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Biomedical subjects

G Otto

Publications and source records attributed to G Otto.

At least 109 records · Page 6Linked to original sources
PubMed1995

Soluble thrombomodulin--a marker of reperfusion injury after orthotopic liver transplantation.

Thrombomodulin is an endothelial cell membrane protein that is released into the blood in soluble forms (soluble thrombomodulin [sTM]) in response to endothelial cell damage. We evaluated intraoperative sTM as a marker of reperfusion injury in 29 liver transplant recipients using an ELISA. Preoperative sTM levels were significantly elevated, as compared with healthy control subjects (75 +/- 61 ng/ml vs. 17 +/- 10 ng/ml; P < 0.001) and remain unchanged at the end of the anhepatic phase (58 +/- 40 ng/ml). There is an increase to 194 +/- 182 ng/ml 3 min after reperfusion (P < 0.001). Post-reperfusion sTM levels correlate significantly with the early liver enzyme release (aspartate transaminase) (P < 0.001). Patients with pronounced reperfusion injury (postreperfusion arterial sTM > 138 ng/ml, n = 16) present significantly higher maximum aspartate transaminase levels within the first 24 postoperative hr, as compared with patients with less reperfusion injury (arterial sTM < 138 ng/ml, n = 12) (P = 0.001). Released sTM is derived from the graft, since patients with pronounced reperfusion injury present significantly higher sTM levels in the hepatic vein 3 min after reperfusion compared with the portal vein (P < 0.001) and artery (P = 0.025), respectively. In patients with higher reperfusion injury, we found significantly more adherent intrasinusoidal granulocytes in the liver biopsy taken 1 hr after reperfusion (P = 0.006), indicating an interrelation of endothelial damage and the important phenomenon of "leukocyte sticking" in reperfusion injury. Thus the postreperfusion increase of sTM as a marker of reperfusion injury correlates with the early liver enzyme release and the accumulation of intrasinusoidal granulocytes.

Adolescent↗
PubMed1995

Modes of reperfusion in clinical liver transplantation.

A retrospective analysis of 60 orthotopic liver transplantations was performed to elucidate the effect of three types of rinse solutions (Ringer's solution, modified Carolina rinse, and autologous blood) and two types of revascularization (simultaneous vs sequential portal and arterial reperfusion) on various parameters of early postoperative graft function. The only statistically significant association revealed by multivariate analysis was a positive correlation between donor age and SGOT/SGPT peak levels postoperatively. In this limited sample no beneficial properties of Carolina rinse and/or simultaneous arterialization were verified. Despite modifications of reperfusion, there were 2 cases of primary nonfunctioning graft. However, these cases were associated with elderly donors, prolonged cold storage and, in 1 case, marked steatosis. Large-scale prospective trials are required to verify or disprove experimental data on the use of varying modes of reperfusion.

Adolescent↗
PubMed1995

In patients with orthotopic liver transplantation, serum markers of cholestasis are unreliable indicators of biliary secretion.

BACKGROUND/AIMS: In patients after orthotopic liver transplantation, treatment with the novel immunosuppressant FK 506 may lead to elevated levels of alkaline phosphatase, gamma glutamyl transferase and bilirubin. Up to now it was unclear whether the excretory capacity of the liver in such patients is impaired. METHODS: We measured quantitatively the secretion of bile acids, phospholipids and cholesterol using the duodenal perfusion method, which allows assessment of biliary secretion without interruption of the enterohepatic circulation. Six healthy volunteers served as controls. RESULTS: All patients studied after orthotopic liver transplantation had elevated concentrations of serum alkaline phosphatase and gamma glutamyl transferase, whereas only half of them had slightly abnormal serum bilirubin levels. On average, the FK 506-treated patients excreted 1.23 +/- 0.27 mmol/h bile acids, 0.23 +/- 0.04 mmol/h phospholipids and 0.11 +/- 0.02 mmol/h cholesterol, which was not significantly different from the healthy controls. CONCLUSIONS: The normal secretion rates of biliary bile acids and lipids in FK 506-treated patients with elevated serum alkaline phosphatase and gamma glutamyl transferase indicate that the excretory capacity of the transplanted liver has completely recovered 2-3 months after surgery. In addition, in the majority of these patients elevated serum levels of alkaline phosphatase, gamma glutamyl transferase and bilirubin do not reflect impaired biliary secretion.

Adult↗
PubMed1995

When should isolated liver transplantation be performed in primary hyperoxaluria type 1? Follow-up report of two children.

The value of isolated liver transplantation in primary hyperoxaluria type 1 (PH1) and its timing are controversial. Two children with PH1 were followed up for 6 years after liver transplantation. A boy aged 5 years with a glomerular filtration rate (GFR) of 65 ml/min/1.73 m2 at the time of transplantation subsequently showed regression of calcium deposits in the kidneys, but GFR slightly declined, probably related to cyclosporin A toxicity. A girl with a severe neonatal form of PH1 received a liver at the age of 2 years when GFR had already declined to about 15 ml/min/1.73 m2 and extrarenal manifestations (bones, eyes) were present. In spite of these and further complications post-transplantation GFR stabilized. Growth failure was efficiently treated by growth hormone. Plasma and urinary oxalate concentrations, however, remained increased. It is suggested that in PH1 liver transplantation should be considered only if GFR is not rapidly declining and stays above 30 ml/min/1.73 m2. For an individual decision the different risks of liver transplantation and of combined kidney-liver transplantation as well as the possible benefits from previous conservative treatment must be considered.

Child, Preschool↗
PubMed1995

Cadherin transfection of Xenopus XTC cells downregulates expression of substrate adhesion molecules.

Cadherins are discussed not in terms of their adhesive function but rather as morphoregulatory proteins. Changes in gene expression following cadherin transfection of cells in culture or by overexpression in embryos have, until now, not been reported. We established a protocol for stable transfection of Xenopus XTC cells and generated cells bearing high levels of membrane-integrated mouse uvomorulin (E-cadherin) or Xenopus XB-cadherin. These cell lines showed drastically impaired substrate adhesion on fibronectin and laminin. In immunoblot and radioimmunoprecipitation experiments, we found that fibronectin and alpha 3/beta 1 integrin are downregulated. The reduced amounts of proteins result from a decrease of the respective mRNAs as proven by RNase protection assays. Coprecipitations revealed that transfected cadherin molecules are complexed with alpha-catenin and beta-catenin at plasma membranes. However, the alpha-catenin present in the XB-cadherin complex differs immunologically from that found in the uvomorulin complex. When a truncated form of XB-cadherin lacking 38 of the most C-terminal amino acids was expressed in XTC cells, complex formation with endogenous catenins was abolished. In these transfectants, substrate adhesion was not affected. These results prove that complex formation of transfected cadherins in XTC cells with endogenous beta-catenin correlates with altered synthesis of certain substrate adhesion molecules.

Animals↗
PubMed1995

[Ischemic type lesions of the bile ducts after liver transplantation: 2 years results].

Ischemic type lesions (ITL) after orthotopic liver transplantation are characterized by bile duct necroses leading to alterations of the ductal lumen, biliary leakage, cast formation and, thereby, to cholestasis. After exclusion of causative factors, such as arterial thrombosis, ABO incompatibility and chronic rejection, ITL occurred in 21 of 165 patients. The rate of ITL after UW preservation was higher (25%) in grafts preserved for > 10 hours in comparison to < 10 hours (7%; p < 0.05). Treatment consisted of endoscopic and percutaneous intervention, surgical revision and retransplantation. Retransplantation is indicated in many patients with lesions of extra- and intrahepatic bile ducts (type A). Other methods are of palliative character and may only be successful in type B (extrahepatic) lesions. Morbidity in patients with ITL is considerable. In comparison to patients without ITL, mortality, however, is not increased.

Bile Ducts↗
PubMed1995

[Effect of anastomosis reconstruction on vascular complications after liver transplantation].

AIM: Besides primary non function (PNF), vascular complications are responsible for the majority of early surgical and interventional therapy following liver transplantation. The purpose of this study was to evaluate the influence of the variety of arterial anastomosis on postoperative morbidity and mortality. METHOD USED: In 179 liver transplantations, vascular (arterial and portal) complications within the first 3 months were analyzed with respect to the type of reconstruction. The arterial anastomoses were divided into 3 groups according to the recipient artery used [Group (I): common hepatic artery (CHA), (II): hepatic artery (HA), (III): aorta]. For statistical analysis comparison of two proportions and the logrank test were used. RESULTS: The reconstruction was done primarily to the recipient CHA (69%, n = 124), less often to the HA (15%, n = 26) or directly to the aorta (16%, n = 29). The portal anastomosis-with the exception of two cases (dacron graft and internal iliac vein interposition)-was always end to end and resulted in four reinterventions (2.2%, kinking: n = 1, thrombosis: n = 3). Arterial complications (11.7%) like thrombosis, stenosis and dissection (n = 17), bleeding (n = 2) and steal phenomenon (n = 2) occurred more frequently. The difference in one year survival between patients with (n = 12/25, 47%) and without (n = 42/53, 79%) vascular complications was significant (chi 2 = 4.72, FG 1, logrank test p < 0.05). CONCLUSION: The rate of complications causing surgical or interventional therapy is independent of the choice of arterial reconstruction. The one year survival rate in patients with vascular complications is significantly decreased.

Adolescent↗
PubMed1995

[Induction of impaired hepatic microcirculation by in situ hilus preparation in liver explantation].

AIM: Usually, in-situ preparation of the hepatic hilar structures is performed prior to the perfusion with preservation solution. Aim of this study was to investigate mechanical effects of liver preparation on the hepatic microcirculation. METHODS: 16 pigs (German landrace) were randomized in two groups. In both groups, laparotomy was performed after intratracheal intubation. Subsequently, a thermal diffusion probe was implanted into the medial left liver lobe for quantification of microperfusion. In group A (n = 8), bile duct, hepatic artery, and portal vein were exposed and the lesser omentum transsected thereafter. Ultrasound-volume-probes were placed around the hepatic artery and portal vein. Simultaneous measurement of hepatic microperfusion and total liver blood flow was performed five minutes after the end of liver preparation. In group B (n = 8) hepatic microperfusion was quantified 45 minutes after laparotomy without further manipulations. RESULTS: By the preparation, liver perfusion was significantly reduced in group A from 78 +/- 13 ml/100g/min to 61 +/- 16 ml/100g/min. After preparation a total liver blood flow of 137 +/- 46 ml/100g/min was recorded indicating a shunt fraction of 51 +/- 21%. In contrast, hepatic microperfusion in group B remained at baseline during the whole observation period (79 +/- 3 ml/100g/min vs. 78 +/- 5 ml/100g/min). CONCLUSION: In-situ liver preparation induces a relevant disturbance of hepatic microcirculation. Preservation perfusion shortly after surgical manipulation could become ineffective because of an increase in shunt flow. If the regeneration period is too short, e.g. lack of heart explantation, the quality of the liver graft could be limited.

Animals↗
PubMed1995

[Are surgical shunts still indicated?].

The indication for portosystemic shunts has been influenced by endoscopic approaches, liver transplantation and TIPSS. Underlying disease and functional capacity of the liver are crucial for the therapeutic strategy in patients with esophageal variceal hemorrhage. In Child B and C cirrhosis results of liver transplantation are superior to surgical shunts. In transplantation candidates shunt surgery should not interfere with the transplantation procedure. Therefore, TIPSS, mesocaval shunt or Warren shunt are recommended. If transplantation is not indicated, surgical shunts are generally justified for intractable variceal bleeding. Due to the high mortality following surgical shunts TIPSS may be preferentially used in patients with Child C cirrhosis.

Esophageal and Gastric Varices↗