PubMed Health⌕ Search

Biomedical subjects

F O Belzer

Publications and source records attributed to F O Belzer.

At least 55 records · Page 3Linked to original sources
PubMed1994

Portal hypertension: surgical management in the 1990s.

BACKGROUND: Although liver transplantation offers definitive treatment for portal hypertension with end-stage liver failure, surgical portosystemic shunts avoid the risks of transplantation and immunosuppressive therapy, and transjugular intrahepatic portosystemic shunt (TIPS) creates a portosystemic shunt with minimal operative risk. The appropriate applications of these modalities are discussed. METHODS: All adults undergoing primary liver transplantation alone (PLT, n = 265), PLT after TIPS (n = 34), PLT after surgical shunts (n = 12), surgical shunt alone (n = 13), TIPS alone (n = 35), or surgical shunt after PLT (n = 5) served as the basis of this study. RESULTS: In contrast to surgical shunts before PLT, TIPS before PLT increased the 1-year graft survival. Surgical shunts alone were done in 18 patients with normal or near normal liver function with 100% survival. TIPS alone offered effective symptomatic relief to most patients, all of whom were judged not to be surgical candidates. CONCLUSIONS: TIPS, surgical shunts, and liver transplantation each have a logical role in management of portal hypertension. Surgical candidates with Child's B or C liver failure should be treated with liver transplantation, and TIPS offers effective treatment for nonsurgical candidates. Surgical shunts can be performed with excellent results in patients with Child's A liver disease. Portal vein occlusion with normal liver function can be successfully treated with surgical shunts.

Adolescent↗
PubMed1994

Prolonging myocardial preservation with a modified University of Wisconsin solution containing 2,3-butanedione monoxime and calcium.

The University of Wisconsin solution is an effective preservative for cold storage of the cardiac allograft. In an earlier study we showed that addition of calcium and 2,3-butanedione monoxime, a reversible inhibitor of myocardial contracture, further improved preservation of the rabbit heart. In this study we investigated the following: (1) the effects of different concentrations of 2,3-butanedione monoxime and calcium on function of the preserved rabbit heart, (2) how heart preservation is affected when 2,3-butanedione monoxime and calcium are added to the St. Thomas' Hospital and Stanford solutions, and (3) how 2,3-butanedione monoxime and calcium, at optimal concentrations in University of Wisconsin solution, affect hearts preserved up to 48 hours. Rabbit hearts were flushed with preservative and stored at 4 degrees C for 24, 30, 40, or 48 hours. Myocardial function was assessed during 60 minutes of isolated reperfusion, and myocardial adenine nucleotide content was measured after completion of reperfusion. Three concentrations of 2,3-butanedione monoxime (15, 30, and 60 mmol/L) in the University of Wisconsin solution were studied in hearts preserved for 30 hours. Storage with 2,3-butanedione monoxime at 30 mmol/L resulted in significantly better left ventricular developed pressure (p < 0.01), left ventricular end-diastolic volume (p < 0.01), rate of left ventricular pressure rise (p < 0.01), coronary flow (p < 0.05), rate-pressure product (p < 0.001), and adenine nucleotide regeneration (p < 0.05) than with 60 mmol/L, although function was not significantly different when the osmolarity of the solutions was equalized. There was significant reduction in end-diastolic volume (p < 0.05) and adenine nucleotide recovery (p < 0.01) when 2,3-butanedione monoxime was lowered to 15 mmol/L. Decreasing the calcium concentration from 1.0 to 0.1 mmol/L also had a deleterious effect on myocardial function (p < 0.05). The addition of 30 mmol/L 2,3-butanedione monoxime and 1.0 mmol/L calcium to the St. Thomas' or Stanford solutions improved preservation of the heart when compared with the unmodified solutions, but to a lesser degree than with the modified University of Wisconsin solution. After 24 to 48 hours of storage in University of Wisconsin solution containing 30 mmol/L 2,3-butanedione monoxime and 1.0 mmol/L calcium, there was substantial improvement in developed pressure (p < 0.001), end-diastolic volume (p < 0.05), and rate pressure product (p < 0.001), although there was little effect on heart rate and coronary flow, when compared with the unmodified University of Wisconsin solution.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine↗
PubMed1994

Urological complications and enteric conversion after pancreas transplantation with bladder drainage.

In summary, we feel that excellent 5-year patient and graft survival results can be obtained using SPK transplantation with bladder drainage technique. Despite the good results, a significant morbidity with prolonged hospitalization is seen after pancreas transplantation. This increased morbidity is due to infectious complications, rejection and urological complications. As a result of the popularity of bladder drainage, the complications after pancreas transplantation have shifted from intraabdominal to urological. Enteric conversion after SPK transplantation is the treatment of choice for chronic hematuria and a duodenal segment leak. In our hands this method appeared to be a safe and reliable procedure with a low complication rate. Enteric conversion should be considered in early leaks after failure of one attempt to suture repair the anastomotic site. In larger leaks or late leaks, it is advisable to perform an immediate enteric conversion. With the considerations above one might ask why enteric conversion is not our current primary choice for the initial transplant procedure. We have, however, noted a higher incidence of postoperative intraabdominal septic complications as well as mycotic aneurysms at the arterial suture line in a small series of 16 primarily enterically drained pancreas transplants. We also fear that the leakage rate after primary duodenoenteric drainage could be higher because of significant edema after transplantation in the preserved duodenal segment. We doubt, therefore, that the primary anastomosis with the bowel is as safe as one performed during enteric conversion when preservation injury has been resolved. At that point the patient is in stable condition and on significantly lower doses of immunosuppression than at the time of transplantation. This study demonstrates that urological complications constitute a major part of the morbidity after SPK transplantation. Despite this fact, appropriate treatment including enteric conversion can resolve most of the complications and prevent long-term morbidity or even graft loss.

Drainage↗
PubMed1993

Cytoprotective effect of glycine in cold stored canine renal tubules.

Reperfusion injury has been suggested to cause delayed graft function in renal transplantation. Methods to reduce reperfusion injury could lead to improved clinical renal transplantation. Glycine has been shown to suppress reperfusion injury in rabbit renal tubules and rat hepatocytes. In this study we have determined the effects of glycine on viability of isolated canine renal tubules. Renal tubules were cold stored at 4 degrees C under hypoxic conditions for up to 96 h in the UW solution and rewarmed to 37 degrees C for up to 2 h under oxygenated conditions to simulate reperfusion of an organ after cold static storage. Short-term storage (24 to 48 h) did not cause membrane injury (leakage of lactate dehydrogenase (LDH)) on rewarming. However, after 72 and 96 h cold storage reperfusion injury was evident and LDH leakage increased from about 25% to 59 +/- 3% and 71 +/- 2% at 72 and 96 h cold storage, respectively. The presence of 3 mM glycine in the reperfusion medium suppressed injury to cold-stored renal tubules. After cold storage for 72 and 96 h LDH leakage was reduced to control concentrations (31 +/- 3% and 29 +/- 1%, respectively). After cold storage for 72 h there was a reduction in ATP concentration in rewarmed renal tubules (3 nmol/mg protein at 48 h to 1.25 nmol/mg protein at 72 h). Also, there was a loss of mitochondrial functions including decreased stimulation of oxygen consumption by uncoupling of oxidative phosphorylation. Although glycine suppressed LDH leakage in renal tubules cold stored for 72 h it had no effect on the regeneration of ATP or mitochondrial functions, which remained depressed.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

A controlled, double-blind, randomized trial of verapamil and cyclosporine in cadaver renal transplant patients.

Calcium channel blockers have immunomodulating effects in vitro and may be effective in preventing cyclosporine nephrotoxicity. We studied the effect of verapamil following renal transplantation on the incidence of rejection and cyclosporine nephrotoxicity in a double-blind, placebo-controlled trial. Patients were randomly assigned to placebo (n = 28) or verapamil (n = 32) at doses of 80 mg twice a day. There was no difference in the incidence of rejection or cyclosporine toxicity in the two study arms. Recipients randomized to verapamil had lower mean cyclosporine doses at all intervals during a 1-year follow-up. Although cyclosporine doses were lower in the placebo group, the mean cyclosporine levels were equivalent in the two groups. Recipients in the verapamil-treated group had a higher mean serum creatinine at the end of the study--1.7 mg/dL versus 1.4 mg/dL in the placebo group. Actual 1-year graft survival was 89% for the placebo recipients versus 91% in the verapamil-treatment group. When compared with placebo, the concomitant use of low-dose verapamil results in lower cyclosporine doses but equivalent cyclosporine blood levels. Reduction in the incidence of rejection or cyclosporine nephrotoxicity were not observed.

Adult↗
PubMed1993

Urological complications in 210 consecutive simultaneous pancreas-kidney transplants with bladder drainage.

OBJECTIVE: The urological complications of 210 patients who underwent simultaneous pancreas-kidney (SPK) transplantation over a 7-year period were reviewed. SUMMARY BACKGROUND DATA: Worldwide, bladder drainage has become the accepted method of exocrine drainage after pancreas transplantation. With the increasing use of bladder drainage, the surgical post-transplant complications have shifted from intra-abdominal complications to urological complications. METHODS: Two hundred ten diabetic patients received SPK transplants with bladder drainage. A retrospective review was conducted to analyze the incidence, type, and management of urological complications. RESULTS: The most frequent urological complications were hematuria, leak from the duodenal segment, recurrent urinary tract infections, urethritis, and ureteral stricture and disruption. Complications related to the renal transplant included ureteral stricture and leaks, as well as lymphoceles. CONCLUSIONS: Despite the high incidence of urological complications, 5-year actuarial patient and graft survival are excellent. Only one graft and one patient were lost secondary to urological complications.

Adult↗
PubMed1993

Prolongation of canine intestinal allograft survival with RS-61443, cyclosporine, and prednisone.

The efficacy of RS-61443 and cyclosporine utilized either alone or in combination was assessed in both a segmental heterotopic and total orthotopic canine intestinal transplant model. Twenty-eight dogs underwent segmental (150-cm) heterotopic intestinal transplants and five dogs total orthotopic transplants. Five heterotopic groups were compared: group 1, no immunosuppression; group 2, cyclosporine and prednisone; group 3, RS-61443, cyclosporine and prednisone; group 4, RS-61443 and prednisone; and group 5, RS-61443 and subtherapeutic cyclosporine. Group 3 animals achieved a median survival of 136 days, while the median survivals of groups 1, 2, 4, and 5 were < or = 10 days (P < .001). Twenty deaths in groups 1 through 5 were secondary to allograft rejection, two were due to infection, and two were unexplained. Four animals in group 3 were sacrificed, one at 83 days due to diarrhea and weight loss and three at the termination of the study. The median survival of five dogs undergoing total orthotopic transplantation (group 6) was 27.0 days and was significantly longer than groups 1, 4, and 5 (P < .01). No dog in this group had intestinal rejection--however, four were sacrificed due to weight loss and one died of malnutrition. The combination of RS-61443 and cyclosporine significantly prolonged intestinal allograft survival in both the heterotopic and orthotopic transplant models. Clinically, this combination may be promising for both combined liver-intestinal and isolated intestinal transplantation.

Animals↗
PubMed1993

Livers from fasted rats acquire resistance to warm and cold ischemia injury.

Successful liver transplantation is dependent upon many factors, one of which is the quality of the donor organ. Previous studies have suggested that the donor nutritional status may affect the outcome of liver transplantation and starvation, due to prolonged stay in the intensive care unit, may adversely affect the liver. In this study we have used the orthotopic rat liver transplant model to measure how fasting the donor affects the outcome of liver transplantation. Rat livers were preserved with UW solution either at 37 degrees C (warm ischemia for 45-60 min) or at 4 degrees C (cold ischemia for 30 or 44 hr). After preservation the livers were orthotopically transplanted and survival (for 7 days) was measured, as well as liver functions 6 hr after transplantation. After 45 min of warm ischemia 50% (3 of 6) animals survived when the liver was obtained from a fed donor about 80% (4 of 5) survived when the liver was obtained from a three-day-fasted donor. After 60 min warm ischemia no animal survived (0 of 8, fed group). However, if the donor was fasted for 3 days 89% (8 of 9) of the animals survived for 7 days. Livers cold-stored for 30 hr were 50% viable (3 of 6) and fasting for 1-3 days did not affect this outcome. However, if the donor was fasted for 4 days 100% (9 of 9) survival was obtained. After 44-hr preservation only 29% (2/7) of the recipients survived for 7 days. If the donor was fasted for 4 days, survival increased to 83% (5/6). Liver functions, bile production, and serum enzymes were better in livers from the fasted rats than from the fed rats. Fasting caused a 95% decrease in liver glycogen content. Even with this low concentration of glycogen, liver viability (animal survival) after warm or cold ischemia was not affected, and livers with a low glycogen content were fully viable. Thus liver glycogen does not appear to be important in liver preservation. This study shows that fasting the donor does not cause injury to the liver after warm or cold ischemia. In fact, the livers appeared to be better able to tolerate ischemia when obtained from fasted rats. Thus donor nutritional status may be an important factor for outcome of liver transplantation. Livers from fasted donors may be capable of tolerating long-term preservation better than livers from fed donors.

Adenosine↗
PubMed1993

Risk factors for primary dysfunction after liver transplantation--a multivariate analysis.

In a retrospective analysis on 323 orthotopic liver transplant procedures performed between July 1984 and October 1991 the incidence of two forms of primary dysfunction (PDF) of the liver: primary nonfunction (PNF), and initial poor function (IPF) were studied. The incidence of PDF was 22% (73/323) with 6% PNF (20/323) and 16% IPF (53/323), while 78% (250/323) had immediate function (IF). Occurrence of both IPF and PNF resulted in a higher graft failure rate (P < 0.001), retransplantation rate (P < 0.001), and patient mortality (P < 0.003) within the first three months after OLTx. Univariate analyses of donor and recipient factors and their influence on PDF demonstrated that longer donor hospitalization (> 3 days), older donor age (> 49 years), extended preservation times (> 18 hr), and fatty changes in the donor liver biopsy, as well as reduced-size livers, younger recipient age, and renal insufficiency prior to OLTx, significantly affected the incidence of IPF and PNF. Multivariate analysis of potential risk factors showed that reduced-size liver (P = 0.0001), fatty changes on donor liver biopsy (P = 0.001), older donor age (P = 0.009), retransplantation (P = 0.01), renal insufficiency (P = 0.02), and prolonged cold ischemia times (P = 0.02) were independently associated with a higher incidence of IPF and PNF. No statistical correlation was found between PDF and etiology of ESLD, nutritional status of the recipient, UNOS status, and Child-Pugh classification in this study. We conclude that PNF and IPF are both separate clinical entities that have a significant effect on outcome after OLTx. Routine donor liver biopsies are recommended to decrease the rate of IPF and PNF. The combination of risk factors shown to be significant for PDF should be avoided--and, if that is not possible, the only variable that can be controlled, the preservation time, should be kept as short as possible.

Adolescent↗
PubMed1993

Retransplantation of the liver--a seven-year experience.

Three hundred and four patients underwent 362 liver transplants between July 1984 and April 1992. Fifty-eight retransplants were performed in 44 patients (14.5%). Thirty-four patients underwent two (77.3%), seven patients three (15.9%), two patients four (4.5%), and one patient five (2.3%) transplants. Poor function accounted for 23 retransplants (6.4%), technical problems for 19 retransplants (5.2%), and rejection for 15 retransplants (4.1%). One-month patient survivals after retransplantation for poor function, technical problems, or rejection were similar (79.0%, 73.4%, and 80.0%, respectively). No difference in retransplantation rates were seen between adults and children receiving whole liver transplants (WLT) (11.6% versus 19.1%). However, retransplantation for poor function was more common in pediatric recipients receiving reduced-size liver transplants (RLT) (20.0% versus 0.0%, P < 0.01), while retransplantation for hepatic artery thrombosis (HAT) was more common in pediatric recipients receiving WLT (16.7% versus 2.8%, P < 0.05). The presence of multiorgan system failure of greater than four was associated with a high mortality (90%), whereas patients undergoing emergent retransplantation who had less than four systems fail had a survival of 73.9% and patients who underwent elective retransplantation had a survival rate of 81.8%. Length of stay and cost of liver transplantation was higher in patients undergoing retransplantation when compared with primary transplants (29.7 +/- 14.9 days versus 58.4 +/- 38.9 days and $122,358 +/- 59,782 versus $289,302 +/- 126,907, P < 0.01). The overall actuarial one-year patient survival in primary transplants was 86.6% and in retransplants 74.8%, and at five years these were 71.4% versus 62.5%, respectively (P < 0.05). Our results support continued retransplantation of the liver unless the patient's medical condition dictates otherwise.

Adolescent↗
PubMed1993

Effect of glycine in dog and rat liver transplantation.

Glycine has been shown to protect renal tubule cells and hepatocytes from ischemia, ATP depletion, and cold storage injury. Glycine may be a useful additive to organ preservation solutions or suppress reperfusion injury by infusion into recipients of liver transplantation. In this study, the effects of glycine on survival and postoperative liver injury were studied in the rat and dog orthotopic transplant model. Rat livers preserved for 30 hr in the University of Wisconsin (UW) solution were 50% viable (3 of 6 survivors for 7 days). When glutathione was replaced by 10 mM glycine, survival increased to 100% (6 of 6). There was a significant reduction in hepatocellular injury at the end of preservation (lactate dehydrogenase [LDH] in the pretransplant flush-out of the liver was lower in the glycine group) and after transplantation (serum LDH concentration 6 hr after transplant was lower in the glycine group). In the dog, omission of glutathione from the UW solution resulted in 33% survival (48-hr preservation model) versus 100% survival with glutathione. Replacing glutathione in the UW solution by glycine did not improve survival (33% after 48 hr of preservation). However, when glycine was given to recipients of livers preserved in the UW solution for 24 or 48 hr, there was a decrease in the degree of hepatocellular injury. After 48 hr of preservation, peak aspartate aminotransferase, alanine aminotransferase, and LDH were reduced by about 45-55% when glycine was given to the recipient. Although the differences, with and without glycine treatment of the recipients, did not reach statistical significance, there was a noticeable reduction in hepatocellular injury with glycine. There was 100% survival of dogs in the groups that received livers preserved with the UW solution plus or minus glycine infusion. Hepatamine, a parenteral nutrition solution containing glycine and other amino acids increased hepatocellular injury (higher concentrations of aspartate aminotransferase, alanine transferase, and LDH versus control 48-hr preserved livers), although all dogs survived. This study shows that glycine is cytoprotective when administered to recipients of livers preserved for 24 or 48 hr and suppresses hepatocellular injury, as reflected in a reduction in the concentration of serum enzymes. However, the differences, with and without glycine, were, at best, marginal and further studies are needed to determine whether glycine would make a significant improvement in liver preservation and prevent primary nonfunction.

Adenosine↗
PubMed1993

Effect of fasting on hepatocytes cold stored in University of Wisconsin solution for 24 hours.

Although there have been improvements in liver preservation, liver dysfunction still remains a serious consequence of liver transplantation. This may be related to cold ischemic injury since the incidence of dysfunction increases with longer preservation times. However, even some livers preserved for short periods of time (less than 15 hr) develop liver dysfunction. One possible cause may be the lack of adequate nutritional support, and the donor may be exposed to prolonged periods of hyponutrition. In this study, we have compared the effects of fasting on functions of hepatocytes isolated from the rat. Hepatocytes were cold stored in University of Wisconsin solution for 24 hr and analyzed at the end of preservation as well as at the end of rewarming in Krebs-Henseleit buffer for 120 min. The glycogen content of fed cells was 1.57 mumol/mg protein and this was reduced by 95% in cells from fasted rats. After cold storage and rewarming, hepatocytes from fasted rats lost 84.2 +/- 2.5% of the total cellular lactate dehydrogenase versus only 32.7 +/- 3.8% (P < 0.001) in cells from fed rats. Also, ATP and reduced glutathione content of fasted cells were significantly reduced, free fatty acids were higher (P = 0.0154), and protein synthesis was reduced to 41% of controls (versus only 88% in fed cells), although there were no differences in phospholipid content. When hepatocytes from fasted rats were rewarmed in Krebs-Henseleit buffer containing fructose (10 mM), lactate dehydrogenase release was reduced from 80% to 34.4 +/- 0.2% and ATP content was significantly higher with fructose than without. Hepatocytes from fasted rats, therefore, are more sensitive to cold ischemic injury than cells from fed rats. The increased sensitivity appears related to the lack of glycogen as a source of substrates for metabolism during rewarming. This is supported by the fact that addition of fructose, which is metabolized readily by hepatocytes through glycolysis, suppressed rewarming injury to cells from fasted rats. The nutritional status of the donor, therefore, may play a pivotal role in the results of liver preservation and transplantation. Effective donor nutritional management may reduce the incidence of liver dysfunction after transplantation.

Adenosine↗