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Biomedical subjects

F V Lucas

Publications and source records attributed to F V Lucas.

At least 37 records · Page 2Linked to original sources
PubMed1986

Peripheral artery and bypass graft thrombolysis with recombinant human tissue-type plasminogen activator.

Recombinant tissue-type plasminogen activator (t-PA) is a DNA-synthesized thrombolytic agent recently approved for clinical trials. We present the results of t-PA infusions in 18 patients with thrombosed peripheral arteries (12 patients) and peripheral bypass grafts (six patients). The duration of occlusion ranged from 1 to 21 days (mean, 6.8 days). Infusions of t-PA were done by way of an intra-arterial approach at a dose of 0.1 mg/kg/hr. All patients demonstrated thrombus lysis angiographically. Fifteen of 18 (83%) had clinical as well as angiographic improvement. Secondary procedures to maintain patency of the arterial segment were required in seven patients. No complications occurred that were related to the t-PA infusion. No significant prolongation of the prothrombin, thrombin, or activated partial thromboplastin times occurred. At the end of t-PA infusion, the mean circulating fibrinogen level was 59% of the starting value. The therapeutic use of t-PA is still in its preliminary stages and the efficacy and safety of this promising agent need to be further established. From our early experience with t-PA, it appears to be safe as well as effective.

Adult↗
PubMed1986

Recombinant human tissue-type plasminogen activator for thrombolysis in peripheral arteries and bypass grafts.

Recombinant human tissue-type plasminogen activator (rt-PA) was infused intraarterially at 0.1 mg/kg/h for 1-6 1/2 hours in 25 patients with lower extremity thromboembolic occlusions (13 thrombosed arteries, 12 thrombosed bypass grafts). Occlusion duration ranged from 1 hour to 21 days. Thrombolysis occurred in 23 of 25 patients (92%). Time to lysis varied from 1 to 6.5 hours, with an average time of 3.6 hours. Twenty of 23 patients (87%) in whom thrombolysis was successful benefited clinically from thrombolytic therapy. Twelve of 23 patients (52%) required secondary procedures to maintain arterial segment patency. In 15 of 25 patients (60%) fibrinogen levels were maintained above 50% of baseline values. No major complications directly attributable to rt-PA infusions occurred. rt-PA is a potent, relatively fibrin-specific thrombolytic agent that can achieve rapid thrombolysis while usually avoiding the profound systemic fibrinogenolysis associated with currently available thrombolytic agents.

Adult↗
PubMed1986

Pharmacodynamics of tissue-type plasminogen activator characterized by computer-assisted simulation.

Prospective characterization of pharmacodynamics of tissue-type plasminogen activator (t-PA) is needed for diverse clinical applications. Accordingly, we used physiologically based, computer simulation of participating biochemical reactions in response to concentrations of circulating t-PA seen with infusions of 1 to 7 hr duration in 45 patients. Predicted values were compared with those from a "training set" obtained in six patients given t-PA for coronary thrombosis and six receiving therapy for peripheral arterial occlusion. Subsequently, results of simulation were compared prospectively with observations from a "test set" of 33 consecutive patients given low doses of t-PA for as long as 7 hr or higher doses for 1 to 2 hr and with data from 101 patients given t-PA in the European Cooperative Trial. Fits between observed and predicted values were close. Based on observations in the training set, the alpha 2-macroglobulin reaction with circulating plasmin and ongoing synthesis of plasminogen were incorporated in the simulations. Fibrinogenolysis in vitro was documented despite supplementation of samples with aprotinin, particularly when concentrations of t-PA were high. This phenomenon can lead to overestimation of fibrinogen depletion and was found to be obviated by the use of PPACK, a novel serine protease inhibitor. Results indicate that the simulation approach developed permits economic, prospective evaluation of regimens of t-PA suitable for diverse conditions and delineation of the impact of individual constituents and reactions on pharmacodynamics of t-PA and on the risk of induction of a systemic lytic state.

Adult↗
PubMed1986

Thrombolysis with recombinant human tissue-type plasminogen activator in patients with peripheral artery and bypass graft occlusions.

Thirty-three patients with thrombosed peripheral arteries and bypass grafts, as confirmed by angiography, were treated with recombinant human tissue-type plasminogen activator (rt-PA). Twenty-six patients were treated with a dose of 0.1 mg/kg/hr and seven patients with 0.05 mg/kg/hr. Thrombus lysis and clinical improvement occurred in 22 of 26 (85%) patients in the 0.1 mg/kg/hr group. In seven of seven (100%) patients in the 0.05 mg/kg/hr group angiographic as well as clinical improvement were observed. Fifteen of the 33 patients required anticoagulation to maintain patency. Sixteen required secondary procedures to maintain patency. One (3%) patient required a blood transfusion for a hematoma at the catheter entry site. Three other patients developed small hematomas that were controlled without transfusion or intervention. Sixty-one percent of patients treated with the 0.01 mg/kg/hr dose and 86% of patients treated with the 0.05 mg/kg/hr dose maintained fibrinogen levels greater than 50% of their initial values. Infusion durations ranged from 1 to 6 hr (mean 3.9 hr). rt-PA appears to be a potent and selective thrombolytic agent that rapidly and safely lyses thrombi in peripheral arteries and occluded bypass grafts.

Adult↗
PubMed1986

Intravenous administration of prostacyclin in rabbits: elimination kinetics and blood pressure response.

Prostacyclin (PGI2) has been used extensively in human clinical trials and animal studies, but because of its instability, knowledge of its pharmacokinetics has progressed slowly. We assayed plasma PGI2 concentrations with a quantitative chromatographic method following bolus intravenous injection and during continuous infusion in rabbits. Blood pressure response was correlated with plasma PGI2 concentrations and compared with the concentrations necessary to inhibit platelet aggregation in vitro. A two-compartment model was used to analyze the elimination kinetics for PGI2 after a single injection. The half-life of the terminal elimination phase was 2.7 minutes. The calculated systemic clearance and whole body volume of distribution were 93 ml/kg/min and 357 ml/kg, respectively. During continuous infusion, steady-state plasma concentrations were reached within 15 minutes and increased linearly with increasing infusion rate from 4.2 to 604 ng/kg/min, which resulted in PGI2 concentrations of 0.06 +/- 0.01 to 7.6 +/- 2.1 ng/ml, respectively. At steady-state plasma concentrations of PGI2 greater than 0.1 ng/ml, the mean arterial blood pressure decreased in a concentration-dependent manner, reaching a decrease of 45 mm Hg when the plasma concentration was 7.6 ng/ml. Prostacyclin caused a concentration-dependent inhibition of adenosine diphosphate-induced platelet aggregation in vitro with 10% inhibition at 0.4 ng/ml. These results indicate that in the rabbit the level of PGI2 at which the onset of hypotension occurs coincides with the inhibition of platelet aggregation.

Animals↗
PubMed1985

Platelet glutathione and thromboxane synthesis in diabetes.

The relationship of the reduced glutathione (GSH) content in unstimulated platelets and their capacity to synthesize thromboxane A2 (TXA2), measured by radioimmunoassay of TXB2, was investigated in diabetic and matched control subjects. The GSH content in platelets from diabetic subjects (6.52 +/- 0.73 microgram/10(9) platelets, mean +/- SD) was significantly (P less than 0.001) lower than in platelets from control subjects (10.10 +/- 1.58 microgram/10(9) platelets). When platelet-rich plasma (PRP) was stimulated with 1.65 mM arachidonic acid, significantly (P less than 0.001) more TXB2 was formed in PRP from diabetic subjects (344 +/- 87 ng/2.5 X 10(8) platelets) than in PRP from control subjects (132 +/- 35 ng/2.5 X 10(8) platelets). Furthermore, the plasma level of TXB2 was increased in diabetic subjects (522 +/- 117 pg/ml) in comparison with control subjects (187 +/- 63 pg/ml). An inverse correlation (r = 0.98) was observed between the GSH content in unstimulated platelets and their capacity to synthesize TXA2 when stimulated with 1.65 mM arachidonic acid. These data suggest that platelet GSH may have an important regulatory effect on platelet TXA2 synthesis and that increased TXA2 synthesis by platelets from diabetic subjects may be the result of low intracellular GSH levels.

Adolescent↗
PubMed1984

Immunophenotypic characterization of acute leukemia by immunocytology.

The potential for specific immunophenotypic characterization of the acute leukemias has been enhanced greatly by the development of monoclonal antibodies. Currently, this immunologic data is obtained most commonly by flow cytometric analysis or cellular cytotoxicity assays. The former is an expensive technic that lacks morphologic evaluation unless cell sorting is performed. The latter precludes morphologic assessment by the nature of the assay. The authors have developed an immunostaining procedure utilizing cytospin preparations and immunoperoxidase methods that are relatively inexpensive and allow simultaneous assessment of the immunologic markers and cellular morphology. Although a comparison of flow cytometry and immunocytology revealed quantitative differences for individual cell surface markers, the "qualitative" immunologic phenotype of the leukemic population was virtually identical by the two technics.

Acute Disease↗
PubMed1984

Thromboxane synthetase inhibition in acute focal cerebral ischemia in cats.

The purpose of this investigation was to study the effects of a selective thromboxane A2 (TXA2) synthetase inhibitor (TSI) upon the evolution of cerebral infarction in the cat. Adult cats, lightly anesthetized with nitrous oxide, underwent right middle cerebral artery (MCA) occlusion for 4 hours followed by a 2-hour period of reperfusion before sacrifice. Ten cats received 3 mg/kg TSI intravenously immediately before, and 10 cats received 3 mg/kg TSI intravenously immediately after MCA occlusion. Ten cats were used as controls receiving no treatment. The bleeding time was determined at baseline and at the end of each experiment. Electroencephalographic (EEG) recordings were obtained before and after MCA clipping and MCA release, and at hourly intervals thereafter. Regional cerebral blood flow (rCBF) was measured using the xenon-133 (133Xe) clearance technique before and after MCA occlusion, after MCA reopening, and before terminating each experiment. Thirty minutes before each cat was sacrificed, Evans blue dye and sodium fluorescein were given intravenously. The animals were then perfused with colloidal carbon and the brains removed and evaluated for midline shift. Evans blue dye and sodium fluorescein extravasation, carbon staining, and infarct size. The bleeding time, arterial blood pressure, rCBF changes, brain swelling, and vital dye extravasation were not statistically different between the three treatment groups. The EEG changes, carbon staining, and infarct size differences between the three groups also failed to reach statistical significance, but there was a suggestion that these parameters were adversely affected in the cats pretreated with TSI. Ten additional cats undergoing MCA occlusion and reperfusion were used for pharmacological studies. Five of them received 3 mg/kg TSI intravenously immediately after MCA occlusion, and serial drug and thromboxane B2 (TXB2) levels (a stable metabolite of TXA2) were determined. Another five cats were not treated and serial TXB2 levels were obtained. Production of TXA2 was inhibited by 95% in cats receiving TSI. In conclusion, thromboxane synthetase inhibition failed to modify favorably the evolution of cerebral infarction. When TSI was given before MCA occlusion, cerebral infarction tended to be more extensive.

Animals↗
PubMed1982

A comparative study of the use of fluorescein and the Doppler device in the determination of intestinal viability.

Fluorescein is a reliable indicator of mucosal viability in dogs. This fact is probably applicable to humans. The Doppler device was not a reliable predictor of intestinal nonviability, and in the instance of mesenteric venous occlusion, with ischemic intestine, it was totally inaccurate in assessing intestinal viability. Short segments of intestine failing to take up fluorescein stain will retain viability, owing to the lesser nutrient requirements of resting smooth muscle. However, segments should not be used for anastomoses, since the mucosa will, to some degree be ischemic.

Animals↗
PubMed1981

Platelet-bound IgG in systemic lupus erythematosus with and without thrombocytopenia.

A new assay for IgG bound to autologous platelets is described, in which IgG is dissociated from platelets washed at low pH, then measured by radioimmunoassay. Platelet-bound IgG was found to be elevated in thrombocytopenic patients with SLE and reduced in non-thrombocytopenic patients with this disease. There was a close inverse correlation of platelet-bound IgG and platelet count. Immune complexes did not interfere with the assay.

Antigen-Antibody Complex↗
PubMed1981

Isolation of prostacyclin from whole blood.

A method was development for the isolation of prostacyclin (PGI2) from whole blood in a fraction suitable for high pressure liquid chromatography (HPLC) separation of PGI2 and 6-keto-prostaglandin F1 alpha (6-K-PGF1 alpha). Prostacyclin was stabilized in whole blood by rapidly raising the pH to 10 with Na2CO3 and cooling the samples to 0 degree C. Under these conditions, 2.9% hydrolysis was observed after 20 min. Reverse phase extraction columns were used to directly extract both PGI2 and 6-K-PGF1 alpha from the alkaline plasma with recoveries of greater than 95% using an acetonitrile/2mM Na2B4O7, pH 10, 40/60 elution solvent mixture. An additional 1.7% hydrolysis was found during the column extraction procedure. Final separation of PGI2 and 6-K-PGF1 alpha was performed with HPLC using an alkaline solvent system. This method is capable of rapidly and efficiently extracting and separating PGI2 and 6-K-PGF1 alpha from whole blood or plasma. It introduces less than 5% hydrolysis of PGI2, thus providing a means of applying highly sensitive 6-K-PGF1 alpha assays to the determination of PGI2 levels in physiological samples.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Alternate chromogens as substitutes for benzidine for myeloperoxidase cytochemistry.

Myeloperoxidase staining methods for classification of leukemias have traditionally employed benzidine dihydrochloride as the chromogen. Recent Occupational Safety and Health Administration regulations have classified benzidine as a carcinogen, which severely restricts its use in the clinical laboratory. Twenty-two specimens from normal control subjects and leukemia patients, previously classified by FAB criteria, were stained with benzidine and two alternate chromogens, diaminobenzidine and Hanker-Yates reagent (p-phenylenediamine and pyrocatechol). In a random, blind fashion, three experienced observers scored the stains from each case according to quality of smear, degree of peroxidase positivity, tinctorial distinction between nucleus and cytoplasm, and overall acceptability of the stain. All three observers rated the substitute chromogens as adequate for routine myeloperoxidase cytochemical staining. It is concluded that either of the methods studied would have clinical utility and can substitute for benzidine as a myeloperoxidase chromogen.

Benzidines↗
PubMed1981

Morphology and cytochemistry of "microgranular" acute promyelocytic leukemia (FAB M3m).

Three cases of a newly recognized "microgranular" variant of acute promyelocytic leukemia (FAB M3) are described. This poor-prognosis variant is easily confused with myelomonocytic (M4) or monocytic (M5) leukemia, but is associated with disseminated intravascular coagulation as is "hypergranular" M3. Such patients may be inappropriately treated unless the promyelocytic nature of the leukemia is recognized.

Adolescent↗