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G Gubernatis

Publications and source records attributed to G Gubernatis.

At least 55 records · Page 3Linked to original sources

Postoperative recovery of mitochondrial function of the human liver graft procured and preserved with University of Wisconsin (UW) solution.

Changes in arterial blood ketone body ratio (KBR) were investigated in 47 human liver transplantations. Of the 20 grafts preserved with University of Wisconsin (UW) solution, 10 had a cold preservation period of less than 10 h (UWS group) and 10 of more than 10 h (UWL group). In 27 other cases, grafts were preserved with EuroCollins (EC) solution for less than 10 h (EC group). In the EC group, KBR increased over 0.7 within 6 h after reperfusion of the graft in 17 cases (63%) and within 24 h in 7 cases (26%). In the 3 other cases, KBR failed to recover, and these patients underwent retransplantation. In the UW group, KBR recovered within 6 h in 13 cases (65%) and within 24 h in 7 cases (35%). There were no significant differences between the UWS and UWL groups. It is shown that the mitochondrial function of liver grafts preserved with UW solution can be well maintained even after extended preservation periods of more than 10 h.

Adenosine↗

HTK-solution (Bretschneider) for human liver transplantation. First clinical experiences.

The cardioplegic HTK-solution (Bretschneider) has not been used in human liver transplantation as yet. Herein the first results obtained from 14 patients with HTK-preserved liver grafts are presented. The suitability of HTK-solution could be shown. All grafts functioned primarily except one, where initial non-function was obviously due to donor reasons. The early postoperative peak values of transaminases as a sign of ischemic damage were average and similar to the values of other flushout solutions. Using HTK primary function could be achieved even in livers prospectively assessed as only of fair quality, and livers with poor donor function tests (MegX) functioned from the beginning. HTK-solution therefore seems to allow widening of the acceptance criteria for donor livers. It was not the aim of this trial to extend cold ischemic time, but 3 livers with 11 h and 12 h 25 showed immediate function. How far cold ischemic time can be extended is a still open question. All livers were rapidly cooled and homogeneously flushed out due to the low viscosity of HTK-solution. All livers had a soft consistency after perfusion indicating a low degree of cell edema. HTK therefore is an effective solution for liver preservation.

Adenosine↗

Fat emulsions in parenteral nutrition after liver transplantation: The recovery of the allografts RES function and histological observations.

Following liver transplantation, the effect of post-operative parenteral nutrition with MCT LCT (Medium Chain Triglycerides/Long Chain Triglycerides) fat emulsions on the recovery of allografts RES function was investigated in a randomised prospective study of three groups of patients (group I, n = 14: 50g MCT LCT fats twice weekly, group II, n = 15: 0.7 g/kg body weight per day MCT LCT fats, group III, n = 17: 1.5 g/kg body weight per day MCT LCT fats). RES function was assessed using the (99m)Tc-HSA-MM-Clearance ((99m)Technitium-Human serum albumen-Millimicrosphere-Clearance). There were no statistically significant differences in the recovery of RES function between the groups. A negative effect on RES function as a result of the administration of MCT LCT fat emulsions up to 1.5 g/kg b.w. per day can therefore be excluded. The evaluation of liver biopsies before the administration of fats and at the end of TPN (Total Parenteral Nutrition) showed no evidence, in the 20 patients investigated, of any fatty changes in the liver caused by the infusion of fat.

Journal Article↗

Significance of arterial ketone body ratio measurement in human liver transplantation.

Arterial ketone body ratio (KBR), which reflects the NAD+/NADH ratio of hepatic mitochondria, was measured sequentially in 39 liver transplantations. In 22 cases, KBR was increased to above 0.7 within 6 hr after reperfusion (group A). In 11 cases, restoration of KBR was delayed until the first postoperative day (group B) and in 6 cases, KBR failed to recover (group C). The patients in group A survived liver transplantation without complications. By contrast, morbidity and mortality were significantly higher in groups B and C. In 2 cases in group C, the livers were clinically diagnosed as initially nonfunctioning grafts and the patients underwent retransplantation. Another two died of hepatic failure soon after the operation. It is suggested that delayed recovery of KBR is an early indicator of metabolic overload in the liver allograft, and that a delay exceeding 24 hr may imply the need for retransplantation.

Adult↗

The course of untreated acute rejection and effect of repeated anti-CD3 monoclonal antibody treatment in rhesus monkey liver transplantation.

The effect of single and repeated treatment of liver allograft rejection using an anti-CD3 monoclonal antibody (FN18) was studied in a rhesus monkey model. Eight RhLA-mismatched monkeys received initial postoperative immunosuppression with CsA/prednisolone for 28 days. After cessation, acute rejection occurred in all animals (days 28-50). Control animals (n = 3) receiving no rejection treatment developed a chronic progressive rejection and died at days 112-160. In the animals treated with FN18 (n = 5), the first acute rejection was successfully reversed. T lymphocytes were cleared from the peripheral blood and the graft. Increased class I and class II MHC-antigens on hepatocytes were reduced to normal levels within 5 days of treatment. The second rejection treatment remained ineffective in two animals with antiidiotypic antibodies to FN18 but was successful in two animals with a low antimouse response. These four animals survived 160-509 days. The results have a number of implications regarding the course of untreated rejection in human liver transplant recipients and repetitive rejection treatment with monoclonal antibodies.

Animals↗

[Fat emulsions in parenteral feeding following liver transplantation. I. Effect on the recovery of RES function in the transplant].

Following liver transplantation, the effect of postoperative parenteral nutrition with MCT/LCT fatty emulsions on the recovery of RES function in the allograft was investigated in a randomised prospective study of three groups of patients (group I: 50 g MCT/LCT fats twice weekly, group II: 0.7 g/kg body weight per day MCT/LCT fats, group III: 1.5 g/kg body weight per day MCT/LCT fats). RES function was assessed using 99mTc-HSA-MM clearance. There were no statistically significant differences in the recovery of RES function after transplantation between the three groups. A negative effect on RES function as a result of the administration of MCT/LCT fats up to 1.5 g/kg body weight per day can therefore be excluded.

Fat Emulsions, Intravenous↗

Evaluation of the liver graft before procurement. Significance of arterial ketone body ratio in brain-dead patients.

Hepatic energy metabolism was assessed by measuring the blood ketone body ratio (KBR), that is, the ratio of acetoacetate to beta-hydroxybutyrate in the arterial blood, in 31 brain-dead patients in an intensive care unit (ICU) in Japan and in 25 donors just before procurement of the liver for transplantation in Germany. In the study in Japan, 7 of the 12 brain-dead patients treated with high-dose catecholamine showed significantly decreased KBRs, revealing the detrimental effect of catecholamine on liver metabolism. In contrast, 8 of the 9 untreated patients with blood pressure below 80 mm Hg showed almost normal KBRs. In the 25 donors in Germany, KBR was maintained within the normal range. Based upon conventional criteria, 21 livers were selected for use and the other 4 were discarded. Nineteen of the grafts were able to normalize KBR within 24 h after reperfusion, while 2 failed to function and required a second transplantation. It was suggested that a KBR in the normal range in donors is a prerequisite to immediate recovery of metabolic function of the liver graft after transplantation, and that hypotensive donors as a potential source of liver grafts may warrant further study.

Adolescent↗

Lignocaine metabolite formation as a measure of pre-transplant liver function.

A method for rapid assessment of hepatic function in liver donors based on the formation of the lignocaine metabolite monoethylglycinexylidide (MEGX), was used in a prospective study of 69 donor-recipient pairs. The probability of graft survival over 120 days was significantly higher for livers from donors with MEGX test values above 90 micrograms/l than for those from donors with MEGX values of 90 micrograms/l or below. Other liver function tests (bilirubin, prothrombin time, activity of aminotransferases, glutamate dehydrogenase, and cholinesterase, indocyanine green clearance, and galactose elimination capacity) were inefficient at predicting early outcome of transplantation. For a 20-day graft survival, the MEGX test showed prognostic sensitivity of 73% and specificity of 78%. These findings suggest that the MEGX formation test could be valuable for selection of donor organs.

Adolescent↗

[Liver transplantation in low portal vein flow: separation of portal vein areas with divided portal-venous and arterialized caval-venous liver perfusion. 1. Clinical case report].

A new method for the performance of a hepatic transplantation in spite of a low portal blood flow situation is described casuistically. In a 36-year-old-patient suffering from liver cirrhosis due to hepatitis B, the portal blood system of the right and left liver parts were divided, the left part was perfused with a low flow of portal blood, the right one with arterialized caval blood. The function of the transplanted liver and the early postoperative course were excellent. During the further postoperative course portal perfusion presumably diminished or stopped on the left side from three weeks and on the right side from two months postoperatively. Nevertheless the general condition of the patient improved continuously; transient elevations of transaminases may reflect the disturbance of portal perfusion. The technique of this arterialized caval blood perfusion of the portal system is presumably applicable also for situations, in which there is no portal blood flow available for perfusion of a liver graft. Thus, the absence of possibility for reconstruction of portal blood inflow or a situation with a hypoplastic portal vein may no longer be considered as a technical contraindication for liver grafting.

Adult↗

Potential various appearances of hyperacute rejection in human liver transplantation.

Out of 81 liver transplantations 2 graft failures were diagnosed to be due to hyperacute rejection. In the first patient the operative procedure was difficult requiring 19 units of blood and plasma, but the graft was functioning well from the beginning until day 1-2, when rapid deterioration occurred. The cross-match was positive. The second patient received a third graft after the first graft had failed due to donor reasons and the second AB0-incompatible graft had been rejected. The third graft transplanted in an uncomplicated operation requiring only 10 units of blood and plasma failed within hours. Both incidences are thought to be a consequence of an immunological assault, consistent with hyperacute rejection. Thus two different clinical appearances could be observed: the so-called delayed type in the first patient and the more classical type in the second patient. For establishing diagnosis of hyperacute rejection two prerequisites were considered essential: 1) histological findings of necrosis and patchy deposits of immunoglobulins, namely IgG, IgM, IgA, C-3 complement component, properdine and fibrinogen, and 2) the proof of at least a short period of an initial function of the graft prior to deterioration in order to exclude primary non-function due to other causes. The low frequency of the appearance of the classical hyperacute rejection and hypothetical causes for the more frequent appearance of the delayed type are discussed.

Adult↗

Bile duct injury as a part of diagnostic criteria for liver allograft rejection.

The decisive criterium of acute liver allograft rejection was found to be the presence of the diagnostic triad of acute rejection; ie, the presence of portal inflammatory mixed infiltrates, venous endothelialitis (both portal and central), and bile duct injury. On the basis of the presence of each of the components of the diagnostic triad, criteria for the diagnosis of different degrees of acute rejection were developed, particularly focusing attention on a detailed analysis of bile duct injury. Bile duct injury was shown to be an essential part of the histopathologic changes in all grades of acute rejection in the liver allograft, the grade of severity of bile duct injury correlating to a certain extent with the grade of severity of acute rejection. Our analyses have made it evident that bile duct injury, which most probably occurs earlier in the process of acute rejection than endothelialitis, is a more sensitive parameter than endothelialitis in the diagnosis of acute rejection. Furthermore, our analyses have revealed that bile duct injury in acute rejection is likely to be an irreversible process, depending on the number of episodes of acute rejection that previously occurred. On the other hand, it has become clear from our results that bile duct injury must not be considered to be an absolute histopathologic marker of acute rejection; however, it does have to be judged synoptically in connection with the other components of the diagnostic triad and the changes that the triad cause in the hepatic parenchyma. Additional analyses of the grade of severity of cholostases have shown that the cholostases are, to a certain degree, an accompanying phenomenon of the histopathologic changes characterizing acute rejection rather than a histopathologic change that is as significant as the presence of the components of the diagnostic triad.

Bile Ducts↗

Techniques of organ procurement and preservation of liver and pancreas.

The continuously improving success rate in transplantation imposes an obligation to implement the treatment for the increasing number of waiting recipients. In consideration of the increasing number of waiting recipients, all suitable organs of one donor should be harvested, including both liver and segmental or whole pancreas. The supreme goal of multiple organ harvesting is to ensure that none of the organs are damaged during preparation, perfusion and removal of one of the other organs. In general, several surgical teams are involved in multiple organ harvesting. The procedure therefore has to be highly standardized. One of the most important aspects of the procedure described here is the well-defined division into individual preparatory phases, each with its specific objectives: Phase I: preparation of organs, including evaluation of their suitability and delineation of important anatomical structures. Phase II: special preparations immediately before start of perfusion. Phase III: perfusion. Phase IV: removal of organs. Phase V: additional procedures and preparation of donor's body. Phase VI: preparation of transplant outside of body. This chapter describes the procedure by which liver and whole pancreas can be harvested from one donor. The surgical technique represents a compromise between two extremes: excessive dissection before perfusion and perfusion as the first step. The procedure described herein is considered to be an effective, safe, rapid and reasonably standardized one, especially for the co-operative effort between different surgical teams.

Humans↗