Cadaver transplantation in Recent Era: Is Cadaveric Graft Survival Similar to Living Kidney Transplantation?

BACKGROUND: Renal transplantation is the procedure of choice for most of patients with end-stage renal disease. The graft, however can be procured from either cadaver or living donors. OBJECTIVE: To compare graft and patient survival among patients who underwent kidney transplantation from cadaver donor vs. living donor. METHODS: From April 2002 to February 2010, we performed 138 cadaver kidney transplantations. We reviewed and compared one-year graft and patient survival with 138 living kidney transplantations. RESULTS: One-year graft and patient survivals in cadaveric groups were 93% and 96%, respectively, and in living groups were 92% and 97%, respectively. CONCLUSION: There was no significant difference in one-year graft and patient survival between living and cadaver donor kidney transplantation.

Single-stranded oligonucleotides can inhibit cytokine production induced by human toll-like receptor 3.

Toll-like receptor 3 (TLR3) can signal the production of a suite of cytokines and chemokines in response to double-stranded RNA (dsRNA) ligands or the dsRNA mimic poly(I-C). Using a human embryonic kidney 293T cell line to express human TLR3, we determined that poly(I-C)-induced signal could be significantly inhibited by single-stranded DNAs (ssDNAs), but not ssRNA or dsDNA. The ssDNA molecules that down-modulated TLR3 signaling did not affect TLR4 and do not require the hypomethylated CpG motif found in TLR9 ligands. The degree of modulation can be altered by the length, base sequence, and modification state of the ssDNAs. An inhibitory ssDNA was found to colocalize with TLR3 in transfected cells and in a cell line that naturally expresses TLR3. The inhibitory ssDNAs can compete efficiently with dsRNA for binding purified TLR3 ectodomains in vitro, while noninhibitory nucleic acids do not. The ssDNAs also decrease the levels of several cytokines produced by the human bronchial epithelial cell line BEAS-2B and by human peripheral blood mononuclear cells in response to poly(I-C) stimulation of native TLR3. These activities indicate that ssDNAs could be used to regulate the inflammatory response through TLR3.

Small molecule and biologic modulators of the immune response to hepatitis C virus.

Hepatitis C virus represents a major global health problem, with approximately 3% of the world population infected. Immune-response modifiers represent the standard of care, given the lack of approved antiviral agents having direct activity against the viral proteins. Although in recent years, improvements in therapy have been attained by combined treatment with pegylated interferon and ribavirin, the discovery and development of next-generation small molecule and biologic agents is ongoing. Several of these newer therapeutics are focused on modulating Toll-like receptors, interferon-alpha signaling, and the pro-inflammatory cytokine balance. A comprehensive account of the lead compounds in development, the bioassays used for optimization of these immune response modifiers and their clinical status is presented.

Renal allograft accumulation of technetium-99m sulfur colloid as a predictor of graft rejection.

Differentiation between rejection (the most common cause) and many other possibilities for detrimental effects on graft function represents a difficult issue to diagnose the cause of renal allograft dysfunction. This study was designed to determine whether technetium-99m sulfur colloid (TSC) accumulation predicted graft rejection. We prospectively studied 54 episodes of allograft dysfunction in 53 kidney transplant recipients who underwent TSC scintiscanning and graft biopsy. Visual analysis of TSC uptake compared uptake, in the allograft with that in the marrow of the fifth lumbar vertebra (L5). A 3+ result meant that allograft uptake was greater than L5 marrow uptake; 2+, the same; 1+, less and finally 0, no allograft uptake. Transplant accumulation of 2+ or more was considered consistent with rejection (P = .01). Allograft biopsies interpreted based on the Banff Working Classification showed rejection in 45 of 54 renal biopsies with 42 the biopsy-proven rejection episodes showing at least 2+ graft uptake. Furthermore, this nuclear medicine technique had a sensitivity of 93.3%, a specificity of 44.4%, a positive predictive value of 89.3%, a negative value of 57.1% and an efficiency of 83.3% for the diagnosis of renal allograft rejection.

Transureteral lithotripsy in pediatric practice.

PURPOSE: The present study reviews ureteroscopy intervention for the treatment of ureteral stones in pediatric patients in the last 6 years at three institutions in Iran. PATIENTS AND METHODS: Sixty-six ureteroscopies were performed in 66 prepubertal patients (mean age 9 years; range 2-15 years) with a male/female ratio of 31/35. Ultrasonography, plain film, or intravenous urography was performed in all cases. The mean stone size was 8 mm (range 5-15 mm). All the interventions were performed under general anesthesia with semirigid ureteroscopes of 8F to 11.5F. The stone was located in the left ureter in 32 patients and in the right in 34 patients. Stones were located in the distal ureter in 59 patients, in the midureter in 5, and in the proximal ureter in 2. Before ureteroscopy, ureteral dilatation with a balloon was done to 12F if necessary. If the calculus could not be removed with the basket (stone.8 mm), lithotripsy using ultrasonic, electrohydraulic (EHL), or pneumatic equipment was performed. RESULTS: Ureteroscopy with an 11.5F, 9F, 8.5F, or 8F ureteroscope were performed in 26, 14, 5, and 21 patients, respectively, and ureteral dilatation was necessary in 23, 0, 0, and 2 cases, respectively. We were unable to introduce the ureteroscope into the ureter in three patients (two boys with an 11.5F ureteroscope and one girl with an 8.5F ureteroscope) with distal ureteral stones. The stones moved to the kidney in four patients. Stone management was with basketing alone in 14, EHL in 3, ultrasonic lithotripsy in 8, and ballistic lithotripsy in 34 patients. The stone-free rate was 88% (58 patients) at 48 hours postprocedure. The complication rate was 23% and included renal colic (1), gross hematuria (11), and pyelonephritis (3). No patient had obvious perforation or stricture of the ureter at 3-month follow-up. CONCLUSION: Our series demonstrates the high success rate that can be achieved with ureteroscopic removal of ureteral calculi in children. Ureteroscopic treatment, especially with a small-caliber ureteroscope, should be considered the first choice for treatment of calculi in the distal ureter in children.

Fas/Fas ligand deficiency results in altered localization of anti-double-stranded DNA B cells and dendritic cells.

Autoantibodies directed against dsDNA are found in patients with systemic lupus erythematosus as well as in mice functionally deficient in either Fas or Fas ligand (FasL) (lpr/lpr or gld/gld mice). Previously, an IgH chain transgene has been used to track anti-dsDNA B cells in both nonautoimmune BALB/c mice, in which autoreactive B cells are held in check, and MRL-lpr/lpr mice, in which autoantibodies are produced. In this study, we have isolated the Fas/FasL mutations away from the autoimmune-prone MRL background, and we show that anti-dsDNA B cells in Fas/FasL-deficient BALB/c mice are no longer follicularly excluded, and they produce autoantibodies. Strikingly, this is accompanied by alterations in the frequency and localization of dendritic cells as well as a global increase in CD4 T cell activation. Notably, as opposed to MRL-lpr/lpr mice, BALB-lpr/lpr mice show no appreciable kidney pathology. Thus, while some aspects of autoimmune pathology (e.g., nephritis) rely on the interaction of the MRL background with the lpr mutation, mutations in Fas/FasL alone are sufficient to alter the fate of anti-dsDNA B cells, dendritic cells, and T cells.

Alterations in splenic architecture and the localization of anti-double-stranded DNA B cells in aged mice.

Aging is characterized by a decline in humoral immunity and a concommitant increased incidence of anti-DNA and other autoantibodies. To define how the regulation of autoreactive B cells is altered with age, we have used BALB/c mice with an Ig heavy H chain transgene to track the fate of anti-double-stranded (ds) DNA B cells in vivo. In young adult mice, anti-dsDNA B cells are developmentally arrested and excluded from the splenic B cell follicle, whereas in most aged mice they are mature and localize within the B cell follicle. Furthermore, we have detailed global changes in lymphoid architecture that accompany aging: CD4(+) T cells are found not only in the periarteriolar lymphoid sheath, but also in the B cell follicles. Strikingly, these disruptions are similar to those that precede serum anti-dsDNA antibody expression in autoimmune MRL-lpr/lpr mice.

The origin of anti-nuclear antibodies in bcl-2 transgenic mice.

bcl-2 transgenic mice develop anti-double-stranded (ds) DNA antibodies similar to those present in systemic lupus erythematosus. To begin to understand where a breakdown in the regulation of autoreactive lymphocytes is occurring, we have used a bcl-2 transgene (Tg) in conjunction with an Ig Tg that allows us to identify and track anti-dsDNA B cells. Previously, we have shown that anti-dsDNA B cells are actively tolerized in BALB/c mice as manifested by their developmental arrest, follicular exclusion, increased in vivo turnover rate and lack of their antibody in the serum. The bcl-2 Tg mice increased the lifespan of anti-dsDNA B cells, but did not alter the other features of tolerance, indicating that the anergy of the anti-dsDNA B cells is independent of their reduced lifespan. Furthermore, these data suggest that the serum anti-dsDNA antibodies in bcl-2 transgenic mice are not due to a breakdown in the induction or maintenance of B cell anergy; rather they may originate from B cells that have transited through a germinal center.

Functional consequences of the developmental arrest and follicular exclusion of anti-double-stranded DNA B cells.

Anti-dsDNA B cells are actively tolerized in nonautoimmune BALB/c mice, as manifested by their developmental arrest, follicular exclusion, and rapid turnover rate. Previously, we have documented changes in the maturation status and follicular localization of anti-dsDNA B cells in autoimmune-prone MRL (+/+ and lpr/lpr) mice. To determine whether these differences in developmental status and follicular localization affect the functional capacity of anti-dsDNA B cells, we have now compared their in vivo life spans and their responses to in vitro stimuli. Our study shows that although anti-dsDNA B cells from both BALB/c and MRL-+/+ mice are localized to the T/B interface, only those in BALB/c mice have a rapid turnover rate. Therefore, the immature status and not the exclusion from the B cell follicle correlates with a shortened life span. Interestingly, apoptotic anti-dsDNA B cells were not detected at the T/B interface in BALB/c mice, suggesting that they are not dying there. This study also demonstrates that anti-dsDNA B cells, regardless of maturation status or follicular localization, are able to proliferate and up-regulate the costimulatory molecule B7-2 in response to CD40 ligand and IL-4. Therefore, one of the critical in vivo differences between anti-dsDNA B cells in BALB/c and MRL-+/+ mice compared with MRL-lpr/lpr mice may be the availability of T cell help.

Detection of small airway dysfunction using specific airway conductance.

STUDY OBJECTIVE: To assess the potential utility of specific airway conductance (sGaw) in detecting small airways dysfunction, the postlung-transplant bronchiolitis obliterans syndrome (BOS) was used as a model of small airways dysfunction. BOS is defined as an otherwise unexplained 20% reduction in FEV1. We hypothesized that if sGaw is sensitive to small airways dysfunction, it should decrease before the decline in FEV1. DESIGN/METHODS: The pulmonary function test and sGaw measurements of patients who underwent heart-lung or bilateral lung transplantation between May 1981 and January 1993 were reviewed. Patients with and without BOS were identified. A significant decrease in sGaw was defined as a 20% fall from baseline. RESULTS: Twenty-six BOS and 15 non-BOS patients had at least three sGaw measurements such that trends could be examined. Eleven of the 26 BOS patients (42%) had a significant decrease in sGaw before a 20% decrease in FEV1, as compared to 2 of the 15 non-BOS patients (13%) (p=0.08). In comparison, 12 of the 26 BOS patients (46%) and 4 of the 15 non-BOS patients (27%) had a significant decrease in forced expiratory flow at 25 to 75% of the forced lung volume (FEF(25-75)) (p=0.32), an accepted test of small airways dysfunction. CONCLUSION: sGaw tended to decrease before FEV1 in BOS. The trend in sGaw was similar to the trend in FEF(25-75). We conclude that (1) small airways may contribute more to airway conductance than previously thought, and (2) further prospective studies are warranted to better define the relative contribution of small and large airways to sGaw.

Actinomyces odontolyticus thoracopulmonary infections. Two cases in lung and heart-lung transplant recipients and a review of the literature.

We present the first case of mediastinitis and the third case of pneumonia attributed to Actinomyces odontolyticus. The first patient presented 10 months after single-lung transplant with a subacute apical infiltrate in the native lung and responded to therapy with oral penicillin. The second patient developed pyogenic mediastinitis 25 days after a heart-lung transplant and required sternal debridement and intravenous penicillin. We also review the literature on thoracopulmonary infections due to A odontolyticus.

A case of fulminant human immunodeficiency virus dementia.

Human immunodeficiency virus (HIV) dementia is characterized by cognitive, motor, and behavioral abnormalities that develop over weeks or months. Fulminant presentations are not well described in the literature. In this report we describe a patient with HIV dementia who presented with acute changes in mental status that occurred over 2 days, resulting in rapid deterioration and death in 1 month.