Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure.

Apolipoprotein L1 gene (APOL1) nephropathy variants in African American deceased kidney donors were associated with shorter renal allograft survival in a prior single-center report. APOL1 G1 and G2 variants were genotyped in newly accrued DNA samples from African American deceased donors of kidneys recovered and/or transplanted in Alabama and North Carolina. APOL1 genotypes and allograft outcomes in subsequent transplants from 55 U.S. centers were linked, adjusting for age, sex and race/ethnicity of recipients, HLA match, cold ischemia time, panel reactive antibody levels, and donor type. For 221 transplantations from kidneys recovered in Alabama, there was a statistical trend toward shorter allograft survival in recipients of two-APOL1-nephropathy-variant kidneys (hazard ratio [HR] 2.71; p = 0.06). For all 675 kidneys transplanted from donors at both centers, APOL1 genotype (HR 2.26; p = 0.001) and African American recipient race/ethnicity (HR 1.60; p = 0.03) were associated with allograft failure. Kidneys from African American deceased donors with two APOL1 nephropathy variants reproducibly associate with higher risk for allograft failure after transplantation. These findings warrant consideration of rapidly genotyping deceased African American kidney donors for APOL1 risk variants at organ recovery and incorporation of results into allocation and informed-consent processes.

The APOL1 gene and allograft survival after kidney transplantation.

Coding variants in the apolipoprotein L1 gene (APOL1) are strongly associated with nephropathy in African Americans (AAs). The effect of transplanting kidneys from AA donors with two APOL1 nephropathy risk variants is unknown. APOL1 risk variants were genotyped in 106 AA deceased organ donors and graft survival assessed in 136 resultant kidney transplants. Cox-proportional hazard models tested for association between time to graft failure and donor APOL1 genotypes. The mean follow-up was 26.4 ± 21.8 months. Twenty-two of 136 transplanted kidneys (16%) were from donors with two APOL1 nephropathy risk variants. Twenty-five grafts failed; eight (32%) had two APOL1 risk variants. A multivariate model accounting for donor APOL1 genotype, overall African ancestry, expanded criteria donation, recipient age and gender, HLA mismatch, CIT and PRA revealed that graft survival was significantly shorter in donor kidneys with two APOL1 risk variants (hazard ratio [HR] 3.84; p = 0.008) and higher HLA mismatch (HR 1.52; p = 0.03), but not for overall African ancestry excluding APOL1. Kidneys from AA deceased donors harboring two APOL1 risk variants failed more rapidly after renal transplantation than those with zero or one risk variants. If replicated, APOL1 genotyping could improve the donor selection process and maximize long-term renal allograft survival.

Donor-recipient relationships in African American vs. Caucasian live kidney donors.

PURPOSE: The purpose of the study was to characterize differences in donor and recipient relationships between African American (AA) and Caucasian living kidney donors. METHODS: Data from all successful living kidney donors at a single institution between 1991 and 2009 were reviewed. Relationships between donor and recipient were categorized and between-group comparisons performed. RESULTS: The study sample consisted of 73 (18%) AA and 324 Caucasian living kidney donors. The distribution of donor-recipient relationships differed significantly between AA and Caucasians. AA donors were more likely to be related to the recipient (88% vs. 74%, p = 0.007) than Caucasians. AA donors were more likely to participate in child to parent donation and were less likely to participate in parent to child donation or to donate to unrelated individuals. Sibling and spousal donations were similar in both groups. Caucasian donors were more likely to be unrelated to the recipient than AA donors. CONCLUSIONS: Differences exist in donor-recipient relationships between AA and Caucasian living kidney donors. Future studies exploring cultural differences and family dynamics may provide targeted recruitment strategies for AA and Caucasian living kidney donors. Living unrelated kidney transplantation appears to be a potential growth area for living kidney donation in AA.

Short-term renal outcomes in African American and Caucasian donors following live kidney donation.

INTRODUCTION: Although African Americans (AA) are considered higher risk kidney donors than Caucasians, limited data are available regarding outcomes of AA donors. METHODS: We performed a single-center retrospective review of all kidney donors from 1993 to 2007 and evaluated race/ethnic differences in post-donation changes in renal function, incident proteinuria, and systolic blood pressure (SBP) using linear mixed models. RESULTS: A total of 336 kidney donors (63 AA, 263 Caucasian, 10 other) were evaluated. Before donation, AA had higher serum creatinine concentrations, estimated glomerular filtration rate (GFR) values, and SBP levels than Caucasians. No significant changes in SBP or renal function were observed between the two groups within the first year after donation, although results were limited by incomplete follow-up. CONCLUSION: AA had higher pre-donation serum creatinine, GFR, and SBP values compared to Caucasians; however, the degree of change in renal function and blood pressure did not differ between groups following kidney donation. Although long-term studies are needed, our study suggests that AA and Caucasians experience similar short-term consequences after donation. The incomplete data available on donor outcomes in our center and in prior publications also indicates a global need to implement systems for structured follow-up of live kidney donors.

Impact of race and gender on live kidney donation.

BACKGROUND: African Americans (AA) and women are less likely to receive a live kidney donor (LKD) transplant than Caucasians or men. Reasons for non-donation are poorly understood. METHODS: A retrospective review of 541 unsuccessful LKD was performed to explore reasons for non-donation and to assess for racial and/or gender differences. RESULTS: We identified 138 AA and 385 Caucasian subjects who volunteered but did not successfully donate. Females (58.2%) were more likely to be excluded than males due to reduced renal function (glomerular filtration rate < 85 mL/min, 7.9% vs. 0.9%, p < 0.0001) or failure to complete the evaluation (6.4% vs. 1.8%, p = 0.01). AA were more commonly excluded due to obesity (body mass index >or= 32 kg/m(2); 30.4% AA vs. 16.6% Caucasian, p = 0.0005) or failure to complete the evaluation (12.3% AA vs. 1.8% Caucasian, p < 0.0001) whereas Caucasians were more often excluded due to kidney stones (1.5% AA vs. 7.3% Caucasian, p = 0.01). CONCLUSIONS: Significantly different reasons for exclusion of LKD exist between potential Caucasian and AA LKD, particularly among women. Among the differences that we observed are potentially modifiable barriers to donation including obesity and failure to complete the donor evaluation. A further understanding of these barriers may help point to strategies for more effective recruitment and successful LKD.

Improvement in duration of erection following phosphodiesterase type 5 inhibitor therapy with vardenafil in men with erectile dysfunction: the ENDURANCE study.

OBJECTIVE: The ENDURANCE study evaluated the efficacy of vardenafil, a phosphodiesterase type 5 (PDE5) inhibitor, in men with erectile dysfunction (ED), by measuring the duration of erection leading to successful intercourse using a stopwatch as the assessment instrument. METHODS: This was a randomised, multicentre, double-blind, placebo-controlled, crossover study consisting of a 4-week treatment-free run-in phase after which patients were randomised to either fixed-dose vardenafil 10 mg or placebo (to be administered 60 min prior to intercourse) and entered the first of the two 4-week double-blind treatment periods, separated by a 1-week washout. The primary efficacy end-point was the stopwatch-assessed duration of erection, which was defined as the time from erection perceived hard enough for penetration until withdrawal from the partner's vagina leading to successful intercourse as measured by Sexual Encounter Profile Question 3 (SEP-3). Secondary efficacy end-points included SEP-2 and SEP-3 success rates, the erectile function domain of the International Index of Erectile Function, global assessment questionnaire, change from baseline in duration of erection and duration of erection not leading to successful intercourse. Safety was assessed by adverse events (AEs), laboratory samples, vital signs and ECGs. RESULTS: Of the 191 men included in the safety population, 40% had moderate ED and 33% had severe ED at baseline. The duration of erection (least squares mean +/- SE) leading to successful intercourse was longer with vardenafil than with placebo (12.81 +/- 1.00 min vs. 5.45 +/- 1.00 min; p < 0.001). The differences recorded for all secondary end-points were statistically significant in favour of vardenafil compared with placebo (p < 0.001), with the exception of duration of erection not leading to successful intercourse. Vardenafil was well tolerated in this study; the majority of AEs being mild-to-moderate in intensity. CONCLUSION: Vardenafil 10-mg therapy provided a statistically superior duration of erection leading to successful intercourse in men with ED compared with placebo.

Equine amnionitis and fetal loss: the case definition for an unrecognised cause of abortion in mares.

A series of abortions occurred in mares in New South Wales during 2004 that involved similar and unusual findings on post mortem examination of aborted fetuses and fetal membranes. The term Equine Amnionitis and Fetal Loss (EAFL) was developed to describe the condition. This form of abortion had not been previously recognised in Australia. The pathology alone is not specific for EAFL and diagnosis requires demonstration of a combination of certain pathological and bacteriological features. The purpose of this paper is to describe patterns considered consistent with EAFL cases as a working case definition for use by veterinarians and veterinary pathologists in identifying future cases of EAFL. More detailed papers are in preparation to fully describe the epidemiological, histopathological, and microbiological aspects of EAFL.

Outcomes of extended donors in pancreatic transplantation with portal-enteric drainage.

OBJECTIVE: Limited data are available on extended (EX) donor criteria in pancreatic transplantation (PTX). METHODS: This retrospective study from February 2007 through April 2007 compared 2 cohorts of simultaneous kidney-pancreas transplantations (SKPT): the first from EX donors, which were defined as age <10 years or > or =45 years, or donation after cardiac death [DCD]), and the second from conventional (CONV) donors. RESULTS: Among 79 SKPT, 19 (24%) were from EX donors (12 older than age 45 [mean age, 50.2 years], 3 pediatric donors <10, and 4 DCD donors) and the remaining 60 SKPT from CONV donors. The mean donor age was higher in EX than CONV donors (38 vs 25 years, P < .05). There were no other differences between the 2 cohorts. With a similar median follow-up of 29 months, patient, kidney and pancreatic graft survival rates were 89%, 89%, and 79%, for the EX, whereas corresponding outcomes for CONV donors were 93%, 87%, and 80%, respectively (all P = NS). The incidences were similar for delayed kidney graft function (5% in each group), early pancreatic graft loss due to thrombosis (5% EX vs 8% CONV donors), acute rejection (16% EX vs 18% CONV donors), surgical complications, and infections. There were no significant differences in 1-year mean serum creatinine (1.4 mg/dL in each group) or glycohemoglobin (5.2% vs 5.5%) levels between the EX and CONV donor groups, respectively. CONCLUSION: Short-term outcomes among SKPT from selected EX donors were comparable to CONV donors. Donors at the extremes of age and DCD donors may represent underused resources in SKPT.

Analysis of bacteremia after pancreatic transplantation with enteric drainage.

OBJECTIVE: The objective of this study was to review the incidence, risk factors, and impact of bacteremia after pancreas transplantation (PTX). METHODS: We performed a retrospective analysis of consecutive simultaneous kidney-pancreas transplantations (SKPTs) and solitary PTXs from January 2002 through April 2007. Positive blood cultures were correlated with other coexisting infections and parameters. RESULTS: One hundred ten PTXs with enteric drainage included 80 SKPTs and 30 solitary PTXs. Mean follow-up was 32 months. Bacteremia occurred in 29 (26%) patients with 5 (17%) being recurrent; it was seen during the first month after transplantation in 13 (12%), between 1 and 3 months in 12 (11%), between 3 and 12 months in 3 (3%), and after the first year in 3 cases (3%). Typical organisms were as follows: MRSE, MSSE, Klebsiella, Escherichia coli, vancomycin-resistant enterococci (VRE), and Acinetobacteri. Bacteremia was associated with coexisting site infection in 20 cases (69%): deep abdominal wound (31%); line (31%); urinary tract (34%); and pulmonary (7%). Similar bacterial species in blood and a coexisting site occurred in 15 cases (52%). No correlation was seen with cytomegalovirus (CMV) infections. In the first year, bacteremia was associated with more acute rejection episodes (32% vs 17%; P = .09), surgical complications (54% vs 42%; P = .267), mortality (11% vs 4%; P = .15), and death-censored pancreatic (14% vs 9%; P = .39) and kidney (4% vs 0; P = .08) graft loss. Fewer patients with bacteremia received alemtuzumab compared with rATG induction (14% vs 39%; P = .04). CONCLUSIONS: Bacteremias were common within 3 months of PTX. A significant number (39%) were multidrug resistant. The majority were accompanied by abdominal, urinary, or line infections. Bacteremias were associated with slightly higher incidences of rejection, mortality, and graft loss.

Do pretransplant C-peptide levels influence outcomes in simultaneous kidney-pancreas transplantation?

OBJECTIVE: To analyze outcomes in simultaneous kidney-pancreas transplantation (SKPT) recipients who retain C-peptide production at the time of SKPT. METHODS: This retrospective analysis of SKPTs from January 2002 through January 2007 compared outcomes between patients with absent or low C-peptide levels (<2.0 ng/mL, group A) with those having levels > or =2.0 ng/mL (group B). RESULTS: Among 74 SKPTs, 67 were in group A and seven in group B (mean C-peptide level 5.7 ng/mL). During transplantation, group B subjects were older (mean age 51 vs 41 years, P = .006); showed a later age of onset of diabetes (median 35 vs 13 years, P = .0001); weighed more (median 77 vs 66 kg, P = .24); had a greater proportion of African-Americans (57% vs 13%, P = .004); and had a longer pretransplant duration of dialysis (median 40 vs 14 months, P = .14). With similar median follow-up of 40 months, death-censored kidney (95% group A vs 100% group B, P = NS) and pancreas (87% group A vs 100% group B, P = NS) graft survival rates were similar, but patient survival (94% group A vs 71% group B, P = .03) was greater in group A. At 1-year follow-up, there were no significant differences in rejection episodes, surgical complications, infections, readmissions, hemoglobin A1C or C-peptide levels, serum creatinine, or MDRD GFR levels. CONCLUSIONS: Diabetic patients with measurable C-peptide levels before transplant were older, overweight, more frequently African-American and had a later age of onset of diabetes, longer duration of pretransplant dialysis, and reduced patient survival compared to insulinopenic patients undergoing SKPT. The other outcomes were similar.

Tick histamine-binding proteins: lipocalins with a second binding cavity.

Tick histamine-binding proteins (HBPs) are lipocalins with two binding pockets. One of these binds histamine with a high affinity and is found at the position expected from other lipocalins, adjacent to the omega-loop at the open-end of the beta-barrel. A second binding cavity, which is a low-affinity site for histamine in one of the HBPs, is located at the end of the barrel that is closed off in other lipocalins. In order to create the second site, the 'closed-end' region has undergone a major reconstruction. Typical lipocalin characteristics, such as the 3(10) helix and a structural cluster of highly conserved residues, have been lost, while an alpha-helix now shields the cavity from the exterior. The prominence of acidic residues in the binding pockets is another distinctive characteristic of HBPs. Whereas most lipocalins have highly hydrophobic binding cavities designed to bind lipophilic compounds, HBPs have evolved to trap cationic, hydrophilic molecules.

Successful simultaneous kidney-pancreas transplantation from extreme donors.

UNLABELLED: The purpose of this study was to retrospectively review our experience with "extreme" pancreas donors compared to conventional (CONV) donors. METHODS: "Extreme" (EX) pancreas donors were defined as deceased donors (DDs) age >50 years, <8 years, donation after cardiac death (DCD), and targeted for organ discard. RESULTS: From January 2002 through January 2005, we performed 40 simultaneous kidney-pancreas transplants (SKPT) with Thymoglobulin induction, including 9 (22.5%) from EX and 31 from CONV DDs. Mean DD age was higher in EX DD (41.2 years EX vs 26.0 CONV, P < .05), but mean recipient age and cold ischemia times did not differ between groups. With a mean follow-up of 16.8 months in the EX DD group, patient and kidney graft survival rates are both 100%, and the pancreas graft survival rate is 89%. With a mean follow-up of 21.7 months in the CONV DD group, patient and kidney graft survival rates are both 93.5% and the pancreas graft survival rate is 77.4%. All patients with surviving grafts exhibited good initial (1 case of delayed kidney graft function in a CONV DD) and stable long-term kidney and pancreas graft function. Mean length of initial hospital stay and the incidences of acute rejection, readmissions, operative complications, and infections were similar between groups. CONCLUSIONS: The results of this study suggest that the limits of donor acceptability continue to evolve as excellent outcomes can be achieved in SKPTs from selected EX DDs.

Experience with alternate-day thymoglobulin induction in pancreas transplantation with portal-enteric drainage.

The purpose of this study was to retrospectively review outcomes in patients undergoing pancreas transplantation (PTX) with a novel induction protocol of alternate-day thymoglobulin (rATG) in combination with tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. From January 2002 through January 2005, we performed 55 PTXs in 53 patients. The first dose of rATG (1.5 mg/kg) was given intraoperatively, and subsequent doses were given on alternate days until therapeutic TAC levels (>8 ng/mL) were achieved. All patients underwent PTX with enteric drainage, including 51 with portal and 4 with systemic venous drainage. Patients received a minimum of 2 and maximum of 6 doses of rATG induction (median 3 doses). The patient group had a mean age of 42.8 years and included 40 simultaneous kidney-PTX, 11 sequential PTX after kidney, and 4 PTX-alone transplant recipients. Patient, kidney, and pancreas graft survival rates are 96%, 96%, and 84%, respectively, with a mean follow-up of 21 months. The incidence of acute rejection was 18%; there were no graft losses due to isolated acute rejection. The incidence of infection was 60%, but there were no cases of polyomavirus or Epstein-Barr virus infection and only 6 cases (11%) of cytomegalovirus infection. The composite endpoint of no rejection, graft loss, or mortality was attained by 71% of patients. At present, 94% of surviving patients are both dialysis and insulin-free, including 5 successful PTX retransplants. These findings suggest that PTX with portal-enteric drainage and alternate day rATG induction may result in excellent intermediate-term outcomes.

Lower gastrointestinal tract dysfunction in patients receiving long-term hemodialysis.

Severe bowel dysfunction developed in 25 of 945 patients receiving long-term hemodialysis during a ten-year period. Colonic perforation occurred in 12 patients, six of whom died due to peritonitis. In seven instances, the perforation occurred spontaneously. Ten other individuals exhibited prolonged, severe adynamic ileus that progressed to colonic pseudo-obstruction in eight patients. Medical decompression (eight patients) and surgical bowel decompression (two patients) resulted in recovery in nine. Aluminum hydroxide gel, which was taken regularly by all patients, was associated with notable chronic constipation prior to the occurrence of bowel perforation or protracted adynamic ileus in 78% of these individuals.

The effect of the American Heart Association step one diet on hyperlipidemia following renal transplantation.

Cardiovascular disease is a frequent cause of morbidity and mortality following renal transplantation. The percentage of deaths due to ischemic cardiovascular disease and cerebrovascular accidents nearly equals that caused by infection among patients receiving their first transplant, according to data from the European Dialysis and Transplant Association Registry. Hypercholesterolemia is a risk factor for cardiovascular disease frequently identified following renal transplantation, and diets low in fat and cholesterol have been suggested as treatment. Previous studies have not reported the response of LDL cholesterol to dietary treatment, and it is this form of cholesterol that is most closely related to cardiovascular disease. The American Heart Association has provided nutritionists with guidelines for the treatment of hyperlipidemic patients which include the Step One Diet. Previous dietary studies of renal transplant recipients have allowed a slightly higher intake of fat than that currently recommended by the AHA. We wondered if an easily reproducible diet well known to nutritionists such as the AHA Step One Diet would be effective in lowering cholesterol levels in hyperlipidemic renal transplant recipients. The purpose of our study was not to define the mechanisms of posttransplant hyperlipidemia, but rather to assess the effectiveness of dietary intervention on hyperlipidemia following renal transplantation.

Relationship between underlying renal disease and renal transplantation outcome.

The purpose of this study is to better characterize graft and patient survival posttransplantation by examining survival according to underlying renal disease for all first-time renal allograft recipients in the United Network for Organ Sharing (UNOS) registry. From 1987 through 1996, the UNOS registry collected data on 23,838 living and 67,183 cadaveric renal transplantations. This investigation included all patients undergoing their first renal transplantation for whom the underlying cause of renal failure could be identified and categorized. Gross 1- and 3-year patient and graft survival according to underlying renal disease are included. In addition, a Cox proportional hazards model was created to analyze the effect of underlying disease on graft and patient survival after adjusting for comorbid conditions, demographics, and type of renal transplant (living versus cadaveric). The association between underlying disease and graft and patient survival is shown. Amyloidosis, sickle cell anemia, scleroderma, and radiation nephritis are associated with poor graft and patient survival. The risk ratio for patient mortality was more than twice that for immunoglobulin A nephropathy for a number of conditions, including analgesic nephropathy, amyloidosis, and both forms of diabetes mellitus.

Development of a model using polypeptide antibodies for scintigraphy of the pancreas.

A study was designed to develop an agent for pancreatic scintigraphy with greater specificity for the pancreas than selenomethionine. A series of successful experiments was performed using rabbit-produced antibodies to the recently discovered hormone, pancreatic polypeptide. Via hemagglutination and radiolabeled hemagglutination studies, the antibody activity was demonstrated. Gel diffusion studies showed selective uptake by the rat pancreas of intravenously injected antibody and no uptake by the liver and spleen. Immunocytochemical studies on human tissue demonstrated the same selectivity for the pancreas. Also, the titers of different batches of rabbit-produced antibody were quantitated by the enzyme-linked immunospecific assay system. These studies indicate that polypeptide antibody has the potential for carrying a radionuclide selectively to the pancreas.

Racial differences in HLA antigen frequency and hypertensive renal failure.

Black patients with hypertension are six times more likely to develop end-stage renal disease than are their white counterparts. To determine if genetic differences associated with the Human Leukocyte Antigen (HLA) system account for racial variation in hypertensive renal failure, we examined antigenic frequencies from a large renal transplant registry. Human Leukocyte Antigen phenotypes from cadaveric renal transplant recipients and donors in the South Eastern Organ Procurement Foundation database from 1982 to 1986 were analyzed. One thousand six hundred four renal transplant recipients with hypertensive renal failure as the cause of end stage renal disease (cases) were compared with 4506 race-matched cadaveric kidney donors (controls). Log-linear models were used to assess the relationship between hypertensive renal failure and prevalence of each HLA phenotype. Bonferroni adjustments of P values were used to correct for multiple comparisons. Comparison of HLA frequencies between blacks and whites with hypertensive renal failure demonstrated that blacks had an increased frequency of HLA-DR3 beyond that normally known to exist between black and white populations. Black cases compared to black controls had an 8.6% increase in HLA-DR3 frequency contrasted with a 1.6% decrease in the frequency of this antigen between white cases and white controls. This absolute 10.2% difference between the races was significant (P = .02) because the control black and white populations had nearly identical frequencies for this antigen. White cases compared to white controls had lower HLA-A1 and B8 frequencies (21.2% v 30.6%, P = .0005 and 13.7% v 22.3%, P = .001, respectively) and a greater HLA-B35 frequency (20.7% v 14.2%, P = .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Endometrial carcinoma diagnosed by examination of peritoneal dialysate.

Well-differentiated adenocarcinoma of the endometrium was diagnosed by cytologic examination of peritoneal dialysate during continuous ambulatory peritoneal dialysis in a 70-year-old woman. The patient had undergone estrogen therapy for 16 years. The carcinoma was localized, noninvasive, and apparently at an early stage of development. Surgical removal was followed by megestrol acetate chemotherapy and the patient currently remains on peritoneal dialysis, free of recurrence, at 14 months. This case suggests that cellular material from the endometrium can be retrieved from intraperitoneal dialysate in patients undergoing peritoneal dialysis. Therefore, cytologic examination should be performed on peritoneal fluid with elevated counts associated with sterile cultures or atypical features.

Effect of nabumetone on hemostasis during arthroscopic knee surgery.

The known effects of commonly used nonsteroidal anti-inflammatory drugs (NSAIDs) on hemostatic parameters have led to concern over their use in the perioperative period. Nabumetone, unlike other NSAIDs, has little effect on collagen-induced platelet aggregation. To evaluate the effect of nabumetone 2000 mg daily on other hemostatic parameters (e.g., bleeding time, prothrombin time, and partial thromboplastin time) in the clinical setting, this double-masked study was conducted in patients with osteoarthritis undergoing arthroscopic knee surgery. After a 1-week placebo washout period, 58 patients were randomized to receive nabumetone and 53 were randomized to receive placebo. They were assessed before surgery (after 1 to 2 weeks of treatment) and again after surgery (after an additional 3 weeks of treatment). The study was designed to have 90% power to show equivalence in bleeding time to within 1.5 minutes, a difference assumed to be of no clinical importance. No meaningful differences were observed between the groups in any of the measured hemostatic parameters. Before surgery, the bleeding time increased by only 0.3 minutes with nabumetone and decreased by 0.2 minutes with placebo. The mean (+/- SD) difference between the groups in change from baseline was 0.5 +/- 0.3 minutes. After surgery, the changes were 0.1 minutes and 0.0 minutes, respectively, and the difference between groups was 0.2 +/- 0.3 minutes. These differences were neither statistically nor clinically significant, and maximum individual increases were similar in each group. Furthermore, there were no reports of abnormal bleeding in the operative knees. The results of this study show that nabumetone had little or no effect on hemostasis and suggest that this drug can be used safely in the perioperative period.