bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics of azathioprine and 6‐mercaptopurine after oral administration of azathioprine
Authors: Salemans Jan , Hoitsma Andries J. , De Abreu Ronney A. , de Vos Dick , Koene Robert A. P.
Published: September 2024

The pharmacokinetics of azathioprine (AZA) and its primary metabolite, 6‐mercaptopurine (6‐MP), were studied in 12 kidney transplant recipients after a single oral dose (3 mg/kg) of either azathioprine‐Pharmachemie® (AZA‐PCH) or azathioprine‐Wellcome (Imuran®, AZA‐IM), two commercially available AZA preparations, in a randomized crossover design. Plasma levels of AZA and 6‐MP were determined by high‐performance liquid chromatography (HPLC). No AZA was detected at any time after oral administration of AZA. The mean peak plasma concentration of 6‐MP (Cmax) was 144 nmol/l with a mean time to peak plasma concentration (Tmax) of 1.8 h for both AZA preparations, indicating that AZA was rapidly converted to 6‐MP. The mean plasma elimination half‐life of 6‐MP (T½) was 1.9 h after AZA‐PCH and 2.0 h after AZA‐IM. The 6‐MP levels fitted a simple first order kinetic process. At 12 h after administration, 6‐MP levels in all patients were below the detection limit. Thus, the bio‐availability of both preparations appeared to be the same. There was wide interpatient differences in 6‐MP levels. Intrapatient differences after AZA‐PCH and AZA‐IM, however, were almost negligible. One patient who was on phenobarbital and phenytoin medication had markedly lower 6‐MP levels than the other 11 patients, probably due to induction of drug‐metabolizing liver enzymes. A subsequent retrospective analysis revealed that the incidence of acute rejections was significantly higher in recipients using phenobarbital. No AZA was detected in the urine. Less than 1% of the dose of AZA was excreted in the urine as 6‐MP. There was no correlation between creatinine clearance and either urinary excretion or T½ of 6‐MP. We conclude that 1) AZA is rapidly converted to 6‐MP in vivo, 2) determination of 6‐MP plasma levels in kidney transplant recipients who receive AZA might be of clinical importance because of marked differences in 6‐MP metabolism and possible drug interactions, 3) reduction of the AZA dosage at lower creatinine clearances is disputable and may lead to undertreatment, because 6‐MP is mainly cleared by non‐renal mechanisms, 4) more frequent daily administration of AZA may be preferable because of the short half‐life of 6‐MP.
Impact of HBs antigenemia on long‐term patient survival and causes of death after renal transplantation
Authors: Hiesse C , Buffet C. , Neyrat N. , Rieu P. , Charpentier B. , Etienne J. P. , Fries D.
Published: September 2024

The impact of hepatitis B virus in renal transplantation remains a controversial subject. To evaluate the long‐term consequences of chronic HBs antigenemia on patient survival, we studied 615 consecutive patients who received a kidney transplant in a single center from 1970 to 1984, including 107 HBs Ag‐positive, and 508 HBs Ag‐negative patients. Pretransplant HBs Ag‐negative patients had a significantly better long‐term survival rate (80% vs 64% survival in HBs Ag‐positive patients at 10 years posttransplant, p<0.05). This difference was strongest in the subgroup of patients who had a functional graft at 3 months posttransplant (81% vs 60% at 10 yr, p<0.001), and in the subgroup of patients whose graft never failed (71% vs 53%). The overall mortality incidence was more important in pretransplant HBs Ag‐positive patients (34.4% vs 20.5% in HBs Ag‐negative patients, p<0.001), and liver failure was the main cause of death in the HBs Ag‐positive group after the 5th yr posttransplant (30% vs 4.2% in HBs Ag‐negative patients, p<0.05). Pretransplant serum transaminases did not predict posttransplant hepatic failure or death. Finally, the impact of HBs antigenemia was only seen in patients over 40 yr old at the time of transplant (50% vs 69% at 10 yr, p<0.01), and in patients receiving conventional drugs. We conclude that HBs Ag‐positive patients had an obvious moderately increased risk of mortality with renal transplantation, seen over the long term (16% at 10 yr). We recommend that candidates for renal transplantation should not be excluded from the procedure, but must be submitted to a careful pretransplant check‐up, and to routine liver monitoring if renal transplantation is to be performed.
Standard versus low‐dose OKT3 induction therapy of cadaveric renal transplants: Comparison of outcome data versus OKT3 dose and serum levels
Authors: Alloway Rita R. , Kotb Malak , Gaber Lillian W. , Vera Santiago R. , Boskey Freda , Gaber A. Osama
Published: September 2024

Lymphocytoreductive therapy with the polyclonal antithymocyte globulin or the monoclonal anti‐CD3 antibody (OKT3) has been an integral part of sequential immunosuppressive protocols. The optimum dosage of OKT3 in early posttransplant induction is unknown, although the use of lower doses of OKT3 than those used in rejection treatment have been shown to be effective in cadaveric renal transplant recipients. We compared immune monitoring data from 25 recipients of primary cadaver renal allografts receiving low‐dose (2 mg) induction with data from a retrospective cohort of 27 patients who received 5‐mg standard dose. Both groups were treated with the identical sequential quadruple‐therapy protocol. Monitoring parameters included daily CD3 measurement, and twice weekly measurements of serum OKT3 levels and anti‐OKT3 antibodies. Patient and graft survival were similar in both groups. OKT3 dosage increases due to high peripheral CD3 levels were necessary in 4 out of 27 patients receiving the 5‐mg doses and in 8 out of 25 patients receiving the 2‐mg dose (p<0.05). The mean total dose in the standard‐dose group was 48 mg (range 30‐70 mg), while the mean total dose for the low‐dose group was 23 mg (range 10‐58 mg) (p<0.05). Circulating OKT3 levels were significantly higher in the standard‐dose group of patients than in that group receiving low‐dose therapy (p<0.0l). None of the patients with low circulating OKT3 levels developed major post‐transplant infections while 5 of 15 patients with high circulating levels (>700 ng/dl) required hospitalization for bacterial (n = 3) or viral (n = 2) infections in the first 3 months posttransplant (p<0.0001). Antimurine antibodies developed in 5 (19%) of the patients receiving standard‐dose therapy while only 2 (8%) of the patients receiving low‐dose induction became sensitized. These data indicate that the success of OKT3 induction therapy is not correlated to the dosage or to the circulating levels achieved and that higher circulating levels may be associated with increased risk for infection.
Renal transplantation in patients with systemic lupus erythematosus1
Authors: Hariharan Sundaram , Schroeder Timothy J. , Carey Mark A. , First M. Roy
Published: September 2024

A total of 23 renal transplants were performed in 18 patients with systemic lupus erythematosus (SLE) between 1974–1990. Posttransplantation, these patients were followed up for a mean period of 45.1 months (1–180). There were 14 graft losses including 2 patients who died with functioning grafts. Patient and graft survival were calculated by life table analysis. Patient survival at 1,5 and 10 years was 94.2%. 94.2% and 75.3%: and the corresponding graft survival was 61.2%, 50.9%, and 36.3% respectively. There was no significant difference between blacks vs whites, live vs cadaver donors, but there was significantly lower survival in retransplants vs first transplants (p = 0.010). Six grafts were lost within 6 months after transplantation: elevated panel‐reactive antibody (PRA) level (>20%) was the only significant factor for early graft loss (p<0.05). The timing of transplantation and presence of an auto‐antibody did not significantly impact on early graft loss. The graft survival between SLE, diabetes and the remaining end‐stage renal disease (ESRD) patients transplanted between 1980–1990 were calculated using a statistical analytical software; this revealed that the homogenicity of the survival curves between these groups was not significantly different (p = 0.1730). although patients with SLE had poorer outcomes than the other patient groups.
Risk of a false‐positive HLA crossmatch after administration of Rh0(D) immune globulin
Authors: Mahoney R. J. , Emmons R. A. , Given S. R. , Munson M. E. , Lovett E. J. , Stocks J. F. , Leeher D. A.
Published: September 2024

Rh0(D) immune globulin (RhIg) was tested for HLA antibody prior to administration in vivo. RhIg preparations were found to contain multispecific HLA class I alloantibodies that reacted with as many as 97% of a 35‐member T‐lymphocyte panel. Pooled platelets absorbed 80–90% of the anti‐HLA‐A‐B class I reactivity in the antihuman immunoglobulin (AHG) cytotoxicity test. Rh‐positive red blood cells completely absorbed Rh antibody but not HLA antibody. To determine if passively transferred HLA antibody is detectable in vivo, sera from 9 Rh‐negative recipients of RhIg were tested pre‐ and post‐RhIg injection for Rh and HLA antibody. Exogenous Rh antibody was detectable in vivo by the red blood cell agglutination technique in all 9 post‐RhIg injection sera. In contrast, exogenous HLA reactivity in pre‐RhIg injection samples was not detected in post‐RhIg injection sera that were screened against a T‐lymphocyte panel and crossmatched against kidney donor lymphocytes in the sensitive AHG and flow cytometric crossmatch tests. The absence of passively transferred HLA alloantibody in vivo has an important impact for Rh‐negative renal transplant candidates who receive RhIg with Rh‐positive donor‐specific transfusions (DST) prior to transplant crossmatch. We conclude that the passive transfer of concentrated HLA class I alloantibody present in full doses of injected RhIg results in a negligible risk of a pretransplant false‐positive HLA crossmatch in DST candidates who are Rh‐incompatible.
Fatal varicella with liver necrosis after kidney transplantation
Authors: Schröter Gerhard P. J.
Published: September 2024

A young adult died in the early phase of varicella with massive liver necrosis. Severe abdominal pain was the predominant complaint. Liver necrosis is a characteristic, albeit uncommon, but usually fatal complication of varicella in the compromised host and is heralded by severe abdominal pain. Children and young adults should be screened by history or a sensitive antibody test for immunity to varicella before transplantation. After transplantation susceptible patients should receive passive immunization with zoster hyperimmune globulin in case of exposure and early therapy with acyclovir in case of infection. Vaccination of susceptible patients with an attenuated live virus vaccine before transplantation has promise for reducing the risk of varicella after transplantation.
Effects of the calcium channel blocker diltiazem on cyclosporin nephrotoxicity in renal transplant patients
Authors: Ferguson C. J. , Williams J. D. , Hillis A. N. , Parry‐Jones D. , Salaman J. R.
Published: September 2024

In a prospective study, renal hemodynamics were measured in renal transplant patients who were at least 6 months post‐transplant and who had good stable renal function. Single injection isotopie techniques were used to measure glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) before, during and after the administration of the calcium channel blocking drug, diltiazem. When patients treated with cyclosporin monotherapy were given 60 mg of diltiazem twice daily for 6 weeks followed by withdrawal of the drug, there was a significant rise and fall pattern in GFR and ERPF. There were no changes in an equivalent group of patients receiving azathioprine and prednisolone as immunosuppressive therapy. The beneficial effect of diltiazem on renal function in the cyclosporin‐treated group occurred despite a marked rise in cyclosporin trough whole blood levels. It is concluded that diltiazem may ameliorate the renal hemodynamic effects of chronic cyclosporin nephrotoxicity.
Pancreatic graft survival after arterial thrombosis in simultaneous renal‐pancreatic transplantation
Authors: Schaapherder Alexander F. M. , van Oosterhout Etnile C. A. A. , Bode Paul J. , van der Woude Fokko J. , Lemkes Herman H. P. J. , Gooszen Hein G.
Published: September 2024

Vascular thrombosis following pancreas transplantation is one of the main causes of early graft loss. Successful thrombectomy after pancreatic graft thrombosis has not been reported yet. A patient with arterial graft thrombosis in whom the graft survived after thrombectomy is described. Different varieties of pancreatic graft thrombosis are discussed.
Immune thrombocytopenic purpura following orthotopic liver transplantation
Authors: Kuo Paul C. , Lewis W. David , Dzik Walter , Jenkins Roger L.
Published: September 2024

Immune thrombocytopenic purpura (ITP) is characterized by autoimmune platelet destruction. Thrombocytopenia in the immediate postoperative period following liver transplantation is common but ITP in the late postoperative period has never been reported. Two cases of ITP presenting 9 and 39 months following orthotopic liver transplant are described. Evaluation must include eliminating secondary causes such as hypersplenism, drug toxicity, infection and lymphoproliferative disorders. In contrast to the treatment of ITP in the normal population, ITP in these transplant patients was refractory to routine medical therapy. The patients underwent splenectomy without complications. Platelet counts have remained normal at 9 and 12 months of follow‐up.
Cytokine changes in thrombotic thrombocytopenic purpura following kidney transplantation
Authors: Burke G. W. , Cirocco R. , Carreno M. , Pardo V. , Roth D. , Castillo A. , Temple J. D. , Esquenazi V. , Milgrom M. , Miller J.
Published: September 2024

The occurrence of thrombotic thrombocytopenic purpura (TTP) following kidney transplantation is rare. We report a patient who developed TTP within 36 hours of kidney transplantation. For 5 months preoperatively, serum levels of Interleukin‐2 (IL‐2) and gamma interferon (IFN‐G) were markedly elevated. Subsequent to kidney transplantation and steroid administration, thrombocytopenia, with schistocytic anemia and severe neurologic changes (TTP), abruptly occurred. This was associated with a dramatic fall in the levels of IL‐2 and gamma‐IFN. There was no clinical improvement with plasmapheresis. The patient's serum was not cytotoxic when added with complement to the donor renal vein endothelial cells in vitro. Removal of the allograft corrected the TTP.
Clinical and pathological features of graft‐versus‐host disease after liver transplantation: A case report and review of the literature
Authors: Rosen Charles B. , Ng Christine S. , Moore S. Breanndan , Batts Kenneth P. , Santrach Paula J. , Noel Pierre , Wiesner Russell H. , Krom Ruud A. F.
Published: September 2024

A 59‐year‐old female developed symptoms of graft‐versus‐host disease 3½ weeks after liver transplantation for primary biliary cirrhosis. Symptoms of graft‐versus‐host disease included fever, erythroderma with bullae formation, and mucosal surface ulceration. Donor lymphocytes were present in the peripheral blood. Despite treatment with equine antilymphoblast globulin, steroids and, eventually, cyclosporine withdrawal, she developed neutropenia and succumbed to sepsis. At autopsy, she had marked lymphocyte depletion involving the bone marrow and both native and donor origin lymph nodes. As expected, the liver was normal. The clinical and pathological features were remarkably similar to those of the few other reported cases of graft‐versus‐host disease after liver transplantation and transfusion‐associated graft‐versus‐host disease; therapy is usually ineffective, and progression of disease leads to pancytopenia and death from sepsis.
A comparison of duplex doppler ultrasonography and intrarenal manometry in the diagnosis of acute renal transplant rejection
Authors: Krishnan H. , Cochlin D. , Moore R. , Griffin P. , Salaman J. R.
Published: September 2024

Renal transplant rejection is frequently difficult to differentiate from other causes of renal dysfunction. This study examined the use of duplex doppler ultrasound and intrarenal manometry in a consecutive series of 73 patients who underwent renal transplantation. Altogether 327 duplex scans were analyzed and, for each, a resistive index (RI) was calculated. A raised RI predicted rejection in patients with grafts that functioned immediately, but not in those that had delayed function. A rise in intrarenal pressure (≥40 mmHg) indicated the presence of rejection in both groups. However, neither lest had a sensitivity of more than 71% and this was not improved by combining the results of the two tests for each patient. Although both tests have a place in transplantation, renal biopsies may still be required to confirm rejection.
Kaposi's sarcoma in two primary liver allograft recipients occurring under FK506 immunosuppression
Authors: Kadry Zaklyah , Bronsther Oscar , Van Thiel David H. , Randhawa Parmjeet , Fung John J. , Starzl Thomas E.
Published: September 2024

Of 1463 liver allograft recipients receiving the combination of FK506 and steroids as their primary immunosuppressive regimen, 2 patients developed Kaposi's sarcoma. Although previously described as a complication of organ transplantation, this is the first case report of Kaposi's sarcoma occurring in association with the macrolide immunosuppressive agent FK506. A discussion of the clinical presentation and course of Kaposi's sarcoma in these 2 patients, as well as a review of the past literature on Kaposi's sarcoma in organ transplant recipients, emphasizes the therapeutic difficulties encountered. Kaposi's sarcoma is also compared to lymphoproliferative disorders, another well‐recognized complication of immunosuppression, highlighting the differences between these two entities.
OKT3‐induced acute pulmonary edema in a euvolemic patient despite premedication with methylprednisolone and antithymocyte globulin
Authors: Lo C. Y. , Chan T. M. , Lo W. K. , Cheng I. K. P.
Published: September 2024

Acute pulmonary edema is a well‐recognized complication after the first dose of OKT3 therapy in patients with fluid overload. The first‐dose effect is thought to be related to the action of cytokines, namely tumor necrosis factor‐alpha (TNF‐α), interleukin 2 (IL‐2) and interferon gamma (IF‐γ), which are released from activated T lymphocytes. Premedications such as high‐dose methylprednisolone (MP) and more recently antithymocyte globulin (ATG) has been shown to alleviate the severity of the first‐dose effect by reducing the level of cytokines released. We hereby report a euvolemic patient who developed acute pulmonary edema 5 hours after OKT3 therapy despite premedications with high‐dose MP and ATG.
A comparison of cadaver donor kidney storage methods: Pump perfusion and cold storage solutions
Authors: Koyama Hiroto , Cecka J. Michael , Terasaki Paul I.
Published: September 2024

The effects of preservation methods and cold storage solutions on the outcome of more than 17000 first cadaver kidney transplants were studied from data reported to the UNOS Scientific Renal Transplant Registry and to the UCLA Transplant Registry between 1987 and 1991. Early graft function was better in pump‐preserved than cold‐stored kidneys: 84% vs 73% at 1 week; and 87% vs 80% at discharge, respectively (p<0.01 in both comparisons). However, graft survival rates were similar at 3 months (87% vs 86%) and 1 year (80% vs 80%) (p>0.05 in both comparisons). Rejection episodes prior to discharge were the same in both groups. An analysis of results from 17 transplant centers where more than 50 pump‐stored kidneys were transplanted yielded similar results. Good early graft function of pump‐stored kidneys did not necessarily lead to better graft survival, when all current perfusion methods were compared. There was no clear superiority in terms of graft survival for pump‐stored kidneys, even with long cold ischemia lime or with kidneys from older donors. A comparison of UCLA Registry data survival results of different preservation solutions showed that 78% of 4565 kidneys preserved in University of Wisconsin (UW) solution had good immediate function, which was significantly better than those achieved with Collins' (74%) or Euro‐Collins' solutions (68%) (p<0.01). The 1‐year graft survival rale was significantly better with UW (83%) or Collins' (81%) solutions than with Euro‐Collins (78%) solution.
Neurological complication following cyclosporin therapy – A case report
Authors: Koh M. K. , Habib N.
Published: September 2024

Cyclosporin therapy is now the mainstay of immunosuppression in allotransplants. The past decade has seen a vast improvement in the clinical outcome of transplant patients. We have also learned more about the properties and side effects of cyclosporin. Numerous publications in the past have highlighted these side effects and toxic manifestations. We wish to report on a bizarre neurological complication of cyclosporin therapy following orthotopic liver transplantation. The neurological complication manifested itself as migratory focal epilepsy and hyperacusis. Withdrawal of cyclosporin therapy promptly resulted in cessation of the above symptoms.
An assessment of the need for the voiding cystourethrogram for urologic screening prior to renal transplantation
Authors: Shandera K. , Sago A. , Angstadt J. , Peretsman S. , Jaffers G.
Published: September 2024

A retrospective review of the records of 450 patients who were evaluated for renal transplantation was undertaken to determine whether a voiding cystourethrogram (VCUG) influenced the surgical care of the recipient. Three hundred and forty eight of these patients proceeded to transplantation, with 333 of them receiving a VCUG as part of their evaluation. A urologic abnormality was identified by VCUG in 51 individuals, 19 of whom had a known urologic abnormality as the etiology of their renal disease. None of the other 32 patients with abnormalities discovered by VCUG required surgical correction. In the remaining 282 patients the VCUG was normal. The VCUG is not essential for the preparation of potential recipients for renal transplantation and should be utilized selectively in individuals with a history of urologic disease or when urinary tract abnormalities are identified by physical examination or an abnormal urine analysis.
Invalidation by extreme assay artefacts of immunoassayable urinary insulin as a parameter of pancreatic allograft function
Authors: Metz Stewart A. , Rabaglia Thomas C. , Rabaglia Mary E.
Published: September 2024

There are several reasons to believe that declines in pancreatic beta cell function should presage clinical rejection of pancreatic allografts; furthermore, assessments of urinary insulin might be more informative than plasma determinations to assess pancrcaticocystostomy function. However, the previous literature on urinary insulin is inconsistent. We examined endogenous insulin values, and recovery of exogenously‐added insulin in urine from control subjects and patients, before and after ultrafiltration to remove proteolytic enzymes derived from the pancreas. In patients with a pancreatic graft, major artefacts in the radioimmunoassay were found (attributable to degradation of tracer and/or antibody, presumably by proteases) which could not be obviated by ultrafiltration or other approaches. These included spuriously high endogenous “insulin” levels, and virtually total inability to recover authentic insulin added to PxTx (pancreas transplant) urine. These findings raise significant doubts about the validity of most previous studies on urinary insulin (or other markers for pancreatic rejection) based on the use of immunoassay measurements.
Hypoglycemic symptoms following pancreas transplantation
Authors: Larsen Jennifer L. , Stratta Robert J. , Miller Suzanne A. , Taylor Rodney J.
Published: September 2024

Vascularized pancreas transplantation (PTx) with non‐portal venous drainage results in peripheral hypcrinsulinemia which may predispose to hypoglycemia. The incidence and pattern of hypoglycemic symptoms following PTx was characterized in our patient population to determine if hypoglycemia could be a significant problem. A total of 54 PTx recipients (49 combined pancreas‐kidney, 4 pancreas alone, and 1 pancreas after kidney) were surveyed 2 to 33 months post‐transplant. Twenty‐nine of 54 PTx recipients (54%) reported symptoms of hypoglycemia at any time following their transplant operation. Of those reporting hypoglycemic symptoms, most had very few episodes (26/29 had ≤ 1–3/month). The symptoms were reported as occurring before meals or at night in 10 (34.5%), post‐prandial in 10 (34.5%), both pre‐ and postprandial in 1 (3.5%), and or with no specific pattern in 8 (27.5%). Only 12 of 29 tried to document blood glucose during any episode. Of those 12, only 5 documented a blood glucose during the episode of less than 60 mg/dl although another 5 documented a blood glucose from 60–70 mg/ dl. The PTx recipients with hypoglycemic symptom episodes had a lower body mass index (BMI), a longer post‐PTx time interval, a lower prednisone dose (alt p≤0.01), a lower glycohemoglobin (p = 0.0196) and a higher fasting glucagon (p = 0.035) compared to recipients without symptoms. In summary, symptoms of hypoglycemia were reported by 54% of PTx recipients, but the symptoms, when present, were infrequent. The recipients reporting symptoms were less likely to be insulin‐resistant (longer post‐PTx, lower BMI, and on lower doses of prednisone). Although hypoglycemia was documented during some episodes, no glucose concentration was available for most episodes of hypoglycemic symptoms so the incidence of actual hypoglycemia among PTx recipients is still unknown.
Removal of FK 506 by continuous hemofiltration: Report of two allograft recipients with renal and liver failures
Authors: Hopp Laszlo , Lombardozzi Susan , Gilboa Nisan , Ellis Demetrius , Shapiro Ron , Scantlebury Velma , Webb Marc , Weichler Nancy , Warty Vijay S. , Venkataramanan Raman
Published: September 2024

We report the cases of 2 organ allograft recipients whose abnormally high FK506 plasma levels were successfully reduced by continuous hemofiltration. The 1st patient, a renal allograft recipient, developed posttransplantation lymphoproliferative disease, liver failure and anuric renal failure during FK 506 rescue therapy. The 2nd patient, the recipient of a bilateral lung and heart allograft, developed multiorgan failure following repeated episodes of therapy‐resistant hypotension. The plasma FK 506 concentrations in both patients remained elevated despite cessation of the drug for several days. In the first patient the FK 506 plasma concentration remained high despite 4 d of hemodialysis. During continuous hemofiltration of the 1st patient and continuous hemodiafiltration of the 2nd patient, the half‐life of FK 506 in the plasma decreased by a factor of 20 and 5 times, respectively. These cases suggest that continuous hemofiltration or hemodiafiltration may be effective in reducing toxic concentrations of FK 506 in the plasma. The 1st case also implies that continuous hemofiltration may be a viable alternative when hemodialysis fails to provide appropriate drug clearance.
Evaluation of Doppler ultrasound in primary non‐function of renal transplants
Authors: Phillips Aled O. , Deane Colin , O'Donnell Patrick , Bewick Michael , Hillis Andrew N.
Published: September 2024

Doppler ultrasound investigation was performed in the renal grafts of 86 patients with primary non‐function following cadaveric renal transplantation. Pulsatility Index, defined as:

urn:x-wiley:09020063:ctrbf01006:equation:ctrbf01006-math-0001 was assessed to examine its predictive use in the diagnosis of rejection episodes as judged by a retrospective analysis of histological data. Altogether 415 Doppler examinations and 228 renal biopsies were performed. In our population the incidence of rejection was 57%. Using a pulsatility index (PI) > 1.8 to be indicative of rejection, the sensitivity of our lest was 68% for vascular rejection and 65% for all rejection episodes. The specificity was 25%. We conclude that Doppler ultrasound cannot replace the need for transplant renal biopsy in patients with primary non‐function.
Recurrent renal thrombotic angiopathy after kidney transplantation in two patients with primary antiphospholipid syndrome (PAPS)
Authors: Mondragón‐Ramírez G. , Bochicchio T. , Garcia‐Torres R. , Amigo M. C. , Martinez‐Lavin M. , Reyes P. , Herrera‐Acosta J.
Published: September 2024

Renal artery and venous thrombosis and thrombotic microangiopathy have been related to PAPS. This condition may lead to end‐stage renal disease (ESRD). We present 2 patients with PAPS and ESRD who received a living unrelated kidney transplant. Despite intensive anticoagulant therapy, the disease recurred in the grafts.
Effect of prolonged delayed graft function on long‐term graft outcome in cadaveric kidney transplantation
Authors: Yokoyama Itsuo , Uchida Kazuharu , Kobayashl Takaaki , Tominaga Yoshihiro , Orihara Akira , Takagl Hiroshi
Published: September 2024

One‐hundred‐and‐twenty‐six cadaveric renal transplantations were analyzed for the effect of post‐transplant renal function on graft outcome. Thirty‐one grafts functioned immediately after transplantation (Group 1), 54 grafts failed to function temporarily up to 8 posttransplant days as evidenced by urine output <400 ml/day or hemodialysis support (Group 2), 33 grafts showed temporary nonfunction >8 days (Group 3) and 8 grafts never functioned (group 4). Five‐year graft failure rates were 6.5% (2/31), 13.0% (7/54). 42.4% (14/33) and 100% (8/8) for Groups 1. 2, 3 and 4, respectively. Actuarial 5‐year graft survivals were 89.4%. 84.8%. 50% and 0% for Groups 1. 2, 3 and 4, respectively (p<0.05). The most common cause of graft failure was the chronic rejection in 13, of which 9 were in Group 3. Acute rejection episodes during the first 3 months post‐transplant in Group 3 (15 of 33, 45.5%) was slightly higher than that in Group 1 (10 of 30. 33.3%) or Group 2 (19 of 54. 35.2%) but the differences were not significant. Acute rejection episodes were associated with graft loss only 1 of 19 (5.3%) patients in Group 2 whereas 9 of 15 (47.4%) were seen in Group 3. The authors conclude that prolonged DGF is associated with a higher incidence of graft failure, particularly secondary to chronic rejection after 1 year posttransplant. Moreover, acute rejection based on prolonged DGF probably plays a major role in the development of chronic rejection.
Pilot evaluation of 15‐deoxyspergualin for refractory acute renal transplant rejection
Authors: Matas Arthur J. , Gores Paul F. , Kelley Susan L , Bielefield‐Skrokov Mariana , Kinaszczuk Michael , Gruessner Rainer W. G. , Najarian John S.
Published: September 2024

15‐deoxyspergualin (DSG) is a novel immunosuppressant which has been shown to be effective in preventing and treating rejection in animal allo‐ and xenotransplant models. Preliminary clinical studies suggest that DSG is an effective antirejection agent. In our study, 4 patients with biopsy‐proven rejection episodes that were resistant to steroid and antibody therapy were then treated with DSG. All 4 rejection episodes responded to DSG therapy and all 4 kidneys continue to function (follow–up 7‐15 months). However, 2 patients had additional rejection episodes after DSG therapy. Side effects during DSG treatment were minimal; 1 patient, who had also had multiple courses of antibody, developed a lymphoproliferative tumor 2 months after DSG administration. We conclude that DSG is effective in treating refractory renal transplant rejection episodes. Additional studies are necessary to determine the ideal place for DSG in treating renal transplants recipients with rejection.
Distal tubular acidosis induced by FK506
Authors: Heering P , Ivens K , Aker S , Grabensee B
Published: September 2024

This study was designed to investigate the effect of tacrolimus (FK506) and of cyclosporine (CSA) on tubular function in renal graft recipients. Patients were randomised after renal transplantation to immunosuppressive treatment with FK506 (n = 8) or CSA (n = 8). Patients had a mean age of 45.7 ± 3.4 yr; there was no difference in age, sex, HLA status or CMV mismatches. Neither was there any difference in the frequency of episodes of acute kidney failure between the groups, nor was there a significant difference in the frequency of episodes of kidney rejection within the first year. The mean FK506 level at the time lay at 14.7 ± 14.4 ng/mL whole blood, and the mean CSA level at the time of study was 162± 25 ng/mL whole blood. We performed renal function studies 6 months after transplantation: Cins CPAH NaHCO, loading, and Na2SO4 loading. There was no significant impairment of GFR in patients treated with FK506 with 53.6±2.5 mL/min as compared to 586 mL in group 2. Plasma renin activity (0.6±0.4 ng/mL vs 2.3±3; p <0.01) and aldosterone (69 ±17 vs 157±28.2 pg/mL; p<0.05) were significantly decreased during treatment with FK506. Fractional HCO3 excretion was low in both groups, indicating that bicarbonate reabsorption in the proximal nephron was unimpaired. Distal renal tubular acidosis was demonstrated in 4 patients of group 1 but in only 1 of group 2. Potassium levels were slightly increased in patients treated with FK506 (5.4±0.2 mmol/L) as compared to cyclosporine (4.9±0.3 mmol/L; p<0.05). Distal hydrogen ion secretion, evaluated by the ability to increase urinary PCO, in a highly alkaline urine, was impaired in patients treated with FK506 (U‐B pCO2: 16.1±4 vs 36 ± 5.8; p<0.05) as compared to patients treated with CSA. The maximum acidification capability (NAE) was slightly lowered during therapy with FK506 (67.5±11.8 versus 86.6± 16.5 μmol/min, ns). We conclude that FK506 administration results in a decrease in the rate of hydrogen ion secretion by the collecting tubules. This defect was disclosed by the finding of a subnormal pCO2 in a highly alkaline urine. These results show that FK506 is able to induce distal tubular acidosis. Distal tubular acidosis is part of FK506 induced nephrotoxicity, the pathogenesis of this type of hyperkalemic metabolic acidosis found in patients treated with FK506 after renal transplantation has to be further elucidated.
Serum total homocysteine concentration does not predict outcome in renal transplant recipients
Authors: Dimény Emöke , Hultberg Björn , Wahlberg Jan , Fellström Bengt , Arnadottir Margret
Published: September 2024

Established cardiovascular risk factors such as hypercholesterolemia have been claimed to adversely influence the outcome of renal transplants. The aim of the present study was to assess the effect of another risk factor, hyperhomocysteinemia, on graft outcome. This was relevant for two reasons; hyperhomocysteinemia is by now recognized as an independent risk factor for the development of atherosclerosis and it is highly prevalent in both dialysis patients and renal transplant recipients. The serum concentration of total homocysteine (tHcy) was analyzed in samples collected before transplantation in 81 patients and at 6 months after transplantation in 57 of these patients. Before transplantation, mean tHey was 33.2±19.2 μmol/L and the prevalence of hyperhomocysteinemia was 94%. Six months after transplantation. mean they was 27.7±14.6 μmol/L and the prevalence of hyperhomocysteinemia was 88%. The patients were followed up for 5 yr. Six months and 5 yr after transplantation, serum creatinine concentration and endogenous creatinine clearance were determined. After 6 months, allograft biopsy was evaluated. Neither prenor post‐transplant tHey was found to influence patient or graft survival, graft function or histopathology. Thus, tHey does not seem to predict either short‐term or long‐term outcome of renal transplantation.
Management of recipients of hepatic allografts harvested from donors with malignancy diagnosed shortly after transplantation
Authors: Detry Olivier , Honoré Pierre , Jacquet Nicolas , Meurisse Michel
Published: September 2024

Transmission of undiagnosed malignancy with the graft is a dramatic complication of liver transplantation. Alternatives in the management of the recipients of livers, harvested from donors with malignancy diagnosed shortly after transplantation, are either early re‐transplantation or close follow‐up without re‐operation. We reported 4 cases of liver recipients whose allografts were harvested from donors who were diagnosed with malignancy shortly after the liver transplantation. One recipient underwent re‐transplantation, and the three other allografts were not removed. No recipient developed recurrence in the follow‐up. While graft removal may be the only way to avoid tumor recurrence in recipients of liver graft harvested from donor with malignancy, close follow‐up without re‐operation may also be considered. The risk of tumor transferral may depend on the histopathological aggressiveness and metastatic potential of the donor tumor, and may be low for low‐grade, local tumors. This risk should be evaluated by analyzing large series, using databases of Eurotransplant or United Network for Organ Sharing.
Treatments with versus without medication for children with behavioural difficulties in clinical practice: an economic evaluation with observational data
Authors: Kiernan Caitlin K. , Dijk Hermien H. , van den Hoofdakker Barbara J. , Hoekstra Pieter J. , Groenman Annabeth P.
Published: September 2024

Background

Economic evaluations of treatments for children with behavioural difficulties (i.e., characteristics of attention‐deficit/hyperactivity disorder (ADHD) and/or oppositional defiant disorder (ODD)) usually rely on data of randomised controlled trials or are model‐based. Findings of such studies may not be representative of cost‐effectiveness and cost‐utility in clinical practice. The current longitudinal study aimed to perform an economic evaluation of treatments for children with hyperactivity, impulsive behaviours, inattention, and/or behavioural difficulties using observational data that were obtained in clinical practice.

Methods

Parents of 209 children (aged 5–12) who were referred to 1 of 10 Dutch youth mental healthcare institutions and who received treatment with (n = 108) or without (n = 101) the use of medication, filled out questionnaires at three timepoints (baseline, and ~ 6 and ~12 months later). Propensity score matching was used to make both groups comparable. Outcomes included quality‐adjusted life years (QALYs), ADHD and ODD symptom severity, and impairment. Costs were measured from a societal perspective. Incremental cost‐effectiveness ratios (ICERs) were estimated, and cost‐effectiveness acceptability curves (CEACs) were derived to show uncertainty around the ICER.

Results

Results did not show statistically significant differences in costs and effects between children who were treated with medication (alone or in combination with non‐medication treatment) and those who were treated without medication. CEAC suggested that medication treatment has a 55% probability of being cost‐effective at the €80,000 threshold and 36% at the €20,000 threshold compared with treatment without medication.

Conclusions

Using observational data, our study did not provide clear evidence of the cost‐effectiveness and cost‐utility of treatment with medication compared with treatment without medication in clinical practice.
Get unbent! R tools for the removal of arching and bending in fish specimens for geometric morphometric shape analysis
Authors: Arbour Jessica Hilary
Published: September 2024

Geometric morphometrics is a powerful tool for studying fish body shape; however, body posture can be a hindrance to these analyses. Here I introduce new R language tools for correcting multiple types of bending of 3D data based on the TPS suite (geometric morphometric software) “unbend specimens” methodology. In a sample dataset of darters, these R tools adequately accounted for posture artifacts otherwise evident across multiple principal component axes. I hope these new tools will facilitate the incorporation of 3D landmark data into the comparative analysis of fish body shape.
Use of cardiac cell cultures from salmonids to measure the cardiotoxic effect of environmental pollutants
Authors: Krebs Torben , Bauer Julia , Graff Sarah , Teich Lukas , Sterneberg Markus , Gebert Marina , Seibel Henrike , Seeger Bettina , Steinhagen Dieter , Jung‐Schroers Verena , Adamek Mikolaj
Published: September 2024

Environmental stressors such as micro‐ and nanosized plastic particles (MNPs) or crude oil have a detrimental effect on aquatic animals; however, the impact upon the cardiovascular system of fish remains relatively under‐researched. This study presents a novel approach for investigating the effect of crude oil and MNPs on the cardiac system of fish. We used salmonid larvae and cardiac cell cultures derived from hearts of salmonid fish and exposed them to environmental stressors. Following exposure to plastic particles or crude oil, the larvae exhibited some variation in contraction rate. In contrast, significant alterations in the contraction rate were observed in all cardiac cell cultures. The greatest differences between the control and treatment groups were observed in cardiac cell cultures derived from older brown trout. Following 7 days of exposure to MNPs or crude oil in Atlantic salmon larval hearts or cardiac cell cultures, there were only minor responses noted in mRNA expression of the selected marker genes. These findings show the use of a novel in vitro technique contributing to the existing body of knowledge on the impact of MNPs and crude oil on the cardiovascular system of salmonids and the associated risk.
Harnessing Plant Growth–Promoting and Wilt‐Controlling Biopotential of a Consortium of Actinomycetes and Mycorrhizae in Pigeon Pea
Authors: Dave Anand , Ingle Sanjay , Perveen Kahkashan , Bukhari Najat A. , Sayyed Riyaz , Mastinu Andrea
Published: September 2024

Fusarium‐induced wilt significantly affects the cultivation and yield of pigeon peas. This warrants sustainable disease management while promoting plant growth. The present study investigated the biopotential of coinoculation of Streptomyces pseudogriseolus S‐9 and Rhizophagus irregularis for plant growth promotion and mitigation of the impact of Fusarium wilt on pigeon pea over three seasons at pot and field levels. Pigeon pea plants were subjected to Fusarium wilt stress and treated with different inoculation strategies, including single and combined applications of S. pseudogriseolus S‐9 and R. irregularis. Plant growth parameters and yields were assessed to evaluate the efficacy of the coinoculation. In the pot experiment, T‐6 treatment resulted in the longest root (62.56 ± 0.01 cm) and shoot (70.24 ± 0.01 cm) lengths compared to the application of commercial biofungicide T‐8 (Trichoderma). This treatment also significantly influenced the yield of potted plants. It resulted in the highest fresh root weight (62.27 ± 0.01 g), fresh shoot weight (70.24 ± 0.02 g), maximum root (55.25 ± 0.01 g) and shoot dry weights (52.25 ± 0.01 g). In the field experiment, pigeon pea plants treated with the bioinoculant also demonstrated a substantial increase (р ≤ 0.05) in total grain yield, the weight of 100 grains, and the number of filled grains compared to the control group in all experimental seasons. In vitro, antagonism assay of compatibility of mycorrhizae and bacteria showed good activity using powder formulation. Thus, the consortium application inspired the broad application of Streptomyces and Trichoderma as effective bioinoculants for wilt management and yield improvement in pigeon peas.
Assessing the phenology and reproductive output of loggerhead turtles in relation to climatic variables at Patara Beach, Türkiye
Authors: Şirin A. , Başkale E.
Published: September 2024

Loggerhead turtles (Caretta caretta), being ectothermic organisms, could be especially susceptible to climate change effects, and may exhibit climate‐related variation in their reproductive behaviours such as phenology, annual nest numbers, clutch size, hatching success, incubation period and sex ratio. This study investigated the reproductive phenology and outputs of loggerhead turtles and their relationships with climatic variables over a 5‐year period (2019–2023) at Patara Beach, Türkiye. We found significant fluctuations in atmospheric temperature, sea surface temperature and relative humidity, and that female turtle emergences on Patara Beach could temporarily adjust their phenology in response to these minor environmental changes. We highlight the importance of understanding the impacts of phenological shifts on the ability to satisfy the conditions over the nesting season that determine reproductive output. Our statistical analyses also showed that increasing sea water temperatures and atmospheric temperatures, as well as decreasing precipitation and relative humidity, had direct and/or indirect effects on the nesting phenology and reproductive output of loggerhead turtles. The findings from this study indicate that atmospheric temperature significantly affected incubation period, hatching success rate, the number of dead embryos and the number of empty eggshells. Additionally, relative humidity had a significant impact on the incubation period and the number of empty eggshells. In this context, rising temperatures led to drier nest conditions, decreased incubation periods and increased nest temperatures, resulting in higher proportions of female offspring. In conclusion, there are still gaps in our understanding of the effects of climate change on the reproductive biology of loggerhead turtles, and more studies are needed at both the Mediterranean and global scales to better understand these effects.
A landscape analysis of investors in the global breast milk substitute industry to target for advocacy
Authors: Wood Benjamin , Robinson Ella , McCoy David , Baker Phillip , Sacks Gary
Published: September 2024

The International Code of Marketing of Breast‐milk Substitutes and subsequent resolutions (the Code) was adopted to address increases in mortality and morbidity resulting from the practices of the breast‐milk substitute (BMS) industry. The lack of success in ensuring company compliance with the Code has prompted advocates to consider engaging with investors to shape the governance of BMS companies. To support these efforts, this paper aimed to identify prominent investors in the global BMS industry and explore their Code‐related policies and practices. Using multiple methods and data sources, we developed a novel approach to identify and rank investors in the world's leading publicly listed BMS companies. We also examined the policies and voting behaviour of a sample of investors using publicly accessible materials from 2020 to 2022. We found that a small number of large investors, led by BlackRock and Vanguard, hold a substantial share in the global BMS industry. Of the top‐10 ranked investors, only Norway's Government Pension Fund (NBIM) reported policy information relating specifically to BMS marketing. Most of these large investors also opposed the sample of public health‐related shareholder proposals analysed. In addition, we identified several investors that have reported engaging with BMS companies on Code‐related issues, including NBIM, Pictet, and UBS, along with several potential investor targets for future advocacy efforts, including some North American public pension funds. The inclusion of Code‐related issues as part of broader policies, disclosures and regulations related to environmental, social and governance oriented investment warrants increased attention.