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F O Belzer

Publications and source records attributed to F O Belzer.

At least 163 records · Page 9Linked to original sources
PubMed1990

A prospective, randomized, double-blind study of trimethoprim-sulfamethoxazole for prophylaxis of infection in renal transplantation: clinical efficacy, absorption of trimethoprim-sulfamethoxazole, effects on the microflora, and the cost-benefit of prophylaxis.

PURPOSE: To determine the efficacy of long-term prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMZ) for prevention of bacterial infection following renal transplantation, the absorption of TMP-SMZ in transplant patients, the effects of prophylaxis on the microflora, and the cost-benefit of prophylaxis. PATIENTS AND METHODS: One hundred thirty-two adult patients selected to undergo renal transplantation participated in a randomized, double-blind, placebo-controlled trial. RESULTS: Patients randomized to receive TMP-SMZ experienced fewer hospital days with fever (3.3% versus 7.7%, p less than 0.001) and significantly fewer bacterial infections during the transplant hospitalization after removal of a urethral catheter (0.76 versus 1.88 per 100 days, p less than 0.005) and following discharge from the hospital (0.08 versus 0.30 per 100 days, p less than 0.001). During the transplant hospitalization, a daily dose of 320/1,600 mg was highly effective for prophylaxis whereas 160/800 mg daily gave unexpectedly low blood levels and was effective only for prevention of urinary tract infections after catheter removal. Prophylaxis was most effective in prevention of infections of the urinary tract (24 versus 54, p less than 0.005) and bloodstream (one versus nine, p less than 0.01) and infections caused by enteric gram-negative bacilli (four versus 46, p less than 0.001), enterococci (six versus 22, p = 0.006), or Staphylococcus aureus (one versus nine, p = 0.01). Prophylaxis did not prevent urinary tract infection associated with urethral catheters in the early posttransplant period, but after catheter removal, reduced the risk of urinary tract infection threefold (p less than 0.001). No significant differences in colonization by TMP-SMZ-resistant gram-negative bacilli were identified between the two groups; patients given TMP-SMZ were, paradoxically, less likely to become colonized by candida, probably because of less exposure to antibiotics for treatment of infection. Recipients of prophylaxis did not have a higher rate of infection caused by TMP-SMZ-resistant bacteria or Candida; however, their infections were more likely to be caused by resistant bacteria than infections in patients in the placebo group (62% versus 18%, p less than 0.001). CONCLUSIONS: Prophylaxis with TMP-SMZ, which is well tolerated, significantly reduces the incidence of bacterial infection following renal transplantation, especially infection of the urinary tract and bloodstream, can provide protection against Pneumocystis carinii pneumonia, and is cost-beneficial. Subnormal absorption of TMP-SMZ in the early posttransplant period mandates 320/1,600 mg daily for optimal benefit. Prophylaxis has little discernible effect on the microflora.

Absorption↗
PubMed1990

Hypothermic preservation of hepatocytes. II. Importance of Ca2 and amino acids.

The importance of the components of a tissue culture media, Leibovitz-15 (L-15), for maintaining viability of hypothermically preserved hepatocytes was analyzed. Hepatocytes isolated from rat livers were incubated at 5 degrees C in an oxygenated environment with continuous shaking (to simulate organ perfusion preservation). L-15 + 5 g% polyethylene glycol (PEG) or variants of this solution were used as the preservation media. After 48 hr of storage, hepatocyte viability was assessed by measuring the release of LDH into the incubation medium and cell volumes were determined. Following 90 min of normothermic incubation (to simulate organ reperfusion), mitochondrial function was measured. Hepatocytes stored in the complete L-15 solution were about 90% viable at the end of 48 hr of storage, while cells stored in a solution containing only the principle electrolytes (PE) lost viability (70% viable). Only the addition of a combination of divalent cations (Ca/Mg) and amino acids was sufficient to maintain viability equivalent to that obtained in the complete L-15 mixture. Hepatocytes suspended in L-15 maintained normal cell volumes (3.85 microliters/mg protein), while cells in the PE solution were swollen with cell volumes of 4.66 microliters/mg protein. Only the addition of Ca/Mg to the PE solution was effective at suppressing cell swelling similar to the complete L-15 media. Both basal and uncoupler-stimulated respiration were depressed in cells stored in the PE solution (15 and 28 nmol O2/min/mg protein) as compared to cells in L-15 (21 and 41 nmol O2/min/mg protein).(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1990

Important components of the UW solution.

The UW solution for preservation of the liver, kidney, and pancreas contains a number of components, and the importance of each of these has not been fully resolved. In the studies reported here the importance of glutathione and adenosine is demonstrated in isolated cell models (rabbit renal tubules and rat liver hepatocytes) of hypothermic preservation and reperfusion and in dog renal transplantation. Glutathione in the UW solution is necessary for the preservation of the capability of the cell to regenerate ATP and maintain membrane integrity. Adenosine in the UW solution provides the preserved cell with substrates for the regeneration of ATP during the reperfusion period following cold storage. The omission of GHS from the UW solution results in poorer renal function in the 48 hr dog kidney preservation-transplant model. The role of other components of the UW solution is discussed including lactobionic acid; other impermeants; and the colloid, hydroxyethyl starch. It is concluded that the development of improved preservation solutions will require a more detailed understanding of the mechanism of injury due to cold storage and, once obtained, solutions more complex than the UW solution may be required for improved long-term storage of organs.

Adenosine↗
PubMed1990

Seventy-two-hour preservation of the canine liver by machine perfusion.

The UW solution effectively preserves the dog liver for up to 48 hr by simple cold storage. This solution contains lactobionate as the primary impermeant. Another solution developed for machine perfusion of the kidney is similar to the UW solution but contains gluconate in place of lactobionate. In this study the UW gluconate solution was used for the continuous hypothermic machine perfusion of dog livers for 72 hr. Dog livers were continuously perfused at 5 degrees C through the portal vein at a pressure of 16-18 mm Hg and transplanted. Seven of 8 dogs survived for 7 or more days following orthotopic transplantation. The livers functioned as well as those preserved for 48 hr by cold storage in the UW solution as indicated by various liver-function tests. Successful machine perfusion was only achieved when the perfusate contained a high concentration of potassium (125 mM) but not with a high concentration of sodium (125 mM). This study demonstrates the feasibility of machine-perfusion preservation of the liver that yields longer preservation of equal quality compared to simple cold storage. For the development of truly long-term preservation (5 or more days) and better quality short-term preservation, machine perfusion may be the method of choice.

Alanine Transaminase↗
PubMed1990

Prolonged survival of murine thyroid allografts after 7 days of hyperbaric organ culture in the UW preservation solution at hypothermia.

Organ culture of murine thyroid allografts in hyperbaric oxygen (95% O2 at 25 psi, 37 degrees C) for 48 hr, results in prolonged allograft survival. Endocrine tissues can be cultured at 37 degrees C--however, this method may not be applicable to vascularized organs at normothermia. The aim of this study was to apply hyperbaric oxygen culture (HOC) under organ preservation conditions (hypothermia, UW solution) that have been shown to be successful in clinical organ transplantation. B10BR/SGSNJ murine thyroid lobes were transplanted beneath the kidney capsule of C57BL/10J recipients. Thyroids were cultured in Eagle's MEM at 37 degrees C (controls) and at 5 degrees C, under hyperbaric conditions (95% O2:5% CO2, 25 psi). Alternatively, thyroids were cultured in UW solution (+/- allopurinol/GSH) at 5 degrees C, for up to 7 days. Graft survival was determined 21 days posttransplant by 125I uptake and by histology. In Eagle's MEM, HOC at 37 degrees C/48 hr and 5 degrees C/7 days, resulted in 93% and 20% allograft survivals, respectively. In UW solution (- allopurinol/glutathione [GSH]), HOC at 5 degrees C/7 days resulted in 83% allograft survival: immunoperoxidase staining showed a decrease of MHC class I alloantigen expression. Oxygen free radical scavenger (allopurinol/GSH) addition to the UW solution diminished this effect and suggested an oxygen free radical-mediated mechanism in immunoalteration. These results demonstrate that HOC for 7 days reduced the antigenicity and immunogenicity of murine thyroid grafts under conditions that simulate organ preservation. Hypothermic hyperbaric oxygen culture conditions require testing in a higher animal species and in vascularized grafts to determine if this method can be applied to whole-organ transplantation.

Adenosine↗
PubMed1990

The effects of fasting on the quality of liver preservation by simple cold storage.

Although livers can be successfully preserved for 24 hr or more, often the transplanted livers have poor or no (primary nonfunction) function. The quality of the liver does not appear dependent upon the time of preservation but may be dependent upon the condition of the donor. In this study we have investigated the effects of fasting on the quality of livers for transplantation. Rabbits were fasted (48 hr) and livers preserved in the UW solution for 6-8 hr. Functions of the liver were analyzed by isolated perfusion for 2 hr. Also, pigs were fasted for 72 hr, livers preserved for 12 hr, and viability determined by orthotopic transplantation. Fasting depleted the liver glycogen by 85% but had no effect on ATP or glutathione concentrations. Rabbit livers from fasted animals produced similar amounts of bile, released similar concentrations of lactate dehydrogenase (LDH) and aspartate amino transaminase (AST) into the perfusate, maintained similar concentrations of ATP and glutathione in the tissue, and had a similar intracellular K:Na ratio after 24-hr preservation when compared to livers from fed animals. After 48-hr preservation, livers from fasted animals were less viable than livers from fed animals, including: reduced bile production (2.0 +/- 0.3 vs. 5.0 +/- 0.9 ml/2 hr, 100 g), greater release of LDH (3701 +/- 562 units vs. 1123 +/- 98 units) and AST, less ATP (0.326 +/- 74 vs. 0.802 +/- 160 nmol/g), less glutathione (0.303 +/- 13 vs. 0.933 +/- 137 nmol/g), and a lower K:Na ratio (1.5 +/- 0.9 vs. 7.4 +/- 0.6). Pigs receiving livers from fed animals preserved for 12 hr had better survival (5/6, 83%) than livers from fasted animals (3/6, 50%). The results show that the nutritional status of the donor can affect the outcome of liver preservation and transplantation. Increased injury in livers from fasted animals may be due to the loss of glycogen that may be an essential source of energy in the initial posttransplant period. In clinical liver transplantation the nutritional status of the donor may be an important factor in the initial function of the liver, and methods to increase the nutritional status of the donor may be important in increasing the quality of livers.

Adenosine Triphosphate↗
PubMed1990

Effect of oxidized and reduced glutathione in liver preservation.

Glutathione spontaneously oxidizes in the UW solution for organ preservation and reduced glutathione (GSH) is converted to oxidized (GSSG) glutathione. To determine the effects of the oxidized or reduced forms of glutathione on liver preservation dog livers were preserved for 24 and 48 hr with the UW solution containing either GSH or GSSG. After 24 hr of preservation the form of glutathione did not affect survival or the postoperative course of the animals. All animals survived (three per group) with near-normal liver functions by the third to fifth postoperative day. When preservation was extended to 48 hr survival was 100% (6/6) with GSH and 29% (2/7) with GSSG. The dogs that died developed primary nonfunction of the liver. This study shows that GSH is an important component of the UW solution for 48-hr preservation of the dog liver. The presence of GSSG does not prevent successful 24-hr preservation of the liver, which has been confirmed in clinical studies. However, for 48-hr preservation GSH is required and GSSG is not suitable.

Adenosine↗
PubMed1990

Organ preservation: experience with University of Wisconsin solution and plans for the future.

Transplantation of organs continues to be a primary therapeutic modality for treatment of end-stage organ disease, and 1-year graft survival rates show increasing improvements for most organs. A number of transplant centers show 1-yr graft survival rates approaching 90% or more for the kidney, liver and pancreas. Rejection continues to be the major cause for loss of organs and there is still a major shortage of organs for transplantation. Additionally, many organs showed delayed graft function (or primary nonfunction) which may be related to either donor factors or preservation factors. The University of Wisconsin solution for organ preservation has increased the safe time of preservation for the liver, kidney, and pancreas and helped to increase the quality and number of organs available for transplantation. However, the long-range goal of organ preservation (unlimited preservation) is still far from being reached. In the past, preservation could accurately be categorized as an art and preservation solutions were developed based upon theoretical rationales about the mechanisms of organ injury at hypothermia and what agents would suppress injury. The utility and success of this approach is exemplified by the developments of Collins solution and the UW solution. However, further developments in methods to increase the quality and duration of preservation of all transplantable organs would appear to be dependent upon defining, systematically, how organs are injured and what can be done to suppress the injury.(ABSTRACT TRUNCATED AT 250 WORDS)

Forecasting↗
PubMed1990

Living-unrelated renal transplantation at the University of Wisconsin.

1. Use of LUrDs under a DST protocol results in a 70% actuarial graft survival at 6 years which is not statistically different from haploidentical or primary cadaver recipients transplanted over the same time period. 2. Sensitization is common, despite the use of Aza, especially in husband-to-wife donor-to-recipient relationship. 3. Rejection occurs frequently, despite the use of DST, however, it is usually reversible. The high rejection rate did not influence the quality of long-term graft survival with very few patients losing grafts to chronic rejection. 4. Expansion of the use of LUrDs could help provide additional organs for transplantation.

Adult↗