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Biomedical subjects

E C Lasser

Publications and source records attributed to E C Lasser.

At least 37 records · Page 2Linked to original sources
PubMed1991

Alpha-2-macroglobulin-kallikrein complex: a temperature-sensitive mediator in contact-system-induced inflammation with a potential role in late and delayed hypersensitivity responses.

Maximal complexing of alpha 2-macroglobulin (alpha 2M) and kallikrein (KK) occurs at a temperature of 22-24 rather than at 37 degrees C. The protease expressivity of the complex is also maximal at 22-24 degrees C. alpha 2M-KK complex, sustained permeability changes in guinea pig skin. These findings suggest that the complex, rather than free KK, could play a role in the kinin release reported in some late-phase reactions, some instances of delayed-type hypersensitivity and some cold-induced reactions.

Animals↗
PubMed1990

Inhibition of angiotensin-converting enzyme by contrast media. I. In vitro findings.

There is increasing evidence that activation of the plasma contact system that results in the production of bradykinin plays an important role in contrast material systemic reactions. The effects of bradykinin in anaphylaxis depend on its rate of destruction and its rate of production. The highest percentage of contrast material reactions occur after intravenous injections, and the major enzyme hydrolyzing bradykinin (kininase II; angiotensin-converting enzyme) is found on pulmonary vascular endothelial surfaces. The inhibitory effects of numerous ionic and nonionic contrast material solutions on the enzyme have been determined. Additionally, the role in this inhibition of the chelators found in all commercial contrast material vials has been studied. In vitro, all such preparations combined with their chelators inhibit angiotensin-converting enzyme. Whether this inhibition plays a role in vivo remains to be established.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1988

A general and personal perspective on contrast material research.

Nonionic media have substantially reduced local toxicity in animal and human studies. The impact on systemic toxicity is less clear. In the final analysis, an understanding of the pathophysiologic mechanisms that appear to play a role in the genesis of reactions invoked with ionic media will be important in understanding the reactions invoked by nonionic media. We believe that bradykinin may contribute significantly to contrast media (CM) reactions. An underlying allergic diathesis may "prime" plasmas for potentiated contact system activation with subsequent bradykinin production. Three factors have been identified in increased concentrations in the plasmas of allergics/asthmatics that potentiate contact system activity in vitro. These are: (1) an endogenous heparin-like material having functional heparin properties; (2) an endogenous heparin-like material without functional heparin properties; and (3) a complex of the plasma inhibitor alpha 2-macroglobulin, with kallikrein, a plasma contact system protease. In clinical studies, we have demonstrated that corticosteroids administered as pretreatment will diminish significantly the incidence of reactions, and that similar pretreatment will diminish the plasma concentrations of heparin-like substances without functional heparin properties. Finally, we have shown in preliminary studies that CM can inhibit angiotensin-converting enzyme, the substance having a major responsibility for in vivo bradykinin hydrolysis.

Anaphylaxis↗
PubMed1988

Protective effects of corticosteroids in contrast material anaphylaxis.

A prospective, randomized study of the potential protective effects of corticosteroids administered as pretreatment against contrast material (CM) reactions is reported. Patients (n = 6,763) from multiple institutions received either a single dose of steroids (32 mg of oral methylprednisolone, approximately 2 hours before CM challenge), a double dose (32 mg approximately 12 hours and 2 hours before CM challenge), or placebo. All contrast injections were with ionic media and were given intravenously. The two-dose (but not the one-dose) corticosteroid regimen provided significant protection. The effect on reaction incidences of a number of historical variables is also tabulated.

Anaphylaxis↗
PubMed1988

Primers of contact system activity in asthmatic patients and contrast material reactors.

An accelerated prekallikrein transformation is present at 4 degrees C in plasmas obtained from asthmatic patients (asthma plasmas) and in prereaction plasmas from contrast material (CM) reactors. Preliminary data show that (1) higher levels of alpha 2-macroglobulin bound kallikrein (alpha 2M-KK) may be found in asthma plasmas and pre-contrast medium reactor plasmas in comparison with control plasmas. In the asthma plasmas, these differences approach, but do not quite attain, significance; (2) complexes of alpha 2M-KK potentiate prekallikrein activation in buffer (BA) and dextran sulfate activation (DSA) assays; and (3) polybrene (factor XII inhibitor) induces an early blockage in the production of kallikrein activity in BA and DSA, indicating the presence in these plasmas of cryptic surfaces with a function analogous to dextran sulfate. These results indicate that, in asthma and probably in CM reactors plasmas, cryptic surfaces and alpha 2M-KK may each contribute to contact system activity induced at 4 degrees C.

Asthma↗
PubMed1987

Modification of an amidolytic heparin assay to express protein-bound heparin and to correct for the effect of antithrombin III concentration.

A modification of an anti-Xa assay for plasma heparin has been devised using a low molecular weight dextran sulfate that competitively binds protein heparin neutralizers and displaces masked heparin. The addition of 0.12 mg dextran sulfate per ml of plasma permits heparin, neutralized by the products of platelet aggregation, to recover full functional activity against Xa. The assay will permit a more accurate assessment of both exogenous plasma heparin and endogenous heparin-like activity in blood samples collected with varying techniques. A further modification is proposed employing polybrene to neutralize the plasma heparin-like material providing a concurrent control for each sample that increases accuracy by eliminating the effect of varying AT-III levels which have anti-Xa activity.

Antithrombin III↗
PubMed1987

Pretreatment with corticosteroids to alleviate reactions to intravenous contrast material.

The x-ray contrast mediums used over the past three decades have been salts of iodinated acids administered in highly hypertonic concentrations. We conducted a multiinstitutional randomized study of the protective effects of pretreatment with corticosteroids against reactions to intravenous contrast material. We gave 6763 patients two doses of oral corticosteroids (methylprednisolone, 32 mg) approximately 12 hours and 2 hours before challenge with contrast material, one dose of oral prednisolone approximately 2 hours before challenge, or placebo in the same dosages. The two-dose corticosteroid regimen, but not the one-dose regimen, significantly reduced the incidence of reactions of all types (P less than 0.05) except a category of reactions dominated by hives, for which the reduction approached significance (P = 0.055). In recent years, several relatively expensive monomeric nonionic iodinated compounds having approximately half the osmolality of the corresponding ionic compounds and a lower reaction rate have become available. With our two-dose corticosteroid regimen, the incidence of reactions necessitating therapy in patients receiving the ionic medium approximated that reported in an unblinded nonrandomized study of patients receiving a newer intravenous nonionic medium without corticosteroid pretreatment. We conclude that the much less expensive ionic medium, if administered with corticosteroid pretreatment, may serve as a reasonable alternative to intravenous nonionic medium, without loss of safety.

Administration, Oral↗