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F O Belzer

Publications and source records attributed to F O Belzer.

At least 37 records · Page 2Linked to original sources
PubMed1995

Relationships between sclerosing cholangitis, inflammatory bowel disease, and cancer in patients undergoing liver transplantation.

BACKGROUND: Liver transplantation has emerged as the definitive treatment for primary sclerosing cholangitis (PSC). Its relationships to inflammatory bowel disease and cholangiocarcinoma were evaluated in this series. METHODS: Fifty-three liver transplantations were performed in 41 patients with PSC at the University of Wisconsin from 1986 through 1994. Fourteen of the patients underwent colectomies for inflammatory bowel disease, eight before transplantation and six after transplantation. Five patients had cholangiocarcinoma on the hepatectomy specimen, and another two had been diagnosed before transplantation. RESULTS: Patient survival for PSC without cholangiocarcinoma was 85% and 62% at 2 and 9 years, respectively. No patient with PSC and cholangiocarcinoma has survived 2 years, although two patients were free of disease 11 and 20 months after transplantation. Despite maintenance immunosuppression seven patients with liver transplants had reactivation of inflammatory bowel disease and colon carcinoma developed in three after liver transplantation. CONCLUSIONS: Liver transplantation should be performed early in the course of PSC to avoid the lethal complications of cholangiocarcinoma. Careful colonoscopic follow-up is necessary in patients undergoing transplantation for PSC because immunosuppressive therapy does not necessarily cause inflammatory bowel disease to be quiescent, nor does it reduce the risk of colon carcinoma developing.

Adenocarcinoma↗
PubMed1995

Organ preservation.

Organ preservation is the supply line for organ transplantation. Currently, the liver, pancreas, and kidney can be successfully preserved for up to two days by flushing the organs with the University of Wisconsin (UW) organ preservation solution and storing them at hypothermia (0-5 degree C). The UW solution is effective because it uses a number of cell impermeant agents (lactobionic acid, raffinose, hydroxyethyl starch) that prevent the cells from swelling during cold ischemic storage. Additionally, the UW solution contains glutathione and adenosine, agents that may stimulate recovery of normal metabolism upon reperfusion by augmenting the antioxidant capacity of the organs (glutathione) or by stimulating high-energy phosphate generation (adenosine) upon reperfusion. Although this method of organ preservation is effective, some organs (5-15% of livers and 20-30% of kidneys) do not function well upon transplant. Injury may be preservation related but may also result from donor and recipient factors that render the organs more susceptible to preservation damage. Results with continuous perfusion of kidneys in the clinics show a reduction in preservation/reperfusion damage. This may be a more appropriate preservation method than cold storage. In this chapter we discuss the development and use of the UW solution and present clinical results. Although intraabdominal organs are well preserved at present, intrathoracic organs (lungs and heart) are less well preserved, and better methods for preservation of these organs are needed for increased use of lung and heart transplantation.

Adenosine↗
PubMed1995

Long-term renal preservation and prevention of acute tubular necrosis by inhibition of arachidonate metabolism.

Experimental preservation time for pulsatile perfused dog kidneys was extended from three to five days by phospholipase A2 inhibition suggesting a pathomechanical role of products of phospholipolysis like thromboxane and leukotrienes in the development of acute graft failure after renal transplantation. We therefore investigated the effects of thromboxane- and leukotriene synthase inhibitors on postoperative renal transplant function in a model of pulsatile perfusion preservation as well as a cold storage preservation of dog kidneys. Addition of a thromboxane-synthase-inhibitor to the perfusion medium in pulsatile perfused kidneys and the combined application of a thromboxane-synthase-inhibitor and a leukotriene-synthase-inhibitor to the recipient of a cold storage preserved graft, improved graft function and reduced the incidence of delayed graft function as well as histopathological features of acute tubular necrosis.

Adenosine↗
PubMed1994

Kupffer cells depress hepatocyte protein synthesis on cold storage of the rat liver.

The causes of liver failure after transplantation are multifactorial. An understanding of the mechanisms of injury to the liver could help to define methods to improve preservation and transplantation. We measured protein synthesis by 3H-leucine incorporation into acid precipitable protein in rat liver tissue slices, isolated hepatocytes, and isolated perfused liver (IPL) after cold storage for 24 or 48 hr in University of Wisconsin (UW) solution. Some rats were pretreated with dexamethasone prior to liver harvest. Protein synthesis was depressed in all in vitro models after 24 hr storage. The percent decrease was greater in tissue slices and IPL (about 70% decrease relative to fresh livers) than in isolated hepatocytes (about 30% decrease). Dexamethasone pretreatment improved protein synthesis significantly after 24 hr preservation in tissue slices and in IPL, but had no significant effect on protein synthesis in isolated hepatocytes. The greater loss of protein synthesis in tissue slices and IPL compared with that in isolated hepatocytes was considered in relation to the presence of Kupffer cells in the former systems and lack of Kupffer cells in the isolated cell suspensions. Kupffer cells generate cytotoxins that could cause injury to metabolically depressed hepatocytes or endothelial cells. Dexamethasone has been shown to modulate Kupffer cell inhibition of hepatocyte functions. The results suggest that preservation damage to hepatocytes sensitizes them to further damage on reperfusion by Kupffer cell-generated agents.

Animals↗
PubMed1994

Effect of glycine on isolated, perfused rabbit livers following 48-hour preservation in University of Wisconsin solution without glutathione.

Glycine has been shown to decrease membrane injury in isolated cells due to hypoxia or cold ischemia. The mechanisms of action of glycine are not known, but glycine may be useful in organ preservation solutions or in treating recipients of liver transplantation. In this study the isolated, perfused rabbit liver was used to measure how glycine affected liver performance after 48-h preservation in University of Wisconsin (UW) solution without added glutathione. UW solution is less effective for 48-h liver preservation when glutathione is omitted. Rabbit livers stored for 48 h without glutathione show a large increase in enzyme release (LDH and AST) from the liver and a reduction in bile production. The addition of 15 mM glycine to UW solution, in place of glutathione, did not improve bile production or reduce enzyme release. However, infusion of 10 mM glycine into the reperfused liver lowered LDH release significantly (from 2383 +/- 562 units/100 g to 1426 +/- 286 units/100 g) during the initial reperfusion of the 48-h preserved liver. Hepatamine, a parenteral nutrition solution containing glycine, as well as other amino acids, was also effective in lowering LDH release from the preserved liver. Although glycine reduced LDH release, it did not decrease the amount of AST released from the liver, nor did it improve bile production. Thus, we conclude that glycine, either in UW solution or given to the liver upon reperfusion, has no significantly beneficial effect as tested in this model. Further testing of glycine, however, should be conducted in an orthotopic transplant model in the rat or dog.

Adenosine↗
PubMed1994

Forty-hour preservation of the rabbit heart: optimal osmolarity, [Mg2+], and pH of a modified UW solution.

The University of Wisconsin solution modified with 2,3-butanedione monoxime and calcium experimentally extends the limits of ischemic preservation of the heart. This study evaluates other characteristics of this modified solution that may further enhance preservation: osmolarity, Mg2+ concentration ([Mg2+]), and pH. Rabbit hearts were flushed with the modified University of Wisconsin solution and stored for 40 hours at 4 degrees C. Maximal left ventricular developed pressure (LVDP), left ventricular end-diastolic volume (LVEDV), maximum rate of increase of left ventricular pressure (dP/dt), heart rate, and coronary flow were measured during 60 minutes of isolated crystalloid reperfusion with an isovolumic left ventricular balloon at constant end-diastolic pressure. Creatine kinase release and myocardial adenine nucleotide content were measured at completion of reperfusion. Solution osmolarity was tested at 357, 327, 297, and 277 mOsm/L by reducing K+, Na+, and lactobionate concentrations. [Mg2+] was assessed at 5 and 16 mmol/L. Solution pH was studied at 7.0, 7.4, and 7.8. A control group of hearts was flushed and immediately reperfused to establish baseline function. Hearts stored in either hypertonic (357 mOsm/L) or hypotonic (277 mOsm/L) solutions functioned poorly, reaching 58% and 50% of control LVDP (p < 0.001), 49% (p < 0.01), and 58% (p = not significant) of LVEDV, 56% and 49% of +dP/dt (p < 0.001), respectively, and released substantially more creatine kinase (p < 0.001 versus control).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1994

100 consecutive liver transplants in infants and children: an 8-year experience.

Orthotopic liver transplantation has become the treatment of choice for most children and infants with end-stage liver disease. The purpose of this retrospective study was to examine the results of 100 consecutive liver transplants performed in infants and children at a single institution. During an 8-year study period (July 1984 to December 1992), 100 pediatric liver transplants were performed in 76 patients. Thirty-four patients (44.7%) were infants (mean age, 7.0 months; mean weight, 6.1 kg), and 42 (55.3%) were children (mean age, 8.2 years; mean weight, 30.6 kg). There were 36 reduced-size liver transplants (RLT) and 64 whole-size transplants (WLT). Eight infants (23.5%) and 10 children (20.7%) required retransplantation. After transplantation, 71% of the patients had one or more rejection episodes, 66% had one or more infections, 17.1% had biliary complications, and 39.4% required one or more reoperations. There were 17 deaths. The actuarial 8-year survival rate for the patients with biliary atresia was 82.3%; for all infants in this series, it was 77.6%. No difference in patient survival was noted when RLT was compared with WLT. The overall 8-year actuarial patient survival rate for infants and children was 77.3%.

Adolescent↗
PubMed1994

Clinical experience with human anodal trypsinogen (HAT) for detection of pancreatic allograft rejection.

To date one of the major dilemmas in clinical pancreas transplantation is the lack of a reliable indicator for pancreas rejection. In a consecutive series of 52 patients undergoing simultaneous pancreas and kidney (SPK) transplantation with bladder drainage technique between October 1991 and December 1992 a new test using serial levels of serum human anodal trypsinogen (HAT) was evaluated for its efficacy to detect pancreas rejection. Postoperative baseline levels of HAT were compared to peak HAT values at time of rejection. HAT profiles at time of rejection were calculated and compared to profiles of urinary amylase, serum amylase, fasting blood sugar and serum creatinine. In this series one year patient survival was 97%, graft survival of the pancreas 86% and of the kidney 90%. In 71% of the patients at least one rejection episode occurred. At time of kidney-biopsy proven rejection with a concurrent serum creatinine rise a significant HAT level rise to more than 1000 ng/ml was observed from baseline levels of 200 ng/ml (P < 0.001) indicating kidney and pancreas rejection (73%). Urinary amylase levels decreased in the majority of rejection episodes at the same time from baseline levels to less than 20,000 U/l. In 25% of the rejection episodes a significant serum creatinine rise was observed without a HAT rise or urinary amylase decrease indicating kidney-only rejection, while in 2% a urinary amylase decrease and simultaneous HAT also was observed with a negative kidney biopsy indicating pancreas-only rejection. We feel that increase in HAT levels significantly correlates with pancreas rejection. After SPK, determination of HAT is an additional helpful non-invasive test. In pancreas transplantation alone HAT can be a useful indicator to detect rejection and facilitate timing of a pancreas biopsy and initiation of antirejection treatment.

Adult↗
PubMed1994

Successful 48-h liver preservation by controlling nutritional status of donor and recipient.

The nutritional status of the donor has been shown to affect the outcome of liver transplantation in the rat. It has been proposed that this may be due to inhibition of Kupffer cell induced injury to the reperfused organ, which leads to an inflammatory type response. In this study we investigated how altering the nutritional status of the recipient affects the outcome of liver transplantation after preservation of the liver for 44 or 48 h in the University of Wisconsin (UW) solution. The nutritional status of the rats was altered by either fasting or by feeding an essential fatty acid free diet (EFAD) for 2 months. This type of diet has been shown to reduce significantly the inflammatory response in rats. Survival after 44-h preservation of livers from fed donors (fed a standard laboratory diet) transplanted to fed recipients was 29% (2/7) but increased to 80% (4/5) when the recipient was fed the EFAD diet. After 48-h preservation, there were no survivors under either of these two dietary combinations. However, survival was 100% after 48-h preservation if the donor had been fasted for 4 days and the recipient was fed the EFAD. These results showed that the nutritional status of the donor and recipient are important factors in the outcome of liver transplantation. How nutritional factors affect liver preservation and transplantation are not clear but may be related to the inflammatory response regulated by Kupffer cells and circulating neutrophils in the liver, both of which are influenced by the diet of the animal.

Adenosine↗
PubMed1994

Living-unrelated renal donor transplantation: the UNOS experience, 1987-1991. United Network for Organ Sharing.

1. LURD transplants were associated with excellent one-year graft survival of 92%. This survival was superior to that for cadaver transplants performed during the same period. 2. High-risk groups for LURDs are children (age < 18 years) and repeat transplant recipients. Both groups were associated with significantly decreased graft survival. 3. The effects of HLA matching and donor-specific transfusions are not significant. 4. Because of the critical shortage of donor organs and the increasing waiting time for renal transplantation, the use of LURDs can be recommended as a means to expand the number of available organs.

Adolescent↗
PubMed1994

Organ preservation.

Our clinical transplantation results have been very satisfying, with about 90% graft survival after 1 year. Currently, preservation of the liver, pancreas, and kidney, although not ideal, appears to meet all our clinical needs. Improvements in heart and lung preservation are needed and will result in increasing the number of cadaveric organs available for patients with end-stage intrathoracic organ diseases. In the future, machine perfusion may become the standard method for organ preservation for most organs because of the excellent preservation results and long-term preservation achieved.

Adenosine↗
PubMed1994

The "sacred cow".

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Academic Medical Centers↗