Heterologous antilymphocyte globulin: studies in vitro.

Incubation of dog-lymphocyte cultures with globulin from antiserum to lymphocytes resulted in a greater percentage of transformed cells than incubation with phytohemagglutinin. Viability counts demonstrated that this globulin and phytohemagglutinin had approximately equal degrees of cytotoxicity.

Hepatic angiosarcoma and liver transplantation: case report and literature review.

Hepatic angiosarcoma is a rare malignant vascular tumor that accounts for up to 2% of all primary liver tumors. Accurate diagnosis of this tumor is difficult, especially if the patient has no history of exposure to specific carcinogens including thorotrast, arsenicals, and vinyl chloride monomer. Diagnosis of diffuse angiosarcoma by means of liver biopsy has been reported as treacherous and nondiagnostic. Herein, we present a case of a 61-year-old Caucasian male with history of cryptogenic cirrhosis, normal alpha-fetoprotein, and pretransplant abnormal liver MRI who underwent nondiagnostic liver biopsies followed by liver transplantation. High grade diffuse angiosarcoma was diagnosed in the explanted liver. The patient developed bone metastases at 8 months and is alive 1 year posttransplantation. Diffuse liver tissue infiltration seen pretransplant on CT scan or MRI, suggesting the possibility of diffuse liver lesions (HCC, angiosarcoma, etc) must be fully investigated with all techniques available including multiple open liver biopsies to avoid the sacrifice of a liver allograft in these patients.

A model for planning health care in patients with end-stage renal disease.

Treatment modalities of end-stage renal disease (ESRD) patients include in-center dialysis, home dialysis, and kidney transplant. We present a model to account for all aspects of modality use to aid in planning regional facilities. Five years of data for 979 patients on dialysis in Wisconsin between 1970 and 1975 are used. The model shows movement (transit probabilities) from one modality to another, eg, transition from in-center dialysis to transplantation, and data were used to derive all transitional probabilities characterizing patient movement from one modality to another. Model and probabilities were used to predict number of patients in each modality in 1976, and the model was used to predict number of patients in each treatment modality through 1990. These figures may be used for planning regional facilities. Extrapolation of this model and derived probabilities for nationwide projections may be possible.

The human splenic suppressor cell.

Studies of human spleen cell suspensions show that they contain a population of cells which can inhibit the mixed lymphocyte reaction. The cells appear to be able to suppress the patient's own response to an antigenic challenge in slightly greater degree than their ability to suppress a nonspecific mixed lymphocyte culture. The suppressive effect is dependent on cell dose and is linearly related to the log of cell concentration. At low dose these cells have no suppressive effect and, in fact, behave as stimulators. Exposure of these cells to an environment containing immunosuppressive drug abrogates their suppressor activity. Manipulation of these cells may prove to be of value in the control of graft rejection.

First report of the United Network for Organ Sharing Transplant Tumor Registry: donors with a history of cancer.

BACKGROUND: Severe organ shortages have led to donor pool expansion to include older individuals, patients with hypertension, diabetes, and a past history of cancer. Transmission of cancer from cadaveric donors is a risk of transplantation and carries a high mortality rate. METHODS: During a 33 month period, UNOS recorded 14,705 cadaveric donors of which 257 had a past history of cancer (PHC). A total of 650 organs (397 kidneys, 178 livers, and 75 hearts) were transplanted from these 257 donors. Type of cancer, tumor-free interval at organ procurement, and whether any PHC donor transmitted a tumor to the recipient were analyzed. RESULTS: Three PHC donor tumor types (skin, brain, genitourinary) were associated with 549 of the transplanted organs (85%). Twenty-eight recipients of PHC donor organs developed posttransplantation tumors (18 skin, 2 PTLD, 8 solid cancers). During a mean follow-up of 45 months (range 30-61 months), no recipients of organs from PHC donors developed a donor derived cancer. The majority (71.5%) of all non-skin and non-CNS system cancer donors had a cancer-free interval of greater than five years. CONCLUSIONS: Risks of cancer transmission from donors with a history of non-melanoma skin cancer and selected cancers of the CNS appear to be small. Risks of tumor transmission with certain other types of cancer may be acceptable, particularly if the donor has a long cancer-free interval prior to organ procurement while certain other cancers pose a high transmission risk. Selective use of PHC donors may permit expansion of the donor pool.

National impact of pulsatile perfusion on cadaveric kidney transplantation.

BACKGROUND: The simplicity and success of cold storage of cadaveric kidneys have led to the infrequent use of pulsatile perfusion. However, there may be advantages to pulsatile perfusion for less optimal donors. METHODS: United Network for Organ Sharing data were analyzed retrospectively to determine the impact of pulsatile perfusion on initial function and 1-year graft survival. The analysis included 60,827 cadaveric kidney transplants performed between 1988 and 1995. Multivariate logistic regression analyses were used to determine the effect of preservation method on both early kidney function (need for first-week dialysis after transplant) and 1-year graft survival, after adjusting for other known risk factors. RESULTS: The preservation method exhibited a highly significant impact on the need for first-week dialysis. Ice-preserved kidneys were associated with a 2.13-fold increase in the odds of requiring dialysis compared with perfused kidneys. If the donor age was > or =55 years, the odds were 2.33-fold higher for ice-preserved as compared with perfused. If cold ischemic time was > or =24 hr, there was a 2.19-fold increase in the odds of dialysis for ice-preserved kidneys. African-American recipients of cold-stored kidneys had a 2.29-fold greater odds of first-week dialysis. CONCLUSIONS: Based on these findings, it was estimated that the increased cost of perfusing kidneys from all donors > or =55 years of age would be balanced by the decreased need for posttransplant dialysis if the cost related to dialysis were $14,700 or greater per patient. These facts, coupled with the ability to assess an older donor kidney before transplant, could make pulsatile perfusion for the expanded donor financially as well as medically desirable.

Association of the type of induction immunosuppression with posttransplant lymphoproliferative disorder, graft survival, and patient survival after primary kidney transplantation.

BACKGROUND: The use of antilymphocyte antibodies for induction therapy or for treatment for rejection has been associated with an increased risk of posttransplant lymphoproliferative disorder (PTLD). The authors investigated the incidence of PTLD after monoclonal antilymphocyte, polyclonal antilymphocyte, interleukin (IL)-2 receptor antibody, or no induction therapy in primary kidney transplant recipients. METHODS: A multivariate Cox analysis of 38,519 primary kidney transplants from January 1, 1997, to December 31, 2000, was performed to compare the incidence of PTLD, graft survival, and patient survival among the induction groups. RESULTS: The actual incidence of PTLD was 0.85% in 2,713 recipients with monoclonal, 0.81% in 4,343 with polyclonal, 0.50% in 7,800 with IL-2, and 0.51% in 23,663 recipients with no induction therapy (P=0.02). The Cox model indicated that as compared with no induction, the increased risk of PTLD was 72% with monoclonal (P=0.03), 29% with polyclonal (P=0.27), and 14% with IL-2 induction (P=0.52). IL-2 receptor antibody was associated with a 17% reduced risk of graft loss (P=0.002) and a 21% reduced risk of mortality (P=0.005) compared with no induction. Monoclonal and polyclonal induction therapies were not associated with a reduced risk of graft loss or mortality. Mycophenolate mofetil discharge maintenance immunosuppression was associated with a significantly reduced risk of PTLD and graft loss compared with azathioprine. CONCLUSIONS: Among induction therapies, IL-2 receptor antibody induction was associated with the smallest risk of PTLD and improved graft and patient survival. Monoclonal or polyclonal induction was not associated with improved graft or patient survival, and monoclonal induction was associated with an increased risk of PTLD.

Severe bleeding diathesis associated with invasive aspergillosis in transplant patients.

A severe bleeding disorder developed in eight renal transplant patients with invasive aspergillosis. The hemorrhagic diathesis was characterized by wound oozing, severe upper and lower gastrointestinal tract hemorrhage, and mucosal bleeding at other sites. This unusual coagulopathy was characterized by a prolonged thrombin time, which was corrected with protamine sulfate, and an abnormal Reptilase time. The bleeding disorder antedated the diagnosis of invasive aspergillosis in all cases. The probability that the coagulopathy was due to proteolytic enzymes elaborated by Aspergillus sp. is discussed.

Early diagnosis of acute postoperative renal transplant rejection by indium-111-labeled platelet scintigraphy.

A prospective evaluation of 111In-labeled platelet scintigraphy (IPS) for the early diagnosis of acute postoperative renal transplant rejection (TR) was undertaken. The results of IPS were compared with in vitro biochemical tests, the clinical finding of graft tenderness, and combined [99mTc]DTPA and [131I]orthoiodohippurate scintigraphy. With a sensitivity of 0.93 and a specificity of 0.95, IPS provided otherwise unavailable diagnostic information. Furthermore, postoperative IPS was a good predictor of long-term allograft survival.

Determinants of waiting time for heart transplants in the United States.

BACKGROUND: Reports have been published on factors affecting the variations in waiting times for kidney and liver transplant candidates who have been registered on the United Network for Organ Sharing's waiting list. This study reports on determinants of waiting time differences that occur in the eleven UNOS regions for heart transplant candidates. METHODS: Retrospective analysis of 11,345 primary heart waiting-list registrations and 15,868 cadaveric donors, from whom 7,043 hearts were recovered and transplanted for the years 1994-96. Because estimated populations in the eleven UNOS regions vary from 10.8 to 43.2 million, analyses utilized Registrations/million population and Transplants/million population to obtain an R/T ratio. The relationship of the R/T ratio to the median waiting time was then examined for different demographic variables. RESULTS: The numbers of new heart candidate registrations, heart transplants performed, and waiting list deaths have undergone little change from 1991 through 1996. National median waiting times varied by basic demographic variables such as ABO blood type, race, age group, and UNOS medical urgency status. In the eleven UNOS regions, registrations per million ranged from 11.5 to 33.0 and transplants per million from 5.3 to 10.7. Registration/Transplant ratios correlated with median waiting times for urgency Status 1 and 2 as well as for blood group O recipients. Correlation with blood type AB recipients was less consistent, in part, due to the small number of AB recipients. CONCLUSIONS: There are wide variations in the number of heart transplant candidate registrations and in the number of heart transplants performed in the eleven UNOS regions. The registration to transplantation ratio correlated with median waiting times in these regions. Factors possibly contributing to the observed variations were examined.

Gastrointestinal complications in renal transplant recipients.

In a 16-year study, 101 gastrointestinal (GI) lesions (16 fatal) developed in 580 renal transplant recipients seen in the authors' institution. Lesions were seen at all levels of the GI tract, but colonic lesions were the most common (42 patients) and were fatal in 8. Segmental ischemic colitis was the single most common morphologic diagnosis (14 patients). Seven of these patients had an unusual syndrome that clinically, at surgery, and on gross examination resembled inflammatory bowel disease. Lesions were segmental; involved bowel was thickened and erythematous with creeping peritoneal fat. Histologically, mucosa adjacent to the frank necrosis showed simplification and striking epithelial atypia. Specific identifiable viral infections caused 28% of the GI complications in this series. This incidence is higher than that in other reported series. Most of these infections can be diagnosed from endoscopically obtained material. These findings have therapeutic implications.

Deep inferior epigastric arteriovenous shunt for hemodialysis.

The deep inferior epigastric artery and vein may be satisfactorily utilized for chronic hemodialysis in patients who have no extremity vessels available.

Indirect inguinal hernia in patients undergoing peritoneal dialysis.

There is an increasing number of patients whose permanent renal failure is managed by chronic peritoneal dialysis. Four adult male patients developed symptomatic indirect inguinal hernias shortly after the institution of dialysis. The hernia sac in each of the patients was both narrow and elongated. We postulate that in each patient the hydrostatic pressure of the dialysis fluid converted a patient processus vaginalis into a symptomatic indirect hernia.

Suppressor activity of the human spleen and thymus.

Both the spleen and thymus of man contain a population of cells which can suppress the mixed lymphocyte reaction. Splenic cells suppress the MLC 58 +/- 4.8 percent, and the thymus is able to suppress the MLC 90 +/- 2.6 percent. However, splenic cells require stimulation by vegetable mitogens before suppressor activity can be observed, and the thymus displays spontaneous suppressor activity without prior stimulation. The suppressor effect is linearly related to the log of the cell dose (r = 0.8, p less than 0.01), and at low doses the suppressor cells stimulate rather than inhibit the MLC. The cells are exquisitely sensitive to immunosuppressive drugs, and blood levels encountered in clinical organ transplantation abrogate their suppressive activity. The suppressive activity of the cells is nonspecific, and they are able to inhibit the MLC between individuals totally unrelated to the spleen or thymus donor. Since these cells likely play a role in the development of tolerance, further characterization of their properties is required.

Unexpectedly high incidence of cytomegalovirus infection in apparent peptic ulcers in renal transplant recipients.

Gastroduodenal ulcers in renal transplant recipients are usually accepted as being acid-peptic in origin. In a series of 573 renal transplant recipients there was histologic material available for examination from eight patients with gastroduodenal ulcers and three patients with gastric erosions. All ulcers had originally been diagnosed as peptic or stress ulcers. However, on review, five of them proved to contain cytomegalovirus (CMV); CMV was also present in all the stomachs with erosions. We suggest that CMV infection plays as important a role in upper gastroduodenal ulcers and erosions in renal transplant recipients as it does in similar lesions elsewhere in the gastrointestinal tract of these immunosuppressed patients.

Prevention of transplant renal artery stenosis.

Transplant renal artery stenosis occurred in 17 of 142 consecutive transplants (12 percent). All stenoses were in the renal artery distal to the anastomosis and two separate forms are recognized: angulation and segmental stenosis. Successful surgical correction in 12 of 17 patients relieved the hypertension and resulted in improved renal function. No patients receiving dipyridamole, a drug which inhibits platelet aggregation and intravascular fibrin deposition, developed segmental renal artery stenosis. No other factors could be identified which were important in either causing or preventing renal artery stenosis. Since intrarenal vascular changes are an integral aspect of rejection, the protection afforded by dipyridamole against segmental renal artery stenosis indicates that segmental stenosis is probably a manifestation of rejection.

Homotransplant renal artery stenosis.

Transplant renal artery stenosis occurred in 12 of 101 consecutive kidney transplants. Stenoses were all located in the renal artery distal to the anastomosis. Two separate forms of stenosis are recognized: angulation and segmental. All transplant patients with severe diastolic hypertension, refractory to medical management, and an audible abdominal bruit should undergo angiography. Surgical correction of the stenosis was accomplished in nine of 12 patients with cure of their hypertension.

Cyclosporine therapy and refractory Pneumocystis carinii pneumonia. A potential association.

In surveillance of 75 patients receiving renal transplants in 1984 at our institution, five cases of Pneumocystis carinii pneumonia were detected. All five cases occurred in a subgroup of 11 patients who had received cyclosporine. A retrospective epidemiologic survey of the infected patients revealed all five were heterosexual white men with onset of Pneumocystis pneumonia two to six months after cadaveric transplantation. All received cyclosporine and corticosteroids, and four of five patients also received azathioprine; none was neutropenic or had evidence of concurrent cytomegalovirus infection. Only one of these patients responded to therapy with sulfamethoxazole and trimethoprim, one patient responded to pentamidine therapy, and the remaining three patients died. Cyclosporine use may be related to development of Pneumocystis infections that are refractory to conventional antiprotozoal therapy, and transplantation programs should closely survey patients for such complications.

Bilateral pheochromocytoma and islet cell adenoma of the pancreas.

An 18-year-old woman with bilateral pheochromocytomas and an asymptomatic islet cell adenoma of the pancreas represents the 11th patient to be described with this combination of endocrine tumors. No other components of any multiple endocrine adenomatosis (MEA) syndromes were present. Because of this "overlap syndrome," in which tumors that have traditionally been considered to be components of separate and mutually exclusive MEA syndromes have occurred concomitantly in the same patient, a question is raised regarding the validity of a rigid classification of these various MEA syndromes. The possibility of a pancreatic tumor should be kept in mind in any patient with a pheochromocytoma, especially if it is bilateral of multicentric in origin.

Immunological responses in identical twins with renal transplants from a common donor.

Two identical twins suffering from end stage renal failure due to chronic pyelonephritis received cadaver renal allografts from one donor. Immune status was measured in both by in vitro responses to vegetable mitogens and by reactivity in mixed lymphocyte culture with a random volunteer. Both patients underwent rejection episodes at different times; these were of differing severity. Reactivity to PHA and in MLC was minimal during rejection and increased following recovery in spite of continued high levels of immunosuppression. In contrast, reactivity to pokeweed mitogen and concanavalin A increased at the time of rejection and fell with recovery. The changes seen in the twins, while qualitatively similar, differed in magnitude and timing. It is concluded that environmental factors as well as histocompatibility play a part in influencing immune responsiveness, and that studies of immune responsiveness should be interpreted with caution in the management of renal allograft recipients.