Risk factors for delayed graft function and their impact on graft outcomes in live donor kidney transplantation

International Urology and Nephrology - Delayed graft function (DGF) is a manifestation of acute kidney injury uniquely framed within the transplant process and a predictor of poor long-term graft...     

Prostatitis and serum prostate-specific antigen

Prostatitis is an inflammatory condition of the prostate and has been divided into four categories according to the National Institutes of Health classification. This article reviews the various types of prostatitis and their effect on serum prostate-specific antigen levels. Various proposed mechanisms of this elevation include leakage of prostatespecific antigen (PSA) into the blood stream, hypervascularity, and altered vascular permeability secondary to inflammation. Acute prostatitis can lead to an increase in PSA, which usually returns to normal levels with appropriate antibiotics within 1 to 3 months. Patients with chronicprostatitis have a less well-defined decrease in PSA after an antibiotic course. Whether a course of antibiotics prior to biopsy increases the yield has not been well established. Asymptomatic inflammation of the prostate has been recognized to be an important confounding factor in patients with an elevated PSA. Inflammation has been proposed to be a precursor of prostate adenocarcinoma.     

Bilirubin,a new therapeutic for kidney transplant?

In patients with end-stage renal disease, kidney transplantation has been associated with numerous benefits, including increased daily activity, and better survival rates. However, over 20% of kidney transplants result in rejection within five years. Rejection is primarily due to a hypersensitive immune system and ischemia/reperfusion injury. Bilirubin has been shown to be a potent antioxidant that is capable of potentially reversing or preventing damage from reactive oxygen species generated from ischemia and reperfusion. Additionally, bilirubin has several immunomodulatory effects that can dampen the immune system to promote organ acceptance. Increased bilirubin has also been shown to have a positive impact on renal hemodynamics, which is critical post-transplantation. Lastly, bilirubin levels have been correlated with biomarkers of successful transplantation. In this review, we discuss a multitude of potentially beneficial effects that bilirubin has on kidney acceptance of transplantation based on numerous clinical trials and animal models. Exogenous bilirubin delivery or increasing endogenous levels pre- or post-transplantation may have therapeutic benefits.     

Cardiac alpha-myosin heavy chains differ in their induction of myocarditis. Identification of pathogenic epitopes.

BALB/c mice develop autoimmune myocarditis after immunization with mouse cardiac myosin, whereas C57B/6 mice do not. To define the immunogenicity and pathogenicity of cardiac myosin in BALB/c mice, we immunized mice with different forms of cardiac myosin. These studies demonstrate the discordance of immunogenicity and pathogenicity of myosin heavy chains. The cardiac alpha-myosin heavy chains of BALB/c and C57B/6 mice differ by two residues that are near the junction of the head and rod in the S2 fragment of myosin. Myosin preparations from both strains are immunogenic in susceptible BALB/c as well as in nonsusceptible C57B/6 mice; however, BALB/c myosin induces a greater incidence of disease. To further delineate epitopes of myosin heavy chain responsible for immunogenicity and disease, mice were immunized with fragments of genetically engineered rat alpha cardiac myosin. Epitopes in the region of difference between BALB/c and C57B/6 (residues 735-1032) induce disease in both susceptible and nonsusceptible mice. The data presented here demonstrate that pathogenic epitopes of both mouse and rat myosin residue in the polymorphic region of the S2 subunit. In addition, these studies suggest that polymorphisms in the autoantigen may be part of the genetic basis for autoimmune myocarditis.     

p53-stabilizing Agent CP-31398 Prevents Growth and Invasion of Urothelial Cancer of the Bladder in Transgenic UPII-SV40T Mice

The high prevalence of bladder cancer and its recurrence make it an important target for chemoprevention. About half of invasive urothelial tumors have mutations in p53. We determined the chemopreventive efficacy of a p53-stabilizing agent, CP-31398, in a transgenic UPII-SV40T mouse model of bladder transitional cell carcinoma (TCC) that strongly resembles human TCC. After genotyping, six-week-old UPII-SV40T mice (n = 30/group) were fed control (AIN-76A) or experimental diets containing 150 or 300 ppm of CP-31398 for 34 weeks. Progression of bladder cancer growth was monitored by magnetic resonance imaging. At 40 weeks of age, all mice were killed; urinary bladders were collected to determine weights, tumor incidence, and histopathology. There was a significant increase in bladder weights of transgenic versus wild-type mice (male: 140.2 mg vs 27.3 mg, P < .0001; female: 34.2 mg vs 14.8 mg, P < .0001). A significant decrease in the bladder tumor weights (by 68.6–80.2%, P < .0001 in males and by 36.9–55.3%, P < .0001 in females) was observed in CP-31398-treated mice. Invasive papillary TCC incidence was 100% in transgenic mice fed control diet. Both male and female mice exposed to CP-31398 showed inhibition of invasive TCC. CP-31398 (300 ppm) completely blocked invasion in female mice. Molecular analysis of the bladder tumors showed an increase in apoptosis markers (p53, p21, Bax, and Annexin V) with a decrease in vascular endothelial growth factor in transgenic mice fed CP-31398. These results suggest that p53-modulating agents can serve as potential chemopreventive agents for bladder TCC.     

Urine versus stent cultures and clinical UTIs

International Urology and Nephrology - Current American Urological Association guidelines recommend pre-operative antimicrobial therapy based on prior urine cultures (UC); however, the role of...     

Mesh contraction: in vivo documentation of changes in apparent surface area utilizing meshes visible on magnetic resonance imaging in the rabbit abdominal wall model

Introduction and hypothesis

Our aim was to analyze the apparent contraction of meshes in vivo after abdominal wall reconstruction and evaluate histological and biomechanical properties after explantation.

Methods

Nine New Zealand female rabbits underwent repair of two full-thickness 25 × 30-mm midline defects in the upper and lower parts of the abdomen. These were primarily overlaid by 35 × 40-mm implants of a polyvinylidene fluoride (PVDF) DynaMesh (n?=?6) or polypropylene meshes Ultrapro (n?=?6) and Marlex (n?=?6). Edges of the meshes were secured with iron(II,III) oxide (Fe₃O₄)-loaded PVDF sutures. Magnetic resonance images (MRIs) were taken at days 2, 30 and 90 after implantation. The perimeter of the mesh was traced using a 3D spline curve. The apparent surface area or the area within the PVDF sutures was compared with the initial size using the one-sample t test. A two-way repeat analysis of variance (ANOVA) was used to compare the apparent surface area over time and between groups.

Results

PVDF meshes and sutures with Fe₃O₄ could be well visualized on MRI. DynaMesh and Marlex each had a 17 % decrease in apparent surface area by day 2 (p?<?0.001 and p?=?0.001), respectively, which persisted after day 90. Whereas there was a decrease in apparent surface area in Ultrapro, it did not reach significance until day 90 (p?=?0.01). Overall, the apparent surface area decreased 21 % in all meshes by day 90. No differences in histological or biomechanical properties were observed at day 90.

Conclusions

There was a reduction in the apparent surface area between implantation and day 2, indicating that most mesh deformation occurs prior to tissue in-growth.