Outcome in recipients of dual kidney transplants: an analysis of the dual registry patients.

BACKGROUND: A novel but controversial method to increase the utilization of aged donor kidneys is the transplantation of both kidneys as a dual transplant. Initial single-center reports demonstrated outcomes similar to single kidneys from younger donors. In this report, we compare outcome in recipients of kidneys from donors > or =54 years of age who received a single kidney transplant reported to the United Network for Organ Sharing Scientific Registry versus a dual kidney transplant reported to the Dual Kidney Registry. METHODS: A retrospective analysis was performed, comparing four donor and nine recipient and outcome variables between recipients of a single versus a dual transplant between March 1993 and March 1999. RESULTS: Dual versus single transplants from donors > or =54 years of age have a significantly decreased incidence of delayed graft function, and lower serum creatinines up to 2 years after transplant despite having kidneys from significantly older donors with poorer HLA matching. CONCLUSIONS: Dual kidney transplants improve graft performance and outcome in recipients of kidneys from donors > or =54 years of age.

The LifeLink Foundation and cadaver kidney transplantation in Tampa.

1. LifeLink Foundation, a not-for-profit organization, has been the driving force and absolutely essential entity for kidney and liver transplantation in Tampa providing all the components (patient, organs and clinicians) save for inpatient hospitalization. It also plays a big role in the heart transplant program. LifeLink has increased the kidney transplant rate from the first 1,000 done in 17 years to the second 1,000 in 7 years and is on a pace for the third 1,000 in 5 1/2 years. 2. Because of its innovative programs, cadaver donor procurement by the Tampa LifeLink OPO has been roughly double the national average for the past 10 years. Because of cadaver kidney availability the median wait time from activation on the wait list to transplantation over the past 5 years was 159 days. The recent transplant rate is 14.7-22.7% higher than the national average, dependent upon the parameter measured. Similar results are seen for Tampa patients awaiting heart and liver transplantation. 3. The overall outcome of 1,184 cadaver kidney transplants performed in the decade 1989-98 was similar to that reported from the UNOS database in this series of publications. a) One- and 2-year graft survival increased 2% per year over the decade with a recent one-year graft survival rate of 96%. The overall T1/2 was 10 years. b) Our disastrous 1994 results were quickly reversed by a more intense pretransplant medical evaluation, the introduction of mycophenolate mofetil, more aggressive and earlier treatment of rejection episodes, and mandatory T- and B-cell flow cytometry crossmatching for all transplants. The incidence of rejection episodes decreased from 40 to 20%, and the first year immunological graft loss decreased from 5%, to 1.9%, to 0.8%, to 1.4% and 0% over the succeeding 4 years. 4. Individual factors affecting allograft survival were strikingly similar to national data, although all did not react statistical significance probably due to the smaller numbers. a) Primary and second grafts had similar survival rates (p = 0.97) whereas the third or subsequent graft survival was 7-32% poorer (p = 0.02). b) Black recipients had survival rates 10-13% lower than Caucasians and other races (p = 0.003). c) Patients with a peak PRA > 50 had survival values 4-13% poorer than those with < 50 PRA (p = 0.14). d) Patients with 2-4 HLA mismatches had graft survival rates 4-10% poorer than those with 0-1 mismatch (p = 0.12), whereas those with 5-6 mismatches had rates 6-17% poorer (p = 0.04). e) Although 22% of our transplants were to patients > 60 years of age, there was no difference (p = 0.81 to 0.90) in graft survival for the age groups 0-40, 41-60 and > 61. However, the proportion of grafts lost due to patient death compared with all allografts lost, was very different at 21% in the youngest group, 43% in those 41-60 years of age, and 63% in recipients > 61 years. 5. The rate of delayed graft function with imported kidneys was higher (27 vs. 16%, p = 0.006) but essentially the same as local kidneys with the same ischemia times. However, 41% of local kidneys were transplanted within 12 hours of procurement. Totally, 78% of local kidneys were transplanted within 18 hours (11% DGF rate) versus 79% of imports being transplanted at > 18 hours (32% DGF rate). Ischemia time, not the kidney source is the key issue since: a) There was no difference in overall graft survival of imported versus local kidneys (p = 0.95) nor in comparing local versus import kidneys with (p = 0.66) or without (p = 0.69) DGF. b) There was, however, a 11-17% overall poorer graft survival over 3 years in kidneys with DGF (p < 0.001) seen with both local (9-18% poorer, p = 0.0002) and imported (12-19% poorer, p = 0.008) kidneys. c) Kidneys displaying DGF came from older donors (40 vs. 34 years, p = 0.023) and had longer ischemia times (21 vs. 15 hours, p < 0.0005). 6. Dual kidney transplants were started in late 1996 with older or marginal donors to provide a better chance of success fo

TNF but not IL-1 decreases pancreatic acinar cell survival without affecting exocrine function: a study in the perfused human pancreas.

Substantial quantities of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) are produced within the pancreatic parenchyma during acute pancreatitis. Recent evidence suggests that IL-1 beta and TNF-alpha propagate acute pancreatitis and intensify the resulting pancreatic acinar cell death. This study examines the direct effect of IL-1 beta and TNF-alpha on pancreatic acinar cells. Human pancreata (n = 6), harvested during organ procurement, were perfused ex vivo through the splenic artery using a sterile, oxygenated colloid solution. Each pancreas was perfused with either recombinant human IL-1 beta or TNF-alpha for 2 h and subsequently with the cholecystokinin analogue caerulein (positive control). Venous effluent was collected continuously and amylase and lipase were determined at 15-min intervals. Pancreatic histology was graded at baseline and following cytokine and caerulein perfusion. To examine the long-term effects of these cytokines on acinar cell viability, additional in vitro studies utilized the AR42J acinar cell line which was exposed to either IL-1 beta or TNF-alpha with survival determined daily by MTT assay. Perfusion of the human pancreas with either IL-1 beta or TNF-alpha did not alter amylase, lipase, or histology. Caerulein did induce pancreatitis as measured by increased amylase, lipase, and pancreatic histology. Survival of pancreatic acinar cells decreased when they were incubated with TNF-alpha but not IL-1 beta. Although present in large amounts within the pancreas during acute pancreatitis, IL-1 beta and TNF-alpha have no direct effect on acinar cell viability or exocrine function acutely nor do they induce pancreatitis. When present for more than 24 h, however, TNF-alpha but not IL-1 beta has a dramatic effect on acinar cell survival.

Flow cytometry crossmatching and primary cadaver kidney graft outcome: relevance of T and B cell targets, historic sera and autologous controls.

There is limited information regarding the role of flow cytometry crossmatching (FCXM) in primary cadaver kidney allografting and even less about B cell reactivity and graft survival (GS). Furthermore, there is little or no published data concerning reaction strength (cutoff value), the effect of historic sera reactions, and the usefulness of performing autologous crossmatches (XMs) on GS. These factors were examined retrospectively on 214 primary transplants performed from August 1991 to January 1994 with follow-up to July 1995. Three-color FCXMs were done on a 1024-channel BD-FACScan, and the shift in median channel fluorescence (MCF) over the negative control was calculated. All patients had a negative T cell (AHG) and warm B cell (2 was, extended incubation) cytotoxicity XM, and none was excluded in calculating GS. A quantitative effect was noted as stronger MCF shifts vs. T or B cells correlated with decreased GS (r = 0.98 and 0.92, respectively). Significant differences were seen with cutoff values of T = 50 and B = 110 which were 1.7-1.8 times the SD above the mean MCF of normal sera controls T neg patients (n = 198) and 1- and 3-yr actuarial GS of 86% and 79% compared to T pos patients (n = 16) of 75% and 49%, p = 0.008. B neg patients (n = 177) had 1- and 3-yr GS od 86% and 81% compared to B pos patients (n = 37) of 78% and 47%, p = 0.005. Most informative was the analysis of combined T and B cell FCXM results. Three years GS for T neg - B neg patients (n = 171) was 81% and for T pos - B neg patients (n = 6), it was 83%, p = 0.98. The 27 T neg - B pos group's GS was lower at 62% but did reach significance. Poorest GS was seen for T pos - B pos patients (n = 10) at 23%, p = 0.0001. Reaction patterns showed that T cells detected only HLA Class I antibodies, whereas B cells detected both Class I and II. Historic sera (> or = 1 month old) reactivity influenced GS. Patients with > or = 2 past sera positive but current serum negative reactions vs. T or T plus B cells (n = 7) had a poor 29% GS, while those historically positive only vs. B cells (n = 7) had 100% GS. On the other hand, patients positive only with the current serum (n = 16) had 2-yr GS of 100% (false positive test?), while patients whose current and historic sera reactions were positive (n = 21) had a 25-50% GS (true positive test?). About 1 in 15 patients (19%) displayed positive autologous FCXM reactions. Subtraction of autologous MCF shift values from those vs. the donor converted 17 patients to the T neg - B neg or T pos - B neg group whose 2-yr actual GS was not significantly different (p > 0.8) from those initially testing T neg B neg vs. their donors.

Neurofibromatosis and arterial aneurysms.

Neurofibromatosis (NF) is a common autosomal dominant disease characterized by the development of hamartomatous or neoplastic lesions due to the proliferation of neural crest cells. An association of aneurysmal arterial lesions with NF, which may have catastrophic complications, has been rarely reported. Our recent experiences with the diagnosis and management of three male NF patients with aneurysms is described. A 19-year-old-man with refractory hypertension due to unilateral, complex, unreconstructable renal artery aneurysms was successfully treated by nephrectomy. Histopathology demonstrated intramural renal artery Schwann cell proliferation. A 44-year-old patient underwent ligation of a ruptured superior mesenteric artery aneurysm. Finally, a femoral-popliteal artery saphenous vein bypass graft with aneurysm exclusion was performed in a 58-year-old-man with a 3.5 cm symptomatic popliteal artery aneurysm. In NF, the underlying pathology in large arteries is intramuscular Schwann cell proliferation with secondary fibrosis. Mesodermal dysplasia may affect small arteries resulting in stenosis, post-stenotic dilatation, or aneurysmal degeneration. Clinicians should be aware of the unusual association of NF with aneurysms, particularly the occult development of visceral and renal artery aneurysms. These lesions are subject to sudden rupture with potentially devastating consequences, and they mandate a high index of suspicion in NF patients.

Sclerosing peritonitis.

Sclerosing peritonitis (SP) is an uncommon and devastating problem which involves the visceral and parietal peritoneal surfaces of the abdominal cavity. SP has been reported in association with peritoneal dialysis, with medications, and following peritonitis. No clear etiology or preventative treatment exists for this unusual problem. Herein, we report 3 cases with the unusual aspect of apparent progression of this fibrotic and sclerosing process after the termination of the peritoneal dialysis and successful renal transplantation. Each of these cases resulted in a mechanical small bowel obstruction secondary to a densely fibrosing and encasing peel of reactive connective tissue visibly different from the usual postoperative adhesions. Sclerosing peritonitis should be included in the differential diagnosis of a current peritoneal dialysis patient who exhibits signs of partial small bowel obstruction with a continual decrease in peritoneal clearance and/or successfully transplanted patients who had utilized peritoneal dialysis therapy in the past and now exhibit signs and symptoms of a mechanical small bowel obstruction.

The hemodynamic effects of Cremophor-EL.

A problem associated with parenteral cyclosporine has been the increased incidence of renal toxicity. Cremophor-EL, the vehicle for parenteral cyclosporine has been associated with massive histamine release and anaphylaxis in certain animal models. We investigated the effects of Cremophor-EL on the cardiac output (CO); mean arterial pressure (MAP); and hepatic, renal and pancreatic blood flow in the anesthesized canine model. Doppler flow probes were utilized to calculate individual organ blood flow. Profound adverse affects were noted on the CO, MAP, and hepatic blood flow. There were negative trends noted in the renal and splenic arterial flow that did not reach statistical significance. It was noted that the changes in organ blood flow were partially independent on MAP and the total dose of Cremophor-EL. We therefore conclude that it is prudent to consider the possible adverse hemodynamic role of Cremophor-EL in canine allograft dysfunction.

Perioperative blood transfusion adversely affects prognosis of patients with stage I non-small-cell lung cancer.

It has been speculated that blood transfusion might adversely affect prognosis in cancer patients by immunosuppression. To avoid the confounding affect of advanced disease, we tested this hypothesis in 117 patients with stage I non-small-cell lung cancer. Mean and median follow-up were 49.7 months and 47 months, respectively. Patients who died during the postoperative period were not included. Perioperative transfusion was defined as administration of whole blood or packed cells within 30 days of operation. The overall cumulative 5-year disease-free survival rate was 67%. In patients with transfusion, it was 53% and in patients without transfusion it was 81% (p = 0.0055). A multivariate analysis was performed that included patient age, race, sex, cell type, extent of operation (pneumonectomy versus lobectomy/segmentectomy), operative blood loss, admission hematocrit, discharge hematocrit, and the presence or absence of perioperative transfusion. The only variable that significantly correlated with 5-year disease-free survival was the presence or absence of perioperative transfusion (p = 0.0278), and this effect was not related to the number of transfusions. Retrospective analysis of long-term results of patients surviving curative operation for stage I lung cancer shows that any perioperative transfusion significantly worsens the patient's prognosis and suggests very strongly that this association is due to an adverse effect of the transfusion rather than the transfusion serving as a marker for another risk factor.

Purification of a membrane glycoprotein with an inositol-containing phospholipid anchor from Dictyostelium discoideum.

Large-scale purification of a Dictyostelium discoideum cell surface glycoprotein, which is anchored in the membrane via a glycosylphosphatidylinositol (GPI) moiety, is described. The purification protocol involved four steps: separation of crude cell membranes by low-speed centrifugation, delipidization of these membranes using acetone, extraction of the membrane proteins using the detergent Octyl beta-D-thioglucopyranoside (OTP), and purification of a specific membrane protein by monoclonal antibody immunoaffinity chromatography. The protein purified, PsA (prespore-specific antigen), is a developmentally regulated membrane glycoprotein found on a subset of cells from the cellular slime mould, D. discoideum. The protocol provides an efficient, economical, and technically simple way to purify GPI proteins in sufficient quantities for structural and functional studies. PsA was recovered at a yield of about 60%; with a purity of 97%, the extraction of 1 x 10(10) cells (1.1 g dry weight) yielded about 0.5 mg PsA glycoprotein. Techniques are described for growing kilogram quantities of D. discoideum cells in stainless steel trays at little cost. D. discoideum has considerable potential as a novel expression system for the production of foreign membrane-associated proteins. The purification strategy provides a means of purifying other GPI proteins, including those produced by protein engineering techniques.

A micromechanical technique for monitoring cell-substrate adhesiveness: measurements of the strength of red blood cell adhesion to glass and polymer test surfaces.

We report a novel method for rapid comparison of the relative strength of adhesion of cells to different solid surfaces. A vertically oscillating micropipette is brought above an individual cell in such a manner that it makes contact with the cell at the lower limit of its travel. The pressure within the micropipette is gradually reduced until the cell attaches to the micropipette by suction and is lifted from the solid surface. The reduction in pressure required to detach a cell depends on the specific cell/substrate combination and serves as a relative measure of the strength of cell adhesion. A particular advantage of this approach over conventional methods is the ability to select particular cells from a population. As a test of the reproducibility of the method and its ability to distinguish the strength of adhesion of cells to different solid surfaces, we have used it to measure the adhesiveness of human red blood cells to hydrophilic glass, tissue culture grade polystyrene, polyethylene terephthalate, and polymethyl methacrylate. We find that results for the same surface are highly reproducible and that the method is capable of distinguishing small differences in the adhesiveness of red blood cells to the above surfaces.

Blunt trauma to the thoracic outlet and angiography.

When major injuries occur to the thoracic outlet, common practice is to obtain an arteriogram without other clinical evidence of vascular injury, because of the purported high association of thoracic outlet trauma and vascular injuries, including ruptured aortae. In order to evaluate this association, a review was undertaken of all patients admitted to a major hospital over 5.5 years who underwent angiography or other evaluative measures as a result of their thoracic outlet trauma. There were no great vessel or aortic injuries without overt clinical criteria. Angiography for aortic and great vessel injury is unnecessary unless there is a widened mediastinum or other overt clinical indications of vascular injury. Judicious use or avoidance of angiography is therefore encouraged for multiple reasons.

Benign hemangiomyoma of the uterus.

A benign cavernous hemangiomyoma of the uterus in a 52-year-old woman is described. The tumor consisted of large venous channels within a stroma composed chiefly of smooth muscle and was confined to the corpus, without involvement of the endometrium or cervix. Considerable thrombosis had occurred within the vascular spaces. Hemangiomas of the uterus are very uncommon and the great majority are benign. A classification of uterine hemangiomas is presented, together with a discussion of their histogenesis and their relation to malformations.