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Eric L R Bédard

Publications and source records attributed to Eric L R Bédard.

7 recordsLinked to original sources

Prevention of chronic renal allograft rejection by SERP-1 protein.

BACKGROUND: In previous studies we have demonstrated that Serp-1, a myxoma virus encoded serine protease inhibitor, dramatically inhibits neointimal hyperplasia in vascular injury and aortic transplant models. Here we examined the effect of peritransplant Serp-1 administration on chronic renal allograft rejection. METHODS: Rat renal transplants were performed with sequential recipient sacrifice on postoperative days 2, 10 and 140 to examine both the acute and chronic effects of Serp-1 in recipient rats. RESULTS: Serp-1 administration reduced early posttransplant injury (POD 2) with less acute tubular and vascular necrosis. This translated into a reduction of the characteristic late stage changes of chronic rejection (POD 140), with significantly decreased glomerulosclerosis and neointimal hyperplasia. Effects of Serp-1 treatment were already evident as early as POD 2 with markedly decreased levels of TGF-beta mRNA witnessed at both the early and late time points (POD 2, 10 and 140). CONCLUSION: We have demonstrated that peritransplant Serp-1 viral protein decreased early injury and allowed reduced chronic rejection in a rat renal model. Recipients treated with Serp-1 are associated with a decrease in TGF-beta mRNA levels in the allografts suggesting that the serine protease inhibitor may inhibit TGF-beta transcription and its profibrotic effects.

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Palliative laparoscopic resections for Stage IV colorectal cancer.

PURPOSE: Issues surrounding the safety and efficacy of palliative laparoscopic resections for patients with Stage IV colorectal cancer have not been explicitly examined in the literature. This article describes our experience with laparoscopic procedures for patients with Stage IV colorectal cancer and compares their perioperative outcomes to a contemporaneous group of patients with clinically curable (Stages I-III) disease. METHODS: A prospective database of laparoscopic resections for colorectal cancer performed between 1991 and 2002 was reviewed. Data regarding patient demographics, perioperative morbidity and mortality, operative times, conversion rates, and length of stay were extracted. Statistical analysis included chi-squared and Student's t-tests as required and P<or=0.05 was considered significant. RESULTS: A total of 375 cases were identified, of these 49 (13 percent) underwent laparoscopic palliative resections while 326 (87 percent) patients had resections for cure. When comparing palliative to curative procedures, there were no differences in intraoperative (4 percent vs. 9 percent) or postoperative complications (14 percent vs. 12 percent), perioperative mortality (8 percent vs. 4 percent), or length of hospital stay. Patients with Stage IV disease had larger tumors (5.4+/-2.3 cm vs. 4.6+/-2.6 cm, P=0.04) which contributed to an increased rate of conversion (22 percent vs. 11 percent, P=0.05) with most conversions secondary to tumor fixation or bulk (64 percent) preventing determination of resectability. CONCLUSIONS: A palliative laparoscopic resection is a safe and feasible option and presents acceptable morbidity and mortality in patients with Stage IV colorectal cancer. Importantly, in this difficult group of patients, our results compare favorably with those from previously published series of open procedures.

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Bleeding "downhill" varices: a rare complication of intrathoracic goiter.

We report a case of a 68-year-old woman with a 16-year history of a benign goiter. The patient presented with hematemesis and a clinically evident superior vena cava syndrome. Preoperative evaluation demonstrated upper esophageal varices and large posterior mediastinal goiter. The patient underwent successful resection of the mass with complete resolution of both the superior vena cava syndrome and "downhill" varices.

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Peritransplant treatment with cobalt protoporphyrin attenuates chronic renal allograft rejection.

Allogen-independent injury contributes to chronic rejection in renal allografts and heme oxygenase-1 (HO-1) has been shown to be protective in a number of settings. This study evaluated the effect of renal allograft recipient HO-1 up-regulation on chronic rejection in a rat model. Rat (F344 to Lewis) renal transplantation recipients were grouped: (i) cyclosporine (CsA) alone (0.75 mg/kg s.c. x 10 day; n = 5); (ii) CsA + low dose cobalt protoporphyrin (CoPP) an HO-1 inducer (0.5 mg/kg i.p. on days -5,0,5; n = 13) and (iii) CsA + high dose CoPP (5.0 mg/kg i.p. on days -5,0,5; n = 8). Renal function was assessed by serum creatinine levels on day 140. Histopathologic changes in allografts were graded. Morphometric analyses performed to objectively quantify the vascular changes and glomerulosclerosis. HO-1 expression quantified by Western blot and both HO-1 and endothelin (ET-1) localized using immunohistochemistry. Recipients treated with CsA + high dose CoPP had significantly decreased cortical scarring, vascular hyalinization and intimal thickness. They also had a significant, dose-dependent, reduction in luminal obliteration and glomerulosclerosis by morphometric analyses. This freedom from chronic rejection in recipients treated with CoPP translated into quiescent grafts at postoperative day 140 with immunostaining and Western blot demonstrating decreased level of HO-1 versus controls (P = 0.012). In summary, the peritransplant up-regulation of HO-1 in renal allograft recipients significantly attenuates chronic rejection in rat renal allografts by inhibiting transplant vasculopathy.

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Chemokine-binding viral protein M-T7 prevents chronic rejection in rat renal allografts.

M-T7 is a myxoma virus-encoded protein that has been found to bind and disrupt human chemokine gradients. This study examined whether purified M-T7 could prevent chronic rejection in a rat renal allograft model. Fisher F344 renal allografts were transplanted into Lewis rats. Recipients were randomly grouped into two groups: control animals treated with cyclosporine alone and animals treated with cyclosporine combined with low-, medium- and high-dose M-T7 viral protein. The survival rate was not significantly different between allograft groups. Renal allografts treated with high-dose M-T7 demonstrated a significant reduction in tubular atrophy, glomerular atrophy, vascular hyalinization, cortical scarring, and lymphocyte infiltration. Morphometric analyses demonstrated that the high-dose M-T7 group also showed a significantly decreased amount of glomerulosclerosis and transplant arteriosclerosis. These data demonstrate for the first time that the immunoregulatory viral protein M-T7 can effectively attenuate chronic rejection in rat renal allografts.

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