Drainage of the exocrine pancreas in clinical transplantation: comparison of bladder versus enteric drainage in a consecutive series.

The purpose of this study was to define the incidence of urologic and metabolic complications after simultaneous kidney/pancreas transplantation (SKPT) with bladder drainage (BD). Review of 55 SKPT with BD performed between 1989 and 1995 demonstrated patient, kidney, and pancreas survival rates of 95%, 89%, and 78%, respectively, with a mean follow-up of 41 months (range 12-78 months). Over this follow-up period 78% of these patients experienced a urinary tract infection, 27% had hematuria, and 38% had at least one hospital admission for dehydration. Recent experience with primary enteric drainage of the exocrine secretions of the transplanted pancreas (n = 11) has demonstrated the total absence of these complications (follow-up range 2-12 months). These results suggest the value of continuous re-evaluation of surgical techniques as the care of transplant patients evolve.

Microchimerism and rejection in clinical transplantation.

BACKGROUND: Haemopoietic microchimerism has been identified in recipients of solid-organ transplants and is thought by some to be critical for the development and maintenance of immunological tolerance. The aim of this study was to correlate prospectively the persistence of donor cells with clinical outcome in recipients of kidney, kidney and pancreas, and liver transplants. METHODS: Persistence of donor cells in recipient peripheral blood was assessed at 3 days, and at 1, 3, 6, and 12 months after transplantation by a two-stage nested PCR technique to detect donor MHC HLA DR gene specifically. A pretransplant blood sample was collected from each patient to serve as an individual negative control. Seven liver, six kidney and pancreas, and 17 kidney patients were enrolled. 12 of the 17 kidney patients and all of the kidney and pancreas, and liver recipients were suitable for analysis. Exact matches for donors and recipients at the HLA DR loci (n = 1) or inability to obain primer pair specificity among similar HLA DR types (n = 4), meant that we were unable to analyse five patients. FINDINGS: Donor DNA was detected in 20 (80%) of 25, ten (40%) of 25, seven (30%) of 23, five (22%) of 23, and six (32%) of 19 recipients at 3 days, and 1, 3, 6 and 12 months post-transplant, respectively. Within individuals, the detection of donor DNA varied over time; only two patients had detectable donor DNA at all times. Analysis of the whole group of transplant patients showed a similar frequency and severity of rejection episodes in patients with and without microchimerism as defined by detectable donor DR genes. INTERPRETATION: These data suggest that a significant percentage of the recipients had persistent donor class II DNA in the peripheral circulation for at least 1 year after transplantation. We showed that a pretransplant blood sample is critical to avoid a false-positive result, and suggest that detectable chimerism may vary over time in individual patients. Therefore, analysis of microchimerism with a single, post-transplant analysis may not help in making clinical decisions for individual patients.

Evolving strategies in immunosuppressive therapy: the Emory experience.

We have reviewed our experience with various immunosuppression regimens over the past 11 years in 2,065 renal transplant recipients. Patients received triple-drug maintenance therapy with CsA, imuran and prednisone following either no induction therapy or treatment with polyclonal (PCA) or monoclonal (MCA) antibody. The most recent immunosuppressive regimen has included CsA, MMF, and prednisone without induction therapy. We observed that those patients receiving PCA had a better graft survival 5 years after transplantation than recipients with MCA induction or those receiving standard triple drug therapy without induction. Patients receiving MMF experienced superior one-year graft survival compared with those receiving induction with PCA, MCA or standard triple drug therapy. A similar one-year graft survival rate for both Black and White recipients was observed in the MMF group and raises the possibility of achieving improved long-term graft survival in Black recipients with a MMF-based immunosuppression strategy. Our experience indicates that excellent short-term graft survival can be achieved with an immunosuppressive protocol of MMF, CsA and prednisone without induction. Graft survival in MMF-treated recipients was equal to or superior to that which we previously achieved with induction therapy.

Ureteral obstruction due to calculi in the early postoperative period in renal cadaveric transplantation: a case report and discussion of ureteral obstruction in the renal transplant patient.

We report a case of obstruction secondary to multiple ureteral calculi on postoperative day 3 after cadaveric renal transplantation. Treatment consisted of ureterolithotomy with stenting of the ureteroneocystotomy and convalescence was otherwise unremarkable. Obstructive complications of the ureter after renal transplantation are reviewed.

Simultaneous pancreas kidney transplantation: initial experience of the Emory University transplant service.

The successful replacement of islet tissue by pancreas transplantation appears to be beneficial in the early course of those uremic diabetic recipients who receive a simultaneous renal transplant. The long-term advantages of SKP transplantation remain to be determined, however, current improvement in patient and graft survival following SPK and the difficulties thus far reported in islet cell transplantation have renewed clinical interests in SPK, PAK and PA transplantation. In our experience, pancreas transplantation has been a challenging technical, immunological and physiological endeavor which was well received by our patients despite the initial problems and complications we and they encountered. Notwithstanding extensive preparation, our team experienced a "learning curve" and we present many of the lessons we learned. This knowledge has aided our transplant team in the successful management and avoidance of these complications and other inherent problems associated with SKP transplantation in subsequent patients.

Epitope specificity of HLA class I alloantibodies. I. Frequency analysis of antibodies to private versus public specificities in potential transplant recipients.

Sera obtained sequentially from 419 patients awaiting solid organ transplantation were screened and analyzed for HLA class I epitope specificity. Antibodies detected in each serum were defined as "private" if reactivity could only be demonstrated against a single specificity within one of the eight major CREGs, or as "public" if reactivity in a serum could be demonstrated against two or more specificities within a single CREG. A total of 139 sera contained % PRA > 0, in which 147 specific antibodies were identified. Of the 103 positive sera, 93 (90%) contained antipublic antibodies, with or without additional antiprivate antibodies, whereas just 10 (10%) sera contained only apparent antiprivate antibodies. The success rate in defining antibody specificities was low at PRA values of 1%-20% due to weak reactivity and high false-positive rates. Specificity analysis with high test sensitivity and specificity was achieved with PRA values between 40% and 80%. At PRA values > 80%, test sensitivity remained high but specificity declined. We conclude that most anti-HLA antibodies are directed against high frequency public epitope clusters (CREGs), and highly sensitized patients develop antibodies in a fairly predictable fashion, a feature that significantly improved the success rate of specificity analysis. Since high frequency antipublic antibodies are common sequelae of CREG mismatches, further definition of HLA class I public epitopes eventually may be important in donor-recipient matching.

Comparison of fine-needle aspiration biopsy, Doppler ultrasound, and radionuclide scintigraphy in the diagnosis of acute allograft dysfunction in renal transplant recipients: sensitivity, specificity, and cost analysis.

150 episodes of allograft dysfunction in 128 renal transplant recipients, 77 due to acute rejection, 32 secondary to acute-on-chronic rejection, 33 due to either prerenal factors, acute tubular necrosis, or ciclosporin A nephrotoxicity, and 8 secondary to multiple causes, were evaluated by fine-needle aspiration biopsy (FNAB), Doppler ultrasound (DUS), and radionuclide scintigraphy (RS), each performed within a 24-hour period and prior to any specific therapeutic intervention. Tests were interpreted by appropriate specialists in a large transplant center without access to clinical information. The final diagnosis was based primarily upon response to therapeutic maneuvers with histological (core biopsy) confirmation in 123 episodes. RS was the most sensitive (70%) test for the diagnosis of acute rejection during the early posttransplant period, exceeding both FNAB (52%) and DUS (43%). The predictive accuracy of either FNAB, DUS, RS, or core biopsy in the detection of a steroid-responsive component to acute rejection when superimposed upon chronic rejection was low at approximately 50%. When the underlying cause of renal dysfunction was either prerenal, acute tubular necrosis, or ciclosporin A nephrotoxicity, FNAB, DUS, and RS each gave an erroneous diagnosis of acute rejection in about 50% of the episodes. Cost analysis revealed that core biopsy was the most expensive test, but only 9% more than RS, with FNAB the least costly. In conclusion, the lack of ideal sensitivity and specificity combined with the expense of present-day FNAB, DUS, RS, and core biopsy in the diagnosis of a therapeutically reversible component to acute-on-chronic rejection and of FNAB, DUS, and RS in the diagnosis of acute rejection during the early posttransplant period should prompt research into ways to improve their diagnostic yield or alternate modalities.

Atrial natriuretic factor does not improve the outcome of cadaveric renal transplantation.

Atrial natriuretic factor (ANF) ameliorates renal damage in animal models of acute ischemic renal failure. Consequently, ANF could blunt acute tubular necrosis related to ischemia that occurs frequently in cadaveric renal transplants. Ten pairs of cadaveric kidneys were transplanted into 20 recipients. Paired recipients received either alpha-human ANF (hANF) or vehicle alone in a prospective, double-blind protocol. Upon revascularization of the allograft, either hANF or vehicle was administered intravenously as a 50-micrograms bolus, followed by a 4-h infusion (0.1 microgram/kg/min). Glomerular filtration rate ([125I]iothalamate clearance) was measured between 4 and 7 days posttransplant and again between 14 and 21 days posttransplant. Serum creatinine was measured daily when patients were in the hospital, then twice weekly as patients were examined in the outpatient clinic. Between the groups, there was no significant difference in age of the recipients or donors, cold ischemia time, or histocompatibility leukocyte antigen match. Infusion of hANF had no adverse effects. When subjects receiving hANF were compared with those treated with vehicle alone, there were no significant differences in serum creatinine or glomerular filtration rate. Three hANF and four vehicle recipients required dialysis postoperatively. At 1 month posttransplant, 19 of 20 patients had functioning allografts; an allograft from one hANF recipient never functioned. It was concluded that hANF, when given by the protocol of this study, had no beneficial effect on the outcome of cadaveric renal transplantation in humans.

Alterations in myocardial thallium-201 distribution in patients with chronic systemic hypertension undergoing single-photon emission computed tomography.

To characterize thallium-201 distribution in single-photon emission computed tomography (SPECT) cardiac images and polar bullseye maps, 100 patients with chronic systemic hypertension due to end-stage renal disease were studied and the results compared with those in 35 normotensive control subjects. Thallium-201 SPECT was performed after exercise in all control subjects and 70 hypertensive patients, and after intravenous dipyridamole in 30 patients. A frequent finding in hypertensive patients was a fixed decrease in the normal lateral-to-septal count density ratio in immediate thallium-201 SPECT images (1.02 +/- 0.10 vs 1.17 +/- 0.08 in control subjects, p less than 0.00001) and in 3-hour delayed images (1.02 +/- 0.11 vs 1.11 +/- 0.08 in control subjects, p less than 0.00001). No significant difference in count density ratio was present in patients undergoing treadmill versus diypridamole intervention. In 35 patients the count density ratio was greater than 2.0 standard deviations below the normal mean, creating the false impression of a fixed lateral defect (i.e., myocardial infarction). In 12 patients, myocardial wall thickness was measured at end-diastole by 2-dimensional echocardiography. Wall thickness was increased (greater than 11 mm) in all patients. The mean lateral-to-septal wall thickness ratio was 1.08 +/- 1.11; in no patient was the ratio less than 0.76 to indicate selective septal hypertrophy. The lateral-to-septal wall thickness and lateral-to-septal thallium-201 count density ratios correlated poorly (r = 0.43).(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of OKT3 monoclonal antibody therapy in steroid-resistant, predominantly vascular acute rejection. A report of three cases with morphologic and immunophenotypic evaluation.

We describe three patients who became oliguric and uremic in the early posttransplantation period. Following treatment with pulse methylprednisolone, all had biopsy evidence of severe residual rejection that was predominantly vascular. T cells formed the bulk of the infiltrates. Subsequent treatment with the monoclonal antibody OKT3 was associated with an immediate diuresis and improvement in serum creatinine. Repeat renal biopsy, obtained in clinical remission, in two of the three patients, showed marked improvement in the vascular lesions. All three patients maintain normal renal function 9, 13, and 18 months later. We conclude that OKT3 was effective in reversing steroid-resistant rejection despite a predominantly vascular pattern of cellular infiltration not usually considered amenable to any antirejection therapy.

Use of cryopreserved bone in spinal surgery.

One hundred fifty-two consecutive spinal fusions were performed over a 4-year period in 143 patients. Autogenous bone was used in 62 patients and frozen cryopreserved bone in 90. A variety of anterior and posterior procedures with and without instrumentation were performed. The percentage of successful arthrodesis was 87 in those who received autogenous bone, and 86.6 in those who received allograft bone. Thirty-four spinal fusions were surgically explored. Histologic evaluation of the bone taken at the time of surgical exploration showed viable osteocytes laying down osteoid, woven and lamellar bone, and no inflammatory or foreign body reaction. The authors conclude that cryopreserved bone, harvested and processed as described, is advantageous, safe, and results in a rate of bone union comparable to that of autogenous bone.