Clinical trial: switch to combined mycophenolate mofetil and minimal dose calcineurin inhibitor in stable liver transplant patients--assessment of renal and allograft function, cardiovascular risk factors and immune monitoring

BACKGROUND: Calcineurin inhibitor (CNI)-related nephrotoxicity significantly contributes to chronic renal failure after liver transplantation. METHODS: In this prospective study, liver transplantation patients with renal dysfunction were randomized either to receive mycophenolate mofetil (MMF) followed by stepwise reduction of CNI with defined minimal CNI-trough levels (MMF group), or to continue their maintenance CNI dose (control group). Immune monitoring was performed in a subgroup of the patients. RESULTS: In the MMF group (n = 50), renal function assessed by serum creatinine improved >10% in 62% of patients, was stable in 36% and deteriorated >10% in 2% after 12 months compared with baseline values. Mean serum creatinine levels (+/- s.d.) significantly decreased from 1.90 +/- 0.44 mg/dL to 1.61 +/- 0.39 mg/dL and the corresponding calculated glomerular filtration rate significantly increased from 38.8 +/- 9.6 mL/min/1.73 m(2) to 47.0 +/- 11.8 mL/min/1.73 m(2) over a 12-month follow-up period. Blood pressure and levels of liver enzymes significantly decreased. In the control group (n = 25), there were no significant changes with respect to the investigated parameters. The MMF group had significantly lower numbers of circulating cytotoxic T cells compared with the controls; whereas regulatory T cells significantly increased. CONCLUSION: Combined MMF and minimal dose CNI therapy after liver transplantation is nephroprotective and may promote allograft tolerance.     

Efficacy of C0 and C2 monitoring in adult liver transplant recipients treated with neoral, mycophenolate mofetil, and steroids

BACKGROUND: Adjustment of induction therapy with Neoral after liver transplantation according to C2 levels yields a reduced incidence of rejection compared with C0 monitoring. A combination with mycophenolate mofetil may further reduce episodes of acute rejection. The purpose of this analysis was to evaluate the predictive value of C0 and C2 monitoring and the influence of primary dysfunction in liver transplant recipients receiving induction therapy with Neoral, mycophenolate mofetil, and steroids. PATIENTS AND METHODS: One hundred consecutive adult liver transplant recipients were analyzed. Neoral doses were solely adjusted according to C0 target levels in the first week by daily analysis of C0 levels. C2 levels were also measured, but results did not influence the decision process of daily Neoral adjustments. RESULTS: The 3-month survival rate for all patients was 83%. For a further analysis, 35 patients were excluded, the remaining 65 patients experienced 15 rejections (23.1%). Patients who did reach C0 target levels by days 3, 5, or 7 had rejection rates no different from those who did not reach C0 target levels. The patients who did reach C2 target levels by day 7 showed a significantly lower rejection rate compared with those who did not reach these levels. Comparison of rejection rates among patients with primary function grades I and II versus grades III and IV revealed a significant difference. There was no correlation between Model for End-Stage Liver Disease (MELD) score and acute rejection episodes. CONCLUSION: Achievement of C2 target levels by day 7, especially in the combination of Neoral with mycophenolate mofetil, led to a remarkably low acute rejection rate following liver transplantation.     

Positive end-expiratory pressure induces liver congestion in living donor liver transplant patients: myth or fact

Living-donated liver transplant (LDLT) patients may develop lung edema during reperfusion, requiring higher positive end-expiratory pressure (PEEP) levels, which may impair liver outflow. The aim of the study was to assess the effect of increased PEEP levels on venous liver outflow and systemic hemodynamics in patients after LDLT. Thirty-nine LDLT recipients were enrolled in this study. All patients were postoperatively pressure-controlled ventilated and three different PEEP levels (0, 5 and 10 mbar) were randomly set. Systemic hemodynamic parameters and flow velocities of the hepatic artery, portal vein, and right hepatic vein were recorded at each PEEP level. PEEP of 10 mbar increased significantly central venous and pulmonary capillary pressure. Flow velocities in the right hepatic vein, the portal vein, the hepatic artery, mean arterial pressure, pulmonary arterial pressure, and cardiac index were not influenced by PEEP. Our study demonstrated that PEEP up to 10 mbar did not impair liver outflow in LDLT recipients.     

Hepatic Hilar and Sectorial Vascular and Biliary Anatomy in Right Graft Adult Live Liver Donor Transplantation

Introduction

The aim of this study was to analyze vascular and biliary variants at the hilar and sectorial level in right graft adult living donor liver transplantation.

Methods

From January 2003 to June 2007, 139 consecutive live liver donors underwent three-dimensional computed tomography (3-D CT) reconstructions and virtual 3-D liver partitioning. We evaluated the portal (PV), arterial (HA), and biliary (BD) anatomy.

Results

The hilar and sectorial biliary/vascular anatomy was predominantly normal (70%-85% and 67%-78%, respectively). BD and HA showed an equal incidence (30%) of hilar anomalies. BD and PV had a nearly identical incidence of sectorial abnormalities (64.7% and 66.2%, respectively). The most frequent “single” anomaly was seen centrally in HA (21%) and distally in BD (18%). A “double” anomaly involved BD/HA (7.2%) in the hilum, and HA/PV and BD/PV (6.5% each) sectorially. A “triple” anomaly involving all systems was found at the hilum in 1.4% of cases, and at the sectorial level in 9.4% of instances. Simultanous central and distal abnormalities were rare. In this study, 13.7% of all donor candidates showed normal hilar and sectorial anatomy involving all 3 systems. A simultaneous central and distal “triple” abnormality was not encountered. A combination of “triple” hilar anomaly with “triple” sectorial normality was observed in 2 cases (1.4%). A central “triple” normality associated with a distal “triple” abnormality occurred in 7 livers (5%).

Conclusions

Our data showed a variety of “horizontal” (hilar or sectorial) and “vertical” (hilar and sectorial) vascular and biliary branching patterns, providing comprehensive assistance for surgical decision-making prior to right graft hepatectomy.     

Familial defective apolipoprotein B-100 in Slovakia: are differences in prevalence of familial defective apolipoprotein B-100 explained by ethnicity?

The objective of this study was to examine frequency of familial defective apo-B-100 (FDB, R3500Q mutation) in probands with the phenotype of familial hypercholesterolemia (FH) and in the general population of 40-year-old subjects in Slovakia and to characterize their lipid and clinical criteria and to compare the frequency of FDB with other populations. We identified 35 patients with FDB among 362 probands with clinical diagnosis of FH and two cases of FDB in the 40-year-old cohort of 2323 subjects from general Slovak population. Probands with FDB differed from those with FH only in plasma triglyceride concentrations (1.84+/-1.4 mmol/l versus 1.45+/-0.98 mmol/l, respectively, p<0.01). Evaluation of personal history of premature atherosclerosis did not show any differences (11.4% in FDB versus 20% in FH, p<0.16). The FDB patients had similar manifestation of xanthomatosis as the FH patients (17.1% versus 8.25%, p<0.25). The frequency of FDB of 9.7% found in the FH patients is among the highest of those reported to date. The frequency of R3500Q mutation of 0.09% found in Slovak 40-year-old subjects did not differ significantly from published population molecular data. Our comparison of estimated FDB frequencies with those which were found by DNA analysis demonstrated that estimated frequencies were not only wider in range, but also significantly higher than those which were assessed by the analysis. The definitive answer to the prevalence of FDB and its biochemical and clinical characteristics requires screening of unbiased samples of the general population from different ethnic groups based on molecular genetic methods.     

Psychometric properties of the MacNew heart disease health-related quality of life instrument in patients with heart failure

Rationale, aims and objectives Heart failure (HF) is a severe chronic disease and impairs health‐related quality of life (HRQL). While validated specific HRQL instruments are required for evaluation of treatment and rehabilitation in patients with HF, a single validated measure to document changes in HRQL for patients with different heart disease diagnoses would be invaluable. The purpose of this analysis was the psychometric analysis of the German MacNew Heart Disease Questionnaire (MacNew) in HF patients, which has previously been shown to be reliable and valid in patients with myocardial infarction, angina pectoris and arrhythmia. Methods We recruited 89 patients (61.7 ± 11.5 years; 84.3% male) in two Austrian and one Swiss cardiology department with documented HF (effect sizes 28.9 ± 10.1%). The self‐administered MacNew, the Short Form‐36 (SF‐36) and the Hospital Anxiety and Depression Scale were completed. Internal consistency reliability (Cronbach's α), discriminative and evaluative validity were assessed. Results Cronbach's α exceeded 0.80. Each MacNew scale differentiated between patients with and without anxiety (3.9 ± 1.0 vs. 5.3 ± 0.8, all P < 0.001), with and without depression (4.2 ± 1.2 vs. 5.2 ± 0.9 all P < 0.03) and by the SF‐36 health transition item (deteriorate = 4.39, no change = 4.95, improve = 5.45, all P < 0.02). Evaluative validity was demonstrated with effect sizes >0.70 for a subsample attending a 12‐week outpatient rehabilitation programme. Conclusions The German language version of the MacNew demonstrates consistently acceptable psychometric properties of reliability, validity and responsiveness in patients with documented HF. Together with previous documentation of reliability, validity and responsive, these findings strengthen the argument for the MacNew as a potential ‘core’ HRQL measure, at least in the German language.     

固相萃取GC－FID和GC－MS分析血浆中碱性药物

报道了用Ｘ－５固相萃取分离、毛细管ＧＣ－ＦＩＤ和ＧＣ－ＭＳ定性定量分析人血浆中３４种碱性药物的方法。在优化的提取条件下，大部分药物的最低检测浓度在０．５～２．０μｇ·ｍｌ－１之间，线性范围、定量精密度等满足临床中毒分析的要求。