bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between G−308A polymorphism of the tumor necrosis factor‐α gene and 24‐hour ambulatory blood pressure values in type 1 diabetic adolescents
Authors: Krikovszky D , Vásárhelyi B , Tóth‐Heyn P , Körner A , Tulassay T , Madácsy L
Published: March 2003

Krikovszky D, V´s´rhelyi B, Tóth‐Heyn P, Körner A, Tulassay T, Madácsy L. Association between G−308A polymorphism of the tumor necrosis factor‐α gene and 24‐hour ambulatory blood pressure values in type 1 diabetic adolescents.  Clin Genet 2002: 62: 474–477. © Blackwell Munksgaard, 2002

Tumor necrosis factor‐α (TNF‐α) is an inflammatory cytokine, which also influences blood pressure (BP). The G−308A polymorphism of the TNF‐α gene is associated with altered TNF‐α production. The prevalence of the TNF‐α−308A allele is reportedly higher among patients with type 1 diabetes mellitus (T1DM) than in the healthy population. In this study we investigated whether this genetic polymorphism might correlate with BP values in diabetic adolescents. Ambulatory BP monitoring (ABPM) was performed in 126 adolescents with T1DM (mean age: 14 ± 2.4 years). The TNF‐α G−308A genotype was determined by using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methodologies. ABPM results were related to healthy reference values and are given as standard deviation score (SDS). The prevalence of the −308A allele was higher in diabetic adolescents than the Hungarian reference population (0.26 vs 0.14, p < 0.01). TNF‐α genotype was associated both with systolic and diastolic BP values (p < 0.01 and p < 0.01, respectively). In patients with TNF‐α−308GG and −308GA/AA genotypes, the 24‐h systolic BP average values were 0.37 ± 1.33 and −0.38 ± 1.28 SDS, while 24‐h diastolic BP average values were 0.09 ± 1.30 and −0.67 ± 1.31 SDS. Hence, the TNF‐α−308A allele carrier state appears to be associated with lower systolic and diastolic BP values.
Prevalence and ethnic differences of autosomal‐dominant cerebellar ataxia in Singapore
Authors: Zhao Y , Tan EK , Law HY , Yoon CS , Wong MC , Ng I
Published: March 2003

Zhao Y, Tan EK, Law HY, Yoon CS, Wong MC, Ng I. Prevalence and ethnic differences of autosomal‐dominant cerebellar ataxia in Singapore.  Clin Genet 2002: 62: 478–481. © Blackwell Munksgaard, 2002

We report the prevalence and ethnic differences of autosomal‐dominant cerebellar ataxia (ADCA) in Singapore. Amongst 204 patients with ataxia who underwent genetic testing for dentatorubral‐pallidoluysian atrophy (DRPLA) and for spinocerebellar ataxias (SCA) 1, 2, 3, 6, 7, 8, 10 and 12, 58 (28.4%) patients from 36 families tested positive. SCA 3 was identified in 31 (53.4%) patients from 15 families, SCA 2 in 17 (29.3%) patients from 12 families and SCA 1 in four (6.9%) patients from four families. Other SCA subtypes were rare. SCA 2 was the only subtype identified amongst ethnic Malay and ethnic Indian families. The estimated prevalence of ADCA in Singaporean families was at least 1 : 27,000. Based on the history and ancestry of Singaporeans, our study supported a founder effect for specific SCA subtypes and the association of ethnicity‐specific SCA subtypes. Our findings suggest that SCA 2 is relatively common amongst the Malay race and that priority testing for SCA 3 and SCA 2 for ethnic Chinese, and SCA 2 for ethnic Malay, may be cost effective and relevant for the region.
Analysis of urinary donor‐derived DNA in renal transplant recipients with acute rejection
Authors: Zhang Zhihong , Ohkohchi Nobuhiro , Sakurada Masatoshi , Mizuno Yutaka , Miyagi Shigehito , Satomi Susumu , Yamaguchi Masaaki , Okazaki Hajime
Published: March 2003

Abstract: In renal transplantation we usually diagnose an acute rejection by based on the results of a needle biopsy; however, this takes time and findings in some cases are not definite. We analysed the urine of renal recipients for the presence of donor DNA in an attempt to establish a diagnostic means of acute rejection. Sixty‐four renal transplant recipients were examined. Thirty‐seven patients had no trouble after transplantation and 22 patients developed acute rejection, diagnosed based on serum creatinine levels and/or needle biopsy findings of the graft. Five patients had drug‐induced renal dysfunction. In female recipients with a male graft we examined urine for the presence of Y‐chromosome (SRY and DYZ‐1) and in recipients receiving a HLA mismatched graft we investigated the HLA‐DR gene (DRB1) by the polymerase chain reaction (PCR) method. Among female recipients with a male graft there were 14 patients with stable renal function and SRY and DYZ‐1 on Y‐chromosome were negative in 13 (93%) and positive in one, whereas SRY and DYZ‐1 of urine were positive in the four female patients with acute rejection and these DNA fragments disappeared in three after rejection therapy. One patient was subjected to haemodialysis. Among 23 recipients of a graft from HLA mismatched donors with stable renal function, DRB1 was negative in 21(91%). Among 18 patients with acute rejection DRB1 was positive in 16 (93%) and negative in two. These DNA fragments disappeared in 13 patients after rejection therapy. In all patients with drug‐induced renal dysfunction donor‐derived DNA was negative. Presence of donor‐specific DNA in the urine of the recipient is associated strongly with acute rejection and analysis of DNA derived from donor cells in urine might be an effective and accurate method for the diagnosis of acute rejection of a renal transplant.
A randomized trial of surgical antimicrobial prophylaxis with and without vancomycin in organ transplant patients
Authors: Pfundstein J , Roghmann M‐C , Schwalbe Rs , Qaiyumi Sq , McCarter Jr Rj , Keay S , Schweitzer E , Bartlett St , Morris Jr Jg , Oldach Dw
Published: March 2003

Background. Gram‐positive organisms, including vancomycin‐resistant enterococci (VRE), have emerged as major pathogens on the organ transplant service at our institution. We hypothesized that our use of vancomycin as part of routine surgical prophylaxis increased the risk of VRE colonization and infection; conversely, there was concern that failure to use vancomycin prophylaxis would increase peri‐operative morbidity due to gram‐positive organisms.Methods. Renal transplant recipients (n=88) were randomized to receive either a) vancomycin/ceftriaxone or b) cefazolin; and pancreas transplants (n=24) to receive either a) vancomycin/gentamicin or b) cefazolin/gentamicin. Stool samples or rectal swabs were obtained for culture for enterococci within 24 h of transplantation and weekly while hospitalized.Results. Enterococci were isolated on stool culture from 38 (34%) of 102 patients at the time of transplantation; 4 (11%) of the isolates were VRE. The percentage of patients who subsequently acquired VRE was low (1–7% per wk) but remained constant during hospitalization. There was no association between new VRE detection and vancomycin use for either prophylactic or therapeutic purposes. Forty‐four patients (39%) had a post‐operative infection with 46% of these infections due to gram‐positive organisms; rates were unaffected by prophylactic vancomycin use. Pancreas transplant patients who did not receive vancomycin prophylaxis had a significantly longer initial hospitalization (p=0.03); however, differences were not statistically significant when total length of stay (LOS) within the first 90 d of transplantation was compared.Conclusions. Vancomycin surgical prophylaxis does not appear to have an effect on VRE colonization or infection, or on rates of infection with gram‐positive bacteria. Elimination of vancomycin prophylaxis in renal transplant patients may be a reasonable part of an overall program to limit vancomycin usage, although as a single measure, its impact may be minimal. Vancomycin surgical prophylaxis may be of greater importance in pancreas transplants.
Clostridium difficile colitis after kidney and kidney‐pancreas transplantation
Authors: West M , Pirenne J , Chavers B , Gillingham K , Sutherland Der , Dunn Dl , Matas Aj
Published: March 2003

Objective – To determine the timing and risk factors involved in the development of Clostridium difficile (CD) colitis in kidney and kidney‐pancreas transplant recipients.Summary background data – The incidence of CD colitis after kidney and kidney‐pancreas transplantation has not been studied in detail. The question of whether the immunosuppressed transplant recipient is more prone to CD colitis and its complications (i.e., megacolon, perforations) and the risk factors involved have not been determined.Methods – We retrospectively reviewed our experience in kidney and kidney‐pancreas recipients who received transplants between January 1, 1985 and December 31, 1994. We divided these recipients into three groups: pediatric kidney recipients, adult kidney recipients, and kidney‐pancreas recipients. For each group, we assessed the timing of infection, primary disease, colitis treatment, and any concurrent complications or risk factors.Results – Of 1932 transplants, 159 recipients developed post‐transplant CD colitis. 132 charts were available for review. Forty‐three pediatric kidney recipients developed CD colitis. Their mean age was 3.2 yr; 74% (n=37) of them developed their colitis during their initial hospital stay, with the mean timing of infection being 33 d. Forty‐one (95%) had undergone intra‐abdominal placement of the graft, with renal artery anastomoses to the aorta.Fifty adult kidney recipients developed CD colitis. Thirteen (26%) developed colitis during their initial hospital stay, with the mean timing of infection (for all adult kidney recipients) being 15 months.Thirty‐nine kidney‐pancreas recipients developed CD colitis. Mean timing of infection was 6 months.The overall incidence of CD colitis was 8%, with 16% in the pediatric kidney group, 15.5% in the kidney‐pancreas group, and 3.5% in the adult kidney group. The difference in mean timing of infection was significant between the three groups (p<0.001 for pediatric versus adult kidney recipients, p=0.002 for pediatric kidney versus kidney‐pancreas recipients, and p=0.2846 for adult kidney versus kidney‐pancreas recipients).Conclusion – The incidence of CD colitis is increased in pediatric kidney and kidney‐pancreas recipients. Young recipient age (<5 yr), female gender, treatment of rejection with monoclonal antibodies, antibiotic use, and intra‐abdominal graft placement have been shown to increase the incidence of this disease. Further studies concerning prevention in the high‐risk groups are needed.
The clinical status of cadaveric renal transplant patients treated for 10 year with cyclosporine therapy
Authors: Ponticelli Claudio , Aroldi Adriana , Elli Attilio , Montagnino Giuseppe , Vegeto Antonio , Tarantino Antonio
Published: March 2003

In this paper we assessed the clinical status of 150 cadaveric renal transplant patients who received cyclosporine without interruption for 10 yr. The mean creatinine clearance was 59.2±15.71 at 1 yr and 55.6±24.91 mL/min at 10 yr (p=0.039). Patients were subdivided into four quartiles according to the mean creatinine clearance at 1 yr. The 14 patients with the lowest quartile showed a significant decrease of creatinine clearance from the 1st to 10th year (from 31.5±5.83 to 24.8±14.00 mL/min; p=0.038) while no difference between the mean creatinine clearance at 1 and at 10 yr was found in the other three quartiles. At 10 yr, 84.6% patients needed antihypertensive therapy, a rate similar to that seen at 1 yr (81.4%). The mean plasma cholesterol (253±57.8 mg/dL) and triglyceride (197±113.1 mg/dL) at 10 yr were similar to those found at 1 yr (243±48.2 and 201±143.0 mg/dL, respectively). Most patients have a high degree of rehabilitation 10 yr after uninterrupted cyclosporine therapy and all patients but 3 were able to work.
The public's willingness to discuss their preference for organ donation with family members
Authors: Guadagnoli E , Christiansen Cl , DeJong W , McNamara P , Beasley C , Christiansen E , Evanisko M
Published: March 2003

We sought to assess the public's willingness to discuss their preference for organ donation with family members and to identify factors associated with willingness to discuss donation. We categorized individuals (N=4365) with a preference for donation according to their willingness to discuss donation and used ordinal logistic regression analysis to identify factors related to their level of willingness. About half of those who want to donate have discussed this with a family member. Others were at various stages with respect to their commitment to discuss donation. Those in the more committed stages were more likely than others to have signed an organ donor card, to have seen information about organ donation, to be male, to be white or Hispanic, to know about donation issues, and to be comfortable with the idea of their own death. The decision to donate is ultimately made by family members of a suitable candidate for donation, yet nearly half of those who wish to donate have not made their wishes known. Interventions targeted to individuals at different stages of commitment are needed so that more family members can respond in accordance with their loved one's wishes.
Does subclinical rejection contribute to chronic rejection in renal transplant patients?
Authors: Rush David N , Karpinski Martin E , Nickerson Peter , Dancea Sylvia , Birk Patricia , Jeffery John R
Published: March 2003

Renal allograft biopsies have traditionally been performed in the setting of acute graft dysfunction. However, several groups have performed graft biopsies at times of stable graft function, and more recently, after treatment of rejection episodes. Surprisingly, unequivocal histologic criteria for acute rejection have been demonstrated in a high proportion of these protocol biopsies. The Winnipeg Transplant Group has documented the high prevalence of clinically silent inflammatory infiltrates in early protocol biopsies, and demonstrated their inflammatory and cytotoxic potential by immunohistochemical and molecular biological techniques. Furthermore, in a randomized trial, our group has demonstrated that subclinical rejection, if untreated, is associated with the development of early chronic pathology and late graft dysfunction. In this overview, we will summarize the early data on subclinical allograft inflammation, present the experience of the Winnipeg Transplant Group, and discuss the possible implications of subclinical rejection on the development of chronic rejection.
Fever in liver transplant recipients in the intensive care unit 1
Authors: Singh Nina , Yee Chang Feng , Gayowski Timothy , Wagener Marilyn , Marino Ignazio R
Published: March 2003

Whether febrile illnesses in the intensive care unit (ICU) have unique spectrum, etiologies, and outcome has not been determined in liver transplant recipients. We studied 78 consecutive febrile patients over a 4‐yr period; 49% (38/78) were in the ICU and 51% (40/78) were in the non‐ICU setting. Of febrile patients in the ICU, 87% (33/38) had infection and 13% had non‐infectious etiology for fever. Seventy‐nine percent (26/33) of the infections associated with fever in the ICU were bacterial, 9% (3/33) were viral, and 9% (3/33) were fungal in etiology. Pneumonia (30%), catheter‐related bacteremia (15%), and biliary tree (9%) were the predominant sources of infections associated with fever in the ICU. Bacteremia was documented in 45% of the patients with fever in the ICU. Fifty‐three percent (20/38) of the febrile episodes in the ICU occurred during the initial post‐transplant stay, and 47% (18/38) during a subsequent readmission. Pneumonia accounted for 41% of all febrile infections during the first 7 d of ICU stay, but only 14% of those after 7 d. Febrile patients in the ICU had higher APACHE II scores (p=0.001), higher APS scores (p=0.0001), higher bilirubin (p=0.001), lower cholesterol (p=0.019), higher prothrombin time (p=0.001), were more tachycardiac (p=0.002), and were more likely to have abnormal blood pressure (p=0.001) than those in the non‐ICU setting. Twenty‐three percent of all infections in the ICU were unaccompanied by fever and 9% were accompanied by hypothermia. Mortality at 14 d (24 versus 0%, p=0.001) and at 30 d (34 versus 5%, p=0.001) was significantly higher in febrile patients in the ICU, as compared to the patients in the non‐ICU setting. These data have implications for diagnostic evaluation and management of critically ill febrile liver transplant recipients.
Rejection of peritubular capillaries in renal allo‐ and xeno‐grafts
Authors: Shimizu Akira , Colvin Robert B , Yamanaka Nobuaki
Published: March 2003

The microvasculature plays an important role in the pathogenesis of humoral‐ and cell‐mediated renal allo‐ and xeno‐graft rejection. Peritubular capillary (PTC) endothelium expresses the major histocompatibility complex (MHC) class I and II antigens in the resting phase, as does the glomerular capillary endothelium, suggesting that these cells may be major immune targets. However, the role of PTCs in renal allo‐ and xeno‐graft rejection is unclear. In this review, we discuss injury and subsequent remodeling of PTCs in both humoral‐ and cell‐mediated rejection in allo‐ and xeno‐grafts. Recent evidence suggests that PTC injury and endothelial cell death occur during both cell‐ and humoral‐mediated rejection. Severe PTC rejection contributes to deterioration of graft function and acute graft loss. The mild but recurrent form of PTC rejection is associated with progressive interstitial fibrosis and chronic rejection. Following endothelial injury, the remaining PTC endothelium activates with up‐regulation of allo‐antigens and adhesion molecules, and down‐regulation of anti‐coagulant proteins. Subsequent to this, more severe rejection and graft dysfunction occur. Therefore, a careful analysis of cellular‐ and antibody‐mediated rejection in PTCs is important in the diagnosis of rejection, prediction of graft prognosis, and in further development of new anti‐rejection therapies.
A peculiar vacuolization in the kidney transplant of a child treated with tacrolimus
Authors: Watanabe Seiji , Yamaguchi Yutaka , Hattori Motoshi , Chikamoto Hiroko , Matsumoto Naoko , Suzuki Toshiaki , Oonishi Makiko , Horita Shigeru , Tokumoto Tadahiko , Tanabe Kazunari , Shiraga Hiroshi , Toma Hiroshi , Ito Katsumi
Published: March 2003

Tacrolimus (TAC) is a useful immunosuppressive agent in the prevention of rejection. However, the blood level between its therapeutic and toxic levels is narrow such that its nephrotoxicity is a problem. Moreover, its bioavailability and pharmakokinetics are highly variable. We experienced a case of acute nephrotoxicity, in which the blood level rose about 10 times above the expected level. We found a peculiar vacuolization in the transplant biopsy specimen. This change showed a marked vacuolization of the tubular cells, suggestive of acute nephrotoxicity by TAC.
Infusion of donor spleen cells and rejection in liver transplant recipients
Authors: Scornik Juan C , Lauwers Gregory Y , Reed Alan I , Howard Richard J , Dickson Rolland C , Rosen Charles B
Published: March 2003

Intact or inactivated donor lymphoid cells have been found to downregulate the alloimmune response in a number of experimental models. We conducted a randomized, prospective, double blind, and placebo‐controlled trial to determine whether heat‐treated donor spleen cells would affect early rejection after liver transplantation. Donor spleen was obtained during organ procurement for 40 patients undergoing liver transplantation. All patients were treated with cyclosporine, azathioprine and steroids. The patients were randomized after surgery to receive either heat‐treated (45°C for 1 h) spleen cells or placebo. Patients underwent protocol biopsies at 1 wk, 4 and 12 months, or as needed. Biopsies were reviewed in a blind fashion and scored according to the Banff consensus criteria. Randomization resulted in 19 patients in the spleen cell group and 21 in the placebo group. One‐yr graft survival was 94 and 100%, respectively. Early rejection was more frequent in the spleen cell group (61 vs. 35%, p, not significant). The histopathological rejection activity index at 7 d was also higher for the patients in the spleen cell group: 39% of spleen cell treated patients had a score of 4 or higher as opposed to 5% in the placebo group (p<0.01). The mean score was 2.9±2.8 for the spleen cell group versus 1.3±1.7 for the placebo group (p=0.034). It is concluded that heat‐treated donor spleen cells given within 24 h after liver transplantation were not clinically beneficial and increased the intensity of rejection in 7‐d protocol liver biopsies.
Mycophenolate mofetil increases cytomegalovirus invasive organ disease in renal transplant patients
Authors: Sarmiento Juan M , Dockrell David H , Schwab Thomas R , Munn Stephen R , Paya Carlos V
Published: March 2003

The impact of cytomegalovirus (CMV) infection post‐transplantation is in part influenced by the degree of immunosuppression. While mycophenolate mofetil (MMF) does not increase the overall incidence of CMV infection, we have questioned whether or not it increases its severity. Using a case–control study design in which 29 renal transplant patients developed CMV disease [17 (59%) of which received azathioprine (AZA) and 12 (41%) received MMF], increases in the frequency of organ involvement with CMV (58 vs. 18%; p=0.03) and in the number of organs involved with CMV were noted in the MMF versus the AZA group (2.0 vs. 1.0; p=0.015). These results indicate that the increased immunosuppressive activity of MMF impacts the morbidity of CMV infection, thus warranting the use of effective anti‐CMV preventive regimens while patients are treated with MMF.
A tale of two kidneys – how long can a kidney transplant wait?
Authors: Tandon V , Botha Jf , Banks J , Pontin Ar , Pascoe Md , Kahn D
Published: March 2003

This paper compares early graft function (EGF) of the first transplanted kidney (group 1) with the kidney transplanted second (group 2) in kidney pairs from the same cadaver donor. Thirty‐one pairs of kidneys were harvested from cadaver donors between January 1997 and October 1998.  Each pair was transplanted using a standard technique by the same team of surgeons, one after the other, as a result of limitations in theatre time and staff availability. Incidence of acute rejection (AR), acute tubular necrosis (ATN) and need for post‐transplant dialysis was recorded for both groups, and was compared using the relevant statistical methods.  Patients in both groups were well matched for age, gender and mode of dialysis pre‐transplant. Human leucocyte antigen (HLA) matching and panel reactive antibody (PRA) status were similar in the two groups (p>0.05). Cold ischaemia time (CIT) in the two groups was 14.1±5.7 and 19.2±6.9 h, respectively, the difference being statistically significant (p<0.05). The incidence of AR was similar in the two groups. However, ATN (on renogram) was significantly more common in group 2 (p<0.05; 12 patients versus 5 patients in group 1). All patients with ATN required post‐transplant dialysis. Hospital stay was significantly prolonged in group 2 patients (p<05; 20±10.6 versus 16.3±6.2 d for group 1).  Even a relatively short increase in CIT can cause the second transplanted kidney of a pair to have a significantly higher incidence of ATN, resulting in need for dialysis and prolongation of hospital stay. Simultaneous transplantation, in areas lacking organ sharing networks, would not only improve EGF, but also improve long term graft survival. In addition, the reduced requirement for post‐transplant dialysis and a shorter hospital stay would balance any increased demand on resources.
Scanning electron microscopic analysis of endothelial cell coverage and quality in large vessels from multi‐organ donors: effects of preservation on endothelial cell integrity
Authors: Van Leeuwen Ebm , Molema G , Van Luyn Mja , De Jong Kp , Dijk F , Slooff Mjh , Ruiters Mhj , Van Der Meer J
Published: March 2003

Endothelial cell integrity (coverage and quality) of large donor vessels is important because these vessels are used for vascular reconstructions in solid‐organ transplantation. Disruption of the endothelial cell monolayer will initiate blood coagulation and may lead to thrombosis of large vessels, often resulting in the loss of the transplanted organ. Iliac arteries and veins, removed from 10 heart‐beating multi‐organ donors at the end of the donor procedure, were analyzed using scanning electron microscopy at three different time points of preservation. Endothelial cell coverage and quality were determined immediately after removal from the donor, after 10 h (time of transplantation) and 7 d storage in ‘University of Wisconsin’ cold preservation solution (UW). Endothelial cell coverage decreased during the preservation of arteries, but was maintained in veins. Storage of the veins for 7 d in plastic bags showed a decreased endothelial cell coverage compared to storage in glass vials. Early removal of the blood vessels and proper storage, free floating and in clean UW, may improve maintenance of the endothelial cell integrity. These findings may be important in order to reduce the risk of thrombosis and, consequently, organ failure after transplantation. Furthermore, vessels with maintained endothelial cell integrity after 7 d may be used for in vitro research.
Usefulness of quantitative real‐time polymerase chain reaction in following up patients with Epstein–Barr virus infection after liver transplantation
Authors: Orii Takashi , Ohkohchi Nobuhiro , Kikuchi Hiroyuki , Koyamada Nozomi , Chubachi Seiji , Satomi Susumu , Kimura Hiroshi , Hoshino Yo , Morita Makoto
Published: March 2003

Background. Post‐transplant lymphoproliferative disease (PTLD), which is mainly induced by Epstein–Barr virus (EBV) infection, is a cause of significant morbidity and mortality for patients undergoing liver transplantation, especially when it is detected at such an advanced stage as monoclonal malignant lymphoma.  Methods. In this series, 6 of 22 1iver transplant patients suffered from EBV infection. We tested quantitative DNA (Qt‐DNA) by real‐time polymerase chain reacton (PCR), qualitative DNA in plasma (Ql‐pDNA) by PCR, and EBV‐encoded mRNA 1 (EBER 1) byin situhybridization to clarify which of them is a better marker for the early diagnosis and prediction of EBV‐associated disorders.  Results. Four had signs or symptoms of PTLD, but 2 did not develop individualized lymphoid lesions. In all patients, both Qt‐DNA and EBER 1 exceeded the cut‐off level of 102.5copies/μg DNA and 0.002%, respectively, at the time of diagnosis. In 2 patients, when Qt‐DNA had a poor decline, EBER 1, even if it seemed to decrease after antiviral therapy, increased again after a few months and the clinical symptoms recurred. In 2 patients, Qt‐DNA and EBER 1 increased again after a few months of antiviral therapy, and Ql‐pDNA remained positive, whereas, in 3 patients, no reaction of EBV could be detected once Ql‐pDNA became negative, even after the cessation of therapy.  Conclusions. These results suggest that real‐time PCR for Qt‐DNA was more sensitive to the real‐time activity of EBV and that Ql‐pDNA could indicate when to stop antiviral therapy.
Efficacy and safety of Amphotericin B Lipid Complex Injection (ABLC) in solid‐organ transplant recipients with invasive fungal infections
Authors: Linden Peter , Williams Penny , Chan Kevin M
Published: March 2003

Background: Fungal infections following solid‐organ transplantation are a major source of morbidity and mortality. This report describes the efficacy and safety of Amphotericin B Lipid Complex Injection (ABLC) in solid‐organ transplant recipients.  Methods: Three open‐label, second‐line treatment studies evaluated ABLC as a treatment for severe, life‐threatening mycoses in patients who were refractory to or intolerant to conventional antifungal (mostly amphotericin B [AmB]) therapy or had pre‐existing renal disease.  Results: The 79 solid‐organ transplant recipients (25 heart, 20 liver, 17 kidney, 11 lung, 5 multiple, 1 pancreas) who received ABLC in these studies had the following fungal infections: aspergillosis (n=39); candidiasis (n=20); zygomycosis (n=8); cryptococcosis and histoplasmosis (n=3 each); and blastomycosis, cladosporiosis, fusariosis,Bipolaris hawaiiensis,Dactylaria gallopava, and an unspecified fungal infection (n=1 each). The median duration of ABLC therapy was 28 d (1–178 d). The daily dose ranged between 1.6 and 7.4 mg/kg (median, 4.6 mg/kg). The clinical response rate for the patients who could be assessed was 58% (39/67). Clinical response rates for heart, liver, kidney, and lung recipients were 59, 60, 67, and 40%, respectively; response rates for aspergillosis and candidiasis were 47 and 71%, respectively. Forty‐six of the 79 patients (58%) survived for more than 28 d after the last dose of ABLC. Mean baseline serum creatinine was 3.2 mg/dL; 64 patients (81%) had stable (n=37) or improved (n=27) serum creatinine at the end of treatment.  Conclusions: ABLC is safe and effective treatment for fungal infections in solid‐organ transplant recipients. Its renal‐sparing properties are particularly suited for this high‐risk population for renal failure.
A comparison of daclizumab to ATGAM induction in simultaneous pancreas‐kidney transplant recipients on triple maintenance immunosuppression
Authors: Rasaiah Suvi B , Light Jimmy A , Sasaki Truman M , Currier Charles B
Published: March 2003

Daclizumab (DAC) is a molecularly engineered humanized IgGa monoclonal Ab directed against the alpha chain of the interleukin‐2 receptor (IL2R). Inhibiting the amplification of the immune response by blocking IL2R can reduce the frequency of acute rejection without the attendant risk of infection.  The purpose of this retrospective study was to compare DAC to anti‐thymocyte (ATGAM) induction in 24 simultaneous pancreas–kidney (SPK) transplants performed between September 1995 and September 1998. The primary endpoints were the incidence within 6 months post‐transplant of: 1) biopsy‐proven acute rejection; and 2) infection. The two groups (DAC, n=12; ATGAM, n=12) were matched on age, race, ESRD, number of HLA mismatches, PRA level, and cold ischemia time. DAC (1 mg/kg) was given on the day of transplant, then every other week (a total of five doses); ATGAM (15 mg/kg) was given on post‐transplant day 1, then daily for 7–10 d. Immunosuppressive therapy consisted of cyclosporine (Neoral®– 8–10 mg/kg/d) or Prograf® (0.16–0.2 mg/kg/d), mycophenolate mofetil (CellCept®– 2–3 g/d) and steroids.  Of the 12 DAC patients, 3 patients (25%) had biopsy‐proven acute rejection versus 8/12 (67%) of the ATGAM patients. The time to acute rejection was significantly different by group (DAC=110 d; ATGAM=26 d). There was a reduction in the number of patients receiving antilymphocyte drugs for moderate to severe rejection (DAC=2/12; ATGAM=4/12), with 2 of the 4 ATGAM patients experiencing more than two episodes of biopsy‐proven rejection. There was an increase in infection by group (DAC=4/12; ATGAM=7/12): total of three septic infections occurred in the ATGAM group opposed to none in the DAC group. Patient, pancreas, kidney 6‐month survival rates were 100% for both groups.  We conclude that DAC induction coupled with triple immunosuppressive therapy reduces the incidence of rejection in SPK transplant patients. The time to acute rejection was prolonged in the DAC group compared with the ATGAM group without the attendant risks of rejection.
A single center's clinical experience with quadruple immunosuppression including ATG or IL2 antibodies and mycophenolate mofetil in simultaneous pancreas–kidney transplants
Authors: Hesse Uj , Troisi R , Jacobs B , Van Vlem B , De Hemptinne B , Van Holder R , Vermassen F , De Roose J , Lameire N
Published: March 2003

Acute rejection remains a major problem in simultaneous pancreas–kidney (SPK) transplant and occurs in 60–100% of the cases.  With the introduction of mycophenolate mofetil (MMF) replacing azathioprine (AZA) as a basis immunosuppressant, reduced rates of rejection have been reported. This study investigates the frequency and clinical relevance of allograft rejection in SPK patients receiving anti‐thymocyte globulin (ATG) or Basiliximab® induction therapy and cyclosporine Neoral® (CyA), MMF, steroid basis immunosuppression.  Between December 1996 and October 1999, 21 consecutive patients (15 males, 6 females) received a SPK transplant at our institution with a mean±standard deviation (SD) age of 42±6 yr. Of these, 14 patients were treated with anti‐thymocyte globulin (ATG) Fresenius® (rabbit) 3–5 mg/kg for 6±2 d, cyclosporine Neoral (CyA) (trough levels 350–400 ng/mL), MMF 3 g/d and low dose steroid therapy. Seven SPK patients were treated with Basiliximab (Simulect®, Novartis 20 mg on d 0 and d 4 post‐transplant) instead of ATG. The patients had an average human leucocyte antigen (HLA) mismatch of 3.9/6 and a negative cross match. All patients remained on triple drug therapy. Three patients were switched to tacrolimus instead of Neoral for CyA intolerance. The mean±SD cold ischemia time (CIT) of the organs was 10.1±2.4 h for the pancreas and 10.5±2.6 h for the kidney.  Results: Biopsy‐proven rejection occurred in the kidney of 1 ATG patient (8%), which responded to steroid bolus therapy. One of the patients (14%) with Basiliximab induction developed renal allograft rejection, which was resolved after a 6‐d course of anti‐CD3 mAb (OKT3) treatment. All patients (100%) were free from rejection in the pancreas, as measured by urine amylase levels and glycemic control without the need for exogenous insulin with a mean glycosylated hemoglobin (HBA1C) of 5.1±0.7% and serum creatinine with a mean of 1.24±0.24 mg/dL in a mean follow‐up period of 17±15 months (median 12, range 2–37).  Conclusion: Triple drug immunosuppression including cyclosporine, MMF and low dose steroids with ATG or interleukin 2 (IL2) receptor antibodies induction therapy appears to be a very suitable immunosuppressive regimen for combined pancreas–kidney transplant (PKT) with a marked reduction in the incidence of rejection.
Glomerulonephritis is the major cause of proteinuria in renal transplant recipients: histopathologic findings of renal allografts with proteinuria1
Authors: Chung Jaegul , Kil Park Su , Sik Park Jung , Kim Song‐Cheol , Han Duck‐Jong , Yu Eunsil
Published: March 2003

The proteinuria in renal allograft recipients has been regarded as a sign of poor prognosis. The causes of post‐transplant proteinuria include chronic rejection, chronic transplant glomerulopathy, glomerulonephritis (GN), acute rejection, and cyclosporine nephrotoxicity. Among them, chronic rejection is known to be most frequent. We analyzed the histopathologic findings of renal allograft biopsies in 197 Korean recipients with proteinuria. Among them, 26 patients developed proteinuria over 500 mg/d. All patients received baseline immunosuppression with cyclosporine. From 26 patients with post‐transplant proteinuria, 29 biopsies were performed and their histologic diagnoses were immunoglubulin A nephropathy (IgAN) in 17, IgAN combined with chronic allograft nephropathy in 1, focal segmental glomerulosclerosis in 2, crescentic GN in 1, membranous GN in 1, diabetic nephropathy in 1, acute tubulointerstitial nephritis in 1, and chronic rejection in 3 biopsies. The remaining two biopsies showed nonspecific findings. The most common cause of post‐transplant proteinuria was IgAN (62% of biopsies). The incidence of chronic rejection was relatively low and predominant cyclosporine‐associated changes were not observed. In conclusion, our data suggest that the main causes of post‐transplant proteinuria in Korea are primary glomerulonephritides rather than chronic rejection or cyclosporine nephrotoxicity, and the kidney allograft biopsies from patients with proteinuria should be handled as native kidney.
The kinetics of CD154 (CD40L) expression in peripheral blood mononuclear cells of healthy subjects in liver allograft recipients and X‐linked hyper‐IgM syndrome
Authors: Bartlett A , McCall J , Ameratunga R , Munn S
Published: March 2003

The costimulatory pathways play a key role in T cell activation during allograft rejection (AR). Inhibition of the T cell costimulatory molecule CD154 (CD40 ligand) has been effective in producing long‐term allograft survival in rodents and non‐human primates. The role of the CD40‐CD154 pathway in human orthotopic liver transplantation (OLT) has not been examined.  Aim: To describe the patterns of CD154, CD69 and CD152 (CTLA4) expression in OLT recipients and to determine their temporal relationship to AR.  Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 15 OLT allograft recipients just prior to and for seven consecutive days postoperatively. Gene and protein expression of CD154, CD69 and CD154 were examined by reverse transcription‐polymerase chain reaction (RT‐PCR) and flow cytometry (FC), respectively.  Results: FC failed to demonstrate an up‐regulation of CD154 and CD152 protein expression during the first postoperative week. Intracellular FC did not increase the sensitivity. There was an increased level of CD3+CD8+ T cells expressing CD69 at the time of rejection compared to that on day 0. RT‐PCR demonstrated a sporadic expression of CD154 and CD69 mRNA, with no correlation to episodes of acute cellular rejection. In vitro stimulation of PBMCs revealed an impaired up‐regulation of CD154 in patients receiving conventional immunosuppression compared to healthy controls. The assays were validated using positive and negative controls, including a family with X‐linked hyper‐IgM syndrome.  Conclusion: We found no evidence of spontaneous CD154 gene or protein expression in PBMCs associated with acute rejection episodes following OLT. Immunosuppression resulted in impaired responses to ex vivo stimulation.  Lymphocyte costimulatory pathways play a critical role in mediating acute allograft rejection. However, we found no evidence of spontaneous CD154 gene or protein expression in PBMCs associated with acute rejection episodes following OLT. Furthermore, stimulation in vitro resulted in less up‐regulation of CD154 than for healthy controls.
Serial measurements of serum transaminases in renal transplant recipients with chronic hepatitis C: do they reflect disease severity?
Authors: Besisik Fatih , Sükrü Sever Mehmet , Dincer Dinc , Çevikbas Ugur , Türkoglu Salih , Çakaloglu Yılmaz , Kaymakoglu Sabahattin , Ökten Atilla
Published: March 2003

Chronic hepatitis C infection is a common problem in renal allograft recipients. This study was designed to investigate the association of serum aminotransferase levels with liver histology, in renal transplant patients with chronic hepatitis C virus (HCV) infection, in the long term.  Methods. In this study, 82 HCV‐infected renal allograft recipients, who were followed up with functioning grafts for at least 6 months, were analyzed. Patients were classified according to their transaminase values as persistently normal, intermittently abnormal, or continuously abnormal liver function tests. Serum transaminase levels exceeding at least 1.5 times the upper limit of normal (40 IU) for periods longer than 1 month were taken as abnormal. Patients with abnormal liver function tests owing to HCV unrelated causes (drugs, alcohol, or other toxic substances, other viruses, etc.) were excluded from the study. Forty‐eight of these patients underwent at least one liver biopsy.  Results. Of the 82 patients, 34 (41.5%) had persistently normal (liver biopsy revealed normal or minimal changes in 77.0%, chronic persistent hepatitis in 15.3%, chronic active hepatitis in 7.7%; no patient had cirrhosis), 29 (35.3%) intermittently abnormal (liver histology was consistent with minimal changes in 50%, chronic persistent hepatitis in 27.8%, chronic active hepatitis in 16.7%, cirrhosis in 5.5%), 19 (23.2%) persistently abnormal (liver biopsy showed minimal changes in 41.1%, chronic persistent hepatitis in 17.6%, chronic active hepatitis in 35.3%, cirrhosis in 5.9%) transaminase values.  Conclusion. Although continuously or intermittently elevated transaminases do not always indicate morphologically advanced disease, the normal course of serum transaminases is mostly accompanied by normal, or near‐normal, liver histology, in HCV‐infected renal transplant patients. Liver biopsy is not indicated in deciding disease severity in these patients unless clinical findings dictate otherwise.
Specificity of preformed alloantibodies causing B cell positive flow crossmatch in renal transplantation
Authors: Lobashevsky Andrew L , Senkbeil Rhonda W , Shoaf James , Mink Cindy , Rowe Charyl , Lobashevsky Elena S , Burke Rebecca , Hudson Sharon , Deierhoi Mark H , Thomas Judith M
Published: March 2003

The specificity of alloantibodies (alloAb) and their clinical significance in association with T−/B+ flow cytometry crossmatch (FCXM) in kidney transplantation are not clearly defined. This study was undertaken to examine the HLA specificity and clinical relevance of Ab causing B+ FCXM in pre‐transplant (final XM) recipients’ serum samples. Final FCXM serum samples were analyzed from 457 renal transplant patients followed for 10 months post‐transplantation. Two hundred and sixty patients had T−/B+ final FCXM. The control group included 197 recipients with T−/B− FCXM at time of transplantation. Class I/class II PRA and specificity of anti‐HLA class I and class II Ab in final FCXM serum samples were analyzed by FlowPRA Class I Screening Test and FlowPRA Class II Screening Test. We found no correlation between graft outcome and pre‐transplant T−/B− and T−/B+ FCXM status. Additionally, we observed no clinical relevance of B+ FCXM in retransplant patients. However, MCS≥200 in B+ FCXM retransplant recipients was associated with anti‐class II Ab to previous mismatches in regrafted patients (n=46). This finding was confirmed by specificity analysis of anti‐DR/DQ Ab in patients with high (≥15%) class II PRA. In 63% (12 of 19) of retransplants having T−/B+ FCXM, we defined the specificity of alloAb to first graft mismatched class II antigens. In contrast, anti‐class II Ab was detected in only 5.7% (2 of 35) of single‐graft recipients with different PRA values. Significantly greater MCS (240±61 vs. 163±48; p=0.022) was observed in retransplant patients having short (≤5 m) previous graft survival time (PGST) than in those with long PGST (≥5 m). Only 2% of retransplant recipients with B+ FCXM had non‐HLA Ab. In contrast, the overwhelming majority of primary recipients had no detectable alloAbs. No significant difference in class I PRA was found between B− and B+ FCXM recipients. However, class II PRA was significantly higher in patients having B+ FCXM (p=0.028). Collectively, these data show that MCS intensity is not always a reliable criterion for anti‐HLA Ab detection because of the presence of non‐HLA Ab. These results can be explained by low titers of anti‐class II Ab, at which concentration these Ab cannot produce a deleterious effect. FlowPRA and Flow screen beads appeared to be reliable and sensitive methods for detection and specificity analysis of anti‐class II alloAb.
A case of persistent acute allograft glomerulopathy with long‐standing stable renal function
Authors: Katafuchi Ritsuko , Masutani Kousuke , Mizumasa Tohru , Fujita Emi , Tanaka Hiroshi , Ikeda Kiyoshi , Yanase Tetsuro , Ando Takashi , Fujimi Satoru
Published: March 2003

Katafuchi R, Masutani K, Mizumasa T, Fujita E, Tanaka H, Ikeda K, Yanase T, Ando T, Fujimi S. A case of persistent acute allograft glomerulopathy with longstanding stable renal function. Clin Transplantation 2001: 15 (Supplement 5): 2–10. ©Munksgaard, 2001

Acute allograft glomerulopathy (AAG) characterized by hypercellularity, enlargement of endothelial cells, infiltration of glomeruli by mononuclear cells and webs of PAS‐positive material has been reported as an unusual but distinct form of acute rejection in kidney transplant recipients. We present a case of persistent AAG proven by serial biopsies. The patient was 53 years old when she received kidney transplantation from her mother. The immunosuppressants were methylprednisolone, azathioprine and FK506. She developed several acute rejections and received antirejection therapy. The patient transferred to our hospital 15 months after transplantation. Serum creatinine was 2.11 mg/dL. The level of serum creatinine was gradually elevated from 2.11 mg/dL to 3.09 mg/dL. Graft biopsy, performed 16.5 months after transplantation, represented prominent intraglomerular infiltration of mononuclear cells, segmental thickening of glomerular basement membrane (GBM) with double contour, grade 1 tubulitis, marked accumulation of mononuclear cells in peritubular capillaries and margination of mononuclear cells in a small artery. It was diagnosed as acute allograft glomerulopathy (AAG). Intravenous methylpredniso‐lone pulse therapy, discontinuation of FK506 and administration of cyclosporin (CYA) resulted in decrease of serum creatinine. To evaluate histological evolution of AAG we performed two sub‐sequent biopsies over 3 yr. Severe glomerulitis persisted as a prom‐inent feature 8 months later and still existed 53.4 months after transplantation with decreased severity. The extent of GBM reduplication also decreased, but the percentage of glomerular sclerosis increased gradually. Multi‐layering of basement membrane of peritubular capillary and interstitial fibrosis also increased. The prominence of infiltration of mononuclear cells in peritubular capillary was unchanged. At the last follow‐up, i.e. 71 months after transplantation, her serum creatinine was 1.34 mg/dL. Neither proteinuria nor haematuria was observed. We consider that our immunosuppressive treatment has been successful so far, because the patient is still maintaining stable graft function since the transplantation over 6 yr ago. It is thus suggested that AAGper seprobably has no influence on acute aggravation of graft function, but AAG and capillaritis in peritubular capillaries may cause an evolution of chronic allograft nephropathy, resulting in a slowly progressive deterioration of graft function.
Hyperlipidemia as a risk factor of renal allograft function impairment
Authors: Carvalho Maria Fernanda C , Soares Vitor
Published: March 2003

In this study, the graft outcome in renal allograft recipients with [high cholesterol group (HCG), n=30] or without [normal cholesterol group (NCG), n=42] hypercholesterolemia and with [high triglyceride group (HTG), n=33] or without [normal triglyceride group (NTG), n=36] hypertriglyceridemia were prospectively compared. At 6 months post‐transplantation, no significant difference was observed between the groups (NTG compared with HTG, and NCG compared with HCG) regarding age, presence of arterial hypertension, kind of donor (living related or cadaveric), immunosuppressive therapy, number of rejection episodes per patient, frequency of patients with acute cellular rejection, prevalence of patients with diabetes mellitus or proteinuria >3 g/24 h, and mean serum creatinine. The probability of doubling serum creatinine during follow‐up was statistically different between NTG and HTG (12 months: NTG=0.03, HTG=0.15; 36 months: NTG=0.08, HTG=0.33; 60 months: NTG=0.08, HTG=0.48; and 120 months: NTG=0.18, HTG=0.48), but not between NCG and HCG (12 months: NCG=0.05, HCG=0.13; 36 months: NCG=0.13, HCG=0.24; 60 months: NCG=0.19, HCG=0.31; 84 months: NCG=0.27, HCG=0.31). There was no significant difference in actuarial graft survival between HCG and NCG or between NTG and HTG. Hypertriglyceridemia, but not hypercholesterolemia, was associated with loss of graft function.