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Biomedical subjects

L Fink

Publications and source records attributed to L Fink.

At least 55 records · Page 3Linked to original sources
PubMed1991

Thrombomodulin activity on human saphenous vein grafts prepared for coronary artery bypass.

Thrombomodulin, a membrane glycoprotein present on normal vascular endothelium, binds circulating thrombin and is important in protein C activation. These functions contribute to the nonthrombogenic nature of endothelium. Damage during harvest and ex vivo storage of vein grafts may result in dysfunction of this endothelial anticoagulant barrier and possibly contribute to early graft thrombosis. We studied the functional activity and antigenic expression of thrombomodulin on saphenous veins before (initial) and after (harvested) harvest and storage for coronary artery bypass grafting in 15 patients. Also, fresh saphenous vein was studied after mechanical endothelial stripping. After storage for 2.7 +/- 0.6 hours at room temperature in heparinized saline, thrombomodulin functional activity in harvested vein segments was 28% less than initial segments (p = 0.08). Endothelial stripping resulted in a 79% reduction in thrombomodulin activity compared with initial segments (p = 0.04). Immunohistochemical staining confirmed thrombomodulin antigen on vein grafts after harvest and storage, but not on segments stripped of endothelium. Thrombomodulin functional activity and antigenic expression on human saphenous vein grafts is not significantly changed by harvest and relatively short periods of storage at room temperature in heparinized saline.

Antigens↗
PubMed1991

Intravenous recombinant soluble human thrombomodulin prevents venous thrombosis in a rat model.

Thrombomodulin is an endothelial surface thrombin receptor. Thrombin bound to thrombomodulin loses all procoagulant activity and instead activates the protein C anticoagulant pathway. We developed a recombinant thrombomodulin analog and compared the effects of recombinant thrombomodulin (100 micrograms/ea), saline (controls), recombinant hirudin (1.0 mg/kg), and heparin (100 units/kg) on thrombus formation, activated partial thromboplastin time, and tail transection bleeding time in a rat model of stasis-induced venous thrombosis. Results showed that thrombus was detected in the vena cava in six of the six rats treated with saline solution, in zero of the six rats treated with recombinant thrombomodulin (p less than 0.05), in one of six rats treated with recombinant hirudin (p less than 0.05), and in zero of six rats treated with heparin (p less than 0.05). The activated partial thromboplastin time in rats receiving recombinant thrombomodulin was slightly longer than controls (22 +/- 8 vs 37 +/- 6, p less than 0.05). The bleeding times in rats receiving recombinant thrombomodulin were approximately twice as long as controls (215 +/- 68 vs 545 +/- 173, p = 0.037). In all rats treated with recombinant hirudin or heparin, activated partial thromboplastin times were greater than 120 seconds and bleeding times were greater than 1200 seconds. We conclude that recombinant thrombomodulin inhibits venous thrombosis in a rat model with less prolongation of activated partial thromboplastin time and bleeding time than heparin or hirudin.

Animals↗
PubMed1990

A modified quantitative whole blood clot lysis method for general laboratory analysis of fibrinolysis.

Because fibrinolysis is now recognized as an important factor in hypercoagulable states, we have developed and characterized an easily performed, rapid, and quantitative screening test that assesses a patient's fibrinolytic activity. This modification of the dilute whole blood clotting time (DWBCT) counts the number of intact erythrocytes released from the clot formed in samples obtained before and after the application of a venous occlusion cuff. Samples were corrected for the plasma volume changes that occurred during venous occlusion. This test was performed on nine healthy volunteers. Specimens were diluted 1:1 with PBS, rapidly clotted with thrombin and incubated at 37 C. Starting thirty minutes after the thrombin was added and then at twenty minute intervals until 110 minutes, the number of RBCs released from the clot were counted using a Coulter S Plus counter. There were consistently more RBCs released at each time period after venous occlusion (p less than 0.001). Aliquots were also obtained for measuring PAI activity and TPA levels. PAI activity was lower post-cuff at every point (p less than 0.001). TPA level was higher at every point (p less than 0.001) post-cuff. The addition of exogenous TPA, activated protein C, or anti-PAI antibodies increased the amount of clot lysis; while the addition of anti-TPA antibodies and EACA each prevented the post-cuff increase. Unlike the euglobulin lysis time (ELT) this modified DWBCT (mDWBCT) measures the patients intact fibrinolytic system, including PAI and erythrocytes, in a quantitative fashion. Unlike either the ELT or the DWBCT the mDWBCT can be performed within two hours, so results are rapidly available for clinical decisions. These studies have demonstrated an easily performed, inexpensive, quantitative screening test of a patient's overall fibrinolytic system that reacts appropriately to pharmacologic manipulations.

Aminocaproic Acid↗
PubMed1989

Early treatment with intravenous metoprolol for suspected acute myocardial infarction: a phase IV United States trial. Phase IV Metoprolol in Myocardial Infarction Study Group.

Recent randomized clinical trials have shown that total mortality and cardiovascular mortality are reduced by the early intravenous administration of beta-blockers to patients suspected of suffering from acute myocardial infarction. These trials were conducted on patients meeting strict entry criteria. In order to assess this therapy when applied to a broader range of myocardial infarction patients, we performed a Phase IV study of metoprolol in acute myocardial infarction. The study was designed to test whether early (less than 8 hours from onset of chest pain) intervention by practicing physicians with open label intravenous metoprolol for cases of suspected acute myocardial infarction achieved mortality results similar to those obtained in large randomized clinical trials. We studied 3824 patients treated by 741 physicians representing a broad spectrum of clinical practice in the United States. Seventy-two percent of the patients entered into the study had confirmed myocardial infarction (39% anterior, 39% inferior, 22% other locations) and 85% of all individuals treated tolerated the full intravenous dose of 15 mg of metoprolol. The 15 day total mortality and cardiovascular mortality rates were 4.9% and 4.5%; 90 day mortality rates were 6.9 and 5.9%. Patients with anterior infarctions had a significantly greater cumulative mortality rate than patients with other types of infarctions. Marked bradycardia (heart rate less than 45 beats per minute) in the first 8 hours post treatment occurred in 4.7% cases and hypotension (systolic blood pressure less than 90 mm Hg) occurred in 9.8% of cases. When compared with the results of the Göteborg and MIAMI trials of metoprolol, it appears that there is no appreciable increase in mortality or morbidity when metoprolol is used in the community practice of acute coronary care.

Adult↗
PubMed1987

Congestive cardiomyopathy in association with AIDS.

During a 10-month period in 1985 and 1986, three cases of acquired immunodeficiency syndrome (AIDS) and a rapidly progressive fatal cardiomyopathy were encountered. All three patients originally presented with common opportunistic infections and later experienced marked congestive heart failure associated with echocardiographic and radiologic findings consistent with four-chamber cardiomyopathy. Diffuse cardiomyopathy was confirmed postmortem, but in each case a specific cause was not found.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Evaluation of energy metabolism in skeletal muscle of patients with heart failure with gated phosphorus-31 nuclear magnetic resonance.

Exertional fatigue is a major limiting symptom in patients with heart failure. To investigate the metabolic basis of this fatigue, we used gated nuclear magnetic resonance spectroscopy to compare inorganic phosphate (Pi), phosphocreatine (PCr) and pH levels, and fatigue (1 to 4+) during mild forearm exercise in eight normal men and nine men with heart failure. Wrist flexion every 5 sec for 7 min was performed at 1, 2, and 3 J (average power output = 0.2, 0.4, and 0.6 W). In both groups linear relationships were noted between power output and Pi/PCr; the slope of this relationship was used to compare PCr depletion patterns. At rest both groups had similar Pi/PCr ratios (normal subjects 0.12 +/- 0.06, those with heart failure 0.15 +/- 0.03) and pH (normal subjects 7.04 +/- 0.13, those with heart failure 7.10 +/- 0.11). In normal subjects exercise resulted in a progressive increase in Pi/PCr (slope = 1.17 +/- 0.20 Pi/PCr units/W), a reduction in pH only at 0.6 W (0.2 W: 7.03 +/- 0.10, 0.4 W: 7.01 +/- 0.10, 0.6 W: 6.88 +/- 16) and moderate fatigue (0.2 W: 0 +/- 0, 0.4 W: 1.3 +/- 0.5, 0.6 W: 1.9 +/- 0.6). In patients with heart failure exercise resulted in significantly greater fatigue at all workloads (0.2 W: 1.0 +/- 0.5, 0.4 W: 1.9 +/- 0.6, 0.6 W: 2.9 +/- 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMedDate not supplied

Ca2+ dynamics in neuronal growth cones: regulation and changing patterns of Ca2+ entry.

Digital ratio imaging of Fura-2 fluorescence was used to determine spatially resolved dynamics of Ca2+ changes in neuronal growth cones from the molluscs, Helisoma and Aplysia. Time resolution was approximately 1 s and spatial resolution a few mm depending upon the thickness of the cell region examined. Isolated growth cones of Helisoma were shown to recover from large Ca2+ loads over a time course of minutes, therefore demonstrating Ca2+ regulation mechanisms not dependent on the rest of the cell. Ca2+ changes monitored during action potential discharge showed sharply defined spatial gradients within the growth cones, probably arising from clustering of voltage-gated Ca-channels in the surface membrane. The regions of peak concentration change appeared to shift from central regions to the growth cone periphery as the growth cones matured. There was a marked difference in soma Ca2+ changes produced by action potentials depending on whether or not the soma had sprouted neurites. Neurite-free somata showed large Ca2+ changes, whereas in somata that had recently sprouted neurites there were almost no changes for similar electrical stimulation. Measurements on growth cones of N1E115 neuroblastoma cells showed static distributions of Ca2+ similar to those in the molluscan neurons.

Animals↗