peroxidation and of free radical scavenging, as topical radioprotectants for the intestine. A loop of rat midintestine was exteriorized and radiated while the remainder of the animal was protected in a lead box. The intestine was first compartmentalized and each segment filled with a test solution. Radiated segments of intestine were compared, drug filled with vehicle filled, and both with normal unradiated intestine. The animals were killed 5 days after 1100 cGy radiation to the exteriorized loop. Crypt numbers and mucosal height were used as the measures of injury protection. On the basis of crypt numbers, the 21-amino steroid (U-74500A) gave approximately 40% and the vitamin E-like compound (U-78518F) gave 60% reduction in crypt loss. The authors conclude that lumenal antioxidant drugs can provide partial protection of the intestinal mucosa from acute radiation damage and that these two specific agents are effective and potentially useful.

Animals↗
PubMed1992

Acute radiation enteritis in rats: bile salts and trypsin.

Surgically exteriorized rat intestine divided into segments containing saline solution, a bile salt binder, or a trypsin inhibitor were radiated (1100 cGy) and subsequently evaluated for histologic damage. Five days after radiation, crypt cell numbers, mucosal height, and mucous cell numbers were significantly greater in segments protected by the binding of bile salts or the absence of trypsin activity compared with saline-bathed mucosa. Thus both proteolytic enzymes and bile salts in the lumen contribute to the acute enteritis that follows a single dose of x-radiation.

Acute Disease↗
PubMed1990

Linkage of the multiple endocrine neoplasia type 2B gene (MEN2B) to chromosome 10 markers linked to MEN2A.

The syndrome of multiple endocrine neoplasia type 2B (MEN 2B) resembles that of MEN 2A in that both include medullary carcinoma of the thyroid, pheochromocytoma, and autosomal dominant inheritance, but is distinct in that MEN 2B patients have neuromas of the mucous membranes. MEN2A has been linked to RBP3, D10S5, FNRB, D10S15, and D10Z1 near the centromere of chromosome 10. We examined linkage between MEN2B and RFLPs on chromosome 10 in all available members in two or three generations of 14 kindreds. The centromere marker D10Z1 was linked to MEN2B with a peak lod score of 5.42 at theta = 0.02. One possible recombinant was observed between D10Z1 and MEN2B. Multipoint analysis of RFLPs at FNRB, D10Z1, RBP3, and D10S15 gave a peak lod score of 7.12 at the midpoint between D10Z1 and RBP3 on the long arm (band q11). The most likely gene order FNRB-D10Z1-MEN2B was 27 times more likely than MEN2B-FNRB-D10Z1 and 31/2 times more likely than FNRB-MEN2B-D10Z1. Additional data will be required to establish the order of these loci with confidence.

Chromosomes, Human, Pair 10↗
PubMed1989

Axillary dissection: use of a mechanical retractor.

Operative axillary exposure can be conveniently maintained by means of a table-based retractor which serves to displace the pectoral muscles medially. The shoulder is abducted and the arm hung from the horizontal cross bar of the device. By means of this method, complete axillary clearance can be accomplished with less assistance and improved visibility for the participants.

Axilla↗
PubMed1989

Abdominal radiation causes bacterial translocation.

The purpose of this study was to determine if a single dose of radiation to the rat abdomen leads to bacterial translocation into the mesenteric lymph nodes (MLN). A second issue addressed was whether translocation correlates with anatomic damage to the mucosa. The radiated group (1100 cGy) which received anesthesia also was compared with a control group and a third group which received anesthesia alone but no abdominal radiation. Abdominal radiation lead to 100% positive cultures of MLN between 12 hr and 4 days postradiation. Bacterial translocation was almost nonexistent in the control and anesthesia group. Signs of inflammation and ulceration of the intestinal mucosa were not seen until Day 3 postradiation. Mucosal damage was maximal by Day 4. Bacterial translocation onto the MLN after a single dose of abdominal radiation was not apparently dependent on anatomical, histologic damage of the mucosa.

Abdomen↗
PubMed1989

Neochondrogenesis in free intraarticular periosteal autografts in an immobilized and paralyzed limb. An experimental investigation in the rabbit.

The purpose of this investigation was to determine whether neochondrogenesis can be induced in free intraarticular autografts of periosteum in the complete absence of motion. In 17 adolescent rabbits, a rectangular graft of periosteum was elevated from the medial aspect of each proximal tibia and folded back on itself so that its deep (cambium) layer was facing outward on both sides. The grafts were transplanted into both ipsilateral knee joints that had been paralyzed by section of the femoral and sciatic nerves, and a cast was applied to one hind limb to provide immobilization. The opposite knee joint of each animal was then placed in the continuous passive motion (CPM) apparatus. At the time of death (21 days postoperatively), some degree of neochondrogenesis was evident in 69% of the grafts in the group with casts and in 100% of the grafts in the CPM group. Hyaline cartilage was the predominant tissue in 13% of the grafts in the group with casts compared to 63% of the grafts in the CPM group. Although this investigation has confirmed the chondrogenic potential of free periosteal grafts in a synovial fluid environment (and the significantly stimulating effect of CPM), the results have also demonstrated that at least some hyaline cartilage can be formed by periosteal grafts even with paralysis of the limb plus immobilization of the joint (presumably complete immobilization). Thus, other factors capable of stimulating neochondrogenesis warrant investigation.

Animals↗
PubMed1988

Effects of low amine diet on gastric endocrine cell proliferation in the rat.

The effects of a liquid diet low in amines on gastrin cell and somatostatin cell functions were studied in the rat. Significant decreases in portal gastrin levels (44% at 5 days) were noted in animals maintained on a liquid diet (Vivonex). Refeeding solid rat chow resulted in a significant, but transient, hypergastrinemia. Portal somatostatin levels were significantly increased during ingestion of the liquid diet. With refeeding, portal somatostatin promptly returned to baseline values. Gastrin cell density decreased progressively during liquid diet ingestion (37% decline by Day 5). Antral somatostatin cell numbers were increased during this time period (86% versus controls). With solid chow refeeding, both gastrin cell and somatostatin cell densities returned to baseline.

Amines↗
PubMed1988

Methylene blue protects intestinal mucosa from free radical-mediated sublethal radiation damage.

Susceptibility of the intestine to radiation damage is a primary reason for the failure of external beam radiation to cure intra-abdominal cancer. High-dose irradiation causes intestinal denudation, fluid loss, and resultant shock. Simple and effective methods for protecting the intestine from irradiation damage are not available. Many biological effects of ionizing irradiation are caused by free radical intermediates. We have previously reported that many of the toxicities of doxorubicin, a classic free radical generating anticancer agent, are blocked by methylene blue pretreatment. We have now found that pretreatment with methylene blue protects rats from intestinal damage, as measured histologically and by quantitative stool blood determinations. Whereas the exact mechanisms of this protection remain elusive, we believe this method of modulating the therapeutic index of ionizing radiation deserves additional preclinical and clinical study.

Animals↗
PubMed1988

Diverticulitis in the multiple endocrine neoplasia type II B syndrome.

Diffuse ganglioneuromatosis of the entire alimentary tract is a characteristic finding in the multiple endocrine neoplasia type II B syndrome. Symptoms and complications of colonic involvement are common. We report a 37-yr-old woman with multiple endocrine neoplasia type II B syndrome and a colovesical fistula complicating sigmoid diverticulitis.

Adult↗
PubMed1987

Cellular origin and evolution of neochondrogenesis in major full-thickness defects of a joint surface treated by free autogenous periosteal grafts and subjected to continuous passive motion in rabbits.

A graft of periosteum from the tibia of 27 rabbits was incubated in vitro with tritiated thymidine for 24 hours and then transplanted into a full-thickness defect in the patellar groove. The rabbits were managed after the operation on continuous passive motion (CPM), and the joints excised at intervals of two to 21 days. After one week the cells had begun to synthesize glycosaminoglycan and by two weeks the tissue resembled immature hyaline cartilage. Thymidine-labeled cells were seen throughout the entire regenerated tissue. The cellular origin of the hyaline-like tissue that filled the defects was the progenitor cells of the periosteal graft.

Animals↗
PubMed1985

Pancreatic islet cell carcinoma with gastrin and vasoactive intestinal polypeptide production.

The case history of a patient with an islet cell carcinoma, which produced both gastrin and vasoactive intestinal polypeptide (VIP), is presented. Although several examples have been observed of the combined production of these hormones by pancreatic endocrine tumors, few reports have related the clinical details of such cases. Resolution of diarrhea occurred in our patient after institution of nasogastric suction and cimetidine therapy, suggesting that gastric hypersecretion, rather than VIP activity, accounted for this problem. Chemotherapy with streptozotocin and 5-fluorouracil was highly effective in ameliorating clinical symptoms, diminishing serum levels of gastrin and VIP, and greatly reducing the bulk of metastatic disease in this case.

Adenoma, Islet Cell↗
PubMed1985

Proliferation of gastric endocrine cells after vagotomy in the rat.

The effects of truncal vagotomy on gastrin cell and somatostatin cell populations and circulating hormone levels were studied in rats. Truncal vagotomy produced significant gastrin cell hyperplasia, with the largest increase in gastrin cell density observed 2 weeks postvagotomy. Gastrin cell hyperplasia was sustained up to 6 months. Both antral somatostatin cell and corpus somatostatin cell numbers demonstrated significant and sustained increases after vagotomy; the largest increases were observed 2 weeks after operation. Early elevation of circulating gastrin to 3 times the baseline level was followed by sustained, lower level hypergastrinemia. Plasma somatostatin levels were decreased 2 days after vagotomy, with a return to control values 2 weeks after operation. Gastrin cells and somatostatin cells are dynamic populations, capable of changes in both number and secretory function after truncal vagotomy.

Animals↗
PubMed1985

The role of luminal pH in production of gastrin cell hyperplasia in the rat.

Truncal vagotomy is associated with diminished gastric acid production, gastrin cell hyperplasia, and elevated serum gastrin levels. To study the role of reduced antral luminal acidity in the production of gastrin cell proliferation, gastrin cell densities were quantitated in preparations involving exposure of the antral mucosa to a non-acid lumen at different levels of the gastrointestinal tract. Female Sprague-Dawley rats were divided into the following experimental groups: intact controls, shams, antral diverticulum on the jejunum, antral diverticulum on the ileum, and antral diverticulum on the colon. At death, 2 weeks, 2 months, and 6 months after operation, luminal pH was at least 5.8 for each group of rats with antral diverticula. No significant changes in gastrin cell numbers were observed in rats with jejunal or ileal diverticula. For those animals with colonic diverticula, gastrin cell counts were increased 55% at 2 weeks (503 +/- 23 cells per cm versus 320 +/- 13 cells per cm for shams). At 2 months gastrin cell numbers had increased further (639 +/- 54 cells per cm) in rats with antral diverticula on the colon. Gastrin cell proliferation was sustained at 6 months in this group. A factor other than reduced luminal acidity induces gastrin cell proliferation in antral mucosa exposed to colonic content. The responsible agent is not present in the small-bowel lumen. A non-acid luminal environment is not, by itself, a sufficient stimulus for gastrin cell hyperplasia.

Animals↗