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Biomedical subjects

W O Bechstein

Publications and source records attributed to W O Bechstein.

At least 253 records · Page 14Linked to original sources

"Goal-directed" transfusion management leads to distinct reduction of fluid requirement in liver transplantation.

Complications in patients undergoing OLT, such as hemorrhagic events, are caused not only by surgical problems but also by the profound functional disturbances arising from hepatic insufficiency, which are at least partially cured by the procedure itself. Preoperative clotting data give insight only into the dysfunction of the explanted organ. Hence, we tried to perform a standardized, "goal-directed" anesthesiologic management in the perioperative phase in OLT, following strict indications for blood replacement according to diuresis, hemoglobin level, and hemodynamic parameters. We performed 200 OLTs in 185 patients, according to usual methods. The mean intraoperative fluid requirement was 884 ml of balanced salt solution, 8.1 units of RBC, and 9.4 units of FFP. During the first 24 hours postoperatively, an average of 2.4 units of RBC and 5.6 units of FFP had to be transfused. Currently, 170 of the 185 patients (91.9%) are alive and well. Our data demonstrate that a distinct reduction of transfusion rates in OLT is possible, neglecting clotting data and improving clotting function by avoiding hemodilution.

Aprotinin↗

Changes in urokinase-type plasminogen activator in orthotopic liver transplantation.

Elevated levels of u-PA Ag and scu-PA preoperatively and before revascularization of the graft are explained by an impaired clearance function by the diseased liver. They are parallel preoperatively and in the beginning of OLT by increased tcu-PA activity. This may reflect a role of the intrinsic fibrinolytic system in the "hyperfibrinolytic state" observed in patients with end stage liver disease. u-PA Ag and scu-PA normalize following reperfusion. The increase in tcu-PA observed during the anhepatic phase coincided with greatly increased fibrinolysis, as demonstrated by thrombelastography. This indicates that u-PA seems to be involved in the development of fibrinolysis during OLT. It had been demonstrated in previous investigations that a significant increase of t-PA activity was seen in the late anhepatic phase leading to an elevated plasmin generation. Since plasmin is a major activator of scu-PA, a t-PA mediated scu-PA activation would explain the concomitant increase in both plasminogen activators.

Aprotinin↗

[Color duplex sonography of liver transplantation. The vascular status].

The present study deals with the value of CDS in liver transplantation. Between September 1988 and October 1991 CDS of hepatic vessels was carried out in 194 liver transplants. Flow direction and flow velocity in the portal vein could be demonstrated in 97%. Measurement of flow velocity indicates the extent of portal hypertension; this can be confirmed by determining flow direction in the splenic and superior mesenteric veins. In 47 of 179 patients venous collaterals were demonstrated and in 15 of 179 patients there was retrograde flow in the splenic vein. In 95% of patients CDS indicated flow direction in the hepatic artery and in 93% in the hepatic veins. Thrombosis of liver vessels (portal and hepatic veins) was demonstrated in 11 out of 13 patients by means of CDS.

Budd-Chiari Syndrome↗

Enhancement of allograft survival by combination RS-61443 and DUP-785 therapy.

Current maintenance immunosuppressive therapy consists of cyclosporine in combination with prednisone and azathioprine. Unfortunately these agents are associated with significant side effects resulting in post-transplant morbidity and mortality. Therefore, the search for new immunosuppressive agents is essential, not only to improve the results after organ transplantation but equally important to reduce morbidity. Recently two new antiproliferative drugs, RS-61443 (RS) and DUP-785 (DUP), have become available. RS (mycophenolate mefotil), a semisynthetic derivative of mycophenolic acid, inhibits purine de novo synthesis by noncompetitively and reversibly inhibiting inosine monophosphate dehydrogenase. DUP (brequinar sodium) inhibits pyrimidine synthesis by reversibly inhibiting dehydroorotate dehydrogenase. We evaluated subtherapeutic combination RS and DUP therapy in the rat (ACI-->LEW) heterotopic heart allograft model. Median graft survival with no treatment, RS (20 mg/kg/day), DUP 3 mg/kg (3x /week), or DUP 6 mg/kg (3x/week) was 6.5, 11.5, 9.5 and 14.5, respectively. Median graft survival with combination therapy (RS 20 mg/kg, DUP 6 or 3 mg/kg 3x/week) was 133 days and 121 days, respectively. Furthermore, mean survival following cessation of all therapy at 100 days posttransplant was dramatically prolonged to 65.7 +/- 43.8 days in animals receiving combination therapy (RS 20 mg/kg/day, DUP 6 mg/kg 3x/week). Despite the potent immunosuppressive activity, recipients treated with combination therapy demonstrated no side effects and gained body weight during the treatment. To determine if low-dose combination therapy was effective in reversing ongoing rejection, treatment was delayed until the 5th postoperative day. Four of 5 recipients (80%) receiving RS monotherapy (60 mg/kg/day), 5 of 5 recipients (100%) receiving DUP monotherapy (12 mg/kg/day), and 4 of 5 grafts (80%) receiving combination therapy (RS 40 mg/kg/day and DUP 6 mg/kg/day) survived over 21 days. Our results demonstrated that combination therapy significantly prolonged graft survival, and that the progression of advanced rejection was halted immediately. RS and DUP combination may provide a potent immunosuppressive therapy in clinical transplantation.

Animals↗

Evidence that intraoperative prostaglandin E1 infusion reduces impaired platelet aggregation after reperfusion in orthotopic liver transplantation.

Recent investigations measuring platelet aggregation during 10 orthotopic liver transplantations showed a significant decrease in platelet aggregation immediately after reperfusion and in the perfusate. As prostaglandin E1 has been shown to exhibit a beneficial effect in the treatment of ischemic injury of the liver, we investigated in a prospective, randomized, and open study the effect of PGE1 infusion during OLT on platelet function. Ten patients were randomized to receive a continuous PGE1 infusion (PG group) and another ten patients served as controls. Platelet function was determined ex vivo by measuring the adenosine diphosphate-, collagen-, and ristocetin-induced aggregation in platelet-rich plasma. A significantly higher platelet aggregability was measured in the PG group throughout the whole operation for ADP (1 and 2 mumol/L) and collagen (0.5 micrograms/ml). The same was true for collagen (1 microgram/ml) and ristocetin (1.2 mg/ml) after reperfusion. Not only the postreperfusional decrease in platelet aggregation but also the decline in platelet count that occurred in the control group could be prevented greatly by PGE1 infusion. In the perfusate, released from the liver graft vein by flushing with arterial blood, a significantly lower platelet aggregability was seen in comparison with the systemic circulation before reperfusion in the control group, a difference that was not found when PGE1 infusion was given intraoperatively. However, blood product requirements during OLT were comparable in both groups. In conclusion, PGE1 therapy during OLT preserves platelet function and prevents the drop in platelet count observed in the control group after revascularization.

Adenosine Diphosphate↗

Comparison of quadruple immunosuppression after liver transplantation with ATG or IL-2 receptor antibody.

Treatment with monoclonal IL-2 receptor antibodies has been successfully used for immunosuppressive induction therapy following organ transplantation in the recent past. The present study was conducted to compare for the first time a cyclosporine-based quadruple immunosuppressive regimen including a monoclonal IL-2 receptor antibody or ATG as induction therapy after orthotopic liver transplantation. In two groups of 33 patients each, postoperative survival, graft biopsies, liver function enzymes, and the clinical courses after OLT were evaluated. Our results indicate that monoclonal IL-2 receptor antibody therapy as part of a quadruple immunosuppressive regimen is better tolerated and is at least as effective as ATG in prevention of allograft rejection following OLT. Furthermore, our data indicate that a slightly better liver function in general and a lower incidence of rejection reactions necessitating treatment could be observed in the group of patients treated with the monoclonal IL-2 receptor antibody. This study provides evidence that monoclonal IL-2 receptor antibody therapy may be a useful tool for the immunosuppressive induction therapy following clinical orthotopic liver transplantation.

Adult↗

[Porphyrin-induced biliary cirrhosis in protoporphyria: indications for liver transplantation].

A 51-year-old patient, who had experienced photosensitivity from childhood on, fell ill with an icterus accompanied by abdominal complaints. At the age of 46 years an erythropoietic protoprophyria had been diagnosed by an excessive protoporphyrinemia. Meanwhile, in consequence of the protoporphyria's erythrohepatic progression, a biliary liver cirrhosis developed, associated with portal hypertension and marked splenomegalie. As a remission of the protoporphyria-induced hepatobiliary complication could not be achieved by conservative medical treatment, the indication for orthotopic liver transplantation was established. The operation proceeded without complications, and the postoperative course, too, revealed no problems. With primarily good bile production, bilirubin and aminotransferases soon declined to normal values. Urinary coproporphyrin excretion was found to be normal after transplantation, only a domination of isomer I still peristed. Furthermore, a distinct elevation of protoprophyrin continued to exist both in erythrocytes and plasma as expression of the immanent enzyme deficiency typical for the genodermatosis protoporphyria. In the liver explant a micronodular transformation of parenchyma was found besides a deposition of reddish-brown protoporphyrin pigment in hepatocellular cytoplasma and Kupffer's cells, in addition to pigment casts in the canaliculi and within single portal bile ducts.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗

[Special "supportive" therapy (nutrition, control of infection, intensive care) in transplantation medicine].

With the increase in clinical organ transplantation the importance of specific "supportive" therapy in addition to surgical technique and immunosuppression is being recognized more widely. Our own experience is based on 273 orthotopic liver transplants which were performed in 255 adult patients between September 1988 and May 1992 with an one-year survival rate of 91%. With the routine use of selective bowel decontamination (SBD) pre- and postoperatively 63 bacterial or fungal infections occurred in 57 of 230 liver graft recipients during the first 4 postoperative weeks, 4 of these infections with fatal outcome. The incidence of cytomegalovirus (CMV) disease reached 18.6% (39 of 210 patients). The risk of developing CMV disease depended upon the previous serological status of donor and recipient but also showed an increase after anti-rejection therapy with steroids or OKT3. One death due to CMV pneumonitis occurred. The importance of nutritional support, infectious disease control and intensive care therapy for solid organ transplantation is being discussed in general.

Critical Care↗