bluuebunny/crossref_metadata_2025 huggingface dataset:
Administration of prostacyclin after liver transplantation: a placebo controlled randomized trial
Authors: Neumann Ulf P. , Kaisers Udo , Langrehr Jan M. , Glanemann Matthias , Müller Andrea R. , Lang Martina , Jörres Achim , Settmacher Utz , Bechstein Wolf O. , Neuhaus Peter
Published: March 2003

The shortage of suitable organs for liver grafts is responsible for the use of marginal donors for liver transplantation (OLT). If these liver grafts function poorly initially after OLT, a supportive therapy is necessary. The purpose of this study was to evaluate the effects of prostacyclin (PGI2) on postoperative liver graft function after OLT.A total of 30 adult recipients of primary OLT were randomized to either receive PGI2 (4 ng/kg per min body weight, n=15) or a placebo for 6 d. To evaluate regional splanchnic oxygenation a fiberoptic pulmonary‐artery catheter was inserted into a hepatic vein and the difference between mixed venous oxygen content and hepatic venous oxygen content was determined (ΔO2). Measurements were performed directly after transplantation and at 6, 12, 24 and 48 h postoperatively.A significant correlation between ΔO2 and the level of transaminases (ALT/AST) was observed 24 and 48 h after transplantation (p<0.05). PGI2 treatment induced a significant decrease in ΔO2 after 24 and 48 h after reperfusion (p<0.05). Peak AST levels tended to be lower in the PGI2 treatment group (418±99 vs. 638±156 U/L, p<0.1).These results suggest that administration of PGI2 after OLT improves hepatic‐splanchnic oxygenation and may thereby reduce reperfusion injury after OLT.
Therapeutic drug monitoring of sirolimus: correlations with efficacy and toxicity
Authors: Kahan BD , Napoli KL , Kelly PA , Podbielski J , Hussein I , Urbauer DL , Katz SH , Van Buren CT
Published: March 2003

We sought to examine the potential benefits of therapeutic drug monitoring of sirolimus, a potent immunosuppressive agent that displays a pleiotropic array of side effects.  Methods. A high‐performance liquid chromatography (LC) procedure combined with ultraviolet detection (UV) was used to measure serial concentrations of parent compound sirolimus in 150 renal transplant recipients over a period of 4 yr. Drug concentrations in whole blood at trough time, as well as within pharmacokinetic profiles, were correlated with clinical events using contingency tables, logistic regression analysis, and receiver operating characteristic (ROC) curves.  Results. The LC/UV method showed an excellent correlation with detection of LC‐resolved components by tandem mass spectrometry, demonstrating that the LC/UV method selectively detected parent compound. Sirolimus displayed the characteristics of a critical‐dose drug: Its concentration could not be predicted by a standard body or demographic measure, or by dose, and it showed high degrees of intra‐ and inter‐individual variability. However, there was a good correlation between trough and area‐under‐the‐curve measurements. There was a significant association between trough values expressed as either observed (<5 ng/mL) or dose‐corrected parameter (<1.7 ng/mL per mg administered drug) and the occurrence and severity of acute rejection episodes – despite the low overall incidence of 23 episodes among the cohort of 150 patients. Similarly, ROC functions showed a correlation of the occurrence of hypertriglyceridemia, thrombocytopenia, and leukopenia, but not hypercholesterolemia, with trough concentrations above 15 ng/mL.  Conclusion. Due to its behavior as a critical‐dose drug, therapeutic monitoring to measure sirolimus concentrations by a LC/UV method may provide clinicians with a tool to optimize outcomes.
Extracorporeal membrane oxygenation support of donor abdominal organs in non‐heart‐beating donors
Authors: Ko Wen‐Je , Chen Yih‐Sharng , Tsai Pi‐Ru , Lee Po‐Huang
Published: March 2003

Both family consent and legal consent were required for organ/tissue donation from non‐heart‐beating donors (NHBD) in Taiwan. A district attorney had to come to the bedside to confirm the donor's asystole, confirm the family consent, and complete some legal documents before a legal consent was issued for organ donation. The resultant warm ischemic time would be unpredictably long and in fact precluded the organ donation from NHBD in Taiwan. We developed a method of using extracorporeal membrane oxygenation (ECMO) to maintain NHBD for a longer time and prevent warm ischemic injury of the donor abdominal organs. After ventilator disconnection in NHBD, phentolamine and heparin were injected and mannitol infusion was given. After the donor's asystole was confirmed by the electrocardiogram (EKG) strip recording, the ECMO support was set up through the right femoral veno‐arterial route, an occlusion balloon catheter was inserted through the left femoral artery to occlude the thoracic aorta, and bilateral femoral arteries were ligated. Usually, the ECMO could begin within 10 min after the donor's asystole. The ECMO, combined with a cooler, provided cold oxygenated blood to the abdominal visceral organs, and prevented their warm ischemic injuries. Under the ECMO support (range: 45–70 min), eight renal grafts were procured from 4 NHBD. With the exception of the first two renal grafts with delayed function, all others had immediate function postoperatively and dialysis was no longer needed. In conclusion, by our ECMO technique, NHBD could be maintained for a longer time and the renal grafts had better immediate postoperative function than those reported by other methods.
Graft‐versus‐host disease after liver transplantation: documentation by fluorescent in situ hybridisation and human leucocyte antigen typing
Authors: Au WY , Ma SK , Kwong YL , Ng IOL , Hawkins BR , Wan TSK , Liu CL , Fan ST , Lo CM
Published: March 2003

Graft‐versus‐host disease (GVHD) after liver transplantation is uncommon and the outcome is often fatal. A firm diagnosis of GVHD is difficult because the clinical triad of skin rash, marrow failure and diarrhoea can be indistinguishable from drug reaction or viral infection, and the presence of donor lymphocyte chimerism is not specific. We describe a case of severe GVHD in a female patient after liver transplantation from a male cadaveric donor. Skin biopsy showed characteristic changes of GVHD. Using Y‐chromosome‐specific fluorescent in situ hybridisation (FISH), male lymphocytes were demonstrated in 10% of marrow cells and in 90% of lymphocytes infiltrating the dermal–epidermal junction. Donor human leucocyte antigens (HLAs) were detected in the peripheral blood, buccal mucosa and skin by polymerase chain reaction. The GVHD subsided with steroid and anti‐thymocyte globulin, but recurred on tailing off of treatment. Despite maximum supportive therapy, including random donor leucocyte infusion, and marrow infusion from a HLA‐identical sibling, the patient succumbed to sepsis. Our results showed the utility of combining morphological features with molecular techniques using FISH and HLA typing in confirming a diagnosis of GVHD.
The influence of age, gender and ethnicity on cadaveric organ recovery rate
Authors: Nelson Paul W. , Aeder Mark I. , Andrews Walt , Forster Jameson , Muruve Nic , Shield Charles F. , Finn Jan , Bryan Christoper F.
Published: March 2003

In view of the influence of donor factors such as age on graft outcome and the performance standards that measure OPO productivity by the number of organs recovered and transplanted, it is important to understand the relationship of certain donor factors on organ recovery for transplantation from cadaveric donors. We examined the influence of donor age, gender and ethnicity on the number and type of transplanted organs recovered from 598 consecutive cadaveric donors in our OPO between 1994 and July 1999. The highest number of organs/donor ocurs in the 11–20 donor age range and declines significantly with each age range. The type of organ recovered is also influenced by age, but the least effect is on liver recovery. No difference was seen in the number of organs recovered/donor by race. When the data were re‐analyzed with regard to renal and extra‐renal organs transplanted/million donor population, 78% of the kidneys (n=781/1006) were from the 11–50 age range and 81% of the extra‐renal organs (n=822/1192) were from that age range. Stepwise regression yielded a model where donor age significantly influenced (P=0.001) the number of organs recovered. Finally, the incidence of recovered and transplanted organs was significantly higher in males compared with females for hearts [51% (187/360) vs. 40% (86/214); P<0.006] and pancreata [18% (66/360) vs. 11% (24/214); P<0.02]. The number of organs recovered and transplanted from cadaveric organ donors is influenced predominantly by the age of the donor, with the exception being liver donors. Increasing organ recovery and transplantation of organs from donors from the two age extremes results in less gain in the number of organs/million population than recovery from the 11–50 age range.
Lifestyle behaviors affect cardiovascular risk status in men 1 year after kidney transplantation
Authors: Martin J. C. , Hathaway D. K. , Egidi M. F. , Gaber A. O.
Published: March 2003

Persons with end‐stage renal disease have an accelerated risk for cardiovascular (CV) morbidity and mortality. Unfortunately, their accelerated CV risk persists even after kidney transplantation associated with pretransplant and post‐transplant vascular disease, number of rejections treated with high‐dose steroids, prolonged use of immunosuppressive therapy post‐transplant, effects of comorbid chronic conditions and male gender. Unhealthy, modifiable lifestyle practices often augment their CV risk. The purpose of this study was to examine health‐related lifestyle behaviors and estimate CV risks of men 1 year following kidney transplantation. Using the Healthier People Network Health Risk Appraisal (HPN‐HRA), we examined CV risk characteristics of 34 men (M age=47.3 years) enrolled in an urban, mid‐southern transplant center. Participants were assessed via self‐administered paper‐and‐pencil questionnaires and medical record review provided biological data for analyses. HPN‐HRA software was used to analyze biological and behavioral characteristics to compute CV risk estimates. Data were analyzed using descriptive, inferential and correlational analyses. The majority of participants reported smoke cessation (n=19) or never having smoked (n=8), and consumption of one or less alcoholic drinks per week (n=28). On the other hand, increased risk for heart attack and stroke were associated with advancing age (P<0.0001), white race (P<0.05) and higher systolic blood pressure (P<0.01).While risk for heart attack was associated with current cigarette smoking (P<0.01), risk for stroke was not. Conversely, risk for stroke was associated with higher BMI (P<0.05), risk for heart attack was not. Thus, the study provides evidence that male kidney transplant survivors exhibit a significant number of non‐modifiable and modifiable characteristics that contribute to their posttransplant CV risk.
Echocardiographic ultrasonic tissue characterization in a case of Fabry's disease following renal transplantation
Authors: Panichi Vincenzo , Di Bello Vitantonio , Taccola Daniele , Giorgi Davide , Bertini Alessio , Migliori Massimiliano , Talini Enrica , Giusti Costantino
Published: March 2003

We report a case of Fabry's disease where stabilization of progressive cardiac involvement was recorded in a 29‐yr‐old Caucasian man, to our knowledge, for the first time by ultrasonic tissue characterization echocardiography after 1 yr of successful renal transplantation.   Three echocardiographic evaluations have been made: the first 3 months before, the second 6 months after, and the third 1 yr after kidney transplantation.   The myocardial structural damage – evaluated by integrated backscatter index – shows a persistence of the impairment of intrinsic myocardial contractility at septum level, probably due to coexistent hypertensive status, which is able to induce per se alterations of myocardial textural parameters. On the other hand, the cyclic variation index at posterior free wall, which is less dependent on strictly hemodynamic factors than the septum, appears quite normal at the third observation.   These data could reflect the improvement of the ultrastuctural myocardial findings in relation to renal transplantation, which could correct not only renal failure but also the enzymatic deficiency by replacement of α‐galactosidase A through the transplanted kidney.
Impact of clinical pharmacy services on renal transplant patients’ compliance with immunosuppressive medications
Authors: Chisholm Marie A , Mulloy Laura L , Jagadeesan Muralidharan , DiPiro Joseph T
Published: March 2003

Background: Non‐compliance with immunosuppressive medications may result in allograft rejection and is regarded as an important impediment to post‐transplant care. This randomized, controlled trial evaluates the impact of clinical pharmacy services on renal transplant patients’ compliance with immunosuppressive agents.  Methods: Patients who received a renal transplant at the Medical College of Georgia from February 1997 through January 1999 were randomized in the intervention or control group provided they met study criteria. In addition to routine clinic services at each clinic visit, patients in the intervention group received clinical pharmacy services, which included medication histories and review of patients’ medications with an emphasis on optimizing medication therapy to achieve desired outcomes and minimizing adverse medication events. The clinical pharmacist also provided recommendations to the nephrologists with the goal of achieving desired outcomes. To promote medication compliance by using compliance enhancement strategies, the clinical pharmacist counseled patients concerning their medication therapy and instructed them how to properly take their medications. Patients in the control group received the same routine clinic services as the intervention group except that they did not have any clinical pharmacist interaction. Compliance rate (CR) was calculated and patient's compliance status was determined from the CR. The CR, the fraction of patients remaining compliant for each month, and the mean time patients were compliant were compared between groups. Whether there was a difference in the frequency of patients achieving ‘target’ immunosuppressive levels in the control and study groups was evaluated.  Results: The mean CR for patients who had clinical pharmacist intervention (n=12) was statistically higher than the control group's (n=12) mean CR (p<0.001). During the 12‐month post‐transplant study period, patients in the intervention group had a longer duration of compliance than patients in the control group (p<0.05). Additionally, patients who had clinical pharmacy services had a greater achievement of ‘target’ levels than patients who did not receive these services (p<0.05).  Conclusions: Patients who received clinical pharmacy services with traditional patient care services had better compliance with immunosuppressants than patients who only received traditional patient care services. Results of this study suggest a multidisciplinary team that includes a clinical pharmacist as part of the care for post‐transplant patients is beneficial for enhancing medication compliance.
Characteristics and clinical relevance of chronic anemia in adult heart transplant recipients
Authors: Müller Helmut M , Horina Jörg H , Kniepeiss Daniela , Tripolt Michael B , Stadelbauer Vanessa , Schweiger Martin , Tscheliessnigg Karl‐Heinz
Published: March 2003

Background: Mild chronic anemia following heart transplantation (HTX), with hemoglobin (Hb) values of 10–14 g/dL in men and 10–12 g/dL in women, is frequent. It has continued to be of uncertain etiology yet clinical relevance. Nonetheless, therapeutic immunosuppression has been regarded as a major cause of chronic anemia in HTX patients.  Methods: Sixty outpatients were observed over a period of 5 yr after HTX. Laboratory values related to anemia such as Hb, erythropoietin (EPO), ferritin, transferrin, iron, and vitamin levels were obtained and analyzed monthly. Patients were divided into two groups retrospectively. Patients with persistent anemia for more than 1 yr were compared with non‐anemic patients.  Results: Forty‐three (72%) of the 60 patients were anemic. Anemia was normochromic, normocytic, and slightly anisocytic. Anemic and non‐anemic patients showed EPO levels within the expected range as defined by Erslev (Erythropoietin. N Engl J Med 1991: 324: 1339). Reticulocyte counts were found to be normal in all patients. Iron deficiency and deficiency of vitamin B12 or folic acid were not observed. Patients with persistent anemia showed a significantly shorter survival period than non‐anemic patients (p<0.02).  Conclusions: Mild anemia following HTX shows the same characteristics as anemia in chronic diseases. Persisting mild anemia used to be associated with a shorter life expectancy. There is no evidence that standard immunosuppression causes anemia.
Renal failure after liver transplantation: outcome after calcineurin inhibitor withdrawal
Authors: Neau‐Cransac Martine , Morel Delphine , Bernard Pierre‐Henri , Merville Pierre , Revel Philippe , Potaux Luc , Saric Jean
Published: March 2003

Neau‐Cransac M, Morel D, Bernard P‐H, Merville P, Revel P, Potaux L, Saric J. Renal failure after liver transplantation. Outcome after calcineurin inhibitor withdrawal. Clin Transplant 2002: 16: 368–373. © Blackwell Munksgaard, 2002

Chronic nephrotoxicity is one of the most serious side‐effects of calcineurin inhibitor treatment and a factor in mortality and morbidity after liver transplantation. In our transplant centre, among patients who underwent a liver transplantation between January 1989 and December 2000, 14 liver graft recipients (6.86%) developed de novo severe renal dysfunction as defined by a serum creatinine concentration above 200 micromol/L. Renal biopsy was performed in nine cases and evidenced histological lesions compatible with chronic nephrotoxicity related to calcineurin inhibitor treatment. For nine patients, we report the results of a prospective non‐randomized study consisting of cyclosporine or tacrolimus withdrawal associated with administration of mycophenolate mofetil or azathioprine. Despite this therapeutic modification, we did not observe a significant renal function improvement but on the other hand, there was no graft rejection.
Risk factors for slow graft function after kidney transplants: a multivariate analysis
Authors: Humar A , Ramcharan T , Kandaswamy R , Gillingham K , Payne WD , Matas AJ
Published: March 2003

Humar A, Ramcharan T, Kandaswamy R, Gillingham K, Payne WD, Matas AJ. Risk factors for slow graft function after kidney transplants: a multivariate analysis. Clin Transplant 2002: 16: 425–429. © Blackwell Munksgaard, 2002

Background: We previously defined an intermediate group of cadaver kidney transplant recipients who do not have immediate graft function (IGF), but do not have sufficient graft dysfunction to be classified as having delayed graft function (DGF). We showed that this group with slow graft function (SGF) had an increased risk of rejection and inferior long‐term results vs. recipients with IGF. The aim of our current study was to determine risk factors for SGF, which have not been well defined (in contrast to risk factors for DGF).

Methods: Between January 1, 1984 and September 30, 1999, we performed 896 adult cadaver kidney transplants at the University of Minnesota. Recipients were analysed in three groups based on initial graft function: IGF [creatinine (Cr) < 3 mg/dL by post‐operative day (POD) no. 5], SGF (Cr > 3 mg/dL on POD no. 5, but no need for dialysis), and DGF (need for dialysis in the first week post‐transplant). A multivariate analysis looked specifically at risk factors for SGF, as compared with risk factors for DGF. Outcomes with regard to graft survival and acute rejection (AR) rates were determined for the three groups.

Results: Of the 896 recipients, 425 had IGF, 238 had SGF, and 233 had DGF. A multivariate analysis of risk factors for SGF showed donor age >50 yr (RR=3.3, p=0.0001) and kidney preservation time >24 h (RR=1.6, p=0.01) to be the most significant risk factors. A multivariate analysis of risk factors for DGF showed similar findings, although high panel‐reactive antibodies (PRA) and donor Cr >1.7 mg/dL were also significant risk factors for DGF. Initial function of the graft significantly influenced the subsequent risk of AR: at 12 months post‐transplant, the incidence of AR was 28% for those with IGF, 38% for those with SGF, and 44% for those with DGF (p=0.04 for SGF vs. DGF). Initial graft function also significantly influenced graft survival: the 5‐yr death‐censored graft survival rate was 89% for recipients with IGF, 72% for those with SGF, and 67% for those with DGF (p=0.01 for IGF vs. SGF; p=0.03 for SGF vs. DGF).

Conclusions: SGF represents part of the spectrum of graft injury and post‐transplant graft dysfunction. Risk factors for SGF are similar to those seen for DGF. Even mild to moderate graft dysfunction post‐transplant can have a negative impact on long‐term graft survival.
The impact of impaired insulin release and insulin resistance on glucose intolerance after renal transplantation*
Authors: Hjelmesæth Jøran , Hagen Monica , Hartmann Anders , Midtvedt Karsten , Egeland Thore , Jenssen Trond
Published: March 2003

Abstract: The current knowledge of the pathogenesis of post‐transplant glucose intolerance is sparse. This study was undertaken to assess the relative importance of insulin secretion (ISec) and insulin sensitivity (IS) in the pathogenesis of post‐transplant diabetes mellitus (PTDM), impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) after renal transplantation.

An oral glucose tolerance test (OGTT) was performed in 167 non‐diabetic recipients 10 wk after renal transplantation. Fasting, 1‐h and 2‐h insulin and glucose levels were used to estimate the insulin secretory response and IS. One year after transplantation 89 patients were re‐examined with an OGTT including measurements of fasting and 2 h glucose.

Ten weeks after transplantation the PTDM‐patients had significantly lower ISec and IS than patients with IGT/IFG, who again had lower ISec and IS than those with normal glucose tolerance (NGT). One year later, a similar difference in baseline ISec was observed between the three groups, whereas baseline IS did not differ significantly. Patients who improved their glucose tolerance during the first year, were mainly characterized by a significantly greater baseline ISec, and they received a significantly higher median prednisolone dose at baseline with a subsequent larger dose reduction during the first year, than the patients who had their glucose tolerance unchanged or worsened.

In conclusion, both impaired ISec and IS characterize patients with PTDM and IGT/IFG in the early course after renal transplantation. The presence of defects in insulin release, rather than insulin action, indicates a poor prognosis regarding later normalization of glucose tolerance.
Nerve conduction study on patients with severe liver syndrome and its change after transplantation
Authors: Lee Jung H , Jung Woo J , Choi Kyoung H , Chun Min H , Ha Sang B , Lee Seung K
Published: March 2003

Abstract:  This study is to investigate the character of peripheral neuropathy associated with end stage liver disease and the effect of liver transplantation on peripheral neuropathy. Twenty‐five patients admitted for a liver transplantation were involved in this study. All patients underwent neural conduction study before liver transplantation and 6 months after liver transplantation. Based on results of this study, motor amplitude score, motor velocity score (MVS), sensory amplitude score (SAS), and sensory velocity score were calculated. The changes between before and after liver transplantation were evaluated. The SAS and MVS substantially increased after transplantation. Nerve conduction study showed the improvement in sensory and motor nerve after liver transplantation.
Plasma amino acids in cirrhosis and after liver transplantation: influence of liver function, hepatic hemodynamics and circulating hormones
Authors: Tietge Uwe JF , Bahr Matthias J , Manns Michael P , Böker Klaus HW
Published: March 2003

Liver cirrhosis is characterized by substantial changes in amino acid (AA) metabolism, resulting in a deranged plasma AA profile. To investigate the effect of liver transplantation (OLT), we studied arterial AA profiles in 52 patients with advanced cirrhosis, 16 stable patients over 6 months after OLT and 48 controls. Changes in AA levels were correlated with portal pressure (hepatic venous pressure gradient), functional hepatic blood flow (indocyanine green extraction) and circulating hormone levels (catecholamines, insulin, C‐peptide). Fourteen of 18 measured AA were significantly altered in cirrhosis and 11 of 18 remained abnormal after OLT compared with controls. Aromatic AA (AAA) and methionine were elevated in cirrhosis (p<0.001 each), increasing with disease stage, and normalized after OLT. Branched chain AA (BCAA) levels were decreased in cirrhosis (p<0.001) and were unrelated to disease stage. After OLT, BCAA levels remained subnormal (p<0.01), although higher than in cirrhosis (p<0.001). AAA levels increased with decreasing functional hepatic blood flow (r=−0.67; p<0.001) and increasing portal pressure (r=0.59; p<0.001). BCAA levels decreased with increasing catecholamine (r=−0.54, p<0.001) and insulin levels (r=−0.40, p=0.001). We conclude that despite normal liver function, AA metabolism is only partially normalized after OLT. AAA levels mainly determined by hepatic metabolic function and functional liver blood flow return to normal, while BCAA levels remain subnormal, indicating persistent changes in muscular AA metabolism after OLT.
Immunoadsorption of sensitized kidney transplant candidates immediately prior to surgery
Authors: Hickstein H , Korten G , Bast R , Barz D , Nizze H , Schmidt R
Published: March 2003

Patients with anti‐human leucocyte antigen (HLA) antibodies from previous transplantation, blood transfusion are highly sensitized and at risk to hyperacute renal graft loss. As these antibodies are identified to be of pathogenic importance, an effective removal may allow successful transplantation. Six `high risk patients' [panel‐reactive antibodies (PRA) >30% or retransplanted patients with an acutely rejected first graft within 6 months from surgery] were treated by protein A immunoadsorption (IA) immediately prior to transplantation. We treated the calculated plasma volume one to three times prior to surgery: mean 4600 mL (range 2100–10 200 mL). After transplantation we repeated the sessions according to antibody (Ab) recurrence, graft function and signs of rejection. The panel reactive Ab were reduced from mean 65% pre‐IA (range 35–85) to lowest 15% (range 0–55). After the course they reappeared to 30% (range 0–90). Five of the six patients had no clinical signs of vascular rejection. At a follow‐up of mean 54 months (±14) four grafts still function with a mean serum creatinine of 172 μmol/L (±57). Protein A IA is a safe and effective adjunct in the treatment of highly sensitized patients awaiting renal transplantation. The treatment immediately prior to operation can prevent hyperacute rejection and increases the graft survival in these patients.
The changes in serum leptin, body fat mass and insulin resistance after renal transplantation
Authors: Kayacan S Mehmet , Yildiz Alaattin , Kazancioglu Rumeyza , Sahin Sevgi , Sever M Sükrü , Ark Ergin
Published: March 2003

Abstract: Background:  In this prospective‐controlled study, we aimed to investigate the effect of changes in insulin resistance and anthropometrical parameters on serum leptin levels (SLL) after renal transplantation (Tx).

Patients and methods:  Thirty‐four patients (M/F: 19/15, mean age: 29 ± 9 yr) and 30 age and sex‐matched healthy controls (C) were included. Body weight, subscapular, suprailiac, periumbilical, biceps and triceps skinfold thicknesses, neck, wrist, hip and waist circumferences, as well as body mass index and body fat mass were measured as anthropometrical parameters. In order to measure the serum glucose, insulin and SLL, blood samples were obtained before and 1 wk, 1 and 6 months after Tx. Homeostasis Model Assessment (HOMA) values were calculated as an index of insulin resistance.

Results:  Serum leptin levels (SLL) of the patients at pre‐Tx were significantly higher than C (21.5 ± 3.5 vs. 7.8 ± 0.9 ng/mL, p = 0.002) and decreased at first week after Tx (from 21.5 ± 3.5 to 8.4 ± 1.5 ng/mL, p < 0.001). Thereafter, it gradually increased to 12.8 ± 2.1 ng/mL in the first month and to 14.4 ± 2.1 ng/mL in the sixth month after Tx. Serum leptin levels at sixth month were significantly higher than C (p = 0.005). Serum insulin and HOMA values changed similar to SLL after Tx. Correlations between SLL and HOMA persisted during the study period [pre‐Tx (r: 0.40) and at first (r: 0.38) and sixth (r: 0.47) months]. In linear regression analysis, HOMA and fat mass were found as independent variables for predicting SLL at the sixth month after Tx.

Conclusion:  Serum leptin levels dramatically decreased immediately after Tx and significantly correlated with serum insulin levels and HOMA during the entire study. Increase in SLL at sixth months was probably because of increase in fat mass, insulin resistance and steroid use in renal transplant recipients.
Gabapentin in bipolar disorder: a placebo‐controlled trial of adjunctive therapy1
Authors: Pande Atul C , Crockatt Jerri G , Janney Carol A , Werth John L , Tsaroucha Georgia ,   Gabapentin Bipolar Disorder Study Group
Published: March 2003

Objectives:

To assess efficacy and safety of gabapentin in the treatment of bipolar disorder.

  Methods: This was a double‐blind, placebo‐controlled trial of adjunctive gabapentin (dosed flexibly between 900 and 3600 mg/day). Patients with a lifetime diagnosis of bipolar disorder (type I), and who were currently suffering from symptoms of either mania, hypomania or a mixed state despite ongoing therapy with lithium, valproate, or lithium and valproate in combination were eligible for inclusion. The primary efficacy measures were the baseline to endpoint change in total score on the Young Mania Rating Scale (YMRS) and the Hamilton Depression Rating Scale (HAM‐D).

  Results: Both treatment groups had a decrease in total YMRS from baseline to endpoint, but this decrease was significantly greater in the placebo group (−9) than the gabapentin group (−6) (p<0.05). No difference between treatments was found for the total score on the HAM‐D. Secondary efficacy measures were not different between treatment groups. More patients in the placebo group had changes made to their ongoing lithium therapy (n=12) compared to the gabapentin group (n=4). When these patients are removed from the efficacy analysis, the YMRS treatment difference still favors placebo, but is no longer statistically significant. Based on gabapentin plasma levels at termination, some patients did not take the study drug as prescribed.

  Conclusions: The findings of this study did not demonstrate that gabapentin is an effective adjunctive treatment when administered to outpatients with bipolar disorder.
Bipolar disorder during adolescence and young adulthood in a community sample
Authors: Lewinsohn Peter M , Klein Daniel N , Seeley John R
Published: March 2003

Objectives:

To compare the incidence and prevalence of bipolar disorder (BD) between adolescence and young adulthood; to explore the stability and consequences of adolescent BD in young adulthood; to determine the rate of switching from major depressive disorder (MDD) to BD; and to evaluate the significance of subsyndromal BD (SUB).

  Methods: A large, randomly selected community sample (n=1507) received diagnostic assessments twice during adolescence, and a stratified subset (n=893) was assessed again at 24years of age. In addition, direct interviews were conducted with all available first‐degree relatives. Five mutually exclusive groups, based on diagnoses in adolescence, were compared: BD (n=17), SUB (n=48), MDD (n=275), disruptive behavior disorder (n=49), and no‐disorder (ND) controls (n=307).

  Results: Lifetime prevalence of BD was approximately 1% during adolescence and 2% during young adulthood. Lifetime prevalence for SUB was approximately 5%. Less than 1% of adolescents with MDD ‘switched’ to BD by age 24. Adolescents with BD had an elevated incidence of BD from 19 to 23 years, while adolescents with SUB exhibited elevated rates of MDD and anxiety disorders in young adulthood. BD and SUB groups both had elevated rates of antisocial symptoms and borderline personality symptoms. Compared to the ND group, adolescents with BD and SUB both showed significant impairment in psychosocial functioning and had higher mental‐health treatment utilization at age 24 years of age. The relatives of adolescents with BD and SUB had elevated rates of MDD and anxiety disorders. The relatives of SUB probands had elevated BD, while the relatives of BD had elevated rates of SUB and borderline symptoms.

  Conclusions: Adolescent BD showed significant continuity across developmental periods and was associated with adverse outcomes during young adulthood. Adolescent SUB was also associated with adverse outcomes in young adulthood, but was not associated with an increased incidence of BD. Due to high rates of comorbidity with other disorders, definitive conclusions regarding the specific clinical significance of SUB must await studies with larger numbers of ‘pure’ SUB cases.
Transcranial magnetic stimulation in an amphetamine hyperactivity model of mania
Authors: Shaldivin Alona , Kaptsan Alexander , Belmaker Robert H , Einat Haim , Grisaru Nimrod
Published: March 2003

Objectives:
Transcranial magnetic stimulation (TMS) of the brain has been reported to have therapeutic effects in mania, as well as depression. TMS has previously been reported to have effects similar to those of electroconvulsive shock in rat models of depression.   Methods: We, therefore, studied TMS in amphetamine‐induced hyperactivity as a rat model of mania.   Results: While two and seven daily TMS sessions significantly reduced activity after amphetamine, twice‐daily TMS for 7 days enhanced activity after amphetamine.   Conclusions: The results suggest that TMS treatment to rats interacts with the effects of amphetamine; the specific effects may be dependent on the schedule of treatment.
Neuropsychological frontal lobe tests indicate that bipolar depressed patients are more impaired than unipolar
Authors: Borkowska Alina , Rybakowski Janusz K
Published: March 2003

Objectives:
The aim of this study was to compare the neuropsychological performance of patients with bipolar or unipolar mood disorders during acute episodes of depression using intelligence and frontal lobe tests.   Methods: Fifteen patients with bipolar depression (BP) and 30 with unipolar depression (UP) were studied. For the neuropsychological assessment, the following tests: the Wechsler Adult Intelligence Scale‐Revised (WAIS‐R), the Trail Making Test (TMT), the Stroop test, the verbal fluency test and the Wisconsin Card Sorting Test (WCST) were used.   Results: The mean intensity of depression and mean duration of illness were similar in both groups. Patients in the BP group achieved significantly lower levels of performance in the non‐verbal part of WAIS‐R, in both parts of the Stroop test, in the verbal fluency test and also showed a tendency to achieve poorer results in TMT‐B than those in the UP group. Bipolar depressed patients also produced significantly poorer results with the WCST as they made twice as many perseverative errors and only completed half of the correct categories compared with the UP patients. The results of the TMT‐A tests, which measure psychomotor slowness, were similar in BP and UP patients. No differences between the results of male and female patients were noted in either group. Deterioration of the results associated with duration of the illness was only observed in the UP patients.   Conclusions: A higher degree of cognitive dysfunction connected with frontal lobe activity during an acute depressive episode was found in bipolar compared with unipolar depressed patients. These results may corroborate other findings pointing to pathogenic distinctions between bipolar and unipolar affective illness and to some similarities between bipolar illness and schizophrenia.
ECT in bipolar and unipolar depression: differences in speed of response
Authors: Daly James J , Prudic Joan , Devanand Dp , Nobler Mitchell S , Lisanby Sarah H , Peyser Shoshana , Roose Steven P , Sackeim Harold A
Published: March 2003

Objectives:
There is sparse evidence for differences in response to electroconvulsive therapy (ECT) between patients with bipolar or unipolar major depression, with virtually no information on speed of response. We contrasted a large sample of bipolar (BP) and unipolar (UP) depressed patients in likelihood and rapidity of clinical improvement with ECT.   Methods: Over three double‐blind treatment protocols, 228 patients met Research Diagnostic Criteria for UP (n=162) or BP depression (n=66). Other than lorazepam PRN (3 mg/day), patients were withdrawn from psychotropics prior to the ECT course and until after post‐ECT assessments. Patients were randomized to ECT conditions that differed in electrode placement and stimulus intensity. Symptomatic change was evaluated at least twice weekly by a blinded evaluation team, which also determined treatment length.   Results: Patients with BP and UP depression did not differ in rates of response or remission following the ECT course, or in response to unilateral or bilateral ECT. Degree of improvement in Hamilton Rating Scale for Depression scores following completion of ECT was also comparable. However, BP patients received significantly fewer ECT treatments than UP patients, and this effect was especially marked among bipolar ECT responders. Both BP I and BP II patients showed especially rapid response to ECT.   Conclusions: The BP/UP distinction had no predictive value in determining ECT outcome. In contrast, there was a large effect for BP patients to show more rapid clinical improvement and require fewer treatments than unipolar patients. The reasons for this difference are unknown, but could reflect a more rapid build up of anticonvulsant effects in BP patients.
Review of studies of child and adolescent offspring of bipolar parents
Authors: DelBello Melissa P , Geller Barbara
Published: March 2003

Objective:
The authors reviewed studies of child and adolescent offspring of bipolar (BP) parents. Findings from these studies are critically discussed with respect to methodological issues that can inform future designs.   Methods: A Medline search was performed to identify studies that examined child and adolescent offspring of BP parents. Publications were excluded if they did not separate offspring of BP parents from offspring of major depressive disorder or schizoaffective parents (‘affective offspring’) or did not separately analyze data from child‐ and adolescent‐age versus adult offspring.   Results: Seventeen studies fit these review criteria. Rates of mood disorders in child and adolescent offspring of BP parents ranged from 5 to 67% compared with rates in offspring of healthy volunteers of 0–38%. Rates of non‐mood disordered psychopathology ranged from 5 to 52% in offspring of BP parents and from 0 to 25% in offspring of healthy volunteers. Rates of mood disorders and of other psychopathology were increased in offspring of BP parents compared with offspring of healthy volunteers in all of the eight studies that included a comparison group of offspring of healthy volunteers.   Conclusions: Studies suggest that children (≤21 years) of BP parents are at increased risk for developing mood and other disorders (e.g., disruptive, anxiety). Therefore, additional investigations are clearly warranted. In the context of current research on diagnosis, assessment, longitudinal course and comorbidity of childhood mania, the following suggestions for the design of future studies should be considered: 1) Phenotypic specification of bipolar manifestations (e.g., BP‐I, BP‐II, BP‐NOS) in child/adolescent offspring and in bipolar parents themselves. 2) Control groups that are pediatric‐age relevant and thus include attention‐deficit hyperactivity disorder. 3) Assessments that include items for prepubertal mania and for onsets and offsets of all occurrences of symptoms and of environmental factors (e.g., life events) in offspring and in parents so that trajectories of overlap and sequence between child and parental mania can be investigated. 4) These detailed onsets and offsets of symptoms are also necessary to investigate prodromal manifestations of mania in the offspring. 5) Unaffected offspring present a unique opportunity to study pre‐ and postmorbid cognitive and physiological endophenotypes and structural and functional brain abnormalities. Findings from offspring studies will be crucial to inform research on the development of early intervention and prevention strategies.
Coping and its correlates among caregivers of patients with bipolar disorder: a preliminary study
Authors: Chakrabarti Subho , Gill Sapna
Published: March 2003

Objectives:
 In contrast to schizophrenia, coping patterns of caregivers of bipolar patients have not received much attention. Previous evidence suggests that demographic factors, illness variables, caregiver burden, appraisal, etc can significantly influence coping styles. This study thus attempted to examine coping and its correlates in caregivers of bipolar patients, in comparison with schizophrenia.

Method:
 Structured assessments of dysfunction, burden, appraisal, social support available, and coping styles were carried out in caregivers of 38 bipolar patients and 20 patients with schizophrenia (ICD – 10 diagnoses).

Results:
 Caregivers used a wide variety of coping strategies, both problem and emotion‐focused. In bipolar disorder, demographic parameters, illness duration, levels of dysfunction, burden and social support, and appraisal by caregivers demonstrated significant associations with coping styles of caregivers. Problem‐focused coping strategies were more common in caregivers of bipolar patients and emotion‐focused strategies in caregivers of schizophrenic patients. These differences appeared to be linked to differences in caregiver‐burden and appraisal between the two groups.

Conclusions:
 Appraisal by, and burden on caregivers play a major role in determining their style of coping. These factors largely accounted for the differences in coping observed between caregivers of patients of bipolar disorder and schizophrenia, in this study. Reducing burden on caregivers and enhancing their awareness of illness could lead to adoption of more adaptive coping styles by them.
Topiramate versus Bupropion SR when added to mood stabilizer therapy for the depressive phase of bipolar disorder: a preliminary single‐blind study
Authors: McIntyre Roger S , Mancini Deborah A , McCann Sonia , Srinivasan Janaki , Sagman Doron , Kennedy Sidney H
Published: March 2003

Objective:
 Antiepileptic drugs (AEDs) are commonly employed in the treatment of bipolar disorder. The efficacy and tolerability of topiramate, a novel anticonvulsant, and bupropion SR when added to mood stabilizer therapy were compared under single‐blind conditions (rater‐blinded) in patients meeting DSM‐IV criteria for bipolar I/II depression.

Methods:
 A total of 36 out‐patients with Hamilton Depression Rating Scale (HDRS‐17) scores ≥16 were randomized to receive escalating doses of either topiramate (50–300 mg/day) or bupropion SR (100–400 mg/day) for 8 weeks. Data were analyzed on an intent‐to‐treat basis using the last observation carried forward method.

Results: 
The percentage of patients meeting a priori response criteria (≥50% decrease from baseline in mean HDRS‐17 total score) was significant for both topiramate (56%) and bupropion SR (59%) [t(17)=2.542, p=0.04 and t(17)=2.661, p=0.03, respectively]. Baseline demographic and clinical parameters were comparable between the two treatment groups. The mean doses of study medication were 176 mg/day (SD=102 mg/day) for the topiramate‐treated group and 250 mg/day (SD=133 mg/day) for the bupropion SR‐treated group. A significant and comparable reduction in depressive symptoms was observed from baseline to endpoint following topiramate and bupropion SR treatment, according to a ≥ 50% reduction in the HDRS‐17. Total mean HDRS‐17 scores significantly decreased from baseline to endpoint in both groups (p=0.001), however, differences between the topiramate‐treated group and the bupropion SR‐treated group were not significant [t(36)=1.754, p=0.097]. Both topiramate and bupropion SR were generally well tolerated. Thirteen patients discontinued the study: 2 because of lack of efficacy, 1 due to withdrawal of consent and 10 following side‐effects (six in the topiramate and four in the bupropion SR‐treated group). There were no cases of affective switch in either arm. Weight loss was experienced by patients in both groups (mean weight loss at endpoint was 1.2 kg in bupropion SR and 5.8 kg in topiramate) [t(17)=2.325, p=0.061 and t(17)=2.481, p=0.043, respectively].

Conclusions:
 These preliminary data suggest that adjunctive topiramate may reduce depressive symptom severity in acute bipolar depression. The antidepressant efficacy of this compound requires confirmation via double‐blind placebo controlled investigation.
Clinical indicators for the use of antidepressants in the treatment of bipolar I depression
Authors: Fagiolini A , Frank E , Cherry CR , Houck PR , Novick DM , Buysse DJ , Kupfer DJ
Published: March 2003

Objectives:  Current guidelines provide little practical information on the clinical characteristics of bipolar I patients who are likely to benefit from the combination of a mood stabilizer and an antidepressant. Rather, guidelines simply state that an adjunctive antidepressant is recommended in cases of ‘severe’ depression. Our objective was to evaluate the clinical and demographic differences between patients who remitted on a mood stabilizer alone and patients who subsequently required an adjunctive antidepressant to achieve stabilization.

Methods:  We retrospectively compared the pharmacological treatment strategies of 39 patients with bipolar I disorder who were in a current depressive episode. Patients who did not respond to mood stabilizer monotherapy were prescribed an adjunctive antidepressant. We evaluated the clinical differences at baseline and week 1, 2 and 3 of treatment between patients stabilizing on a mood stabilizer alone and patients that did not remit until they subsequently received an adjunctive antidepressant.

Results:  Patients who required an adjunctive antidepressant had significantly higher total Hamilton Depression Rating (HRS‐D) scores at week 1, 2 and 3 of treatment, but not at baseline. Patients who remitted on mood stabilizer monotherapy were more likely to be married, achieved stabilization in less time, presented with higher Young Mania Rating Scale (YMRS) scores, and experienced the previous episode of depression more recently than patients who required an antidepressant.

Conclusions:  Our findings suggest that rapid improvement after achieving a therapeutic dose of a mood stabilizer is clinically significant and represents a surrogate endpoint in the treatment of bipolar I depression. Larger, prospective, and controlled studies are needed to verify our results and to identify additional indicators for a mood stabilizer and antidepressant combination treatment strategy.