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PubMed2005

Resection arthrodesis of the knee for osteosarcoma: an alternative when mobile joint reconstruction is not feasible.

BACKGROUND: Wide resection and mobile joint reconstruction are preferable for treating an osteosarcoma around the knee. In certain situations, resection arthrodesis or an amputation is suggested. METHODS: During the past decade, 86 patients with an osteosarcoma around the knee were treated surgically in our institution. Wide resection and endoprosthetic reconstruction were performed in 35 patients, resection arthrodesis was performed in 36 patients, and an amputation was performed in 15 patients. The oncological and functional results were compared. Special attention was paid to the indications, techniques, and complications of patients receiving resection arthrodesis. RESULTS: Extensive tumor involvement was the main reason, followed by inappropriate previous treatment, for precluding mobile joint reconstruction. The local recurrence rates were similar among the 3 groups (11.4% for the endoprosthetic group, 11.1% for the arthrodesis group, and 6.7% for the amputation group). The 5-year survival rate was 39% for the arthrodesis group, which was significantly lower than that of the endoprosthetic group (60%, p = 0.040), although it was higher than that of the amputation group (13%, p = 0.056). Major complications were found in 7 patients receiving resection arthrodesis (7/24, 29%), and these included nonunion, infection, and allograft fracture. Functional results for the arthrodesis patients were inferior to those of the endoprosthetic patients, but most patients were grateful for preservation of the limb despite certain handicaps. CONCLUSIONS: The importance of early and proper planning of treatment cannot be over-stressed when treating osteosarcomas. Resection arthrodesis offers a durable reconstruction alternative to amputation in a special group of patients when extensive resection precludes mobile joint reconstruction.

Adolescent↗

PubMedDate not supplied

Transesophageal echocardiographic assessment of pulmonary venous flow after single lung transplantation.

Transesophageal echocardiography was used to evaluate pulmonary venous flow velocity and pulmonary venous diameter of both the transplanted and native lungs in six single lung transplant recipients. Mean pulmonary venous velocity (50 +/- 10 versus 27 +/- 8 cm/sec) and pulmonary venous diameter (1.39 +/- 0.16 versus 0.98 +/- 0.18 cm) were significantly greater in the transplanted lung than in the native contralateral lung. An index of allograft perfusion, QD-transesophageal echocardiography (pulmonary venous velocity x pulmonary venous diameter), correlated highly with previously measured technetium 99m-labeled macroaggregated albumin quantitative lung perfusion studies (r = 0.94). A pressure gradient in pulmonary venous flow velocity across the left atrial anastomosis was detected in two patients (8 and 12 mm Hg). Analysis of previous resting supine and upright incremental hemodynamic exercise testing showed no significant differences in these two patients with respect to maximum oxygen uptake, mean pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac index, or pressure-flow relationships. Therefore these left atrial anastomotic gradients did not appear to adversely affect the pulmonary vascular response to incremental exercise. Transesophageal echocardiography may be an invaluable technique in the expedient evaluation of cardiac function and allograft perfusion after lung transplantation.

Adult↗

PubMed1994

Influence of diltiazem on renal function and rejection in renal allograft recipients receiving triple-drug immunosuppression: a randomized, double-blind, placebo-controlled study.

In a prospective, randomized and placebo-controlled study we evaluated the influence of treatment with the calcium-channel blocker diltiazem on the course and results of cadaveric kidney transplantation in 39 graft recipients. The grafts were reperfused with Euro-Collins solution containing diltiazem 20 mg/l. All recipients except those in chronic treatment with a calcium-channel blocker received preoperatively a bolus of diltiazem or placebo 0.3 mg/kg and in all an infusion of diltiazem or placebo 3 mg/kg/24 h was started preoperatively. After that, diltiazem or placebo was given orally for 3 months. Donors were not treated. Immunosuppressive therapy consisted of prednisone, azathioprine and CsA. There were no significant differences between the groups concerning donor or recipient characteristics, HLA-mismatching, and ischaemic time. Thrombosis leading to graft loss occurred in 3 recipients (diltiazem:2, placebo:1) and one graft was lost due to septicaemia (diltiazem). For the remaining 35 grafts no beneficial effect of treatment with diltiazem was found for the rate of delayed graft function, the rate of rejections, time to first rejection, whole blood CsA concentration, or graft function. The CsA dose needed to reach target whole blood concentration was significantly less in the diltiazem group. In conclusion, our results do not indicate any beneficial effects of treatment with diltiazem in cadaveric kidney transplantation, except a reduction of costs because of a significant reduction of the CsA dosage.

Adult↗

PubMed2000

Effect of adding Mycophenolate mofetil in paediatric renal transplant recipients with chronical cyclosporine nephrotoxicity.

Cyclosporine (CyA) has made a great impact on 1-year allograft survival, however, after years, renal function deteriorates, possibly due to chronic toxicity. Recently, Mycophenolate mofetil (MMF) was introduced as a non-nephrotoxic immunosuppressant that might be effective in chronical transplant arteriolopathy. We therefore started MMF at a dose of 600 mg/m2 b. i. d. in 18 pediatric renal transplant recipients (10.8 +/- 3.9 (SD) years of age at transplantation, 11/18 with a history of rejections) with biopsy-proven chronic arteriolopathy and other signs of CyA toxicity at a mean follow up time of 6.2 +/- 2.7 (range 2.3-11.8) years after transplantation. One month prior to conversion, mean serum creatinine was 171 +/- 96 micromol/l, lower than at the time of conversion (188 +/- 100 micromol/l, P = 0.003, paired t-test). At last follow-up (median 13.7 months, range 5.0 to 25.0 months) after conversion, mean serum creatinine decreased significantly to 127 +/- 69 micromol/l (P = 0,0003, paired t-test). The CyA dosage was reduced from a mean of 150 +/- 39 mg/ m2 per day to 59 +/- 13 mg/m2 per day in 7 patients, and CyA was discontinued in 11 patients after a median period of nine months (range 1-18 months). After a median period of 21 days, a pharmacokinetic profile was performed in all patients. The mean MMF dose was 1117 +/- 319 mg/m2 per day (range 675-1774 mg/m2 per day). The mean Mycophenolic acid (MPA) trough concentration was 4.0 +/- 2.0 microg/ml, range 1.4-7.9 microg/ml. Mean 12 h MPA AUC was 70.6 +/- 28.1 (range 31.9-127) microg x h/ml. Except for one patient with diarrhea associated with a high AUC, and for one patient with a steroid-sensitive rejection episode after 566 days, no other patient experienced side effects or a rejection episode. Prednisolone was left unaltered at 2-4 mg/m2 per day. We conclude that MMF allows safe reduction of CyA with markedly better graft function, suggesting that chronical CyA-toxicity partially accounts for deteriorating allograft function.

Adolescent↗

PubMed1984

Evolving use of OKT3 monoclonal antibody for treatment of renal allograft rejection.

OKT3, a monoclonal antibody reactive with a surface glycoprotein present on all postthymic T cells, was used to treat the initial acute episode of rejection in 30 recipients of cadaveric donor renal allografts. The first 16 patients received 1-5 mg daily for a period of 10-21 days during which the azathioprine and prednisone dosages were sharply reduced. Circulating T cells were eliminated within minutes after the first OKT3 infusion. T cells reactive with OKT3 remained depressed throughout the period of treatment, although a significant number of cells reactive with other T cells subset reagents became detectable after several days of OKT3 treatment. In all instances, the established rejection episode was reversed in 2-8 days without the addition of other immunosuppressive measures. Recurrent rejection occurred in 12 of 16 patients, but with further conventional immunosuppression, 50% of the renal allografts remain functional 20-44 months after transplantation. Fever, chills, and, in some instances, dyspnea following the first dose of OKT3 were the only side-effects observed. Most patients developed antiidiotypic or antimouse immunoglobulin antibodies without apparent clinical sequelae. In the subsequent 14 patients, modifications in the protocol included a steroid bolus prior to the first OKT3 infusion, limitation of therapy to 10 days, resumption of maintenance levels of azathioprine and prednisone prior to discontinuing OKT3, and addition of 3 i.v. doses of cyclophosphamide at the termination of treatment. Respiratory symptoms after the first infusion of the reagent have been eliminated. Antibody responses to OKT3 have been reduced, occurring in 38% as compared with 73% of patients treated previously. Recurrent rejection episodes observed in 8 of 14 patients have been reversible in all but one case. Allograft survival is 86% at 6-17 months posttransplantation. In the entire series of 30 OKT3-treated patients, only 4 grafts (13%) have been lost because of recurrent episodes of rejection.

Antibodies, Monoclonal↗

PubMed2003

Removal of the surface layers of human cortical bone allografts restores in vitro osteoclast function reduced by processing and frozen storage.

A major complication of cortical bone grafting is nonunion at the host-graft junction. Many factors are thought to be involved in successful engraftment including the quality of the graft and the host response to it. In particular, the recipient osteoclasts (OCs) play a critical role by resorbing the engrafted bone. Thus, effective engraftment may depend on the inherent biological properties of the bone graft, which subsequently correlates with early and effective OC resorption. Normally, bone grafts are stored and processed by freezing, freeze-drying, irradiation, and lipid extraction. We sought to determine whether processing and storage affected bone quality, as evaluated by OC bone resorption. Cortical bone specimens from six human donors were either fresh, frozen at -75 degrees C, or had undergone combinations of freezing at -75 degrees C, freeze-drying, lipid extraction, irradiation, and treatment with hydrogen peroxide. Bone slices of 0.5-mm thickness taken from the surface, beneath the surface, and at a depth of 7.5 mm were incubated with isolated rabbit OCs and resorption lacunae were measured. We observed highest OC activity with fresh bone followed by frozen, partially processed, and fully processed bone. When allografts were stored at -75 degrees C for 12 months, there was up to a 4.2-fold reduction in OC activity on the surface layer. Additionally, we found reduced OC activity upon the outer surface bone compared to the inner layers. Removal of more than 0.5 mm of frozen and processed bone significantly improved OC activity. These results imply that inner bone layers of stored and processed bone allografts are protected against degradation of bone matrix components, except when frozen for extended periods of time. Taken together, these data suggest that bone allografts should be stored for less than 1 year and require the removal of at least 0.5 mm from their surface prior to transplantation.

Animals↗

PubMed2006

Function of indoleamine 2,3-dioxygenase in corneal allograft rejection and prolongation of allograft survival by over-expression.

Indoleamine 2,3-dioxygenase (IDO) suppresses T cell responses by its action in catabolising tryptophan. It is important in maintenance of immune privilege in the placenta. We investigated the activity of IDO in the cornea, following corneal transplantation and the effect of IDO over-expression in donor corneal endothelium on the survival of corneal allografts. IDO expression was analysed and functional activity was quantified in normal murine cornea and in corneas following transplantation as allografts. Low levels of IDO, at both mRNA and protein levels, was detected in the normal cornea, up-regulated by IFN-gamma and TNF. Expression of IDO in cornea was significantly increased following corneal transplantation. However, inhibition of IDO activity in vivo had no effect on graft survival. Following IDO cDNA transfer, murine corneal endothelial cells expressed functional IDO, which was effective at inhibiting allogeneic T cell proliferation. Over-expression of IDO in donor corneal allografts resulted in prolonged graft survival. While, on one hand, our data indicate that IDO may augment corneal immune privilege, up-regulated IDO activity following cytokine stimulation may serve to inhibit inflammatory cellular responses. While increasing IDO mRNA expression was found in allogeneic corneas at rejection, over-expression in donor cornea was found to significantly extend survival of allografts.

Animals↗

PubMed2006

Long-term posttransplantation care: the expanding role of community nephrologists.

Improvements in transplantation practices, immunosuppressive agents, and management of comorbid conditions have led to better outcomes for kidney transplant recipients. Transplantation has become the treatment of choice for patients with end-stage renal disease (ESRD). This has resulted in continued growth in the number of patients living with a functioning kidney allograft as a percentage of the total ESRD population. These patients require long-term follow-up care, which already is straining the limited resources of transplant centers. Community nephrologists are the logical choice to assume responsibility for the posttransplantation care of these patients after discharge from transplant centers when they are stabilized. Optimal management of kidney transplant recipients depends on regular interactive communication between the patient's community nephrologist and the transplant center. Open communication will not only facilitate the initial transition of care, it also will decrease the frequency of referrals back to the transplant center. In an ideal situation, the transplant center and community nephrologist would develop and discuss plans for discharge and transition of care for the individual patient before the actual kidney transplantation. Important issues for effective communication include changes in laboratory results and kidney function; pretransplantation and posttransplantation comorbid conditions, surgical complications, or adverse effects of medications; modifications to immunosuppressive therapy or other medications; recurrent hospitalizations or emergency care; and changes in biopsy results.

Communication↗

PubMed1997

Prolongation of rat islet allograft survival by the immunosuppressive agent leflunomide.

The purpose of this study was to investigate the effect of Leflunomide (Lef), alone or in combination with a suboptimal dose of cyclosporine (CsA), on rat allogeneic islet transplantation. Two thousands islets were transplanted under the left kidney capsule of a streptozocin-induced diabetic Lewis recipient. In the ACI to Lewis combination, the mean survival time (MST) of the untreated group was 5.2 +/- 0.8 days. Lef at 2.5, 5, and 10 mg/kg/day for 14 days significantly prolonged MSTs to 19.0 +/- 1.6, 29.8 +/- 3.7, and 29.0 +/- 5.3 days (P<0.01), respectively. CsA at 5 mg/kg/day also prolonged graft survival to 21 +/- 3.5 days. When CsA (5 mg/ kg/day) was combined with Lef (5 or 10 mg/kg/day) and administered for 14 days, the survival rate of the islet allografts was further increased to 34.8 -/+ 4.7 and 36.0 -/+ 6.6 days, respectively. When Lef or CsA monotherapy was extended to 28 days at a dose of 5 mg/kg/ day, MSTs were further increased to 45.8 -/+ 8.8 or 37.4 -/+ 4.7 days, respectively. Graft MST was 56.4 -/+ 9.9 days when Lef and CsA combination therapy was administered for 28 days. In the Brown-Norway to Lewis combination, MST of the allogeneic islets in untreated rats was 6.2 -/+ 0.8 days. When Lef or CsA alone, at 5 mg/kg/day, was administered for 28 days, two of seven Lef-treated rats remained normoglycemia for more than 100 days. Graft survival longer than 100 days occurred in one of five CsA-treated rats, and in five of eight rats treated with the combination of Lef and CsA. The graft-bearing left kidney was removed after 100 days in rats with functional islet allografts, and a second Brown-Norway islet graft was transplanted into the right kidney. In all recipients, the second graft was rejected by 9.8 -/+ 1.5 days. In summary, our findings demonstrate that Lef prolonged allogeneic islet graft survival, and its immunosuppressive effect was improved when combined with CsA.

Animals↗

PubMed1990

In vitro analysis of T cell-mediated cytotoxicity displayed by rat heart allograft recipients rendered unresponsive by total-lymphoid irradiation and extracted donor antigen.

The addition of 3M KCl-extracted donor antigen (HAg) to immunosuppressive therapy with 16 Gy total lymphoid irradiation produces a significantly higher fraction of Wistar-Furth (WFu) recipients displaying indefinite survival of heterotopic buffalo (BUF) heart allografts, namely 80 versus 20%. The experiments presented herein analyzed the direct activity as well as estimated the potential precursor numbers at 1 and 3 months in treated recipients. At 1 month post-TLI/HAg therapy, recipients showed reduced proliferative responses in mixed lymphocyte reactions (MLR) in a specific pattern toward donor but not third-party stimulators. Both TLI/Graft and TLI/HAg/Graft groups showed a higher frequency of BUF antigen-directed T-cytotoxic cells (fTc) than TLI-treated, but nontransplanted, WFu hosts. In addition, the TLI/HAg group alone displayed alloantigen-specific suppressor cells that suppressed the MLR proliferative responses of normal spleen T cells against donor, but not third-party, alloantigens. At 3 months postirradition, both TLI/Graft and TLI/HAg/Graft groups displayed variable MLR proliferative responses toward donor and third-party alloantigens. Whereas nontransplanted, TLI-treated WFu rats recovered their fTc to normal levels at 3 months, the TLI and TLI/HAg treated recipients bearing functional heart allografts demonstrated significantly decreased splenic fTc. These results show that reduced numbers of cytotoxic cell precursors may afford more reliable indices of prolonged heart allograft survival than MLR responses. The observations suggest that TLI/HAg transplant hosts display both reduced cytotoxic precursors and activated suppressor elements.

Animals↗

PubMed2003

Early detection of left ventricular dysfunction related to transplant coronary artery disease.

BACKGROUND: Transplant coronary artery disease (TxCAD) is a major limitation to the long-term success of cardiac transplantation. We assessed left ventricular (LV) function in relation to severity of coronary lesions to improve both early diagnosis of TxCAD and evaluation of the severity of myocardial damage. METHODS: Echocardiographic evaluation of LV function, including pulsed-wave tissue Doppler imaging (PW-TDI) wall motion analysis, was performed in 304 heart recipients before each of their follow-up cardiac catheterizations. LV systolic and diastolic parameters obtained both invasively and non-invasively were tested for their relation to angiographic and intravascular ultrasound (IVUS) findings. RESULTS: LV end-diastolic pressure and most of the PW-TDI parameters differed significantly (p < 0.001) between patients with and without TxCAD. In comparison to patients without the disease, even those with moderate, angiographically non-visible TxCAD showed significant differences for all systolic PW-TDI parameters. Wall motion alterations during angiographic TxCAD were almost always global and related mainly to diffuse Type B lesions. Systolic PW-TDI parameter changes showed highly predictive values for TxCAD. At systolic wall motion peak velocity (Sm) values constantly <10 cm/sec, we found a 97.37% likelihood of TxCAD (angiographically and/or IVUS-visible), whereas Sm values of > or =11 cm/sec excluded angiographic TxCAD with 90.41% probability. CONCLUSIONS: Among all parameters investigated for the evaluation of allograft LV function, PW-TDI systolic parameters were of the greatest diagnostic value. Wall motion assessment allows early detection of myocardial dysfunction and provides information on both local and global LV dysfunction linked to TxCAD, with potential usefulness for both timing of cardiac catheterizations and prognostic evaluation.

Adult↗

PubMed2006

Assessing relative risks of infection and rejection: a meta-analysis using an immune function assay.

BACKGROUND: Long-term use of immunosuppressants is associated with significant morbidity and mortality in transplant recipients. A simple whole blood assay that has U.S. Food and Drug Administration clearance directly assesses the net state of immune function of allograft recipients for better individualization of therapy. A meta-analysis of 504 solid organ transplant recipients (heart, kidney, kidney-pancreas, liver and small bowel) from 10 U.S. centers was performed using the Cylex ImmuKnow assay. METHODS: Blood samples were taken from recipients at various times posttransplant and compared with clinical course (stable, rejection, infection). In this analysis, 39 biopsy-proven cellular rejections and 66 diagnosed infections occurred. Odds ratios of infection or rejection were calculated based on measured immune response values. RESULTS: A recipient with an immune response value of 25 ng/ml adenosine triphosphate (ATP) was 12 times (95% confidence of 4 to 36) more likely to develop an infection than a recipient with a stronger immune response. Similarly, a recipient with an immune response of 700 ng/ml ATP was 30 times (95% confidence of 8 to 112) more likely to develop a cellular rejection than a recipient with a lower immune response value. Of note is the intersection of odds ratio curves for infection and rejection in the moderate immune response zone (280 ng/ml ATP). This intersection of risk curves provides an immunological target of immune function for solid organ recipients. CONCLUSION: These data show that the Cylex ImmuKnow assay has a high negative predictive value and provides a target immunological response zone for minimizing risk and managing patients to stability.

Graft Rejection↗

PubMed2003

Successful renal transplantation in children with posterior urethral valves.

PURPOSE: The treatment of children with posterior urethral valve (PUV) and end-stage renal disease can be challenging. Some series have had poor outcomes after renal transplantation with an increased risk of graft dysfunction and urinary tract infections. We present our experience with a pediatric population and compare it to all the other pediatric renal transplants done at our institution. MATERIALS AND METHODS: We identified 10 patients with PUV who underwent a total of 13 renal transplants between 1990 and 2000. The comparison group included 120 transplants done in 95 patients during the same period. Cumulative allograft survival and function were recorded. RESULTS: Overall patient survival in the PUV group was 100%. Mean age at transplant in the PUV group was 10.0 years and mean followup was 3.9 years. Six patients underwent high proximal urinary tract diversion, while the remainder had primary transurethral valve ablation. Three patients had bladder augmentation before transplantation. Cumulative allograft survival in the PUV group at 1 and 5 years was 85% and 64%, respectively. Of the 10 patients 9 currently have functioning living related donor transplants. One patient lost 3 cadaveric donor transplants to chronic rejection. No patients lost grafts due to infection or bladder dysfunction. Mean serum creatinine of the functioning grafts was 1.1 mg/dl. CONCLUSIONS: Renal transplantation can be performed safely and effectively in patients with PUV, including those who have undergone previous proximal urinary tract diversion. Preoperative bladder management and continued monitoring of bladder and kidney function postoperatively are paramount in the preservation of allograft function.

Child↗

PubMed1996

Auxiliary liver transplantation: regeneration of the native liver and outcome in 30 patients with fulminant hepatic failure--a multicenter European study.

Auxiliary liver transplantation (LT) is a special procedure of LT which could be proposed to patients with fulminant hepatic failure (FHF) and has for aim that complete regeneration of the native liver (NL) left in place will allow the graft recipient to resume normal liver function after allograft withdrawal. We report 30 cases of auxiliary LT performed for FHF in 12 European centers. Twenty-five of 30 patients were younger than 50 years. The cause of FHF was hepatitis A virus (HAV) in 4 patients, hepatitis B virus (HBV) in 7, paracetamol overdose in 5, ecstasy in 2, hepatotoxic drugs in 4, autoimmune hepatitis in 2, liver lesions of preeclampsia in 1 and unknown in 5. A postoperative, both clinical and histological follow-up of more than 3 weeks was obtained in 22 patients, enabling us to look for indicators predictive of NL regeneration and outcome. Histological changes observed in the NL included complete regeneration in 68%, incomplete regeneration with obvious fibrous sequelae in 14% and severe liver fibrosis or cirrhosis in 18%, of the 22 patients studied. The percentage and distribution of necrosis observed in tissue samples of the NL at the time of transplantation was not related to the final outcome. Complete NL regeneration was observed in 15 patients, out of whom 14 were younger than 40 years. Patients with complete regeneration were mainly affected by FHF due to HAV, HBV, or paracetamol overdose. After a follow-up of 18/11 (mean/median) months (range, 3 to 67 months), 19 of the 30 patients (63%) survived and 13 of them (68%), i.e., 43% of the 30 patients, had resumed normal NL function, with interrupted immunosuppression, the ultimate goal of emergency auxiliary LT. We conclude that, in patients with FHF, auxiliary LT is a procedure feasible in a number of centers and is associated with a complete regeneration capability of the NL in a majority of survivors, especially in those younger than 40 years. Confirmation of these encouraging preliminary results by large-scale prospective studies is required.

Adolescent↗

PubMed2004

Sex and the pregnant kidney: does renal allograft gender influence gestational renal adaptation in renal transplant recipients?

BACKGROUND: Animal work indicates that ovarian hormones are important in initiating and maintaining enhanced renal function in pregnant rats and that a renal response resembling pregnancy can be provoked in male rats exposed to pregnancy hormones. Women becoming pregnant following renal transplantation provide an opportunity to compare the functional response of male and female allografts to the gestational endocrine environment. METHODS: This retrospective observational study included 20 renal allograft recipients (age 29.7 +/- 2.4 yrs) (mean +/- SE) who had 22 pregnancies beyond 24 weeks (gestation at delivery 35.5 +/- 0.6 weeks). Donor characteristics, transplant details, renal follow-up data, and information about pregnancy and allograft function were obtained from hospital notes. RESULTS: Thirteen women received male allografts (donor age 30.0 +/- 3.9 years) (mean +/- SEM) and 7 women, female allografts (donor age 45.1 +/- 6.0 years) (P = .04). There were no significant differences between the two groups in maternal recipient age, transplant to pregnancy interval, antenatal complications, pregnancy outcome, or postnatal graft function. Compared to prepregnancy values serum creatinine (SCr) decrements and augmented 24-hour creatinine clearance (CrCl) were observed over the first trimester in both male and female allografts: Delta CrCl from 106.8 +/- 13.2 mL/min to 114.4 +/- 11.4 mL/min (35.6% increase) and 71.8 +/- 7.4 to 89.5 +/- 11.3 mL/min (24.7% increase), respectively, and Delta SCr from 90.1 +/- 5.4 micromol/L to 73.6 +/- 6.6 micromol/L (17.8% decrease) and 99.8 +/- 9.7 micromol/L to 78.0 +/- 5.7 micromol/L (13.5% decrease), respectively. Differences between the two groups did not reach statistical significance. CONCLUSIONS: Donor gender and/or age do not appear to influence the gestational renal response in kidney transplant recipients.

Adult↗

PubMed1991

Diagnosis of pancreatic transplant dysfunction: value of gadopentetate dimeglumine-enhanced MR imaging.

Sixteen MR studies performed in four patients who had undergone combined pancreatic and renal transplantation were reviewed retrospectively to determine if dynamic gadopentetate dimeglumine-enhanced gradient-echo imaging is useful in the early diagnosis of pancreatic transplant rejection. The MR studies were performed between 3 days and 6 months after transplantation and consisted of T1- and T2-weighted spin-echo images as well as a gradient-echo image prior to administration of an IV bolus of gadopentetate dimeglumine (0.1 mmol/kg). After injection of gadopentetate dimeglumine, a static dynamic gradient-echo scan was obtained. Signal-intensity measurements were determined for each of the gradient-echo images and used to generate an enhancement curve. Because T2 values have previously been used as an objective indicator of rejection, the mean T2 of each pancreatic transplant was calculated also. The MR results were compared with clinical and laboratory data and/or percutaneous biopsy results. In six studies of normally functioning pancreatic allografts, the percent enhancement during the first minute of the enhancement curve was 98 +/- 23% (1 SD). In six episodes of acute dysfunction (rejection or infarction), the first-minute enhancement was 42 +/- 20%. In four cases of dysfunction, the finding of an abnormal enhancement curve preceded a significant drop in urinary amylase by 1-4 days. The calculated T2 value was prolonged in only two cases in which biopsy-proved pancreatic infarction had occurred. No prolongation of T2 was evident in four cases of rejection alone. These results suggest that mean T2 calculation at 1.5 T may not be a reliable indicator of pancreatic transplant rejection, but that gadopentetate dimeglumine-enhanced gradient-echo MR imaging of the pancreatic transplant may be a reliable early indicator of pancreatic transplant dysfunction.

Adult↗

PubMed1998

Endothelial prostacyclin (PGI-2) production of human and porcine valve allografts related to ischemic history.

BACKGROUND: The significance of cellular viability in human valve allografts for functional clinical longevity continues to be debated. Meaningful tests for this biological entity are therefore in demand to quantify the relative merits of graft origin and procurement techniques. The valve leaflet endothelium is recognized as a particularly sensitive target to noxes and its continued ability to produce prostacyclin (PGI-2) after explantation has been suggested as indicating viability. OBJECTIVE: Graft ischemic history and species differences were therefore studied in human and porcine valve leaflets by the measurement of endothelial prostacyclin production, post-explantational, basal and after stimulation with bradykinin. METHODS: Four groups of aortic valve donors were established. Fresh human heart-beating donors (h-HBD), cadaveric human donors (h-NHBD) processed within 24 h, fresh porcine donors (p-HBD) and cadaveric porcine donors (p-NHBD) also processed within 24 h. Leaflets were separately incubated at 37 degrees C for successive periods of 30 min up to 5 h in Earle's Medium 199. After 240 min PGI-2 production was stimulated by 10 microM bradykinin. Postincubational release was stopped with indomethacin 10 microg/ml. Prostacyclin production was measured as 6-kPGF1a using an ELISA. RESULTS: Initial PGI-2 production is significantly higher in porcine than in human grafts and in both species enhanced by previous warm ischemia. While baseline species differences disappear during progressive incubation, differences resulting from graft history are maintained. After PGI-2 stimulation species differences dominate again while ischemic history has no effect. CONCLUSION: Ischemia and surgical manipulation are stimulators of endothelial PGI-2 production in both human and porcine allografts and, therefore, a correlation of this metabolic activity with cellular integrity may be misleading. Valid data are obtained only if the natural time-course and reaction to stimulation of PGI-2 production are duely recognized and species differences in the response to mechanical and ischemic stress are considered.

Adult↗

PubMed1996

A longitudinal study of the natural history of growth post-transplantation.

We have evaluated 587 patients with a functioning renal allograft for at least 54 months in whom baseline and continuous bi-annual height measurements were available. All height data were converted into SD score (SDS) or Z-score using normative tables. The results obtained in these patients were compared to our previous data collected at two years (N = 300) and three years (N = 412) post-transplantation. The demography of the study groups in the three time periods was similar. The height deficit in the first study was -2.41; it was -2.46 at the end of the second study period and was -2.29 at the end of the third study period. Children in the first study period had an improvement in height SDS (delta Z) of +0.18, of +0.16 in the second period, and of +0.11 at the end of the third study period. When improvement in height SD was evaluated by donor source, no differences were noted between living related and cadaver donor transplants. Analysis of height SDS by race revealed that, whereas for Caucasian children a steady improvement of 0.18 was noted during both second and third study periods, there was actual deceleration of growth for the African-American and Hispanic children at the end of the third study period (P < 0.02). Multivariate analysis showed that only initial height deficit and recipient age were independent predictors of improved height post-transplantation. Catch up growth, defined as an improvement of 1 SDS, was seen only in those with the greatest deficit or in children 0 to 1 year of age. Overall, catch up growth was seen in only 47% of 2 to 5 year olds. For children over the age of six years who form 72% of the total study cohort, little catch up growth was noted. Our long-term studies reveal that in the first years post-transplantation, when renal function is still stable, height acceleration does not occur in most of the children over the age of six years, and alternative strategies are necessary to improve the quality of life of these children.

Adolescent↗