First clinical experience with the DeBakey VAD continuous-axial-flow pump for bridge to transplantation.
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BACKGROUND: A shortage of donor organs and increased numbers of deaths of patients on the waiting list for cardiac transplantation make mechanical circulatory support for a bridge to transplantation a standard clinical procedure. Continuous-flow rotary blood pumps offer exciting new perspectives. METHODS AND RESULTS: Two male patients (ages 44 and 65 years) suffering from end-stage left heart failure were implanted with a DeBakey VAD axial-flow pump for use as a bridge to transplant. In the initial postoperative period, the mean pump flow was 3.9+/-0.5 L/min, which equals a mean cardiac index (CI) of 2.3+/-0.2 L. min(-1). m(-2). In both patients, the early postoperative phase was characterized by a completely nonpulsatile flow profile. However, with the recovery of heart function 8 to 12 days after implantation, increasing pulse pressures became evident, and net flow rose to 4.5+/-0.6 L/min, causing an increase of mean CI up to 2.7+/-0.2 L. min(-1). m(-2). Patients were mobilized and put through regular physical training. Hemolysis stayed in the physiological range and increased only slightly from 2. 1+/-0.8 mg/dL before surgery to 3.3+/-1.8 mg/dL 6 weeks after implantation. CONCLUSIONS: The first clinical implants of the DeBakey VAD axial-flow pump have demonstrated the device to be a promising measure of bridge-to-transplant mechanical support. (+info)
The relationship between fertility potential measurements on cryobanked semen and fecundity of sperm donors.
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Sperm penetration assay (SPA) scores obtained from cryobanked semen were correlated with therapeutic insemination (TI) fecundity in a group of established sperm donors, thereby evaluating the efficacy of the SPA in screening donors for sperm banking. While the SPA has been used to separate fertile from infertile males, we altered assay conditions to use frozen semen and to distinguish performance among fertile donors. Three frozen ejaculates from 11 pregnancy-proven donors were analysed. Of 905 TI cycles, 275 recipients achieved 95 pregnancies. There were no significant relationships between fecundity and donor semen, washed sperm parameters, sperm recoveries or recipient age. A significant relationship was revealed between mean SPA scores (range 8.7-66.6 penetrations/ovum) and donor fecundity (range 0.04-0.16, P < 0.03). Sperm concentration was varied in an effort to establish the most sensitive test condition. Using 0.25x10(6) motile spermatozoa/ml, a highly significant relationship was observed (P < 0.002). The four donors with the lowest SPA scores achieved the four lowest fecundities. It is concluded that a modified SPA can be used on frozen donor semen to estimate donor fertility potential. If applied routinely in donor semen banking, poor quality applicants could be excluded, thereby increasing pregnancy rates while decreasing donor screening costs. (+info)
Counselling couples and donors for oocyte donation: the decision to use either known or anonymous oocytes.
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In order to avoid a long waiting period, the Centre for Reproductive Medicine of the Free University of Brussels suggests that couples in need of donor oocytes search for a donor among family and friends. Recipient couples can choose between two types of donation: known donation, i.e. treatment with the oocytes of the donor recruited by the couple, or anonymous donation, i.e. an exchange of the donor recruited by the couple with a donor recruited by another couple in order to ensure anonymity between donor and recipients. In total, 144 couples were counselled by a psychologist in the decision-making process with regard to the kind of donation to be used. Some 68.8% of the recipient couples preferred known donation. This choice was mainly motivated by reasons related to fears associated with anonymity, such as fear of the unknown origin of genetic material and the trust that couples had in 'their' donor. Almost one-third of the couples opted to use anonymous oocytes. The desire to establish explicit boundaries between the two families involved was the major motivation for this choice. Approximately 44% of the couples were willing to tell the child about the oocyte donation. (+info)
Renal transplantation from non-heart beating donors: a promising alternative to enlarge the donor pool.
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The aim of this study was to compare the survival and midterm function of kidneys from non-heart beating donors (NHBD) with those of kidneys from heart beating donors (HBD). From 1989 to 1998, 144 kidneys were procured from NHBD at the Hospital Clinico San Carlos in Madrid, of which 95 were transplanted. The kidney grafts were maintained from the moment of the diagnosis of cardiac arrest until the time of procurement by cardiopulmonary bypass. There was no significant difference in renal function and the number of rejection episodes between the NHBD and HBD transplants. The NHBD kidneys showed a 5.73-fold increase in the incidence of delayed graft function (adjusted relative risk 95% confidence interval, 2.82 to 11.62). One- and five-year survival rates for NHBD grafts were 84.6 and 82.7%, respectively, compared with 87.5 and 83.9% for HBD (P = 0.5767). Cox analysis showed that the predictive factors for worse NHBD graft survival were type of NHBD donor and the occurrence of corticoresistant rejection. Ninety of the NHBD organs were procured from subjects suffering irreversible cardiac arrest on the street who were transferred to our center for the sole purpose of donation. Fifty-four of these kidneys were transplanted and all showed primary function. When a strict protocol is adhered to, the outcome of renal transplant from NHBD compares well with that from HBD. It is believed that the high number of organs obtained from subjects undergoing irreversible cardiac arrest on the street might encourage the adoption of new criteria for the management of this type of pathology with the ultimate goal of kidney donation. (+info)
A randomized placebo-controlled trial of lisofylline in HLA-identical, sibling-donor, allogeneic bone marrow transplant recipients. The Lisofylline Marrow Transplant Study Group.
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The purpose of the study was to evaluate the effect of lisofylline (LSF) on engraftment, regimen-related toxicities (RRT), and mortality in patients undergoing allogeneic bone marrow transplantation (BMT). We performed a multicenter, randomized placebo-controlled trial in 60 patients with hematologic malignancies receiving BMT from HLA-identical sibling donors. Patients were randomized to receive either placebo, 2 mg/kg LSF or 3 mg/kg LSF every 6 h, beginning before conditioning and continuing to day 21 or hospital discharge. Treatment groups were balanced with respect to conditioning regimen and disease stage. However, significantly more patients in the 2 mg/kg LSF group were at high risk for RRT due to performance status >/=1, age >/=40 years, and prior exposure to CMV. Nausea and vomiting were the only adverse events observed in a higher proportion of LSF-treated patients that led to study withdrawal in six of 42 patients (14%). The times to neutrophil recovery to >/=500/microl and platelet recovery (>20 000/microl) were not improved by LSF treatment. Nevertheless, no patient who received treatment with 3 mg/kg LSF developed a documented infection between day 0 and 35 or had a serious or fatal infection between day 0 and 100 (P = 0.003 vs placebo for both). The day-100 survival rate was also significantly improved in the 3 mg/kg LSF group (89%), compared with either the 2 mg/kg LSF (48%) or placebo (61%) groups (log-rank test, 3 mg/kg LSF vs placebo, P = 0. 026). We conclude that treatment with LSF 3 mg/kg reduced the incidence of infections and improved 100-day survival in patients receiving related-donor allogeneic bone marrow transplantation. Bone Marrow Transplantation (2000) 25, 283-291. (+info)
Evidence for heterogeneity in recombination in the human pseudoautosomal region: high resolution analysis by sperm typing and radiation-hybrid mapping.
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Accurate genetic and physical maps for the human pseudoautosomal region were constructed by use of sperm typing and high-resolution radiation-hybrid mapping. PCR analysis of 1,912 sperm was done with a manual, single-sperm isolation method. Data on four donors show highly significant linkage heterogeneity among individuals. The most significant difference was observed in a marker interval located in the middle of the Xp/Yp pseudoautosomal region, where one donor showed a particularly high recombination fraction. Longitudinal models were fitted to the data to test whether linkage heterogeneity among donors was significant for multiple intervals across the region. The results indicated that increased recombination in particular individuals and regions is compensated for by reduced recombination in neighboring intervals. To investigate correspondence between physical and genetic distances within the region, we constructed a high-resolution radiation-hybrid map containing 29 markers. The recombination fraction per unit of physical distance varies between regions ranging from 13- to 70-fold greater than the genome-average rate. (+info)
Specific B cell tolerance is induced by cyclosporin A plus donor-specific blood transfusion pretreatment: prolonged survival of MHC class I disparate cardiac allografts.
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Donor-specific blood transfusion (DST), designed to prolong allograft survival, sensitized recipients of the high-responder PVG-RT1u strain, resulting in accelerated rejection of MHC-class I mismatched (PVG-R8) allografts. Rejection was found to be mediated by anti-MHC class I (Aa) alloantibody. By pretreating recipients 4 wk before grafting with cyclosporin A (CsA) daily (x7), combined with once weekly (x4) DST, rejection was prevented. The investigation explores the mechanism for this induced unresponsiveness. CD4 T cells purified from the thoracic duct of CsA/DST-pretreated RT1u rats induced rejection when transferred to R8 heart-grafted RT1u athymic nude recipients, indicating that CD4 T cells were not tolerized by the pretreatment. To determine whether B cells were affected, nude recipients were pretreated, in the absence of T cells, with CsA/DST (or CsA/third party blood) 4 wk before grafting. The subsequent transfer of normal CD4 T cells induced acute rejection of R8 cardiac allografts in third party- but not DST-pretreated recipients; prolonged allograft survival was reversed by the cotransfer of B cells with the CD4 T cells. Graft survival correlated with reduced production of anti-MHC class I (Aa) cytotoxic alloantibody. The results indicated that the combined pretransplant treatment of CsA and DST induced tolerance in allospecific B cells independently of T cells. The resulting suppression of allospecific cytotoxic Ab correlated with the survival of MHC class I mismatched allografts. The induction of B cell tolerance by CsA has important implications for clinical transplantation. (+info)
Development of virus-specific CD4(+) T cells during primary cytomegalovirus infection.
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Although virus-specific CD4(+) T cells have been characterized extensively in latently infected individuals, it is unclear how these protective T-cell responses develop during primary virus infection in humans. Here, we analyzed the kinetics and characteristics of cytomegalovirus-specific (CMV-specific) CD4(+) T cells in the course of primary CMV infection in kidney transplant recipients. Our data reveal that, as the first sign of specific immunity, circulating CMV-specific CD4(+) T cells become detectable with a median of 7 days after first appearance of CMV-DNA in peripheral blood. These cells produce the T helper 1 type (Th1) cytokines IFNgamma and TNFalpha, but not the T helper 2 type (Th2) cytokine IL4. In primary CMV infection, the vast majority of these circulating virus-specific T cells have features of recently activated naive T cells in that they coexpress CD45RA and CD45R0 and appear to be in the cell cycle. In contrast, in people who have recovered from CMV infection earlier in life, virus-specific T cells do not cycle and express surface markers characteristic of memory T cells. After the initial rise, circulating virus-specific CD4(+) T cells decline rapidly. During this phase, a strong rise in IgM and IgG anti-CMV antibody titers occurs, concomitant with the reduction of CMV-DNA in the circulation. (+info)