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Biomedical subjects

R Nowygrod

Publications and source records attributed to R Nowygrod.

At least 55 records · Page 3Linked to original sources

A new method for the direct incorporation of antibiotic in prosthetic vascular grafts.

A procedure for the bonding of antibacterial agents directly to prosthetic vascular grafts has been developed. This method does not involve the use of carriers or surfactants which may cause local toxicity or thrombogenesis. Using this procedure, antibiotics can be bonded to the graft alone or in combination with a metal, such as silver. Incorporation of silver along with the antibiotic enhances the antibacterial activity and prolongs retention of the antibiotics in the prosthetic grafts. Silver mediated bonding appears to release the antibiotic biphasically. In the initial phase (40 to 50 per cent), the drug is rapidly released and, in the second phase, the rest is diffused gradually enabling the graft to retain antibacterial activity for a longer period of time.

Animals↗

Common iliac artery-ureteral fistula: case report and literature review.

Arterial-ureteral fistulas are rare complications of iliac artery reconstruction or ureteral manipulation. The diagnosis should be considered in patients with intermittent hematuria who have had ureteral catheterization, arterial bypass, or nephrectomy. The following case demonstrates the difficulty in making the diagnosis preoperatively. A review of the literature and alternative methods of surgical management are described.

Aged↗

Selective lymphoid irradiation. V. Synergism with pretransplant thymectomy or thymic irradiation in cardiac transplantation in rats.

Selective lymphoid irradiation (SLI) using palladium-109-hematoporphyrin (Pd-H), given four days prior to transplantation, combined with two doses of antilymphocyte globulin (ALG) (10 mg, days -2 and -1), was evaluated as a method of induction of permanent heterotopic cardiac allograft survival in the highly histoincompatible rat strain combination of ACI (RT1(1))-to-Lewis (RT1a). Both Pd-H and ALG localize poorly in the thymus, so this study evaluated whether thymic irradiation (TI) or thymectomy (TX) of the adult recipient results in indefinite allograft survival. Immunosuppression with Pd-H or ALG alone gave a mean survival time (MST) of 6.7 +/- 0.6 days, but the combination of the two agents led to an MST of 17.6 +/- 3.4 days. When TI was combined with Pd-H and ALG, cardiac allograft survival was prolonged to 50.2 +/- 13.9 days, but TI alone showed an MST of 10.3 +/- 1.8 days. Permanent cardiac allograft survival (greater than 250 days) was achieved in all thymectomized recipients treated with the combination of Pd-H and a brief course of ALG. These animals also accepted second-set skin grafts and rejected third-party skin grafts following more than 150 days of ACI cardiac allograft survival. Thymic irradiation, although effective in acting synergistically with SLI and ALG, led to prolonged, but limited allograft survival, although thymectomy with SLI and ALG is synergistic in prolonging allograft survival permanently without chronic immunosuppression.

Animals↗

Selective lymphoid irradiation and cyclosporin A in rat heart allografts.

Short-term peritransplant treatment utilizing 2-dose ALG and 1-dose Palladium-109-hematoporphyrin (PD-H) for selective lymphoid irradiation (SLI) leads to donor-specific permanent acceptance of heart allografts in the Fisher to Lewis rat model. The same treatment significantly prolongs survival of hearts transplanted to strongly histoincompatable , presensitized, and xenogeneic recipients. The purpose of this study was to evaluate synergistic effects of short-term, low-dose cyclosporin treatment and SLI in an attempt to develop a nontoxic protocol utilizing peritransplant treatment for immune preconditioning with minimal subsequent immunosuppression. Single-agent treatment alone with cyclosporin, ALG, or Pd-H resulted in a maximal mean graft survival time (MST) of 33 days. Immunosuppression with 1-dose Pd-H, 2-dose ALG, and low-dose cyclosporin (5 mg/kg) for 14 days doubled the MST to 78 days. Use of therapeutic-dose cyclosporin (20 mg/kg), given for just 3 days, was also quite effective, MST of 57 days with SLI and 43 days with ALG, but toxic; 3 of 12 recipients died of infection with functioning grafts. These results demonstrate that the use of low-dose cyclosporin over a short interval, when combined with peritransplant SLI, is a highly effective and safe method for prolonging heart allograft survival.

Animals↗

Simple methods for direct antibiotic protection of synthetic vascular grafts.

Two simple methods for direct antibacterial protection of synthetic vascular grafts were investigated. In the first protocol the highly protein-bound antibiotics nafcillin (90% protein bound), cefazolin (80%), and cefamandole (70%) were added directly to preclotting blood. Knitted Dacron grafts preclotted in the presence of one of these drugs absorbed significant amounts. Although at high concentrations these antibiotics exhibited anticoagulant effects, significant antibacterial protection was obtained at lower antibiotic levels. Washing treated grafts for 6 hours failed to eliminate the antibacterial activity. Antibiotics remained on the grafts for at least 96 hours. In the second protocol knitted Dacron grafts were soaked in a suspension of silver-pefloxacin, a silver-nalidixic acid analogue with intense antistaphylococcic activity. Using 110Ag-labeled complexes, significant antibiotic activity was documented on the graft after 19 days of washing. Four nafcillin-treated prostheses, six silver-pefloxacin-coated grafts, and 11 control grafts were interposed in the infrarenal aorta of dogs and immediately challenged with an intravenous infusion of 1 X 10(7) Staphylococcus aureus. None of the four nafcillin-treated grafts was infected at 3 weeks. One of the six silver-pefloxacin-coated grafts grew staphylococci, and 9 of 11 controls had positive graft cultures for Staphylococcus when harvested. These studies suggest that prosthetic grafts can be simply coated at the time of implantation with antibiotics selected for appropriate binding and antibacterial characteristics to obtain an infection-resistant prosthesis.

Animals↗

Long-term function of duct-ligated and free-duct whole pancreas transplants.

This report compares endocrine and exocrine responses of "free-duct" and "duct-ligated" whole pancreas isografts in Lewis diabetic rats during a 1-year period of observation. Fasting blood sugar, serum amylase, serum insulin, pancreozymin-secretin test, and L-arginine tolerance test assays were performed prior to and at periodic intervals after transplantation. Histological examinations of transplanted and native pancreas were performed monthly on animals in each group. Whole pancreas transplantations led to immediate and sustained normalization of FBS and insulin levels. In the "duct-ligated" group there was a gradual but insignificant decrease of serum insulin levels after 9 months. Depressed serum amylase levels in diabetic rats were reversed in both groups. Isolated islet iso- and allografts also reversed depressed amylase levels. The results of pancreozymin-secretin tests in islet isografted animals supported the postulated trophic effect of endocrine pancreas on exocrine pancreas. Although both whole-pancreas transplant groups showed a normal response to GTT for 12 months after transplantation, the "duct-ligated" group showed a significantly lower response to L-arginine tolerance test than the "free duct" model as early as 4 months after transplantation, suggesting a defect in B-cell function in long-term "duct-ligated" graft. Serial histological examinations of transplanted pancreases revealed more rapid atrophy and more intense fibrosis of acinar tissue in the "duct-ligated" group than in the "free duct" group. These results suggest that a "free duct" pancreatic isograft maintains a more stable endocrine function in a long-term study than does the "duct-ligated" pancreas, and that exocrine dysfunction in diabetic rats may be related to the endocrine disorder which can be reversed by both islet cell and whole-organ pancreatic transplantation.

Amylases↗

Nonoperative management of a traumatic peroneal artery false aneurysm.

The standard approach to management of traumatic false aneurysms is operative. This report describes successful treatment of a traumatic peroneal artery aneurysm following a gunshot wound in a 29-year-old man by an intraluminal steel coil occlusion technique. The coil was guided through the popliteal artery and aneurysm into the distal peroneal artery via a percutaneously placed catheter: following disengagement of the coil the outflow tract of the aneurysm was occluded, and another passed and released into the proximal peroneal artery occluded the inflow tract.

Adult↗

Use of indium-111-labeled cells in measurement of cellular dynamics of experimental cardiac allograft rejection.

This study evaluates the kinetics and utility of infused indium-111-labeled cells in detecting rejection in ACI to Lewis rat heart allografts. Syngeneic leukocytes, lymph node lymphocytes, and platelets were isolated and labeled with indium-111 (111In) oxine, respectively, and were infused i.v. into Lewis rats carrying beating ACI or syngeneic hearts from post-transplant days 0 to 6. Recipients were imaged serially at 24 hr after infusion of labeled cells followed by excision of both native and transplanted hearts for direct isotope count. Labeled leukocytes accumulative progressively in the allograft with the scan becoming positive by post-transplant day 4. The ratio of allograft to native heart isotope counts rose from 1.25 on day 1 to 10.07 (P less than 0.0001) on day 7. The Lewis recipients infused with labeled lymphocytes showed a positive scan on days 6 and 7 whereas the allograft to native heart isotope count ratio rose from 0.97 on day 1 to 5.33 (P less than 0.001) on day 7. Recipients infused with 111In-labeled platelets showed a positive scan on days 5 to 7 and the allograft to native heart isotope count ratio rose sharply from 2.56 on day 4 to 16.98 (P less than 0.005) on day 7. Syngeneic heart grafts failed to demonstrate significant accumulation of any of the labeled cell population. These studies confirm the importance of nonlymphocytic cells in cellular rejection, evaluate the kinetics of graft invasion by the various cell types, and suggest that the techniques used afford a method for a safe and an early detection of allograft rejection.

Animals↗

Donor pretreatment: rat heart allograft survival and measurement of passenger leukocyte depletion with indium-111.

The present experiment was designed to study the relationship between rat heart allograft survival and passenger leukocyte depletion in donor-pretreated animals. Untreated Lewis rats served as recipients of cardiac allografts from treated Fischer rats. Passenger leukocyte depletion was assayed with indium-111 oxine-labeled leukocytes (predominantly lymphocytes) which were infused into donor rats 6 hr before treatment with cyclophosphamide, antilymphocyte globulin (ALG), sublethal total body irradiation, or in vitro perfusion-preservation of the isolated beating heart. In vivo pretreatment of the donor with cyclophosphamide resulted in a significant prolongation of heart allograft survival but effected no reduction in graft-labeled lymphocytes. In vitro perfusion-preservation of the donor heart, for 1 to 2 hr, led to a 50 to 60% reduction in graft-labeled lymphocytes but failed to significantly prolong the survival of the heart allografts. Both ALG and sublethal total body irradiation donor pretreatments resulted in significant prolongation of heart allograft survival and a 20 to 25% labeled passenger lymphocyte depletion. This study demonstrates that there is no direct correlation between allograft survival and the degree of mobile passenger lymphocyte depletion, suggesting that the efficacy of leukocytotoxic donor pretreatment methods may depend in part on alternative mechanisms.

Animals↗

Selective lymphoid irradiation. I. An approach to transplantation.

The kinetics, distribution, and radiobiologic effects of palladium (Pd)-109-hematoporphyrin were determined in the rat. In addition, we studied the effect on rat heart allograft survival of Pd-109-hematoporphyrin, with and without antilymphocyte serum (ALS). A single sublethal dose of Pd-109-hematoporphyrin (up to 36 muCi/kg) resulted in the following: predominant concentration in lymphoid tissue and proximal bone marrow, complete central and proximal bone marrow ablation with preservation of distal bone marrow, massive depletion of lymphocytes from lymph nodes and spleen, an 80% reduction in peripheral blood lymphocytes which was completed by the addition of ALS, full recovery of lymphoid tissue and blood cellularity within 60 days of administration of radionuclide, and a 100% animal survival rate. This method of selective lymphoid irradiation (SLI) prolongs indefinitely Fisher cardiac allografts in Lewis recipients and significantly prolongs cardiac allograft survival across major histocompatibility barries (ACI to Lewis or to Fisher). Specific tolerance to donor strains was demonstrated by the acceptance of Fisher skin by Lewis recipients carrying 150-day-old Fisher hearts. Third party (ACI) skin allografts were rapidly rejected by the same animals. Further studies of SLI in larger animals are required to determine the optimal safe dose of SLI in man.

Animals↗