bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment of recalcitrant cardiac allograft rejection with methotrexate
Authors: Chan Gary L. , Weinstein Samuel S. , Vijayanagar Raghavendra R. , Team Cardiac Transplant
Published: September 2024

Acute rejection continues to be a major cause of mortality and morbidity among cardiac allograft recipients. In this retrospective analysis, we evaluated the efficacy and safety of methorexate in the treatment of recalcitrant rejection in 16 heart transplant patients. Methotrexate was initiated in these patients for rejection refractory to conventional therapy or for multiple, recurrent rejection episodes. Before methotrexate therapy, these patients had experienced 3.2±1.1 (mean±SD) episodes of allograft rejection. Methotrexate was administered at 5.9±5.3 months postransplant, at a starting oral dose of 7.8±2.7 mg/week. The methotrexate dose was increased as tolerated by white blood cell counts to 10‐25 mg/week. These patients had been followed for 26±12 months after initiation of methotrexate. All ongoing rejection episodes were reversed with methotrexate. Rejection resolution was typically delayed and was observed at 19±15 days after methotrexate initiation. Compared to the 6 months before methotrexate thereapy, there was significant reduction in the linearized rejection rate (0.44±0.14 vs 0.06±0.09 episodes/patient/month), and the time spent in rejection (29.8±14.0 vs 5.8±8.7 days) in the 6 months after methotrexate initiation. Nadir white blood cell counts were observed at 4.0±1.8 weeks after methotrexate initiation, but were above 2000/mm3 in all patients. Multiple infections occurred in 2 patients who received repeat courses of methotrexate and the highest cumulative doses of methotrexate. These findings suggest that methotrexate may be effective in the management of recalcitrant cardiac allograft rejection. Methotrexate therapy appears to be well tolerated by most patients. However, multiple treatment courses of methotrexate and high cumulative dose may predispose patients to an increased risk of infections.
Surveying donor families: A comparison of two organ procurement organizations
Authors: Gordon Audrey K. , Herzog Allen , Lichtenfeld Dean
Published: September 2024

The primary purpose of this study was to identify variables that affect cadaveric donor family satisfaction with the donation process and coping with grief. A secondary purpose was to describe the variation of respondents from two different donor populations to establish whether donor families in one geographic region differ from donor families in another. A survey was mailed to 233 families over a 16‐month period. Data analysis of returned surveys was based on frequency distributions, measures of association and factor analysis. Identical items in the Regional Organ Bank of Illinois (ROBI) Survey and the Hartford Transplant Center (HOPO) Survey were compared and tested for significance. Eighty‐nine percent of the donor families understood what “brain death” meant, and 85% felt that the donation request was appropriate when it was made less than 6 hours after a diagnosis of brain death. Family members provided the most helpful information about donation to other family members 65% of the time. The two most important reasons for donation were “to make something positive come out of the death” and “family member's belief in helping others”. These responses also ranked highest in the HOPO survey. The support of family, friends and religion were the most frequent coping mechanisms for grief. In comparing responses from ROBI and HOPO, significant differences were found on two items relating to agency procedure, but no significant differences were found when family responses were compared. Factors were identified which predicted the desire to donate, the likelihood of increased stress and a “sharing” factor that related to the wishes of the family member and further participation with the organ procurement organization. Some relationship was found between “emotional stress at the time of donation”, “family belief in helping others” and religion as a coping mechanism. We conclude that families of cadaveric organ donors retrieved by ROBI are generally satisfied with the donation request process. The survey data are generalizable to geographically disparate communities in the United States and should be considered by organ procurement organizations to maximize the procurement of cadaver donor organs and tissues.
Long‐term follow‐up of hepatitis C virus (HCV) infection in liver transplant patients
Authors: Villa E. , Grottola A. , Buttafoco P. , Merighi A. , Ferretti I. , Trande P. , Zoboli P. , Camellini L. , Callea F. , De Palma M. , Vecchi C. , Troisi R. , Camisasca M. , Rossi S. , Tordato G. , De Hemptinne B. , Podda M. , Manenti F.
Published: September 2024

Chronic hepatitis represents a frequent event after orthotopic liver transplantation (OLT). To ascertain the influence of HCV infection on the clinical and histological outcome of these patients, we have investigated the long‐term outcome of 22 patients with end‐stage chronic liver disease undergoing liver transplant focusing the attention on the role of different HCV genotypes in determining recurrence and severity of post‐OLT liver disease. For all patients blood samples taken before OLT and 3 months, 1, 2 and 3 years after OLT were tested for antiHCV antibodies by two different enzyme‐linked immuno‐assays and by recombinant immuno‐blot II and for the presence and type of HCV RNA by nested PCR (5' untranslated region and core gene primers). Of the 16 pre‐OLT antiHCV‐positive patients, 14 (87.5%) had recurrence of HCV infection while 2 cleared HCV. Pre‐OLT genotype recurred in 11 of these 14 patients (2 genotype I, 8 genotype II ‐ in 1 case associated with genotype III and 1 genotype IV). Of the 6 pre‐OLT antiHCV‐negative patients, only 1 (16.6%) became persistently HCV‐infected, with genotypes I and II. The recurrence of genotype II strictly related with development of severe chronic hepatitis while genotype I and IV were associated with milder forms of liver disease and were more easily cleared.
Clinical importance of pre‐morteum blood lymphocytes in cadaver donor tissue typing
Authors: Vaidya Smita , Orchard Perry , Schroeder Nancy , Haneke Rock , Brooks Karl , Thomas Alice , Corba Angela , Asfour Ayman , Fish Jay C.
Published: September 2024

We have refined our immunomagnetic bead (IM bead) procedures to isolate pure and viable lymphocyte subpopulation from premortcum (PM) blood for cadaver donor HLA typing, preliminary and final crossmatches (XMs). The results of 1220 XMs were compared using T/B lymphocytes isolated either from PM blood or spleen/lymphnode (SPLN) tissue. IM bead technique was used to isolate T/B cells from PM blood and nylon wool column (NWC) techique was used to isolate T/B cells from SPLN. When we compared the outcome of 800 T‐cell crossmatches using T cells from PM blood or SPLN of 5 separate cadaver donors, NWC TXMs tended to be more falsenegative for high PRA (>10%, total 500 XMs) as well as low PRA (<10%, total 300 XMs) did not reach statistical significance. In contrast, NW BXM (420 B XM) were found to be far more false negative than IM bead BXM regardless of the PRA of the patients. In order to ensure that NWC BXMs were indeed false negative, 23 sera with known anti‐DR antibodies were BXMed where antigen‐specific B cells were isolated by both the techniques. Our results showed that IM bead BXM identified the DR specificities greater than 90% of the time, the titers of ab specificities were stronger (1:8). In comparison, NWB cell XMs were weak (titers 1:2), and the false negative rate for some ab was as high as 73%. Using IM bead and NWC techniques we compared our turnaround time (TAT) for cadaver donor typing, preliminary and final XMs. Using PM blood with IM bead, our TAT was less than 5 hours for the entire cadaver donor work‐up. In contrast, TAT from SPLN with NWC technique was as long as 8 hours. We also compared graft survival statistics of 153 patients transplanted on a basis of negative T/BXM using either PM blood lymphocytes (98 patients) or SPLN lymphocytes (55 patients). However, lymphocytes in either case were isolated by IM bead assay. We found no adverse outcome due to usage of PM blood lymphocytes in terms of longor shortterm graft survival or incidence of hyperacute rejection. In fact, cold ischemia time (CIT) was much shorter (median 12 hours) in the PM group versus more than 20 hours in SPLN group. In summary, PM blood is an ideal source of T/B lymphocytes for the solid organ pretransplant workup and final XM.
Measurement of malondialdehyde as a marker of oxygen free radical production during renal allograft transplantation and the effect on early graft function
Authors: Davenport A. , Hopton M. , Bolton C.
Published: September 2024

We prospectively measured malondialdehyde (MDA), a marker of free radical oxygen damage during 44 renal transplant operations. When corrected for intra‐operative changes in plasma volume, there was a significant increase in the ratio of MDA to total cholesterol ( × 10 3), from a median of 0.32 (0.24‐0.44) (interquartile range) to 0.39 (0.31‐0.50) at 30 minutes following reperfusion, p<0.01 and to 0.36 (0.31‐0.51) after 60 minutes, p<0.01; whereas there was no intra‐operative increase in MDA in 10 patients undergoing routine elective surgery, who acted as controls. The change in MDA/cholesterol ratio at both 30 and 60 minutes following reperfusion was greater in those patients with poor early graft function (serum creatinine >250 umol/l at the end of the 1st post‐operative week), mean 0.32 (sem 0.08) at 30 min and 0.32 (0.09) at 60 min, compared to those with good function (serum creatinine <250 umol/l), 0.12 (0.05) and 0.10 (0.04) respectively, p<0.05. This suggests that the products of oxygen free radical damage can be measured during renal transplantation, and that they may have an adverse effect on early graft function.
HMGCoA reductase inhibitors and omega‐3 fatty acids as adjunctive agents in maintenance immunosuppression after solid organ transplantation
Authors: Katznelson S. , Wilkinson A. H.
Published: September 2024

Omega‐3 fatty acids have been shown to play a role in preventing the development of both acute and chronic rejection. New evidence also suggests that HMGCoA reductase inhibitors may have an immunomodulatory effect and may decrease the incidence of rejection in both animal and human transplant models. Omega‐3 fatty acids and HMGCoA reductase inhibitors may be important adjunctive agents in improving shortand long‐term allograft function.
Efficacy of octreotide in controlling refractory diarrhea following bone marrow transplantation
Authors: Morton A. J. P. , Durrant S. T. S.
Published: September 2024

We report the use of octreotide in 10 patients with severe diarrhea, refractory to loperamide, following bone marrow transplantation (BMT). Five patients had regime‐related toxicity (RRT) and 5 were suffering from acute intestinal graft versus host disease (GVHD). Complete responses were observed for all patients with RRT, with optimal response being observed with dose escalation to 250 ug tds. Only partial responses were observed in the patients with intestinal GvHD. Increased doses of systemically administered cyclosporin‐A (CSA) were necessary to maintain therapeutic levels for 2 patients. Octreotide is very effective in controlling RRT diarrhea. It is less effective in the control of GvHD‐related diarrhea. CSA levels require close monitoring, whether the drug is administered systemically or orally.
Hepatocyte transplantation and gene therapy
Authors: Raper S. E.
Published: September 2024

Trials of liver‐directed gene therapy are a clinical reality. Technology is rapidly developing for the isolation of large numbers of human hepatocytes. Recombinant DNA techniques are available to engineer recombinant retroviruses which express genes of clinical relevance. Familial hypercholesterolemia serves as the clinical paradigm for liver‐directed gene therapy, and the clinical protocol is underway. Early results are promising. Techniques for hepatocyte delivery, optimization of gene transfer, and safety considerations are important considerations in designing a human trial. Other diseases which are likely to be among the first treated with this new approach are ornithine transcarbamylase deficiency, hemophilia B, and Crigler‐Najjar syndrome.
New strategies for the control of viral infection in organ transplantation
Authors: Tolkoff‐Rubin N. E. , Rubin H.
Published: September 2024

Control of viral infection in organ transplant recipients requires attention to the following interventions: prevention, whenever possible of viral acquisition; the proper deployment of active and passive immunization, with hyperimmune globulin preparations directed against cytomegalovirus, hepatitis B, varicella, and, perhaps, respiratory syncytial virus, offering significant benefit when used appropriately; and the prescription of antiviral agents at critical points in the post‐transplant course. Two important principles should be kept in mind when approaching this problem: prevention is the goal, as treatment of established infection is fraught with difficulty; and effective preventative strategies must be linked to the intensity of the immunosuppressive program being employed. To achieve these goals, the addition of pre‐emptive therapy (therapy geared to a laboratory marker of impending disease or to escalation in the immunosuppressive program) to standard prophylactic regimens represents a significant advance.
Role of liver transplantation in patients with hepatitis B infection
Authors: Holt C. D. , Millis J. M. , Busuttil R. W.
Published: September 2024

Liver transplantation is currently considered definitive therapy for end‐stage liver disease (1‐4). The hepatitis B virus (HBV) affects a large group of candidates for liver transplantation (1‐4), however, liver transplantation for HBV is associated with unique and serious problems due to post‐transplant predisposition for HBV re‐infection of the allograft (5‐10, 12‐14). Patients with actively replicating HBV infection, as demonstrated by positive pre‐transplant hepatitis surface antigen (HBsAg), hepatitis e antigen (HBeAg), and HBV‐DNA, patients retransplanted for HBV infection, patients not receiving long term hepatitis B immunoglobulin (HBIG) therapy (5‐10, 12, 14), and patients of Asian descent (15), appear to be most likely to experience clinically significant recurrent hepatitis (2, 3, 6‐14). Recurrent HBV can produce acute or chronic liver disease leading to graft failure, retransplantation, or death (2, 3, 5, 13, 14). For these reasons, liver transplantation for HBV remains controversial. In this review, we describe the proposed mechanisms, predisposing factors, and clinical presentation associated with HBV recurrence in liver allograft recipients. We also discuss current and potential methods of prevention of HBV infection following liver transplantation.
Hepatic venous catheterization in patients undergoing positive end‐expiratory pressure ventilation after OLT: technique and clinical impact
Authors: Kaisers U. , Langrehr J. M. , Haack M. , Mohnhaupt A. , Neuhaus P. , Rossaint R.
Published: September 2024

The objective of this study was to determine the feasibility and clinical impact of hepatic venous oxygenation monitoring in patients undergoing positive end‐expiratory pressure (PEEP) ventilation after OLT. The design comprised a prospective study using repeated‐measures design, within an intensive‐care unit for liver‐transplanted patients in a university hospital. Sixteen consecutive adult patients undergoing orthotopic liver transplantation were enrolled. Postoperatively, a fiber‐optic pulmonary artery catheter was inserted into the right hepatic vein. Patients were submitted to controlled ventilation with three different levels of endexpiratory pressure (PEEP): 0, 5 and 10 mbar. Hemodynamics, hepatic venous pressure, mixed venous (SvO2) and hepatic venous oxygenation (SvhO2) were measured. The average time required for hepatic venous catheterization was 2.9±1.2 min; serious complications were not observed. PEEP 5 mbar did not alter hemodynamics and SvhO2; PEEP 10 mbar significantly reduced cardiac index, SvO2 and widened arteriovenous content difference (p<0.05). The mean difference between SVO2 and SvhO2 was 6.3±6.0% and did not change during PEEP ventilation. A significantly positive relationship was observed between SvO2 and SvhO2 (r=0.91, p<0.05). Hepatic venous catheterization appeared to be practical and could be utilized to evaluate the effects of therapeutic interventions on the transplanted liver. However, the small number of patients studied will not allow the assessment of any risk‐benefit ratio of the technique investigated. Low levels of PEEP provided hemodynamic stability and did not alter hepatic oxygen supply‐demand ratio. Maintenance of an adequate cardiac index during ventilation with higher levels of PEEP appeared to be mandatory to insure appropriate oxygen delivery to the liver graft.
Attitudes of commercial renal transplant recipients toward renal transplantation in India
Authors: Qunibi Wajeh , Abulrub Daad , Shaheen Faisal , El‐Din A. B. Shehab , Alfurayh Osman , Almeshari Khalid
Published: September 2024

Renal transplantation offers patients with end‐stage renal disease the best opportunity for rehabilitation and long‐term survival. However, there is a critical shortage of transplantable kidneys worldwide. This plays well into the hands of transplanters and entrepreneurs involved in commercial renal transplantation, particularly in India. This practice has been condemned by all transplant societies. In our fight against rampant commercialism in renal transplantation, we sought to describe feelings of patients who had received transplants in India, and the difficulties they faced during their stay there. The results show that the two reasons that motivated patients to go to India were lack of livingrelated donors and the need for prompt transplant. More than half of the patients did not meet their donors. Their experience, however, has been largely positive except for some negative feelings toward the broker and the standard of hospital hygiene. The total cost of the transplant was far less than that in the West but, despite that, some patients felt financially exploited. Communication with them was poor, as most patients did not get adequate pretransplant education and were not informed of possible complications including rejection and graft loss. Furthermore, almost half of the patients were not given medical reports. These results substantiate the impression that CRT in India does not conform to the high standards of renal transplant medicine.
Induction therapy with cyclosporine without cytolytic agents results in a low incidence of acute rejection without significant renal impairment in heart transplant patients
Authors: Jazzar A. , Fagiuoli S. , Sisson S. , Zuhdi N. , Cooper D. K. C.
Published: September 2024

Since 1989, the immunosuppressive regimen used in all heart transplant patients at our center has consisted of (i) cyclosporine induction therapy (pretransplant p.o. 2‐6 mg/kg depending on serum creatinine level, with immediate post‐transplant i.v. therapy at 1‐3 mg/h until p.o. therapy alone maintains a whole blood trough level of 300 ng/ml by RIA); (ii) azathioprine (2.5 mg/kg/d i.v./p.o.); (iii) methylprednisolone i.v. for 24 h and then prednisone p.o. at 1 mg/kg/d, tapering to 0.1 mg/kg/d at 1 yr. No prophylactic cytolytic agents (ALG, OKT3) were given. One hundred consecutive patients have been followed for periods of 4‐56 months (mean 27 months). The incidence of acute rejection requiring increased therapy was 24%, with only 7% requiring i.v. steroids, 2 of whom (2%) also required ALG and/or OKT3, and with 17% requiring increased oral immunosuppression alone. Mean creatinine levels (mg/dl) were 1.3 pretransplant, 1.4 on d 7, 1.5 at 30 d, and 1.8 after 2 yr. Only I patient required temporary hemodialysis. Survival was 98% at 30 d. 94% at 1 yr, and 92% at 2 yr. We conclude that cyclosporine induction therapy with steroids and azathioprine without any cytolytic agent results in a low incidence of acute rejection without jeopardizing renal function.
Gastrointestinal tuberculosis in renal transplantation: a case report and review
Authors: Ahsan Nasimul , Blanchard Robert L. , Mai Martin L.
Published: September 2024

The pattern of tuberculosis has changed and in recent years: extrapulmonary tuberculosis has become more common, especially in immuno‐compromised individuals. A case of primary intestinal tuberculosis in a patient with kidney transplant is reported. The patient presented with persistent fever and right‐sided abdominal pain. Histopathology of colonic tissue showed granulomatous inflammation containing acid fast bacilli, and culture of the tissue grew Mycobacterium tuberculosis. Clinical improvement occurred after institution of appropriate anti‐tubercular treatment.
Nutrition support following liver transplantation: comparison of jejunal versus parenteral routes
Authors: Mehta P. L. , Alaka K. J. , Filo R. S. , Leapman S. B. , Milgrom M. L. , Pescovitz M. D.
Published: September 2024

Liver failure patients are chronically malnourished at the time of transplant. We have used jejunostomy tubes (j‐tube) placed at the time of liver transplantation for immediate postoperative enteral nutrition. We compared the effectiveness of this means of nutrition to total parenteral nutrition (TPN). Sixty‐three adult patients fed enterally (ENT) with a semi‐elemental diet were retrospectively compared to 21 adult controls alimented with TPN, both beginning after liver transplantation. Data collected included: day to initiation of nutrition, day of achieving goal nutrition, day of removal of nasogastric tube, day of initiation of oral nutrition, day of achieving oral nutritional goal, and serum albumin, cholesterol, SGOT, SGPT, GGT, and bilirubin. Intestinal complications of diarrhea, ileus, and perforation were analyzed. Statistical analyses used an unpaired t‐test for continuous data, and Chi square for categorical data. Caloric requirements, percentage ideal body weight, age, and initial cholesterol and albumin were equal. Fifty‐four of the ENT patients were fed only by j‐tube; 9 ENT patients also required TPN. ENT patients started on nutrition sooner (3±1.7 vs. 1.7±0.9 days, p=0.001), reached goal oral nutrition sooner (19.5±11 days vs. 38.6±24.6 days, p=0.0061, Mann‐Whitney U test), and had a lower frequency of prolonged postoperative ileus (8.3%, vs. 33%, p=0.009) than TPN patients. ENT patients had a greater frequency of diarrhea than TPN controls (73% vs. 25%, p<0.001). This diarrhea was self‐limited, lasting 3 to 5 days, and responded to anti‐motility drugs. When oral goal intake was not achieved, patients were able to be sent home on j‐tube feeding. We conclude that immediate j‐tube feeding is safe and effective, promotes resumption of oral feeding and allows discharge from the hospital before adequate oral intake is achieved in liver transplant recipients. Selection criteria are needed to determine the most appropriate candidates for jejunostomy tube placement during liver transplantation.
Erythrocytosis after renal transplantation: Risk factors and relationship with GFR
Authors: Nankivell Brian J. , Allen Richard D. M. , O'Connell Philip J. , Chapman Jeremy R.
Published: September 2024

Post‐transplant erythrocytosis (PTE) has been increasingly recognized as a complication of kidney transplantation, and several risk factors have been defined. Recent evidence suggests renal function may also play a role in hematological recovery after transplantation and risk of PTE. In this study of kidney transplant recipients (n=123), simultaneous Tc99m DTPA GFR (n=710) and hemoglobin levels were compared with possible clinical determinants. The frequency histogram of post‐transplant hemoglobin was bell‐shaped and continuously distributed above and below the arbitrary definition of PTE, suggesting that PTE is not a separate disease entity. Hemoglobin reached a plateau at 12 months after transplantation and was correlated with isotopic GFR (r=0.46, p<0.001). This consistent and statistically independent relationship became prominent 3 months after transplantation. Hemoglobin was independently predicted by multivariate analysis by time after transplantation, presence of polycystic renal disease, greater serum albumin and reduced serum urea (which in turn were reflected by number of infective and rejection episodes). shorter kidney anastomosis time and a higher GFR, but not by immunosuppressive therapy. Rejection or infection episodes impaired hematological recovery. The independent determinants of GFR included hemoglobin level, kidneys from young, male donors, fewer HLA‐DR mismatches. and rejection episodes, shorter time on dialysis and greater azathioprine dose. Renal function was not altered by therapeutic phlebotomy. Determination of hemoglobin level by both donor and recipient variables supports the relevance of tubular and glomerular function in control of erythrocystosis after renal transplantation. A role for renin‐angiotensin mediation in the alteration of intraglomerular hemodynamics and erythropoietin secretion is postulated.
Echo‐Doppler diagnosis of renal allograft artery stenosis
Authors: Merkus Jos W. S. , Hoitsma Andries J. , van Asten Wim N. J. C. , Zeebregts Clark J. A. M. , van der Vliet J. Adam , Strijk Simon P. , Koene Rob A. P. , Skotnicki Stefan H.
Published: September 2024

For the diagnosis of allograft artery stenosis in recipients of a renal transplant with hypertension a noninvasive investigation such as echo‐ Doppler is preferable to invasive methods such as angiography. Therefore we analyzed our experience with echo‐Doppler diagnosis of renal allograft artery stenosis. In 131 renal transplant recipients with hypertension echo‐Doppler examinations were performed. During the examinations several features indicative of stenosis were measured, and intrarenal Doppler spectra were quantitatively analyzed with a user‐written program. Four patients showed signs of iliac artery stenosis. In 12 patients a renal allograft artery stenosis was suspected on echo‐Doppler examination. In 8 of these 12 patients angiography was performed. All these showed a stenosis, 6 of which had more than >75% stenosis. In 8 patients with normal echo‐Doppler findings angiography was performed because of highly suggestive clinical signs of stenosis. In 7 of these no stenosis was found and in one a 50% stenosis was found. Comparison of quantitative Doppler spectrum features from patients with (n=6) and without severe (>75%) stenosis on angiography (n=10) showed significant differences in several Doppler parameters. Subsequently an analysis of the best differentiation between these to groups on the basis of quantitative Doppler criteria was performed. In conclusion, echo‐Doppler examinations with quantitative analysis of Doppler spectra enables reliable identification of renal allograft artery stenosis.
Rejection episodes after liver transplantation during primary immunosuppression with FK506 or a cyclosporine‐based regimen: A controlled, prospective, randomized trial
Authors: Jonas S. , Kling N. , Bechstein W. O. , Blumhardt G. , Lohmann1 R. , Lobeck H. , Neuhaus P.
Published: September 2024

As part of a European multicenter study to investigate the potency of FK506 in primary immunosuppression after liver transplantation, this comparison with our conventional cyclosporine‐based quadruple regimen was carried out as a controlled, prospective, randomized trial. The 121 patients entering the study were randomly assigned to receive immunosuppressive regimens consisting either of FK506 and prednisolone (FK/n=61) or of cyclosporine, prednisolone, azathioprine, and a 7‐day course of rabbit antithymocyte globulin (CsA/n=60). Rejection was suspected in the case of scant production of light bile or biochemical graft dysfunction, without evidence of vascular, biliary, or infectious complications. A liver biopsy for confirmation of the diagnosis was obtained each time. Initial therapy entailed a 3‐d course of high‐dose methylprednisolone. Steroid resistant rejections were treated with OKT3 monoclonal antibody or, in the group of primary CSA administration, conversion to FK506 as another treatment option. One‐year patient (FK: 90.2%; CsA: 96.7%) and graft survival (FK: 88.5%; CSA: 91.7%) did not differ significantly. Overall, 41 patients (33.9%) experienced 50 acute, cellular rejection episodes (RE) [FK: 25 RE in 21 patients (34.4%); CSA: 25 RE in 20 patients (33.3%)]. The histological grading ranged from mild (FK: 14/25; CSA: 8/25) to moderate (FK: 9/25; CsA: 16/25) and severe (FK: 2/25; CSA: 1/25): not significantly different between the two groups. In the CSA‐based group, three additional rejection episodes were classified as early chronic (n=1) and chronic rejection (n=2). A higher share of late‐onset rejections in the CSA‐group (FK: 1/25, 617d; CsA: 6/25, 164±66d) as well as a more frequently observed occurrence of light bile (FK: 8/25; CsA: 4/25) and overlapping cholangitis (FK: 9/25; CSA: 3/25) in the FK‐group were not significant either. In each group, 10 RE were steroid‐resistant. In the FK‐group, all of them resolved under OKT3; in the CSA‐group, I patient was directly switched to FK506, 6 RE resolved during the OKT3 course, whereas 3 RE were resistant to OKT3. Two OKT3 non‐responders were successfully converted to FK506, the other was suffering from early severe rejection and underwent retransplantation. After another retransplantation for severe hepatitis C reinfection, concomitant findings of chronic rejection type changes were evident and the patient was switched to FK506.

These results reflect a comparable low incidence of RE in both groups. Safety in terms of patient and graft survival was high. FK506 as a reported rescue agent seems to hold further potential in reducing late‐onset, ductopenic, and histologically higher‐degree cellular rejections.
Immunologic monitoring of OKT3 induction therapy in cardiac allograft recipients
Authors: Toyoda M. , Galfayan K. , Wachs K. , Czer L. , Jordan S.C.
Published: September 2024

OKT3 induction therapy was monitored in 31 cardiac allograft recipients during the 1st year posttransplant. Serum level of OKT3, anti‐OKT3 antibodies, and interleukin‐2 (IL‐2) were monitored during the first 2 months posttransplant. These values were retrospectively correlated with allograft rejection episodes which occurred during the 1st year posttransplant and allograft survival rates over a 3‐year observation period. We found that OKT3 induction therapy (10‐14 days) was not associated with the development of anti‐OKT3 antibodies manifest by dropping OKT3 levels during OKT3 therapy, and is not associated with the development of vascular rejection in our patient population. Patients with high titer ant‐OKT3 antibodies, erratic serum OKT3 levels, and/or high serum IL‐2 levels (≥5 ng/ml) during the first 2 months posttransplant showed a higher incidence of allograft rejection (predominantly cellular rejection) during the 1st year posttransplant and showed lower allograft survival rates. We also showed that a concomitant elevation of serum IL‐ 2 levels was found in patients who developed anti‐OKT3 antibodies. CD3+T‐cell levels were not predictive of inefficacy of OKT3 therapy. We conclude that immunologic monitoring of serum OKT3, anti‐OKT3 antibody, and possibly serum IL‐2 levels is critical for identification of patients who develop early, OKT3‐resistant rejection episodes and for the identification of patients who may be more susceptible to allograft rejection and decreased allograft survival long after completion of OKT3 therapy.
Does re‐exposure to mismatched HLA antigens decrease renal re‐transplant allograft survival?
Authors: Farney Alan C. , Matas Arthur J. , Noreen Harriet J. , Reinsmoen Nancy , Segall Miriam , Schmidt Wally J. , Gillingham Kristin , Najarian John S. , Sutherland David E. R.
Published: September 2024

We analyzed 420 kidney retransplants at the University of Minnesota, 87 of which did and 333 which did not share HLA mismatches with the previous transplant. There was no difference in outcome. We conclude that exceptions to routine HLA matching policies do not have to be made for kidney retransplants.

Objective

To determine if the kidney graft functional survival rate for retransplants is influenced by presence of HLA mismatches in common with the previous (failed) transplant.

Summary background data

Kidney retransplants have a lower function. rate than primary grafts. An anamnestic response to HLA antigens shared with the previous donor could be one factor responsible, but reports in the literature are conflicting.

Methods

Of 420 kidney retransplants with HLA information done at the University of Minnesota, 87 shared ≥1 HLA antigens specifically mismatched with the previous donor (63 cadaver and 24 living donor retransplants), while 333 did not (247 cadaver, 86 living donor). Patient and graft survival rates were calculated by life‐table analysis for recipients with vs. without repeat mismatches, with the significance of differences determined by the Lee‐Desu statistic.

Results

Patient and kidney graft retransplant survival rate curves were not significantly different (p≥0.41) for those exposed or not exposed to the same HLA mismatches as before. At 2 years, 70% vs. 61%, respectively. of cadaver grafts and 71% vs. 78%, respectively, of living donor grafts were functioning.

Conclusions

The probability of a successful outcome with a kidney retransplant is no different for patients who do than for those who do not receive an organ sharing HLA mismatches with the previous donor. Exceptions to routine HLA matching policies do not need to be made for kidney retransplants.
Disseminated histoplasmosis in renal allograft recipients
Authors: Peddi V. Ram , Hariharan Sundaram , First M. Roy
Published: September 2024

Histoplasmosis, an opportunistic fungal infection endemic in the Ohio and Mississippi river valleys, is caused by a dimorphic fungus Histoplasma capsulatum. Most infections are asymptomatic or self‐limited febrile illness. Immunosuppressed renal transplant recipients are susceptible to a disseminated disease. We report 5 cases of disseminated histoplasmosis seen in our institute over a period of 25 years amongst 1074 renal transplant recipients. The duration of immunosuppression prior to the diagnosis of infection ranged from 84 days to 14 years. All patients had pulmonary involvement. Three patients recieved an antilymphocyte preparation and 1 patient received intravenous pulse steroids in the 3 months prior to the onset of infection. Histopathologic examination of the involved organ(s) provided rapid diagnostic information allowing early treatment with amphotericin B. All infections resolved with no relapses to date. In conclusion immunosuppressed patients are more prone to disseminated histoplasmosis. Early recognition and prompt treatment with amphotericin B resolved the infection without relapse.
Selective use of veno‐venous bypass in orthotopic liver transplantation
Authors: Johnson Mark W. , Powelson John A. , Jr. Hugh Auchincloss , Delmonico Francis L. , Cosimi A. Benedict
Published: September 2024

The use of veno‐venous bypass (VVB) during the anhepatic phase of orthotopic liver transplantation (OLT) remains controversial. We employ VVB on a selective basis: patients who tolerate intra‐operative supra‐hepatic IVC test cross‐clamping undergo OLT without VVB while patients who, despite maximal volume resuscitation, develop hemodynamic instability during test cross‐clamping, undergo OLT with VVB. The records of 150 adult orthotopic liver allograft recipients transplanted at the Massachusetts General Hospital from January 1984 to December 1994 were reviewed to identify any potential adverse affects on peri‐operative, 6 months, I year outcomes in recipients foregoing VVB during liver transplantation. Thirty‐eight patients (25%) underwent OLT without VVB with actuarial survivals of 78.4% and 69% at 6 months and 1 year. 112 patients (75%) underwent OLT with VVB with actuarial survivals at 6 months and 1 year of 73% and 72%. Demographic data, UNOS status, and diagnoses were similar in each group. There were no significant differences in intra‐operative PRBC requirements; lengths of hospital stay; retransplantation rates; or 30 day, 6 months and 1 year survivals between these two groups. There was no significant difference in renal function as determined by preoperative, peak post‐operative, discharge serum creatinine levels, or number of patients requiring HD between these two groups. There were two major complications (1.8%) possibly resulting from VVB. In conclusion, patients who tolerate IVC test cross‐clamping can safely undergo orthotopic liver transplantation without veno‐venous bypass. In our experience, there were no significant differences in perioperative parameters, post‐operative renal function, or short‐term survival when compared to patients who, due to hemodynamic instability during IVC cross‐clamping, underwent OLT with VVB. Given the potential complications associated with VVB, we feel that in those patients who tolerate intra‐operative IVC cross‐clamping, it is better to proceed without the use of VVB.
Outcome of cadaveric renal transplantation by induction treatment in the cyclosporine era
Authors: Hariharan Sundaram , Alexander J. Wesley , Schroeder Timothy J. , First M. Roy
Published: September 2024

A total of 358 cadaveric renal transplantations performed between 1984 and 1993 received induction therapy with Minnesota antilymphoblast globulin (MALG) 95, muromonab‐CD3 (OKT3) 58, antithymocyte globulin ‐ Upjohn (ATGAM) 104, rabbit antithymocyte serum (RATS) 37, or cyclosporine (CyA) 64. There were no differences in age, gender, HLA mismatches and maintenance immunosuppression between these groups of recipients. A significantly higher proportion of OKT3 induction patients were retransplants (50%, p<0.0001). There were fewer diabetic recipients in the group that received RATS (8%) compared to the other groups (p=0.0009). There was no significant difference in overall graft survival with the various forms of induction treatment (log rank test, p=0.48). Similarly, primary cadaveric graft outcome was not different with various forms of induction treatment (p=0.62). Acute rejection was higher with ATGAM, occurring in 65% of patients, compared to MALG (52%), OKT3 (55%), RATS (43%) and CyA (55%). A significantly lower number of patients were rejection‐free with ATGAM (35%) compared to MALG (48%) (p=0.04). Patients who received ATGAM induction also had a higher rate of rebound rejection. Patients receiving ATGAM induction had a significantly higher serum creatinine level at 1 and 6 months post‐transplantation (p<0.005) compared to other induction treatments. In conclusion, the prevalence of acute rejection was higher with ATGAM, which was also reflected by higher serum creatinine levels. However, the long‐term graft function and survival were not different with the various induction treatments.
Laparoscopic‐assisted colectomy in heart transplant recipients
Authors: Detry O. , Defraigne J.O. , Chiche J.D. , Meurisse M. , Joris J. , Honoré P. , Jacquet N. , Limet R.
Published: September 2024

Reports of laparoscopy in heart graft recipients are scarce and, to our knowledge, laparoscopic colectomy has not yet been reported in heart transplant patients. The magnitude and the tolerance of the hemodynamic changes induced by pneumoperitoneum are unknown in heart. graft recipients, who have a denervated heart and are “preload‐dependent”. The authors report the clinical courses of 2 heart graft recipients who developed acute diverticulitis without perforation or peritonitis and who underwent laparoscopic‐assisted colectomy without complications.
Successful treatment of intraoperative malignant hyperthermia during renal transplantation
Authors: Goss J. A. , Brennan D. C. , Miller B. T. , Shenoy S. , McClure S. , Howard T. K. , Flye M. W.
Published: September 2024

Malignant hyperthermia is a complication of general anesthesia that is especially problematic if it occurs during renal transplantation because myoglobinemia, shock, and ischemia play a role in injuring the transplanted kidney. In this report, we describe a case of malignant hyperthermia, its clinical course, and the measures taken to successfully treat it and preserve the function of a kidney allograft.
Diagnosis and management of the urologic complications of renal transplantation
Authors: Ghasemian Seyed M. R. , Guleria Anshu S. , Khawand Nabil Y. , Light Jimmy A.
Published: September 2024

669 patients who received a renal transplant from January 1988 to December 1993 at a single institution were evaluated for urologic complications. Urologic complications were assessed and categorized by organ involvement: kidney, ureter, bladder, lymphatic, calculus and complicated urinary tract infection. Complications were also classified as “early” if they occurred within 14 d after transplant and those diagnosed after this period were called “late.” The management of all complications is presented. There were a total of 98 urologic complications identified in 669 patients, of which 51 were complicated urinary tract infections. The other 47 complications were divided among renal (8), ureteral (19), bladder (3), lymphatic (10) and calculi (7). Preventive measures, such as technical management of ureteral reimplantation, periodic renal scan or ultrasound examinations, and long‐term urinary antibiotic prophylaxis could further reduce the incidence of urologic complications. The result should be further improvement in transplant patient and graft survival.
Parvovirus B19 infection in a liver transplant recipient: case report and review in organ transplant recipients
Authors: Chang Feng‐Yee , Singh Nina , Gayowski Timothy , Marino Ignazio R.
Published: September 2024

We report an adult liver transplant recipient with parvovirus B19 infection, presenting as chronic transfusion‐dependent anemia ensuing I month post‐transplantation. Both serum and bone marrow cells were positive for parvovirus B19 DNA detected by polymerase chain reaction. The bone marrow biopsy revealed erythroid hypoplasia with a selective decrease of nucleated red cell precursors, and giant pronormoblasts with prominent intranuclear inclusions, characteristic of parvovirus B19 infection. Anemia and viremia resolved shortly after administration of immunoglobulin, suggesting a therapeutic role. This case and several similar ones in the literature provide justification for a controlled clinical trial of immunoglobulin for parvovirus‐induced anemia in transplant recipients.
Mesenteric arteriovenous fistula after vascularized pancreas transplantation resulting in graft dysfunction
Authors: A.Lowell Jeffrey , Stratta Robert J. , Taylor Rodney J. , Bynon J. Stevenson
Published: September 2024

Mesenteric arteriovenous fistula (AVF) is an unusual complication after vascularized pancreas transplantation. We report the case of a patient who developed a mesenteric AVF in the transplanted mesenteric bundle which resulted in severe and protracted endocrine insufficiency necessitating reinstitution of insulin therapy. This was reversible with surgical correction of the AVF. This complication should be included in the differential diagnosis of pancreas allograft dysfunction.
Human syngeneic intestinal transplantation: evaluation of enterocyte viability with serum levels of intestinal fatty acid binding protein
Authors: Kuo Paul C. , Morris Jonathan , Marks William H. , Lieberman Joshua M. , Johnson Denise L. , Alfrey Edward J. , Bastidas J. Augusto , Dafoe Donald C.
Published: September 2024

In a case of human syngeneic intestinal transplantation, the postoperative course was complicated by the Systemic Inflammatory Response System (SIRS). This syndrome was characterized by negative cultures and elevated levels of the pro‐inflammatory cytokines, IL‐1β, IL‐6 and TNF. In keeping with current concepts of translocation across the enterocyte barrier as the etiology of SIRS, levels of intestinal fatty acid binding protein (I‐FABP), an enterocyte‐specific protein, also increased. These observations suggest that (i) a clinical syndrome consistent with translocation may occur in the absence of rejection in intestinal transplantation, and (ii) I‐FABP may serve as a clinically relevant marker for enterocyte injury.
Pancreaticocystostomy revision for obstructive pancreatitis and pancreatic fistula after segmental pancreatic transplantation
Authors: Esterl Robert M. , Gupta Navyash , Reese Jeffrey C. , Patel Bhargavi K. , Fairchild Ralph B. , Solomon Harvey , Garvin Paul J.
Published: September 2024

Combined kidney‐pancreas transplantation is an effective surgical therapy for end‐stage renal failure secondary to type I diabetes mellitus. However, obstructive pancreatitis and pancreaticocutaneous fistula remain significant postoperative complications unique to extraperitoneal segmental pancreatic transplantation. We present our experience with 13 patients (7 with obstructive pancreatitis and 6 with pancreaticocutaneous fistulae) after segmental extraperitoneal pancreatic transplantation, who subsequently underwent intraperitoneal reconstruction of the pancreaticocystostomy. This reconstruction was successful in 11 of 13 (85%) patients with minimal morbidity and no mortality. This intraperitoneal approach to reconstruction of the pancreaticocystostomy after segmental extraperitoneal pancreatic transplantation is a safe and effective means of graft salvage and this technique has not been described in the literature.
Effect of oral pentoxyfylline on the OKT3‐induced cytokine‐release syndrome among renal allograft recipients
Authors: Vasquez Eva M. , Pollak Raymond
Published: September 2024

Recent data suggest that pentoxyfylline administration results in a significant reduction in serum TNF levels among OKT3‐treated patients. However, the effect of pentoxyfylline on the clinical syndrome that ensues following OKT3 administration remains undefined. We evaluated 32 OKT3‐treated renal transplant recipients to assess the impact of pentoxyfylline on OKT3 adverse reactions. The study population consisted of two groups: (i) a prospective group comprising 16 patients who received oral pentoxyfylline 600 mg 1‐2 h prior to the first dose of OKT3 and then 600 mg every 8 h for 72 h, in addition to corticosteroids, acetaminophen and diphenhydramine, and (ii) an historical control group (n=16) treated with corticosteroids, acetaminophen and diphenhydramine alone. All patients were evaluated for signs and symptoms consistent with the OKT3‐induced cytokine‐release syndrome. The incidence and clinical severity of OKT3‐related adverse reactions were similar among the two groups. We conclude that oral administration of pentoxyfylline does not appear to affect the incidence or severity of OKT3‐related adverse reactions