An Analysis of Early Renal Transplant Protocol Biopsies - the High Incidence of Subclinical Tubulitis

To investigate the possibility that we have been underestimating the true incidence of acute rejection, we began to perform protocol biopsies after kidney transplantation. This analysis looks at the one-week biopsies. Between March 1 and October 1, 1999, 100 adult patients undergoing cadaveric kidney or kidney/pancreas transplantation, or living donor kidney transplantation, underwent 277 biopsies. We focused on the subset of biopsies in patients without delayed graft function (DGF) and with stable or improving renal function, who underwent a biopsy 8.2 ± 2.6 d (range 3-18 d) after transplantation (n = 28). Six (21%) patients with no DGF and with stable or Improving renal function had borderline histopathology, and 7 (25%) had acute tubulitis on the one-week biopsy. Of the 277 kidney biopsies, there was one (0.4%) serious hemorrhagic complication, in a patient receiving low molecular weight heparin; she ultimately recovered and has normal renal function. Her biopsy showed Banff 1B tubulitis. In patients with stable or improving renal allograft function early after transplantation, subclinical tubulitis may be present in a substantial number of patients. This suggests that the true incidence of rejection may be higher than is clinically appreciated

Randomized Phase 2b Trial of Tofacitinib (CP‐690,550) in De Novo Kidney Transplant Patients: Efficacy, Renal Function and Safety at 1 Year

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93568/1/j.1600-6143.2012.04127.x.pd

New Civil Rights Strategies for Latino Political Empowerment

Latinos became the largest minority group and significantly increased their political representation in Massachusetts in the past decade. Even with these gains, their political power is not nearly commensurate with the size of their population. Many aspects of Latino political demographics, including a large immigrant population with low citizenship rates, high poverty rates, and dispersion across many electoral districts, contribute to their underrepresentation. The political demographics facing Massachusetts Latinos have led many analysts to prescribe alternative electoral systems as avenues to achieve increased political representation. This article reviews the critiques of the 1970s and 1980s civil rights redistricting strategies and explores the prospects that the new 1990s strategies could offer Latinos in the six cities where they are highly concentrated and at the state level. The author projects gains for most legislative bodies, but at a rate lower than suggested by proportionality advocates

Kidney transplantation under minimal immunosuppression after pretransplant lymphoid depletion with Thymoglobulin or Campath

BACKGROUND: Multiple drug immunosuppression has allowed the near elimination of rejection, but without commensurate improvements in longterm graft survival and at the cost of quality of life. We have suggested that transplantation outcomes can be improved by modifying the timing and dosage of immunosuppression to facilitate natural mechanisms of alloengraftment and acquired tolerance. STUDY DESIGN: Two therapeutic principles were applied for kidney transplantation: pretransplant recipient conditioning with antilymphoid antibody preparations (Thymoglobulin [Sangstat] or Campath [ILEX Pharmaceuticals]), and minimal posttransplant immunosuppression with tacrolimus monotherapy including "spaced weaning" of maintenance doses when possible. The results in Thymoglobulin- (n = 101) and Campath-pretreated renal transplantation recipients (n = 90) were compared with those in 152 conventionally immunosuppressed recipients in the immediately preceding era. RESULTS: Spaced weaning was attempted in more than 90% of the kidney transplant recipients after pretreatment with both lymphoid-depleting agents, and is currently in effect in two-thirds of the survivors. Although there was a much higher rate of acute rejection in the Thymoglobulin-pretreated recipients than in either the Campath-pretreated or historic control recipients, patient and graft survival in both lymphoid depletion groups is at least equivalent to that of historic control patients. In the Thymoglobulin-conditioned patients for whom followups are now 24 to 40 months, chronic allograft nephropathy (CAN) progressed at the same rate as in historic control patients. Selected patients on weaning developed donor-specific nonreactivity. CONCLUSIONS: After lymphoid depletion, kidney transplantation can be readily accomplished under minimal immunosuppression with less dependence on late maintenance immunosuppression and a better quality of life. Campath was the more effective agent for pretreatment. Guidelines for spaced weaning need additional refinement. © 2005 by the American College of Surgeons

Amino Acid Requirements in Critically Ill Patients with Acute Kidney Injury Treated with Continuous Renal Replacement Therapy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90284/1/phco.28.5.600.pd

Legal construction of racial discrimination in contemporary Brazil

Thesis (Ph.D.)--Massachusetts Institute of Technology, Dept. of Political Science, 2002.Includes bibliographical references (p. 396-406).This dissertation, an in-depth empirical study of Brazilian racial discrimination law, examines the trends in complaining and surprising variation in official decisionmaking over the past decade. I collected more than 300 racial discrimination complaints, police investigations and court proceedings filed since 1989. I claim that Brazil's racial ideology and its theory of racial discrimination as an act of racial prejudice have been jointly constituted and, in turn, fully shape the making and the using of anti-discrimination law. I show that Brazil constructed racial discrimination narrowly compared to US theories of racial discrimination and the Brazilian understanding of other forms of discrimination, such as gender and age. Brazilians disproportionately file racial discrimination complaints about insults by a neighbor or co-worker. Officials treated these and most allegations as private, interpersonal disputes, even for allegations of firing and other problems protected in the law. I located approximately 40 findings for the plaintiff, a small fraction of the tens of hundreds of allegations, and analyze the variation in judicial inquiry and outcomes. Brazil's racial ideology and weak rule of law strongly influenced litigation. Defendants destroyed evidence and threatened plaintiffs and witnesses. Officials often erased the testimony of Black plaintiffs and witnesses in their holdings. Defendants often claimed to be Mulato or to have treated the plaintiff cordially as evidence of being Brazilian and inherently unprejudiced. Many officials accepted that defense. I hold the Brazilian theory of racial discrimination as overt prejudicial acts responsible for the use of the law.(cont.) The law has focused attention on the mind and attitude of the aggressor. Although all judges invoke their ideology in their findings, Brazil's anti-discrimination law has increased that tendency by requiring judges to decide whether a defendant was prejudiced. Instead of providing clear standards to try cases, the law has encouraged judges to consult their own racial ideology.by Seth Racusen.Ph.D

Clinical Relevance of Pretransplant HLA Class II Donor-specific Antibodies in Renal Transplantation Patients with Negative T-cell Cytotoxicity Crossmatches

Background: We evaluated the clinical relevance of pretransplant donor-specific HLA antibodies (DSA) in renal transplantation patients who had negative T-cell cytotoxicity crossmatches. Methods: From 328 consecutive renal transplant recipients, we selected 28 patients who had positive pretransplant (historical or at the time of transplantation) flow cytometry crossmatches, but negative T-cell cytotoxicity crossmatches at the time of transplantation. The presence of DSA and its level at the time of transplantation were retrospectively tested using Luminex single antigen assays. Results: DSA was present in 16 (57.1%) of 28 patients. Biopsy-proven acute rejection (9 patients) occurred more frequently in patients with DSA than in those without DSA (56.3% vs. 0.0%; P =0.003). The positivity rate of class II DSA was significantly higher in patients with antibody-mediated rejection (AMR) than in those without AMR (100 % vs. 21.7%; P = 0.003). However, the positivity rate of class I DSA was not different between the two groups (40 % vs. 40.9%). Among patients with class II DSA, those with AMR tended to have higher antibody levels (median fluorescence intensity, MFI) than those without AMR (16,359 vs. 5,910; P =0.056). A cut-off MFI value of 4,487 for class II DSA predicted the occurrenc

Tolerogenic immunosuppression for organ transplantation

Background: Insight into the mechanisms of organ engraftment and acquired tolerance has made it possible to facilitate these mechanisms, by tailoring the timing and dosage of immunosuppression in accordance with two therapeutic principles: recipient pretreatment, and minimum use of post-transplant immunosuppression. We aimed to apply these principles in recipients of renal and extrarenal organ transplants. Methods: 82 patients awaiting kidney, liver, pancreas, or intestinal transplantation were pretreated with about 5 mg/kg of a broadly reacting rabbit antithymocyte globulin during several hours. Post-transplant immunosuppression was restricted to tacrolimus unless additional drugs were needed to treat breakthrough rejection. After 4 months, patients on tacrolimus monotherapy were considered for dose-spacing to every other day or longer intervals. Findings: We frequently saw evidence of immune activation in graft biopsy samples, but unless this was associated with graft dysfunction or serious immune destruction, treatment usually was not intensified. Immunosuppression-related morbidity was virtually eliminated. 78 (95%) of 82 patients survived at 1 year and at 13-18 months. Graft survival was 73 (89%) of 82 at 1 year and 72 (88%) of 82 at 13-18 months. Of the 72 recipients with surviving grafts, 43 are on spaced doses of tacrolimus monotherapy: every other day (n=6), three times per week (11), twice per week (15), or once per week (11). Interpretation: The striking ability to wean immunosuppression in these recipients indicates variable induction of tolerance. The simple therapeutic principles are neither drug-specific nor organ-specific. Systematic application of these principles should allow improvements in quality of life and long-term survival after organ transplantation

In vivo and in vitro synthesis of CM-proteins (A-hordeins) from barley (Hordeum vulgare L.)

CM-proteins from barley endosperm (CMa, CMb, CMc, CMd), which are the main components of the A-hordein fraction, are synthesized most actively 10 to 30 d after anthesis (maximum at 15–20 d). They are synthesized by membranebound polysomes as precursors of higher apparent molecular weight (13,000–21,000) than the mature proteins (12,000–16,000). The largest in vitro product (21,000) is the putative precursor of protein CMd (16,000), as it is selected with anti-CMd monospecific IgG's, and is coded by an mRNA of greater sedimentation coefficient (9 S) than those encoding the other three proteins (7.5 S). CM-proteins always appear in the soluble fraction, following different homogenization and subcellular fractionation procedures, indicating that these proteins are transferred to the soluble fraction after processing