Conflict of interest issues pertinent to Veterans Affairs Medical Centers.

Conflicts of interest exist when an arrangement potentially exerts inappropriate influence on decision making or professional judgment, or is perceived to do so, and can thus damage the public trust and undermine the integrity of those decisions. Concerns regarding financial conflicts of interest in the medical arena have reached their height as of late, given that physicians now function in a milieu of complex and delicate relationships with pharmaceutical, biotechnology, and medical device industries. Even when such relationships do not correlate with actual compromise of judgment or patient care, it threatens the credibility of both the health care professional and the institution because of the social perception of the effect of these relationships. Although most institutions in the Western world set forth a code of ethics and conflict-of-interest policies to be followed under threat of termination, the Veterans Health Administration (VHA) presents itself as a unique environment in which conflicts of interest are subject to governmental laws, violation of which may not only result in employment-related discipline, but may be sanctioned by civil and criminal penalties. Moreover, these provisions are developed by a national authoritative organization rather than being institution-specific guidelines. Given that many academic physicians working within the VHA may also have a component of their practice in a University setting, it becomes important to understand the differences in policy between these contexts so as not to threaten the public trust in the veracity of decisions made and, therefore, maintain the integrity of the relationship between physician and patient. This article will review aspects of conflict-of-interest policies in the realm of research, financial relationships, foreign travel, and vendor contracting that are particular to the VHA and make it a unique environment to function in as a physician and scientist.

Functional evaluation of the grafted wall with porcine-derived small intestinal submucosa (SIS) to a stomach defect in rats.

BACKGROUND: Small intestinal submucosa (SIS) represents a novel bio-scaffolding material that may be used to repair hollow-organ defects. However, it is unclear whether neurophysiologic responses return to SIS-grafted areas in the gut. We evaluated the functional recovery of a stomach defect grafted with the porcine-derived SIS. METHODS: Twelve rats had a full-thickness defect created in the stomach. SIS was secured to the gastric wall. After 6 months, muscle strips were harvested from within the grafted area to perform both a histologic and a functional study. Additional full-thickness muscle strips were harvested from the posterior in the same stomach as controls. A dose response curve was obtained with carbachol (CCH) or sodium nitroprusside (SNP). Activation of intrinsic nerves was achieved by electrical field stimulation (EFS). RESULTS: The response to CCH and amplitude in EFS showed tonic contraction in both controls and SIS strips in a concentration-dependent and frequency-dependent manner. The magnitude after each stimulation was significantly lower in SIS strips compared with controls (P < .01). However, the contraction ratio of EFS to ED(50) of CCH was not significantly different between the groups. Additionally, SNP produced relaxation in both strips in a concentration-dependent manner. Histologic findings revealed that an insufficient amount of smooth-muscle cells existed in the muscularis propria, whereas compensated growth was observed in the submucosa with nerve regeneration. CONCLUSIONS: This study demonstrates that SIS provides a template for nerve migration to the graft in the rodent stomach. Innervations showed a similar distribution to that observed in the controls. The clinical implications of such findings warrant additional investigation.

Clinical application of porcine small intestinal submucosa in the management of infected or potentially contaminated abdominal defects.

The repair of abdominal wall defects in potentially contaminated or grossly infected fields presents a difficult clinical problem. Polypropylene mesh is relatively contraindicated in these settings because of the potential for chronic infection. The alternatives to polypropylene include polyglactin mesh, which is not associated with chronic infection but is associated with a 100% recurrence of hernia. The ideal prosthetic for this patient group should be resistant to infection and ensure a low rate of hernia recurrence. We studied the use of small intestinal submucosa, which has been reported to be resistant to infection and incorporates into the fascia over 3 to 6 months, in 20 patients with ventral or inguinal hernias (18 ventral, 2 inguinal hernia) in the setting of bacterial contamination. The early postoperative complication rate was 50%. One patient with fasciitis had degradation of the small intestinal submucosa and loss of the bioprosthesis within 7 days. Other early complications included seroma (n=2), ileus (n=1), and wound infection (n=8). No patient experienced chronic infection. Mean follow up was 15.7 months and the rate of recurrence documented by CT or physical examination was 30%. We concluded the following: (1). small intestinal submucosa is an effective alternative bioprosthesis in the management of ventral/inguinal hernia when there is associated bacterial contamination; (2). human vs. pig immune response has not been seen in this patient population; (3). early graft failure due to overwhelming fascial infection was noted in one patient and may be a limitation of this technology in a minority of patients; and (4). early hernia recurrence is relatively low but long-term follow-up has not been completed.

Evaluation of porcine-derived small intestine submucosa as a biodegradable graft for gastrointestinal healing.

High-risk anastomoses in the gut may benefit from the application of a synthetic reinforcement to prevent an enteric leak. Recently a porcine-derived small intestine submucosa (SIS) was tested as a bioscaffold in a number of organ systems. The aim of this study was to evaluate the effectiveness of SIS in stimulating healing in the stomach. Twelve rats underwent surgical removal of a full-thickness gastric defect (1 cm) and subsequent repair with a double-layer patch of porcine-derived SIS. The graft was secured with interrupted sutures placed within 1 mm of the edge of the graft. After 21 days, the animals were killed and their stomachs harvested for histologic examination. Cross sections were processed for paraffin embedding and 4-micron sections were stained with hematoxylin and eosin. All animals survived, gained weight, and demonstrated no signs of peritonitis over the 3-week postoperative period. On postmortem examination, the defect was completely closed in all animals by granulation tissue and early fibrosis. Although most of the luminal surface of the grafted areas remained ulcerated, early regeneration of normal gastric mucosa was seen at the periphery of the defect. SIS may act as an effective scaffolding agent for intestinal mucosa and may offer protection in high-risk anastomoses.

Celecoxib (celebrex) increases canine lower esophageal sphincter pressure.

BACKGROUND: Prostaglandins inhibit the contraction of gastrointestinal smooth muscle and may decrease lower esophageal sphincter tone. The purpose of this study was to determine whether the cyclooxygenase-2 inhibitor celecoxib (Celebrex) could increase lower esophageal pressure (without affecting gastric emptying) compared to placebo and cisapride (Prepulsid), a compound previously used to treat reflux disease. MATERIALS AND METHODS: Six mongrel dogs were assigned to receive celecoxib, cisapride, and placebo using a randomized cross-over design with a 1-week washout period between treatments. Prior to dosing, each dog underwent an esophagopexy to provide access to the esophagus and stomach. On the fourth day of dosing, sphincter tone was measured in awake unsedated dogs using radial manometry. In a different set of six dogs, liquid and solid gastric emptying rates were scintigraphically determined. RESULTS: Celecoxib significantly increased mean and average maximum lower esophageal pressures compared to placebo without affecting the gastric emptying rate. The magnitudes of these increases were similar to that produced by cisapride. CONCLUSIONS: Celecoxib had a positive effect on canine lower esophageal sphincter tone. This finding, combined with the drug's low incidence of gastrointestinal toxicity, suggests that celecoxib may warrant consideration and investigation as a pharmacotherapy for human reflux disease.