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At least 721 records · Page 40Linked to original sources

PubMed2000

Serum antibodies to heat shock proteins are of no diagnostic value for human kidney allograft rejection.

Because of the prevailing evidence that heat shock proteins (hsp) are involved in transplantation immunology, we investigate in this study the serum levels of anti-hsp60, and anti-hsp70 antibodies in human kidney allograft recipients. We analyzed 67 sera from 20 patients immediately before and 2 weeks after receiving a kidney allograft, and from 27 healthy age-matched controls with an ELISA. Eleven kidneys had normal allograft function, six had a mild rejection episode, all of which could be reversed successfully; three kidneys had to be removed later on because of resistant rejection. Hsp antibody frequency and titres were the same for transplant recipients and for healthy controls. In patients receiving a kidney allograft, no difference in the level of hsp-antibodies before and after transplantation was observed. Additionally, anti-hsp60 and anti-hsp70 antibody titres were found to be independent of the clinical course. These data suggest that the determination of anti-hsp60 and 70 antibody titers are of no diagnostic value for renal allograft rejection.

Adult↗

PubMed1997

Mitral valve replacement and tricuspid valve repair after cardiac transplantation.

Efforts aimed at limiting the pool of cardiac retransplantation candidates have focused increasingly on attempts to preserve cardiac allograft function. The present report reviews the course of a patient who underwent mitral valve replacement and tricuspid annuloplasty for bivalvular incompetence after cardiac transplantation and examines the limited reported world experience with valve replacement after transplantation. The limited yet successful experiences with these and other operations in cardiac allograft recipients suggest that worsening donor organ shortages will likely lead to increased clinical experience with conventional operations in the transplanted heart.

Cardiomyopathy, Dilated↗

PubMed2004

Quality of life after pediatric intestinal transplantation: the perception of pediatric recipients and their parents.

The objective was to examine the perception of physical and psychosocial functioning of pediatric intestinal transplant recipients who are beyond the perioperative period and compare these with normal and chronically ill children. Child and parent forms of the Child Health Questionnaire were administered to all 29 pediatric intestinal transplant recipients between the ages of 5 and 18 years who had had a small bowel transplantation 1 year previous and had a functional allograft. Comparison was made with published norms and scores for pediatric patients on hemodialysis. Intestinal transplant recipients (on average 5 years after intestinal transplantation and at a mean age 11 years) reported similar scores in all domains compared with normal children. Parents of intestinal transplant recipients noted decreased function in several domains related to their child's general health, physical functioning, and the impact of the illness on parental time, emotions and family activities. Intestinal transplant recipients beyond the perioperative period perceive their physical and psychosocial functioning as similar to normal school children. Parental proxy assessments differ from the recipients, with the parent's perception of decreased general health and physical functioning for intestinal transplant recipients compared with norms.

Adolescent↗

PubMed1993

Cardiac function during graded bicycle exercise: Doppler-echocardiographic findings in normal subjects and heart transplant recipients.

Orthotopic heart transplantation results in altered atrial anatomy and denervation of the donor heart. To assess the impact of these sequelae on left ventricular filling and systolic performance, 16 heart transplant recipients and 10 normal controls were evaluated by Doppler echocardiography at rest and during graded bicycle exercise. Global and regional systolic ventricular allograft function was normal at rest and during exercise. Resting Doppler profiles demonstrated diminished atrial contribution to ventricular filling in transplant recipients. The response to dynamic exercise was different in both groups; controls increased heart rate, while mitral time-velocity integral was unchanged. Heart transplant recipients, in contrast, showed a blunted heart rate response and increased time-velocity integral. Atrial contribution to ventricular filling was not augmented during exercise as in normal controls. Alterations in transmitral flow profiles in heart transplant recipients do not necessarily reflect ventricular myocardial damage, but may be related to impaired atrial function.

Adult↗

PubMed1999

Cryptococcal meningitis in renal transplant patients associated with environmental exposure.

Fungal infections in renal transplant recipients are less common than bacterial infections; however, the morbidity from fungal infections is high. There is limited information in the literature concerning post-transplantation cryptococcal infection due to environmental exposure of patients living in high-risk areas. We report three patients who were diagnosed with cryptococcal meningitis after kidney transplantation. Cryptococcal titers prior to transplant surgery were negative in all three patients. These patients all lived in rural areas and demonstrated evidence of environmental exposure leading to subsequent cryptococcal meningitis. All patients had exposure to pigeon and chicken excreta and, after treatment, two patients are alive and well with excellent allograft function. The third patient has marginal renal function but is currently not on dialysis. Early diagnosis is essential for salvage from these potentially lethal infections. Intense headache was a prominent feature in the clinical presentation of our patients, and should signal the need for early sampling and culture of spinal fluid. Meningismus was not present in any of our patients, even when other systemic symptoms were identified. We recommend a high index of suspicion post-transplantation for all patients who may have environmental or occupational exposure to cryptococcus. If infection is detected quickly and treatment instituted promptly, patient recovery and allograft survival are possible. Long-term therapy with fluconazole, a non-nephrotoxic agent, should permit eradication of the infection with preservation of kidney function.

Amphotericin B↗

PubMed2002

Interleukin-8 release during early reperfusion predicts graft function in human lung transplantation.

Cytokines have been shown to play an important role in promoting inflammation in the setting of ischemia-reperfusion injury. However, their role in human lung transplantation has not been systematically explored. This study was undertaken to examine the kinetics of cytokine release in 18 consecutive human lung transplantation procedures and to examine the relationships between their levels and donor factors, length of ischemic time, and allograft function. TNF-alpha, IFN-gamma, IL-10, IL-12, and IL-18 were found at higher levels during the ischemic time, whereas IL-8 predominantly increased after reperfusion. IL-8 levels after 2 h of reperfusion correlated with lung function assessed by the Pa(O2 )/FI(O(2)) ratio, the mean airway pressure, and the APACHE score during the first 24 postoperative hours. The length of ICU stay also correlated with IL-8 levels after 2 h of reperfusion. Longer ischemic time was associated with significantly higher levels of IL-18 before reperfusion, and older donors had significantly lower levels of IL-10 after reperfusion. We have demonstrated the importance of IL-8 in predicting early graft function after human lung transplantation. In addition, we showed that donor age and ischemic time may influence release of specific cytokines during ischemia-reperfusion.

APACHE↗

PubMed2005

Detection of acute tubulointerstitial rejection by proteomic analysis of urinary samples in renal transplant recipients.

This study investigates proteomic analysis of urinary samples as a non-invasive method to detect acute rejection of renal allografts. Capillary electrophoresis coupled to mass spectrometry (CE-MS) was used to analyze urinary samples in 19 patients with different grades of subclinical or clinical acute rejection (BANFF Ia to IIb), 10 patients with urinary tract infection and 29 patients without evidence of rejection or infection. A distinct urinary polypeptide pattern identified 16 out of 17 cases of acute tubolointerstitial rejection, but was absent in two cases of vascular rejection. Urinary tract infection resulted in a different polypeptide pattern that allowed to differentiate between infection and acute rejection in all cases. Potentially confounding variables such as acute tubular lesions, tubular atrophy, tubulointerstitial fibrosis, calcineurin inhibitor toxicity, proteinuria, hematuria, allograft function and different immunosuppressive regimens did not interfere with test results. Blinded analysis of samples with and without rejection showed correct diagnosis by CE-MS in the majority of cases. Detection of acute rejection by CE-MS offers a promising non-invasive tool for the surveillance of renal allograft recipients. Further investigation is needed to establish polypeptide patterns in vascular rejection and to explore whether changes in the urinary proteome occur before the onset of histologically discernible rejection.

Adult↗

PubMed2006

Living donor kidney transplant recipients and clinical trials: participation profiles and impact on post-transplant care.

Many transplant physicians believe that transplant candidates who enroll in clinical trials may have better outcomes than those who do not enroll. We examined a 7-year cohort (1997-2003) of adult primary, non-HLA identical, living donor kidney transplant (LDKT) recipients to determine whether demographic characteristics predisposed to enrollment and whether participation affected posttransplant care intensity and/or allograft function. Overall, 146 of 512 (28.5%) LDKT recipients enrolled in clinical trials. LDKT recipients who were male and those who lived <100 miles from our transplant center were significantly more likely to participate. During the first post-transplant year, study patients (SPs) had more clinic visits (p < 0.0001) and more allograft biopsies (p = 0.024) compared to nonstudy patients (NSPs), but comparable numbers of hospital readmissions and allograft ultrasounds. SPs and NSPs did not differ in 1-year creatinine clearance, delta creatinine or rejection incidence. Overall graft and patient survival were comparable. We conclude that clinical trial participants were disproportionately male, had increased intensity of post-transplant care but comparable outcomes to nonparticipants.

Adolescent↗

PubMed1999

Ex vivo transfection of transforming growth factor-beta1 gene to pulmonary artery segments in lung grafts.

OBJECTIVE: Proximal pulmonary artery segment transfection may provide beneficial downstream effects on the whole-lung graft. In this study, transforming growth factor-beta1 was transfected to proximal pulmonary artery segments, and the efficacy of transforming growth factor-beta1 transfection was examined in ischemia-reperfusion injury and acute rejection models of rat lung transplantation. METHODS: In the ischemia-reperfusion injury model, orthotopic left lung transplantation was performed in F344 rats. In group I, the PPAS was isolated and injected with saline solution. In 2 other groups, lipid67:DOPE:sense (group II) or antisense transforming growth factor-beta1pDNA construct (group III) was injected instead of saline solution. After cold preservation at 4 degrees C for 18 hours, lung grafts were implanted. Graft function was assessed 24 hours later. In the acute rejection model, donor lung grafts were harvested. Proximal pulmonary artery segments were injected with saline solution (group I) or sense (group II) or antisense lipid gene construct (group III) and then implanted. Graft function was assessed on postoperative day 5. RESULTS: In the ischemia-reperfusion injury study, there were no significant differences in oxygenation, wet-to-dry weight ratios, graft myeloperoxidase activity, or transforming growth factor-beta1 levels in platelet-poor serum or proximal pulmonary artery segment homogenates. In the acute rejection study, oxygenation was significantly improved in group II receiving transforming growth factor-beta1 (group II vs I and III, 136.0 +/- 32.5 vs 54.0 +/- 9.6 mm Hg and 53.8 +/- 14.8 mm Hg; P =.016 and.016). There were no significant pathologic differences. Transforming growth factor-beta1 concentrations from proximal pulmonary artery segment homogenates in group II were significantly higher compared with controls. CONCLUSIONS: Ex vivo transfection of transforming growth factor-beta1 to proximal pulmonary artery segments did not affect reperfusion injury of lung isografts. In acute rejection, however, ex vivo transfection of transforming growth factor-beta 1 to proximal pulmonary artery segments improved allograft function. This suggests that transfection to proximal pulmonary artery segments exerts beneficial downstream effects on the whole-lung allograft.

Acute Disease↗

PubMed1988

Early diagnosis and treatment of pancreas allograft rejection.

A major problem in vascularized pancreas transplantation is the lack of reliable methods for the early diagnosis and effective treatment of allograft rejection. Over a 2-year period, 54 rejection episodes occurred in 31 patients (13 isolated pancreas, 18 simultaneous pancreas-kidney recipients) with pancreaticoduodenocystostomy. A total of 253 radionuclide pancreas examinations were performed (mean 8.4 per patient) utilizing 99mtechnetium-DTPA. Computer analysis generated a quantitative measure of blood flow to the allograft caused the technetium index (TI). Rejection episodes were characterized as isolated pancreas (22), combined pancreas-kidney (16), or isolated renal (16) allograft rejection in combined engraftments. The majority of rejection episodes occurred early (within 3 months of transplant, N = 47) and were more responsive than late rejection to anti-rejection therapy (89.4% vs 42.9%, P = 0.01). Mean urinary amylase (UA) levels and TI during normal allograft function were 29,398 U/l and 0.55%, while levels heralding rejection were 6,528 U/l and 0.40%, respectively (P less than 0.05). The treatment of rejection based upon renal dysfunction or combined renal and pancreas dysfunction resulted in significantly higher graft salvage with a lower incidence of hyperglycemia when compared to isolated pancreas allograft rejection. Of the 11 patients who developed hyperglycemia, 8 (72.7%) ultimately lost their pancreas grafts (P less than 0.001). Following therapy, a TI above 0.3% was associated with 97.4% graft survival, while levels below 0.3% resulted in a 70% rate of graft loss (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

PubMed1998

Reduced-size orthotopic composite liver-intestinal allograft.

A composite graft consisting of a reduced left lateral hepatic segment in continuity with the small intestine was procured from an adult cadaveric donor using a modified in situ split technique. The primary recipient was a 3-year-old boy with hepatointestinal failure. The right side of the liver was transplanted into a 63-year-old man with a central hepatoma and hepatitis C cirrhosis. This was accomplished with center-to-center sharing of the liver portion of the allograft. The in situ split technique was feasible, with good initial allograft function. However, both grafts failed subsequently because of peri-operative recipient-related complications. The adult patient died of an infected pseudoaneurysm of the arterial graft, and the pediatric patient required repeat transplantation as a result of the late diagnosis of a native pancreatic fistula with cholestatic damage to the reduced liver allograft. The child is currently alive 8 months after repeat transplantation.

Humans↗

PubMed1994

Management of the renal allograft recipient: immunosuppressive protocols for long-term success.

To determine the benefits of long-term cyclosporine (CsA) immunosuppression, renal allograft recipients were randomly assigned to a protocol of either: CsA+azathioprine (Aza)+prednisone (TD), or to a protocol in which CsA was discontinued from the regimen of Aza+prednisone (CsA D/C). With a mean follow-up of nearly 7 years since transplantation, 30/47 (64%) CsA D/C and 27/45 (60%) TD had functioning allografts. Although long-term survivals were similar, hazards of the CsA D/C protocol were evident (40% rate of acute rejection following CsA D/C). Conversely, continued CsA in the TD protocol provided the opportunity for prednisone reduction, or even complete prednisone withdrawal in selected patients. A TD protocol which can provide equivalent long-term success, and eventually lower or omit prednisone, is preferable to a protocol of CsA D/C.

Acute Disease↗

PubMed2005

Risk factors associated with the deterioration of renal function after kidney transplantation.

Renal function early after transplantation is associated with a large number of risk factors, including donor age and acute rejection. During the 1990s, donor age increased and the incidence of acute rejection decreased. Renal function between the third and sixth month improved slightly, while renal function deterioration between the third or sixth month and the 12th month improved significantly. This modification coincides with the introduction of mycophenolate mofetil and tacrolimus. The tendency for sustained renal improvement early after transplantation became more evident after the introduction of anti-calcineurin-free regimens. Studies of protocol biopsies have shown that there is an increase of glomerular volume after transplantation and that a larger glomerular volume at 4 months is associated with a better glomerular filtration rate. This adaptation mechanism is impaired in patients with chronic allograft nephropathy or in patients with high cyclosporin levels. Taken together, these data suggest that the steady improvement of renal allograft function may be partly explained by a better glomerular adaptation after transplantation because of the avoidance of the vasoconstrictive effect of anti-calcineurinic agents, and a significant decrease in the prevalence of chronic allograft nephropathy early after transplantation.

Aging↗

PubMedDate not supplied

Left ventricular function of heart allografts during acute rejection: an echocardiographic assessment.

Left ventricular function was evaluated in nine patients during biopsy proven acute rejection of heart allografts using computer-assisted analysis of echocardiograms. The results were compared with data obtained during their non-rejection state and with data obtained from 10 normal subjects. Left ventricular dimensions and parameters of diastolic and systolic function of non-rejecting hearts were similar to those of normals. Acute rejection was associated with increased left ventricular mural thickness and mass, and abnormal diastolic function characterized by a prolongation of the rapid filling period from 155 msec +/- 14 msec to 183 msec +/- 16 msec (p less than 0.05, mean +/- SE), and decreased normalized peak rates of left ventricular lengthening (from 5.3 sec-1 +/- 0.8 sec-1 to 3.9 sec-1 +/- 0.4 sec-1, less than 0.05) and posterior wall thinning (from 7.4 sec-1 +/- 1.0 sec-1 to 3.8 sec-1 +/- 0.6 sec-1, p less than 0.05). Parameters of systolic function as defined by fractional shortening, peak normalized rates of left ventricular shortening and posterior wall thinning were not altered by acute rejection. We conclude that the left ventricular function of non-rejecting hearts is similar to that of normals; however, acute rejection is associated with abnormal left ventricular diastolic dynamics without adverse effect on systolic function.

Adult↗

PubMed1985

Beta-2-microglobulin in the assessment of renal function of the transplanted kidney.

Plasma and urine beta-2-microglobulin (B2m) were measured in 37 renal transplant recipients and 34 healthy subjects. Serum B2m was found to be a more sensitive index of renal function than serum creatinine. Renal transplant recipients had significantly higher urine B2m when compared with normal controls. Normal subjects had a higher serum to urine B2m ratio (SUR) while those with renal impairment had a lower SUR. Serum B2m used alone or together with urine B2m and SUR appears a useful index for assessment of renal allograft function as well as detection of potential renal damage.

Adult↗

PubMed1997

Chronic allograft failure: the clinical problem.

Long-term survival statistics for organ allografts have not improved substantially over time, despite improved immunosuppression and organ preservation and better surgical and perioperative management. Chronic rejection is the most important long-term limitation in allografts and increasingly seems to be caused by a multifactorial series of antigen-dependent and antigen-independent factors. Early injury is critical to late events, whether antigen driven (early acute rejection episodes and human leukocyte antigen mismatching) or antigen independent (ischemia/reperfusion injury and brain death). Ongoing alloimmunologic injury to the host and inadequate organ mass functioning (donor age, gender, race, and organ size) also seem to be important to this persisting process. Associated recipient conditions, which includes hypertension and hyperlipidemia, and postoperative complications, which include drug nephrotoxicity and infections, may affect this late-phase graft loss. These deleterious risk factors for chronic rejection of long-functioning allografts are an important subject for future investigation.

Graft Rejection↗

PubMed1998

The effect of cyclosporine on regulators of fibrinolysis in plasma from renal allograft recipients.

Fibrinolytic disturbances are thought to play an important role in processes leading to deterioration of renal allograft function. We investigated the effect of CsA therapy on the regulation of fibrinolysis in kidney graft recipients by measuring plasma concentration and activity of plasminogen activators (tPA, uPA) and their inhibitors (PAI-1, 2). We found an increase in tPA activity and in PAI-1 concentration as well as a decrease in PAI-1 activity in renal allograft recipients as compared to healthy controls, but did not confirm a correlation between these observations and CsA administration. tPA and PAI-2 concentrations as well as uPA activity did not significantly differ between the studied groups. We showed a significant decrease in uPA plasma concentration in patients treated with azathioprine. The significance of this finding is unknown.

Adult↗

PubMed2006

Hematopoietic chimerism induces renal and skin allograft tolerance in DLA-identical dogs.

OBJECTIVE: Hematopoietic chimerism, a state where donor and recipient bone marrow cells coexist, is associated with donor-specific tolerance. Nonmyeloablative bone marrow transplantation (BMT) has been shown to induce stable mixed hematopoietic chimerism in dog leukocyte antigen (DLA)-matched dogs. The potential for inducing renal and skin allograft tolerance with nonmyeloablative BMT was investigated in DLA-identical and DLA-haploidentical dogs in this study. MATERIALS AND METHODS: Renal allografts were performed in 8 DLA-identical and 4 DLA-haploidentical dogs with nonmyeloablative conditioning (200 cGy TBI) and transient immunosuppression with cyclosporine (CSP) and mycophenolate mofetil (MMF) with (n = 8) and without (n = 4) simultaneous BMT. Skin allografts were performed in 2 DLA-identical and 4 DLA-haploidentical dogs after stopping CSP and MMF. Two DLA-identical control dogs received renal allografts without TBI, BMT, or immunosuppression with CSP and MMF. Molecular chimerism was determined with a PCR-based DNA microsatellite assay. Serum creatinine (Cr) concentration, urine specific gravity, and sequential renal biopsies were monitored to assess renal allograft function. RESULTS: Donor-type blood cells were first detected 4 weeks posttransplantation in both the myeloid and lymphoid lineages. Donor chimerism was present for at least 76 weeks in the DLA-identical dogs. Mixed chimerism was not observed in the DLA-haploidentical dogs or DLA-identical dogs that did not undergo BMT. The renal allografts were acutely rejected within 14 days in the 2 DLA-identical control dogs. There was long-term (> 5 yrs) renal allograft survival as evidenced by a normal (< 2.0 mg/dL) serum Cr concentration in both the DLA-identical and DLA-haploidentical dogs that underwent 200 cGy TBI and transient immunosuppression with CSP and MMF either with or without simultaneous BMT. Renal allograft inflammation was severe in the control dogs, mild to moderate in the DLA-haploidentical dogs, and minimal in the DLA-identical dogs. Donor-specific skin grafts were accepted in the DLA-identical dogs but rejected in the DLA-haploidentical dogs. Nonmyeloablative conditioning (200 cGy TBI) and transient immunosuppression with CSP and MMF induce renal and skin allograft tolerance in DLA-identical and permit long-term renal allograft survival in DLA-haploidentical dogs. These findings suggest it may possible to obtain long-term allograft survival in DLA-identical and -haploidentical dogs without the need for chronic immunosuppressive therapy.

Animals↗