bluuebunny/crossref_metadata_2025 huggingface dataset:
Apolipoprotein molecular variation in Moroccan Berbers: pentanucleotide (TTTTA)n repeat in the LPA gene and APOE‐C1‐C2 gene cluster
Authors: Harich N , Esteban E , López‐Alomar A , Chafik A , Moral P
Published: March 2003

Apolipoprotein LPA, APOE, APOC1, and APOC2 genotype frequencies have been determined for the first time in a North African population. A sample of 140 Berber individuals from the Moroccan Moyen Atlas region has been analyzed. Allelic and haplotypic data have been used to compare our sample with other world populations and the results clearly differentiate Berbers from Europeans and Sub‐Saharans, suggesting several distinctive features of Moroccan Berbers as the extreme high values of LPA PNR*11 pentanucleotide allele (10.5%) and the relatively high and low values of APOE*E4 (15.7%) and *E2 (4.5%) in comparison to other Mediterraneans. Another remarkable result is the frequency distribution of the two APOC2 alleles (70% vs 30%) in comparison with the European pattern (50% of each allele). The high values of APOE*E4 and LPA PNR*7 together with the intermediate linkage disequilibrium values between APOE and APOC1 alleles in comparison with Europeans and Africans suggest a certain degree of Sub‐Saharan influence in the current Moroccan population.
Ring syndrome caused by ring chromosome 7 without loss of subtelomeric sequences
Authors: Vermeesch JR , Baten E , Fryns J‐P , Devriendt K
Published: March 2003

Ring chromosome 7 is an unusual chromosome anomaly. Here we describe a patient with ring chromosome 7 and we show that both subtelomeres are still present. The diagnosis agrees with ‘ring syndrome’. This report helps to further delineate the clinical manifestations of ‘ring syndrome’ and to distinguish the phenotypic consequences of the presence of a ring chromosome 7 from the phenotypic consequences of terminal chromosome 7 submicroscopic deletions.
X‐linked recessive Menkes disease: identification of partial gene deletions in affected males
Authors: Poulsen L , Horn N , Heilstrup H , Lund C , Tümer Z , Møller LB
Published: March 2003

Poulsen L, Horn N, Heilstrup H, Lund C, Tümer Z, Møller LB. X‐linked recessive Menkes disease: identification of partial gene deletions in affected males.  Clin Genet 2002: 62: 449–457. © Blackwell Munksgaard, 2002

Menkes disease is an X‐linked recessive lethal disorder of copper metabolism, caused by defects in the ATP7A gene. Partial gene deletions comprise about 15% of the mutations causing Menkes disease. We have previously demonstrated identification of partial ATP7A deletions in patients by Southern blot analysis. In the present study, we report the use of three fast and reliable polymerase chain reaction (PCR)‐based methods for the identification of partial ATP7A deletions in Menkes disease patients. First we demonstrate the use of multiplex PCR, a fast method for identification and rough localization of partial gene deletions, in which two exons of ATP7A are coamplified. Second, we present PCR amplification of genomic DNA across the deletion junctions, a method enabling identification of the deletion breakpoints and hence the exact size of the deletion. Finally, application of reverse transcription PCR (RT‐PCR) for identification and localization of gene deletions at the cDNA level is demonstrated. By studying the mutation at the cDNA level the predicted effect of the mutation on the amino acid sequence and consequently the protein structure and function can be inferred. We demonstrate characterization of partial gene deletions in five patients, and in three of these we were able to determine the breakpoint sequences.
FOXC2 truncating mutation in distichiasis, lymphedema, and cleft palate
Authors: Bahuau M , Houdayer C , Tredano M , Soupre V , Couderc R , Vazquez M‐P
Published: March 2003

Bahuau M, Houdayer C, Tredano M, Soupre V, Couderc R, Vazquez M‐P. FOXC2 truncating mutation in distichiasis, lymphedema, and cleft palate.  Clin Genet 2002: 62: 470–473. © Blackwell Munksgaard, 2002

We report a family showing autosomal‐dominant segregation of upper‐ and lower‐eyelid distichiasis (double row of eyelashes) in seven affected relatives over three generations, in addition to below‐knee lymphedema of pubertal onset (lymphœdema prœcox) in three. Two children had cleft palate in addition to distichiasis, but without the previously reported association with the Pierre–Robin sequence. Other ophthalmologic anomalies included divergent strabismus and early‐onset myopia. This family was found to be completely linked to markers mapped to 16q24.3 and thereby proposed to be allelic to the distichiasis–lymphedema syndrome (DL, MIM 153400), although pterygium colli, congenital heart disease, or facial dysmorphism were not features found here. As FOXC2/FKLH14 mutations were found to underlie DL and diverse hereditary lymphedema conditions, this gene was examined by sequence analysis. An out‐of‐frame deletion (914–921del) was identified and found to segregate with the disease, further highlighting the phenotypic heterogeneity of lymphedema conditions linked to FOXC2 truncating mutations. Whether such heterogeneity is related to genotype–phenotype correlation, a hypothesis not primarily supported by the apparent loss‐of‐function mechanism of the mutations, or governed by modifying genes, remains to be determined.
Calcineurin inhibitor‐induced chronic nephrotoxicity in liver transplant patients is reversible using rapamycin as the primary immunosuppressive agent
Authors: Cotterell Adrian H , Fisher Robert A , King Anne L , Gehr Todd W B , Dawson Sherfield , Sterling Richard K , Stravitz R Todd , Luketic Velimir A , Sanyal Arun J , Shiffman Mitchell L , Posner Marc P
Published: March 2003

Abstract: The purpose of this study was to determine whether calcineurin inhibitor (CNI)‐induced chronic nephrotoxicity in liver transplant patients is reversible by replacement of the CNI with rapamycin as the primary immunosuppressive agent. CNIs, while providing potent immunosuppression for liver transplant patients, exhibit nephrotoxicity as a major side‐effect. Whereas acute CNI‐induced nephrotoxicity is reversible by withdrawal of the CNI, chronic nephrotoxicity due to CNIs is a progressive process thought to be irreversible. Eight liver transplant patients with CNI‐induced chronic nephrotoxicity were converted to rapamycin as the primary immunosuppressive agent. The CNI was either discontinued (four patients) or the dosage lowered to maintain a subtherapeutic level (four patients). Renal function as assessed by serum creatinine was measured before and after conversion to rapamycin. Two patients progressed to dialysis dependence following conversion to rapamycin. These two patients had been on CNIs for a mean of 112 months (range 93–131 months) prior to conversion to rapamycin. Five patients experienced improvement in renal function. These patients had been on calcineurin inhibitors for a mean of 60 months (range 42–75 months) prior to conversion. One patient with chronic nephrolithiasis as a contributing factor to his renal dysfunction has progressed to dialysis dependence despite conversion to rapamycin following exposure to a CNI for 24 months. In the five patients with improved renal function, serum creatinine levels decreased significantly (2.4 ± 0.3 mg/dL to 1.5 ± 0.1 mg/dL, p < 0.05) by a mean of 7.2 months (range 5–10 months) after conversion from CNI to rapamycin‐based immunosuppression. Liver function remained stable after conversion to rapamycin. CNI‐induced chronic nephrotoxicity can be reversed upon withdrawal of the CNI. Rapamycin is an effective replacement agent as primary immunosuppressive therapy following withdrawal of CNIs in liver transplant patients with CNI‐induced chronic nephrotoxicity.
Utility of CT angiography for evaluation of living kidney donors
Authors: Slakey Dp , Florman S , Lovretich J , Zarifian Aa , Cheng Ss
Published: March 2003

We reviewed our initial experience with helical computed tomography (CT) angiography in the evaluation of living kidney donors which, until now, has necessitated arteriography. Nineteen donors (12 women, 7 men) have had their renal anatomy evaluated solely by CT angiography preoperatively.All scans demonstrated normal collecting systems and single ureters. Five donors (26%) had supernumerary renal arteries. Fourteen donors had single, 4 donors had two, and 1 donor had three renal arteries. Helical CT demonstrated small polar vessels in several donors. Two donors (10%) had supernumerary renal veins. Accuracy of vascular anatomy defined on CT was 90% when confirmed at operation. Anatomically all CT findings were consistent with operative findings except in 1 donor who was found to have a 0.8 cm lesion near the renal hilum.At our institution, the total charges for selective renal arteriography are $3845 and for helical CT with three‐dimensional (3‐D) reconstruction are $1546. The amount of contrast dye (approximately 100 mL) is equivalent. Patients uniformly reported that the CT scan was a convenient and painless procedure.The accuracy of helical CT angiography is equivalent to arteriography in assessing renal vascular anatomy (with the additional benefit of imaging venous and parenchymal anatomy). Charges for helical CT are 59% less. There is greater patient acceptance and potentially less morbidity associated with the non‐invasive nature of helical CT. We believe that CT angiography is the radiologic procedure of choice for the assessment of renal anatomy in potential living kidney donors.
Pseudoaneurysm of the superior mesenteric artery with an arteriovenous fistula after simultaneous kidney–pancreas transplantation
Authors: Khan Taqi F Toufeeq , Ciancio Gaetano , Burke Iii George W , Sfakianakis George N , Miller Joshua
Published: March 2003

Vascular complications remain a significant source of morbidity after pancreatic transplantation. We describe a pseudoaneurysm of the superior mesenteric artery (SMA) with an arteriovenous fistula (AVF) involving the SMA and the superior mesenteric vein (SMV) discovered and treated surgically in the second week after kidney–pancreas transplantation. The patient experienced pain over the graft, and subsequent radionuclide and Doppler ultrasound scan were suggestive of a pseudoaneurysm in the head of the pancreas. Awaiting confirmatory angiography, the patient became hypotensive and after resuscitation, underwent emergency surgery when a pseudoaneurysm was found in the head of the pancreas. After looping the proximal and distal recipient iliac artery and base of the donor Y vascular graft, the AVF was separated and ligated. The SMV was dissected off the pancreatic head and repaired over a tamponading intraluminal Foley catheter. Graft function was preserved. Based on this experience, an AVF with or without a pseudoaneurysm in the pancreas allograft should be corrected as soon it is suspected.
Severe late acute allograft rejection in a child after living‐related auxiliary partial orthotopic liver transplantation for ornithine transcarbamylase deficiency
Authors: Komatsu H , Inui A , Fujisawa T , Sogo T , Miyagawa Y , Inui M , Uemoto S , Inomata Y , Tanaka K
Published: March 2003

Auxiliary liver transplantation (ALT) is known to correct liver‐based metabolic disorders. However, it remains unclear whether the presence of a native liver influences the long‐term prognosis of ALT for metabolic diseases. We reported on a 4‐yr‐old girl who had undergone living‐related auxiliary partial orthotopic liver transplantation (APOLT) for ornithine transcarbamylase deficiency and experienced severe late acute rejection 18 months after liver transplantation, during weaning of immunosuppressive agents. Results of histological analysis of the graft indicated very severe acute rejection (rejection activity index, 9/9), and computed tomography revealed graft liver atrophy. These observations suggest the possibility that severe rejection might occur in APOLT, especially during weaning of immunosuppression.
Improved survival after bone marrow transplantation for early leukemia using busulfan–cyclophosphamide and individualized prophylaxis against graft‐versus‐host disease: a long‐term follow‐up
Authors: Aschan Johan , Carlens Stefan , Hägglund Hans , Klaesson Sven , Mattsson Jonas , Remberger Mats
Published: March 2003

To minimize immunosuppression, allow a graft‐versus‐leukemia (GVL) effect, and reduce relapse incidence, 73 leukemic recipients of human leukocyte antigens‐identical sibling marrow were given graft‐versus‐host disease (GVHD) prophylaxis based on the estimated risk of GVHD development. Methotrexate (MTX) monotherapy was given to patients with an estimated low risk of developing GVHD, whereas MTX+cyclosporine (CsA) was given to ‘high‐risk’ patients. After engraftment, CsA was discontinued, and weekly MTX was reinstituted and given until 3 months post‐bone marrow transplant. Conditioning consisted of busulfan (BU)+cyclophosphamide (CY) (n=35) or CY+total body irradiation (TBI) (n=38). Retrospective controls were given CY+TBI and MTX+CsA (n=39). The median observation time was 5 yr 11 months. Chronic GVHD increased to 53% in the individual BU+CY group and 46% in the individual CY+TBI group, compared to 25% in the control group (p=0.05). This increase was restricted to the limited form. The actuarial relapse incidence decreased to 20% in the individual BU+CY group, compared to 52% in the control group, p=0.03. In the individual CY+TBI group, the relapse incidence was 44% (n.s. versus controls, p=0.04 versus individual BU+CY). The 5‐yr relapse‐free survival (RFS) in the individual BU+CY group was 66%, in the control group, 41% (p=0.07), and in the individual CY+TBI group, 45% (p=0.1 versus individual BU+CY). Patients with early leukemia in the individual BU+CY group had a RFS of 83%, compared to 44% in the control group (p=0.02) and 42% in the individual CY+TBI group (p=0.01). In the multivariate analysis, advanced leukemia beyond first complete remission and first chronic phase and conditioning with CY+TBI were correlated to poor RFS. In summary, the individualized prophylaxis itself did not reduce the relapse incidence. However, in patients with early leukemia conditioning with BU+CY, our method of individualizing the GVHD prophylaxis might be of value, since this group had the best RFS in this study.
Bronchiolitis obliterans organizing pneumonia associated with Pneumocystis carinii infection in a liver transplant patient receiving tacrolimus
Authors: Kleindienst Roman , Fend Falko , Prior Christian , Margreiter Raimund , Vogel Wolfgang
Published: March 2003

We report on a case of bronchiolitis obliterans organizing pneumonia (BOOP) associated with Pneumocystis carinii pneumonia (PCP) after liver transplantation and tacrolimus based immunosuppression.
Radiologically, bilateral diffuse interstitial shadowing and patchy alveolar infiltrates developed after switching the patient from cyclosporin A to tacrolimus for persistent rejection. Bronchoalveolar lavage (BAL) fluid showed inflammatory cells but no pathogenic organisms. Open lung biopsy revealed BOOP with granulomatous PCP. Thus, even in the case of negative BAL the possibility of an atypical P. carinii infection has to be considered for differential diagnosis of pneumonia in immunocompromised patients after organ transplantation. The combination of BOOP with PCP after liver transplantation and tacrolimus medication has not been reported previously.
Pulmonary Rhizopus infection in a diabetic renal transplant recipient
Authors: Demirag A , Elkhammas Ea , Henry Ml , Davies Ea , Pelletier Rp , Bumgardner Gl , Dorner B , Ferguson Rm
Published: March 2003

Infectious complications after renal transplantation remain a major cause of morbidity and mortality. Mucormycosis is a rare infection in renal transplant recipients; however, mortality is exceedingly high. Risk factors predisposing to this disease include prolonged neutropenia, diabetes, and patients who are immunosuppressed (Singh N, Gayowski T, Singh J, Yu LV. Invasive gastrointestinal zygomycosis in a liver transplant recipient: case report and review of zygomycosis in solid‐organ transplant recipients, Clin Infect Dis 1995: 20: 617). Life‐threatening infections can occur, as this fungus has the propensity to invade blood vessel endothelium, resulting in hematological dissemination. We report a case of cavitary Rhizopus lung infection, 2 months after renal transplantation, where the patient was treated successfully with Amphotericin B and surgical resection of the lesions with preservation of his allograft function. In this era of intensified immunosuppression, we may see an increased incidence of mucormycosis in transplant population. Invasive diagnostic work‐up is mandatory in case of suspicion; Amphotericin B and, in selected cases, surgical resection are the mainstays of therapy.
Preliminary experience with midodrine in kidney/pancreas transplant patients with orthostatic hypotension
Authors: Hurst George C , Somerville Kenneth T , Alloway Rita R , Osama Gaber A , Stratta Robert J
Published: March 2003

In an effort to ameliorate the problem of orthostatic hypotension in pancreas transplant patients, current medical management consists of maximizing the patient's hydration, altering antihypertensives, increasing sodium intake, initiation of fludrocortisone, compression stockings, and behavioral modifications. Despite these medical interventions, a subset of patients remains symptomatic. Midodrine (ProAmatine®), an alpha‐adrenergic agonist, was approved for the treatment of symptomatic orthostatic hypotension in the US. This preliminary report attempts to assess the safety and efficacy of midodrine use in kidney/pancreas (KP) or pancreas alone (PA) transplant recipients. A retrospective review was performed of 7 KP and 1 PA recipient experiencing symptomatic postural hypotension after maximizing other medical treatments. Blood pressure, serum creatinine (SrCr), and objective responses to postural hypotension were assessed at routine intervals. Pre‐midodrine monitoring revealed a mean orthostatic change in systolic blood pressure from sitting to standing of 43 mmHg (range 20–100 mmHg). Patients received a mean starting midodrine dose of 18 mg/d, which was titrated to a maximum dose of 30 mg/d. Systolic blood pressure monitoring revealed a mean orthostatic change of 27 mmHg (range 0–81 mmHg) after initiation of treatment with midodrine and a mean follow‐up of 3.2 months. All study patients reported improvement in symptoms of orthostatic hypotension. SrCr was not affected based upon comparison of pre‐treatment and current SrCr values of 1.4 and 1.3 mg/dL, respectively. The most common side effect experienced was supine hypertension. These preliminary results suggest that midodrine is safe and effective in transplant recipients; however, the dosage should be titrated to symptomatic relief or a maximum dose of 30 mg. Careful monitoring for supine hypertension is necessary.
Are lipid‐dependent indicators of cardiovascular risk affected by renal transplantation?
Authors: Schena Antonio , Di Paolo Salvatore , Morrone Luigi F , Resta Francesco , Stallone Giovanni , Schena F Paolo
Published: March 2003

Hyperlipoproteinemia has been reported to frequently occur in kidney transplanted patients, thus possibly explaining, at least in part, the increased incidence of cardiovascular disease in this population. To evaluate the impact of renal transplantation (Tx), and related immunosuppressive therapy, on plasma lipoprotein and Lp(a) profile, we selected a cohort of kidney transplanted patients (36 M/14 F; age 33.8±12.0 yr, range 13–62) lacking significant causes of hyperlipidemia. All patients received a triple immunosuppressive regimen and showed a stable renal function after Tx (plasma creatinine: 1.36±0.35 mg/dL). One year after Tx, we found a significant increase of total cholesterol (TC), LDL, HDL, ApoB and ApoA‐I (p<0.005), while plasma triglyceride levels remained unmodified. Lp(a) plasma levels after Tx were within the normal range and displayed a significant inverse relationship with apo(a) size. Noteworthy, LDL/HDL ratio and ApoB/ApoA‐I ratio in kidney transplanted patients were almost superimposable with those of normal controls. Specifically, LDL/HDL ratio significantly decreased in 64% of patients after Tx, due to a prevalent increase of HDL, and was associated with a moderate amelioration of plasma TG. In a multiple linear regression model, post‐Tx HDL level was significantly related to recipient's age, gender, BMI and cyclosporine (CyA) trough levels (Adj‐R2=0.35, p=0.0002), with gender and CyA trough levels being the better predictors of HDL. In conclusion, immunosuppressive regimens, in themselves, do not appear to significantly increase the atherogenic risk related to lipoproteins. Rather, other factors can affect the lipoprotein profile and its vascular effects in renal transplant recipients.
Flow cytometry crossmatching as a predictor of acute rejection in sensitized recipients of cadaveric renal transplants
Authors: O'rourke Robert W , Osorio Robert W , Freise Chris E , Lou Calvin D , Garovoy Marvin R , Bacchetti Peter , Ascher Nancy L , Melzer Juliet S , Roberts John P , Stock Peter G
Published: March 2003

Flow cytometry crossmatching (FCXM) was developed as a more sensitive assay than the standard complement‐dependent cytotoxicity crossmatch (CDCXM) for the detection of anti‐donor antibodies, that mediate hyperacute rejection and graft loss in the early post‐transplant period in renal transplant recipients. The role of FCXM in predicting long‐term clinical outcome in renal allograft recipients is unclear. This study examines the role of FCXM in predicting long‐term clinical outcome in highly sensitized recipients of cadaveric renal transplants. All patients (n=100) with peak panel reactive antibody (PRA) levels>30%, who received cadaveric renal transplants between 1/1/’90 and 12/31/’95 at our institution, were divided into FCXM+ and FCXM− groups. The incidence of acute rejection was determined for each group during the first yr after transplant. Graft survival rates at 1, 2, and 3 yr, and creatinine levels were also compared between groups. FCXM+ patients experienced a higher incidence of acute rejection during the first yr after transplant (69 vs. 45%), and a higher percentage of FCXM+ patients had more than one episode of acute rejection during the first yr after transplant (34 vs. 8%) when compared to FCXM− patients. There was no statistically significant difference in 1‐, 2‐, or 3‐yr graft survival between FCXM+ and FCXM− patients (76 vs. 83, 62 vs. 80, 62 vs. 72%, respectively). These results suggest that sensitized FCXM+ cadaveric renal transplant recipients have a higher incidence of acute rejection episodes in the first yr after transplant. Given the association of multiple rejection episodes with poor long‐term allograft survival, FCXM may be a useful predictor of long‐term clinical outcome in this sub‐group of renal transplant recipients.
Improved outcome of pulmonary aspergillosis in heart transplant recipients with early diagnosis and itraconazole treatment
Authors: Utili Riccardo , Zampino Rosa , De Vivo Fabrizio , Maiello Ciro , Andreana Augusto , Mormone Gennaro , Marra Claudio , Tripodi Marie‐Francoise , Sarnataro Giuseppe , Cione Piera , Cuccurullo Susanna , Cotrufo Maurizio
Published: March 2003

Pulmonary aspergillosis is a severe complication in heart transplant recipients. The drug of choice for this infection is amphotericin B, but its use is limited because of its side effects. We observed six cases of pulmonary aspergillosis in a group of 200 patients who had received heart transplants from January 1988 to January 1999. Predisposing factors such as previous rejection, neutropenia and/or cytomegalovirus reactivation were present in all patients. The clinical presentation was characterized by fever and a non‐productive cough. X‐rays showed monolateral or diffuse infiltrate with or without nodular lesions. The median interval between symptoms and diagnosis was 5 d (range 4–7). Diagnosis was made by culturing trans‐tracheal aspirate samples.Aspergillus fumigatuswas isolated in 3 patients andA. nigerin the other 3. All patients were treated with itraconazole at 200–400 mg/day for 20–60 d and all recovered. One patient treated with the lowest dosage for the shortest term had a recurrence after 1 month and needed a second 30‐day course of itraconazole at a higher dosage. No significant side effects were registered. Itraconazole is effective in the therapy of pulmonary aspergillosis, particularly when an early diagnosis is made.
Outcome for arterio‐venous fistula at the elbow for haemodialysis
Authors: Revanur Vasanth K , Jardine Alan G , Hamilton David H , Jindal Rahul M
Published: March 2003

Background: Few studies have examined the outcome of arterio‐venous fistulas (AVF) at the elbow for haemodialysis.  Methods: All AVFs at the elbow created between 1994 and 1998 were identified retrospectively from case notes and the computerised database. Patients were followed until fistula failure, death, or for a minimum of 6 months until June 1999. Life table analysis and Kaplan–Meier actuarial curves with the log rank test were used to assess the influence of age, sex, diabetes, hypertension, heart disease, cerebrovascular disease, use of erythropoietin, aspirin or warfarin, previous insertion of subclavian vein catheter and the levels of haemoglobin and serum albumin on long‐term AVF survival.  Results: A total of 137 AVFs (primary procedure in 84 and as a secondary procedure in 53 cases) at the elbow were performed in 130 patients; 7 patients had AVFs attempted at both elbows. The mean age was 56.57 yr with a mean follow‐up of 48.54 months. Twenty‐two patients died with a functioning AVF, while 7 patients also with a functioning AVF received a renal transplant. Overall 74% of AVF were patent at the end of 1 yr, while 22.5% failed or did not mature immediately after the procedure. Two patients had their AVFs tied off due to steal syndrome. Of the various factors known to affect long‐term survival of AVF in patients receiving haemodialysis, only plasma albumin> 35 g/L was associated with poorer long‐term patency in our study.  Conclusion: Our report supports the view that AVF at the elbow may obviate the disadvantages of AVF at the wrist in elderly patients, females and in diabetics. In this group of patients it may be preferable to create a primary AVF at the elbow rather than the wrist. Patients who have a failed attempt at creating an AVF at the wrist should undergo AVF at the elbow before the placement of a synthetic graft. This strategy will result in saving time and avoid multiple operations. There may also be a reduction in the use of synthetic grafts resulting in cost savings and avoiding the complications associated with synthetic grafts.
A prospective economic evaluation of basiliximab (Simulect®) therapy following renal transplantation
Authors: Lorber Marc I. , Fastenau John , Wilson David , DiCesare Joseph , Hall Michael L.
Published: March 2003

Background: Immunoprophylaxis with basiliximab (Simulect®), an anti‐interleukin‐2‐receptor (anti‐IL‐2R; CD25) chimeric monoclonal antibody, has been demonstrated to significantly reduce the incidence of acute cellular rejection in adult renal allograft recipients (32% vs. placebo, p<0.01).  Methods: An economic evaluation was conducted as part of a U.S. multi‐center, randomized, double‐blind, placebo‐controlled clinical trial comparing basiliximab plus dual immunosuppressive therapy (cyclosporine modified [Neoral®] and corticosteroids) to dual therapy alone. Healthcare resources utilized by the 346 subjects in the ‘intent‐to‐treat’ population were prospectively collected over the 1‐yr study period. Direct medical costs were determined for all hospitalizations, outpatient provider visits, procedures (excluding the initial transplant procedure), laboratory and diagnostic tests, and immunosuppressants, including basiliximab when administered.  Results: Total first‐year medical costs were lower for the basiliximab group than for the placebo group ($28 927 vs. $32 300, difference=$3373), although this difference was not statistically significant. First‐year hospital costs for treating acute rejection were also lower for the basiliximab group ($9328 vs. $10 761, difference=$1433); however, this difference did not achieve statistical significance. Importantly, the efficacy analysis demonstrated a significant reduction in the incidence of acute rejection (38 vs. 55%, p<0.01) in the basiliximab arm, and this was accomplished without increasing the overall cost of care. Fewer basiliximab‐treated patients (8 vs. 15%, p=0.03) were hospitalized. This observation suggested less serious illness and reduced treatment costs among basiliximab‐treated patients, because the overall incidence of infection was similar between the groups. The adverse event profile of patients receiving basiliximab was clinically and economically indistinguishable from that of those treated with placebo.  Conclusion: Induction immunosuppression with basiliximab, combined with cyclosporine modified and corticosteroids, was therapeutically beneficial and contained medical costs during the initial post‐transplant year.
The role of percutaneous biopsy in detection of pancreatic transplant rejection
Authors: Lee Brett C , McGahan John P , Perez Richard V , Boone John M
Published: March 2003

The purpose of this study was to investigate the effectiveness and safety of percutaneous pancreatic transplant biopsy guided by ultrasound alone or with a combination of computerized tomography (CT) for pancreas localization and ultrasound for needle placement. We also compare our finding on the use of 18‐gauge and 20‐gauge needles for percutaneous pancreatic transplant biopsy.  In 42 attempted biopsies performed on 21 patients, two different imaging modalities were used. Twenty‐seven attempted biopsies were performed under the guidance of ultrasound alone, and 15 used a combination of ultrasound and CT. Of the 27 ultrasound‐guided biopsies, 24 produced at least one sample adequate for histopathological analysis for an 89% biopsy success rate. Of the 15 biopsies guided by combined ultrasound and CT, 11 produced adequate samples for a 73% success rate. For all biopsies, an 83% success rate was found.  In assessing the use of 18‐gauge versus 20‐gauge needles, 86 out of 110 tissue cores were adequate for histopathological analysis for a 78% yield. In 27 biopsy attempts using the 18‐gauge needle, 75 tissue cores were obtained, for an average of 2.8 cores per biopsy. Fifty‐seven pancreas samples collected using the 18‐gauge needle were adequate for pathological evaluation for a 76% yield. With 15 biopsy attempts using the 20‐gauge needle, 35 tissue cores were collected, for an average of 2.3 cores per biopsy. Twenty‐nine pancreas specimens obtained from using the 20‐gauge needle were adequate for analysis for an 83% yield.  No major complications occurred. Only one incidence of minor complication was reported for a 2% complication rate. The only complication was local, mild bleeding at the biopsy site in one case. Air within the transplant pancreas as revealed by post‐biopsy scans and streaky density appearing adjacent to the biopsy site occurred in a total of four cases and were not included. No complications were reported that required any invasive intervention.  We conclude that percutaneous biopsy guided by ultrasound is a safe, simple, and effective method to detect pancreatic transplant rejection. Our results for biopsies compare favorably with other reported techniques in terms of effectiveness, complication rates, and ease of use. With its high success rate and low complications, ultrasound‐guided percutaneous biopsy is an excellent method to sample pancreatic transplant.
A calcineurin inhibitor‐sparing regimen with sirolimus, mycophenolate mofetil, and anti‐CD25 mAb provides effective immunosuppression in kidney transplant recipients with delayed or impaired graft function
Authors: Chang George J , Mahanty Harish D , Vincenti Flavio , Freise Chris E , Roberts John P , Ascher Nancy L , Stock Peter G , Hirose Ryutaro
Published: March 2003

Delayed graft function (DGF) after renal transplantation is a significant risk factor for early acute rejection and graft loss. Sirolimus (SRL) can be administered in the setting of DGF without exacerbating the impaired renal function after transplantation. We examined a calcineurin‐sparing regimen using SRL during the early post‐operative period in renal transplant patients with delayed or impaired graft function.  A retrospective review of 14 consecutive kidney transplant recipients with delayed or impaired graft function who received SRL was performed. The immunosuppressive regimen consisted of daclizumab induction (2 mg/kg), SRL (5–15 mg load followed by 2–5 mg daily maintenance therapy), corticosteroids, and mycophenolate mofetil (MMF, 1.5–3 g/d). Patients were monitored for allograft function, acute rejection, graft survival, thrombocytopenia, and leukopenia. Serum levels of SRL were determined by high‐performance liquid chromatography performed at an independent commercial laboratory.  Donors were cadaveric in 13 cases and living related in one. The duration of follow‐up was 0.5–5.2 months. Nine patients required hemodialysis after transplantation. The mean time to initiation of calcineurin inhibitors was 21±13 d. Average serum creatinine levels at the initiation of SRL and at 1 month after transplantation were 8.4±2.7 and 2.1±1.2 mg/dL, respectively. There were 2 patients (14%) who experienced acute rejection within the first month after transplantation – 1 with type I (steroid therapy) and 1 with type II (anti‐thymocyte therapy). Serum levels of SRL were initially undetectable in the 2 patients with acute rejection. No grafts were lost during the period of follow‐up. Three patients developed thrombocytopenia (platelets <100×109) and no patients developed leukopenia. The combination of SRL with anti‐CD25 mAb, MMF, and corticosteroids appears to provide effective non‐nephrotoxic immunosuppression for kidney transplantation without the need for a lymphocyte‐depleting regimen. However, it is important to monitor serum SRL levels to determine the optimal dosing regimen. Furthermore, long‐term follow‐up of these patients will be helpful to determine whether improved immunosuppression can be achieved with a fully calcineurin‐sparing regimen using SRL.
The differences between late graft loss group and long‐term graft survival group in renal transplantation
Authors: Tanaka Toshiyuki , Takahara Shiro , Hatori Motoaki , Toki Kiyohide , Wang Jing‐Ding , Permpongkosol Sompol , Yazawa Koji , Kokado Yukito , Oka Kazumasa , Kyo Masahiro , Okuyama Akihiko , Yamanaka Hidetoshi
Published: March 2003

Tanaka T, Takahara S, Hatori M, Toki K, Wang J‐D, Permpongkosol S, Yazawa K, Kokado Y, Oka K, Kyo M, Okuyama A, Yamanaka H. The differences between late graft loss group and long‐term graft survival group in renal transplantation. Clin Transplantation 2001: 15 (Supplement 5): 16–21. ©Munksgaard, 2001

In renal transplantation, the long‐term graft survival rate has not been improved. Until now, the differences between late graft loss and long‐term graft survival have still not been estimated thoroughly. We have attempted to define clinical risk factors and parameters for late graft loss by comparing the differences in these two groups. Data from the Osaka University Database were assessed on 156 renal allografts during a 7‐yr period. Thirty‐six patients comprised the late graft loss group (patients in this group had graft function without need for dialysis for more than 3 yr post‐transplantation, afterwards lost the allograft: ‘loss group’). One hundred and twenty patients comprised the long‐term graft survival group (patients in this group had graft function without need for dialysis until 31 December 1999: ‘survival group’). Various immunological and non‐immunological parameters were included in an univariate regression analysis. This analysis showed that donor age (P < 0.01), HLA mismatch number (P < 0.01) and a repeat of acute rejection (P < 0.01) were significant factors. Serum creatinine levels at 3 months (P=0.01), proteinuria at 1 yr (P < 0.01) and antihypertensive treatment at 2 yr (P=0.03) after transplantation were predictive of the risk of late graft loss. CsA trough concentration at 3–6 months (P < 0.05) and body mass index increase at 1 yr (P=0.046) were elevated in the loss group. These results from a single centre suggest that immunological as well as non‐immunological factors are associated with the pathogenesis of late graft loss.
Clinical and pathological assessment of acute vascular rejection in the transplant kidney
Authors: Koike Junki , Yamaguchi Yutaka , Horita Shigeru , Tanabe Kazunari , Fuchinoue Shohei , Toma Hiroshi , Nihei Hiroshi
Published: March 2003

Koike J, Yamaguchi Y, Horita S, Tanabe K, Fuchinoue S, Toma H, Nihei H. Clinical and pathological assessment of acute vascular rejection in the transplant kidney. Clin Transplantation 2001: 15 (Supplement 5): 41–44. ©Munksgaard, 2001

Acute vascular rejection (AVR) in kidney transplan‐ tation is the most important factor influencing graft prognosis. We focus on patients whose grafts were lost because of AVR, and assessed their clinical characteristics and histological findings of biopsied renal grafts. Biopsied specimens exhibited AVR in 43 patients who underwent kidney transplantation in the Kidney Center of Tokyo Women’s Medical University from 1995 to 1999. In the follow‐up from 1 to 5 yr (median: 2.5 yr) we classified these patients into three groups: favourable prog‐ nosis group (FPG), relatively poor prognosis group (RPPG) and poor prognosis group (PPG). Light microscopic study for histological grading of acute rejection according to the Banff scheme and detection of the C4d complement deposition on peritubular capillaries by the immunofluorescence method were performed. Based on the results, the donors of RPPG and PPG were significantly older than those of FPG, and all factors of acute rejection according to the Banff scheme were not statistically significantly different among the three groups. However, an acute tubular injury mimicking acute tubular necrosis (ATN) was observed in the biopsy specimens from PPG. In conclusion, an older donor is a risk factor of poor prognosis of the graft with AVR, and acute tubular injury mimicking ATN is one of the important features that enables the prediction of graft failure originating from AVR in kidney transplantation.
Factors in older cadaveric organ donors impacting on renal allograft outcome
Authors: Verran Deborah J , DeLeon Cristy , Chui Albert K , Chapman Jeremy R
Published: March 2003

Transplantation of renal allografts (RA) from older donors has become more common, despite conflicting data on outcome between reports from large series versus individual centres. Factors other than donor ageper semay contribute to RA outcome.  The outcome of RA procured from 114 older donors over 55 yr of age in NSW, between 1990 and 1997, was analysed. Corresponding donor factors, including demographics, medical history, inotrope use, major hypotension and findings at procurement, were also analysed.  Of the potential RA, 8% were discarded and the remainder transplanted. Factors significantly associated with renal discard were pre‐transplantation donation biopsy abnormality (p<0.001) and a history of cardiovascular (CV) disease in the donor (p<0.02). Donor aortorenal atherosclerosis (AS; p<0.09) and a donor age of 65 yr or older (p<0.08) were common in the discard group. The never function rate was 7.6% and was associated with a history of a discarded partner kidney (p<0.05). The delayed graft function rate was 33% and was associated with a history of donor CV disease. At a median follow up of 5 yr, the death censored allograft failure rate was 24%. Allograft failure was associated with a history of donor hypertension (p<0.05). Donor AS (p<0.7) tended to have been more common in the allograft failure group.  A number of cadaveric organ donor factors documented at procurement may be associated with inferior outcome of RA. These include biopsy abnormality, history of donor CV disease and history of donor hypertension. A donor age of 65 yr or older or significant visible aortorenal AS may also be factors.  This retrospective review of kidneys procured from 114 older cadaveric organ donors identifies factors apart from donor age, which may have a negative impact on both allograft utilisation and outcome. Theses factors include renal biopsy abnormality, history of donor CV disease, discard of a partner kidney and donor hypertension. Visible AS in the donor aorta documented at renal procurement may also be a factor.
Influence of diabetes mellitus on patient and graft survival in recipients of kidney transplantation
Authors: Revanur Vasantha K , Jardine Alan G , Kingsmore David B , Jaques Brian C , Hamilton David H , Jindal Rahul M
Published: March 2003

Aims. To investigate the outcomes in patients who have pre‐existing diabetes and those who develop post‐transplant diabetes mellitus (PTDM).  Methods. We retrospectively reviewed the charts of 939 patients who received a first functioning renal transplant in the cyclosporine (CyA) era between 1984 and 1999.  Results. Sixty‐six (7%) patients had renal failure due to insulin‐dependent diabetes mellitus (IDDM) and 7 (0.8%) patients due to non‐insulin‐dependent diabetes mellitus (NIDDM). Ten (1.1%) patients had coexistent diabetes and 48 (5.1%) recipients developed PTDM. The mean graft survival for the patients with PTDM was 9.7 yr versus 11.3 yr for the non‐diabetic patients, while mean graft survival was 10.1 yr for patients with IDDM and 2.9 yr with NIDDM and 8.3 yr for those with coexistent diabetes (p=ns). However, there was a statistically significant difference in patient survival between patients who developed PTDM and in those who did not develop this complication. The mean survivals of patients with IDDM, NIDDM, coexistent diabetics and PTDM were 8.4, 3.7, 8.6 and 10.3 yr, respectively. The mean survival of the patients without pre‐existing diabetes or PTDM was 12.8 yr (p<0.001). The survival of patients older than 55 yr with PTDM was no different to the control group. However, in those younger than 55 yr, PTDM was associated with a higher risk of death (relative risk of 2.54, p<0.001). Fifty percent of patients with IDDM developed acute rejection episodes, whereas rejection rate was 57.1% in NIDDM group, 50.0% in the PTDM group, 20.0% in the coexistent diabetes group and 44.3% in the control group (p=ns).  Conclusion. Patient survival, but not graft survival, was adversely affected by both pre‐existing diabetes and by PTDM, particularly in those with an age less than 55 yr.
The use of intravenous tacrolimus and mycophenolate mofetil as induction and maintenance immunosuppression in simultaneous pancreas–kidney recipients with previous transplants
Authors: Ciancio Gaetano , Miller Joshua , Burke George W
Published: March 2003

Clinical trials using quadruple immunosuppression that include the combination of tacrolimus (TAC) and mycophenolate mofetil (MMF) have been shown to reduce the incidence of acute rejection episodes in simultaneous pancreas–kidney (SPK) transplantation. In attempting to obtain a low rejection rate without antibody induction therapy, we proceeded with the combination of TAC intravenous (i.v.), MMF, and steroids as induction therapy and as primary immunosuppression for recipients with previous transplants. In this study, we analyzed 10 patients who received previous transplants, treated with low‐dose TAC i.v. as induction therapy. Group A consisted of 6 patients with previous transplants that underwent SPK and group B consisted of four recipients with previous SPK that underwent cadaveric kidney transplants. For group A, the previous transplants were: living related kidney (LRK) followed by islet cell (IC) transplant (n=2), LRK transplant (n=1), cadaver kidney (CAD) and IC transplant (n=1), SPK (n=1), and three previous CAD kidney transplants (n=1). In group A, all six kidneys were lost due to recurrent diabetic nephropathy, IC possibly to rejection, and the pancreas due to thrombosis. In group B with previous SPK transplants, three recipients lost their kidney to chronic rejection and one to long‐term use of a nephrotoxic antibiotic. Currently, in all group A and B patients, the kidney and the pancreas are functioning, although 1 patient in group A developed type 2 diabetes (normal fasting C‐peptide). Two patients in group A developed three rejection episodes that responded to steroid treatment. The results indicate the TAC i.v. in combination with oral TAC, MMF, and steroids offer effective induction therapy in patients with previous transplants.
Long‐term (≥20 yr) status of 14 cadaveric kidney‐transplant recipients
Authors: Delclaux Caroline , Morel Delphine , Fernandez Philippe , Merville Pierre , Deminière Colette , Potaux Luc
Published: March 2003

The aim of this study was to analyze the status of patients with a successful long‐term (≥20 yr) kidney graft.   Nineteen (8.1%) of the 234 recipients who received a cadaveric kidney transplant between 1968 and 1978 in our center are still alive 21.7±1.6 yr (mean±standard error of the mean) later with a functioning allograft. Function, including measurement of the renal functional reserve (RFR), histological status, and morbidity were evaluated.   Fourteen patients agreed to participate in this study. Their current immunosuppressive regimens combined prednisone (P)+azathioprine (AZA) (n=9), P+AZA+cyclosporine (CsA) (n=3) or P+CsA (n=2). Although they described their quality of life as good, 10 patients had mild hypertension, 5 developed 10 malignancies (9 cutaneous), 5 had replicative hepatitis, 8 had osteopenia, and 6 had cataracts, but none had diabetes mellitus. Proteinuria was detected in 6 patients, but was always less than 1 g/d. Mean serum creatinine was 1.28±0.28 mg/dL and glomerular filtration rate was 54.5±5.3 mL/min/1.73 m2. RFR was present for 4 patients with a mean value of +14.8±1.9 mL/min. Their functional status was not correlated with the histological lesions observed in concomitant transplant biopsies.   Kidney grafts are able to function well even more than 20 yr post‐transplantation, with some having a RFR whose significance remains unknown. Morbidity is of minor clinical severity, but could be further reduced with optimized management. Moreover, transplantation is much less costly than hemodialysis.
Sequential measurement of human herpesvirus 6 DNA with polymerase chain reaction method in pediatric living‐related liver transplantation
Authors: Hasegawa Toshimichi , Kimura Takuya , Sasaki Takashi , Okada Akira , Tanaka‐Taya Keiko , Miyagawa Hiromi , Amou Kiyoko , Mushiake Sohtarou , Yamanishi Koichi , Ishikawa Shirou
Published: March 2003

Background: Human herpesvirus 6 (HHV‐6), a causative virus of exanthem subitum, may occasionally present with a severe clinical form in immunosuppressed patients after transplantation. In this study, HHV‐6 DNA was sequentially measured with a polymerase chain reaction (PCR) method, a quick and sensitive modality in pediatric living‐related liver transplantation (LTx).   Methods: Subjects consisted of 5 post‐operative biliary atresia patients undergoing living‐related LTx at ages from 8 months to 4 yr. Immunosuppression was performed with Tacrolimus (blood trough level 8–18 within 1 month and 5–10 ng/mL thereafter) and low‐dose steroid. Specimens were peripheral blood mononuclear cells (PBMC), plasma, and liver biopsy tissue. The amount of HHV‐6 DNA was semiquantified as follows: 1+, 1–10; 2+, 10–100; 3+, 100–1000; 4+, over 1000 copies/105 PBMCs.   Results: A total of 69 blood samples and three liver biopsies were provided for the examination. HHV‐6 DNA in PBMC was positive in 2 donors and 3 recipients before LTx. Two patients with negative DNA were converted to 3+ at 2–3 wk after LTx and 3 with positive DNA remained 2+ to 3+ throughout the post‐LTx period. Only 1 patient developed clinical symptoms, such as fever, liver dysfunction, petechiae, idiopathic thrombocytopenic purpura, and finally bone marrow suppression. HHV‐6 DNA in the liver biopsy tissue and plasma in this patient were 4+ and 2+, respectively.   Conclusion: HHV‐6 DNA in PBMC measured by the PCR method may be persistently high in pediatric recipients after living‐related LTx. Although HHV‐6 DNA in PBMC may be positive in case of evident infection, positivity in PBMC may not be always associated with the clinical symptoms.