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Biomedical subjects

F V Lucas

Publications and source records attributed to F V Lucas.

At least 19 recordsLinked to original sources
PubMed1992

Retained mucosa after double-stapled ileal reservoir and ileoanal anastomosis.

A study was undertaken to assess the incidence of inflammation and dysplasia in retained mucosa after double-stapled ileoanal reservoir (IAR) for mucosal ulcerative colitis (MUC). Between September 1988 and February 1992, 56 patients with MUC underwent an IAR. Forty-five patients had a double-stapled IAR (DS-IAR), seven patients had a transanal pursestring stapled IAR (PS-IAR), and four patients had a PS-IAR with mucosectomy. Distal donuts obtained from the stapled IAR were submitted for pathologic review in 55 patients. Nine patients had only small bowel, connective tissue, and/or muscle noted on review. Mucosa was qualified as squamous epithelium (SE), transitional epithelium (TE), or columnar epithelium (CE). All samples were examined for evidence of inflammation and dysplasia. Four patients had SE only, one patient had TE, and 18 had CE. In addition, three patients had SE and CE, seven patients had SE and TE, two patients had CE and TE, and nine patients had all three types. The distance from the dentate line to the anastomosis ranged from 0 to 2.5 cm (mean, 1 cm). In 19 patients (35 percent), the distal donut revealed MUC. Of these 19 patients, six had persistent MUC (43 percent) at the time of subsequent biopsy. An additional four patients had MUC evident on follow-up biopsy but not on distal donuts; two of these four patients had no mucosa in their distal donuts. Only one of the patients with evidence of MUC on donuts and/or biopsy experienced any symptoms referable to active MUC (1.8 percent). None of the specimens examined had any evidence of dysplasia. In 31 patients, no MUC was present in the initial donuts or follow-up biopsies. Although the double-stapled technique appears safe, periodic monitoring is suggested.

Adolescent↗
PubMed1991

Stroke in a young adult with familial plasminogen disorder.

BACKGROUND: We report a new plasminogen disorder detected in a 29-year-old man with a cerebellar infarct. To our knowledge, plasminogen disorders have not been previously linked with stroke. SUMMARY OF REPORT: Tests for well-recognized causes of stroke were negative. However, a screening hypercoagulation profile indicated low functional levels of plasminogen activity. Immunologic plasminogen (Laurell technique) was 64% of normal (normal level, 80-130%). The rate of plasmin generation induced by adding urokinase to plasma was also low. Plasminogen activator, free protease, and alpha 2-plasmin inhibitor levels were normal. Family studies detected a similar plasminogen abnormality in the patient's mother and 9-year-old son, both of whom are asymptomatic. CONCLUSIONS: Our patient shows a congenital, heterozygous, functionally abnormal plasminogen. Although the exact relationship to stroke is unclear, we suggest screening young patients with unexplained stroke for plasminogen defects using commercially available assay systems.

Adult↗
PubMed1991

Thrombotic thrombocytopenic purpura treated with plasma exchange or exchange transfusions.

Of 40 patients with thrombotic thrombocytopenic purpura, 17 were treated with plasma exchange, 15 with exchange transfusions, and 6 with both types of therapy. One patient died before being treated and another patient was seen but not treated. Plasma exchange was performed daily for a mean of seven exchanges per patient. The replacement fluid during plasma exchange was fresh frozen plasma in all cases. The complete response rates for each type of treatment were as follows: 88% for plasma exchange (15 patients), 47% for exchange transfusions (7 patients), and 67% for exchange transfusions and plasma exchange (4 patients). Clinical and laboratory factors were examined for any statistically significant association with therapy response. Treatment with plasma exchange was statistically the initial factor most strongly associated with prognosis. Paresis, paresthesias, seizures, mental status change, and coma showed no association with response to treatment. Some of the laboratory factors that did not show significant association with treatment response were the initial creatinine, hemoglobin, platelet count, lactate dehydrogenase, and total bilirubin. This study supports the hypothesis that plasma exchange has significantly improved the prognosis of patients with thrombotic thrombocytopenic purpura. These patients should be treated aggressively regardless of the severity of their symptoms.

Exchange Transfusion, Whole Blood↗
PubMed1990

Intravenous nitroglycerin-induced heparin resistance: a qualitative antithrombin III abnormality.

An ability of intravenous nitroglycerin to interfere with the anticoagulant properties of intravenous heparin would have profound clinical implications. To investigation nitroglycerin-heparin interactions, the following pilot study was performed. Patients (N = 18) admitted to the coronary care unit with a diagnosis of either acute myocardial infarction or unstable angina were divided into four treatment groups: (1) intravenous nitroglycerin and intravenous heparin; (2) intravenous nitroglycerin alone; (3) intravenous heparin alone; or (4) neither intravenous nitroglycerin nor intravenous heparin. Serial determinations of activated partial thromboplastin time (APTT), serum heparin concentration, antithrombin III (ATIII) antigen (ATA), and ATIII activity (ATC) were obtained over a 72-hour period. Overall, patients receiving intravenous nitroglycerin did not differ significantly from other patients in APTT, heparin dose, heparin concentration, ATA, ATC, or ATA/ATC ratio (ATR). However, patients receiving intravenous nitroglycerin at a rate exceeding 350 micrograms per minute had a lower APTT (p less than 0.05), lower ATC (p = 0.02), higher ATR (p = 0.004), and a larger heparin dose requirement than patients receiving lower infusion rates. ATR correlated directly (r = 0.91; p less than 0.05) and ATC inversely (r = -0.78; p less than 0.05) with the intravenous nitroglycerin dose. Serum heparin concentration did not correlate with the intravenous nitroglycerin dose. Intravenous nitroglycerin-induced heparin resistance occurs at a critical nitroglycerin dose. A nitroglycerin-induced qualitative ATIII abnormality may be the underlying mechanism.

Adult↗
PubMed1990

Fibrinogen A alpha and gamma-chain dimers as potential differential indicators of atherosclerotic and thrombotic vascular disease.

Cross-linked fibrin(ogen) dimers are known to be elevated in the plasma of subjects with occlusive vascular disease, and are thought to be fibrin dimers. Immunoelectrophoretic analyses of the dimers, however, indicate that (1) they are predominantly fibrinogen rather than fibrin dimers, and (2) they contain cross-linked A alpha-chains (A alpha-dyads) instead of the gamma-chain dyads that are rapidly formed by factor XIII during blood coagulation. Furthermore, the mobilities of the A alpha-dyads differ from the cross-linked alpha-chain products that accompany the gamma-chain cross-linking by factor XIII. Instead, the mobilities coincide with the distinct A alpha-dyads that are produced by tissue transglutaminase, an intracellular enzyme not normally present in plasma. The intimal fibrinogen deposits in atherosclerotic aortas also possess fibrinopeptide A and cross-linked A alpha-chains. Thus, both the plasma fibrinogen dimers and the intimal fibrinogen deposits appear to derive from the action of released tissue transglutaminase more so than factor XIII. It is proposed that, in the absence of other indications of cytolytic processes, the levels of A alpha-dyads in plasma reflect ongoing cellular injury accompanying atherogenesis. The extent to which gamma-dyads accompany the A alpha-dyads may signal progression of the disease to advanced stages in which ulcerations and occlusive lesions trigger thrombotic complications.

Arteriosclerosis↗
PubMed1988

Factor VIII assays. Assessment of variables.

Factor VIII assays are the most common specific coagulation factor assay performed in the United States. Interlaboratory proficiency studies have documented persistent problems with variation in results between laboratories. The Coagulation Resource Committee of the College of American Pathologists conducted a workshop to analyze variables that may affect performance of the one-stage factor assay. The results indicate that accuracy of the assay can be improved by uniform standardization of reference plasma samples and that reproducibility can be enhanced through appropriate choice of reagents and instruments. Optimizing performance of this assay should lead to more reproducible interlaboratory results.

Evaluation Studies as Topic↗
PubMed1988

Thrombolysis of peripheral arterial bypass grafts: surgical thrombectomy compared with thrombolysis. A preliminary report.

Twenty-two patients were selected from a group of 33 patients who underwent recombinant human tissue-type plasminogen activator (rt-PA) thrombolysis for thrombosed infrainguinal bypass grafts of the lower extremity and were compared with 38 matched patients who had undergone surgical thrombectomy during the same period. The proportion of persons with diabetes mellitus, smokers, and types of bypass grafts was similar in both groups. More patients in the rt-PA-treated group had hypertension (p = 0.01). To evaluate the different lengths of follow-up, Kaplan-Meier survival analysis was used with a log-rank test to compare the proportion of persons with patent grafts in the two treatment groups. At 30 days, 86% of the rt-PA-treated grafts were still patent compared with 42% of the surgically treated grafts (p = 0.001). When risk factors on the Kaplan-Meier curves were compared, there was no statistical difference with regard to graft patency among the groups. According to simultaneous Cox regression analysis, no risk factor was significantly associated with graft patency. When amputation was evaluated between treatment groups simultaneously with other risk factors in a logistic regression analysis, smoking and age of the graft were marginally significant (p = 0.07), whereas all other factors were clearly not significant. In 91% of the rt-PA-treated patients, a secondary surgical procedure was required to maintain patency of the graft segment. Eighty-nine percent of the surgically treated patients required similar graft revisions. Two patients in the surgical group and one patient in the rt-PA-treated group had major complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1987

A novel whole blood capillary technic for measuring the prothrombin time.

The prothrombin time (PT) is frequently performed to monitor anticoagulant therapy. Although relatively simple to perform, it requires venipuncture and laboratory resources for sample handling and analysis. A recently developed capillary whole blood device that uses fingerstick samples was evaluated. Paired capillary whole blood and reference plasma PTs were performed in 858 samples from 732 subjects. The PT for normal volunteers (n = 193) was 11.8 +/- 0.9 seconds with the use of the new instrument and 12.1 +/- 0.5 seconds with the use of the reference method. In samples from 539 patients receiving anticoagulants, the correlation coefficient between the two methods was 0.96. Venous whole blood without anticoagulant and capillary whole blood gave equivalent results, which suggests that the fingersticks do not effect the quality of the specimen. Variation in hematocrit between 23.4% (0.34) and 53.8% (0.538) did not alter the performance of the instrument. The new instrument is easy to use and may allow testing by nonlaboratory personnel and patients. It obviates the need for venipuncture, provides immediate results, and appears to be comparable in accuracy to current reference methods.

Anticoagulants↗
PubMed1987

Bacterial tissue tropism: an in vitro model for infective endocarditis.

Since infective endocarditis may affect individuals without pre-existing valvar heart disease, and Staphylococcus aureus is the organism most commonly involved, the binding characteristics of S aureus to several components of normal vascular endothelium and subendothelium were studied. S aureus adhered specifically to endothelial monolayers (6.08(1.10)%; p less than 0.005), fibronectin (5.43(0.81)%; p less than 0.001), fibrinogen (7.13(1.43)%; p less than 0.001), and acid soluble calf skin collagen (2.38(0.90)%; p less than 0.001). S aureus also adhered specifically to Von Willebrand factor (1.62(0.28)%, p less than 0.001). Protein A containing (Cowan I) and deficient (Wood) strains of S aureus adhered similarly to all surfaces and substrates (NS). Escherichia coli adhered poorly. Immunofluorescence microscopy of preconfluent endothelial cells identified an extensive pericellular fibronectin network at regions of cell to cell contact. Light microscopy showed S aureus binding solely within these regions. Therefore, the ability of S aureus to infect valvar endothelium may be dependent on the presence of a fibronectin receptor. The existence of specific receptor for S aureus on the endothelial cell surface itself remains undetermined.

Animals↗
PubMed1987

Thrombolytic therapy with recombinant human tissue-type plasminogen activator: a comparison of two doses.

The efficacy and safety of two doses of recombinant human tissue-type plasminogen activator (rt-PA) were compared. Forty patients with peripheral arterial occlusions were treated with intraarterial rt-PA. Group A (n = 21) received 0.1 mg/kg/h, and group B (n = 19) received 0.05 mg/kg/h. Infusion durations varied from 4 to 8 hours. Complete thrombolysis occurred in 20 of 21 patients (95%) in group A and in all 19 patients (100%) in group B. In group A, fibrinogen levels were greater than 75% of baseline in ten of 21 patients (48%) at infusion termination. In group B, fibrinogen levels were greater than 75% of baseline in 12 of 19 patients (63%) at infusion termination. Three of 40 patients (7%) had significant complications resulting from rt-PA infusion. The results demonstrate that over similar infusion times, a dose of 0.05 mg/kg/h is as efficacious and results in less systemic fibrinogenolysis than a dose of 0.1 mg/kg/h.

Adult↗
PubMed1986

The influence of glutathione and other thiols on human platelet aggregation.

The platelet membrane contains sulfhydryl groups which are essential for normal platelet function. Reduced glutathione (GSH) and other thiols such as cysteine and 6-mercaptopurine were found to inhibit human platelet aggregation induced by adenosine diphosphate (ADP), collagen and arachidonic acid. The inhibition of ADP-induced aggregation by GSH (IC50 = 0.61 +/- 0.05 mM) was greater than that by cysteine (IC50 = 13 +/- 1 mM) or 6-mercaptopurine (IC50 = 5.4 +/- 0.2 mM). Two other thiols, dithiothreitol and beta-mercaptoethanol were found to cause platelet aggregation instead of inhibition. The interaction of GSH with the ADP receptor was noncompetitive in nature.

Adenosine Diphosphate↗
PubMed1986

Stability of prostacyclin in human and rabbit whole blood and plasma.

The stability of prostacyclin (PGI2) in whole blood and plasma was studied in vitro by measuring the disappearance rate of labeled prostacyclin during a 37 degrees C incubation. Prostacyclin was assayed using a quantitative chromatographic method. The half-life of PGI2 was 6.3 +/- 0.8 minutes (mean +/- s.d., n = 6) in citrated human whole blood, significantly shorter (p less than 0.001) than the 10.7 +/- 2.3 minute half-life in citrated human plasma (n = 7). Prior freezing and thawing of plasma did not affect the rate of PGI2 hydrolysis. These values, including the prolonged half-life in plasma, were similar in the blood (5.4 +/- 1.8 min, n = 7) and plasma (9.0 +/- 1.9 min, n = 14) of diabetic patients. In plasma samples from patients with thrombotic thrombocytopenic purpura, the half-life of prostacyclin (4.9 +/- 1.0 min, n = 4) was significantly shortened (p less than 0.001) compared to that in plasma from normal volunteers. The stability of prostacyclin in rabbit blood and plasma was also quantified. The PGI2 half-life in citrated rabbit plasma (10.8 +/- 1.1 min, n = 3) was similar to that in citrated human plasma from control subjects. In contrast to the findings in human blood, the half-life of PGI2 in citrated rabbit whole blood (11.7 +/- 3.3 min, n = 4) was not different from the rabbit plasma value. Substitution of EDTA for citrate did not affect the half-life in rabbit blood or plasma.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Behavior of intracellular glutathione during platelet thromboxane synthesis in diabetes.

The time-dependent relationship between the levels of the reduced form of glutathione (GSH) and thromboxane A2 (TXA2) synthesis, as measured by the accumulation of TXB2, in platelets from human diabetic and control subjects was investigated during aggregation. In platelets from control subjects, the GSH level decreased to 21% of the initial level within 30 sec in response to arachidonic acid (1.65 mM) and rapidly recovered to 91% by 1 min. In platelets from diabetic subjects, the GSH level decreased to 3% of the initial level within 30 sec and recovered to only 41% by 1 min. During collagen (20 ug/ml) aggregation, platelets from control subjects had a 15 sec lag phase which was followed by a decrease in the GSH level to 21% of the initial level within 1 min and a recovery to 74% by 2 min. Platelets from diabetic subjects in response to collagen showed no lag phase and decreased to 10% of the initial level within 1 min which was followed by a recovery to 34% by 2 min. In all aggregations, the initial GSH level was significantly (p less than .001) lower in platelets from diabetic subjects and remained significantly (p less than .01) lower than GSH in platelets from control subjects throughout the aggregation. The amount of TXB2 formed by platelets from control subjects reached a maximum in response to arachidonic acid and collagen by 1 min and 2 min, respectively, whereas, the TXB2 continued to increase up to 4 min when platelets from diabetic subjects were aggregated. These data indicate that TXA2 synthesis occurs during the decrease in GSH and ceases when the GSH level recovers. The continued synthesis of TXA2 by platelets from diabetic subjects coincides with the gradual recovery of the GSH level.

Arachidonic Acids↗
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↗