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Biomedical subjects

D C Sane

Publications and source records attributed to D C Sane.

50 records · Page 3Linked to original sources
PubMed1991

Racial differences in responses to thrombolytic therapy with recombinant tissue-type plasminogen activator. Increased fibrin(ogen)olysis in blacks. The Thrombolysis and Angioplasty in Myocardial Infarction Study Group.

To determine whether there are differences in responses to thrombolytic therapy in certain populations, the data for the Thrombolysis and Angioplasty in Myocardial Infarction (phase 1) study were analyzed for black and white patients. Baseline variables including risk factors and extent of coronary artery disease were similar in the 352 white and 24 black patients. The time from onset of chest pain to recombinant tissue-type plasminogen activator (rt-PA) therapy and rt-PA dosing regimens were the same in the two groups. The patency rate of the infarct-related artery at 90 minutes was 91% for blacks and was 72% for whites (p = 0.051). Blacks displayed significantly lower nadir fibrinogen levels (0.57 +/- 0.62 versus 1.3 +/- 0.76 g/l, p less than 0.0001), greater delta fibrinogen (baseline-nadir) (2.7 +/- 1.1 versus 1.7 +/- 1.1 g/l, p less than 0.0001), and increased peak levels of fibrin(ogen) degradation products (837 +/- 865 versus 245 +/- 475 micrograms/ml, p less than 0.0001). rt-PA antigen levels tended to be higher in blacks than in whites (2.8 +/- 2.2 versus 2.2 +/- 3.2 micrograms/ml [p = 0.10] at the peak and 1.6 +/- 1.3 versus 0.99 +/- 1.4 micrograms/ml [p = 0.06] at the end of the maintenance infusion). Major clinical outcomes including survival until time of hospital discharge (92% black versus 93% white, p = 0.68) were not significantly different. However, despite undergoing fewer angioplasty procedures (25% versus 46.3%, p = 0.047), blacks received more transfusions (58.8% versus 19.5% were administered greater than or equal to 2 units packed erythrocytes, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Black People↗
PubMed1990

Highly sulfated glycosaminoglycans augment the cross-linking of vitronectin by guinea pig liver transglutaminase. Functional studies of the cross-linked vitronectin multimers.

Vitronectin (VN) is an adhesive glycoprotein with roles in the complement, coagulation, and immune systems. Many of the functions of VN are mediated by a glycosaminoglycan binding site, near its carboxyl-terminal end. In this paper, we show that the highly sulfated glycosaminoglycans (GAGs), dextran sulfate, pentosan polysulfate, and fucoidan effectively augment [14C]putrescine incorporation into VN and cross-linking of VN into high molecular multimers by guinea pig liver transglutaminase (TG). Other GAGs including heparin, low molecular weight heparin, dermatan sulfate, keratan sulfate, and the nonsulfated dextrans were ineffective in accelerating these reactions. Dextran sulfate of average molecular mass 500 kDa was more effective than dextran sulfate of average molecular mass 5 kDa, supporting a template mechanism of action of the GAGs, in which VN molecules align on the GAG in a conformation suitable for cross-linking. The VN multimers catalyzed by TG retained functional activity in binding [3H]heparin, platelets, and plasminogen activator inhibitor type-1 (PAI-1). [3H]Heparin bound selectively to the 65-kDa monomeric band of VN and to the multimers derived from this band. PAI-1, however, bound equally to both the 75- and 65-kDa monomeric forms of VN, suggesting that the PAI-1 binding site on VN is distinct from the GAG binding site. The interaction of GAGs with the TG-catalyzed cross-linking of VN may facilitate studies of VN structure-function relationships.

Animals↗
PubMed1989

Cyclic GMP analogs inhibit gamma thrombin-induced arachidonic acid release in human platelets.

Elevation in intracellular cyclic GMP levels is the proposed proximal mechanism for the vasodilatory and platelet inhibitory action of nitrovasodilators and of nitric oxide, the putative endothelium-derived relaxing factor. In this study, the stable cyclic GMP analogs, 8-bromo-cGMP and N2, 2'-O-dibutyryl-cGMP were found to inhibit the release of [3H]-arachidonic acid from gamma thrombin-stimulated human platelets in a time- and dose-dependent manner. Inhibition of the formation of arachidonic acid metabolites, 12-HETE and thromboxane B2, paralleled that of arachidonic acid release and was accompanied by a dose-dependent inhibition of platelet aggregation. The formation of phosphatidic acid, a metabolite of phospholipase C, however, was relatively preserved. At a concentration of 8-bromo-cGMP (2 mM) that produced near-total inhibition of arachidonic acid release, phosphatidic acid formation remained at 60% of control levels. Thus, cGMP analogs have a preferential inhibitory effect on the release and subsequent metabolism of arachidonic acid. The phospholipase A2/arachidonic acid pathway appears to be an important target for the physiologic action of cGMP, and EDRF, and for the pharmacologic action of nitrovasodilators.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1989

Bleeding during thrombolytic therapy for acute myocardial infarction: mechanisms and management.

Hemorrhage is the major adverse effect of thrombolytic therapy, but its incidence can be reduced by careful selection of patients and avoidance of unnecessary invasive procedures. More than 70% of bleeding episodes occur at vascular puncture sites. Hypofibrinogenemia and elevation of fibrinogen degradation products have been weakly correlated with the risk of hemorrhage. Although depletion of factors V and VIII may occur, the role of such depletion in bleeding is unknown. Several in-vitro studies have shown plasmin-induced platelet dysfunction, but clinical data are limited. Nevertheless, the role of platelet inhibition should be considered because many patients are treated with antiplatelet agents. Most patients who have bleeding can be managed by interruption of thrombolytic and anticoagulant therapy, volume replacement, and manual pressure applied to an incompetent vessel. Protamine should be considered if heparin has been administered within 4 hours of the onset of bleeding. In the few patients who fail to respond to these conservative measures, judicious use of transfusion products may be indicated. Transfusion of cryoprecipitate, fresh frozen plasma, and platelets should be considered with clinical and laboratory reassessment after each administration. A target fibrinogen level of 1 g/L is desirable with cryoprecipitate infusion. Antifibrinolytic agents are available as a last alternative. We have developed an algorithm for using these products.

Antifibrinolytic Agents↗
PubMed1989

Elevated urokinase-type plasminogen activator level and bleeding in amyloidosis: case report and literature review.

Hyperfibrinolytic states are reported to be a cause of bleeding in patients with amyloidosis. We reviewed the literature on excessive fibrinolysis in association with amyloidosis and report our findings from a patient with idiopathic amyloidosis who developed a bleeding diathesis. Coagulation laboratory studies indicated elevated plasminogen activator levels associated with a reduction of plasminogen and alpha 2-plasmin inhibitor (alpha 2-PI) levels. The level of tissue-type plasminogen activator (t-PA) inhibitor and t-PA antigen were normal. However, the patient did have a five- to sevenfold increase in amidolytic activity for the urokinase substrate pyro-Glu-Gly-Arg-pNA (S-2444). This case therefore represents a novel example of a hyperfibrinolytic state associated with amyloidosis caused by elevated urokinase-type plasminogen activator (u-PA). Epsilon-amino caproic acid (EACA) therapy resulted in an increase in alpha 2-PI and plasminogen levels and effectively reduced the blood loss. Hyperfibrinolytic states in amyloidosis have now been reported to be due to elevated t-PA and u-PA and depleted t-PA inhibitor.

Aminocaproic Acid↗
PubMed1988

Vitronectin is a substrate for transglutaminases.

Vitronectin (VN) was found to be a substrate for both plasma transglutaminase (Factor XIIIa) and guinea pig liver transglutaminase (TG). Incorporation of [3H]-putrescine indicated the presence of reactive glutaminyl residues in VN. When VN was incubated with TG or Factor XIIIa, in the absence of putrescine, multimeric covalent complexes were identified, indicating that VN can also contribute lysyl residues to the bond catalyzed by transglutaminases. Cross-linking of VN by TG and Factor XIIIa may modulate the effects of VN on the complement and coagulation systems in hemostatic plugs and extracellular matrix.

Cross-Linking Reagents↗
PubMed1986

Opportunistic lung infection caused by Rhodococcus (Corynebacterium) equi.

Rhodococcus (formerly Corynebacterium) equi, a common animal pathogen, can cause a slowly evolving pneumonia in humans, particularly immunocompromised people. The authors describe two patients; one with acquired immunodeficiency syndrome. On chest radiographs, R. equi produces chronic, localized pulmonary opacities that can cavitate. The main differential diagnoses are tuberculosis and fungal infection.

Acquired Immunodeficiency Syndrome↗