[Show abstract][Hide abstract] ABSTRACT: Venous stenosis is a significant problem in arteriovenous fistulae, likely due to anatomical configuration and wall shear stress profiles. To identify linkages between wall shear stress and the magnitude and pattern of vascular stenosis, we produced curved and straight fistulae in a pig model. A complete wall stress profile was calculated for the curved configuration and correlated with luminal stenosis. Computer modeling techniques were then used to derive a wall shear stress profile for the straight arteriovenous fistula. Differences in the wall shear stress profile of the curved and straight fistula were then related to histological findings. There was a marked inverse correlation between the magnitude of wall shear stress within different regions of the curved arteriovenous fistula and luminal stenosis in these same regions. There were also significantly greater differences in wall shear stress between the outer and inner walls of the straight as compared to curved arteriovenous fistula, which translated into a more eccentric histological pattern of intima-media thickening. Our results suggest a clear linkage between anatomical configuration, wall shear stress profiles, and the pattern of luminal stenosis and intima-media thickening in a pig model of arteriovenous fistula stenosis. These results suggest that fistula failure could be reduced by using computer modeling prior to surgical placement to alter the anatomical and, consequently, the wall shear stress profiles in an arteriovenous fistula.Keywords: AV fistula configuration, computational fluid dynamics, hemodialysis vascular access dysfunction, hemodynamics, wall shear stress
Kidney International 09/2008; 74(11):1410-1419. DOI:10.1038/ki.2008.379 · 8.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Elimination of corticosteroid-related morbidity has been a goal of transplant clinicians from the earliest days of renal transplantation more than 50 years ago. Over the past decade, this goal has begun to be realized. Herein, we describe our efforts to eliminate corticosteroid therapy from maintenance immunosuppression-efforts that have spanned 15 years and have included design and conduct of five multicenter trials and over ten single center trials with over 650 patients at the University of Cincinnati. These efforts have led to a near complete elimination of corticosteroid-related morbidity, and, importantly, a more precise definition of the risk/benefit assessments of corticosteroid withdrawal in individual patient populations, which has allowed individualization and tailoring of corticosteroid-free immunosuppression.
[Show abstract][Hide abstract] ABSTRACT: Liver transplant recipients are at high risk for multi-drug resistant infections because of broad-spectrum antibiotic and immunosuppression. This study evaluates the clinical and financial impact of vancomycin resistant Enterococcus (VRE) in liver transplant recipients.
Liver transplant recipients with VRE from 1995 to 2002 were identified and matched (age, gender, UNOS status, liver disease and transplant date) to controls. Demographics, clinical factors, co-infections, antibiotic use, length of stay, abdominal surgeries, biliary complications, survival and resource utilization were compared with matched controls.
Nineteen patients were found to have 28 VRE infections via evaluation of microbiologic culture results of all liver transplant patients in the transplant registry. Thirty-eight non-VRE patients served as matched controls. The four most common sites VRE was cultured from included blood (35%), peritoneal fluid (35%), bile (20%), and urine (12%). Median time from transplant to infection was 48 d (range of 4-348). No significant differences in demographics were observed. The VRE group had a higher incidence of prior antibiotic use than the non-VRE group (95% vs. 34%; p < 0.05). The VRE group also experienced more abdominal surgery (20/19 vs. 3/38; p = 0.029), biliary complications (9/19 vs. 9/38; p = 0.018) and a longer length of stay (42.5 vs. 21.7 d; p = .005). Survival in the VRE group was lower (52% vs. 82%; p = 0.048). Six of the 19 VRE patients were treated with linezolid for eight infection episodes, and four of six patients survived. Eight patients were treated with quinupristin/dalfopristin for nine infections, and two of eight survived. Increased cost of care was observed in the VRE group. Laboratory costs were higher in the VRE group (6500 dollars vs. 1750; p = 0.02) as well.
VRE was associated with prior antibiotic use, multiple abdominal surgeries, biliary complications and resulted in decreased survival compared to non-VRE control patients. VRE patients also utilized more hospital resources. Linezolid showed a trend toward improved survival.
[Show abstract][Hide abstract] ABSTRACT: Ischemia-reperfusion injury (IRI) in liver and other organs is manifested as an injury phase followed by recovery and resolution. Control of cell growth and proliferation is essential for recovery from the injury. We examined the expression of three related regulators of cell cycle progression in liver IRI: spermidine/spermine N-acetyltransferase (SSAT), p21 (a cyclin-dependent kinase inhibitor), and stathmin. Mice were subjected to hepatic IRI, and liver tissues were harvested at timed intervals. The expression of SSAT, the rate-limiting enzyme in the polyamine catabolic pathway, had increased fivefold 6 h after IRI and correlated with increased putrescine levels in the liver, consistent with increased SSAT enzymatic activity in IRI. The expression of p21, which is transactivated by p53, was undetectable in sham-operated animals but was heavily induced at 12 and 24 h of reperfusion and declined to undetectable baseline levels at 72 h of reperfusion. The interaction of the polyamine pathway with the p53-p21 pathway was shown in vitro, where activation of SSAT with polyamine analog or the addition of putrescine to cultured hepatocytes induced the expression of p53 and p21 and decreased cell viability. The expression of stathmin, which is under negative transcriptional regulation by p21 and controls cell proliferation and progression through mitosis, remained undetectable at 6, 12, and 24 h of reperfusion and was progressively and heavily induced at 48 and 72 h of reperfusion. Double-immunofluorescence labeling with antibodies against stathmin and PCNA, a marker of cell proliferation, demonstrated colocalization of stathmin and PCNA at 48 and 72 h of reperfusion in hepatocytes, indicating the initiation of cell proliferation. The distinct and sequential upregulation of SSAT, p21, and stathmin, along with biochemical activation of the polyamine catabolic pathway in IRI in vivo and the demonstration of p53-p21 upregulation by SSAT and putrescine in vitro, points to the important role of regulators of cell growth and cell cycle progression in the pathophysiology and/or recovery in liver IRI. The data further suggest that SSAT may play a role in the initiation of injury, whereas p21 and stathmin may be involved in the resolution and recovery after liver IRI.