bluuebunny/crossref_metadata_2025 huggingface dataset:
Tetraploidy in a 26‐month‐old girl (cytogenetic and molecular studies)
Authors: Guc‐Scekic M , Milasin J , Stevanovic M , Stojanov LJ , Djordjevic M
Published: March 2003

Liveborn infants with tetraploidy are very rare in human pregnancies and usually die during the first days or months. Seven cases of liveborn infants with tetraploidy have previously been reported. Among them only two 92, XXXX infants survived for longer than 12 months. Here we report on the case of a 26‐month‐old girl with tetraploidy. The main clinical features of tetraploidy are facial dysmorphism, severely delayed growth and developmental delay.

On the basis of molecular studies we discuss the possible origin of the additional chromosome sets in our proband. To our knowledge, this infant is the first reported case of tetraploidy who lived up to 26 months.
Genetic control of caudal development
Authors: Catala M
Published: March 2003

Several lines of evidence suggest that caudal development involves a distinct programme. This is illustrated by the fact that a specific pattern of malformations affects the caudal end of the human embryo. In addition, neurulation, the process leading to the formation of the neural tube, proceeds through different morphogenetic movements caudally. In mammals, as in birds, the caudal neural tube arises from cavitation and not from folding of the neural plate as in more rostral levels. However, recent fate mapping studies have suggested that the two modes of neurulation represent a continuous programme, possibly involving similar cellular or molecular mechanisms. Finally, analyses of mutant mice have shown that T‐box transcription factors and components of the Wnt signalling pathway control cellular migration and the promotion of mesoderm formation in the caudal embryo. In humans, mutation in the HLXB9 transcription factor causes an autosomal dominant form of sacral agenesis. Thus, the combination of classical embryological and molecular genetics approaches has provided critical reference points for the delineation of the developmental programme of the caudal embryo.
An Italian severe Salla disease variant associated with a SLC17A5 mutation earlier described in infantile sialic acid storage disease
Authors: Biancheri R , Verbeek E , Rossi A , Gaggero R , Roccatagliata L , Gatti R , Van Diggelen Op , Verheijen FW , Mancini GMS
Published: March 2003

The present study reports two Italian brothers affected by severe Salla disease (sialic acid storage disease), a slowly progressive autosomal recessive neurodegenerative disorder prevalent in the Finnish population. Mutations of the SLC17A5 gene, which encodes a protein called sialin, are the primary cause of both Salla disease and infantile sialic acid storage disease (ISSD), a clinically distinct severe disorder. All Finnish patients with Salla disease show a R39C mutation. Both patients showed moderate intellectual disability, spastic ataxic syndrome, hypomyelination and cerebellar atrophy on magnetic resonance imaging (MRI), and lysosomal storage, all typical of Salla disease. Mutation analysis of the SLC17A5 gene in the younger brother revealed no R39C mutation, but a 15‐bp deletion in exon 6 on one of the alleles. This mutation is the same described in French‐Canadian patients with ISSD. Salla disease must be suspected in patients with unexplained psychomotor retardation associated with ataxia and/or pyramidal symptoms, and MRI findings consistent with cerebral hypomyelination, irrespective of the patient's ethnic origin. A mutation screening based on R39C change does not exclude Salla disease outside Finland. Conversely, mutations found in ISSD can be expected, even in patients showing the Salla phenotype (e.g. symptoms at the milder end of the spectrum).
Influence of the angiotensin‐converting enzyme gene insertion/deletion polymorphism on lipoprotein/lipid response to gemfibrozil
Authors: Bossé Y , Vohl M‐C , Dumont M , Brochu M , Bergeron J , Després J‐P , Prud'homme D
Published: March 2003

Evidence suggests that fibrate therapy reduces the risk of recurrent coronary heart disease among men with low levels of high density lipoprotein cholesterol (HDL‐C). Indirect observations and new possible biological pathways suggest that the angiotensin‐converting enzyme (ACE) insertion/deletion (I/D) polymorphism might modulate the lipoprotein/lipid profile and its response to fibrate therapy. To assess the possible interaction between fibrate therapy and such variants on plasma lipid and lipoprotein levels, 65 dyslipidemic abdominally obese men were treated for 6 months with or without gemfibrozil (600 mg twice daily). No differences in baseline plasma lipid and lipoprotein levels were found between genotype groups except for the HDL3‐C subfraction, which was higher in the DD group (p = 0.02). A two‐way factorial ANOVA was used to evaluate the effect of the genotype (DD homozygotes vs I allele carriers), the treatment (placebo vs gemfibrozil), and the interaction between these two independent variables on changes observed in lipid and lipoprotein concentrations. A significant genotype‐by‐treatment interaction (p = 0.02) was found for the plasma HDL‐C response to the intervention program. In fact, having the DD genotype and being treated with gemfibrozil had a synergical effect on HDL‐C levels. The results of this study suggest that the ACE I/D polymorphism influences the effect of gemfibrozil on plasma HDL‐C levels.
Flow cytometry beads rather than the antihuman globulin method should be used to detect HLA Class I IgG antibody (PRA) in cadaveric renal regraft candidates
Authors: Bryan Christopher F , McDonald Scott B , Baier Karen A , Luger Alan M , Aeder Mark I , Murillo Daniel , Muruve Nicolas A , Nelson Paul W , Shield Charles F , Warady Bradley A
Published: March 2003

Abstract:HLA Class I antibody screening can be performed by flow cytometry using a mixture of 30 distinct bead populations each coated with the Class I antigen phenotype derived from different cell lines. In this study we compared the efficacy of Class I antibody screens done by flow cytometry beads with the antihuman globulin (AHG) method for patients awaiting cadaveric renal retransplantation. Class I panel reactive antibody (PRA) screening by flow cytometric beads of 21 regraft serum samples that had all been found to be negative by AHG DTT Class I PRA, revealed that 57.1% (12 of 21) had a flow Class I PRA of ≥ 10%. Furthermore, when five regraft sera with an intermediate PRA were screened (mean AHG DTT PRA = 33.2 ± 13%) the mean flow Class I PRA almost doubled (mean flow PRA = 72.4 ± 10.2%) ( p < 0.01). When active UNOS waiting list regraft candidates, after several months of screening the Class I PRA by flow beads, were divided into the three PRA categories based on their peak flow Class I PRA value (0−20%, 21−79% and ≥ 80%), the incidence of a positive flow cross‐match was 0%, 72% and 85% and the incidence of retransplantation was 60%, 22% and 10%, in each of these groups, respectively. These data provided our histocompatibility laboratory with the rationale to stop performing the AHG PRA and perform only the flow Class I PRA method for regraft candidates.
Comparisons of clinicopathological correlations between immediate and slow graft function in renal transplant recipients
Authors: Park Joo Hyun , Yang Chul Woo , Kim Young Soo , Lee Seung Hun , Choi Yeong Jin , Kim Yong Soo , Moon In Sung , Koh Yong Bok , Bang Byung Kee
Published: March 2003

Abstract:The functional recovery state of renal transplants can be divided into three types: immediate graft function (IGF), slow graft function (SGF) and delayed graft function (DGF). In contrast to the well‐known clinical outcomes for IGF and DGF, the pathological findings and clinical outcomes of SGF are undetermined. This study evaluated possible clinicopathological correlations in 237 patients with SGF compared with patients with IGF. IGF and SGF were defined by serum creatinine levels (IGF < 1.2 mg/day l; SGF: ≥1.2 mg/dL) at day 14 after renal transplantation. Graft biopsy was performed on this day, and pathological classification was performed using the Banff schema. The SGF group of patients (n = 121) showed higher rates of cadaver donors and male recipients than the IGF group (n = 116), but there were no significant differences in recipient or donor age, numbers of HLA mismatches, types of immunosuppressant or follow‐up periods between two groups. The SGF group showed higher serum creatinine levels at discharge, and a higher incidence of acute rejection than the IGF group (24.8% vs. 8.6%,P < 0.05) and lower graft survival rates (1 year, 93.3% vs. 100%; 5 years, 85.4% vs. 98.6%, respectively;P < 0.05). The presence of acute rejection in the SGF patients indicated a significantly decreased 5‐year survival rate compared with the IGF group. The SGF group of patients with borderline pathology had a higher incidence of acute rejection than the IGF group, and significant increases in the expression of mRNA for pro‐apoptotic genes (Fas‐ligand, granzyme B and perforin) compared with the IGF group. In conclusion, SGF represents the activated immune state and is associated with poor graft outcome. Anti‐rejection treatment or modified immunosuppressive regimen may thus be indicated for patients with SGF.
Analysis of allograft biopsy specimens from long‐term surviving patients with stable renal function: predictive value of long‐term graft prognosis
Authors: Toki Kiyohide , Takahara Shiro , Moriyama Toshiki , Kyo Masahiro , Morozumi Kunio , Yazawa Koji , Tanaka Toshiyuki , Wang Jing‐Ding , Permpongkosol Sompol , Kokado Yukito , Okuyama Akihiko
Published: March 2003

Abstract:Chronic allograft dysfunction is multi‐factorial, and histology of long‐term renal allograft shows variable findings. It is important to characterize the pathological features of graft kidneys with normal function to understand the natural course of transplants, which in turn would contribute to elucidate the causes of chronic allograft nephropathy (CAN). To address this issue, we performed ‘non‐episode’ biopsies on well‐functioning renal allografts, and evaluated the correlation between clinical outcome and histopathological findings. Patients who underwent a non‐episode biopsy had a serum creatinine concentration less than 2.0 mg/dL, urinary protein of less than 500 mg/day and a stable clinical course. In total, 90 such biopsies were performed. Mean follow‐up period after biopsy was 29 ± 16 months. We evaluated the histopathological findings and clinical outcome on each finding. Moreover, we compared the findings in the patients on tacrolimus with those of patients taking cyclosporin. Twenty‐three biopsy specimens were essentially normal. Graft dysfunction during the follow‐up period was recognized more frequently in patients showing more than one pathological process than in those with isolated findings. Graft outcome was not associated with drug‐induced nephropathy, but with acute rejection (P = 0.0193) and CAN (P = 0.0032). Patients found to have CAN‐b had a worse outcome than those with CAN‐a. CAN‐b was less common in the tacrolimus group than in the cyclosporin group. Non‐episode biopsy has a predictive value of the long‐term outcome of a renal allograft. CAN is associated with graft dysfunction; neither is drug‐induced nephropathy. Patients treated with tacrolimus had lower rates of CAN‐b than did cyclosporin‐treated subjects.
Patient survival after renal transplantation: II. The impact of smoking
Authors: Cosio Fernando G , Falkenhain Michael E , Pesavento Todd E , Yim Susan , Alamir Amir , Henry Mitchell L , Ferguson Ronald M
Published: March 2003

Renal transplant recipients have significantly higher mortality than individuals without kidney disease and the excess mortality is mainly due to cardiovascular causes. In this study, we sought to determine the impact of smoking, a major cardiovascular risk factor, on patient and renal graft survival. The study population included all adult recipients of first cadaveric kidney transplants done in our institution from 1984 to 1991. By selection, all patients were alive and had a functioning graft for at least 1 yr after transplantation. Smoking history was gathered prior to transplantation. The follow‐up period was 84.3±41 months and during this time 28% of the patients died and 21% lost their graft. By univariate and multivariate analysis, patient survival, censored at the time of graft loss, correlated with these pre‐transplant variables: age (p<0.0001); diabetes (p=0.0002); history of cigarette smoking (p=0.004); time on dialysis prior to the transplant (p=0.0005); and cardiomegaly by chest X‐ray (p=0.0005). Post‐transplant variables did not correlate with patient mortality. By Cox regression, patient survival time was significantly shorter in diabetics (p<0.0001), smokers (p=0.0005), and recipients older than 40 yr. However, there were no significant differences between the survival of smokers, non‐diabetics, diabetics, and older recipients. Patient death was the most common cause of renal transplant failure in smokers, in patients older than 40 yr, and in diabetics, but these patient characteristics did not correlate with graft survival. The prevalence of different causes of death was not significantly different between smokers and non‐smokers. In conclusion, a history of cigarette smoking correlates with decreased patient survival after transplantation, and the magnitude of the negative impact of smoking in renal transplant recipients is quantitatively similar to that of diabetes.
Exercise blood flow and microvascular distensibility in skeletal muscle normalize after heart transplantation
Authors: Sørensen Vibeke B , Wroblewski Henrik , Galatius Søren , Haunsø Stig , Kastrup Jens
Published: March 2003

This study investigated the effect of heart transplantation (HTX) on reduced exercise blood flow and microvascular stiffness in patients with congestive heart failure (CHF). Skeletal muscle blood flow (SMBF) during graded maximal supine bicycle exercise and microvascular distensibility (i.e., stiffness) were measured in musculus tibialis anterior by the isotope washout method. Measurements were performed in a cross‐sectional study with 31 CHF patients and 28 patients, mean 9 months after HTX, and in a longitudinal study in 12 CHF patients before, 3 months, and 14 months after HTX, and in 31 healthy controls. Maximal SMBF: In the cross‐sectional study, maximal SMBF was reduced in severe CHF patients (3.6±2.5 mL (100 g min)−1) and increased after HTX (7.7±4.8; p<0.01 versus controls (11±4.1). Maximal SMBF was reduced in CHF patients (5.8±4.0) and reversed to normalization 3 months after HTX (10.3±4.4) in the longitudinal study. Microvascular distensibility: The distensibility was reduced (severe CHF, 12±8%; moderate CHF, 23±14%) in the cross‐sectional study and increased after HTX towards normalization (38±20%; controls: 44±17%). In the longitudinal study, distensibility in CHF patients (14±6%) increased gradually to 32±12% (p<0.005) at 3 months and normalized 14 months after HTX (46±17%). HTX gradually reversed the reduced SMBF and microvascular distensibility in CHF patients towards normalization.
Central nervous system complications in liver transplant recipients – incidence, timing, and long‐term follow‐up
Authors: Bronster David J , Emre Sukru , Boccagni Patrizia , Sheiner Patricia A , Schwartz Myron E , Miller Charles M
Published: March 2003

Background: Neurological impairment is a major source of morbidity and mortality following orthotopic liver transplantation (OLT). We reviewed our experience with neurologic complications among our first 463 consecutive adult OLT recipients.Methods: Between September 1988 and October 1993, 463 adult patients underwent OLT. Data on incidence, time of onset, and outcome of central nervous system (CNS) complications was obtained from patient charts, including autopsy results when available. CNS complications were classified by clinical presentation and by etiology.Results: 93 patients (20.1%) had CNS complications following OLT. Encephalopathy (11.8%) and seizure (8.2%) were the leading complications. The incidence of immunosuppressive drug‐related complications was 5.6%; coma, 1.7%; cerebral hemorrhage, 1.5%; central pontine myelinolysis (CPM), 1.2%; stroke, 0.6%; and primary CNS lymphoma, 0.2%. Most CNS events (80%) were encountered in the first month after OLT. In the majority of cases, encephalopathy (70%) and seizure (50%) presented in the first 2 wk. Although most CNS infections occurred early, 2 patients developed tuberculous meningitis more than 1 yr post‐OLT. In 12 patients, death was directly related to CNS complications (2.6%).Conclusions: Most CNS complications occur early following OLT but may be seen even after 1 yr. Patients may survive serious neurologic events, such as cerebral hemorrhage, CPM, and meningitis.
A longitudinal study of TGF‐β1 protein levels in renal allograft recipients converted from CsA to MMF or AZA
Authors: Van Der Mast Barbara J , Van Besouw Nicole M , De Kuiper Petronella , Vaessen Lenard Mb , Ijzermans Jan Nm , Van Gelder Teun , Weimar Willem
Published: March 2003

Cyclosporine (CsA) is thought to enhance transforming growth factor (TGF)‐β1 production in vitro and in vivo and this may have a negative effect on long‐term graft survival. Therefore, we studied TGF‐β1 plasma levels in 30 patients before kidney transplantation, after transplantation during CsA treatment and after conversion from CsA to azathioprine (AZA) or mycophenolate mofetil (MMF). We questioned whether TGF‐β1 plasma levels would decrease after the discontinuation of CsA and whether the TGF‐β1 plasma levels did correlate with CsA trough levels and kidney function, measured by serum creatinine levels. TGF‐β1 plasma levels measured 1 yr after transplantation were lower compared to levels measured before transplantation, however not significantly (p=0.08). After conversion from CsA to MMF or AZA, a slight increase was observed in some patients, but in the total group TGF‐β1 levels remained unaffected. No correlation was found between the TGF‐β1 levels and CsA trough levels nor with creatinine levels. In conclusion, we did not observe higher TGF‐β1 plasma levels in plasma levels of patients receiving CsA treatment compared to blood from the same patients while on AZA or MMF.
Knowledge and opinions about organ donation among urban high school students: pilot test of a health education program
Authors: Weaver Marcia , Spigner Clarence , Pineda Michele , Rabun Kimi G , Allen Margaret D
Published: March 2003

Background: Increasing the diversity of the organ donor pool might improve the opportunities for people of color on organ transplant waiting lists to receive donated organs. We report on the results of a pilot classroom health education program to improve knowledge about organ donation and transplantation among a diverse student body at an urban high school.  Methods: The effectiveness of the educational program was evaluated with baseline and follow‐up questionnaires which examined: 1) whether the program increased knowledge about organ donation; 2) whether the students’ opinions about organ donation changed; and 3) whether the program was related to any changes in opinion.  Results: On the follow‐up questionnaire, correct answers on 15 factual questions increased by 18% for the treatment group, compared to 5% for the control group (p=0.00). Regarding opinions, at baseline 92% of white students had positive opinions about donation, compared to 48% of the students of color (p=0.00). In the follow‐up survey, the increase in positive opinions among the students of color was significantly greater than among white students (p=0.04). In this pilot study, however, changes in opinions occurred with equal frequency among students in the treatment and control groups.  In regression analysis, both knowledge of the subject and discussing donation with one's family were significantly associated with positive opinions about donation.  Conclusions: Overall, this pilot study provided encouraging evidence that the classroom health education program affected knowledge about organ donation, and that opinions about organ donation are responsive to increases in knowledge.
Bone loss after renal transplantation: role of hyperparathyroidism, acidosis, cyclosporine and systemic disease
Authors: Heaf James , Tvedegaard Erling , Kanstrup Inge‐Lis , Fogh‐Andersen Niels
Published: March 2003

In order to determine risk factors for bone loss after renal transplantation, dual energy X‐ray absorptiometry was performed in 125 renal transplant patients. The bone mineral density (BMD) was expressed as a percentage of the normal population (BMD%) and Z‐score (SD from normal). The whole body, lumbar spine and femoral neck BMD% (Z‐score) values were 93.9±8.9 (−0.90 SD), 91.6±14.9 (−0.98 SD) and 87±15.3 (−1.0 SD)%, respectively. Low BMD% was associated with low creatinine clearance (<40 mL/min: 91.6±7.9, >40 mL/min: 95.6±8.0, p<0.01), repeated graft loss (0: 94.4±9.1, >1: 87.4±9.3, p<0.05), long dialysis duration (<1 yr: 95.2±7.9, >5: 90.1±10.6, p<0.05), acidosis (bicarbonate <21 mmol/L: 89.6±8.0, >27: 96.7±7.2, p<0.01), secondary and tertiary hyperparathyroidism (<50 ng/L: 95.9±7.1, >200: 87.7±5.0, p<0.01), raised alkaline phosphatase (<200 units/L: 95.7±7.2, >300: 85.6±13.2, p<0.001), osteocalcin (<50 μg/L: 95.2±6.7, >100: 89.3±7.6, p<0.01) and urinary deoxypyridinoline (<5 nM/mM creatinine: femoral neck 89.6±10.7, >10: 82.1±20.1, p<0.05), low 25‐OH‐vitamin D (<10 μg/L: 91.3±9.8, >20: 96.9±7.4, p<0.001) and high cyclosporine concentration (0 ng/L: 98.3±7.0, >150: 92.1±9.3, p<0.05). Patients with clinical atherosclerosis (91.7±8.6 vs. 95.4±8.8, p<0.01), hypoalbuminemia (<550 μmol/L: 87.6±13.2, >550: 94.2±7.8, p<0.01), renovascular disease (89.7±5.7 vs. 95.0±5.7, p<0.05) and diabetic nephropathy (femoral neck 76.6±8.8 vs. 89.3±15.1, p<0.01) had lower bone masses. High bone mass was associated with previous dialysis alphacalcidol therapy (0: 92.2±7.5, >3 μg/wk: 97.3±6.9, p<0.05). No relationships with transplantation duration, 1,25‐OH‐vitamin D, aluminium, calcium or steroid dose were found. No involutional changes in tertiary hyperparathyroidism could be discerned.  Conclusion. The major threats to bone mass after renal transplantation appear to be ongoing hyperparathyroid bone disease, low renal function, acidosis, systemic disease and hypo‐vitaminosis D.
Co‐infection of two β‐herpesviruses (CMV and HHV‐7) as an increased risk factor for ‘CMV disease’ in patients undergoing renal transplantation
Authors: Chapenko S , Folkmane I , Tomsone V , Amerika D , Rozentals R , Murovska M
Published: March 2003

The ubiquity of human cytomegalovirus (CMV) and human herpesvirus‐7 (HHV‐7), as well as activation of these viruses during immunosuppression, allows the suggestion that both viruses could participate in the development of ‘CMV disease’ in patients after renal transplantation (RT). The aim of our research was to study the prevalence of latent CMV and HHV‐7 infections in patients before RT, to determine interaction between these viruses in dual infection and possible association of their reactivation with the progression of ‘CMV disease’ after RT. Peripheral blood samples were collected from 49 patients before and up to 10–12 wk after RT. The methods used for diagnostics of viral infections were: serology, nested polymerase chain reaction (nPCR) analysis of peripheral blood leukocytes (PBL) and plasma, and virus isolation in cell cultures (morphological changes, nPCR analysis of cellular and cell‐free samples, indirect immunofluorescence analysis). Before RT, CMV and HHV‐7 DNAs were detected in PBL but not in the plasma samples, which indicates the presence of latent viral infection in patients. Latent dual (CMV+HHV‐7) infection was prevalent (51.0%) in 49 patients, while CMV and HHV‐7 infections alone were detected in 26.5 and 12.2% of patients, respectively.  Risk of viral disease after RT, for recipients with latent dual infection before RT, was 12‐ and 2.2‐fold higher in comparison with CMV and HHV‐7 infections alone, respectively.  Frequency of dual infection in 18 recipients with ‘viral syndrome’ or ‘CMV disease’ after RT was reliably higher (13/18, 81.3%) than CMV (1/18, 6.2%) (p<0.025) and HHV‐7 (2/18, 12.5%) (p<0.025) infections alone. HHV‐7 reactivation preceded CMV reactivation in 77.0% of the cases of dual infection in the recipients with viral disease and reactivation of both viruses preceded the development of viral disease.  Severe ‘CMV disease’ developed in 2 out of 2 recipients with CMV primary infection and ‘viral syndrome’ in 1 recipient with CMV reinfection. The reactivation of CMV was detected in all recipients prior to onset of the disease.  Correlation was shown between reactivation of latent HHV‐7 infection and development of febrile syndrome in 2 out of 2 recipients with HHV‐7 infection alone.  Taking into account that dual infection is an increased risk factor for ‘viral syndrome’ and ‘CMV disease’ development, screening diagnostic should include testing for both viral infections in transplant donors as well as in recipients before and after RT.
Horseshoe kidney transplantation: an overview
Authors: Stroosma Otto B , Scheltinga Marc Rm , Stubenitsky Bart M , Kootstra Gauke
Published: March 2003

The horseshoe kidney is the most common anatomical renal variation. It represents a fusion anomaly, mainly at the lower poles, occurring between the 4th and 6th week of gestation. Horseshoe kidneys display a great variation in origin, number and size of the vasculature. Transplantation of these deviant kidneys can be done en bloc or they can be split into two halves and transplanted into two recipients, depending on the number of vessels and the anatomy of the urinary collecting system. A literature review reveals 31 case histories, published between 1975 and 1998. Of these 21 were transplanted into 38 recipients after division and ten were implanted en bloc. Nineteen grafts (41%) showed immediate function and 21 grafts (46%) showed delayed function. Thrombosis and acute rejection, leading to non‐function was seen in six grafts (13%). The overall success rate was 87% with a mean follow‐up of 22 months. The results of horseshoe kidney transplantation are good, provided that attention is paid to certain technical details. Because of donor scarcity, horseshoe kidneys should be used for transplantation.
Cyclosporin A withdrawal in live related renal transplantation: long‐term results
Authors: Dubey Deepak , Kumar Anant , Srivastava Aneesh , Mandhani Anil , Sharma Ajay Prakash , Gupta Amit , Sharma Rk
Published: March 2003

Cyclosporin A (CsA) withdrawal after 1 yr of stable graft function has been shown to be beneficial in cadaveric renal transplantation. This strategy could be even more suitable for ‘immunologically advantaged’ grafts as in live related renal transplantation. We report the long‐term outcome of patients in a live related transplantation programme undergoing early (between 1989 and 1992) and late (1993 onwards) CsA withdrawal as compared with those on long‐term low dose CsA (1993 onwards). Two‐hundred and fifty‐two patients were divided into three groups based on the following immunosuppressive protocol: group ECyW (n=99), early CsA withdrawal (9 months after transplantation); group LCyW (n=44), late CsA withdrawal (median 16 months, range 13–22 months after transplantation); and group LDCy (n=109), long‐term low dose CsA. The median period of follow‐up was 66 months after transplantation (range 43–84 months). There was no difference in the actuarial 6‐yr patient or graft survival among the three groups. Acute rejection episodes were more frequent in ECyW (54.4%) than in LDCy (31.8%) and LCyW (23.8%) (p=0.001). The risk of developing late (≥9 months) acute rejection was highest in ECyW 32/99 (32.3%) as compared with LCyW 8/44 (18.4%; p=0.08) and LDCy 8/109 (7.3%; p=0.0001). Of the 32 ECyW patients who developed acute rejection episodes after CsA withdrawal, 13 (40.6%) lost their grafts either due to uncontrolled acute rejection or to chronic rejection. Chronic rejection was higher in ECyW (24%) than in LCyW (11%; p=0.04) and LDCy (17%; p=0.17). Antihypertensive requirement was highest in patients maintained on low dose CsA. Graft function, as measured by serum creatinine levels, was significantly better in LCyW (1.24±0.4 mg%) as compared with ECyW (1.49±0.5 mg%) and LDCy (1.48±0.6 mg%). Early CsA withdrawal after live related renal transplantation is associated with a significant risk of acute rejection and subsequent chronic rejection. Slow withdrawal after 1 yr is safe and more economical than the long‐term administration of low dose CsA.
Prospective study of microchimerism in renal allograft recipients: association between HLA‐DR matching, microchimerism and acute rejection
Authors: Tajik N , Singal Dp , Pourmand G , Ebrahimi‐Rad M , Radjabzadeh Mf , Tavasoli P , Khosravi F , Nikbin B
Published: March 2003

The presence of donor‐derived hematopoietic cells in blood and various tissues of the organ recipients, termed allogeneic microchimerism, has been considered to play an essential role in establishment of organ acceptance. In this study, we prospectively determined the presence of peripheral blood microchimerism (PBM) in 20 male‐to‐female renal allograft recipients up to 30 months post‐transplantation. Recipients were categorized according to the pattern of microchimerism into microchimeric and nonmicrochimeric groups, and then state of human leukocyte antigens (HLA) Class II (DR/DQ) matching, episodes of acute rejection, age at transplantation, renal function, and history of blood transfusion were compared. DNA was extracted from donor, pre‐transplant, and post‐transplant (1 wk; 1, 3, 6, 12, 18, 24, and 30 months) peripheral blood samples. We analyzed PBM using nested polymerase chain reaction (PCR) amplification specific for the SRY region of the Y chromosome with a sensitivity up to 1:1 000 000. Microchimerism was detected in 13 (65%) of 20 recipients at various intervals. The highest frequency of microchimerism was at 1 wk (55%). Among microchimeric recipients, none were positive on all post‐transplant analyses. Interestingly, nonmicrochimeric cases were negative throughout the study. The three recipients with an episode of acute rejection during the first week after transplantation were all in the nonmicrochimeric group with completely mismatched HLA‐DR antigens. HLA‐DR incompatibility was significantly lower (t‐test, p<0.05) in microchimeric cases (1.0±0.58) than in nonmicrochimeric ones (1.9±0.38). But regarding HLA‐DQ and other clinical parameters mentioned above, significant difference was not observed. We propose that there is an association between HLA‐DR matching, microchimerism and acute graft rejection in our recipients. Our study demonstrates that, with routine immunosuppressive protocols, higher compatibility of HLA‐DR antigens facilitates microchimerism induction. Then, development of new stronger immunosuppressive protocols (including conditioning) or augmentation of chimeric state (by donor‐specific bone marrow infusion), especially in completely mismatched HLA‐DR renal allograft recipients, may be useful for graft acceptance.
Enhancing transplant patients' adherence to medication therapy
Authors: Chisholm Marie A
Published: March 2003

Despite the importance of proper medication use, many transplant patients do not take their medications correctly. Non‐adherence to medication therapy leads to adverse consequences, and practitioners should encourage adherence by transplant patients. This manuscript discusses several aspects of medication taking behavior including: (1) methods of identifying medication non‐adherence; (2) models used to identify possible determinants of medication taking behavior; (3) strategies to educate patients concerning their therapy; (4) factors promoting adherence and non‐adherence; and (5) practical interventions that we, as practitioners, can employ to enhance adult and pediatric transplant patients' adherence to therapy. By using the strategies suggested, transplant patients' adherence to medication therapy may be enhanced and patients' quality of life improved.
Hepatic copper concentration in children undergoing living related liver transplantation due to Wilsonian fulminant hepatic failure
Authors: Komatsu Haruki , Fujisawa Tomoo , Inui Ayano , Sogo Tsuyoshi , Sekine Isao , Kodama Hiroko , Uemoto Shinji , Tanaka Koichi
Published: March 2003

Liver transplantation is indicated for Wilson's disease (WD) patients having the fulminant form and end‐stage liver failure. To evaluate whether living related liver transplantation (LRLT) can correct the copper metabolism in WD patients, we studied two children who underwent LRLT because of fulminant hepatic failure. They were 7 and 13 yrs old at the time LRLT was performed. Serum ceruloplasmin levels, serum copper levels, copper urine excretion, and hepatic copper concentrations were measured. Serum ceruloplasmin levels (16.7 ± 1.2 mg/dL) and serum copper levels (67.0 ± 1.4 μg/dL) were lower than the normal range after LRLT in case 1. In both patients, urinary copper excretion was reduced markedly after LRLT, but was not normalized (case 1, 191.2 ± 182.2 μg/d; case 2, 140.0 ± 156.7 μg/d). Hepatic copper concentrations were slightly elevated (case 1, 158.8 ± 44.6 μg/g dry weight; case 2, 147.0 μg/g dry weight) after LRLT in both cases, but did not exceed 250 μg/g dry weight. LRLT is a curative procedure in Wilson's disease presenting fulminant hepatic failure or advanced cirrhosis. However, this study indicates that the conditions of copper metabolism in WD patients undergoing LRLT are similar to those in heterozygous genetic carriers. Because the living related donors are the parents who carry the abnormal gene, LRLT cannot completely restore the copper balance in WD patients.
Mycophenolic acid concentrations in long‐term heart transplant patients: relationship with calcineurin antagonists and acute rejection
Authors: Cantin Bernard , Giannetti Nadia , Parekh Hemal , Panchal Shyam N , Kwok Bernard W‐K , Najem Ruhina , Woodman Katina , Hunt Sharon A , Valantine Hannah A
Published: March 2003

Background: When used in conjunction with steroids and cyclosporin, mycophenolate mofetil (MMF) has been shown to significantly reduce mortality and incidence of rejection in the first year after heart transplantation. It also appears that in this early post‐transplantation period, the monitoring of immunosuppressive therapies may be warranted. The current study was undertaken to determine if such monitoring is still useful more than 1 yr after heart transplantation.

Methods: Twenty‐six patients who had survived the first year after orthotopic heart transplantation and had been on MMF therapy for more than 3 months were prospectively followed. At the time of their routine endomyocardial biopsy blood samples were taken to monitor immunosuppressive therapy. Most patients had two samples taken, on average 109 d apart.

Results: There were 22 episodes of asymptomatic rejection documented on a total of 48 biopsies. Of these, only two were of ISHLT (International Society for Heart and Lung Transplantation) grade 3A the remainder being of ISHLT grades 1 or 2. There was no relation between immunosuppressive regimen (tacrolimus and MMF or cyclosporin and MMF) and rejection. There was no relation between monitored immunosuppressive levels and rejection. Patients with the combination of MMF and tacrolimus had significantly higher plasma mycophenolic acid levels despite significantly lower daily MMF dose.

Conclusion: There does not appear to be a benefit in continued monitoring of plasma mycophenolic acid levels beyond the first year of heart transplantation. There were significant differences in plasma mycophenolic acid levels depending on the type of calcineurin inhibitor concomitantly used.
The impact of lithium prophylaxis on the course of bipolar disorder: a review of the research evidence
Authors: Maj Mario
Published: March 2003

A critical review is provided of the available research evidence concerning the efficacy and effectiveness of lithium prophylaxis in bipolar disorder. It is emphasized that, in spite of the limitations of available placebo‐controlled trials and naturalistic studies, lithium is the only drug whose prophylactic activity in bipolar disorder is convincingly proved, and remains the first‐choice medication in the long‐term treatment of bipolar patients. The impact of lithium prophylaxis is likely to be less significant on atypical and comorbid cases of bipolar disorder than in typical manic–depressive illness, but the superiority of other medications over lithium in the long‐term treatment of those cases is at present not convincingly proved by research. Currently available research evidence does not seem to support the idea that lithium exerts its prophylactic effect on relapses but not on recurrences of bipolar disorder. Clinicians should be aware of the fact that the drop‐out rate in bipolar patients receiving long‐term lithium prophylaxis is high even if treatment surveillance is accurate, and that complete suppression of recurrences is a relatively rare outcome of prophylaxis.
Response to placebo among bipolar I disorder patients experiencing their first manic episode
Authors: Chengappa Kn Roy , Tohen Mauricio , Levine Joseph , Jacobs Thomas , Thase Michael E , Sanger Todd M , Kupfer David J
Published: March 2003

Background:
The first episode of an illness may respond differently to any treatment compared to multiple episodes of the same illness. This study details the treatment response of six first‐episode manic patients who participated in a previously reported study of 139 subjects comparing olanzapine to placebo in bipolar I mania (Tohen M, Sanger TM, McElroy SL, Tollefson GD, Chengappa KNR, Daniel DG. Olanzapine versus placebo in the treatment of acute mania. Am J Psychiatry 1999; 156: 702–709).   Methods: Six first‐episode subjects participated in a 3‐week double‐blind, random assignment, parallel group, placebo‐controlled study of olanzapine for bipolar mania. The Young Mania Rating Scale (Y‐MRS), Clinical Global Impression, and Hamilton Depression ratings were administered weekly. Lorazepam as rescue medication was permitted for the first 10 days.   Results: Five subjects were randomized to placebo and one to olanzapine. Two subjects (40%) with psychotic mania (who also had their first‐illness episode) were assigned to placebo and responded with greater than 50% reduction in the Y‐MRS score and also remitted in 3 weeks. Another placebo‐assigned subject had a 46% reduction in the Y‐MRS scores, and two placebo‐assigned subjects worsened. The olanzapine‐assigned subject had a 44% reduction in the Y‐MRS score. In contrast, 34 of 69 (48.6%) multiple‐episode olanzapine subjects responded and 14 of 61 (23.0%) of placebo‐treated subjects did.   Conclusions: This preliminary data set suggest there may be differences in treatment response between first‐illness episode versus multi‐episode bipolar manic subjects. Larger numbers of subjects with these illness characteristics are needed to either confirm or refute this suggestion.
Prior stimulant treatment in adolescents with bipolar disorder: association with age at onset
Authors: DelBello Melissa P , Soutullo Cesar A , Hendricks Wendi , Niemeier R Todd , McElroy Susan L , Strakowski Stephen M
Published: March 2003

Objectives:
To compare demographic and clinical characteristics between bipolar adolescents with and without a history of stimulant treatment, we hypothesized that adolescents treated with stimulants would have an earlier age at onset of bipolar disorder, independent of co‐occurring attention‐deficit‐hyperactivity disorder (ADHD).   Method: Thirty‐four adolescents hospitalized with mania were assessed using the Washington University at St Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH‐U‐KSADS). We systematically evaluated age at onset of bipolar disorder and pharmacological treatment history.   Results: Bipolar adolescents with a history of stimulant exposure prior to the onset of bipolar disorder had an earlier age at onset of bipolar disorder than those without prior stimulant exposure. Additionally, bipolar adolescents treated with at least two stimulant medications had a younger age at onset compared with those who were treated with one stimulant. There was no difference in age at onset of bipolar disorder between bipolar adolescents with and without ADHD.   Conclusions: Our results suggest that stimulant treatment, independent of ADHD, is associated with younger age at onset of bipolar disorder. A behavioral sensitization model is proposed to explain our findings. There are several limitations to our study including the small sample size, the retrospective assessment of stimulant exposure and age at onset of bipolar disorder, and the inclusion of only hospitalized patients, who may be more likely to present with a severe illness. Nonetheless, future prospective longitudinal investigations that systematically assess the effects of stimulant medications in children with or at genetic risk for bipolar disorder are warranted.
A measure for assessing patient perception of provider support for self‐management of bipolar disorder
Authors: Ludman Evette J , Simon Gregory E , Rutter Carolyn M , Bauer Mark S , Unützer Jürgen
Published: March 2003

Objectives:
 Health care providers have an important role in acknowledging and supporting patients' self‐management of chronic illnesses such as bipolar disorder. This report describes the development and evaluation of a brief measure for assessing patient perception of providers' support for self‐management of bipolar disorder.

Methods:
 A 10‐item measure was developed combining generic items from an existing measure of providers' autonomy supportive versus controlling style with items specific to the self‐management of bipolar disorder. The psychometric properties of the measure and its relation to clinical variables were evaluated in a sample of patients enrolled in an ongoing randomized intervention trial.

Results:
 Data were obtained from 420 patients with a chart diagnosis of bipolar disorder (mean age=44, 68% female, 88% Caucasian). The proportion of missing responses for items ranged from 0 to 3%. Reliability coefficient alpha for the full scale was 0.94. Corrected item–total correlations for individual items ranged from 0.70 to 0.83. Factor analysis identified a single factor accounting for 67% of total variance. Factor loadings for individual items were all at least 0.75. The measure showed moderate positive correlations with measures of self‐efficacy for managing bipolar disorder (r=0.34; p < 0.001), treatment satisfaction (r=0.63; p < 0.001), small negative correlations with measures of mania symptoms (r=–0.11; p < 0.03) and depressive symptoms (r=–0.09; p < 0.10).

Conclusions:
 This measure shows good psychometric properties and good evidence for convergent and discriminant validity. It is promising for assessing an important aspect of care for bipolar disorder.
Immune activation, steroid resistancy and bipolar disorder
Authors: Kupka RW , Breunis MN , Knijff E , Ruwhof C , Nolen WA , Drexhage HA
Published: March 2003

Kupka RW, Breunis MN, Knijff E, Ruwhof C, Nolen WA, Drexhage HA. Immune activation, steroid resistancy and bipolar disorder.   Bipolar Disord 2002: 4(Suppl. 1): 73–74. © Blackwell Munksgaard, 2002
Infection, treatment and immune response in patients with bipolar disorder versus patients with major depression, schizophrenia or healthy controls
Authors: Hinze‐Selch Dunja
Published: March 2003

Hinze‐Selch D. Infection, treatment and immune response in patients with bipolar disorder versus patients with major depression, schizophrenia or healthy controls.  Bipolar Disord 2002: 4(Suppl. 1): 81–83. ©Blackwell Munksgaard, 2002

Bipolar disorder is the least studied among the three major psychiatric disorders of schizophrenia, major depression and bipolar disorder. Furthermore, investigations on infection and immunity in bipolar disorder make up only a small portion of the sparse research done on this disorder. However, there are reports that modulation of the immune system and certain infections might be associated with bipolar disorder and that there might be differences between bipolar and the other disorders. The purpose of this paper is to briefly review published data on these issues in bipolar versus the other disorders, and to present an ongoing clinical study on the putative involvement of infection with the parasite Toxoplasma gondii in these three major psychiatric disorders.
Etiology and outcome of second trimester non‐immunologic fetal hydrops
Authors: HEINONEN SEPPO , RYYNÄNEN MARKKU , KIRKINEN PERTTI
Published: March 2003

Background. This investigation was undertaken to study the conditions resulting in midtrimester fetal hydrops and to evaluate its overall prognosis as regards counseling purposes.

Material and methods. The etiology of midtrimester non‐immune fetal hydrops was retrospectively evaluated as regards cases detected in singleton pregnancies (n=58) from January 1987 through December 1996. The condition was diagnosed by way of routine biochemical and ultrasonographic screening of a pregnant population.

Results. The rate of diagnosed midtrimester fetal hydrops was 1 in 1700 pregnancies and the overall survival rate in this usually unexpected condition was less than 10%. Various chromosomal and fetal structural abnormalities dominated as a cause of fetal hydrops, representing 44.8% and 43.1% of the cases, respectively. Infection caused only 6.9%. The underlying etiology remained unknown in only three cases. However, in 78% the diagnosis was already known prenatally.

Discussion. Although the overall prognosis is poor, knowledge of the primary etiology is important to determine a rational therapeutic strategy. If the results of routine investigations rule out malformation and abnormal chromosomes, follow‐up serial ultrasonographic assessment may indicate that the hydropic state is transient, carrying a somewhat better prognosis.
Diagnosing fetal urinary tract abnormalities: benefits of MRI compared to ultrasonography
Authors: POUTAMO JAANA , VANNINEN RITVA , PARTANEN KAARINA , KIRKINEN PERTTI
Published: March 2003

Background. To compare antepartum ultrasonography with magnetic resonance imaging for prenatal diagnosis of malformations in the fetal urinary tract in high risk patients during the last trimester.

Materials and methods. The study involved 22 women and 24 fetuses with either severe oligohydramnios or ultrasonographically or clinically suspected abnormality of urinary tract. Ultrasound examination was carried out with 5 MHz abdominal convex probe and magnetic resonance imaging with superconductive 1.5 T equipment. Postnatal findings were used as reference.

Results. Correct diagnosis of urinary tract anomaly was done in 15 fetuses on ultrasound and in 20 fetuses on magnetic resonance imaging. Both methods enabled correct diagnosis in 12, only ultrasound in three and only magnetic resonance imaging in eight fetuses. Both methods imaged equivocally in one case. The additional information by magnetic resonance imaging was gained from five fetuses out of 12 pregnancies with oligohydramnios and from three fetuses out of ten pregnancies with normal amount of amniotic fluid.

Conclusions. MRI is a valuable additional method to ultrasonography of fetal urinary tract if resolution of ultrasound is impaired for reason of oligohydramnios or technical deterioration.