PubMed Health⌕ Search

Biomedical subjects

H Schrem

Publications and source records attributed to H Schrem.

16 recordsLinked to original sources

Update on liver transplantation using cyclosporine.

After the introduction of cyclosporine into liver transplantation in 1983, 1-year patient survival more than doubled. Later, with the improved microemulsified formulation of cyclosporine (Neoral) more stable pharmacokinetics were achieved. Today, C(2) monitoring of cyclosporine blood levels allows a more accurate estimation of the area under the concentration-versus-time curve as the single best indicator of cyclosporine exposure. As a consequence, with better control of side effects as well as desired effects the results of cyclosporine in liver transplantation have been further improved. The introduction of mycophenolate mofetil and basiliximab/daclizumab combination therapy has provided new options for the prevention of allograft rejection. The safety profile of individual immunosuppressive regimens comes more into focus since acute allograft rejection may be controlled successfully with competing strategies. As the focus in liver transplantation is shifting toward greatly improved long-term results, late posttransplant mortality with a functioning graft is a major concern. Prevention of long-term complications associated with highly effective immunosuppressants--posttransplant lymphoproliferative disease, cytomegalovirus infection, diabetes, hypertension, and hyperlipidemia-gains importance. Technical advances in living-related and cadaveric split-liver transplantation have lead to increasing use of segmental liver transplantation with the need to consider the effects of immunosuppression on liver regeneration and metabolism. The individualized orchestration of immunosuppression taking into account the underlying liver disease as well as other individual predispositions remains a future challenge.

Child↗

[Living kidney transplantation. A comparison of Scandinavian countries and Germany].

The discussion of compensating for shortages of cadaveric donation with increased living donation often reveals differences between the Scandinavian countries and Germany. Possible adoption of Scandinavian structures to improve the rate of living donations in Germany warrants analysis of the actual differences between these two regions. Close examination reveals that significantly higher rates of living donation are achieved only in Sweden and Norway. In Norway, a frequently postulated negative effect on cadaveric donation due to very high rates of living donation could not be confirmed. In contrast to Germany and as a consequence of Norwegian geography, kidney transplantation has been regarded in Norway as the first-line therapy for endstage renal disease for more than 35 years. Living donation has since been actively pursued and is traditionally the transplantation of first choice. In Germany, living donation is still regarded as the second choice after cadaveric donation, due to legal regulations. Significant improvements in living donation frequencies could be achieved there by adopting the active Norwegian approach to living donor identification.

Adult↗

Review: surgical shunts and encephalopathy.

Historically, surgical shunts have played an important role in the treatment of patients with portal hypertension associated with ascites and/or variceal esophageal bleeding. Today, in the era of liver transplantation most patients with end-stage liver disease and concomitant portal hypertension and associated problems are best treated by liver grafting. The successful introduction of transjugular intrahepatic portosystemic shunting (TIPS), performed by radiologists and gastroenterologists, provides a very effective alternative to surgical shunt procedures. One advantage of TIPS is that this procedure does not interfere with subsequent liver grafting. Today, surgical shunts have clearly lost ground to the less invasive TIPS procedure. Surgical shunts still maintain a role: as a salvage procedure in selected cases and in emergency situations. Surgical shunts are associated with a high rate of encephalopathy. In most cases selective surgical shunts should be preferred to nonselective surgical shunts. The role of partial surgical shunts versus selective surgical shunts remains to be determined. Hepatic encephalopathy is a common complication of all shunt procedures and is dependent on the shunt volume. Liver grafting is able to reverse encephalopathy because of a shunting procedure. In our institution, we prefer TIPS over surgical shunts as a bridging procedure before liver transplantation.

Hepatic Encephalopathy↗

[Surgical therapy of cystic echinococcosis of the liver].

This study analyses the results of a surgical deroofing technique that was used for the treatment of cystic echinococcosis of the liver in our institution during the last 18 years. The deroofing technique was used on 106 of 132 patients from January 1981 to December 1998. Other operative techniques (pericystectomy, hemihepatectomy) were performed on 26 patients. In 12 cases (9%) the operative procedure was completed by interventions at the extrahepatic bile ducts. 99 patients (75%) showed one or two cysts, and the remaining 33 patients (25%) had three or more cysts in the liver. 18 (14%) patients had to be reoperated on account of complications: in 5 cases a postoperative hemorrhage, in 11 cases a bile duct leakage and in 2 cases an intraabdominal abscess had to be treated operatively. The follow-up of 74 patients (81%) revealed recurrent disease in 14 (19%) cases. Surgical deroofing of cystic echinococcosis of the liver is easy to perform and in contrast to other minor surgical interventions universally applicable. The recurrence rate and the rate of postoperative complications are comparable to other minor surgical techniques. Therefore in our view this procedure represents the therapy of choice.

Adolescent↗

Liver transplantation after organ preservation with normothermic extracorporeal perfusion.

OBJECTIVE: To study normothermic extracorporeal liver perfusion (NELP) as a means to preserve livers for transplantation and to reverse warm ischemic injury. SUMMARY BACKGROUND DATA: The authors provide experimental evidence that successful transplantation after 4 hours of normothermic extracorporeal liver perfusion is possible and as reliable as 4 hours of cold preservation in University of Wisconsin solution. NELP preserves liver function completely and can reverse 60 minutes of warm ischemic injury in non-heart-beating donors. METHODS: Thirty-six German Landrace pigs received transplants in six groups. Group 1 animals received direct transplantation. Group 2 received transplants after 4 hours of cold preservation with University of Wisconsin solution and Group 3 animals after 4 hours of NELP. Group 4 animals sustained 1 hour of warm ischemia before transplantation. Group 5 animals received transplants after 1 hour of warm ischemia and 4 hours of cold preservation and Group 6 animals after 1 hour of warm ischemia and 4 hours of NELP. RESULTS: All animals receiving livers treated by NELP survived more than 7 days after the transplant (Groups 3 and 6). In contrast, all animals in Group 5 developed primary graft nonfunction within 24 hours after transplantation. CONCLUSION: The technique of NELP holds the potential to keep a mammalian liver outside the body completely functional, possibly for more than 4 hours. NELP can be used for liver preservation before transplantation or for the use of organs from non-heart-beating donors.

Animals↗

[Dynamic and static MRI using superparamagnetic MRI contrast medium Resovist for visualizing primary and secondary liver tumors].

PURPOSE: To analyse characteristics of benign and malignant liver tumours in dynamic and static MR imaging with the superparamagnetic MR contrast medium Resovist. MATERIAL AND METHODS: All 30 patients were examined on a 1.5 Tesla MR unit (Magnetom 63 SP, Siemens AG, Erlangen, Germany) using proton density (PD) weighted (w), T2-weighted-spin-echo, a T1-weighted SE, and a T1-weighted FLASH-2 D gradient echo (GRE) sequence before, during and after the application of Resovist. Dynamic imaging was performed using a T2-weighted GRE-sequence (TurboFLASH; TR/TE = 11/30; flip angle = 10 degrees; Tl = 600 ms). Histopathology revealed benign liver lesions in 8 patients and malignant lesions in 22 patients. RESULTS: Dynamic T2-weighted sequence revealed an early loss of signal intensity in normal liver parenchyma (percentage signal intensity loss (PSIL) = 40.0 +/- 12.2% by 4 mumol Fe/kg, 47.2 +/- 18.8% by 8 mumol Fe/kg and 62.7 +/- 13.0% by 16 mumol Fe/kg), in the spleen, as well as in FNH (PSIL = 49.5 +/- 7.3% by 8 mumol Fe/kg), and regenerating nodules in the first minute after application of Resovist. In two of 4 cases with HCC a short drop in signal intensity was immediately observed after the application, whereas signal intensity remained unchanged in all other malignant liver tumours. Enhanced PDw and T2-weighted SE-sequences revealed an improved detection and delineation of malignant liver lesions versus plain MR imaging. 17 liver lesions of a size lower 10 mm were additionally detected in postcontrast T2-weighted SE-sequences in 4 patients. CONCLUSION: Dynamic and static versus plain MR imaging of primary and secondary liver lesions is markedly improved by the superparamagnetic contrast material Resovist, especially in case of intravenous bolus application of this liver-specific contrast medium.

Adult↗

Hepatitis B virus mutations in the pre-S genome before and after liver transplantation.

Mutational changes in the pre-S region of hepatitis B virus (HBV) were analyzed in 20 patients who experienced HBV reinfection after orthotopic liver transplantation (OLT). HBV DNA was extracted from patient sera before and after OLT. The pre-S sequence was amplified via polymerase chain reaction, subcloned, sequenced, and analyzed. In 18 of 20 patients, mutational changes were found in the pre-S region pre- or post- OLT; 11 showed point mutations (1-10) and 7 cases major changes (insertions/deletions). For the point mutations, there was no trend in the selection of wild-type (wt) HBV before or after OLT in the pre-S region. Additional HBV reinfection during hepatitis B surface antigen antibody (anti-HBS) administration had no influence on selection pressure in the pre-S region. In contrast, insertions/deletions were more frequently found before OLT. In the 7 patients with deletions/insertions, changes in the hepatocyte attachment site were not seen after OLT. Interestingly, the only patient with changes in a major virus population after OLT had changes in the CCAAT-box of the S-promoter. As shown by gel shift analysis, this mutation was associated with loss of specific binding to this element and thus probably led to dysregulation of S-gene transcription. Major changes in the pre-S genome are mainly seen before OLT, and HBV reinfection does occur with the intact hepatocyte attachment sites after OLT. Anti-HBs (hepatitis B immune globulin [HBIg]) creates no selection pressure on the pre-S region. The mutation in the CCAAT-box of the S-promoter potentially leads to its dysregulation and may be associated with the occurrence of fibrosing cholestatic hepatitis after OLT.

Adult↗

Clinical significance of recurrent primary biliary cirrhosis after liver transplantation.

Primary biliary cirrhosis (PBC) represents a classic indication for orthotopic liver transplantation (OLT); as an autoimmune disease, however, the existence and incidence of recurrent PBC is a matter of significant controversy. Between September 1988 and September 1994 a total of 544 OLTs was performed at our institution. Forty-nine patients (40 female) with a median age of 50.5 years and previous surgery in 36.4%, received a liver graft for PBC. The mean serum bilirubin level was 8.9 mg/dl (range 0.7-29.7). Immunosuppression was commenced as a cyclosporine A-based quadruple therapy or with FK 506 and prednisolone. Protocol liver biopsies were taken at defined intervals posttransplant. Two patients died due to Legionella pneumonia and hypoxic brain damage 2 and 8 weeks after OLT, resulting in an actuarial 5-year survival rate of 95% with 47/49 patients being alive compared to 83.5% of all other liver recipients. Evidence of recurrence of PBC, as defined by elevated cholestatic parameters and histological features of PBC, was found in four patients, another five patients showed only histological signs. Recurrence of PBC, which might compromise the long-term outcome after OLT, was suspected in 4/47 patients (8.5%). This evidence of recurrent PBC is in conflict with findings of other groups that did not report recurrent PBC. OLT is still the optimal therapy for advanced PBC, with an excellent prognosis.

Female↗

Magnetic resonance imaging of focal liver lesions. Comparison of the superparamagnetic iron oxide resovist versus gadolinium-DTPA in the same patient.

RATIONALE AND OBJECTIVES: The authors assess the efficacy of static and dynamic magnetic resonance (MR) imaging using the superparamagnetic iron oxide SHU-555A (Resovist) versus standard dose of gadolinium (Gd)-DTPA in patients with focal liver lesions. METHODS: Magnetic resonance imaging was performed in 30 patients suffering from histopathologically verified malignant (n = 22) and benign (n = 8) liver lesions. T2-weighted conventional and fat-suppressed as well as T1-weighted sequences were used before, during, and after fast intravenous administration of Resovist (1 mL/minute) at three doses of 4, 8, and 16 mumol/kg body weight. One week before the Resovist-enhanced MR imaging study 20 patients underwent Gd-DTPA-enhanced MR imaging. RESULTS: Detection rate was improved for metastatic lesions revealing 36 lesions unenhanced versus 53 focal lesions using Resovist-enhanced MR imaging. Gadolinium-DTPA-enhanced scans showed no additional lesion versus unenhanced and Resovist-enhanced MR imaging. Static and dynamic imaging demonstrated no measurable percentage signal intensity loss (PSIL) using Resovist-enhanced MR imaging versus a percentage enhancement of 79.7% in Gd-DTPA enhanced scans. In the dynamic T2-weighted sequences, hepatocellular carcinoma nodules (n = 4) showed a rapid decrease in signal intensity starting at 44 seconds. Postinfusion of Resovist followed by a low, constant increase in signal intensity. Gadolinium-DTPA enhanced scans showed a percentage enhancement of 73.4 focal nodular hyperplasia (FNH) and hemangioma revealed a strong and early dose-dependent PSIL 44 to 60 seconds postinfusion with a prolonged signal loss for the FNH in the late study. Statistical evaluation revealed a statistically significant superiority of Resovist-enhanced MR imaging concerning the detection and delineation of focal liver lesions compared with unenhanced and Gd-DTPA enhanced scans (P < 0.05). CONCLUSIONS: The fast infusion of the new superparamagnetic contrast agent Resovist shows advantages for dynamic and static MR imaging of focal liver lesions.

Carcinoma, Hepatocellular↗

Low incidence of p53 mutations in European hepatocellular carcinomas with heterogeneous mutation as a rare event.

BACKGROUND/AIMS: The aim of this study was to evaluate the role of p53 mutations in European hepatocarcinogenesis. METHODS: DNA extracts from 20 microdissected tumor samples were investigated. Nucleotide sequence analysis of subcloned polymerase chain reaction-fragments of the conserved domain exons 5-8 was performed in order to detect heterogeneous distribution of p53 mutated cells within the tumors. In a screening procedure four clones of each exon 5-8 were analyzed. To confirm the observed mutations polymerase chain reaction and subcloning was repeated. RESULTS: Sequence analysis confirmed a mutation in only two cases (10%). One at codon 220 (exon 6) was a homogeneous transition in nearly all clones from TAT to TGT. The other mutation was a transition from cGG to CAG at the known hot spot codon 248 (exon 7). It was found in 30% of the clones. We conclude that the other mutations from the first step were artefacts due to the infidelity of the taq-polymerase. All tumors had wild type sequence at the reported hot spot codon 249. The minor importance of p53 gene alterations in European hepatocarcinogenesis was further confirmed at the protein level by immunohistochemistry. Only the tumors with the heterogeneous p53 mutation at codon 248 showed a p53 overexpression in nearly 30% of the nuclei. None of the other tumors showed higher levels of p53 expression. CONCLUSIONS: We therefore conclude that the incidence of p53 mutations in European hepatocellular carcinomas is very low. Generally there may be no heterogeneous distribution of p53 mutated cells within a tumor. The contribution of this genetic alteration to hepatocarcinogenesis in Europe seems of little importance.

Adult↗