Optics Concept for a Pair of Undulator Beamlines for MX.

We describe a concept for x-ray optics to feed a pair of macromolecular crystallography (MX) beamlines which view canted undulator radiation sources in the same storage ring straight section. It can be deployed at NSLS-II and at other low-emittance third-generation synchrotron radiation sources where canted undulators are permitted, and makes the most of these sources and beamline floor space, even when the horizontal angle between the two canted undulator emissions is as little as 1-2 mrad. The concept adopts the beam-separation principles employed at the 23-ID (GM/CA-CAT) beamlines at the Advanced Photon Source (APS), wherein tandem horizontally-deflecting mirrors separate one undulator beam from the other, following monochromatization by a double-crystal monochromator. The scheme described here would, in contrast, deliver the two tunable monochromatic undulator beams to separate endstations that address rather different and somewhat complementary purposes, with further beam conditioning imposed as required. A downstream microfocusing beamline would employ dual-stage focusing for work at the micron scale and, unique to this design, switch to single stage focusing for larger beams. On the other hand, the upstream, more highly automated beamline would only employ single stage focusing.

Circulatory assistance with a permanent implantable IABP: initial human experience.

PURPOSE: The Kantrowitz CardioVAD (KCV) is an electrically powered, pneumatically driven circulatory assist device which provides diastolic augmentation and systolic unloading to the failing heart. It consists of a 60cc-pumping chamber, a percutaneous access device (PAD), and an external controller. The pumping chamber, is surgically implanted in the descending thoracic aorta with the patient on cardiopulmonary bypass. Its physiologic function is analogous to that of the intra-aortic balloon pump (IABP). METHODS: Between 1997 and 2000, 5 men (age 59 to 73) with end-stage cardiomyopathy refractory to maximal drug treatment and with documented hemodynamic improvement on an IABP were enrolled in a feasibility study. RESULTS: Mean bypass time was 157 minute (range 120 to 196 minute); mean cross-clamp time was 101 minute (range 69 to 144). Patient 1 died intra-operatively. Compared with preoperative values, at 1 month, cardiac index increased (1.7 to 2.6 L/min/m(2)) and there were significant decreases in creatinine (2.6 to 1.5 mg/dL), pulmonary capillary wedge pressure (PCWP) (32 to 14 mm Hg), and right atrial pressure (RA) (19 to 9 mm Hg). NYHA class improved (IV to II). The mean increase in cardiac index with the KCV OFF to ON was 0.53 L/min/m(2) (36%). Two patients were discharged home. The device was used intermittently without thromboembolic complications. The only device related complications were attributed to PAD design and have been corrected. CONCLUSION Our initial human trial demonstrates successful implantation of the KCV in end-stage patients, the ability of the device to be used intermittently without anticoagulation, and documents hemodynamic and functional improvement in the status of these patients.

Hypotension, acidosis, and vasodilatation syndrome post-heart transplant: prognostic variables and outcomes.

BACKGROUND: In recent years a syndrome characterized by hypotension, acidosis, and vasodilatation, which we have designated HAV syndrome, has been reported to occur more frequently after heart transplantation (HT), but its pathogenesis is unknown. METHODS: We analyzed consecutive patients undergoing HT between January 1994 and June 1998 (aged 50 +/- 8 years; 87% male; 40% African American; ischemia time, 190 +/- 20 minutes; given triple immunosuppression without anti-lymphocyte antibodies) in 2 groups: 38 (54%) who developed HAV (systemic vascular resistance < or = 800 dines x sec x cm(-5) and serum bicarbonate < or = 20 mEq/liter) and 32 (46%) who did not. To identify causes of HAV, we compared 113 pre-HT donor and recipient variables, 28 peri-HT variables, and 46 post-HT variables between groups. We used Mann-Whitney, Fisher exact, and chi-squared tests to compare variables and to determine significance. RESULTS: Univariate analysis showed that HAV patients had significantly greater recipient and donor weight (p = 0.000007 and 0.0017, respectively), longer ischemia times (p = 0.0052), pre-HT use of beta-blockers (p = 0.009), and longer waiting times for HT (p = 0.018). African-American patients had less HAV than Caucasians (p = 0.047). Patients with pre-HT mechanical circulatory assistance had less HAV than pharmacologically treated patients (p = 0.014). Multivariate analysis showed that recipient (p = 0.0004) and donor weight (p = 0.0394) and ischemia time (p = 0.0015) independently predicted HAV and correlated with HAV severity. Deaths at < or =30 days of HT occurred more in patients with (33%) than in those without (15%) HAV. CONCLUSIONS: (1) Hypotension, acidosis, and vasodilatation after HT are associated with high mortality. (2) Recipient and donor weights and ischemia time are independent risk factors for HAV. (3) Pre-HT mechanical circulatory assistance and African-American race confer protection against HAV. (4) Because HAV risk factors can be altered, prevention may be possible. Further study is needed to identify the cellular and humoral mediators of HAV.

Substrate deformation in a hypoxanthine-guanine phosphoribosyltransferase ternary complex: the structural basis for catalysis.

BACKGROUND: Hypoxanthine-guanine phosphoribosyltransferases (HGPRTs) are well-recognized antiparasitic drug targets. HGPRT is also a paradigmatic representative of the phosphoribosyltransferase family of enzymes, which includes other important biosynthetic and salvage enzymes and drug targets. To better understand the reaction mechanism of this enzyme, we have crystallized HGPRT from the apicomplexan protozoan Toxoplasma gondii as a ternary complex with a substrate and a substrate analog. RESULTS: The crystal structure of T. gondii HGPRT with the substrate Mg2+-PRPP and a nonreactive substrate analog, 9-deazaguanine, bound in the active site has been determined at 1.05 A resolution and refined to a free R factor of 15.4%. This structure constitutes the first atomic-resolution structure of both a phosphoribosyltransferase and the central metabolic substrate PRPP. This pre-transition state complex provides a clearer understanding of the structural basis for catalysis by HGPRT. CONCLUSIONS: Three types of substrate deformation, chief among them an unexpected C2'-endo pucker adopted by the PRPP ribose ring, raise the energy of the ground state. A cation-pi interaction between Tyr-118 and the developing oxocarbenium ion in the ribose ring helps to stabilize the transition state. Enforced substrate propinquity coupled with optimal reactive geometry for both the substrates and the active site residues with which they interact contributes to catalysis as well.

Crystal structures of the Toxoplasma gondii hypoxanthine-guanine phosphoribosyltransferase-GMP and -IMP complexes: comparison of purine binding interactions with the XMP complex.

The crystal structures of the guanosine 5'-monophosphate (GMP) and inosine 5'-monophosphate (IMP) complexes of Toxoplasma gondii hypoxanthine-guanine phosphoribosyltransferase (HGPRT) have been determined at 1.65 and 1.90 A resolution. These complexes, which crystallize in space groups P2(1) (a = 65.45 A, b = 90.84 A, c = 80. 26 A, and beta = 92.53 degrees ) and P2(1)2(1)2(1) (a = 84.54 A, b = 102.44 A, and c = 108.83 A), each comprise a tetramer in the crystallographic asymmetric unit. All active sites in the tetramers are fully occupied by the nucleotide. Comparison of these structures with that of the xanthosine 5'-monophosphate (XMP)-pyrophosphate-Mg(2+) ternary complex reported in the following article [Héroux, A., et al. (1999) Biochemistry 38, 14495-14506] shows how T. gondii HGPRT is able to recognize guanine, hypoxanthine, and xanthine as substrates, and suggests why the human enzyme cannot use xanthine efficiently. Comparison with the apoenzyme reveals the structural changes that occur upon binding of purines and ribose 5'-phosphate to HGPRT. Two structural features important to the HGPRT mechanism, a previously unrecognized active site loop (loop III', residues 180-184) and an active site peptide bond (Leu78-Lys79) that adopts both the cis and the trans configurations, are presented.

Crystal structure of Toxoplasma gondii hypoxanthine-guanine phosphoribosyltransferase with XMP, pyrophosphate, and two Mg(2+) ions bound: insights into the catalytic mechanism.

The crystal structure of the Toxoplasma gondii hypoxanthine-guanine phosphoribosyltransferase (HGPRT)-xanthosine 5'-monophosphate (XMP)-pyrophosphate-Mg(2+) ternary complex has been determined at 1. 60 A resolution. This biproduct, post-transition state structure is of a T. gondii HGPRT mutant (Asp150Ala or D150A). The D150A mutant has reduced activity (k(cat) lower by 11-, 296-, and 8.6-fold for hypoxanthine, guanine, and xanthine, respectively) compared to wild-type T. gondii HGPRT. The Michaelis constants for purine bases are altered only slightly, whereas those for alpha-D-5-phosphoribosyl 1-pyrophosphate (PRPP) are lower by approximately 6.5-fold. The ternary complex crystallizes in space group C222(1) (a = 55.21 A, b = 112.25 A, and c = 144.28 A) with two subunits in the asymmetric unit; the HGPRT tetramer is completed by the application of 2-fold crystallographic symmetry. All active sites contain XMP ¿bound in a fashion similar to that of the guanosine 5'-monophosphate (GMP) and inosine 5'-monophosphate (IMP) complexes reported in the preceding article [Héroux, A., et al. (1999) Biochemistry 38, 14485-14494]¿, pyrophosphate, and two Mg(2+) ions. Each Mg(2+) ion is octahedrally coordinated by two terminal pyrophosphate oxygen atoms and several ordered water molecules. This structure shows how HGPRT uses two Mg(2+) ions to orient and activate the pyrophosphate moiety of PRPP for attack by a purine base, and why mutation in humans of the residue corresponding to Asp206, the only HGPRT amino acid that directly contacts the Mg(2+) ions, causes Lesch-Nyhan syndrome (HGPRT(Kinston), D193N). The Leu78-Lys79 peptide bond in the active site adopts the cis configuration, which it must to bind PRPP or pyrophosphate. The contribution of cis-trans isomerization of this peptide bond to the energetics of substrate binding and product release is discussed. A comprehensive description of the HGPRT reaction mechanism is also proposed.

Outpatient inotropic therapy in heart transplant candidates: should its use influence waiting list priority status?

BACKGROUND: The use of outpatient intravenous inotropic therapy in heart transplant candidates is contentious. In addition to concerns about morbidity and mortality rates, the current United Network for Organ Sharing (UNOS) heart allocation system presently grants no waiting list priority status benefit to candidates who receive intravenous inotropic therapy in the outpatient setting (UNOS status 2), whereas identical therapy given in an intensive care unit setting does increase priority status (UNOS status 1). The goal of this study was to determine whether an increase in UNOS waiting list priority status is justified in heart transplant candidates receiving outpatient intravenous inotropic therapy by comparing the waiting list mortality of UNOS status 2 candidates on such therapy with that of UNOS status 2 candidates maintained on oral heart failure agents alone. METHODS: This is a retrospective analysis of the pretransplantation outcomes of heart transplant candidates initially listed as UNOS status 2, comparing 29 candidates receiving intravenous outpatient inotropic therapy (group 1) to 109 candidates maintained on oral heart failure agents alone (group 2). RESULTS: The waiting list mortality was not significantly different between the two groups (group 1=7% vs group 2=20%, p=.18); however, group 1 patients had greater morbidity rates while awaiting transplantation than group 2 patients. A greater percentage of group 1 than group 2 patients clinically deteriorated to UNOS status 1 while awaiting transplantation (45% vs 11%), resulting in more group 1 patients undergoing transplantation overall, (59% vs 33%, p=.01) and more group 1 than group 2 patients undergoing transplantation at a higher priority status, UNOS status 1 (76% vs 33%, p=.003). Group 1 patients had more pretransplantation heart failure admissions (1.2 vs 0.6 admissions/total waiting period, p=.02) and longer hospital stays (26+/-39 vs 8.8+/-16 days, p=.03), spent a greater percentage of their total waiting time hospitalized (7% vs 2%, p=.003), and were more likely than group 2 patients to receive intravenous inotropic therapy during hospitalization (70% vs 25%, p=.001). CONCLUSION: This study suggests that heart transplant candidates who require maintenance outpatient intravenous inotropic therapy represent a subgroup of UNOS status 2 candidates with greater waiting list morbidity, but no greater waiting list mortality than candidates who can be maintained on oral heart failure agents alone. However, the current UNOS heart allocation system provides for this increased illness acuity by assigning a higher priority status when necessary. A larger, prospective study is necessary to determine whether a true difference in waiting list mortality rates exists and if an increase in priority status is justified for UNOS status 2 candidates requiring maintenance inotropic therapy.

Effects of methotrexate on acute rejection and cardiac allograft vasculopathy in heart transplant recipients.

BACKGROUND: In heart transplant recipients methotrexate has been shown to reverse recurrent/persistent acute rejection refractory to intensified conventional immunosuppression. This study sought to determine whether methotrexate produces a sustained decline of heart allograft rejection rates and renders rejection rates of patients with a history of recurrent/persistent rejection similar to those of heart transplant recipients without such history. METHODS: Rejection, infection, and cardiac allograft vasculopathy were compared in 35 patients treated with methotrexate (12 +/- 9 mg/week for 34 +/- 54 weeks) and 236 patients never given methotrexate. Because the mean time from transplantation to initiation of methotrexate was 9.4 months, patients treated without methotrexate were analyzed for events < or = 9.4 versus > 9.4 months after heart transplantation. RESULTS: Demographics, perioperative and maintenance immunosuppression, and postoperative follow-up time (58 +/- 32 vs 57 +/- 33 months) were similar in the two groups. Rejection rates decreased in both groups but remained significantly higher in the patients treated with methotrexate after initiation of therapy than in the patients treated without methotrexate more than 9.4 months after transplantation (0.15 +/- 0.16 vs 0.06 +/- 0.12 episodes/patient/month; p = 0.0014). Infection rates were higher in patients after methotrexate initiation than in patients treated without methotrexate more than 9.4 months after heart transplantation (0.17 +/- 0.24 vs 0.06 +/- 0.13 episodes/patient/month; p = 0.015). At the end of the follow-up period methotrexate- and non-methotrexate-treated groups did not differ in the percentage of patients with angiographically detectable cardiac allograft vasculopathy (17.1% and 21.2%, respectively) and survival (71.4% and 64.0%, respectively). CONCLUSIONS: Even after reversal of rejection by methotrexate, patients requiring methotrexate for the treatment of persistent/recurrent rejection continued to have higher rejection rates than patients not requiring methotrexate. In spite of persistently higher rejection rates, patients treated with methotrexate did not have higher rates of cardiac allograft vasculopathy. This finding raises the question whether methotrexate provides a protective influence on the development of cardiac allograft vasculopathy in this high-risk group.

Does heart transplantation confer additional benefit over medical therapy to patients who have waited > 6 months for heart transplantation?

OBJECTIVES: This study compared the survival of patients with heart failure who have waited > 6 months for heart transplantation with that patients who undergo heart transplantation after a similarly prolonged waiting period. BACKGROUND: There are little data describing outcome in patients with severe heart failure who have waited for extended periods of time on the heart transplant waiting list. METHODS: Sixty-three consecutive patients who spent > 6 months on the heart transplant waiting list were examined. Mean (+/- SD) age was 53 +/- 9 years, mean left ventricular ejection fraction was 19 +/- 6%, and all were taking digoxin and diuretic and vasodilator agents. Patients who underwent transplantation during the follow-up period were censored from the pretransplantation analysis, and their survival was examined as part of the posttransplantation phase of the study. RESULTS: Of the 63 original patients examined, 25 underwent transplantation, 10 during inotropic or mechanical circulatory support. The pretransplantation mortality rate was 6% at 6 months after the 6-month milestone on the waiting list, 12% at 12 months and 22% at 18 months. The posttransplantation mortality rate was 5% at 6 months, 10% at 12 months and 24% at 18 months. There were no differences in survival at any time between the two phases of the study. CONCLUSIONS: Survival of patients who have survived > 6 months on the heart transplant waiting list is generally good. Although heart transplantation did not appear to confer additional survival advantage over medical therapy, a large proportion of the patients who underwent transplantation were critically ill at the time of transplantation and would undoubtedly have died of progressive heart failure had they not undergone transplantation. We conclude that heart transplantation should still be considered a therapeutic alternative in patients with heart failure even after a prolonged waiting period on the heart transplant waiting list.

Factors associated with the development of persistently depressed cardiac output during the first year after cardiac transplantation.

The purpose of this study was to determine factors associated with the development of a persistently depressed cardiac output during the first year after cardiac transplantation. With this aim in mind, the records of 133 consecutive patients undergoing orthotopic cardiac transplantation and surviving for > or = 1 year after transplantation were reviewed. For each patient, the mean cardiac index for each of the 3-month periods, 0-3, 4-6, 7-9, and 10-12 months after transplantation was calculated. Of the 133 patients, 19 (14%) had a mean cardiac index < 2.4 l/min/m2 during > or = 3 of these 3-month periods. The pre- and post-transplantation clinical, immunologic, and hemodynamic data of these 19 patients (study group) were compared with the remaining 114 patients (control group). Compared with the control group, the patients in the study group were older (56 +/- 5 vs. 46 +/- 15 years; p = 0.0001), more frequently had ischemic heart disease as the original diagnosis (58 vs. 37%; p < 0.05), had a lower preoperative cardiac index (1.91 +/- 0.53 vs. 2.71 +/- 1.0 l/min/m2; p = 0.0001), more frequently did not receive perioperative anti-T cell therapy (47 vs. 25%; p = 0.046), and had a greater median number of infections during the first year after transplantation (5 vs. 3; p = 0.027). However, only one factor--a low preoperative cardiac index--emerged as an independent predictor of the development of a persistently depressed cardiac index during the first year after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk/benefit ratio of perioperative OKT3 in cardiac transplantation.

To evaluate the risk/benefit ratio of perioperative OKT3 in cardiac transplant patients receiving triple-drug immunosuppression, patients who underwent cardiac transplantation between July 1, 1988 and December 31, 1989 (n = 33) and who received perioperative OKT3 were retrospectively compared with patients who underwent transplantation between January 1, 1990 and June 30, 1991 (n = 46), and who received no perioperative anti-T cell therapy. To allow similar follow-up, data were analyzed through June 30, 1990 for the OKT3 group and through December 31, 1991 for the no anti-T cell therapy group. Patients in the no anti-T cell therapy group waited longer for a donor organ; other pretransplant characteristics did not differ. The azathioprine dose 1 month after transplant was higher in the no anti-T cell therapy group (144 +/- 63 mg vs 109 +/- 55 mg, p = 0.016); other post-transplant immunosuppression was similar. The incidence of total and treated rejection and the time to the first rejection did not differ between the groups. The OKT3 group had a higher number of infections (0.8 +/- 0.9 vs 0.3 +/- 0.3, p = 0.006) and intravenously treated infections (0.5 +/- 0.6 vs 0.1 +/- 0.2, p = 0.004) per patient per month. Cytomegalovirus infection developed in 46% of the OKT3 group versus 22% of the no anti-T cell therapy group (p = 0.025). Patient survival did not differ between the groups. Thus, an immunosuppressive regimen that includes perioperative OKT3 increases infections, especially cytomegalovirus infections, without decreasing or delaying rejection or increasing survival.

Intracoronary ultrasound assessment of morphological and functional abnormalities associated with cardiac allograft vasculopathy.

BACKGROUND: The diffuse nature of cardiac allograft vasculopathy makes early detection of the disease by traditional noninvasive methods or coronary angiography difficult. The aim of this study was to determine if there is a relation between abnormalities in vessel wall morphology, as assessed by intracoronary ultrasound, and a decreased vasodilatory response to the endothelium-dependent vasodilator papaverine hydrochloride and if cardiac allograft vasculopathy detected by coronary angiography is associated with specific intracoronary ultrasound findings. METHODS AND RESULTS: Twenty-three heart transplant recipients underwent 25 intracoronary ultrasound studies and 24 studies of coronary vasomotor tone 10 days to 8.3 years after surgery using a 20-mHz intracoronary ultrasound catheter. The studies were divided in two groups according to the presence (n = 7, group 1) or absence (n = 18, group 2) of angiographically evident cardiac allograft vasculopathy. Qualitative assessment of vessel wall morphology and quantitative analysis of the vasodilator response to the injection of papaverine hydrochloride into the coronary artery distal to the imaging site were performed off-line, and results for the two study groups were compared. A significantly higher percentage of patients with than without angiographic evidence of cardiac allograft vasculopathy had a three-interface vessel wall morphology by intracoronary ultrasound (100% versus 11%, P < .001). In two recipients who underwent two serial studies, the appearance of three interfaces in the vessel wall or a progressive thickening of the inner interface of the vessel wall occurred in conjunction with the appearance of angiographic cardiac allograft vasculopathy. The vasodilator response to papaverine was less in patients with than in those without angiographically evident cardiac allograft vasculopathy both in terms of absolute and relative increases in lumen diameter (+0.1 +/- 0.12 mm versus +0.3 +/- 0.17 mm, P < .05, and +5.1 +/- 5.3% versus +8.2 +/- 5.3%, P = NS) and lumen cross-sectional area (+0.5 +/- 0.6 mm2 versus +1.7 +/- 1.1 mm2, P < .02, and +7.1 +/- 8.8% versus 16.6 +/- 11.0%, P = .055), respectively. CONCLUSIONS: Intracoronary ultrasound assessment of vessel wall morphology and evaluation of vascular response to endothelium-dependent vasodilators are useful techniques for detecting cardiac allograft vasculopathy.

Abnormal ambulatory left ventricular ejection fraction in heart transplant arteriopathy.

The morbidity and mortality from heart transplantation has been reduced dramatically over the last several years. However, the long-term survival in heart transplant recipients is limited by arteriopathy in the allograft coronary arteries, the pathophysiology of which is poorly understood. The diagnosis of this arteriopathy is at present limited to cardiac catheterization. Noninvasive studies have proven to be of limited benefit in diagnosing this arteriopathy. The authors performed cardiac vest studies in nine heart transplant recipient patients. Six of the vest studies were abnormal; five of the patients had documented transplant coronary artery disease by cardiac catheterization. They found that the sensitivity and negative predictive value of the cardiac vest in identifying arteriopathy in transplant recipients was 100%. The authors propose that cardiac vest could be a sensitive, noninvasive screening test for identifying arteriopathy in heart transplant recipients.

Endocardial infiltrates in the transplanted heart: clinical significance emerging from the analysis of 5026 endomyocardial biopsy specimens.

UNLABELLED: To further elucidate the significance of endocardial infiltrates in heart transplant patients, the presence, frequency, and type of endocardial infiltrates were evaluated in 5026 endomyocardial biopsy specimens obtained from 200 heart transplant patients 0 to 75 months after heart transplantation. The relationship of endocardial infiltrates to immunologic, clinical, and demographic variables was then explored. Endocardial infiltrates were detected in 557 endomyocardial biopsy specimens (11%) from 117 heart transplant patients (58%) at 6.3 +/- 9.4 months (mean +/- SD; range, 0 to 49 months) after heart transplantation. Heart transplant patients with endocardial infiltrates were younger (p = 0.03), had a greater incidence of idiopathic dilated cardiomyopathy before heart transplantation (p = 0.05), and included a greater percentage of females (p < 0.05). Both total and treated rejection rates were significantly higher in patients with endocardial infiltrates versus those without endocardial infiltrates (p = 0.0001). Rejection on the subsequent endomyocardial biopsies was more often present in endocardial biopsy specimens with endocardial infiltrates than in those without endocardial infiltrates, both in the presence (37% versus 24%; p < 0.001) and absence (33% versus 19%; p < 0.0001) of concomitant findings of rejection. No association was identified between endocardial infiltrates and posttransplantation lymphoproliferative disorder, cytomegalovirus infection, Epstein-Barr virus infection, or cardiac allograft vasculopathy. Multivariate regression analysis confirmed that the occurrence of endocardial infiltrates is associated with rejection when adjustment is made for patient's age, gender, heart disease before transplantation, follow-up time, and number of endomyocardial biopsies after heart transplantation (p = 0.0001). CONCLUSIONS: (1) Endocardial infiltrates may occur with or without associated endomyocardial biopsy findings of rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

HLA-DR incompatibility predicts heart transplant rejection independent of immunosuppressive prophylaxis.

To determine whether immunosuppressive prophylaxis reduces the effect of HLA-DR incompatibility on rejection, we compared clinical and immunologic variables of patients given horse antithymocyte globulin, OKT3, or no immunosuppressive prophylaxis. Median follow-up was 27 months. Groups were similar in race; preoperative HLA reactivity; ABO matching; number of HLA-A, -B, -C, and -DR mismatches; and rejection severity. Patients given immunosuppressive prophylaxis were younger (p = 0.04), had a greater frequency of preoperative ischemic disease (p = 0.03), and had a higher 6-month rejection rate (p = 0.02). A highly significant association was found between the number of mismatches at the HLA-DR locus and rejection severity (p = 0.005). Within the OKT3-based immunosuppressive prophylaxis group and the no immunosuppressive prophylaxis group a significant association was found between the number of HLA-DR mismatches and rejection severity (p = 0.01 and p = 0.009, respectively). A similar trend was identified in the group given horse antithymocyte globulin-based immunosuppressive prophylaxis. Logistic regression, used to identify independent predictors of rejection, showed that the number of HLA-DR mismatches and not the use or type of immunosuppressive prophylaxis is significantly associated with rejection (p = 0.0009). One-year patient survival was 83% in the group with two HLA-DR mismatches and 85% in the group with one or no HLA-DR mismatch. Thus the lower rejection rates in patients with one or no HLA-DR mismatch were not associated with a 1-year survival, which was better than that of patients with two HLA-DR mismatches. The potential benefit of HLA-DR matching on rejection and patient survival must be confirmed by larger prospective studies.