Search PubMed⌕ Search

Biomedical subjects

L Makowka

Publications and source records attributed to L Makowka.

At least 91 records · Page 5Linked to original sources
PubMed1992

Pretransplant assessment of human liver grafts by plasma lecithin: cholesterol acyltransferase (LCAT) activity in multiple organ donors.

In spite of the improved outcome of orthotopic liver transplantation (OLTx), primary graft nonfunction remains one of the life-threatening problems following OLTx. The purpose of this study was to evaluate plasma lecithin: cholesterol acyltransferase (LCAT) activity in multiple organ donors as a predictor of liver allograft viability prior to OLTx. Thirty-nine donors were studied during a 5-month period between April and August 1988. Allograft hepatectomy was performed using a rapid technique or its minor modification with hilar dissections, and the allografts were stored cold (4 degrees C) in University of Wisconsin (UW) solution. Early post-transplant allograft function was classified as good, fair, or poor, according to the highest SGOT, SGPT, and prothrombin time within 5 days following OLTx. Procurement records were reviewed to identify donor data, which included conventional liver function tests, duration of hospital stay, history of cardiac arrest, and graft ischemic time. Blood samples from the donors were drawn immediately prior to aortic crossclamp, and from these plasma LCAT activity was determined. Plasma LCAT activity of all donors was significantly lower than that of healthy controls (12.4 +/- 8.0 vs 39.2 +/- 13.3 micrograms/ml per hour, P less than 0.01). LCAT activity (16.4 +/- 8.3 micrograms/ml per hour) in donors of grafts with good function was significantly higher than that in those with fair (8.6 +/- 4.5 micrograms/ml per hour, P less than 0.01) or poor (7.3 +/- 2.4 micrograms/ml per hour, P less than 0.01) function.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

The effect of a new immunosuppressive drug, brequinar sodium, on heart, liver, and kidney allograft rejection in the rat.

Brequinar sodium (BQR) prevents cell proliferation by virtue of its inhibition of de novo pyrimidine biosynthesis. BQR is capable of inhibiting immune responses in vitro and is effective in suppressing the development of contact sensitivity and adjuvant arthritis in rodent models. Based on the antiproliferative and immunosuppressive capacity of BQR, we have evaluated the efficacy of BQR in preventing allograft rejection utilizing experimental models of heterotopic heart and kidney and orthotopic liver transplantation in an MHC and non-MHC mismatched ACI----LEW rat strain combination. The immunosuppressive activity of BQR is illustrated by its ability to inhibit the development of delayed-type hypersensitivity to DNFB in mice. When BQR was administered orally throughout the sensitization and elicitation phases of the DNFB contact sensitivity response, it was found to be a potent immunosuppressant with an ED50 value of 0.5 mg/kg. This immunosuppressive activity is also seen in vitro, where BQR is capable of inhibiting the mixed lymphocyte response between allogeneic ACI and LEW rat strains with an IC50 of 150 ng/ml. The immunosuppressive activity of BQR is highly effective in prolonging heart, liver, and kidney allograft survival in the rat. Cardiac allografts are not rejected during the period of drug treatment at dosage levels of 12 to 24 mg/kg orally three times weekly. The grafts survive until the drug is discontinued (30 days posttransplantation), and the grafts are then rejected approximately 14 days later. Liver and kidney allografts are permanently accepted by approximately 50 to 90% of the recipient rats following 30 days of treatment with BQR at 12 mg/kg. The tolerance that is induced to the liver grafts extends in the majority of animals to greater than 250 days and is specific for the donor ACI strain. Challenge of long-term liver graft survivors with donor cardiac grafts is associated with permanent survival of donor, but not third-party, heart grafts. Combination therapy consisting of suboptimal doses of BQR and CsA demonstrates that the combination of these two immunosuppressive drugs results in an increased efficacy in prolonging graft survival. The results of these allograft experiments demonstrate that this new immunosuppressive agent is highly effective in preventing allograft rejection in the rat. The antiproliferative activity of BQR is effective for inhibiting T-lymphocyte-mediated immune responses, and Brequinar sodium should be an important addition to a polytherapeutic approach in the treatment of organ graft rejection.

Animals↗
PubMed1992

The prolongation of concordant hamster-to-rat cardiac xenografts by brequinar sodium.

Brequinar sodium (BQR) prevents cell proliferation by virtue of its inhibition of de novo pyrimidine biosynthesis. The immunosuppressive activity of BQR is highly effective in prolonging heart, liver, and kidney allograft survival in the rat. In these experiments, we have tested the ability of BQR to prevent the rejection of concordant cardiac xenografts. LEW inbred rats transplanted with heterotopic hamster hearts were treated orally with brequinar sodium as a single agent. The survival of the cardiac xenografts was significantly prolonged with a variety of treatment regimens. The most effective treatment was the daily oral administration of BQR at 3 mg/kg. At this level, the median graft survival was approximately 25 days. Four animals had hamster heart xenografts that functioned for more than 90 days. The prolonged survival of the xenografts was associated with relatively constant plasma drug levels of approximately 1 to 3 micrograms/ml and a marked suppression of IgM production. At rejection, there was a significant rise in IgM levels compared with those of recipients with stable xenografts. In vitro MLR responses were effectively inhibited by BQR, with an IC50 of 0.08 microgram/ml. The results of these experiments demonstrate that BQR is a new immunosuppressive agent that is highly effective as a single agent in prolonging the survival of hamster-to-rat cardiac xenografts. The prolonged xenograft survival is associated with effective suppression of rat antihamster antibody production, suggesting that brequinar sodium may be an important addition to multidrug immunosuppressive regimes designed to prevent B and T lymphocyte-mediated immune responses.

Animals↗
PubMed1992

Relationship between the dose and whole blood level of cyclosporine after liver and kidney transplantation.

Descriptions of the immunosuppression protocols used after organ transplantation typically refer to the dose of cyclosporine (on a per weight basis) given to patients. In actual clinical practice, however, the amount of cyclosporine given to patients is determined principally by the concentration of the drug present in blood. In this study we determined the correlation between the dose of cyclosporine prescribed and the level of cyclosporine achieved in stable organ recipients three or more months following successful grafting. Seventy-five adult liver transplant recipients and 65 kidney transplant recipients who survived for more than three months after the transplant and who had stable graft function were included in the analysis. The cyclosporine dose and the cyclosporine level at the first out-patient visit were recorded for each patient. The median dose of cyclosporine used in liver recipients was 15 mg/kg/day. Seventeen percent of liver transplant recipients were on a maintenance dose of cyclosporine of less than 12 mg/kg/day. Fifteen percent were on a maintenance dose of greater than 22 mg/kg/day. The median dose utilized by kidney transplant recipients was 15 mg/kg/day. Twenty-eight percent of kidney recipients were on a maintenance dose of less than 12 mg/kg/day while 9% were taking more than 22 mg/kg/day. The median whole blood cyclosporine level in liver recipients was 1025 ng/ml (range 18-1925 ng/ml). The median level in kidney recipients was 542 ng/ml (range 79-1451 ng/ml). The majority of the liver and kidney recipients had cyclosporine levels within standard "therapeutic" ranges reported for each type of transplant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Clinical effects of a sorbent suspension dialysis system in treatment of hepatic coma (the BioLogic-DT).

Fifteen patients with acute deterioration of liver function, high serum ammonium, and an average coma level of 3.9 were identified. Eleven of the patients were on respirator support, and eleven had kidney failure pursuant to the liver failure. The patients were treated for 8-12 hours daily with the BioLogic-DT system, in which membranes of a cellulosic plate dialyzer actively pump blood through a single access at over 200 ml/min, and the dialysate contains a suspension of powdered activated charcoal (300,000 square meters surface area) and cation exchanger (160 meq capacity). No anticoagulant was used. In spite of the declining condition of the patients prior to treatment, there was a statistically significant improvement in neurologic status during individual treatments, and a positive trend over 1-12 (average four) daily treatments. Four patients recovered liver function and another four improved enough to receive a liver transplant operation. The BioLogic-DT system appears to be safe in treatment of patients with hepatic insufficiency and coma. The neurologic improvement of these patients indicates that many toxins of hepatic failure are dialyzable across cellulosic membranes and bound by charcoal.

Acute Disease↗
PubMed1991

Improved method of porcine renal allografting for transplantation research.

This study presents a refined, reproducible, and clinically appropriate animal model of renal transplantation. A pair of kidneys are harvested from a donor pig and preserved in Euro-Collins' solution (4 degrees C). After a set period of preservation, the allografts are transplanted to two recipient pigs. The abdomen is entered through a midline incision. The right common iliac artery and vein are dissected and bilateral native nephrectomy is performed. Each allograft is then randomly assigned and transplanted to the recipients. Three minutes before unclamping, 100 mg of furosemide and 10 g of mannitol are given IV. Immediately after reperfusion, urine output is measured for 1 h. The allograft is biopsied and ureteroneocystostomy is created. Cystostomy is then placed using a 16F Foley catheter. The bladder neck is ligated to secure complete diversion of urine, and the abdomen is closed in layers. This kidney transplant model allows an absolutely paired study of the kidney allograft function from the same donor and also collection of pure urine at any time postoperatively, obviating the need for metabolic cages or sedation for urinary collection. This model and its unique modifications allow various transplant studies, including organ preservation, immunosuppressive protocol, and the prevention of reperfusion injury from oxygen free radicals.

Animals↗