Meta-analysis of the prognostic role of perioperative platelet count in posthepatectomy liver failure and mortality.

BACKGROUND: Emerging evidence suggests that the perioperative platelet count (PLT) can predict posthepatectomy liver failure (PHLF). In this systematic review and meta-analysis, the impact of perioperative PLT on PHLF and mortality was evaluated. METHODS: MEDLINE and Web of Science databases were searched systematically for relevant literature up to January 2018. All studies comparing PHLF or mortality in patients with a low versus high perioperative PLT were included. Study quality was assessed using methodological index for non-randomized studies (MINORS) criteria. Meta-analyses were performed using Mantel-Haenszel tests with a random-effects model, and presented as odds ratios (ORs) with 95 per cent confidence intervals. RESULTS: Thirteen studies containing 5260 patients were included in the meta-analysis. Two different cut-off values for PLT were used: 150 and 100/nl. Patients with a perioperative PLT below 150/nl had higher PHLF (4 studies, 817 patients; OR 4·79, 95 per cent c.i. 2·89 to 7·94) and mortality (4 studies, 3307 patients; OR 3·78, 1·48 to 9·62) rates than patients with a perioperative PLT of 150/nl or more. Similarly, patients with a PLT below 100/nl had a significantly higher risk of PHLF (4 studies, 949 patients; OR 4·65, 2·60 to 8·31) and higher mortality rates (7 studies, 3487 patients; OR 6·35, 2·99 to 13·47) than patients with a PLT of 100/nl or greater. CONCLUSION: A low perioperative PLT correlates with higher PHLF and mortality rates after hepatectomy.

[Durable remission under dual HER2 blockade with Trastuzumab and Pertuzumab in a patient with metastatic gallbladder cancer]. / Dauerhafte Remission unter dualer HER2-Blockade mit Trastuzumab und Pertuzumab bei metastasiertem Gallenblasenkarzinom.

Gallbladder cancer represents a rare but dismal disease. The only curative option is complete surgical resection, though patients often develop recurrent disease. In patients with advanced biliary tract cancer, the combination of cisplatin and gemcitabine showed a benefit in overall survival compared to gemcitabine alone. However, there is no standardized second-line regimen after treatment failure. We report on a young patient with early recurrence of a gallbladder cancer with cutaneous and peritoneal metastases. Upon identification of an ERBB2 gene amplification within the NCT MASTER (Molecularly Aided Stratification for Tumor Eradication Research) exome sequencing program with resulting overexpression of HER2 in the tumors cells, the patient received a targeted therapy with the HER2 antibodies pertuzumab and trastuzumab in combination with nab-paclitaxel, which led to a durable remission for more than one year. This case report underlines the potential of molecularly aided personalized targeted therapy for patients with biliary tract cancer and the need for respective clinical trials.

Serum levels of chemokines CCL4 and CCL5 in cirrhotic patients indicate the presence of hepatocellular carcinoma.

BACKGROUND: Most hepatocellular carcinomas (HCCs) are diagnosed at an advanced stage. The prognostic value of serum tumour markers alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) is limited. The aim of our study is to evaluate the diagnostic value of serum growth factors, apoptotic and inflammatory mediators of cirrhotic patients with and without HCC. METHODS: Serum samples were collected from cirrhotic potential liver transplant patients (LTx) with (n=61) and without HCC (n=78) as well as from healthy controls (HCs; n=39). Serum concentrations of CRP, neopterin and IL-6 as markers of inflammation and thrombopoietin (TPO), GCSF, FGF basic and VEGF, HMGB1, CK-18 (M65) and CK18 fragment (M30) and a panel of proinflammatory chemokines (CCL2, CCL3, CCL4, CCL5, CXCL5 and IL-8) were measured. Chi square, Fisher exact, Mann-Whitney U-tests, ROC curve analysis and forward stepwise logistic regression analyses were applied. RESULTS: Patients with HCC had higher serum TPO and chemokines (P<0.001 for TPO, CCL4, CCL5 and CXCL5) and lower CCL2 (P=0.008) levels than cirrhotic patients without HCC. Multivariate forward stepwise regression analysis for significant parameters showed that among the studied parameters CCL4 and CCL5 (P=0.001) are diagnostic markers of HCC. Serum levels of TPO and chemokines were lower, whereas M30 was significantly higher in cirrhotic patients than in HCs. CONCLUSIONS: High serum levels of inflammatory chemokines such as CCL4 and CCL5 in the serum of cirrhotic patients indicate the presence of HCC.

Temporary placement of fully covered self-expandable metal stents in biliary complications after liver transplantation.

In the present study we prospectively evaluated the safety and efficacy of temporary fully covered, self-expandable metal stents (fcSEMS) to treat biliary strictures (n = 9), leaks (n = 9), and combined lesions (n = 1) occurring after liver transplantation, when standard endoscopic attempts had failed. Placement of fcSEMS and their removal in scheduled patients were successful and without complications. Resolution of the biliary lesion was confirmed in 15 of 19 patients (79 %). Treatment was not successful in two patients and not evaluable in 2 other patients. Complications occurred in 9 /19 patients (47 %): stent migration in 6, stent occlusion in 1, and de novo stricture after successful treatment of a biliary leak in 2. After a median follow-up of 12 months, one recurrent anastomotic stricture was noted. Temporary placement of fcSEMS in biliary strictures and leaks after liver transplantation provides satisfactory results even in patients who have undergone multiple previous conventional endoscopic attempts, and offers an alternative approach to surgical intervention.

[Wilson disease--evaluation of disease-related topics through the eyes of patients by patient-generated paintings--a cooperative study with the German patient organisation Verein morbus Wilson e. V]. / Morbus Wilson--künstlerische Darstellung der Erkrankung durch Patienten zur Evaluation subjektiv bedeutender krankheitsassoziierter Themen--eine Gemeinschaftsstudie mit der Patientenorganisation Verein Morbus Wilson e. V.

BACKGROUND: The importance of disease-related topics can vary widely between patients and doctors. Patient organisations such as the German Verein Morbus Wilson e. V. can overcome this discrepancy. The goal of the present cooperative study was the collection of topics important to Wilson patients by asking patients to generate paintings about their disease. METHODS: Patients with Wilson disease were asked by mail to draw paintings about their disease and to donate them to the Verein Morbus Wilson e. V. RESULTS: 32 paintings from 27 patients were donated. The majority of the patients added written comments to their art work. Disease-related topics included in the paintings were as follows: psychological work-up of the disease 33 % (n = 11), presentation of affected organs (liver/brain) 22 % (n = 6), therapy 19 % (n = 5), diagnostic path 15 % (n = 4), inheritance 15 % (n = 4), copper-related diet 11 % (n = 3). 33 % (n = 11) of the paintings were composed of two parts reflecting before and after the disease or presenting the individual time course of the disease. CONCLUSION: Psychological aspects of disease acceptance are the prominent topic in the paintings. The timepoint of diagnosis is experienced as major change in life. The paintings enable both the patient organisation and the caretakers to put more focus on the psychological aspects of the disease. Asking for paintings opens a new channel for patient-physician contacts and produces a feeling of interest and competence in patients.

Effect of mycophenolic acid on inosine monophosphate dehydrogenase (IMPDH) activity in liver transplant patients.

BACKGROUND: Due to the development of immunosuppressants, the focus in transplanted patients has shifted from short-term to long-term survival as well as a better adjustment of these drugs in order to prevent over- and under-immunosuppression. Mycophenolic acid (MPA) is a noncompetitive inhibitor of inosine monophosphate dehydrogenase (IMPDH) and approved for prophylaxis of acute rejection after kidney, heart, and liver transplantation, where it has become a part of the standard therapy. Targeting inosine monophosphate IMPDH activity as a surrogate pharmacodynamic marker of MPA-induced immunosuppression may allow a more accurate assessment of efficacy and aid in limiting toxicity in liver transplanted patients. AIM: Assess IMPDH-inhibition in liver transplant recipients and its impact on biliary/infectious complications, acute cellular rejection (ACR) and liver dependent survival. METHODS: This observational cohort study comprises 117 liver transplanted patients that were treated with mycophenolate mofetil (MMF) for at least 3 months. Blood samples (BS) were collected and MPA serum level and IMPDH activity were measured before (t(0)), 30minutes (t(30)) and 2h after (t(120)) MMF morning dose administration. Regarding MPA, we assessed the area under the curve (AUC). Patients were prospectively followed up for one year and assessed for infectious and biliary complications, episodes of ACR and liver dependent survival. RESULTS: The MPA levels showed a broad interindividual variability at t(0) (2.0±1.8ng/ml), t(30) (12.7±9.0ng/ml) and t(120) (7.5±4.3ng/ml). Corresponding IMPDH activity was at t(o) (23.2±9.5 nmol/h/mg), at t(30) (16.3±8.8 nmol/h/mg) and t(120) (18.2±8.7 nmol/h/mg). With regard to MPA level we found no correlation with infectious or biliary complications within the follow-up period. Patients with baseline IMPDH(a) below the median had significant more viral infections (6 (10.2%) vs. 17 (29.3%); P=0.009) with especially more cytomegalovirus (CMV) infections (1 (3.4%) vs. 6 (21.4%); P=0.03)). Furthermore, patients with baseline IMPDH(a) above the median developed more often non-anastomotic biliary strictures (8 (13.6%) vs. 1 (1.7%), P=0.03). We found the group reaching the combined clinical endpoint of death and re-transplantation showing significantly lower MPA baseline values (t(0) 0.9±0.7 vs. 2.1±1.8µg/ml Mann-Whitney-U: P=0.02). We calculated a simplified MPA(AUC) with the MPA level at baseline, 30 and 120minutes after MPA administration. Whereas we found no differences with regard to baseline characteristics at entry into the study patients with MPA (AUC) below the median experienced significantly more often the combined clinical endpoint (12.1% (7/58) vs. 0.0% (0/57); P=0.002) and had a reduced actuarial re-transplantation-free survival (1.0 year vs. 0.58 years; Log-rank: P=0.007) during the prospective one-year follow-up period. In univariate and multivariate analysis including gender, age, BMI, ACR, MPA (AUC) and IMPDH(a) only BMI, MPA (AUC) and IMPDH(a) were independently associated with reduced actuarial re-transplantation-free survival. CONCLUSION: MPA-levels and IMPDH-activity in liver transplanted patients allows individual risk assessment. Patients with higher IMPDH inhibition acquire more often viral infections. Insufficient IMPDH inhibition is associated with development of non-anastomotic bile duct strictures and reduced re-transplantation-free survival.

Does vancomycin resistance increase mortality in Enterococcus faecium bacteraemia after orthotopic liver transplantation? A retrospective study.

BACKGROUND: The relevance of vancomycin resistance in enterococcal blood stream infections (BSI) is still controversial. Aim of this study was to outline the effect of vancomycin resistance of Enterococcus faecium on the outcome of patients with BSI after orthotopic liver transplantation (OLT). METHODS: The outcome of OLT recipients developing BSI with vancomycin-resistant (VRE) versus vancomycin-susceptible Enterococcus faecium (VSE) was compared based on data extraction from medical records. Multivariate regression analyses identified risk factors for mortality and unfavourable outcomes (defined as death or prolonged intensive care stay) after 30 and 90 days. RESULTS: Mortality was similar between VRE- (n = 39) and VSE- (n = 138) group after 30 (p = 0.44) or 90 days (p = 0.39). Comparable results occurred regarding unfavourable outcomes. Mean SOFANon-GCS score during the 7-day-period before BSI onset was the independent predictor for mortality at both timepoints (HR 1.32; CI 1.14-1.53; and HR 1.18; CI 1.08-1.28). Timely appropriate antibiotic therapy, recent ICU stay and vancomycin resistance did not affect outcome after adjusting for confounders. CONCLUSION: Vancomycin resistance did not influence outcome among patients with Enterococcus faecium bacteraemia after OLT. Only underlying severity of disease predicted poor outcome among this homogenous patient population. TRIAL REGISTRATION: This study was registered at the German clinical trials register (DRKS-ID: DRKS00013285).

Outcome after liver resection for primary and recurrent intrahepatic cholangiocarcinoma.

Background: Liver resection is the only curative therapeutic option for intrahepatic cholangiocarcinoma (ICC), but the approach to recurrent ICC is controversial. This study analysed the outcome of liver resection in patients with recurrent ICC. Methods: Demographic, radiological, clinical, operative, surgical pathological and follow-up data for all patients with a final surgical pathological diagnosis of ICC treated in a tertiary referral centre between 2001 and 2015 were collected retrospectively and analysed. Results: A total of 190 patients had liver resection for primary ICC. The 1-, 3- and 5-year overall survival (OS) rates were 74·8, 56·6 and 37·9 per cent respectively. Independent determinants of OS were age 65 years or above (hazard ratio (HR) 2·18, 95 per cent c.i. 1·18 to 4·0; P = 0·012), median tumour diameter 5 cm or greater (HR 2·87, 1·37 to 6·00; P = 0·005), preoperative biliary drainage (HR 2·65, 1·13 to 6·20; P = 0·025) and local R1-2 status (HR 1·90, 1·02 to 3·53; P = 0·043). Recurrence was documented in 87 patients (45·8 per cent). The mean(s.d.) survival time after recurrence was 16(17) months. Independent determinants of recurrence were median tumour diameter 5 cm or more (HR 1·71, 1·09 to 2·68; P = 0·020), high-grade (G3-4) tumour (HR 1·63, 1·04 to 2·55; P = 0·034) and local R1 status (HR 1·70, 1·09 to 2·65; P = 0·020). Repeat resection with curative intent was performed in 25 patients for recurrent ICC, achieving a mean survival of 25 (95 per cent c.i. 16 to 34) months after the diagnosis of recurrence. Patients deemed to have unresectable disease after recurrence received chemotherapy or chemoradiotherapy alone, and had significantly poorer survival. Conclusion: Patients with recurrent ICC may benefit from repeat surgical resection.

Antecedentes: La resección hepática es la única opción terapéutica curativa para el colangiocarcinoma intrahepático (intrahepatic colangiocarcinoma, iCCA), pero el enfoque terapéutico de la recidiva del iCCA es controvertido. En este estudio se analizaron los resultados de la resección hepática en pacientes con recidiva de un iCCA. Métodos: Se recopilaron de forma retrospectiva y se analizaron los datos demográficos, radiológicos, clínicos, quirúrgicos, de anatomía patológica y de seguimiento de todos los pacientes con diagnóstico anatomopatológico definitivo de iCCA en un centro de referencia terciario entre 2001 y 2015. Resultados: En total, 190 pacientes se sometieron a resección hepática por iCCA primario. La supervivencia global (overall survival, OS) a 1, 3 y 5 años fue del 75%, 57% y 38%, respectivamente. La edad de ≥ 65 años (cociente de riesgos instantáneos, hazard ratio, HR 2,2, i.c. del 95% 1,2­4,0, P = 0,012), la mediana del diámetro del tumor ≥ 5 cm (HR 2,9, i.c. del 95% 1,4­6,0, P = 0,005), el drenaje biliar preoperatorio (HR 2,6, i.c. del 95% 1,3­6,2, P = 0.025) y el estado local R1/2 (HR 1,9, i.c. del 95% 1,0­3,5, P = 0,043) fueron factores pronósticos independientes de la OS. La recidiva se documentó en 87 (45,8%) pacientes. El tiempo medio de supervivencia después de la recidiva fue de 16 ± 2 meses. Los factores pronósticos independientes de recidiva fueron la mediana del diámetro del tumor ≥ 5 cm (HR 1,7, i.c. del 95% 1,1­2,7, P = 0,020), el tumor de alto grado (G3­G4) (HR 1,6, i.c. del 95% 1,0­2,5, P = 0,034) y el estado local R1 (HR 1,7, i.c. del 95% 1,1­2,6, P = 0,020). La resección repetida con intención curativa se realizó en 25 pacientes con iCCA recidivado, con una supervivencia media de 25 meses (i.c. del 95% 16­34 meses) tras el diagnóstico de recidiva. Los pacientes que se consideraron no resecables después de la recidiva se sometieron a quimioterapia o quimiorradioterapia y presentaron una supervivencia significativamente peor. Conclusión: Los pacientes con recidiva de un iCCA pueden beneficiarse de la resección quirúrgica repetida.

Is stenting necessary after balloon dilation of post-transplantation biliary strictures? Results of a prospective comparative study.

BACKGROUND AND STUDY AIMS: Biliary strictures are a major cause of morbidity following liver transplantation. In the present prospective comparative trial, we evaluated balloon dilation vs. balloon dilation plus stenting with regard to technical and clinical efficacy as well as complications. PATIENTS AND METHODS: A total of 32 patients with symptomatic biliary strictures after liver transplantation were assigned to balloon dilation (n = 17) or balloon dilation plus plastic stent placement (n = 15). The main outcome parameter was sustained clinical success defined as an interval of at least 3 months without further endoscopic intervention. Additional outcome parameters were assisted clinical success and treatment failure, as well as procedure-related complications. RESULTS: The initial technical success and primary clinical success rates in the dilation group were both 100%; in the stent group, the corresponding rates were 100% and 93% (n. s.). The sustained clinical success was 71% vs. 73%, respectively (n. s.). The time interval to reach sustained clinical success was 6.1 and 5.1 months, respectively (n. s.). No significant differences were found in assisted clinical success or in treatment failure. Complications were observed in 4.3% in the dilation group and 13.6% in the stent group (P < 0.05). Independent of the treatment group, a sustained clinical success in anastomotic strictures was achieved in 100%, whereas the success rate of strictures of the donor hepatic duct was 50% and of strictures involving the hilum, only 14% (P < 0.05). CONCLUSIONS: In patients with biliary strictures after liver transplantation, endoscopic balloon dilation alone was as effective as dilation plus stent placement. Stent placement was associated with a significantly higher complication rate. Endoscopic treatment of strictures of the biliary anastomosis is highly effective, whereas attempts to treat more complex strictures are less promising.

Cardiac volume overload and pulmonary hypertension in long-term follow-up of patients with a transjugular intrahepatic portosystemic shunt.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPSS) cause haemodynamic changes in patients with cirrhosis, yet little is known about long-term cardiopulmonary outcomes. AIM: To evaluate the long-term cardiopulmonary outcome after TIPSS. METHODS: We evaluated cardiopulmonary parameters including echocardiography during long-term follow-up after TIPSS. Results at 1-5 years after TIPSS were compared to those of cirrhotic controls. Pulmonary hypertension (PH) diagnoses rates were included. Endothelin 1, thromboxane B2 and serotonin were measured. RESULTS: We found significant differences 1-5 years after TIPSS compared to pre-implantation values: median left atrial diameter (LAD) increased from 37 mm [interquartile range (IQR): 33-43] to 40 mm (IQR: 37-47, P = 0.001), left ventricular end-diastolic diameter (LV-EDD) increased from 45 mm (range: 41-49) to 48 mm (IQR: 45-52, P < 0.001), pulmonary artery systolic pressure (PASP) increased from 25 mmHg (IQR: 22-33) to 30 mmHg (IQR: 25-36, P = 0.038). Comparing results 1-5 years post-implantation to the comparison cohort revealed significantly higher (P < 0.05) LAD, LV-EDD and PASP values in TIPSS patients. PH prevalence was higher in the shunt group (4.43%) compared to controls (0.91%, P = 0.150). Thromboxane B2 levels correlated with PASP in the TIPSS cohort (P = 0.033). There was no transhepatic gradient observed for the vasoactive substances analysed. CONCLUSIONS: TIPSS placement is accompanied by long-term cardiovascular changes, including cardiac volume overload, and is associated with an increased rate of pulmonary hypertension. The need for regular cardiac follow-up after TIPSS requires further evaluation.

NMR tomography for the visualization of the diffusion of Gd-DTPA in agar-gel and in brain tissue--in vitro studies.

Serial magnetic resonance images of a diffusion model and of brain specimens have been performed to study the diffusion behavior of a paramagnetic complex (Gd-DTPA). The model consisted of solidified agar gel with layered Gd-DTPA solution on top of the gel. Corresponding studies have been performed with the brain specimen to visualize the penetration of the marker through the extracellular space into the brain tissue. Diffusion coefficients for the agar gel and the brain tissue model have been calculated. Magnetic resonance tomography proves to be a promising method for the study of complicated diffusion processes of paramagnetic complexes in biological tissue.

Reduction in alkaline phosphatase is associated with longer survival in primary sclerosing cholangitis, independent of dominant stenosis.

BACKGROUND: Alkaline phosphatase (ALP) is an important serum marker in primary sclerosing cholangitis (PSC). Patients with obstruction of the large bile ducts due to dominant strictures (DS) are a special, clinically important phenotype. AIM: To determine the impact of ALP reduction on liver transplantation-free survival in PSC patients with DS. METHODS: Prospective cohort study in 215 PSC patients. We performed subgroup analysis for patients without DS (no DS, n = 84), DS at first presentation (DS early, n = 72) and development of DS during the course of the study (DS late, n = 59). We evaluated two scores of ALP reduction. ALP reduction 1 was defined as ALP normalisation, 50% reduction compared with baseline values, or reduction below 1.5 times of upper limit of normal (ULN) within 6 months. ALP reduction 2 was defined as ALP reduction below 1.5 times of ULN within 12 months. RESULTS: Of the patients, 59.5% reached an ALP reduction 1 and 56.7% according to ALP reduction 2. Achievement of each score was associated with longer transplantation-free survival in all three groups (ALP reduction 1: no DS P = 0.001; DS early P < 0.001; DS late P = 0.022; ALP reduction 2: no DS P = 0.014; DS early P = 0.001; DS late P = 0.002). Cox-regression analysis revealed each score as an independent predictor for improved transplantation-free survival (ALP reduction 1 and 2 P < 0.001 each). We further analysed previously published scores of ALP improvement in PSC showing also improved survival in patients with ALP normalisation or a reduction below 1.5 times of ULN (P = 0.003, P = 0.001, respectively), whereas the score determined by 40% reduction did not show significant differences in survival (P = 0.55). CONCLUSIONS: Reduction in alkaline phosphatase values within the first year is associated with improved transplantation-free survival in patients with primary sclerosing cholangitis independent of the presence of dominant strictures. Alkaline phosphatase might be an adequate surrogate marker for outcome assessment in clinical studies both for patients with and without dominant strictures.

Fut2 genotype is a risk factor for dominant stenosis and biliary candida infections in primary sclerosing cholangitis.

BACKGROUND: A recent genome-wide association study identified the FUT2 secretor status and genotype defined by the single-nucleotide polymorphism rs601338 as potential genetic risk factor in primary sclerosing cholangitis (PSC), which significantly influences biliary bacterial composition. AIM: To determine the impact of the rs601338-FUT2 genotype on frequency of biliary infections, development of dominant stenosis and liver-transplantation-free survival in patients with PSC. METHODS: Cohort study of 215 patients with PSC treated at our tertiary care centre with respect to their rs601338-FUT2 genotype. Results of endoscopic retrograde cholangiography and bile culture were analysed; 639 biliary samples were obtained, cultured and subjected to microbial analysis. Clinical and laboratory data were analysed using chart reviews. RESULTS: For the rs601338-FUT2 genotype, 69 patients (32.1%) were found to be wildtype (GG), 97 (45.1%) patients were heterozygous (AG) and 49 patients (22.8%) were homozygous-mutated (AA). In addition to alterations in the bacterial pattern, especially in heterozygous carriers, patients with mutated alleles had a marked increase in the frequency of biliary Candida infections (P = 0.025). Further, patients with mutated alleles showed an increased frequency of episodes of cholangitis (P = 0.0025), development of dominant stenosis (P < 0.002) and a reduced actuarial transplantation-free survival (P = 0.044). Levels of biliary Ca19-9 were significantly elevated in the homozygous-mutated patients. CONCLUSIONS: The rs601338-FUT2 genotype is strongly associated with episodes of cholangitis, fungobilia and the incidence of dominant stenosis, which are three clinical hallmarks of PSC; FUT2 is thus an important genetic risk factor for host-microbial diversity and disease progression in PSC.

An early increase in gamma glutamyltranspeptidase and low aspartate aminotransferase peak values are associated with superior outcomes after orthotopic liver transplantation.

BACKGROUND: Prediction of prognosis after liver transplantation (OLT) remains difficult. The present study determines if standard laboratory parameters measured within the first week after OLT correlate with outcome. PATIENTS AND METHODS: Laboratory parameters measured within the first weak after OLT of 328 patients were grouped either graft loss or death within 90 days after (group 1: graft loss; group 2: death; group 3: neither graft loss nor death within 90 days). RESULTS: Peak AST and ALT were significantly lower in group 3 (1867 and 1252 U/L) than in group 1 (4474 and 2077 U/L) or 2 (3121 and 1865 U/L). Bilirubin was significantly lower and gamma-GT significantly higher in group 3 compared to groups 1 and 2. In multivariate analysis, high AST peaks were independently associated with death or graft loss within 90 days. An increase in gamma-GT and low bilirubin early after transplantation were found to be independently associated with superior outcome. DISCUSSION: Unexpectedly, a disproportionate rise in gamma-GT was associated with graft and patient survival of more than 90 days. This might be explained by regeneration phenomena in the liver indicative of a well functioning graft.

[Nisoldipine in the treatment of essential hypertension. Efficacy and tolerance]. / Nisoldipin in der Therapie der essentiellen Hypertonie. Wirkung und Verträglichkeit.

The antihypertensive effect after a single dose of one tablet of Nisoldilpine (Bay k 5552) containing 5 mg, 10 mg or 20 mg respectively, was tested in a double-blind cross-over trial with intra-individual comparison on 60 patients with stable essential hypertension. Mean age was 51.6 +/- 7.1 years, mean body-weight 78.0 +/- 11.8 kg, mean height 169.8 +/- 8.2 cm and mean duration of illness 6.1 +/- 4.3 years. 34 patients were in WHO stage I, 24 in stage II. After 5 mg nisoldipine the blood pressure fell from 150/96 to 135/92 mm Hg, after 10 mg from 153/98 to 130/88 mm Hg and after 20 mg from 149/97 to 127/84 mm Hg. Compared with placebo pre-test levels there was also a significant reduction in blood-pressure at an exercise level of 100 W. Side effects were rare and dose-dependent.