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Biomedical subjects

E B Silberstein

Publications and source records attributed to E B Silberstein.

At least 73 records · Page 4Linked to original sources

Thrombogenicity of a fibronectin-coated, experimental polytetrafluoroethylene graft.

To determine if pretreatment of polytetrafluoroethylene (PTFE) vascular grafts with fibronectin (FN) increased platelet adherence to them and adversely affected their patency, we labeled autologous canine platelets with indium III-oxine and interposed a FN-coated, experimental, 4 mm inner diameter, 10 cm long PTFE prosthesis into one carotid artery of 10 dogs. An identical graft, lacking only the FN coating, was implanted as a control in the contralateral carotid artery. A second group of 10 dogs was similarly treated, but each animal received 2 grains of aspirin and 50 mg of dipyridamole (Persantine) daily, beginning 3 days before surgery and continuing for the duration of the experiment. By means of a quantitative, gamma-camera, platelet adherence to the grafts was studied for 5 days after implantation. Graft patency was assessed with the Doppler velocity meter and was confirmed by surgical reexploration when thrombosis was suspected. FN coating increased platelet adhesion to the grafts in animals untreated with aspirin by a factor of threefold to fivefold. In those animals receiving antiplatelet drugs, patency of FN-coated grafts at 5 days was significantly (p less than 0.05) higher (80%) than in untreated animals (27.2%). In addition, mean platelet deposition on the grafts in these animals was reduced compared with untreated controls. Thus although FN coating of PTFE grafts significantly increases their affinity for platelets, this effect can be effectively abolished by pretreatment with aspirin and dipyridamole.

Animals↗

Fibronectin coating of an experimental PTFE vascular prosthesis.

Because of the known inefficiency of endothelial cell seeding of vascular prostheses, some investigators have pretreated their grafts with fibronectin in an effort to increase endothelial cell adhesion. However, the most efficient method of coating vascular prostheses with fibronectin has not yet been determined and more importantly, the durability of this coating following restoration of pulsatile perfusion has not yet been established. This experiment measured the adsorption of fibronectin which was perfused at three different concentrations through an experimental, highly porous PTFE vascular graft. Most efficient coating of the prosthetic appeared to occur with a 250 mg/ml concentration of fibronectin perfused through the graft for 60 min. Grafts so prepared were subsequently studied in a pulsatile perfusion system which mimicked the canine circulation. Fifteen additional fibronectin-coated grafts were also interposed in the canine carotid artery. Flow was restored, grafts were removed at varying intervals, and fibronectin disappearance was measured. In both the in vitro and in vivo models, three distinct phases of fibronectin dissociation were seen: an initial rapid loss which resulted in an average 30.5% retention of the initial concentration of fibronectin following 30 min of perfusion; a second phase, which occurred from 30 to 120 min, demonstrated an average 2.5% loss of fibronectin per hour; and a final phase, from 2 to 24 hr, during which no significant additional loss of fibronectin was seen. This study describes a new method by which PTFE vascular prostheses can be effectively coated by perfusing them with physiologic concentrations of fibronectin and demonstrates that the resulting bond between fibronectin and prosthetic is stable following restoration of pulsatile flow.

Adsorption↗

The effect of the thromboxane synthetase inhibitor Dazmegrel (UK-38,485) on wound healing, dermal ink perfusion and skin blood flow measurements in deep partial thickness burns.

A guinea-pig model was used to evaluate the effect of Dazmegrel (UK-38,485), a new highly selective inhibitor of thromboxane synthetase, on burn wound healing. Dazmegrel had a beneficial effect on wound healing when given systemically at a dosage of 3.4 mg kg-1 day-1 but higher doses had no effect. There was no change in dermal perfusion measured by India ink injection or by 133Xe injection in any of the groups receiving parenteral Dazmegrel. Neither was the number of hair follicles in the healing burn wound significantly different between the treated and control animals. When Dazmegrel was applied topically, it inhibited wound healing. These findings are consistent with previous reports from different laboratories that prostaglandin inhibitors impair healing of the burn wound when applied topically but improve wound healing when given parenterally. The present study further suggested that the improvement in wound healing in this model was not mediated by improved dermal perfusion.

Administration, Topical↗

The effect of fibronectin coating on endothelial cell kinetics in polytetrafluoroethylene grafts.

Despite the proven experimental success of endothelial cell seeding of prosthetic vascular grafts, the process has not been widely accepted for clinical use because of its complexity and the need for a relatively large length of autologous vein to provide the requisite number of cells. Using autologous endothelial cells radiolabeled with indium 111-oxine, we studied the effect of fibronectin coating of polytetrafluoroethylene grafts in a canine carotid interposition model on initial endothelial cell adherence and subsequent cell retention for up to 72 hours following restoration of blood flow. Since the number of harvested endothelial cells varied widely depending on the diameter and length of available vein, cellular adherence was best expressed as a percentage of the original cell harvest. More than twice as many (46.7% vs. 19.8%) endothelial cells initially adhered to fibronectin-coated grafts compared with uncoated control grafts. Fibronectin did not appear to influence the loss of cells within the first 30 minutes following restoration of blood flow. However, over the next 24 hours, it clearly reduced the mean cell loss from 3.7%/hr to 2.2%/hr and resulted in a sixfold increase (21.3% vs. 3.4%) in the number of retained cells at the end of a 24-hour period. When the endothelial cell preclot was performed with a solution of culture medium 199, as opposed to heparinized whole blood, there was no significant difference in endothelial cell retention.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Strontium-89 therapy for the pain of osseous metastases.

A Phase I and II study has been conducted of the safety and efficacy of 89Sr (injected i.v. as the chloride) to alleviate bone pain due to osseous metastatic disease. Potential attendant hematologic toxicity was also examined. Strontium-90 impurities were always less than 1.5%, employing a new quality control technique which detects the 90Y "daughter". Thirty-eight patients with pain due to osseous metastases requiring regular narcotic more than twice a day, documented by an abnormal bone scan and radiography, received 45 doses (1-4.5 mCi, 16-70 microCi/kg) of 89Sr after informed consent. The performance status (Karnofsky scale) ranged from 20-80%. One patient had complete pain relief while 22 other doses yielded at least a 25% reduction in narcotic requirement lasting at least 1 mo and/or 20% improvement in Karnofsky scale rating. Two patients had marked to complete relief in tumor sites which were not fractured, with no change in fracture pain. Twenty-two did not respond. Response was independent of narcotic requirements, tumor type, or Karnofsky status. No hematologic toxicity occurred. Strontium-89 may be useful as adjuvant therapy for diffuse bone pain, but a double-blind study comparing it to other nonnarcotic modalities is required.

Bone Neoplasms↗

Indium 111 toxicity in the human lymphocyte.

Indium-labeled lymphocytes were examined for response to a variety of mitogens, ability to synthesize immunoglobulins, mitotic index, and presence of chromosome aberrations at a range of exposures from 0.2 to 500 muCi/10(8) cells. Results of all four tests were found to be abnormal when the lymphocytes were labeled with 111In activities well within those employed for diagnostic testing.

Cell Survival↗

Reverse redistribution phenomenon in thallium-201 stress tests: angiographic correlation and clinical significance.

The reverse redistribution phenomenon (RR) with the apparent worsening of a stress-induced defect or appearance of a new area of relative hypoperfusion does not always indicate coronary artery disease as previously suggested. RR does not correlate closely with the degree of coronary artery disease, nor with the location of the stenosis. Multiple mechanisms are hypothesized wherein the "defect" may be located in the best or worst perfused area.

Coronary Angiography↗

Kinetics of endothelial cell seeding.

Endothelial cell seeding improves patency of small-diameter Dacron grafts and facilitates the development of a complete endothelial flow surface. However, the ideal number of cells relative to the length of graft to be seeded has not been determined. With a canine model previously shown to result in a well-endothelialized graft within 4 to 6 weeks, this study measured the quantity of autogenous endothelial cells labeled with indium 111-oxine that initially adhered to 10 cm long, experimental, porous 4 mm I.D. polytetrafluoroethylene grafts and then calculated their subsequent disappearance following implantation as carotid interposition grafts. Graft radioactivity was monitored with a gamma camera and compared with that of control vials of indium 111 implanted in the same animals. Counts were measured immediately at implantation and for up to 72 hours following restoration of flow. Data were analyzed by linear regression. The mean number of harvested endothelial cells was 6.2 X 10(5). A mean of 19.8% of the harvested cells were adherent to the grafts initially after seeding. In the first 30 minutes following restoration of flow, there was a rapid loss of these cells to a mean value, which was 70.2% of those initially present. From 30 minutes to 24 hours, cell losses continued at a constant rate of 3.7%/hr (r = -0.922, p less than 0.001). Beyond 24 hours, further loss was insignificant. Consequently, approximately 2.72 X 10(4) cells, or only 4.4% of all cells originally harvested, appear adequate to seed 12.5 cm2 of graft.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Treatment of polycythemia vera with hydroxyurea.

Conventional treatment of polycythemia vera (PV) with radioactive phosphorus or alkylating agents is associated with a significant excess of acute leukemia and cancer of the gastrointestinal tract and skin. There is thus a need for a nonmutagenic agent in the treatment of this disorder. Hydroxyurea (HU) was administered to 118 patients with a loading dose of 30 mg/kg/day for 1 week, which was then reduced to 15 mg/kg/day. Initial control of the elevated hematocrit and platelet count was achieved within 12 weeks in over 80% of patients. Long-term disease control was defined and the accumulative 1-year failure-free survival was 73% in the previously untreated patients and 59% in those patients previously treated with other myelosuppressive modalities. The HU was well tolerated and cytopenia, which generally occurred within the first 8 weeks of therapy, was transient and of little clinical significance. However, it is recommended because of this toxicity that HU be administered initially at a dose of 15-20 mg/kg/day. Three patients developed acute leukemia; two were untreated and one had had myelosuppressive therapy. Hydroxyurea is an effective agent in the treatment of PV, but continued assessment of its mutagenic potential is necessary.

Acute Disease↗

Venous uptake of 201T1 as thallous chloride.

Thallium-201, injected as thallous chloride, has been found to adhere to or be taken up by the vein into which it is injected, permitting images to be obtained of human veins up to 4 h following injection. A digoxin-insensitive rat vein model also retained 201Tl but for shorter periods of time. 201Tl uptake is independent of the solution into which it is introduced, whether 5% dextrose or 0.9% sodium chloride. This technique permits multiple delayed views of normal veins to be obtained but is of uncertain value in the evaluation of thrombophlebitis of the calf because of rather poor resolution and high cost.

Animals↗

Laminectomy: effects on postoperative technetium and gallium scintigraphy.

Bone scans using Tc-99m diphosphonate were found to become abnormal within 2 weeks after laminectomy in less than half of patients regardless of the extent of the operation. The degree of new uptake equaled that of the sacroiliac joints in only one of 19 patients with a normal preoperative scan. However, the Ga-67 citrate scan usually became abnormal (89%) postoperatively. Thus the Tc-99m bone scan may be helpful in detecting postoperative infection.

Diphosphonates↗

Tc-99m diphosphonate and sulfur colloid uptake by the spleen in sickle disease: interrelationship and clinical correlates: concise communication.

To determine the clinical significance of splenic uptake in bone scintigraphy and functional asplenia on the radionuclide liver-spleen image, bone and spleen scintigrams of 38 patients with sickle cell disease were reviewed. Eighteen underwent bone and liver-spleen studies, 15 had only bone images, and five had only liver-spleen studies. Sixteen of 33 who had bone scintigraphy showed splenic uptake, but the frequency of homozygous sickle cell (SS) disease was not greater than heterozygous sickle cell disease (S-hetero) in this group. SS patients with splenic uptake of Tc-99m diphosphonate had significantly fewer painful crises of the abdomen and extremities, and fewer inpatient and outpatient hospital visits than SS patients whose bone imaging did not visualize the spleen. Functional asplenia on liver-spleen images (16 cases) was seen only in SS disease. One SS patient, age 8, still had a spleen capable of phagocytizing colloid.

Adolescent↗

Brain scintigraphy in the diagnosis of the sequelae of head trauma.

Computed transaxial tomography (CTT) has become the major imaging tool in the evaluation of any intracerebral lesion, including those due to traumatic injury. Expense and availability sometimes dictate that radionuclide brain scintigraphy (RBS) be performed in place of CTT. Certain situations exist where RBS may be used as a primary tool. These include circumstances where assessment of brain perfusion may be essential, e.g., determination of brain death. Radionuclide cisternography still remains useful in evaluating patients with normal pressure hydrocephalus and cerebrospinal fluid leakage.

Brain Death↗

In vivo chemotaxis and body compartment distribution of indium-111 labelled polymorphonuclear leukocytes in burned guinea pigs.

The in vivo chemotactic response of Indium-111 labelled polymorphonuclear leukocytes (PMNL) and their body compartment distribution have been studied in burned (30% TBSA full-thickness burn) and normal guinea pigs. The in vivo chemotactic response to FMLP 10(-5) M and to zymosan-activated serum of the burned PMNL was not significantly different from that of normal PMNL. However, the burned PMNL leave the circulation more rapidly and localize in the burn area and in the liver to a greater extent. No evidence of increased destruction of burned PMNL by the spleen or by the lungs was found.

Animals↗