bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous pancreas‐kidney transplantation: portal versus systemic venous drainage of the pancreas allografts
Authors: Petruzzo Palmina , Da Silva Marco , Feitosa Luis Carlos , Dawahra Marwan , Lefrançois Nicole , Dubernard Jean Michel , Martin Xavier
Published: March 2003

Simultaneous pancreas‐kidney (SPK) transplantation is considered a valid therapeutic option for patient with type I diabetes mellitus and end‐stage diabetic nephropathy. This study was performed to determine whether the technique of pancreas venous drainage affects patient survival as well as graft survival and function. From October 1996 to April 1999 34 uremic patients with type I diabetes mellitus were randomly assigned to two groups: the first group (SV group=17) received SPK transplantation with systemic venous drainage, and the second group (PV group=17) received pancreas allograft with portal drainage. A Roux‐en‐Y loop was performed in all the patients. Patient follow‐up included clinical course and metabolic studies. At 1 yr, patient survival rates were 88.2% in the SV group and 94.1% in the PV group while graft survival rate was 76.4% in both groups. Several surgical complications were attributed to the enteric drainage without any graft failure in both groups. One venous thrombosis occurred in each group. No significant differences have been evidenced in kidney and pancreas function. The preliminary results of this randomized trial did not evidence any significant differences between portal and systemic venous drainage of pancreas allograft.
Shorter waiting times for hepatitis C virus seropositive recipients of cadaveric renal allografts from hepatitis C virus seropositive donors
Authors: Mandal Aloke K , Kraus Edward S , Samaniego Milagros , Rai Rudra , Humphreys Susan L , Ratner Lloyd E , Maley Warren R , Burdick James F
Published: March 2003

Introduction. The purposes of this study were: 1) to analyze the early results of cadaveric renal transplantation from either hepatitis C virus seropositive (HCV+) or hepatitis C virus seronegative (HCV−) donors into HCV+ recipients; and 2) to determine whether HCV+ patients with end‐stage renal disease (ESRD) might benefit from receiving renal allografts from HCV+ donors.  Methods. From January 1997 to June 1999, 28 patients with ESRD and HCV infection underwent 29 cadaveric renal transplants. The data were reviewed retrospectively. Nineteen of the renal transplants were performed with allografts obtained from 15 HCV+ donors and 10 with allografts obtained from 10 HCV− donors. The median follow‐up was 16.2 months, with an average of 15.4±2 months.  Results. Recipients of HCV+ renal allografts had shorter waiting times for transplantation. On average, patients who received a kidney from HCV+ donors were transplanted 9±3 months after being placed on the transplant list, compared to 29±3 months for patients who received a kidney from a HCV− donor. Shorter waiting times were noted in every blood type group. There were no significant differences in rejection episodes, infectious complications, renal function, liver function, graft survival, or patient survival.  Conclusions. The use of renal allografts from HCV+ donors for HCV+ recipients shortens the waiting time for these patients, with no short‐term differences in renal and liver function, graft loss, or patient survival.
Review of select transplant subpopulations at high risk of failure from standard immunosuppressive therapy
Authors: Deierhoi Mark H , Haug Iii Marcus
Published: March 2003

Despite improvements in short‐term graft and patient survival rates for solid organ transplants, certain subgroups of transplant recipients experience poorer clinical outcome compared to the general population. Groups including pediatrics, African‐Americans, diabetics, cystic fibrosis patients, and pregnant women require special considerations when designing immunosuppressive regimens that optimize transplant outcomes. Problems specific to pediatric transplant recipients include altered pharmacokinetics of immunosuppressive drugs, such as cyclosporine (CsA) and tacrolimus (poor absorption, increased metabolism, rapid clearance), the need to restore growth post‐transplantation, and a high incidence of drug‐related adverse effects. African‐Americans have decreased drug absorption and bioavailability, high immunologic responsiveness, and a high incidence of post‐transplant diabetes mellitus. Diabetics and cystic fibrosis patients exhibit poor absorption of immunosuppressive agents, which may lead to underimmunosuppression and subsequent graft rejection. Pregnant women undergo physiologic changes that can alter the pharmacokinetics of immunosuppressives, thus requiring careful clinical management to minimize the risks of either under‐ or overimmunosuppression to mother and child. To achieve an optimal post‐transplant outcome in these high‐risk patients, the problems specific to each group must be addressed, and immunosuppressive therapy individualized accordingly. Drug formulation greatly impacts upon pharmacokinetics and the resultant level of immunosuppression. Thus, a formulation with improved absorption (e.g., CsA for microemulsion), higher bioavailability, and less pharmacokinetic variability may facilitate patient management and lead to more favorable outcomes, especially in groups demonstrating low and variable bioavailability. Other strategies aimed at improving transplant outcome include the use of higher immunosuppressive doses, different combinations of immunosuppressive agents, more frequent monitoring, and management of concurrent disease states.
The effect of Daclizumab in a high‐risk renal transplant population
Authors: Meier‐Kriesche Herwig‐Ulf , Kaza Harsha , Palekar Sadanand S , Friedman Gary S , Mulgaonkar Shamkant P , Ojo Akinlolu O , Kaplan Bruce
Published: March 2003

Introduction: African–American (AA) renal transplant recipients have a higher incidence of acute rejection when compared to Caucasian renal transplant recipients. This higher rejection rate holds true even with the addition of several of the newer immunosuppressive agents (e.g. mycophenolate mofetil (MMF) and Rapamycin). Acute rejection rates among Hispanic (H) renal transplant recipients are higher in some settings, while lower or the same as in Caucasians in other settings. IL‐2 receptor antibodies have been shown to decrease rejection rates when added to a regimen of cyclosporine (CsA), azathioprine and prednisone. Limited data are available on these agents in conjunction with triple CsA, MMF and prednisone therapy, particularly in higher risk group patients. We studied the effect of the addition of the IL‐2 receptor antibody Daclizumab to a CsA, MMF, prednisone regimen in a group of African–American and high‐risk Hispanic renal transplant recipients.  Methods: This was a non‐randomized, prospective study. A total of 49 renal transplant recipients (29 African–American and 20 Hispanic) were studied and followed. A simultaneous cohort of 56 (31 African–American and 25 Hispanic) renal transplant recipients receiving CsA, MMF and prednisone with no standard induction agent served as the control group. The study cohort received the same regimen with the addition of Daclizumab at 1 mg/kg for five doses over 10 wk. Multivariate analysis was performed to isolate independent factors influencing the study's results.  Results: A total of 56 patients in the control group and 49 patients in the Daclizumab group received an average follow‐up of 17.1±6.9 and 12.7±5.1 months, respectively. Acute rejection rates were lower in the Daclizumab group as compared to the control group 26.4% versus 49.3% per patient years, respectively. A total of eight recurrent rejections in 6 patients occurred in the control group and none in the Daclizumab arm. Graft loss at this follow‐up was no different between the groups.  Conclusion: The addition of Daclizumab to a regimen of CsA, MMF and prednisone decreases acute rejection episodes in a high‐risk group of African–American and Hispanic renal transplant recipients.
Outcomes of simultaneous kidney–pancreas transplantation in African‐American recipients: a case‐control study
Authors: Lo Agnes , Stratta Robert J , Egidi M Francesca , Shokouh‐Amiri M Hosein , Grewal Hani P , Kizilisik A Tarik , Alloway Rita R , Gaber Lillian W , Gaber A Osama
Published: March 2003

Introduction. Previous studies have suggested that African‐American (AA) ethnicity is a risk factor for rejection and graft loss after kidney transplantation. However, little data is available regarding outcomes after simultaneous kidney–pancreas transplantation (SKPT) in AA recipients. The objective of this study was to compare the outcomes of SKPT in AA patients to matched Caucasian patients as controls.  Methods. From January 1996 to September 1999, we performed 79 SKPTs, including 10 in AA recipients. Ten Caucasian controls were selected and matched for age, gender, weight, timing and technique of transplantation, and immunosuppressive regimen. Clinical outcomes were collected and compared between the two groups.  Results. The two groups were well matched for donor and recipient demographic, immunologic and transplant characteristics, including 2 patients in each group with type 2 diabetes. All patients received tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids, and about half in each group received antibody induction therapy. Patient survival was 100% in both groups with a mean follow‐up of 18 months (range 6–47). Kidney and pancreas graft survival rates were both 80% in the AA and 100% in the Caucasian groups, respectively (p=0.14). All but one kidney (in the AA group) and all pancreas grafts experienced immediate function. There were two immunologic kidney and two immunologic pancreas graft losses in the AA group. No grafts were lost due to technical problems. The mean length of initial hospital stay was 16 d in the AA group compared to 10 d in the Caucasian group (p=0.07). The AA group had a slight increase in the number of readmissions (mean 2.2 AA vs. 1.6 Caucasian, p=0.08). The incidence of biopsy‐proven pancreas acute rejection was significantly higher in the AA group (50%) compared to the Caucasian group (10%) (p=0.05). The incidence of either kidney or pancreas acute rejection was also higher in the AA group (60% AA vs. 20% Caucasian, p=0.06). TAC levels were comparable at specific times after transplantation, although there was a trend toward higher doses of TAC in the AA group to achieve therapeutic levels. The incidences of relaparotomy (30% AA vs. 20% Caucasian) and major infection (40% AA vs. 60% Caucasian) were similar between groups. Renal and pancreas allograft functions were comparable between groups at specific times after transplantation.  Conclusions. These results suggest that SKPT in AA recipients may be associated with a higher incidence of rejection and immunologic graft loss compared to matched Caucasian controls.
Diurnal cyclosporine dosing optimizes exposure and reduces the risk of acute rejection after kidney transplantation
Authors: Browne Barry J. , Op'T Holt Cynthia , Emovon Osemwegie E.
Published: March 2003

Acute rejection (AR) following transplantation may be due to episodic subtherapeutic cyclosporine (CsA) levels related to diurnal variation of hepatic drug metabolism. We postulated that asymmetrical dosing of CsA based on individualized pharmacokinetic profiles would optimize drug exposure and decrease the risk of AR. We prospectively treated all patients undergoing kidney transplantation with a diurnally split dose of CsA microemulsion given q 12 hours (3.5 mg/kg q a.m., 3.0 mg/kg qPM). Morning doses were adjusted to reach a day‐time area under the concentration curve (AUC) of 7800 ng hour/ml (utilizing 2 hour and 6 hour levels) and evening doses were adjusted to a morning trough of 300 ng/ml. Patients received high‐dose steroids tapered to 20 mg prednisone by day 6. CsA was started within 36 hours and mycophenolate mofetil (1000 mg q 12 hour) was added on day 3 in most patients and continued for 3 months. Only one patient received antibody induction. Thirty kidneys (67% cadaveric) were transplanted into 28 adult patients (50% African American, 57% men). Therapeutic targets were reached in all patients prior to discharge and maintained during the study period. At 3 months follow‐up, there was not a single episode of documented AR and mean creatinine was 1.5±0.1 mg/ml. Twelve patients required biopsy for allograft dysfunction; however no histological evidence of AR or CsA‐toxicity was identified and the creatinine normalized in each case without altering immunosuppression. Patients continued to require increased CsA doses in the AM compared to the PM (P<0.05) throughout the study to maintain target levels. Diurnal dosing of CsA based on individual pharmacokinetic profiles optimizes CsA exposure and reduces the risk of AR during the first 3 months after transplantation.
Diagnosis of kidney transplant obstruction using Mag3 diuretic renography
Authors: Nankivell Brian J , Cohn Deborah A , Spicer S Timothy , Evans Scott G , Chapman Jeremy R , Gruenewald Simon M
Published: March 2003

Kidney transplant obstruction (KTO) following renal transplantation remains an important reversible cause of allograft dysfunction, requiring prompt diagnosis to prevent long‐term graft damage. Although ultrasound can accurately diagnose renal transplant hydronephrosis, it cannot be used to assess its functional significance. We prospectively assessed the utility of technetium‐99m mercaptoacetyltriglycine (Tc99m MAG3) diuretic renography for the diagnosis of allograft KTO, using standard visual and quantitative parameters, as well as calculated renal output efficiency (OE), which has been postulated to improve diagnostic yield. From a cohort of 45 renal transplant patients, two subgroups were formed. The first group of transplant recipients (n=21) with stable function and no obstruction was used to derive normal values for Tc99m MAG3 scans. A second group of transplant recipients with acute renal dysfunction in whom KTO was clinically suspected was used to test the diagnostic utility of these derived values (n=43 scans). KTO was diagnosed independently of the MAG3 scans by a fall in the serum creatinine in response to renal pelvis urinary drainage. OE in 12 renal allografts with KTO was significantly reduced compared with 31 Tc99m MAG3 scans without KTO (59.6±18.9 vs. 81.6±5.4%, p<0.001). In KTO, the mean time of isotope appearance in the bladder (time to bladder [TTB]) was extended compared with unobstructed allografts (7.9±4.1 vs. 3.6±1.5 min, p<0.001). Measurement of OE significantly improved the accuracy of diuretic MAG3 renography in the diagnosis of renal allograft KTO, especially when supplemented by the TTB, parenchymal transit time and shape of the renogram curve. Ureteric obstruction of the kidney transplant can be diagnosed with an OE reduced to <75% (sensitivity 92%, specificity 87%) and confirmed by isotope hold‐up in the pelvicalyceal system. A normal or slowly declining renogram curve effectively excluded KTO (sensitivity of 96%, negative predictive value of 84%). A parenchymal transit time of >5 min and a TTB of >7 min both yielded a sensitvity of 92% and a specificity of 81%. In conclusion, MAG3 renography is a clinically useful investigation for the diagnosis of KTO.
People's feelings and ideas about receiving transplants of different origins – questions of life and death, identity, and nature's border
Authors: Sanner Margareta A
Published: March 2003

The aim of this study was to explore the public's feelings and ideas with regard to receiving transplants of different origins. Sixty‐nine individuals with varying sociodemographic background, selected from samples who had responded to a questionnaire on receiving and donating organs, were interviewed in‐depth. A wide variety of reactions was displayed. The feelings and ideas about receiving organs were summarized in ten categories: 1) the emergency situation; 2) the functioning of the transplant; 3) the influence of transplants on personality, behaviour, and appearance; 4) the influence of transplants on body image; 5) disgust; 6) cannibalism; 7) trespassing nature's border; 8) tradition; 9) ethical considerations; and 10) the debt of gratitude. Most individuals were willing to accept at least one organ. Animal organs were the least preferred. The hierarchy of organ preferences – with organs from a relative at the top and animal organs at the bottom – was explained in terms of rational, magical, and analogy thinking. Finally, the consequences for the encounter between health care personnel and transplantation candidates were briefly discussed.
Cyclosporine challenge test revisited: does it predict outcome after solitary pancreas transplantation?
Authors: Lane James T , Ratanasuwan Tanaporn , Mack‐Shipman Lynn R , Taylor Rodney J , Leone John P , Miller Suzanne A , Lyden Elizabeth R , Larsen Jennifer L
Published: March 2003

Background: The selection of patients for solitary pancreas transplantation (PTA) requires identification of individuals who will not develop acute renal dysfunction in response to immunosuppressants. A cyclosporine challenge test (CCT) was developed to predict post‐PTA kidney dysfunction secondary to calcineurin inhibitor immunosuppressants. We now report on the long‐term follow‐up of patients who received a PTA after undergoing a CCT.  Methods: Twelve potential PTA recipients were administered cyclosporine A (CsA) for 6 wk. Creatinine clearance (CrCl) was measured at 2, 4, and 6 wk. Those who did not fail the CCT received PTA. Baseline and post‐transplant CrCl were retrospectively evaluated in the original cohort and in a group of matched patients who received PTA without a CCT.  Results: Of the original 12 recipients evaluated with the CCT, 6 received PTA. CrCl was followed for a mean of 45.8 months. Of the 4 who remained alive, 2 went on to develop renal failure (CrCl<30 mL/min) at 18 and 65 months post‐transplant. The baseline CrCl was higher in PTA recipients who had not been selected to be studied with CCT than those that were (117±32 vs 78±13 mL/min). By 12 months post‐PTA, the CrCl was no longer different between the groups selected to be screened with CCT and those that were not.  Conclusions: CCT may help predict risk for short‐term changes in renal function (<18 months) in response to CsA. CCT may be most helpful in candidates for PTA with borderline renal insufficiency (60–80 mL/min).
Decreased effect of immunosuppression on immunocompetence in African–Americans after kidney and liver transplantation
Authors: Nagashima Naoki , Watanabe Takuji , Nakamura Michio , Shalabi Ahmed , Burdick James F
Published: March 2003

Several studies indicate that the poorer outcomes for African–Americans after transplantation may be due to decreased effectiveness of immunosuppressive agents. Using anin vitrotest of immunocompetence (IMC), we measured the effects of immunosuppression on African–American, compared with Caucasian, kidney or liver transplantation recipients.  The IMC result was the highest of three mixed lymphocyte culture responses using validated stimulator cell pools. A total of 293 tests were done in Caucasians and 144 in African–Americans. Overall, the IMC for African–Americans was 38, compared with 19 for Caucasians (p<0.01). This decreased effect of immunosuppression (higher IMC) was the same for liver as for kidney transplant recipients, occurred at the 2–3‐yr interval, and was largely in patients of tacrolimus (FK506), with a strong but not significant trend in cyclosporine (CYA) recipients. The two groups were on the same nominal immunosuppression and FK506 and CYA levels were not different.  We conclude that African–Americans retain more immune responsiveness on equivalent dose immunosuppression, notable particularly in years 2–3 after transplantation when earlier graft loss occurs in this group.
The impact of late acute rejection after cadaveric kidney transplantation
Authors: Joseph JT , Kingsmore DB , Junor BJR , Briggs JD , Mun Woo Y , Jaques BC , Hamilton DN , Jardine AG , Jindal RM
Published: March 2003

Background: Acute graft rejection (AR) following renal transplantation results in reduced graft survival. However, there is uncertainty regarding the definition, aetiology and long‐term graft and patient outcome of AR occurring late in the post‐transplant period.  Aim: To determine if rejection episodes can be classified by time from transplantation by their impact on graft survival into early acute rejection (EAR) and late acute rejection (LAR).  Materials and methods: 687 consecutive adult renal transplant recipients who received their first cadaveric renal transplant at a single centre. All received cyclosporine (CyA)‐based immunosuppression, from 1984 to 1996, with a median follow‐up of 6.9 yr. Details were abstracted from clinical records, with emphasis on age, sex, co‐morbid conditions, HLA matching, rejection episodes, patient and graft survival.  Analysis: Patients were classified by the presence and time to AR from the date of transplantation. Using those patients who had no AR (NAR) as a baseline, we determined the relative risk of graft failure by time to rejection. The characteristics of patients who had no rejection, EAR and LAR were compared.  Results: Compared with NAR, the risk of graft failure was higher for those patients who suffered a rejection episode. A much higher risk of graft failure was seen when the first rejection episode occurred after 90 d. Thus, a period of 90 d was taken to separate EAR and LAR (relative risk of 3.06 and 5.27 compared with NAR as baseline, p<0.001). Seventy‐eight patients (11.4%) had LAR, 271 (39.4%) had EAR and 338 (49.2%) had NAR. The mean age for each of these groups differed (LAR 39.6 yr, EAR 40.8 yr compared with NAR 44 yr, p<0.003). The 5‐yr graft survival for those who had LAR was 45% and 10‐yr survival was 28%. HLA mismatches were more frequent in those with EAR vs. NAR (zero mismatches in HLA‐A: 36 vs. 24%, HLA‐B: 35 vs. 23% and HLA‐DR: 63 vs. 41%, p<0.003). There was no difference in mismatching frequency between NAR and LAR.  Conclusions: AR had a deleterious impact on graft survival, particularly if occurring after 90 d. AR episodes should therefore be divided into early and late phases. In view of the very poor graft survival associated with LAR, it is important to gain further insight into the main aetiological factors. Those such as suboptimal CyA blood levels and non‐compliance with medication should be further investigated with the aim of developing more effective immunosuppressive regimens in order to reduce the incidence of LAR.
Clinical implications of flow cytometry crossmatch with T or B cells in living donor liver transplantation
Authors: Takakura Koji , Kiuchi Tetsuya , Kasahara Mureo , Uryuhara Kenji , Uemoto Shinji , Inomata Yukihiro , Tanaka Koichi
Published: March 2003

Background: Acute allograft rejection (AR) in solid organ transplantation is generally regarded to develop through cell‐mediated immune response following activation of helper T cells. Since production of antibodies is also mediated by helper T cells, humoral immunity may play some roles in AR. Although flow cytometry crossmatch (FCXM) is reported as a useful method for the detection of antibodies against donor antigen, specific role of T‐ or B‐cell FCXM and its sensitivity for AR is controversial.  Methods: T‐ and B‐cell FCXM using fresh donor peripheral lymphocytes were performed before and after blood‐type compatible living donor liver transplantation in 47 patients. IgM and IgG anti‐donor antibodies were analyzed in relation to clinical AR.  Results: Positive pre‐transplant T‐cell FCXM was associated with a high incidence of positive post‐transplant T‐cell FCXM (p=0.017). Four of five cases (80%) with positive pre‐transplant T‐cell FCXM experienced earlier AR (day 8.0±4.4, mean±SD) than 16 of 42 cases (31%) with negative pre‐transplant T‐cell FCXM (17.3±6.8; p=0.016). In addition, higher dose of steroids was given to treat AR episodes in cases with positive pre‐transplant T‐cell FCXM (79.9±10.3 mg/kg/month) than in those with negative pre‐transplant T‐cell FCXM (47.1±26.6; p=0.039). In the first month after transplantation, 13 episodes of positive post‐transplant T‐cell FCXM were all concomitant with or preceded clinical AR compared with seven ARs in T‐cell FCXM‐negative cases (p<0.0001). T‐cell FCXM between positive sera and third parties revealed some crossreactions. In contrast, detection of antibodies by B‐cell FCXM in pre‐ and post‐transplant phases was scarcely associated with AR, and no correlation was found between T‐ and B‐cell FCXM before and after transplantation.  Conclusions: Positive T‐cell FCXM is closely related with AR and that before transplantation is a predictor of early and refractory AR as well as post‐transplant FCXM. In contrast, not a few detections of antibodies irrelevant to AR are observed in B‐cell FCXM, suggesting its low specificity.
Effective oral administration of tacrolimus in renal transplant recipients
Authors: Kimikawa Masaaki , Kamoya Kunimaro , Toma Hiroshi , Teraoka Satoshi
Published: March 2003

Background: Tacrolimus is usually administered orally based on mg/kg or the trough concentration (Cmin) in whole blood. However, it is not easy to determine the optimal oral dose because of considerable variation of tacrolimus bioavailability between patients. In this study, pharmacokinetics of tacrolimus in various conditioning kidney transplant recipients was investigated.  Methods: 1) Thirty‐three patients were randomly assigned to participate in two groups. In 17 patients, tacrolimus was administered orally after an overnight fast with breakfast given 1 h later, and in the other 16 patients it was administered orally 1 h after breakfast. 2) In 4 patients, the same dose tacrolimus was given after an overnight fast and 0.5 h after breakfast on two consecutive days. 3) Five patients who underwent continuous ambulatory peritoneal dialysis (CAPD) before transplantation were studied. All patients were investigated in daily profile of tacrolimus blood levels.  Results: There was a strong correlation between area under the curve (AUC) and the trough concentration in both preprandial and postprandial oral administration, with correlation coefficients of 0.838 and 0.860, respectively. Significant increases in the peak concentration (Cmax) and AUC were observed in the preprandial oral administration subjects. Absorption of CAPD patients was obviously insufficient.  Conclusions: Since tacrolimus absorption was better under fasted condition than under the presence of food, it is thought that the highest medicine effect with the least dosage is provided by preprandial oral administration. Furthermore, preprandial oral administration is recommended from a respect of economic burden reduction and side effect reduction.
Four cases of CMV ureteritis: emergence of a new pattern of disease?
Authors: Thomas Mc , Russ Gr , Mathew Th , Rao Mohan M , Cooper J , Walker Rj
Published: March 2003

Although cytomegalovirus (CMV) infection is common in renal transplant recipients, urinary tract involvement has been rare. Only six cases of symptomatic ureteritis have been reported in renal transplant recipients and all within the last five years. We describe an additional four cases of CMV ureteritis. The presentation of CMV ureteritis is obstructive nephropathy often in the absence of systemic illness. Presentation may also mimic allograft rejection with minimal obstructive symptoms. We hypothesize that CMV ureteritis is an emerging complication of CMV disease, possibly due to changes in transplant practice.
Long‐term results ofen bloctransplantation of pediatric kidneys into adults using a vicryl mesh envelope technique
Authors: Chinnakotla Srinath , Leone John P , Taylor Rodney J
Published: March 2003

En bloctransplantation of pediatric kidneys into adults is a suitable measure to help correct the shortage of available kidneys. This practice, however, is not widespread because of the high incidence of vascular complications. Our institution has previously described a vicryl mesh technique foren blockidneys, with an attempt to reduce the incidence of vascular complications. The purpose of this study was to evaluate the long‐term results of recipients withen blockidneys stabilized with this technique. The charts of 644 adult renal transplants performed between July 1987 and July 1999 were reviewed. During this period, 14 adult patients have received 14 pairs ofen blocpediatric kidneys using the vicryl mesh technique. All patients received OKT3 as an induction immunosuppression with cyclosporine started 10–14 d after the transplant. The median donor age was 24 months (range 14–84 months), and the median recipient age was 49 yr (range 23–68 yr). The mean recipient weight was 79 kg (range 60–114 kg). The mean cold ischemia time was 14.2 hr. None of the patients developed vascular or urological complications. Delayed graft function and moderate acute rejection occurred in one patient each. At a mean follow‐up of 51 months (range 7–96 months), all 14 patients maintained excellent renal function with a mean creatinine of 1.01 mg/dL. Renal measurements pre‐operatively and at follow‐up ultrasound examinations were available in 9 patients, and the mean length of the kidneys had grown approximately 5.0 cm. These data demonstrate that minimal vascular and immunological complication rates can be achieved with pediatricen blockidneys using the vicryl mesh envelope technique.
Neoral® rescue therapy in transplant patients with intolerance to tacrolimus
Authors: Abouljoud Marwan S , Kumar MS Anil , Brayman Kenneth L , Emre Sukru , Bynon JS ,   for the OLN‐452 Study Group
Published: March 2003

Background. The calcineurin inhibitors, cyclosporine and tacrolimus, are the mainstay of current immunosuppressive regimens for the prevention of acute rejection in organ transplantation. The choice of the individual agent used often depends on the preference of the Transplant Center and patient type. Adverse effects associated with tacrolimus may impact its clinical utility in many patients. This study characterizes the clinical outcomes of transplant recipients who experienced adverse effects from tacrolimus and were converted to cyclosporine‐microemulsion‐based (Neoral® [cyclosporine, USP] MODIFIED) therapy.

Methods. Hepatic or renal allograft recipients unable to maintain adequate immunosuppression with a tacrolimus‐based regimen for reasons of toxicity or efficacy were recruited for this study and converted to cyclosporine‐microemulsion‐based therapy. Data were collected on drug dosing, trough concentrations, and treatment duration, as well as detailed information on tacrolimus‐associated toxicities that prompted rescue with cyclosporine‐microemulsion. Furthermore, clinical and laboratory data related to the clinical course of the patients after conversion to cyclosporine‐microemulsion were recorded for up to 1 yr following conversion.

Results. One hundred and fifty‐seven transplant recipients were enrolled in this study. Predominant reasons for discontinuation of tacrolimus were neurotoxicity (55%), diabetes (24%), nephrotoxicity (15%), and gastrointestinal intolerance (24%). Patients frequently had multiple symptoms prompting rescue therapy with cyclosporine‐microemulsion. Over 70% of subjects had improvement or resolution of their tacrolimus‐associated adverse symptoms within 3 months post‐conversion. Acute rejection episodes occurred in 27% of patients converted to cyclosporine‐microemulsion.

Conclusions. Cyclosporine‐microemulsion rescue therapy in patients experiencing adverse clinical effects associated with tacrolimus is an effective treatment option which leads to resolution of these adverse effects in the majority of patients, and allows for satisfactory clinical outcomes.
Angiotensin‐II receptor antagonist losartan reduces microalbuminuria in hypertensive renal transplant recipients
Authors: Ersoy Alparslan , Dilek Kamil , Usta Mehmet , Yavuz Mahmut , Güllülü Mustafa , Oktay Bülent , Yurtkuran Mustafa
Published: March 2003

In recent years, it has been demonstrated that losartan lowers macroproteinuria in diabetic or non‐diabetic renal transplant recipients (RTx) similar to angiotensin converting enzyme (ACE) inhibitors. Microalbuminuria (MAU) may reflect subclinical hyperfiltration damage of the glomerulus. It could be a marker of kidney dysfunction in renal transplantation. The aim of the study was to assess the efficacy of losartan in hypertensive RTx with MAU. This study was conducted in 17 (M/F: 4/13) stable RTx. No change was made in the medical treatment of the patients. All cases received 50 mg/day losartan therapy for 12 wk. Renal functions and MAU were determined 12 and 6 wk and just before the treatment as well as sixth and twelfth week of the treatment in all patients. Losartan satisfactorily lowered systemic blood pressure. A significant reduction in MAU was observed from 103 ± 53 μg/min at the beginning to 59 ± 25 μg/min in the sixth week and 47 ± 24 μg/min in the twelfth week (p=0.0007 and 0.0005, respectively). From the sixth week of the treatment, the therapy significantly decreased hemoglobin, hematocrit and erythrocyte levels but did not change mean leukocyte and platelet counts, urea, creatinine levels and creatinine clearances. No serious side‐effect was observed during the study.

In conclusion, we found that losartan decreased MAU in hypertensive RTx. For that reason, it might be considered as the first choise antihypertensive agent for the renoprotection in selected patients.
De novominimal change disease associated with reversible post‐transplant nephrotic syndrome. A report of five cases and review of literature
Authors: Zafarmand Alireza A , Baranowska‐Daca Elzbieta , Ly Peter DC , Tsao Chun C , Choi Yeong‐Jin , Suki Wadi N , Truong Luan D
Published: March 2003

Zafarmand AA, Baranowska‐Daca E, Ly PDC, Tsao CC, Choi Y‐J, Suki WN, Truong LD.De novominimal change disease associated with reversible post‐transplant nephrotic syndrome. A report of five cases and review of literature. Clin Transplant 2002: 16: 350–361. © Blackwell Munksgaard, 2002

Nephrotic syndrome (NS) is frequent in renal transplant recipients and may be related to a large variety of glomerular lesions. In some of these cases, the transplant biopsy showed no significant glomerular changes and the NS was reversible, but the primary renal disease was not minimal change disease (MCD), suggesting that MCD may developde novoin renal transplant setting. Knowledge of this entity, however, is limited. Among 67 cases of post‐transplant NS encountered in a 12‐yr period, five were found to be associated withde novoMCD.

A critical review of the literature revealed nine additional cases ofde novoMCD. The data from these 14 cases show that patients withde novoMCD had a large variety of primary renal diseases but MCD or focal segmental glomerulosclerosis was not among them. Eight of the 14 transplanted kidneys (60%) were from living related donors, suggesting this as a risk factor. Nephrotic range proteinuria (3–76 g/d) developed immediately or shortly after transplantation (within 4 months for all reported cases, except for one at 24 months). The serum creatinine when NS was first diagnosed was normal or mildly elevated, but acute renal failure occurred in three patients. On biopsy, the glomeruli were normal or, more frequently, displayed mild, focal segmental mesangial sclerosis, hypercellularity, deposition of IgM/C3, or accumulation of mononuclear inflammatory cells in some glomerular capillaries. The tubulointerstitial compartment was normal in cases with normal renal function; displayed mild acute and/or chronic rejection that correlated with a mildly elevated serum creatinine; or showed acute changes including acute rejection, acute tubular necrosis, or acute cyclosporin A toxicity, which accounted for both acute renal failure at presentation and its subsequent reversibility.

Under various treatments, including increased steroids, angiotensin converting enzyme inhibitors, calcium channel blockers and angiotensin receptor blockers, sustained remission of NS was achieved in 13 cases, within a year (0.5–12 months) in 10 and later (24, 34 and 98 months, respectively) in three. In the remaining case, the patient died of septic shock 2 months after transplantation. After remission of the NS, the grafts functioned well without or with minimal proteinuria for several years.De novoMCD has characteristic clinical and pathologic features.

It represents an important but hitherto underemphasized cause of post‐transplant NS, which is potentially reversible and does not adversely affect the renal transplants.
Urodynamic testing predicts long‐term urological complications following simultaneous pancreas–kidney transplantation
Authors: Blanchet Pascal , Droupy Stéphane , Eschwege Pascal , Hammoudi Yacine , Durrbach Antoine , Charpentier Bernard , Benoit Gérard
Published: March 2003

Abstract: Introduction: Combined pancreas–kidney transplantation is the treatment of choice for patients with type I diabetes mellitus associated with chronic renal failure. The introduction of the bladder drainage technique constituted a marked improvement of the surgical technique with a reduction of life‐threatening complications. However, drainage of pancreatic secretions via the urinary bladder causes urological complications leading, in some cases, to cystoenteric conversion. We retrospectively analysed whether pre‐operative urodynamic findings may predict the subsequent development of urological complications and influence the choice of exocrine secretion drainage.

Patients and methods: From 1987 to 1997, 39 bladder‐drained simultaneous pancreas–kidney transplantations were performed in 16 men and 23 women with a mean age of 38.5 yr. All patients underwent a complete urological assessment prior to surgery, including medical history, physical examination, urethrocystography and urodynamic assessment.

Results: Twenty‐eight patients are alive with a mean follow‐up of 62 ± 8 months. In 60% of cases, both kidney and pancreas remain functional. Seven patients experienced recurrent lower urinary tract infections. Six patients suffered from chemical urethritis (four men and two women) and six suffered from recurrent haematuria (blood transfusions were required in two patients). One patient had incrusted stones at the site of duodenal staples. Urological complications were mostly observed in the 22 patients (79%) with abnormal urodynamic characteristics (Relative risk: 5.1). Intravenous Somatostatin®failed to definitively cure these complications in most cases. Seven patients (17%) (five with urethritis, two with haematuria) required cystoenteric conversion. Two patients developed post‐operative ileal fistula, one cutaneous and one into the bladder. All urinary symptoms resolved in these seven patients.

Conclusion: The frequency of specific urinary complications is high (28%) in bladder‐drained simultaneous pancreas–kidney transplantation patients. These complications are statistically more frequent in the case of an abnormal pre‐transplant urodynamic assessment.
Predominant factors associated with bone loss in liver transplant patients – after prolonged post‐transplantation period
Authors: Segal Elena , Baruch Yakov , Kramsky Rimma , Raz Batia , Tamir Ada , Ish‐Shalom Sophia
Published: March 2003

Abstract: Introduction: Osteoporosis is a major cause of morbidity in liver transplant recipients and is associated with multiple factors.

Objectives: To evaluate bone mineral density (BMD), bone turnover and calcium‐regulating hormones in 29 patients (17 men, 12 women) 2–12 yrs following liver transplantation for non‐alcoholic liver diseases.

Results: Fifteen patients (52%) were on immunosuppressive treatment with tacrolimus and 14 (48%) with cyclosporine. Eleven patients (38%) were currently on prednisone, 18 patients (62%) had stopped glucocorticoid treatment 6 months to 11 yrs prior to the study. Nineteen patients (65.5%) had decreased BMD according to WHO criteria, 17 (58.2%) at the femoral neck, 13 (44.8%) at the lumbar spine. Nineteen patients (65.5%) had a subnormal (<15 ng/mL) serum level of 25 (OH) D3. These patients had significantly lower BMD at the femoral neck (p = 0.02). Femoral neck BMD negatively correlated with serum parathyroid hormone level (p = 0.06, r = −0.35), length of the post‐transplantation period (p = 0.025, r = −0.416) and duration of glucocorticoid treatment (p = 0.029, r = −0.406), regardless of its cumulative dose. Symptomatic fractures were less frequent in tacrolimus treated patients than in cyclosporine users (p = 0.03).

Conclusions:  Decreased BMD is frequent following liver transplantation and is affected by vitamin D deficiency, cyclosporine use, and the duration of glucocorticoid therapy, but not by its cumulative dose. Achievement and maintenance of optimal vitamin D status and shortening of glucocorticoid treatment period may have a favorable effect on bone preservation.
Individualized T cell monitored administration of ATG versus OKT3 in steroid‐resistant kidney graft rejection
Authors: Midtvedt Karsten , Fauchald Per , Lien Bjoern , Hartmann Anders , Albrechtsen Dagfinn , Bjerkely Birgitte L. , Leivestad Torbjoern , Brekke Inge B.
Published: March 2003

Abstract: Acute steroid‐resistant rejection episodes are recommended to be treated with set doses of anti‐thymocyte globulin (ATG) or anti‐CD3 monoclonal antibody (OKT3). Individualized T cell monitoring has been proposed as a tool for dose finding. A randomized study comparing the efficacy and safety of ATG (n = 27) with OKT3 (n = 28) in the treatment of biopsy verified acute steroid‐resistant rejection (ASRR) when both drugs were administered on the basis of daily individualized T cell measurements. A drop to below 50 cells/mm3 CD2+ T cells was considered adequate and used to guide the dose of ATG/OKT3. Demographic, clinical and histopathological severities of rejections were equal in the two groups. During the 10 days of T cell monitoring and antibody treatment, 13 patients were in need of dialysis (ATG = 7/OKT3 = 6). Two grafts did not respond to antibody treatment and were lost due to rejection (ATG = 1/OKT3 = 1). There were 26 biopsy verified re‐rejections (ATG = 12/OKT3 = 14) within the first 3 months following antibody treatment. Mean serum creatinine (μmol/L) was similar in the two groups (ATG/OKT3: before rejection 157 ± 72/151 ± 88, at start of antibody treatment 308 ± 125/330 ± 94, end of antibody treatment 254 ± 122/246 ± 144 and at follow‐up after a mean of 32 months 166 ± 55 (n = 24)/164 ± 57(n = 23)). To keep the T cell count below 50 cells/mm3, average dose ATG given was 354 ± 151 mg (2.3 administrations, range 1–4) and average OKT3 was 32.5 ± 6.8 mg in 10 doses. In conclusion, individualized T cell monitored administration of ATG and OKT3 is safe and seems as effective as a standard set dose in treatment of ASRR. Tailoring the dose for each individual patient lowers the cost.
Impact of substance abuse on the course and treatment of bipolar disorder
Authors: Salloum Ihsan M , Thase Michael E
Published: March 2003

Objectives:

The objectives of this article are to review the prevalence, natural history, pathophysiology, and treatment of comorbid bipolar disorder with alcoholism and other psychoactive substance use disorders (PSUDs).

 Methods: All identified bibliographies through a literature search of all Medline files and bibliographies of selected articles focusing on the prevalence, natural history, course, prognosis, inter‐relationship, and treatment of bipolar disorder with comorbid alcoholism and other PSUDs were reviewed.

 Results and conclusions: Comorbidity of bipolar disorder and alcoholism and other PSUDs is highly prevalent. The presence of this so called ‘dual diagnoses’ creates a serious challenge in terms of establishing an accurate diagnosis and providing appropriate treatment interventions. The inter‐relationship between these disorders appears to be mutually detrimental. The course, manifestation, and treatment of each condition are significantly compounded by the presence of the other condition. Substance abuse and alcoholism appear to significantly complicate the course and prognosis of bipolar disorder resulting in increased suffering, disability, and costs. On the other hand, bipolar disorder may be a risk factor for developing PSUDs. Although, there are a number of hypotheses explaining the pathophysiological mechanism involved in such comorbidities, our understanding of the exact nature of such neurobiological mechanisms is still limited. While the antikindling agents and targeted psychotherapeutic techniques may be useful intervention strategies, there is still a significant lack of empirically based treatment options for these patients.
The clinical epidemiology of pure and mixed manic episodes
Authors: Cassidy Frederick , Carroll Bernard J
Published: March 2003

Introduction:
Few large clinical epidemiological studies have been undertaken comparing subjects meeting criteria for mixed and pure states of bipolar disorder. In part, the difficulty comparing these states emanates from confusion in their diagnostic separation. In the current report, we use a definition derived from receiver operating characteristic (ROC) curve analysis as an alternative to the DSM‐IIIR/IV definition, and we compare the two subtypes of manic episodes.   Methods: Three hundred and sixty‐six patients meeting DSM‐IIIR criteria for bipolar disorder, manic or mixed, were categorized using newly described criteria for mixed states. The two subtypes were compared on demographic variables and clinical history variables, using multiple analysis of variance with post hoc univariate F tests. The same analyses were conducted using the DSM‐IIIR‐defined subtypes.   Results: Using the ROC criteria, 79 subjects (21.6%) were characterized as mixed, in contrast to 51 subjects (13.9%) using DSM‐IIIR criteria for bipolar disorder, mixed. The ROC‐defined mixed manic group comprised more Caucasians and more females. Age of first psychiatric hospitalization was earlier and duration of illness longer in the mixed group. First episodes were unlikely to be categorized as mixed (<5%). When the DSM‐IIIR definition was employed, differences were not demonstrated.   Conclusions: An earlier age of first psychiatric hospitalization and increased duration of illness, as well as a lower frequency of mixed subtype of manic episode during first hospitalization, are compatible with the view that mixed manic episodes occur more frequently later in the course of bipolar disorder. Moreover, differences in race, sex, and clinical histories of subjects in mixed episodes tend to support the separation of mixed mania as a diagnostic subtype of bipolar disorder.
3′(2′)‐Phosphoadenosine 5′‐phosphate phosphatase is reduced in postmortem frontal cortex of bipolar patients
Authors: Shaltiel G , Kozlovsky N , Belmaker R H , Agam G
Published: March 2003

Shaltiel G, Kozlovsky N, Belmaker RH, Agam G. 3′(2′)‐Phosphoadenosine 5′‐phosphate phosphatase is reduced in postmortem frontal cortex of bipolar patients. Bipolar Disord 2002: 4: 302–306. © Blackwell Munksgaard, 2002

Objective:
3′(2′)‐Phosphoadenosine 5′‐phosphate (PAP) phosphatase is a novel lithium (Li) inhibitable enzyme. Thus the enzyme seemed an important candidate for studies of the molecular etiology of bipolar disorder.

Methods:
RT–PCR, Western‐blot analysis and Pi liberation were used to measure PAP phosphatase mRNA levels, protein levels and enzyme activity (respectively) in postmortem frontal cortex specimens of bipolar patients versus normal subjects.

Results:
The PAP phosphatase protein levels were 24% significantly lower in bipolar patients than in normal subjects. PAP phosphatase mRNA levels and enzymatic activity did not differ between normal controls and bipolar patients.

Conclusions:
Abnormality of PAP phosphatase in bipolar patients offers a new direction for study of bipolar disorder etiology.