bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of immunosuppression regimen and in vitro lymphokines on natural killer activity in renal transplantation
Authors: Smillie Anne E. , Petrie James J. B. , Rigby Russell J.
Published: September 2024

The effect of various drug regimens on natural killer (NK) activity in renal allograft recipients (RAR) is not absolutely clear from the literature. Our study has shown that cyclosporin‐A (Cs) alone did not reduce NK activity, but the addition of maintenance doses (20 mg) of prednisolone (P) produced a significant, though moderate, decline. Severe depression of NK activity was recorded in the patients treated with azathioprine (Az) + P, including subjects treated with Cs alone, who were cleclively converted to (Az + P) 100 days post‐transplant. The low‐dose triple therapy (Cs + Az+P) caused moderately severe reduction of NK activity. All treatment groups showed a similar degree of stimulation at optimal concentrations of interferon (IFN) or intcrlcukin‐2 (IL‐2). There was a direct correlation between basal and stimulated levels. In RAR with very low levels of NK activity the level of stimulation is of doubtful biological significance.
Adult respiratory distress syndrome following orthotopic liver transplantation
Authors: Takaoka Flavio , Brown Marc R. , Paulsen A. William , Ramsay Michael A. E. , Klintmalm Goran B.
Published: September 2024

Perioperative risk factors and the incidence of ARDS were analyzed retrospectively in 198 patients who received 226 liver transplants. ARDS was diagnosed following 10 of these transplant procedures (4.5%); 8/10 patients died. Clinical signs of ARDS did not develop until the 4th postoperative day (range 4–14th postoperative d). Sepsis syndrome occurred in all ARDS patients. Blood and blood product utilization were similar in ARDS and non‐ARDS groups. The incidence of ARDS in single‐graft recipients was 2.7%, compared with 21% in patients receiving 2 or more grafts. Intraoperative events could not be correlated with the development of ARDS. Sepsis syndrome and retransplantation were clearly identified as risk factors for ARDS in this study.
A report on 123 six‐antigen matched cadaver kidney transplants
Authors: Terasaki Paul I. , Takemoto Steve , Mickey M. Ray
Published: September 2024

A national program of shipping six‐antigen matched cadaver kidneys through the UNOS organization has resulted in higher graft survival than many had anticipated. Compared to the control non‐shipped first cadaver donor kidneys which had 1‐year graft survival of 79%, 91 six‐antigen matched cadaver kidneys shipped from 56 centers had 1‐yr graft survival rates of 90% (p<0.01). Among 30 retransplants, the 1‐yr cadaver graft survival was 87%. The 1‐yr cadaver graft survival was even higher (94%) in first grafts in which the recipient's HLA antigens were well defined types. There were 2 deaths in the 123 transplants and 3 patients lost their grafts within 3 days due to thrombosis. Despite transplantation into 17 patients with peak cytotoxic antibody reactive to more than 80% of the panel, no deleterious effect of sensitization was noted. Also, no adverse effect of long cold ischemia time (up to 51 hours) was seen in this series. Acute tubular necrosis had no effect on survivial of first grafts but did have a small, non‐statistically significant effect on second grafts. A 100% survival rate at 6 months was noted among 67 patients whose serum creatinine levels were less than 3.0 mg/dl at time of discharge. Thirteen patients with creatinine values of more than 3 had an 80% survival. The average creatinine values at 3, 6 and 12 months were 1.7 at all intervals. We conclude that six‐antigen matched cadaver transplants can overcome factors such as prior immunization, effect of shipping with cold ischemia under 40 h and the center effect.
Cyclosporine and hypertension
Authors: Curtis John J.
Published: September 2024

Transplant physicians frequently encounter hypertension as a clinical problem since the widespread use of cyclosporine was established in 1983. While hypertension had been a problem before cyclosporine, this immunosuppressive agent is capable of causing a different form of post‐transplant hypertension. Cyclosporine‐induced hypertension doesn't appear to be mediated by the renin‐angiotensin system and may be associated with vascular volume expansion. The current study observes 50 kidney transplant patients documented to have hypertension while on cyclosporine therapy. Follow‐up of these patients suggests that the hypertensive state does not resolve with time as long as cyclosporine blood levels are maintained.
Renal retransplantation in patients who lost their allografts during management of previous post‐transplant lymphoproliferative disease
Authors: Hickey David P. , Nalesnik Michael A. , Vivas Carlos A. , Lopatin William B. , Jordan Mark L. , Starzl Thomas E. , Hakala Thomas R.
Published: September 2024

There are no reports in the literature pertaining to the management of patients who have developed post‐transplant lymphoproliferative disease (PTLD) and lost their allograft as a result of the management of this condition. From April 1, 1981 to April 1, 1988, 1226 cadaveric renal transplants were performed at the University of Pittsburgh. All received cyclosporine (CyA). During this period, 14 (1.1%) developed PTLD. Treatment of PTLD includes a combination of immunosuppression reduction, or discontinuation, with or without chemotherapy, as indicated. As a result of this management protocol, 6 of the 14 have retained their allografts, 4 are on dialysis, 3 of these were retransplanted, (1 of whom has returned to dialysis), and 2 have died. All retransplanted patients were treated with cyclosporine. Two of the 3 retransplanted allografts are still functioning with serum creatinines of 1.5 mg/dl and 1.6 mg/dl at 26 and 18 months post‐retransplantation. In conclusion, we believe that PTLD patients can be retransplanted effectively and safely with CyA.
Ten‐ to 20‐year follow‐up of 123 consecutive HLA‐identical living‐related kidney transplants from the pre‐cyclosporine era
Authors: Fabrega Alfredo , Matas Arthur J. , Payne William D. , Fryd David S. , Dunn David L. , Sutherland David E. R. , Najarian John S.
Published: September 2024

We studied the long‐term morbidity and mortality of 123 consecutive HLA‐ID living‐related kidney transplants performed at a single institution more than 10 years ago. Type I diabetes was the cause of renal failure in 39% of patients; mean age at transplant was 32 ± 12 yr (range 2–64). Immunosuppression consisted of prednisone and Imuran; most patients received ALG perioperatively. For nondiabetics, 10‐, 15‐, and 20‐yr actuarial patient survival was 85%, 75%, and 68%; for diabetics. 10‐ and 15‐yr survival was 65% and 34% (p = 0.0015). Cardiovascular complications were the main cause of death in diabetics, affecting mostly males; sepsis, malignancy, and graft loss were the main cause of death in nondiabetics. Graft survival paralleled patient survival; 76% of grafts lost were due to patient death. Graft survival at 10 and 15 yr was 81% and 73% for nondiabetics; for diabetics, it was 63% and 24%, respectively (p = 0.0031). When death as a cause of graft loss was excluded, there was no difference between diabetics and nondiabetics. Mean serum creatinine at 10 yr was 1.4 ± 0.5. Thirty‐two patients (26%) had one or more acute rejection episodes, most of them occurring within the 1st yr posttransplant. Only 7 grafts have been lost either to acute (4) or chronic (3) rejection. Twenty‐four percent of the patients had no complications. Cardiovascular complications (28%) were the major cause of morbidity and mortality, affecting mostly diabetic males. Sepsis was also a significant problem (19.5%), CMV being the most common pathogen. Malignancy occurred in 12.2% of cases, affecting most frequently the skin. Liver dysfunction, mainly of viral etiology, was the cause of 2 deaths and contributed to several others. Nontraumatic osteonecrosis occurred in 4.9% of the patients; it tended to present in young patients soon after their transplant. We conclude that the long‐term results of HLA‐ID transplantation are excellent when compared to other options in patients with ESRD. Mortality due to the underlying disease (diabetes) and morbidity due to the immunosuppression remain as major obstacles to the long‐term survival and successful rehabilitation of these patients.
Renal transplantation in patients with ileal conduits
Authors: Moon Marc R. , Roza Allan M. , Johnson Christopher P. , Jacobs Stephen C. , Adams Mark B.
Published: September 2024

Patients with renal failure and lower urinary tract abnormalities of persistent incontinence, neurogenic bladder or previous cystectomy require urinary conduit construction prior to renal transplantation. These patients were traditionally considered poor risks for transplantation. From Nov. 1, 1967 to Dec. 31, 1988, 947 patients underwent 1185 renal transplants at our institution. Since 1972, 15 patients or 1.6% (mean age 26.3 ± 14.3 yr, range 8–51) underwent renal transplantation into an ileal conduit. A total of 19 transplants were performed, (12 cadaveric [CRT], 7 living‐related donor [LRT]). One patient died postoperatively with overwhelming bacterial sepsis and a non‐functioning graft (ATN), 3 grafts were lost in 2 patients in the peri‐operative period from rejection, 3 patients with functioning grafts died at 8, 9 and 10 yr post‐transplant of causes unrelated to the transplant and 5 kidneys were lost in 3 patients from chronic rejection 3 months to 8 yr post‐transplant. Seven patients are currently alive with functioning grafts with follow‐up from 1 to 15 yr. Sixteen urologic complications occurred in 10 recipients, including ureteral stenosis (5), calculi (3), recurrent urosepsis (2), parastomal hernia (1), metabolic acidosis (2) and ileal conduit stenosis (3). The incidence of ureteral stenosis (33%) is higher than that seen in non‐transplant recipients undergoing ureteroileal anastomosis (5–22%) and may be due to ischemia and rejection. Calculi, urosepsis, and metabolic acidosis are related to changes in length or peristalsis of the conduit with stasis leading to increased Cl‐HCO3 exchange and infection. Despite the high rate of urologic complications, satisfactory 5‐yr patient (86%) and graft survival (100% LRD, 42% CRT) were achieved. No patients or grafts were lost as a result of these complications. Recipients who present with renal dysfunction require complete evaluation of their urinary tract, including cultures, loopography and looposcopy, to differentiate rejection from surgically correctable urologic abnormalities.
Post‐renal transplant erythrocytosis: Existence of two distinct types
Authors: Panjwani Dilip D. , Sabawi Naeem M. , White Arthur G. , Kumar M. S. Anil , Aret Mahmoud S. , Philips E M. , Abouna George M.
Published: September 2024

We have reviewed 383 consecutive renal allograft recipients to determine the epidemiology and characteristics of post‐transplant erythrocytosis. Patients in whom the erythrocytosis was associated with a recognizable cause of intravascular volume contraction (e.g. diurectic therapy. uncontrolled diabetes, etc.) were excluded. Erythrocytosis occurred in 25 patients (6.5%). These patients did not differ significantly from the overall patient population in age and sex distribution, original renal disease, donor source or prophylactic immunosuppression. Red blood cell (RBC) mass was determined in 15 patients (11 with post‐transplant erythrocytosis (PTE) and 4 with “high‐normal hemoglobin values”) using51 Cr labelled RBCs. Based upon the RBC mass studies and the clinical characteristics, the erythrocytotic patients could be divided into 2 groups; one with transient and the other with persistent erythrocytosis; the former group was larger (18 patients) and was characterized by a low RBC mass, asymptomatic erythrocytosis, and response to increased salt and water intake; the latter group was smaller (7 patients), and was associated with a higher RBC mass, significant morbidity and the need for therapeutic venesection.
Out of the blue: Psychological profile of an unsolicited organ donor
Authors: Olbrisch Mary Ellen , Levenson James L
Published: September 2024

Transplant centers are occasionally contacted by persons wishing to donate vital organs while still living. Little is known about the motives and psychology of such unsolicited donors. The authors were contacted by one such individual who desired to donate “a lung or a kidney” for avowedly altruistic reasons. Interview and psychological testing revealed a person of superior intelligence without gross psycopathology who had, nonetheless, made a somewhat marginal life adjustment. This individual was involved in a number of other altruistic activities. His desire to be an organ donor was seen as an attempt to create a sense of meaning and accomplishment in a life characterized by underachievement and failure to realize his potential. Although unrelated living donors are not currently considered acceptable in the United States, a number of authors have argued for their use in transplantation, stating that refusal of such donors is both paternalistic and negligent of recipient needs. The advantages and disadvantages of permitting such a patient to be an organ donor are discussed.
UNOS: 1989
Authors: McDonald John C. , Vaughn William K.
Published: September 2024

This paper provides the current data which has been accrued by the UNOS National Scientific Registry as a result of the mandatory sharing of 6‐antigen matched kidneys. The 6‐month graft survival does not show, as yet, any benefit for first grafts (N = 72), but does show substantial benefit for repeat grafts (N = 25). No penalty from sharing could be demonstrated since graft survival for local and shared organs was the same. The rationale for two new UNOS policies are discussed: (1) mandatory sharing of phenotypically identical kidneys, (2) the “payback system” for shared kindeys. Finally, some personal comments of the author regarding the importance of the National Organ Procurement and Transplant Nework are recorded.
The fetal pancreas: a valuable source of tissue for islet transplantation?
Authors: Mandel T. E
Published: September 2024

Fetal pancreas has been widely and successfully used in experimental diabetes in animals as a source of islets for transplantation, but there has been little evidence of its successful use in patients. A variety of sources of immature islets may be available, including tissue from induced abortions, spontaneous abortions, very premature infants who fail to survive, and infants dying of congenital malformations. Xenogeneic fetal donors may also be worthy of further study. The features of fetal islets that may make them a potentially valuable source of tissue for endocrine replacement include their huge capacity for growth, the ability to isolate the islets from non‐islet elements with retention of their capacity for further growth and differentiation, and the possibility of modifying their cellular composition so that their inherent immunogenicity is diminished. Contrariwise, the functionally undifferentiated state of the fetal islets from large animals makes reversal of diabetes in transplanted recipients slow. This, combined with the potentially defective microvascular bed in chronically diabetic recipients, may make isolated islet transplantation, particularly with fetal islets, more suitable for patients with recent‐onset disease, and adult islet and vascularized pancreas grafts more suitable for chronically diabetic recipients.
Effect of cyclosporine on fractional excretion of sodium in renal transplant patients
Authors: Shah Bharat V. , Hong Changgi D. , First M. Roy
Published: September 2024

Cyclosporine (CSA) nephrotoxicity remains a major concern for clinicians. Experimental animal and human studies indicate that CSA causes an increase in renal vascular resistance, a decrease in renal blood flow and a reduction in glomerular filtration rate (GFR). A retrospective analysis of fractional excretion of sodium (FENa) was done in 126 renal allograft recipients treated with CSA to determine whether or not the pattern of FENa in CSA‐treated patients differed from that observed in patients treated with conventional immunosuppression, and to study the behavior of FENa in relation to episodes of acute reversible CSA nephrotoxicity (17 cases). It was shown that CSA induced a significant transient early decline in FENa compared with conventional immunosuppression, and that 76% of cases of acute reversible CSA nephrotoxicity were associated with a drop in FENa, which occurred an average of 2.5 days before the rise in serum creatinine. Close monitoring of FENa may provide a clinically useful early warning for incipient CSA nephrotoxicity in renal allograft recipients.
Long‐term follow‐up of renal transplantation for Wegener's disease*
Authors: Tzardis Periclis J. , Gruessner Rainer W. G. , Matas Arthur J. , Payne William D. , Dunn David L. , Sutherland David E. R. , Najarian John S.
Published: September 2024

Eight patients with end‐stage renal failure due to Wegener's granulomatosis underwent renal transplantation at the University of Minnesota. Seven patients were alive with a functioning graft 40 to 128 months posttransplant (mean follow‐up: 91 months). One patient died 126 months posttransplant with a well‐functioning graft. Posttransplant immunosuppression controlled primary disease in all but 1 patient, who presented with perisinusitis. Recurrent disease was not noted in any of the transplanted organs. We conclude that transplantation is an excellent treatment for renal failure secondary to Wegener's disease.
Ketone body ratio as an indicator of early graft survival in clinical liver transplantation
Authors: Ozaki Nobuhiro , Ringe Burckhardt , Bunzendahl Hartwig , Taki Yoshiro , Gubernatis Gundolf , Oellerich Michael , Kuse Ernst‐Ruediger , Kiuchi Tetsuya , Yamauchi Kiyoaki , Takada Yasutsugu , Yamaguchi Tetsuya , Ozawa Kazue , Pichlmayr Rudolf
Published: September 2024

Arterial ketone body ratio (KBR), which reflects liver mitochondrial redox state, was serially measured after 56 clinical liver transplantations (LTX) on 50 patients. Out of 56 grafts, 46 survived at the end of the 1st month after LTX (group I). The remaining 10 grafts failed or required re‐LTX within 1 month (group II). KBR was significantly higher in group I than in group II at 6 hours (0.88 ± 0.05 vs. 0.62 ± 0.07, mean ± SEM, p < 0.05), on the 1st (1.17 ± 0.05 vs. 0.64 ± 0.08, p < 0.01), on the 2nd (1.67 ± 0.10 vs. 0.74 + 0.10, p < 0.01). and on the 3rd postoperative day (POD) (1.68 ± 0.11 vs. 0.93 ± 0.15, p <0.01). In all cases in group I. KBR increased to over 1.0 within the 2nd POD, whereas it remained below 1.0 within the 2nd POD in 9 of 10 cases in group II. In group I, total ketone body concentration was significantly lower when KBR was maintained above 1.0 than when it was below 1.0. It is suggested that restoration of KBR above 1.0 within 2 d after LTX is a favorable prerequisite for early graft survival, and that enhanced fatty acid oxidation and ketogenesis persist until the mitochondrial function is restored to normal levels.
Technique of pancreas revascularization after combined liver and pancreas harvesting in the same cadaveric donor
Authors: Sanseverino Roberto , Martin Xavier , Caldara Rossana , Faure Jean Louis , Lefrancois Nicole , Dubernard Jean Michel
Published: September 2024

Combined liver and pancreas harvesting in the same donor is nowadays a routine procedure in our institution. In terms of sharing of the vascular pedicule the priority is given in the majority of cases to the liver graft. Thus vascular reconstruction of the pancreatic graft is often required before transplantation. From February 1987 to June 1990 we transplanted 62 pancreases coming from a donor where also a liver graft had been harvested; 46 were segmental grafts prepared by duct injection with neoprene, 14 were pancreatico‐duodenal grafts with bladder diversion of the exocrine secretion, and 2 were whole pancreas scheduled for bladder diversion and secondarily reconverted to duct injection (1 whole and 1 segmental graft) for poor duodenal blood supply. Among the 47 segmental grafts (46 + 1 reconverted from whole to segmental), in only 10 cases was the celiac axis with an aortic patch possible; conversely in 37 cases the splenic artery had been divided at its origin during the harvesting; bench surgery for vascular reconstruction was realized in 33 cases. Among the 14 pancreatico‐duodenal grafts with bladder diversion and the whole pancreas with duct obstruction, in 5 cases the celiac axis and the superior mesenteric artery were harvested on the same aortic patch; in 10 cases the splenic artery was divided at its origin during the harvesting, requiring bench surgery for reconstruction.
Smooth muscle tumor arising de novo in a liver allograft: A case report
Authors: Doyle Howard , Tzakis Andreas G. , Yunis Eduardo , Starzl Thomas E.
Published: September 2024

A case of a primary smooth muscle tumor arising in a liver allograft is presented. This complication has not been previously reported in the literature. The tumor was diagnosed while still asymptomatic, and the patient, a young child, has done well following a left lateral segmentectomy.
Brain death determination in children and the anencephalic donor
Authors: Sommerauer John F.
Published: September 2024

As a result of increased success with pediatric transplantation, there has been an increased demand for donor organs from small children, infants and newborns. There are several differences in the determination of brain death between the adult and the infant and newborn. The controversial medical issues and difficulties in brain death declaration in children, and the medical and ethical controversies of the anencephalic donor are reviewed in this article.
Overview of pediatric renal transplantation
Authors: Nevins Thomas E.
Published: September 2024

Over 35 years, renal transplantation in infants and children has evolved dramatically. Once a desperate effort, transplantation is now the therapy of choice for virtually all children with end‐stage renal disease (ESRD). The number of children less than 10 years old living with ESRD has more than doubled in the last 7 yr, but during that same interval the children with functioning transplants has quadrupled. Since 1963, 386 children and 21 infants have received 495 renal transplants at the University of Minnesota. When examined, several variables strongly influence the outcomes. Primary renal transplants, grafts from living‐related donors, and transplants performed since 1979 have all been associated with markedly improved outcomes. But age of the recipient has no impact on cither patient or graft survival. Beneficially, transplanted infants experience significantly accelerated head growth, returning them to the normal range. Their developmental test scores also significantly improve, again bringing them into the normal range. Finally, statural growth regularly improves following successful transplantation. These results support a strategy of early, aggressive support; prompt renal transplantation; and the use of dialysis primarily as a critical “bridge” to elective transplant surgery.
Liver transplantation in the pediatric population: Indications and monitoring
Authors: A‐Kader Hassan H. , Ryckman Frederick C. , Balistreri William F.
Published: September 2024

Advances in immunosuppressive therapy and surgical technique have brought liver transplantation to an effective therapeutic option for children with end‐stage liver disease. The indications and contraindications for transplantation, recipient selection, ethical and financial considerations, and quality of life after transplantation are outlined in this review.
Induction of immunosuppression in pediatric orthotopic liver transplantation
Authors: McDiarmid Sue V. , Millis Michael J. , Terasaki Paul , Vargas Jorge H. , Ament Marvin E. , Busuttil Ronald W.
Published: September 2024

This report reviews our experience with prophylactic OKT3 in pediatric liver transplantation, induction protocols in use elsewhere, and future new alternatives. In a randomized prospective study we have compared induction with OKT3, steroids and azathioprine to conventional therapy with cyclosporine, steroids and azathioprine. Twelve children were in the OKT3 prophylaxis group and 8 in the cyclosporine group. In the first 14 days patients in the OKT3 group had significantly less rejection (25%) compared to the cyclosporine group (75%). A high incidence of rebound rejection (33%) was seen in the OKT3 group so that overall there was no difference in rejection incidence between the two groups (83% in OKT3 group, 87% in cyclosporine group). The OKT3 group did not have an increased risk of infection. Long‐term follow‐up showed no difference in graft or patient survival, renal function, or the late occurrence of rejection or infection. On recommended doses of OKT3, 45% of children were unable to maintain CD3+ cells less than 5%. Sixty‐seven percent of children developed anti‐OKT3 antibodies after prophylaxis, usually of low titer. OKT3 was re‐used after prophylaxis for treatment of 7 rejection episodes. Two‐thirds of these patients developed CD3+ cells greater than 60%. Two episodes completely resolved and 3 partially responded. Compared to adults in the same study, pediatric recipients had more rejection requiring OKT3 rescue, a higher incidence of increased CD3+ cells during OKT3 use, and developed anti‐OKT3 antibodies more often. Pediatric patients require careful monitoring during OKT3 use and may require higher doses than currently used. As OKT3 prophylaxis offered no long‐term benefits, we reserve its use for treatment of steroid‐resistant rejection. OKT3 prophylaxis is indicated in carefully selected patients in whom intravenous cyclosporine is contraindicated.
Growth in children post‐transplantation and methods to optimize post‐transplant growth
Authors: Tejani Amir , Ingulli Elizabeth
Published: September 2024

With improved renal graft survival, rehabilitation and growth post‐transplantation are the major challenges to pediatric nephrologists. Recent data from the pediatric renal transplant registry shows that children undergoing renal transplantation have a significant statural height deficit which does not improve in the 1st year after receiving a transplant. Two strategies can be developed to optimize growth post‐transplantation. Using the steroid‐sparing effect of cyclosporine, withdrawal of corticosteroids may be possible in 30‐40% of children, enabling them to grow. Recombinant growth hormone adminstered every other day can be utilized in children who continue to need steroid therapy to improve their growth velocity. This review discusses the mode of action of steroids in inhibiting growth, the methodology of steroid withdrawal post‐transplantation, the measurement of stimulated growth hormone levels, and the use of recombinant growth hormone.
Hepatitis C infection in allogeneic bone marrow transplant recipients
Authors: Ljungman P. , Duraj V. , Magnius L. , Aschan J. , Lönnqvist B. , Ringdén O. , Gahrton G.
Published: September 2024

Antibodies to hepatitis C virus (HCV) were determined 2 years after allogeneic bone marrow transplantation (BMT) in 83 long‐term survivors. Seven of 8 patients who seroconverted had signs of acute hepatitis which was more frequent than in patients who did not seroconvert (p < 0.01). Patients who seroconverted had received more platelet transfusions than those who did not (p = 0.013). The importance of HCV infection for long‐term liver function was determined in 69 of the 83 patients who were disease‐free during follow‐up and from whom sera were available. One patient was seropositive before BMT. Eight patients seroconverted to HCV after BMT. The median follow‐up time from BMT was 6.4 yr (range 2.9–7.3 yr) among the patients who seroconverted to HCV and 5.9 yr (range 2.3–9.6 yr) among the patient who did not seroconvert. Seven of 8 patients who seroconverted to HCV had persistent liver function abnormalities at the time of last follow‐up compared to 5 of 61 patients without evidence of HCV infection (p = 0.0001). Two of these patients had biopsy‐verified chronic active hepatitis. We conclude that HCV infection was a major cause of persistent liver abnormalities after allogeneic BMT.
Ganciclovir therapy for viral disease in liver transplant recipients
Authors: Stratta Robert J. , Shaefer Mark S. , Markin Rodney S. , Cushing Kathleen A. , Donovan Jeremiah P. , Wood R. Patrick , Langnas Alan N. , Reed Elizabeth C. , Woods Gail L. , Zetterman Rowen K. , Sorrell Michael F. , Pillen Todd J. , Shaw Byers W.
Published: September 2024

With current immunosuppressive regimens, viral disease has become an important source of morbidity after orthotopic liver transplantation. Over a 5‐year period, we retrospectively analyzed 422 liver transplants in 370 recipients (242 adults, 128 children) under cyclosporine and prednisone immunosuppression. A total of 108 patients (29.2%) received intravenous ganciclovir for viral disease, including 103 for cytomegalovirus (CMV) disease and 5 for Epstein‐Barr virus (EBV) disease. A total of 132 episodes of CMV disease (103 initial, 29 relapse) were treated with ganciclovir, including 22 patients with primary CMV disease. Opportunistic viral hepatitis was the most common clinical presentation of viral disease while recurrent disease often involved extra‐hepatic sites (especially pulmonary). The majority of cases of viral disease (both initial and relapse) were confined to single organ involvement (81.0%), at which time ganciclovir therapy was begun at a dose of 5 mg/kg twice daily for 2 weeks (with dosage adjustments for renal dysfunction). The initial diagnosis of CMV disease was made at a mean time after transplantation of 38 days, with a mean duration of ganciclovir therapy of 16 d. A prompt and lasting response, characterized by clinical improvement and negative viral cultures, was documented in 74 cases (71.8%). Fourteen additional patients were successfully retreated with ganciclovir for CMV relapse, so that CMV disease was ultimately controlled in 85.4% of cases. EBV disease was diagnosed at a mean time of 124 d after transplantation, with a mean duration of ganciclovir therapy of 39 d. Four cases (80%) were successfully treated. Overall patient survival after ganciclovir therapy is 79.0% with a mean follow‐up of 24 months. Adverse drug effects included significant leukopenia and thrombocytopenia in 7 patients (6.5%), with 2 requiring drug withdrawal. Conclusion: ganciclovir is a safe and effective agent for the treatment of viral disease in liver transplantat recipients. The availability of ganciclovir has resulted in successful treatment of viral disease without dramatic reductions in immunosuppression, thus permitting successful rescue of the patient and allograft with an acceptably low incidence of toxicity and viral relapse.
Multi‐organ procurement utilizing cardiopulmonary bypass and profound hypothermic circulatory arrest
Authors: Sekela Michael E. , Young James B. , Short H. David , Whisennand Hartwell H. , Noon George P.
Published: September 2024

Despite advances in preservation solutions, hypothermia remains a critical component of organ preservation for transplantation. Many surgeons involved in multi‐organ procurement procedures have expressed concern about the possible detrimental effects of cardiopulmonary bypass and profound hypothermic circulatory arrest on non‐thoracic transplant organ function. In order to assess the validity of these concerns, a review of 20 multi‐organ harvest procedures performed utilizing cardiopulmonary bypass and profound hypothermic circulatory arrest was undertaken. In all instances this technique was combined with organ flushing utilizing cold preservation solution. Adequate data was available to assess post‐transplant organ function of all organs recovered in 16 procedures. Indication for the use of this technique was procurement of a heart‐lung bloc in 16 instances and donor instability (hypotension) refractory to volume loading and inotropic agents in 4 instances. Organs obtained, including all organs from unstable donors which would otherwise have been lost, functioned, acceptably. Additionally, blood drained into the pump was used for recipient transfusion in 8 instances. This report documents that cardiopulmonary bypass and profound hypothermic circulatory arrest may be easily combined with traditional procurement flushing techniques and it provides excellent organ preservation for subsequent transplantation. This approach can optimize organ recovery from hemodynamically unstable donors, increasing the number available for transplantation.
The ethics of unconventional living organ donation
Authors: Spital Aaron
Published: September 2024

The ongoing organ shortage is perhaps the major barrier facing transplantation today. Liberalizing selection criteria for living donors to include such unconventional sources as unrelated individuals and relatives at added risk could greatly increase the pool of available organs. Yet, transplant centers, appropriately concerned about the donor's motivation and the risk involved, have generally excluded these people from donation. Does this policy make sense? Assuming the donor to be competent, I will show that if traditional genetically related donors are believed to be ethically acceptable, it is inconsistent to exclude emotionally related donors. I will also argue that even the use of altruistic strangers and donors at added risk is ethically justified. These conclusions are based on the principle of respect for persons and the realization that the risk‐benefit ratio of any proposed living donor transplant is determined ultimately by value judgments. These judgments should generally be made by the one most affected by the outcome – the prospective donor.
Human herpes virus 6 infections in hospitalized renal transplant recipients
Authors: Gudnason Thorolfur , Dunn David L. , Brown Nathaniel A. , Balfour Henry H.
Published: September 2024

Herpesviruses are a major cause of morbidity and mortality in renal transplant recipients. Recently, a new member of the herpesvirus family, human herpesvirus 6 (HHV‐6), has been identified. We investigated the incidence and clinical manifestations of HHV‐6 infections in 25 hospitalized renal transplant recipients. HHV‐6 infections were documented serologically by comparing pre‐ and post‐transplantation antibody titers using an indirect immunofluorescence assay. Infections caused by cytomegalovirus, Epstein‐Barr virus, herpes simplex virus and varicella‐zoster virus were also studied. During the mean follow‐up period of 3½ months post‐transplant (range, 2 to 6 months), 9 recipients (36%) had serologic evidence of HHV‐6 infection. Two patients seroconverted, suggesting primary HHV‐6 infection. These patients had febrile illnesses, skin rash and malaise. Seven recipients had a non‐primary HHV‐6 infection (reactivation/reinfection) documented by a > 4‐fold rise in antibody titer that was associated with clinical illness in 5 of 7 patients. Two recipients developed primary cytomegalovirus infection and both had evidence of non‐primary HHV‐6 infection. Seven of 9 recipients (77%) who developed HHV‐6 infection had received acyclovir prophylaxis. We conclude that primary and non‐primary HHV‐6 infections occur in renal transplant recipients and can be associated with fever, skin rash and malaise. HHV‐6 infections can occur despite high‐dose oral acyclovir prophylaxis.
Value of 111indium leukocyte scanning in febrile organ transplant patients
Authors: Alsina Angel E. , Krisiunas Laine , Rosenberg Ronald J. , Sziklas John J. , Schweizer Robert T.
Published: September 2024

Immunosupprcssed febrile organ transplant patients present a diagnostic and therapeutic dilemma since symptomatology is often altered by immunosuppression, which also masks the location of infection. Fifty 111indium leukocyte (111In WBC) scans were performed to determine their usefulness in the organ transplant patient. The results were compared with computerized tomography (CT) and gallium 67‐citrate (Ga) scanning. Eleven patients received both 111In WBC and Ga scans; 22 received both 111In WBC and CT scans. Ten 111In WBC scans had subtraction of 99m Tc sulfur or albumin colloid for liver evaluation and four 111In WBC scans had subtraction of 99m Tc DMSA for kidney evaluation. The overall sensitivity and specificity for 111In WBC scans was 90% and 90%, respectively. Lung uptake was sensitive (89%) and specific (97%) for pulmonary infections, including bacterial, fungal and cytomegalovirus pneumonias. Renal graft uptake occurred in 15 cases (41%), all except 2 being due to rejection, pyelonephritis, urinary tract infections, or cytomegalovirus infections. Pyelonephritis and renal abscesses were diagnosed in 3 cases with 99m Tc DMSA subtraction. Perihepatic abscesses (2), and infected liver cysts (4) were diagnosed with 99m Tc sulfur or albumin colloid subtraction. There were five false‐negative CT scans and three false‐negative Ga scans. Therefore, when compared with 111In: sensitivity = 88% vs 64% (CT), specificity = 80% vs 86% (CT); and sensitivity = 111In 90% vs 67% (Ga), specificity = 100% for both 111In WBC and Ga scans. 111In WBC scans were accurate in detecting infections in organ transplant recipients, particularly liver and renal infections and, while occasionally more useful than Ga scanning, 111In scans serve a complementary role along with other diagnostic modalities.
Immunological behavior of preserved human tracheal allografts: Immunological monitoring of a human tracheal recipient
Authors: Bujia J. , Pitzke P. , Krombach F. , Hammer C. , Wilmas E. , Herberhold C. , Kastenbauer E.
Published: September 2024

The use of preserved tracheal allografting is a discussed method for the reconstruction of tracheal defects. To characterize the systemic and local immunological events following the transplantation of preserved human tracheal allografts, various immunological parameters were measured before and after transplantation in 1 human tracheal transplant recipient. Peripheral mononuclear cells were obtained and prepared for cytological monitoring. Biopsies of the anastomosis region were taken to characterize the histologic changes, as well as the extent and phenotype of cellular infiltrates, as determined by immunoperoxidase labelling. The results were compared with those of another patient who underwent a tracheal resection followed by an end‐to‐end anastomosis. While the biopsies showed a slight inflammatory reaction, signs of systemic immunoactivation were not found. Moreover, the absence of signs of clinical rejection suggests that merthiolate‐preserved human tracheal allografts represent a suitable replacement material for reconstruction of large tracheal defects.
Levels of tumor necrosis factor (TNF) in sera of renal allograft recipients
Authors: Segoloni Giuseppe , Vercellone Antonio , Manes Massimo , Tetta Ciro , Camussi Giovanni
Published: September 2024

A biological assay was used for monitoring serum levels of endogenous tumor necrosis factor in 42 renal transplant recipients. The clinical events occurring in the post‐transplant period were categorized as follows: group I, acute rejection (12); group II, acute tubular necrosis (ATN, 16); group III, cyclosporine A (CyA) nephrotoxicity (13); group IV, uncomplicated transplants (22); group V, viral (6)/bacterial (4) infections. Twenty‐one health subjects served as controls (group VI). Serum TNF levels were measured every other day after transplantation for 44.2 ± 4.18 d (mean ± SEM). The means of serum TNF levels of each week for 3 wk after the beginning of each clinical event were calculated and statistical evaluation was performed between groups. In the 1st, 2nd but not in the 3rd wk of observation, acute rejection was associated with significantly increased serum TNF levels in respect to ATN, CyA nephrotoxicity, uncomplicated transplants and healthy subjects. In the 1st but not in the 2nd wk, acute rejection did not differ from viral/bacterial infections. ATN was associated with significantly increased serum TNF levels vs. uncomplicated transplants at the end of the 1st but not of the 2nd or 3rd wk. CyA nephrotoxicity showed no significant increase in serum TNF levels vs. uncomplicated transplants in all 3 wk of observation. Early monitoring of the concentrations of TNF in serum therefore may provide an additional parameter for the differential diagnosis of acute rejection in respect to CyA nephrotoxicity, provided that intercurrent infections can be excluded.
Renal transplantation associated with HIV infection: A Saudi Arabian experience and review of the literature
Authors: Barri Yoursi M. , Ellis Michael E. , Al‐Furayh Osman , Qunibi Wajeh , Taher Saadi , Al‐Sabban Essam , Bernvil Stener S.
Published: September 2024

Of 504 kidney transplant recipients attending our center, 6 developed serological evidence of human immunodeficiency virus (HIV) infection (1.2%). All 6 patients had been transplanted abroad. Of those, 3 died (mean time from transplantation to death 37 months), 2 having developed full‐blown AIDS and the 3rd from opportunistic infections related to immunosuppressive drugs. Of the remaining 3, one developed Kaposi's sarcoma (KS) which responded to reduction in immunosuppression, but this patient was subsequently lost to follow‐up. The other 2 are asymptomatic with stable renal function. Sixty cases with HIV infection reported in the World Literature were reviewed. The incidence of Western blot positivity among renal transplant recipients ranged from 0.12% to 6.12%. Accelerated course of HIV disease was observed in this population, particularly in those who were HIV‐seropositive prior to transplantation. This study reviews various aspects of HIV infection in renal transplant recipients, including route of infection, natural history of the disease, effect of immunosuppression, allograft function, and whether opportunistic infections are related to immunosuppressive drugs or HIV infection.
Pathology of transplanted human duodenal tissue: A histologic study, with comparison to pancreatic pathology in resected pancreaticoduodenal transplants
Authors: Nakhleh Raouf E. , Gruessner Rainer W. G. , Tzardis Periclis J. , Dunn David L. , Sutherland David E. R.
Published: September 2024

In an effort to define the pathology of transplanted human duodenal tissue, 15 resected human duodenal tissues transplanted as pancreaticoduodenal allografts were reviewed and compared with 12 native jejunal tissues (control tissues) used with segmental pancreatic transplants. Correlation of findings in duodenal and pancreatic tissues was also performed. Features which were present in duodenal allografts but not in control tissues included crypt loss (p = 0.0065), villous atrophy (p = 0.015) and vascular changes (endothelialitis, vasculitis and subintimal thickening). Other findings typical of rejecting duodenal allografts included epithelial cell necrosis, epithelial reactive atypia (p = 0.012), and intraepithelial inflammation. Nine patients had histologic evidence of pancreas rejection. The duodenal allografts from these 9 patients typically showed epithelial necrosis, crypt loss and villous atrophy in the mucosa. These features may be markers of acute pancreatic rejection. CMV infection in the duodenal allografts corresponded to pancreatic CMV infection in 1 of 2 allografts.
Usefulness of non‐invasive indices in the monitoring of heart‐transplanted pediatric patients
Authors: Miro Joaquim , Chartrand Claude , Kangah Michel , van Doesburg Nicolaas H. , Fouron Jean‐Claude
Published: September 2024

Seven patients underwent cardiac transplantation at Ste‐Justine Hospital between June 1984 and October 1988 (age 3‐16 years). Indices derived from M‐mode echocardiography – left ventricular mass (LVM), isovolumetric relaxation time (IRT), shortening fraction (SF), velocity of circumferential fiber shortening (VCF), ejection fraction (EF), LV pre‐ejection period/ejection time (PEP/ET), isometric contraction time (ICT) – and electrocardiography – summation of potentials (Sum Pot) – were used as non‐invasive markers of rejection (367 studies), while rejection status was monitored by serial endomyocardial biopsy (55 biopsies). Spontaneous variation of such indices, as defined by the 90% distribution interval of their variation when biopsy was unchanged, was found to be important: –20% to +28% for IRT, –30% to +28% for LVM, –30% to 32% for Sum Pot, –32% to 42% for PEP/ET, etc. Using limits of spontaneous variation such as thresholds, none of the studied indices could consistently predict the 2 biopsy‐documented episodes of rejection or the 7 episodes of improvement. Among all the studied indices. IRT was the most promising, correctly predicting 1 of the episodes of rejection and almost predicting the 2nd. Remeasurement of all M‐mode tracings by an unique observer, following strict rules to maximize reproducibility, did not decrease the spontaneous variation of these indices, nor did it improve their performance as predictors of changes in the rejection status. These results warrant the continuing search for other non‐invasive methods for accurate monitoring of the rejection status.
Aseptic encephalitis and blindness complicating OKT3 therapy
Authors: Marks W. H. , Perkal M. , Bia M. , Lorber M. I.
Published: September 2024

We report 2 cases of aseptic encephalitis associated with OKT3 therapy occurring within 1 week of each other. One case was further complicated by the acute onset of bilateral optic nerve blindness. While aseptic meningitis and seizures are both described complications of OKT3 therapy, neither aseptic encephalitis nor isolated cranial nerve involvement has been previously reported. In a recent article (Clin Transplantation 1991: 5: 60‐62) reference was made to “cortical” blindness that followed OKT3 treatment for steroid‐resistant rejection, but no details were forthcoming. Review of the Orthoclone® OKT3 Postmarketing Adverse Experience database revealed 2 reports of temporary sixth cranial nerve palsies and 2 cases associated with visual problems. Encephalitis with or without cranial nerve involvement following OKT3 therapy may result in significant morbidity for a small subset of patients. Although not common, these experiences emphasize the importance of continued close follow‐up of all patients who receive OKT3.
A delay in correlation between cyclosporine dosage and trough level measurements
Authors: Takasugi Mitsuo , Koyle Martin A. , Ward Harry J.
Published: September 2024

The adjustment of cyclosporine trough levels within a desired therapeutic range is complex because of the weak correlation between drug dose and immediate measurements. The correlation is significantly improved if a time interval is imposed between the two parameters. The time required to establish a correlation or the delay between dosage and trough measurements varied considerably between patients. This study consisted of applying the linear regression analysis to data from the dose and the corresponding trough level curves followed sequentially by trough measurements from succeeding days. Regardless of the assay used and the wide variability between patients, an initially weak correlation improved significantly after a period of delay. The delay before trough levels corresponded with given dosages indicated an indirect relationship and suggested a linkage between circulating cyclosporine and a bound or storage compartment. A period of instability in trough level measurements is observed upon initiation of cyclosporine immunosupression and after changes in dosages indicating a time interval required to establish a more stable relationship between the circulating and bound compartments.