PubMed Health⌕ Search

Biomedical subjects

Robert Bray

Publications and source records attributed to Robert Bray.

5 recordsLinked to original sources

Identification of unrelated cord blood units for hematopoietic stem cell transplantation in children with sickle cell disease.

This study examined the theoretical availability of compatible unrelated umbilical cord blood (UCB) units for hematopoietic stem cell transplantation (HSCT) of children with sickle cell disease (SCD), matched for DRB1 at high resolution. UCB units registered via Bone Marrow Donors Worldwide were matched with patients who had been previously typed for possible HSCT. Suitable matching was determined after typing at antigen level at A and B loci and allele-level typing at DRB1. Forty patients met criteria for analysis. All matched at four of six loci with at least two UCB units, and 50% (n = 20) matched at five of six loci with at least one unit. In patients matched at four loci or more, significantly more units per patient (median 19 vs. 2 units; P = 0.03) at higher cell dose (median 205 vs. 113 best nucleated cell dose per unit; P < 0.01) were identified compared with patients matched at five loci or more. Hypothetically, at a dose of at least 5 x 10 nucleated cells/kg, 54% of patients weighing 40 kg would match with units at four or more of six loci and 5% at five or more of six loci. This study suggests that cord blood units matching at four or more of six HLA loci at acceptable cell doses can be identified for a majority of children with SCD weighing 40 kg or less. Availability of units matched at five or more of six HLA loci was more limited. Defining procedure-related risks and benefits remains a challenge.

Anemia, Sickle Cell↗

Sagittal alignment and the Bryan cervical artificial disc.

OBJECT: The authors evaluated cervical spine radiographs to determine sagittal alignment in patients who underwent one- or two-level arthroplasty with the Bryan cervical artificial disc prosthesis. METHODS: The curvature of the surgically treated spinal segments and the overall curvature of the cervical spine were evaluated in 13 patients who underwent 16 cervical arthroplasty device placements. Preoperative and postoperative lateral radiographs were reviewed and compared using standardized techniques for measuring spinal curvature. Patients who underwent a single-level cervical arthroplasty had a 4.7 degrees mean reduction (p < 0.05) in lordosis after cervical artificial disc replacement. The three patients who underwent two-level cervical arthroplasty had no significant changes in the sagittal alignment. CONCLUSIONS: Patients who underwent arthroplasty with a Bryan cervical artificial disc had a focal loss of lordosis (that is, kyphosis) at the treated levels after single-level procedures. Nevertheless, there was no significant change in the overall sagittal curvature of the cervical spine after single-level artificial disc replacements. The patients who underwent two-level artificial disc placement had no significant changes in lordosis at the treated levels or in the overall curvature. The likely source of this outcome appears to be the endplate milling procedures that reorient the vertebral endplates.

Adult↗

Persistence of low levels of alloantibody after desensitization in crossmatch-positive living-donor kidney transplantation.

BACKGROUND: : Desensitization protocols have been developed to allow successful kidney transplantation in sensitized recipients. However, a detailed analysis of the impact of these protocols on alloantibody has not been performed. METHODS: : We studied 12 living-donor kidney-transplant recipients with positive antihuman globulin-enhanced complement dependent cytotoxicity (AHG-CDC) crossmatches against their donors. Using a variety of crossmatch techniques and single-antigen flowbeads (SAFBs), we characterized the specificity and amount of alloantibody at baseline before desensitization, after desensitization (using plasmapheresis followed by 100 mg/kg intravenous immunoglobulin, and anti-CD20 antibody), and 4 months after transplantation (after splenectomy and on maintenance immunosuppression). RESULTS: : All 12 patients with a positive baseline AHG-CDC crossmatch were AHG-CDC crossmatch negative at the time of transplant (after desensitization). However, despite desensitization, the majority of patients had low-level donor-specific alloantibodies demonstrable on the day of transplantation by both flow crossmatch (FXM 8/12) and SAFBs (10/11). Four months after transplantation, no patient had a positive AHG-CDC crossmatch, but again the majority had persistent low levels of donor-specific alloantibodies by FXM (6/12) and SAFBs (9/11). No patient experienced hyperacute rejection, and the persistence of low levels of donor-specific alloantibodies did not correlate with the development of humoral rejection in the early posttransplant period. CONCLUSIONS: : Despite desensitization, a majority of positive crossmatch transplant recipients demonstrate low levels of donor-specific alloantibodies both on the day of transplant and 4 months after transplantation. The impact of these antibodies appears to be minimal early after transplant, but their long-term significance bears further study.

B-Lymphocytes↗

Laser Doppler imaging of burn scars: a comparison of wavelength and scanning methods.

UNLABELLED: Laser Doppler perfusion imaging (LDI) is a useful tool for the early clinical assessment of burn depth and prognostic evaluation of injuries that may require skin grafting. We have evaluated two commercially available laser Doppler imagers for the perfusion measurement of normal and burn scar tissue. METHODS: A single wavelength (635 nm), step-wise scanning LDI and a dual wavelength (633 and 780 nm), continuous scanning LDI were used. Twenty patients with hypertrophic burn scars (time since injury: 1 month-8 years) were recruited and the color and elevation of the scar was clinically assessed using a modified Vancouver Burn Scar Scale. Perfusion of each scar region was measured using both imagers. A symmetric contralateral region of unburned skin was also imaged to record baseline perfusion. RESULTS: Comparisons of wavelength and scanning technique were made using perfusion values obtained from 22 burn scars. Highly significant positive correlation was observed in all comparisons. In addition, output from both instruments was strongly and significantly correlated with the clinical grading of the scar. SIGNIFICANCE: Both LDI scanners perform similar perfusion measurements. The results also indicate that red and near-infrared (NIR) wavelength photons provide similar blood flow information. The faster, continuous scanning method provides a clinical advantage without a significant loss of blood flow information. However, a critical evaluation of both instruments suggests that caution must be exercised when using these optical diagnostic techniques and that some knowledge of light-tissue interaction is required for the proper analysis and interpretation of clinical data.

Adult↗

Anti-CD40 therapy extends renal allograft survival in rhesus macaques.

BACKGROUND: Organ transplant recipients currently require lifetime immunosuppressive therapy, with its accompanying side effects. Biological agents that block T-cell costimulatory pathways are important components of strategies being developed to induce transplantation tolerance. The aim of this study was to test the effect of a novel chimeric anti-human CD40 monoclonal antibody (Chi 220), either alone or in combination with CTLA4-Ig, on the survival of renal allografts in a nonhuman primate model. METHODS: Captive-bred adolescent male rhesus monkeys (Macaca mulatta) (4-10 kg) were used as recipients and donors. Four treatment protocols were tested: Chi220 monotherapy, CTLA4-Ig monotherapy, Chi220 combined with CTLA4-Ig, and H106 (anti-CD40L) combined with CTLA4-Ig. Control animals received human albumin. Recipients were followed for survival, renal allograft function as determined by measurement of serum blood urea nitrogen (BUN) and creatinine, chemistries (sodium, potassium, chloride, and bicarbonate), complete blood cell count (CBC) with differential, and the development of donor-specific alloantibody. RESULTS: Treatment with Chi220 for 14 days prolonged renal allograft survival (MST 38.5 vs. 7 days in untreated controls). Notably, simultaneous blockade of the CD28/B7 pathway did not further augment graft survival but did suppress the development of donor-specific antibodies, an effect not achieved with Chi220 alone, despite peripheral B cell depletion. Finally, treatment with Chi220 suppressed the primary immune response to cytomegalovirus, resulting in severe systemic manifestations. CONCLUSIONS: Blockade of the CD40 pathway with anti-CD40 mAb is immunosuppressive in a large animal, preclinical renal transplant model. The potential effect of this therapy on viral immune responses will be important to consider for the design of safe clinical trials.

Abatacept↗