bluuebunny/crossref_metadata_2025 huggingface dataset:
Mycophenolate mofetil, with cyclosporine and prednisone, reduces early rejection while allowing the use of less antilymphocytic agent induction and cyclosporine in renal recipients with delayed graft function
Authors: Arnold Angelo N , Wombolt Duane G , Whelan Thomas V , Chidester Paul D , Restaino Irene , Gelpi Barbara , Stewart Marion , Hurwitz Richard L , McCune Thomas R
Published: March 2003

Antilymphocytic agent induction (ALAI), with antithymocyte globulin or monoclonal antibody, is generally used in renal transplantation (TX) to spare renal allografts with poor initial function from the toxic effects of cyclosporine (CsA) and/or to augment immunosuppression (IS) in the patient at a high risk for early rejection. ALAI, unfortunately, increases the cost of TX and the risk to the patient, having been associated with many adverse side effects. An IS protocol, which results in a low incidence of early rejection while using less CsA and ALAI, is a worthwhile goal.  We compare our experience with mycophenolate mofetil (MMF), CsA, and prednisone (MMFCP; n=62) to our azathioprine (AZA), CsA, and prednisone (AZACP; n=50) triple‐drug IS, with and without ALAI. The patient characteristics for age, race, first TX, cadaveric donor, pediatric recipient, and dialysis in the first post‐op week (DGF) were not different for the MMFCP versus AZACP groups. There were more females in the MMFCP group (51.6% versus 30.0%, p=0.022).  We report that rejection‐free survival at 6 months (RF6) was better in the MMFCP versus AZACP group (83.9% versus 60.0%, p=0.005). Less ALAI and CsA were used in the MMFCP patients. At 1 year, actuarial graft survival was 91.9% in the MMFCP group and 81.9% in the AZACP group (p=0.116). Actuarial 1‐year patient survivals were not different in the two patient groups. In the sub‐population of patients with DGF, the RF6 in the MMFCP (n=13) group was 92.3% versus 57.1% in the AZACP (n=14) group (p=0.041). The reduction in early rejection episodes in the patients on MMFCP with DGF was accomplished while using half as much ALAI and lower CsA doses and levels. The African‐American recipient sub‐population on MMFCP also demonstrated an improvement in RF6 while using less ALAI and CsA (78.6% versus 48.0%, p=0.022).  We conclude that the use of MMF‐based triple‐drug IS results in fewer rejection episodes while allowing for lower CsA levels and less ALAI, even in patients with delayed graft function.
Partial venous thrombosis of the pancreatic allografts after simultaneous pancreas–kidney transplantation
Authors: Ciancio Gaetano , Cespedes Merida , Olson Les , Miller Joshua , Burke George W
Published: March 2003

Despite new advances in transplantation, complete venous thrombosis (VT) of the pancreas after simultaneous pancreas–kidney (SPK) transplantation usually results in graft loss. Data are limited regarding the outcome and treatment of partial VT of the pancreas allograft. From July 1994 to December 1999, 126 patients with IDDM/end‐stage renal disease underwent SPK with systemic bladder drainage at the University of Miami. We retrospectively reviewed our experience regarding the outcome and treatment options of partial VT of the pancreas allografts. From July 1994 to April 1997, partial VT was not seen in the first 66 SPK patients induced with anti‐CD3 rnAb and oral or intravenous (i.v.) tacrolimus (TAC) in the operating room. From May 1997 to June 1999, 14 (29%) out of 48 patients had VT. These cases were identified following the i.v. use of TAC with anti‐IL‐2R antibody‐induction therapy (7/15) or without (7/33). Partial thrombosis of the splenic vein (PTSV) was documented in 10 patients, 2 had complete thrombosis of the splenic vein (CTSV), 1 had partial thrombosis of the superior mesenteric vein (PTSMV), and 1 patient had PTSV and PTSMV. These were identified incidentally during routine color Doppler ultrasonography (CDU). None of these SPK recipients demonstrates a change in clinical parameters. The first 8 patients were systemically heparinized, followed by oral anticoagulation, except 1 patient with CTSV. He progressed to complete thrombosis of the pancreas allograft and was treated with percutaneous thrombectomy and urokinase infusion, followed by heparinization and oral anticoagulation. One patient required exploration for bleeding. In an attempt to reduce the morbidity of heparinization, we treated the next 6 patients with PTSV with aspirin followed by serial CDU. All 14 patients had preservation of the endocrine and exocrine pancreatic functions. CDU showed resolution with recanalization of the thrombosed vein(s). From July 1999 to December 1999, 12 SPK recipients were administered TAC orally with or without induction therapy with anti‐IL‐2R antibody. So far, in this group, VT has not been identified. In summary, a total of 14 out of 126 patients (11%) had isolated VT with a mean follow‐up of 36.4 months. Based on our experience, we suggest that extensive VT after pancreas transplantation, including splenic and superior mesenteric VT, be treated with heparin and subsequent oral anticoagulation for 3 months. For more limited, partial splenic VT, aspirin may be sufficient. Follow‐up CDU is critical for a successful outcome. The i.v. use of TAC appears to be a risk factor for the increased incidence of VT. Currently, using IL‐2rmAb as induction, TAC is started orally on postoperative days 3 or 4 and aspirin on postoperative day 2.
Immunoglobulin A and secretory immunoglobulin A in the bronchoalveolar lavage from patients after lung transplantation
Authors: Bastian Andreas , Tunkel Christine , Lins Markus , Böttcher Heidi , Hirt Stephan W , Cremer Jochen , Bewig Burkhard
Published: March 2003

Secretory immunoglobulin A (sIgA) is the most important Ig on mucosal surfaces. In bronchoalveolar lavage (BAL) fluid, sIgA is mainly produced by bronchus‐associated lymphoid tissue (BALT). The presence of pre‐formed antibodies against donor tissue in kidney transplantation is associated with hyperacute rejection, indicating a humoral (antibody‐mediated) reaction. In heart and liver transplantation, humoral rejection has also been documented. The goal of this study was to evaluate the role of IgA in patients after lung transplantation. An enzyme‐linked immunosorbent assay was established to determine the levels of sIgA, IgA, and total protein in the lavage. IgA and sIgA were both detectable in BAL from transplanted lungs. IgA and sIgA levels were both higher during episodes of infection than during episodes of rejection or during the control episodes. The level of IgA during episodes of rejection equaled the level of IgA during the control episodes. The level of sIgA was significantly decreased during episodes of acute rejection (1.8±1.0 μg/mL) when compared with the control (7.2±1.0 μg/mL; p=0.013). This study demonstrates that BALT retains the ability to produce Ig even after lung transplantation. The levels of IgA and sIgA and their ratio do not contribute to the differentiation between rejection and infection in lung‐transplanted patients.
Pure red cell aplasia caused by Parvovirus B19 infection in solid organ transplant recipients: a case report and review of literature
Authors: Geetha Duvuru , Zachary James B , Baldado Helen M , Kronz Joseph D , Kraus Edward S
Published: March 2003

Human Parvovirus B19 (PV B19) is one of the several recently described ‘emerging viruses’ and has been identified as the etiological agent of ‘fifth disease’ in childhood. Human PV B19, which is the etiological agent of transient erythroblastopenia in hemolytic anemia, is also a recognized rare cause of red cell aplasia in immunocompromised patients, including transplant recipients. To date, 26 cases of PV B19‐induced red cell aplasia have been reported in solid organ transplant recipients. Twelve patients had cyclosporine‐based immunosuppression and 14 had tacrolimus‐based immunosuppression. Sixteen of these patients required treatment with commercial intravenous immunoglobulin alone, 1 required treatment with intravenous immunoglobulin and plasmapheresis, 4 required intravenous immunoglobulin and erythropoietin, 1 required treatment with intravenous immunoglobulin and conversion of tacrolimus to cyclosporine, 1 had improvement in hematocrit with erythropoietin alone and in 3 patients the disease was self‐limiting. Herein, we report a case of pure red cell aplasia caused by acute PV B19 infection in a renal transplant recipient in whom the immunosuppressive regimen included prednisone, mycophenolate mofetil and tacrolimus and the red cell aplasia resolved with discontinuation of mycophenolate mofetil.
IgM antibodies identified by a DTT‐ameliorated positive crossmatch do not influence renal graft outcome but the strength of the IgM lymphocytotoxicity is associated with DR phenotype*
Authors: Bryan C. F. , Martinez J. , Muruve N. , Nelson P. W. , Pierce G. E. , Ross G. , Shield C. F. , Warady B. A. , Aeder M. I. , Harrell K. M. , Helling and T. S. , Luger A. M.
Published: March 2003

A positive crossmatch that is rendered negative by treating the serum with the IgM‐reducing agent dithiothreitol (DTT) is generally reported not to influence short‐term renal graft outcome. Its effect on long‐term (3 years) cadaveric and live‐donor transplant function, however, is less clear. We evaluated the effect of IgM antibodies in a DTT‐ameliorated positive crossmatch (DTT‐APXM) on long‐term renal graft outcome in 1290 consecutive cadaveric renal transplants (8‐year survival) and 384 live‐donor renal transplants (7‐year survival) from patients transplanted between 1990 and 1999. The data show that 1‐ and 8‐year graft survival for cadaveric renal transplants in patients with IgM antibodies (n=72) (DWFG censored=91% and 65%; DWFG not censored=90% and 60%) was not significantly different from the group without IgM antibodies (n=1218) (DWFG censored=92% and 71%; DWFG not censored=87% and 55%) (log‐rank=0.25 for DWFG censored, log‐rank=0.92 for DWFG not censored). The one‐ and seven‐year graft survival for live‐donor renal transplants in patients with IgM antibodies seen in a DTT‐APXM (n=22) (DWFG censored=95% and 83%; DWFG not censored=95% and 66%) was not significantly different from the group without IgM antibodies (n=362) (DWFG censored=94% and 81%; DWFG not censored=92% and 73%) (log‐rank=0.61 for DWFG censored, log‐rank=0.89 for DWFG not censored). DR phenotype was found to be associated with the strong (>40% cell death) IgM reactivity in both black and white patients. In white patients, DR2 was more frequently seen with a strong IgM crossmatch (48.2%) than in molecularly typed controls (28.5%) (P<0.03) and concomitant with that DR increase, DR4 was decreased in white patients (6.8%) compared with controls (25.5%) (P<0.02). In black patients with strong IgM reactivity, DR6 was increased in patients (46.1%) compared with controls (20.5%) (P=0.07) and concomitant with that DR6 increase, DR5 was decreased in frequency in black patients (7.6%) compared with controls (41%) (P<0.03). These data show that long‐term graft survival in renal transplantation is not negatively influenced by the presence of donor‐reactive lymphocytotoxic antibodies in the crossmatch ameliorated by serum DTT treatment. They also suggest that the strength of the IgM antibody response is regulated in part by certain gene (s) of the DR region.
Treatment of severe acute graft‐versus‐host disease with anti‐thymocyte globulin
Authors: Remberger Mats , Aschan Johan , Barkholt Lisbeth , Tollemar Jan , Ringdén Olle
Published: March 2003

Severe acute graft‐versus‐host disease (GVHD) is one of the major complications after haematopoietic stem‐cell transplantation (HSCT). Treatment of severe GVHD is difficult and the condition is often fatal. One proposed method of improving the therapy is to include anti‐thymocyte globulin (ATG). Here, we will report our results in 29 patients using ATG as part of treatment for severe steroid‐resistant acute GVHD. Four patients suffered from grade II, 13 from grade III and 12 from grade IV GVHD. Median time to grade II GVHD was 24 d (range 7–91 d) and to grade III was 29 d (range 8–55 d) after HSCT. Five different ATG preparations were used, rabbit ATG (R‐ATG), BMA 031, OKT®‐3, ATG‐Fresenius and Thymoglobuline®. All patients had skin involvement, 26 also had gut involvement and 25 had liver involvement. The rate of response to treatment was best in skin involvement (72%), while liver and gut involvement showed lower response rates (38%). Eleven patients survived more than 90 d, 7 of them developed chronic GVHD, 1 developed mild GVHD, 1 developed moderate GVHD and 5 developed severe GVHD. Survival at 100 d was 37% and at 1 yr it was 12%. Most patients died of GVHD, with virus or fungal infections as contributing causes of death.   To conclude, treatment of severe acute GVHD is difficult and ATG, in our hands, adds nothing to conventional pharmacological treatment.
Low rejection rates with tacrolimus‐based dual and triple regimens following liver transplantation
Authors: Boillot O , Baulieux J , Wolf P , Messner M , Cherqui D , Gugenheim J , Pageaux G , Belghiti J , Calmus Y , Le Treut Y , Neau‐Cransac M , Samuel D
Published: March 2003

We studied the outcome of 345 liver transplant patients who received tacrolimus‐based immunosuppressive therapy either as a dual regimen (with corticosteroids, n=172) or as a triple regimen (with corticosteroids and azathioprine, n=173) for 3 months after transplantation (3‐month cohort). A further analysis was conducted for the first 195 patients randomised (dual n=100, triple n=95) who were followed up for 12 months after transplantation (12‐month cohort).   For the 3‐month cohort, patient survival was 90.7% (dual) and 91.9% (triple), graft survival after 3 months was 88.4% (dual therapy) and 89.6% (triple therapy). Acute rejections were experienced by 67/172, 39.0% of patients on dual therapy and by 60/173, 34.7% of patients on triple therapy; corticosteroid‐resistant rejections were reported in 9 patients (5.2%) in either treatment group. The overall safety profile was similar for the two treatment groups. Significant differences, however, were found for thrombocytopenia (dual 13/172, 7.6%, triple 37/173, 21.4%, p<0.001) and leukopenia (dual 4/172, 2.3%, triple 24/173, 13.9%, p<0.001).   For the 12‐month cohort, patient survival was 85.6% (dual) and 88.4% (triple) after 1 year. Graft survival was 81.7% (dual) and 85.2% (triple) 12 months after transplantation. Acute rejections were reported for 38/100, 38.0% of patients on dual therapy and 36/95, 37.9% of patients on triple therapy, corticosteroid‐resistant rejections were 7/100, 7.0% (dual) and 7/95, 7.4% (triple) of patients. In the 12‐month cohort, no significant differences in the safety profiles of the treatment groups were found. We conclude that both tacrolimus‐based dual and triple drug regimens provide effective and safe immunosuppression following orthotopic liver transplantation.
The cadaveric kidney and the organ shortage – a perspective review
Authors: Brasile L , Stubenitsky B , Booster M , Kootstra G
Published: March 2003

Despite the technical and logistical hurdles that must be overcome with the reintroduction of non‐heartbeating donor kidneys, the potential of these organs represents the only near‐term solution for effectively alleviating the growing disparity between demand and supply. This review provides an argumentative overview of the history of cadaveric kidney transplantation. During the early years of transplantation retrieval of kidneys from non‐heartbeating donors necessitated a prolonged period of warm ischemic exposure, with a corresponding minimalex vivoperiod since organ preservation was in its infancy. Today we have the inverse situation where warm ischemic times are quite limited and hypothermic preservation times average 24 h because organs are shipped to remote centers due to mandated organ sharing algorithms. The recent experience with the reintroduction of non‐heartbeating donors has necessitated combining the worst aspects from both eras: substantial warm ischemia with prolonged hypothermic preservation.  Nevertheless, recent results from several transplant groups poignantly highlight the potential of this approach in expanding the organ donor pool.
Religious beliefs and opinions on clinical xenotransplantation – a survey of university students from Kenya, Sweden and Texas
Authors: Hagelin Joakim , Hau Jann , Schapiro Steven J , Suleman Mbaruk A , Carlsson Hans‐Erik
Published: March 2003

This study investigated the association between religious beliefs and opinions on xenotransplantation among students from three different countries. A lower proportion of religious students accepted xenotransplantation than did non‐religious students. A higher proportion of Protestant students seemed to accept xenotransplantation than did Muslim and Roman Catholic students. A higher proportion of the religious respondents had not formed an opinion on xenotransplantation compared to non‐religious students. There was no difference according to gender on views on xenotransplantation, but a higher proportion of older students seemed to accept xenotransplantation than did younger students. A higher proportion of non‐vegetarians reported acceptance of xenotransplantation than did vegetarians. Acceptance of xenotransplantation was higher in Sweden compared to the two other regions, and the proportion of students who had formed an opinion was higher as well.
The impact of obesity in renal transplantation: an analysis of paired cadaver kidneys
Authors: Yamamoto Shinji , Hanley Eileen , Hahn Amy B , Isenberg Andrew , Singh T Paul , Cohen Dennis , Conti David J
Published: March 2003

Background: Previous studies indicate that obesity is a risk factor in renal transplantation. However, these analyses did not control for variable donor factors that may strongly influence outcome. To control for donor variables such as age, cause of death, procurement techniques, preservation methods, cold ischaemia time and implantation technique, we analysed patient and graft survival in recipients of paired kidneys, derived from the same procurement procedure, preserved in the same manner, subjected to similar cold ischaemia time and implanted by the same surgical team. Between June 1992 and August 1999, 28 procurement procedures provided kidneys which were transplanted into one obese and one non‐obese recipient. Body mass index (BMI) was calculated as kg/m2. Recipients were classified as obese (BMI > 30) or non‐obese (BMI < 30). Immunotherapy for all recipients consisted of a triple therapy regimen of cyclosporine or prograf, azathioprine or cellcept, and prednisone. Patients with delayed graft function (DGF), defined as the need for dialysis within 72 h of the transplant procedure, were treated with anti‐thymocyte globulin (ATG) or thymoglobulin (TMG) induction for 5–7 d. The rate of DGF (7.1 versus 10.7%) and acute rejection (39.3 versus 35.7%) were similar in the obese and non‐obese recipient groups. Patient survival was similar at 1, 3 and 5 yr in both groups. In addition, graft survival was similar at 1 yr. However, a trend toward decreased medium‐term graft survival, which reached significance at 5 yr, was observed in the obese group. Furthermore, mean serum creatinine at 1 yr was higher in the obese group (2.0) compared with the non‐obese group (1,4) (p=0.12). This analysis of paired cadaver kidneys indicated that obesity is not a risk factor for DGF, acute rejection, and 1‐yr graft survival. However, a decreased medium‐ and long‐term graft survival trend, which reached statistical significance at 5 yr, was observed in obese recipients.
The impact of ethnic miscegenation on tacrolimus clinical pharmacokinetics and therapeutic drug monitoring
Authors: Felipe Claudia R , Silva Helio T , Machado Paula GP , Garcia Riberto , Da Silva Moreira Silvia R , Pestana José OM
Published: March 2003

Abstract: The impact of ethnic miscegenation on tacrolimus clinical pharmacokinetics and therapeutic drug monitoring. We sought to determine the influence of ethnic miscegenation on tacrolimus pharmacokinetics and trough concentrations during the first 6 months after transplantation.

Methods: Tacrolimus concentrations were measured in blood samples obtained from 22 transplant recipients during the first week of transplant, within pharmacokinetic profiles, and throughout the first 6 months post‐transplant, using the Pro Tac II ELISA method. Pharmacokinetic parameters and between‐ and within‐subject blood concentration variability were compared stratifying the total population in two distinct ethnic groups of white (W) and non‐white (NW) patients, according to a stringent criterion.

Results: Between‐subject variability in dose‐adjusted concentrations during dosing interval varied from 38.8 to 69.5%. Compared with W patients, NW patients showed higher variability in blood tacrolimus concentrations during dosing interval (37.40 ± 5.64 vs. 56.95 ± 11.49, p < 0.001) and lower drug exposures (AUC: 229.4 ± 55.5 vs. 66.9 ± 67.1 ng × h/mL, p=0.036). The correlation coefficients (r2) betweenC0,C12orCmaxand AUC were 0.83, 0.91 and 0.5, respectively. An equation derived from early time concentrations (C0,C1.5andC4) accounted for 94% of the variability observed in AUC. Compared with W patients, a higher proportion of tacrolimus blood determinations during the first week were below 10 νg/mL in NW patients (24% vs. 62%, p=0.028). Tacrolimus absorption increased from week 1–4 (1.1 ± 0.53 vs. 1.73 ± 0.97 νg/mL/mg, p < 0.0001) but was still showed high between‐ (41.6–70.4%) and within‐subject (18.2–32.5%) variability, regardless of ethnicity, after stabilization.

Conclusion: Non‐white patients show higher tacrolimus variability and lower drug exposures after transplantation compared with W patients. Therefore, higher initial tacrolimus doses and intensive monitoring are recommended when administering tacrolimus‐based immunosupressive therapy to NW patients of this transplant population.
Reduced dose Thymoglobulin®, tacrolimus, and mofetil mycophenolate results in excellent solitary pancreas transplantation outcomes
Authors: Tan Michael , Cantarovich Marcelo , Mangel Roman , Paraskevas Steven , Fortier Michelle , Metrakos Peter
Published: March 2003

Abstract:  Background:  Graft survival following solitary pancreas transplantation has traditionally lagged behind that of simultaneous pancreas–kidney transplants. Thymoglobulin® (TMG), a polyclonal rabbit‐derived antilymphocyte antibody was originally introduced as treatment for acute rejection of renal allografts. However, data regarding the efficacy of TMG induction in solitary pancreas transplants is lacking. We present the 1‐yr graft survival and acute rejection rate of 22 solitary pancreas transplants performed at the McGill University Health Centre using reduced dose TMG induction with lower dose tacrolimus and mophetil mycophenolate.

Patients and methods:  Eighteen pancreas after kidney and four pancreas transplants alone were performed between January 1998 and October 2000 at McGill University. Induction therapy with TMG at a starting dose of 1.5 mg/kg/d was started 12 h post‐operatively. The daily dose of TMG was held if the total leukocyte count was <2500/mm3 or if the lymphocyte count was <100/mm3. Maintenance therapy was initiated with steroids (tapered to 20 mg prednisone orally once a day) tacrolimus (2 mg twice a day), and mofetil mycophenolate (1 g daily).

Results:  Patients received three to seven doses of TMG over the first seven post‐operative days at a dose of 0.85 ± 0.27 mg/kg/d (mean ± SD). The mean follow‐up was 1.28 ± 0.14 yr. The 1‐yr patient and graft survival was 100% (22 of 22) and 96% (21 of 22), respectively. The 1 yr acute rejection rate was 27.3% (six of 22). Five of the six rejections responded to steroid boluses. One was refractory to steroids and TMG resulting in graft loss. Presumed rejections were diagnosed on the basis of decreasing urine amylase and/or hyperglycemia.

Discussion:  Monitoring the total leukocyte and lymphocyte count resulted in a 43% reduction in the amount of TMG used compared with the recommended dosing. Despite the reduced amounts, patient and graft survival were excellent with acute rejection rates comparing favorably to other published series.
Impact of HLA‐compatibilities in patients undergoing liver transplantation for HBV‐cirrhosis
Authors: Neumann Ulf P , Langrehr Jan M , Naumann Uta , Lang Martina , Rayes Nada , Steinmüller Thomas , Radtke Cornelia , Neuhaus Peter
Published: March 2003

Liver transplantation (OLT) for end‐stage chronic hepatitis‐B‐virus (HBV) infection is frequently complicated by HBV recurrence. In the present study we investigated whether human leucocyte antigen (HLA)‐matching influences the outcome after OLT.

In a retrospective analysis we reviewed 84 recipients of liver transplants for end‐stage HBV‐cirrhosis and complete HLA‐typing for outcome after OLT. Follow‐up ranges from 1 to 110 months (median=55.6 months). Immunosuppression consisted of Cyclosporin A (CsA)‐based quadruple induction therapy or Tacrolimus‐based induction protocols.

Immunoprophylaxis with hepatitis B immunoglobulin was started at OLT and continued long‐term.

Actuarial 1‐ and 5‐yr graft survival figures were 90.5 and 80.4%, respectively. Hepatitis‐B recurrence was responsible for 15 of 20 (75%) graft failures. We observed a significantly improved graft survival in patients with more HLA‐A, ‐B compatibilities (p=0.02), whereas the degree of HLA‐DR compatibilities did not influence the outcome. The occurrence of HBV‐reinfection was significantly lower in HLA‐A, ‐B matched grafts (p < 0.05). Additionally, graft survival was prolonged in patients with HBV‐reinfection and 1 or 2 HLA‐B compatibilities when compared with patients with HBV‐reinfection and a complete HLA‐B mismatch (p=0.02).

In conclusion, this retrospective analysis shows that more HLA‐A, ‐B compatibilities seems to be associated with an improved graft survival in patients after OLT for end‐stage HBV infection.
Significance of serial real‐time PCR monitoring of EBV genome load in living donor liver transplantation
Authors: Matsukura Tadashi , Yokoi Akiko , Egawa Hiroto , Kudo Toyoichiro , Kawashima Mayumi , Hirata Yoshihiro , Tanaka Hirokazu , Kagajo Kiyoko , Wada Hiromi , Tanaka Koichi
Published: March 2003

Background: Quantitative analysis of the Epstein–Barr virus (EBV) genome has been recently reported to be helpful for early identification of EBV viremia which could reduce the risk of post‐transplantation lymphoproliferative disorder (PTLD).

Aim: To demonstrate the significance of serial monitoring of EBV genome load by real‐time quantitative polymerase chain reaction (PCR) after living donor liver transplantation.

Methods: From March 1999 to April 2000, the EBV genome load in peripheral blood mononuclear cells (PBMNC) was measured serially in a total of 15 recipients of living donor liver transplantation (LDLT) who had a symptomatic EBV infection.

Results: In 15 patients, the mean values of the highest EBV DNA levels from the patients who had fever, URS, diarrhea, ascites, lymphadenopathy and PTLD were 36 232, 16 040, 15 968, 2485, 336 858 and 60 486 copies/μg DNA, respectively. Patients were treated by reduction or discontinuation of immunosuppressives and/or antiviral agents. The EBV DNA levels decreased in all these patients following the recovery from their symptoms. We encountered two cases of PTLD during this study period. One of them was referred to us after the onset of PTLD and one had been undergoing aggressive immunosuppression treatment for severe rejection. Both were successfully treated.

Conclusions: Serial quantitative analysis of the EBV genome load by means of real‐time PCR are thought to be useful for preventing PTLD through adjustment of the immunosuppression level in response to the viral genome load following symptomatic EBV infection.
Abnormalities in protein kinase C signaling and the pathophysiology of bipolar disorder
Authors: Hahn Chang‐Gyu , Friedman Eitan
Published: March 2003

Protein kinase C (PKC) is a group of calcium and phopholipid‐dependent enzymes, which plays a pivotal role in cell signaling systems. Recently accumulated evidence indicates that alterations in PKC activity play a significant role in the pathophysiology of bipolar disorder. A number of laboratories investigated the effect of mood stabilizers on the regulation of PKC activity in bipolar patients, in animals, and in cultured cells. Following chronic lithium treatment, PKC activation was significantly reduced in rat brains, as measured by the translocation of cytoplasmic PKC to the membrane compartment, or by quantitative binding of the PKC ligand, PDBu. The effect of the therapeutic concentration of lithium in attenuating PKC‐dependent intracellular parameters was also demonstrated in cultured cells. More importantly, alterations in platelet PKC was shown in bipolar patients during the manic state of the illness. In comparison to patients with major depressive disorder, schizophrenia, or healthy controls, PKC activity was significantly increased in manic patients, suggesting that changes in PKC may be an illness‐specific marker. Interestingly, enhanced PKC activity during mania was suppressed following mood‐stabilizer treatment as manic symptoms improved. In parallel to the findings in platelets, postmortem studies demonstrate that membrane‐associated PKC and stimulation‐induced translocation of cytosolic enzyme to the membrane were also increased in frontal cortex of bipolar patients. Other studies suggest alterations in other signal transduction mechanisms in bipolar disorder. These include alterations in G protein activation, phosphatidylinositol (PI) signaling, cyclic AMP formation, and intracellular calcium homeostasis. The alterations of PKC activity in bipolar disorder may be related to changes in these other intracellular signaling mechanisms. Alternatively, the changes of PKC activity may be the core pathology of the illness. More studies are required to further characterize the association of PKC changes with bipolar disorder, using a proper neuronal model.
Clinical characteristics of familial and non‐familial bipolar disorder
Authors: Moorhead Steven , Scott Jan
Published: March 2003

Objective:

To explore the clinical characteristics of familial and non‐familial bipolar disorder.   Method: Twenty subjects with bipolar disorder, who also had a family history of bipolar disorder in a first degree relative, were matched for current age, age of first onset of bipolar disorder and gender with 20 subjects with bipolar disorder who had no family history of any psychiatric disorders in first or second degree relatives.   Results: Fourteen subjects in each group were female. The mean age at interview was 45.2 years and the mean age at first admission was 26 years. Although familial and non‐familial probands had an equivalent number of illness episodes, familial probands were significantly more likely to experience mixed states as compared to non‐familial probands. The latter experienced significantly more depressive episodes and had significantly higher neuroticism (N) scores on the Eysenck Personality Inventory (EPI; Eysenck H, Eysenck S. Manual of the Eysenck Personality Inventory. London: University of London Press, 1964.).   Conclusions: If the results are replicated, they have important implications. For example, such data may aid decisions about the targeting of additional psychosocial interventions in high N score cases. Researchers will wish to investigate whether mixed states show a stronger association with early age of onset or family history of BD.
Association studies of bipolar disorder
Authors: Craddock Nick , Davé Subodh , Greening Jayne
Published: March 2003

Association studies in outbred populations represent an important paradigm for investigation of complex traits, such as bipolar disorder, both to follow‐up regions of interest from linkage studies (by systematic linkage disequilibrium mapping and positional candidate studies) and for pure functional studies. The advantages of the association method include its relative robustness to genetic heterogeneity and the ability to detect much smaller effect sizes than are detectable using feasible sample sizes in linkage studies.   The candidate gene approach is potentially very powerful, particularly when used within the context of a VAPSE (variation affecting protein structure or expression) paradigm, but a major problem is that the efficiency in the choice of candidates is inevitably a function of the level of previous understanding of disease pathophysiology. To date, most candidate gene studies in bipolar disorder have focussed on the major neurotransmitter systems that are influenced by medication used in clinical management of the disorder. Early studies often used anonymous markers in the hope of detecting linkage disequilibrium but recently direct examination of polymorphisms of known or presumed functional relevance has become more usual. Most studies in the literature have been of the unrelated case–control design with samples rarely exceeding 200–300 subjects. No definitive findings have yet emerged although there have been some interesting preliminary findings including those with polymorphisms within the genes encoding catechol‐o‐methyl transferase (COMT), monoamine oxidase A (MAOA) and the serotonin transporter (hSERT; 5‐HTT).   In this article we critically review the current status of the literature within the context of the important methodological issues and limitations inherent in the use of association studies for genetic dissection of bipolar disorder. We conclude by examining likely future directions and developments in the field.
Childhood mania, attention deficit hyperactivity disorder and conduct disorder: a critical review of diagnostic dilemmas
Authors: Kim Eunice Y , Miklowitz David J
Published: March 2003

Objectives:
 Significant debate exists on whether early onset bipolar disorder is mistakenly attributed to attention deficit hyperactivity disorder (ADHD) or conduct disorder (CD), or whether ADHD and CD are frequently misdiagnosed as mania. We review the literature on the extent to which these disorders can be reliably differentiated, and describe the diagnostic confusion that may be the result of features common to both classes of disorders.

Methods:
 The review focuses on research studies that have examined whether overlapping symptoms of bipolar disorder, ADHD, and CD contribute to misdiagnosis of the two classes of disorders, the prevalence of early onset bipolar disorder with comorbid ADHD or CD, and theories regarding the origins of this comorbidity.

Results:
 Reliable and accurate diagnoses can be made despite the symptom overlap of bipolar disorder with ADHD and CD. Children with bipolar disorder and ADHD may have a distinct familial subtype of bipolar disorder. Some findings suggest that manic symptoms may represent `noise' that indicates the general severity of psychopathology in a child or adolescent.

Conclusions:
 Further prospective studies may confirm whether early onset bipolarity can be successfully differentiated from ADHD or CD, whether all three types of disorders can be recognized in comorbid cases, or whether comorbid cases represent a distinct subtype of bipolar disorder.
Thyroid function in mixed and pure manic episodes
Authors: Cassidy F , Ahearn EP , Carroll BJ
Published: March 2003

Objectives:  Associations of both overt thyroid disease as well as subclinical thyroid abnormalities with affective disorders have been well established. Similar associations have been reported with mixed mania and rapid cycling bipolar disorder. We tested for differences in overt and subclinical thyroid disease and subclinical differences in a large series of bipolar patients examined during mixed or pure manic episodes.

Methods:  Rates of previously diagnosed thyroid disease were compared by sex, race and manic subtype (mixed versus pure) in 443 patients. Serum thyroid stimulating hormone (TSH) and free thyroxine (FT4) concentrations obtained from patients with no clinical thyroid disease collected during manic and mixed bipolar episodes were compared using ANOVA statistics. Race was also included in the model and age was covaried.

Results:  Rates of thyroid disease, in particular hypothyroidism, were higher in females and white people, and increased with advancing age. No differences were noted between subjects sampled during mixed or pure manic episodes. In patients with no history of thyroid disease, serum TSH and FT4 concentrations did not differ between manic subtypes or between sexes. TSH levels however, were significantly lower in African Americans.

Conclusions:  We did not confirm past reports of associations of overt or subclinical thyroid disease with mixed manic episodes. African Americans had significantly lower serum TSH concentrations than white people, while FT4 levels did not differ.
Structural changes in bipolar disorder compared to schizophrenia
Authors: Scherk Harald
Published: March 2003

Scherk H. Structural changes in bipolar disorder compared to schizophrenia.  Bipolar Disord 2002: 4(Suppl. 1): 47. © Blackwell Munksgaard, 2002
Abnormalities of prefrontal cortex SNARE complex proteins in bipolar disorder
Authors: Honer William G , Falkai Peter , Li Hong‐Ying , Knable Michael B , Buslei Rolf , Bayer Thomas A
Published: March 2003

Honer WG, Falkai P, Li H‐Y, Knable MB, Buslei R, Bayer TA. Abnormalities of prefrontal cortex SNARE complex proteins in bipolar disorder.  Bipolar Disord 2002: 4(Suppl. 1): . © Blackwell Munksgaard, 2002
Long‐term synaptic plasticity in affective disorders
Authors: Normann Claus
Published: March 2003

Normann C. Long‐term synaptic plasticity in affective disorders.  Bipolar Disord 2002: 4(Suppl. 1): 59. © Blackwell Munksgaard, 2002
White matter lesions in bipolar disorder
Authors: Ferrier IN
Published: March 2003

Ferrier IN. White matter lesions in bipolar disorder.  Bipolar Disord 2002: 4(Suppl. 1): 86. © Blackwell Munksgaard, 2002
The switch – real threat or overestimated danger? Antidepressant‐associated maniform states in acute treatment of patients with bipolar‐I depression in the Munich study
Authors: Möller Hans‐Jürgen , Bottlender Ronald , Rudolf Daniel , Strauss Anton , Grunze Heinz
Published: March 2003

Möller H‐J, Bottlender R, Rudolf D, Strauss A, Grunze H. The switch – real threat or overestimated danger? Antidepressant‐associated maniform states in acute treatment of patients with bipolar‐I depression in the Munich study.  Bipolar Disord 2002: 4(Suppl. 1): 115. © Blackwell Munksgaard, 2002
Prediction of maternal and fetal complications in preeclampsia
Authors: NISELL HENRY , PALM KERSTIN , WOLFF KERSTIN
Published: March 2003

Introduction. Preeclampsia is associated with an increased risk for maternal and fetal morbidity. The aim of this study was to identify factors predicting for maternal or fetal complications.

Material and methods. One hundred and eleven patients with preeclampsia were included. Endpoint variables were maternal and fetal complications. Any of the diagnosis eclampsia, hemolysis elevated liver low platelet (HELLP) syndrome, oliguria or placental abruption was considered a maternal complication. Fetal complications were: small for gestational age (SGA) infant, umbilical artery pH<7.10 and admittance of the infant to a neonatal intensive care unit (NICU). Independent variables were maternal age, parity, gestational age, renal function, platelet count, liver enzymes and blood pressure. Logistic regression analysis was used for statistical evaluation.

Results. The following independent significant predictors were identified: Maternal complication (n=10) was predicted only by diastolic blood pressure; odds ratio (OR) 1.13 (95% confidence interval 1.01–1.25). SGA (n=21) was associated with maternal prepregnancy weight, OR 0.94 (0.89–0.99) and gestational age at debut of preeclampsia, OR 0.97 (0.94–0.99). NICU admittance (n=31) was only predicted by gestational age at delivery, OR 0.80 (0.67–0.96). No association was found between any of the independent variables and a low umbilical artery pH (n=10).

Conclusions. In the surveillance of patients with established preeclampsia, the value of serial blood and urine sampling, which is common practice in many obstetrical units, might be questioned.
Effects of electro‐acupuncture on anovulation in women with polycystic ovary syndrome
Authors: STENER‐VICTORIN ELISABET , WALDENSTRÖM URBAN , TÄGNFORS ULRIKA , LUNDEBERG THOMAS , LINDSTEDT GÖRAN , JANSON PER OLOF
Published: March 2003

Background. The present study was designed to evaluate if electro‐acupuncture (EA) could affect oligo‐/anovulation and related endocrine and neuroendocrine parameters in women with polycystic ovary syndrome (PCOS).

Methods. Twenty‐four women (between the ages of 24 and 40 years) with PCOS and oligo‐/amenorrhea were included in this non‐randomized, longitudinal, prospective study. The study period was defined as the period extending from 3 months before the first EA treatment, to 3 months after the last EA treatment (10–14 treatments), in total 8–9 months. The menstrual and ovulation patterns were confirmed by recording of vaginal bleedings and by daily registrations of the basal body temperature (BBT). Blood samples were collected within a week before the first EA, within a week after the last EA and 3 months after EA.

Results. Nine women (38%) experienced a good effect. They displayed a mean of 0.66 ovulations/woman and month in the period during and after the EA period compared to a mean of 0.15 before the EA period (p=0.004). Before EA, women with a good effect had a significantly lower body‐mass index (BMI) (p<0.001), waist‐to‐hip circumference ratio (WHR) (p=0.0058), serum testosterone concentration (p=0.0098), serum testosterone/sex hormone binding globulin (SHBG) ratio (p=0.011) and serum basal insulin concentration (p=0.0054), and a significantly higher concentration of serum SHBG (p=0.040) than did those women with no effect.

Conclusion. Repeated EA treatments induce regular ovulations in more than one third of the women with PCOS. The group of women with good effect had a less androgenic hormonal profile before treatment and a less pronounced metabolic disturbance compared with the group with no effect. For this selected group EA offers an alternative to pharmacological ovulation induction.
The effect of vaginal pH on the efficacy of vaginal misoprostol for induction of labor
Authors: GUNALP SERDAR , BILDIRICI IBRAHIM
Published: March 2003

Background. Misoprostol was reported to be an effective agent for cervical ripening and induction of labor. Our purpose was to evaluate whether vaginal pH affected the efficacy of misoprostol for induction of labor.

Methods. The vaginal pH of 103 women admitted for induction of labor were measured. According to the vaginal pH, two groups were generated, those with a vaginal pH <5 (n=65), and those with a vaginal pH ≥5 (n=38). All women received intravaginal misoprostol tablets, 50 μg every 4 hours up to three doses. Further medication was not given after entry into active labor or spontaneous rupture of membranes. In cases of failed induction or arrest disorders oxytocin augmentation was used.

Results. The average interval from start of induction to vaginal delivery was shorter, and oxytocin augmentation was required less commonly in the lower pH group. We did not find any significant difference in cesarean section rates, or incidence of adverse maternal or fetal outcome.

Conclusion. Vaginal pH may affect the pharmacokinetics of vaginally administered misoprostol, and may cause an alteration in induction to delivery interval.
Swedish maternal mortality in the 19th century by different definitions: previous stillbirths but not multiparity risk factor for maternal death
Authors: ANDERSSON TOBIAS , BERGSTRÖM STAFFAN , HÖGBERG ULF
Published: March 2003

Background. The high maternal mortality levels in today's developing countries were also found throughout the history of currently affluent countries. The parish information system in Sweden offers unique possibilities for research in historical cohorts. Furthermore, vital events surveillance systems are scarce in today's developing countries.

Methods. This cohort study covers 42,387 mothers who gave birth to 150,932 infants during the 19th century in the Skellefteå and Sundsvall areas. Among these women, 1 237 were dead within one year after delivery. The analysis of the cause of these deaths was done according to the various ICD definitions. Parity five and above was defined as grand multiparity.

Results. Maternal mortality ratios, deaths per 100,000 live births were as follows: 256.4 (direct obstetric deaths), 320.7 (direct and indirect obstetric deaths), 489.2 (pregnancy‐related deaths), 347.8 (late maternal deaths) and 837.0 (maternal deaths and late maternal deaths). In this study, 59% of all maternal deaths occur within the first 42 days of delivery, two thirds of them having direct and indirect obstetric causes. Of the late maternal deaths, the bulk were infectious or other indirect deaths, mirroring more general female mortality and the pre‐existent endemic situation of tuberculosis and other infectious diseases. The combination of previous stillbirth and infant death represented the highest risk ratios, RR 2.77–3.62, while grand multiparity was not associated with increased risk. Urbanized and industrialized areas tended to have higher maternal mortality.

Conclusions. In conclusion, this study shows that the mother's reproductive history was the most important risk factor measured for all definitions of maternal death. Grand multiparity did not increase the risk of maternal death. Maternal mortality ratio varied threefold in the study population, depending on the definition used. The high mortality ratios found in this study, only declining by the end of the century, should be interpreted as a general condition of the society since no significant differences could be perceived regarding social class, while unmarried women were more at risk.
Increased perinatal mortality among sub‐Saharan immigrants in a city‐population in Sweden
Authors: ESSÉN BIRGITTA , HANSON BERTIL S. , ÖSTERGREN PER‐OLOF , LINDQUIST PELLE G. , GUDMUNDSSON SAEMUNDUR
Published: March 2003

Background. The aim of the study was to investigate whether the maternal country of origin affected the risk for perinatal mortality and to determine its relationship to risk factors.

Methods. A study of 15,639 deliveries in Malmö, Sweden. Data regarding demographic factors, life‐style and perinatal risk factors, together with data pertaining to outcome was obtained from the Malmö database and the Swedish Medical Birth Register.

Results. Perinatal mortality was increased among infants to women of Foreign origin as compared to those delivered by women of Swedish origin (OR 1.5, CI 1.0–2.2). Even after adjustments for maternal background and risk factors (diabetes, anemia, pre‐eclampsia, placental abruption and small‐for‐gestational age), the increased risk of perinatal mortality among women of Foreign origin remained statistically significant. Women from sub‐Saharan Africa, comprising 7.3% of all immigrants, differed from all other subgroups of women of foreign origin by having a higher risk of adverse outcome (small‐for‐gestational age OR 1.9, CI 1.0–3.6, neonatal distress OR 2.7, CI 5.1–4.8 and perinatal mortality OR 4.3, CI 2.1–8.6).

Conclusions. Women of foreign origin, especially from sub‐Saharan Africa, have a higher risk of perinatal mortality than native Swedish women. The differences in mortality could not be explained by risk factors. The results suggest that women and newborns from sub‐Saharan Africa should be given more intense surveillance on all levels of perinatal care in order to reduce perinatal mortality.