Showing papers on "Transplantation published in 1995"
TL;DR: Donor lymphocyte transfusions exert strong effects against myeloid forms of leukemia and induce durable remissions in CML.
2,014 citations
TL;DR: The transfer of CMV-specific clones of CD8+ T cells derived from the bone marrow donor is a safe and effective way to reconstitute cellular immunity against CMV after allogeneic marrow transplantation.
Abstract: Background Cytomegalovirus (CMV) disease in immunocompromised patients correlates with a deficiency of CD8+ cytotoxic T lymphocytes specific for CMV. We evaluated the safety and immunologic effects of immunotherapy with clones of these lymphocytes in recipients of allogeneic bone marrow transplants. Methods Clones of CD8+ cytotoxic T cells specific for CMV proteins were isolated from the blood of bone marrow donors. Fourteen patients each received four intravenous infusions of these clones from their donors beginning 30 to 40 days after marrow transplantation. The reconstitution of cellular immunity against CMV was monitored before and during the period of infusions and for up to 12 weeks after the final infusion. The rearranged genes encoding the T-cell receptor served as markers in evaluating the persistence of the transferred T cells. Results No toxic effects related to the infusions were observed. Cytotoxic T cells specific for CMV were reconstituted in all patients. In vitro measurements showed that ...
1,870 citations
TL;DR: In this paper, the authors report their experience with 84 cases occurring in the soft tissues and viscera of 48 female patients and 36 male patients between the ages of 3 months and 46 years (mean, 9.7 years; median, 9 years).
Abstract: Inflammatory myofibroblastic tumor (IMT) or inflammatory pseudotumor is a spindle cell proliferation of disputed nosology, with a distinctive fibroinflammatory and even pseudosarcomatous appearance. Although the lung is the best known and most common site, inflammatory myofibroblastic tumor occurs in diverse extrapulmonary locations. We report our experience with 84 cases occurring in the soft tissues and viscera of 48 female patients and 36 male patients between the ages of 3 months and 46 years (mean, 9.7 years; median, 9 years). A mass, fever, weight loss, pain, and site-specific symptoms were the presenting complaints. Laboratory abnormalities included anemia, thrombocytosis, polyclonal hypergammaglobulinemia, and elevated erythrocyte sedimentation rate. Sites of involvement included abdomen, retroperitoneum, or pelvis (61 cases); head and neck, including upper respiratory tract (12 cases); trunk (8 cases); and extremities (3 cases). The lesions ranged in size from 1 to 17 cm (mean, 6.4; median, 6.0). Excision was performed in 69 cases. Eight had biopsy only. Five patients received chemotherapy or radiation in addition to undergoing biopsy or resection as initial treatment. Sixteen patients had multinodular masses involving one region. Clinical follow-up in 53 cases revealed that 44 patients were alive with no evidence of disease, four were alive with IMT, and five were dead. Thirteen patients had one or more recurrences at intervals of 1-24 months (mean, 6 months; median, 10 months). No distant metastases were documented. The five patients who died had complications either due to the location of the lesion (heart, peritoneum, retroperitoneum, or mesentery) or related to treatment (lymphoproliferative disorder following hepatic transplantation; sepsis following wound infection). The abdominal masses were the largest. All tumors were firm and white with infiltrative borders and focal myxoid change. Three basic histologic patterns were recognized: (a) myxoid, vascular, and inflammatory areas resembling nodular fasciitis; (b) compact spindle cells with intermingled inflammatory cells (lymphocytes, plasma cells, and eosinophils) resembling fibrous histiocytoma; and (c) dense plate-like collagen resembling a desmoid or scar. Immunohistochemistry demonstrated positivity for vimentin, muscle-specific actin, smooth muscle actin, and cytokeratin consistent with myofibroblasts. Based on this series, inflammatory myofibroblastic tumor is a benign, nonmetastasizing proliferation of myofibroblasts with a potential for recurrence and persistent local growth, similar in some respects to the fibromatoses.
1,429 citations
TL;DR: This study demonstrated that MMF administered at a dosage of 2 g or 3 g daily, in combination with maintenance CsA and corticosteroids as triple therapy following ATGAM® induction therapy, is more effective than an otherwise identical regimen that includes azathioprine instead of MMF in preventing acute allograft rejection in first cadaveric renal transplant patients.
Abstract: Mycophenolate mofetil (MMF), a new immunosuppressant that selectively inhibits proliferation of T and B lymphocytes, may reduce the frequency and severity of acute graft rejection. Acute graft rejection is the leading cause of graft loss in cadaveric renal transplantation. The purpose of this randomized, double-blind, multicenter study was to evaluate the efficacy and safety of MMF for the prevention of acute rejection episodes in adult patients during the first 6 months after renal transplantation. A total of 499 patients who were to receive a primary cadaveric renal allograft as their first transplant were randomized to receive MMF 1.0 g b.i.d. (MMF 2 g treatment group), MMF 1.5 g b.i.d. (MMF 3 g treatment group), or azathioprine 1-2 mg/kg/day. CsA, corticosteroids, and antithymocyte globulin (ATGAM®) were administered as part of a quadruple sequential induction protocol. The primary efficacy endpoint was biopsy-proven rejection or treatment failure (defined as graft loss, death, or premature withdrawal from the study for any reason) during the first 6 months after transplant. All enrolled patients were included in the primary analyses of efficacy on the basis of intent to treat. The 495 patients who received study drug were included in the safety and secondary efficacy analyses. Biopsy-proven acute rejection episodes or treatment failure occurred in 47.6% of patients in the azathioprine group compared with 31.1% (P=0.0015) and 31.3% (P=0.0021) of patients in the MMF 2 g and 3 g treatment groups, respectively. Time to first biopsy-proven rejection episode or treatment failure was significantly longer for MMF 2 g versus azathioprine (P=0.0036) and MMF 3 g versus azathioprine (P=0.0006). First biopsy-proven rejection alone occurred in 38.0% of patients who received azathioprine compared with 19.8% and 17.5% of patients who received MMF 2 g and 3 g, respectively. Patients in the azathioprine group received a greater number of full courses of antirejection treatment as compared with the MMF 2 g and MMF 3 g groups (44.5%, 24.8%, and 21.1%, respectively). The use of antilymphocyte agents to treat rejection was greater in the azathioprine group (20.1%) compared with the MMF 2 g group (10.3%) and the MMF 3 g group (5.4%). At 6 months after transplant, graft and patient survival were similar in all 3 treatment groups. The incidence and types of adverse events were similar among treatment groups, with the exception of a higher incidence of diarrhea, certain other infrequent gastrointestinal adverse events, clinically important leukopenia, and tissue-invasive CMV disease in the MMF groups, particularly in the MMF 3 g group. Three patients who received MMF developed lymphoma/lymphoproliferative disorder. This study demonstrated that MMF administered at a dosage of 2 g or 3 g daily, in combination with maintenance CsA and corticosteroids as triple therapy following ATGAM® induction therapy, is more effective than an otherwise identical regimen that includes azathioprine instead of MMF in preventing acute allograft rejection in first cadaveric renal transplant patients. This regimen also has an acceptable adverse event profile. The MMF 3 g dosage was considered to be somewhat less well tolerated than the MMF 2 g dosage.
1,278 citations
TL;DR: After cardiac transplantation, pravastatin had beneficial effects on cholesterol levels, the incidence of rejection causing hemodynamic compromise, one-year survival, andThe incidence of coronary vasculopathy.
Abstract: Background Hypercholesterolemia is common after cardiac transplantation and may contribute to the development of coronary vasculopathy. Pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has been shown to be effective and safe in lowering cholesterol levels after cardiac transplantation. Cell-culture studies using inhibitors of HMG-CoA reductase have suggested an immunosuppressive effect. Methods Early after transplantation, we randomly assigned consecutive patients to receive either pravastatin (47 patients) or no HMG-CoA reductase inhibitor (50 patients). Results Twelve months after transplantation, the pravastatin group had lower mean (±SD) cholesterol levels than the control group (193±36 vs. 248±49 mg per deciliter, P<0.001), less frequent cardiac rejection accompanied by hemodynamic compromise (3 vs. 14 patients, P = 0.005), better survival (94 percent vs. 78 percent, P = 0.025), and a lower incidence of coronary vasculopathy in the transplant as determined by angiog...
1,261 citations
TL;DR: EBV-specific donor-type T-cell lines seem to offer safe and effective therapy for control of EBV-associated lymphoproliferation in patients with EBV reactivation after bone-marrow transplantation.
1,166 citations
TL;DR: The Phototyping set has been used as the sole method of HLA typing for over 1010 individuals and has capacity to detect new alleles, for example, novel amplification patterns suggestive of 4 new HLA-B alleles have been detected.
Abstract: We have developed a single DNA typing method which uses 144 sequence-specific primer (SSP) reactions to simultaneously detect all known HLA-A, B, C, DRB1, DRB3, DRB4, DRB5 and DQB1 specificities in an allele specific or group specific manner using the same method, reagents, PCR parameters and protocols for all loci. The results from this integrated class I & II method can be visualized on a single photographic or electronic image and hence is described as "Phototyping". Phototyping has an overall resolution greater than or equivalent to good serology and results can be obtained in under 3 hours making the method suitable for genotyping potential cadaver donor peripheral blood without serological backup. This in turn produces the potential for reducing cold ischaemia times in renal transplantation as well as the application of prospective matching to cardiac and liver transplantation. The method has capacity to detect new alleles, for example, novel amplification patterns suggestive of 4 new HLA-B alleles have been detected. The Phototyping set has been used as the sole method of HLA typing for over 1010 individuals. Phototyping is not problem-free; deviations from the standard protocol, poor quality DNA and unsuitable PCR machines can result in individual PCR failures or in incorrect assignment of antigens. Approximately 5% of genotypes were repeated (either partially or fully) because of incomplete or equivocal results.
1,092 citations
Journal Article•
TL;DR: MMF significantly reduced the rate of biopsy-proven rejection or other treatment failure during the first 6 months after transplantation and was well tolerated, although the 3 g dose was somewhat less well tolerated.
1,014 citations
TL;DR: The subsets of HSC that give rise to short-term vs long-term multilineage reconstitution can be separated by phenotype, demonstrating that the fates of H SC are intrinsically determined.
Abstract: Hematopoietic stem cells (HSC) are the only cells in the blood-forming tissues that can give rise to all blood cell types and that can self-renew to produce more HSC. In mouse and human, HSC represent up to 0.05% of cells in the bone marrow. HSC are almost entirely responsible for the radioprotective and short- and long-term reconstituting effects observed after bone marrow transplantation. The subsets of HSC that give rise to short-term vs long-term multilineage reconstitution can be separated by phenotype, demonstrating that the fates of HSC are intrinsically determined. Here we review the ontogeny and biology of HSC, their expression of fate-determining genes, and the clinical importance of HSC for transplantation and gene therapy.
877 citations
TL;DR: Autologous as well as allogeneic bone marrow transplantation results in better disease-free survival than intensive consolidation chemotherapy with high-dose cytarabine and daunorubicin.
Abstract: Background Allogeneic or autologous bone marrow transplantation and intensive consolidation chemotherapy are used to treat acute myelogenous leukemia in a first complete remission. Methods After induction treatment with daunorubicin and cytarabine, patients who had a complete remission received a first course of intensive consolidation chemotherapy, combining intermediate-dose cytarabine and amsacrine. Patients with an HLA-identical sibling were assigned to undergo allogeneic bone marrow transplantation; the others were randomly assigned to undergo autologous bone marrow transplantation (with unpurged bone marrow) or a second course of intensive chemotherapy, combining high-dose cytarabine and daunorubicin. Comparisons were made on the basis of the intention to treat. Results A total of 623 patients had a complete remission; 168 were assigned to undergo allogeneic bone marrow transplantation, and 254 were randomly assigned to one of the other two groups. Of these patients, 343 completed the treatment assi...
855 citations
TL;DR: To establish a formula for calculating the standard LV in the pediatric and adult populations for liver transplantation, whole LVs were measured in 96 patients with normal liver whose disease conditions did not seem to affect body weight (BW) or LV.
TL;DR: Grafts of fetal mesencephalic tissue can survive for a long period in the human brain and restore dopaminergic innervation to the striatum in patients with Parkinson's disease.
Abstract: Background Trials are under way to determine whether fetal nigral grafts can improve motor function in patients with Parkinson's disease. Some studies use fluorodopa uptake on positron-emission tomography (PET) as a marker of graft viability, but fluorodopa uptake does not distinguish between host and grafted neurons. There has been no direct evidence that grafts of fetal tissue can survive and innervate the striatum. Methods We studied a 59-year-old man with advanced Parkinson's disease who received bilateral grafts of fetal ventral mesencephalic tissue in the postcommissural putamen. The tissue came from seven embryos between 61/2 and 9 weeks after conception. The patient died 18 months later from a massive pulmonary embolism. The brain was studied with the use of tyrosine hydroxylase immunohistochemical methods. Results After transplantation, the patient had sustained improvement in motor function and a progressive increase in fluorodopa uptake in the putamen on PET scanning. On examination of the brai...
Book•
01 Jan 1995
TL;DR: The principles and practice of endocrinology and metabolism are studied as well as the practical application of these principles in the field of medicine and sport.
Abstract: This dynamic CD-ROM provides one-click access to the full text and illustrations of Principles and Practice of Endocrinology and Metabolism, Third Edition, plus over 3,400 multiple-choice self-assessment questions and answers--in an interactive format perfect for consultation, study, or review. Coverage includes new chapters on molecular biology, new therapies for pituitary tumors, pancreatic transplantation, appetite regulation, growth factors and cytokines, endocrine effects on lipids, endocrine blood cells, the endocrine adipocyte, adrenal incidentaloma, endocrine disorders of HIV infection, and more. Also included are quick-access references to aid in clinical decisions--a complete endocrine drug formulary, an extraordinary compendium of normal laboratory values, and a detailed listing of dynamic diagnostic testing. The program allows users to select the most helpful mode of review. Study Mode presents questions with immediate feedback through the chapter list. Quiz Mode displays randomized questions based on settings the user chooses. Exam Mode presents a set number of questions in random order and displays results at the end of the exam. Windows Compatible Compatibility: BlackBerry(r) OS 4.1 or Higher / iPhone/iPod Touch 2.0 or Higher /Palm OS 3.5 or higher / Palm Pre Classic / Symbian S60, 3rd edition (Nokia) / Windows Mobile(t) Pocket PC (all versions) / Windows Mobile Smartphone / Windows 98SE/2000/ME/XP/Vista/Tablet PC
TL;DR: Prophylactic fluconazole was safe and significantly reduced systemic fungal infections with other benefits, including improved survival at day 110 after marrow transplantation.
Abstract: A randomized, double-blind, placebo-controlled trial assessed the efficacy and toxicity of 400 mg/day fluconazole in preventing fungal infections during the first 75 days after marrow transplantation. During prophylaxis, systemic fungal infections occurred in 10 (7%) of 152 fluconazole-treated patients compared with 26 (18%) of 148 placebo-treated patients (P = .004). There were no Candida albicans infections in fluconazole recipients compared with 18 in placebo recipients (P < .001) and no significant increase in Candida infections other than C. albicans. Fluconazole also significantly reduced the incidence of superficial fungal infections (P < .001), fungal colonization (P = .037), and empiric amphotericin B use (P = .005). The probability of survival was improved in fluconazole recipients, in whom 31 deaths occurred up to day 110 after transplantation compared with 52 deaths in placebo recipients (P = .004). No clinically significant toxicity was detected with fluconazole use. Prophylactic fluconazole was safe and significantly reduced systemic fungal infections with other benefits, including improved survival at day 110 after marrow transplantation.
TL;DR: The potential lasting nature of corrections performed with the transplantation of fatty tissue and is supported by over 400 infiltrations into the nasolabial folds in the author's practice are demonstrated.
Abstract: To document the amount and rate of re-absorption of fatty tissue transplanted using the author's technique, the author initiated controlled studies in 1987. A selected crease was infiltrated with autologous fatty tissue using a nearby crease as control. At specific time intervals the infiltrated crease was compared to the nearby control crease to evaluate percentage of recurrence. Photographs were taken in the first week, then at least yearly over six years. All views, all positions of the mouth, and all lighting situations demonstrated the continued absence of any crease in the area of infiltration. In contrast, the nearby control crease remained unchanged or deepened from its preoperative condition, giving every indication of a permanent correction. This experiment demonstrates the potential lasting nature of corrections performed with the transplantation of fatty tissue and is supported by over 400 infiltrations into the nasolabial folds in the author's practice.
TL;DR: The results suggest that measures taken to facilitate epithelialization without allowing host fibrovascular ingrowth onto the amniotic membrane might prove this procedure clinically useful for ocular surface reconstruction.
Abstract: After n-heptanol removal of the total corneal epithelium and a limbal lamellar keratectomy, 23 rabbit eyes developed features of limbal stem cell deficiency including conjunctival epithelial ingrowth, vascularization and chronic inflammation. One month later, 10 control eyes received a total keratec
TL;DR: Right ventricular ejection fraction > or = 0.35 at rest and exercise is a more potent predictor of survival in advanced heart failure than VO2 or %VO2;%VO2 rather thanVO2 predicts survival inadvanced heart failure; and neither % VO2 nor VO2 predicting survival to the combined end point of death or admission for inotropic or mechanical support in patients withAdvanced heart failure.
TL;DR: Age below 45 years at the time of transplantation was the most important determinant for increased risk at most sites, consistent with the theory that an impaired immune system allows carcinogenic factors to act.
Abstract: The theory that cancer may arise under conditions of reduced immune capacity is supported by observations of humans with immune deficiencies such as occur following organ transplants. However, no study on humans has been done in which the reference population was the same as that in which the cancer cases arose and in which there was a sufficiently long period of follow-up. Information on 5,692 Nordic recipients of renal transplants in 1964-1982 was linked with the national cancer registries (1964-1986) and population registries. Person-years at risk were calculated from the date of first transplantation until death or the end of the study period and were multiplied by the appropriate age- and calender-specific incidence rates to obtain the expected numbers of cancers. Standardized incidence ratios (SIR) were calculated after stratification by a number of recorded variables. Altogether, 32,392 person-years were accrued, and 471 cancers occurred, yielding overall SIR of 4.6 (95% CI, 4.0 to 5.2) for males and 4.5 (95% CI, 4.0 to 5.2) for females. Significant overall 2- to 5-fold excess risks in both sexes were seen for cancers of the colon, larynx, lung and bladder, and in men also for cancers of the prostate and testis. Notably high risks, 10-fold to 30-fold above expectation, were associated with cancers of the lip, skin (non-melanoma), kidney and endocrine glands, also with non-Hodgkin's lymphoma, and in women also with cancers of the cervix and vulva-vagina. Among a number of donor and recipient variables studied, including tissue types and compatibility (ABO, HLA, DR), age below 45 years at the time of transplantation was the most important determinant for increased risk at most sites. Kidney transplantation increases the risk of cancer in the short and in the long term, consistent with the theory that an impaired immune system allows carcinogenic factors to act. The tumor risk is small in comparison with the benefits of transplants, but patients should be followed up for signs of cancer.
TL;DR: It is concluded that umbilical cord blood is a sufficient source of transplantable haemopoietic stem cells for children with HLA-identical or Hla-1 antigen disparate sibling donors with very low risk of acute or extensive chronic GVHD.
TL;DR: Preliminary results indicate that allogeneic PBSCs mobilized by rhG-CSF can provide rapid hematologic recovery without an appreciably greater incidence of acute GVHD than would be expected with marrow.
TL;DR: There are no specific therapies for FHF, however, liver transplantation is recommended for situations in which spontaneous recovery appears unlikely and a suitable liver graft is available for transplantation.
TL;DR: It is confirmed that blockade of the CD28-B7 pathway after alloantigenic challenge induces donor-specific acceptance of vascularized organ allografts, and indicates in this model that CTLA4Ig inhibits Th1 but spares Th2 cytokines in vivo.
Abstract: Blocking the CD28-B7 T cell costimulatory pathway with the fusion protein CTLA4Ig inhibits alloimmune responses in vitro and in vivo and induces tolerance to cardiac allografts in mice and rats, but the mechanisms mediating the tolerant state in vivo are unknown. Here, we report the effects and potential mechanisms of CTLA4Ig in the rat renal allograft model. LEW rats were nephrectomized and received renal allografts from major histocompatibility complex-incompatible WF rats. While all untreated and control immunoglobulin (Ig)-treated animals acutely rejected their allografts and died, 86% of rats that received a single injection of CTLA4Ig on day 2 after transplantation had prolonged survival (> 60-100 days) with preserved renal function. By contrast, only 29% of animals that received CTLA4Ig on the day of engraftment had prolonged survival. Long-term survivors (> 100 days) exhibited donor-specific tolerance, accepting donor-matched WF but acutely rejecting third-party BN cardiac allografts. Immunohistological analysis of grafts sampled at 1 week after transplantation showed that both control and CTLA4Ig-treated animals had mononuclear cell infiltrates, with a higher percentage of CD4+ cells in the CTLA4Ig-treated group. However, while this was associated with vasculitis and tubulitis in control grafts, there was no evidence of tissue injury in CTLA4Ig-treated animals. The immune response leading to graft rejection in control animals was characterized by expression of the T helper (Th) type 1 cytokines interleukin (IL)-2 and interferon-gamma. In contrast, the persistent CD4+ infiltrate without graft rejection in CTLA4Ig-treated animals was associated with increased staining for the Th2-related cytokines IL-4 and IL-10. Furthermore, grafts from CTLA4Ig-treated animals had marked upregulation of intragraft staining for IgG1, but not IgG2a or IgG2b. Administration of rIL-2 to CTLA4Ig-treated animals restored allograft rejection in 50% of animals tested. These results confirm that blockade of the CD28-B7 pathway after alloantigenic challenge induces donor-specific acceptance of vascularized organ allografts, and indicates in this model that CTLA4Ig inhibits Th1 but spares Th2 cytokines in vivo.
TL;DR: In this paper, the authors developed a strategy to develop programmes for all patients with diabetes, focused on early detection of renal disease followed by intervention, to prevent the development of end-stage renal failure.
TL;DR: At least transient engraftment of DBM appears to be essential for induction of donor specific tolerance in this monkey model of MHC-disparate nonhuman primates.
Abstract: We have developed a nonmyeloablative preparative regimen that can produce mixed chimerism and renal allograft tolerance between MHC-disparate nonhuman primates. The basic regimen includes ATG, nonmyeloablative total-body irradiation (TBI, 300 rads), thymic irradiation (TI, 700 rads), and donor bone marrow infusion. Kidney allografts from MHC-mismatched donors were transplanted with various manipulations of the preparative regimen. Monkeys treated with the basic regimen alone (n = 2) rejected allografts by day 15. With the addition of cyclosporine (CsA) for one month (n = 3), one monkey developed multilineage mixed chimerism and renal allograft tolerance thereafter (> 430 days). To reduce the toxicity of the preparative regimen, TBI was fractionated to 150 rads on two successive days in subsequent studies. All monkeys receiving this modified regimen (n = 4) developed multilineage chimerism with fewer side effects and accepted renal allografts long-term with no further immunosuppression (196 days, 198 days, > 150 days, and > 40 days). In long-term survivors, donor-specific nonreactivity was confirmed by MLR and skin transplantation. Three monkeys treated with the basic regimen plus CsA but with only 150 rads of TBI (n = 1) or no TBI (n = 2) did not develop multilineage chimerism and grafts were rejected (day 40-50) soon after the CsA discontinuation. Monkeys treated with the same regimen, but without DBM (n = 2), rejected kidney allografts by day 52. Therefore, at least transient engraftment of DBM appears to be essential for induction of donor specific tolerance in this monkey model.
TL;DR: The persistent decrease in platelet storage of serotonin after heart-lung transplantation suggests that this platelet abnormality is not secondary to PPH, and normal handling of serotonin by platelets leading to an increase in plasma serotonin occurs in PPH.
TL;DR: A significantly higher level of vascularization was maintained for 1 year in the subcutaneous site in rats and it was found that the larger pore membranes had 80-100-fold more vascular structures.
Abstract: Transplantation of tissues enclosed within a membrane device designed to protect the cells from immune rejection (immunoisolation) provides an opportunity to treat a variety of disease conditions. Successful implementation of immunoisolation has been hampered by the foreign-body reaction to biomaterials. We screened a variety of commercially available membranes for foreign-body reactions following implantation under the skin of rats. Histologic analysis revealed that neovascularization at the membrane-tissue interface occurred in several membranes that had pore sizes large enough to allow complete penetration by host cells (0.8-8 microns pore size). When the vascularization of the membrane-tissue interface of 5-microns-pore-size polytetrafluoroethylene (PTFE) membranes was compared to 0.02-microns-pore-size PTFE membranes, it was found that the larger pore membranes had 80-100-fold more vascular structures. The increased vascularization was observed even though the larger pore membrane was laminated to a smaller pore inner membrane to prevent cell entry into the prototype immunoisolation device. This significantly higher level of vascularization was maintained for 1 year in the subcutaneous site in rats.
TL;DR: Data show that pretreatment of donors with G-CSF polarizes donor T cells toward the production of type-2 cytokines, which is associated with reduced type-1 cytokine production and reduced severity of acute GVHD.
TL;DR: Cryopreserved, filgrastim-stimulated allogeneic PBSCs may be a suitable alternative to allogenic marrow for transplantation with the advantage of more rapid platelet recovery, and further studies are required to assess long-term risks of chronic GVHD.
TL;DR: The impact of delayed graft function on outcome after cadaver renal transplantation has been controversial, but most authors fail to control for the presence or absence of rejection.
Abstract: The impact of delayed graft function on outcome after cadaver renal transplantation has been controversial, but most authors fail to control their analyses for the presence or absence of rejection. We studied 457 adult recipients of primary cadaver allografts at a single institution during the cyclosporine era. All patients received sequential immunosuppression. The incidence of delayed graft function (defined as dialysis being required during the first week after transplant) was 23%. There was a significant association between delayed graft function and cold ischemia time > 24 hr (P = 0.0001) and between delayed graft function and the occurrence of at least one biopsy-proven rejection episode (P = 0.004). Actuarial graft survival was not significantly different when comparing delayed graft function versus no delayed graft function for patients without rejection (P = 0.02). However, it was significantly worse for patients with both delayed graft function and rejection versus those with delayed graft function but no rejection (P = 0.005), as well as for grafts preserved > 24 hr versus 24 hr was also a significant risk factor (relative risk = 1.9, P = 0.02), other variables (preservation mode, 0 HLA Ag mismatch, age at transplantation, gender, diabetic status, and panel-reactive antibody at transplantation) had no impact on graft survival. Patient survival was significantly affected by the combination of delayed graft function and rejection (relative risk = 3.1, P 50 years (relative risk = 2.6, P < 0.0001), and diabetes (relative risk = 1.8, P = 0.006). Further studies are necessary to elucidate the mechanisms linking delayed graft function and rejection, which, in combination, lead to poor allograft outcome.