Margaret E. Bonsack

Abdominal adhesions to prosthetic mesh evaluated by laparoscopy and electron microscopy.

BACKGROUND Most adhesion experiments involve observations at a single time point. We developed a method to evaluate abdominal adhesions to surgical mesh by sequential laparoscopy. STUDY DESIGN An abdominal wall defect was created in rats and repaired with polypropylene mesh. Sequential laparoscopic evaluation of adhesion formation was performed in each animal. The percentage of mesh area involved was scored (0% to 100%). At various time intervals animals were sacrificed and samples were obtained for light and scanning electron microscopy. RESULTS Adhesions were already present on day 1, increased by day 7, and did not progress thereafter. Mesh surfaces free of adhesions were covered with a confluent mesothelial cell layer, first seen by scanning electron microscopy on day 5 and complete by day 7. CONCLUSIONS Intraabdominal adhesions are best studied by sequential laparoscopy. Adhesions develop within 1 day of prosthesis placement. Adhesion-free surfaces are carpeted with mesothelial cells by day 7 and remain free thereafter, for duration of study.

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.

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.

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.

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.

Adrenal Corticosteroids Cause Gastrin Cell Hyperplasia

Chronic exogenous high dose adrenal cortical steroid administration to dogs resulted in a 137% increase in G-cell mass with an associated enhancement of peak serum gastrin levels. Adrenalectomy caused a halving of G-cell numbers without significant changes in serum gastrin levels. Adrenal cortical steroids appear to have an important trophic role for the G-cell.

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.

Two Experimental Models for Generating Abdominal Adhesions

PURPOSE To develop dependable rat models for generating abdominal adhesions that allow for objective evaluation and quantification. METHODS Two adhesion models were devised and compared with conventional side-wall models involving cecal abrasion and peritoneal excision or abrasion. model T (tissue): removal of a 2.5 by 2.5 cm segment of full-thickness abdominal wall with overlying skin closure, exposing the viscera to subcutaneous tissue; model M (mesh): removal of an identical segment, replacing the defect with a 2.5 by 2.5 cm polypropylene mesh sewn to the cut edges. This exposed the viscera directly to the mesh surface. Seven days after operation, the character and extent of the adhesions were assessed at autopsy. Results were expressed as the percent area of subcutaneous tissue involved (T) or of mesh surface involved (M). For model T the percent involvement of the circumference of the defect edge was also recorded. The extent of omental and intestinal adhesions were evaluated individually. RESULTS The classical side-wall models showed inconsistent patterns of adhesion formation and were difficult to evaluate. Every animal from both models M and T developed extensive adhesions. The mean coverage of mesh surface (M) was 93% and subcutaneous surface (T) 82%. In model T the mean involvement of the defect cut edge was 80% of the circumference. All model T animals had both intestinal and omental adhesions whereas there were no intestinal attachments in model M. Tenacity of adhesions did not differ significantly between animals or models. CONCLUSIONS Adhesion models M and T are consistent, predictable, and dependable. They each yield extensive adhesion coverage to a defined site, which allow for standardized measurement.

Gastrin cell populations after highly selective vagotomy in the dog.

Highly selective vagotomy was performed on five dogs. Postoperatively, gastrin cell (G cell) hyperplasia occurred in all dogs. Mean preoperative G cell numbers increased from 350 to 530/cm mucosal length (p less than 0.02). Antral tissue gastrin also increased by 100 per cent (6.7 x 10(6) to 13.7 x 10(6) pg/gm tissue, p less than 0.05). Basal and stimulated serum gastrin were unchanged following highly selective vagotomy. The cause for G cell hyperplasia is not clear, but is probably multifactorial.

Radioprotection of the Intestinal Mucosa of Rats by Probucol

Probucol is a lipid-regulating drug that also has antioxidant properties. This study was designed to test the possibility that probucol could provide radioprotection of the intestine when administered either intralumenally or systemically. Tissue damage was evaluated histologically by quantifying the number of crypts per circumference and the mucosal height. Animals were sacrificed 5 days after 11 Gy of X irradiation. In one series of experiments, a loop of mid small bowel was exteriorized operatively and compartmentalized into segments, each filled with probucol or saline. Intralumenal administration of probucol prior to irradiation led to a significantly greater number of crypts per circumference and mucosal height compared to saline-filled irradiated controls. In another series of experiments, five groups of rats were irradiated: (1) probucol in the small bowel lumen, (2) intravenous probucol, (3) probucol by gavage, (4) probucol added to standard rat chow and (5) saline control. In the rats given probucol intravenously prior to X irradiation, crypt numbers and mucosal height were significantly enhanced. Probucol given by gavage also resulted in protection. Rats fed a diet containing probucol showed no significant protection. Topical administration was more effective than systemic. Probucol protects the intestinal mucosa from acute radiation damage when given topically, intravenously or by gavage, but does not do so when given as a dietary supplement.