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Biomedical subjects

E C Lasser

Publications and source records attributed to E C Lasser.

At least 55 records · Page 3Linked to original sources

Diminished atherosclerotic arterial calcifications in asthma. A possible role for elevated endogenous heparin-like material.

Twenty-seven patients beyond the age of 50 were radiographically compared with age- and sex-matched controls for the degree of calcified atherosclerotic plaque formation in the aorta and its major pelvic branches. Significantly less calcification was present in the aorta, iliac and hypogastric arteries of the asthmatics (P = 0.01). Previous studies in other asthmatic patients have shown elevated endogenous heparin-like material to be present in their plasma. It is speculated that diminished atherosclerosis in asthmatic patients might be a consequence of elevated circulating endogenous heparin-like material.

Aged↗

Heparin-like anticoagulants in asthma.

In a previous study, and in the present study, we have found that the baseline plasma samples of patients with asthma contain average levels of an endogenous heparin-like material (EHM) that is significantly higher than that noted in non-allergic, non-asthmatic controls. This material appears to have properties of both heparin and heparan sulfate. Three out of six patients responding to inhalational antigen challenge displayed an acute increment in EHM concentration that coincided with a fall in FEV values. The relation of EHM concentration to provoked asthma, or to asthma in general, remains to be determined.

Adult↗

Alpha 2-macroglobulin-kallikrein potentiates contact system activity: possible effect in asthma.

Bradykinin release, an end product of contact system activation, is thought to play a significant role in the pathophysiology of asthma. We have found an increased level of native alpha 2-macroglobulin-kallikrein (alpha 2M-KK) in asthma plasmas, and have demonstrated increased levels of contact system activity in these plasmas under certain laboratory conditions. We investigated the possible role of alpha 2M-KK as a modulator of the contact system activity. Alpha 2M-KK potentiated the factor XII activation on kaolin and the kallikrein production in a dextran-sulfate-mediated assay. This potentiation presumably involves a proteolytic effect of alpha 2M-KK on high molecular weight kininogen.

Asthma↗

A coherent biochemical basis for increased reactivity to contrast material in allergic patients: a novel concept.

Bradykinin, the end product of activation of the plasma contact system, may play a significant role in reactions to contrast material and in other forms of anaphylactoid and anaphylactic responses to drugs or antigens. Activation of factor XII initiates activity in the plasma contact system, and we have identified factors (negatively charged surfaces) present in elevated concentrations in the plasma of patients who are asthmatic or allergic that can "prime" their plasma for the initiation and/or potentiation of factor XII activation. In other studies, we have shown that persons who react to contrast material and persons who are asthmatic or allergic share both a potential for accelerated contact system activity and evidence of an increased mean concentration of low-level contact system products. Recently, we have found that contrast media can inhibit angiotensin-converting enzyme, the substance that hydrolyzes bradykinin and limits its systemic effects. Thus, a number of factors suggest that it is the potential for increased production of bradykinin in persons who are allergic or asthmatic that may account for the greatly increased susceptibility of these patients to contrast material. This susceptibility may be critically triggered by the contrast media-induced inhibition of angiotensin converting enzyme. In view of these findings, the possibility exists that most, if not all, significant reactions to contrast material require an underlying allergic diathesis that may, or may not, be apparent by history and conventional diagnostic testing.

Anaphylaxis↗

Acute systemic and renal hemodynamic effects of meglumine/sodium diatrizoate 76% and iopamidol in euvolemic and dehydrated dogs.

We examined the acute systemic and renal hemodynamic effects of intravenous meglumine/sodium diatrizoate-76% and iopamidol in euvolemic and dehydrated dogs. The physiologic responses were compared with acute changes in the level of an endogenous heparin-like material (EHM). One of eight dehydrated dogs receiving diatrizoate (2 ml/kg) had an immediate vomiting reflex associated with a very significant decline in all measured renal hemodynamic parameters; none of eight dehydrated dogs receiving iopamidol experienced a similar reaction. EHM levels did not correspond to the magnitude of the physiologic responses following either iopamidol or diatrizoate. Significant differences between iopamidol and diatrizoate were noted when comparing the magnitude of the decrease in systemic pressure (- delta 3.8 +/- 3.02, iopamidol, n = 8; vs. - delta 19.4 +/- 7.3 mm Hg, diatrizoate, n = 8; P less than .03), increased renal plasma flow (+ delta 6.2 +/- 4.9, iopamidol, n = 8; vs. + delta 33.7 +/- 8.0 ml/min, diatrizoate, n = 8; P less than .05), and decreased filtration fraction (- delta 0.09 +/- 0.01, iopamidol, n = 8; vs. - delta 0.14 +/- 0.02, diatrizoate, n = 8; P less than .03). There was no significant difference in the decrease in glomerular filtration rate (- delta 7.4 +/- 1.0, iopamidol, n = 8; vs. - delta 9.3 +/- 1.3, diatrizoate, n = 8; P greater than .05), since the marked drop in filtration fraction occurring with diatrizoate was counterbalanced by the marked increase in renal plasma flow. Acute systemic and renal hemodynamic effects are significantly lessened when comparing iopamidol with diatrizoate.

Animals↗

Major issues in the organization and implementation of the National Cooperative Gallstone Study (NCGS).

The National Cooperative Gallstone Study (NCGS) was a cooperative, randomized, controlled trial of a drug, chenodiol, for the medical dissolution of gallstones. The design and procedures of the NCGS were complex, having developed as a result of extensive involvement of many experts in the field of gallstone disease and biliary lipids. During the design and implementation of the protocol, many important issues required consideration and resolution. The aim of this article is to review these issues and the deliberations surrounding their resolution and provide personal conclusions and recommendations that may be helpful to other investigators involved in cooperative, controlled trials.

Chenodeoxycholic Acid↗

Low-dose chenodiol to prevent gallstone recurrence after dissolution therapy.

Chenodiol is a safe and effective agent for the medical dissolution of gallstones in selected patients; however, after dissolution and cessation of treatment, gallstones recur. This study was done to determine the recurrence rate after successful medical treatment and cessation of chenodiol therapy; compare the efficacy and safety of low-dose chenodiol, as compared to placebo, for prophylaxis against recurrence; and identify factors predictive of recurrence. In a randomized, double-blind fashion, 53 patients with gallstone dissolution received either chenodiol, 375 mg/d, or placebo, for at least 2 years. Standardized oral cholecystograms were done at 6 months, 1 year, and then yearly thereafter. Routine laboratory testing was done every 6 months. The cumulative rate of recurrence (life-table) was 27% in patients followed for up to 3.5 years. Chenodiol, 375 mg/d, was ineffective in preventing the recurrence of gallstones. No demographic, clinical, roentgenographic, or biochemical characteristics were predictive of recurrence.

Aged↗

The plasma contact system in atopic asthma.

An in vitro test for the rate of appearance of kallikrein in plasma due to contact system activation by dextran sulfate at 0 degree C was applied to plasmas of 19 atopic asthma patients and 19 age- and sex-matched controls without atopy. The average prekallikrein activation rate was markedly higher in the plasmas of the atopic patients. Mean endogenous heparin levels were also elevated.

Adolescent↗

Experience with metrizamide in patients with previous severe anaphylactoid reactions to ionic contrast agents.

Metrizamide was employed in six patients who, during angiography, had had severe anaphylactoid reactions to conventional ionic contrast media. Five of these patients had received corticoid premedication before injection of both conventional contrast medium and metrizamide; anaphylaxis occurred only after administration of conventional contrast media. Four patients had no detectable reaction whatsoever after metrizamide; a fifth had only transient tachycardia. In the sixth patient, delayed edema developed in the region of his cerebral arteriovenous malformation. These observations suggest a marked decrease in the incidence and severity of anaphylactoid reactions when metrizamide is substituted in patients who have reacted to ionic contrast media. Metrizamide, or a comparable nonionic contrast agent, should be strongly considered in patients who have had a severe reaction to conventional contrast medium.

Adolescent↗

Adverse reactions to intravascular administration of contrast media.

Adverse reactions to intravascular administration of contrast media, while low in incidence, merit serious consideration in view of increased utilization of these substances all over the world. Evidence for involvement of soluble mediators, antibody-antigen reactions, psychogenic factors, and the acute activation systems, is reviewed. As a group, the pre-contrast challenge plasmas of reactors are characterized by slightly diminished concentrations of Cl-esterase inhibitor and total hemolytic complement, and by an accelerated rate of conversion of prekallikrein to kallikrein on exposure to contact activators. The role of intravenous pretesting and pretreatment is considered. A rationale for pretreatment with adrenocorticosteroids is presented.

Adrenal Cortex Hormones↗

Prekallikrein-Kallikrein conversion rate as a predictor of contrast material catastrophies.

An in vitro is described that attempts to detect patients with a potential for adverse systemic reactions to contrast material. This test involves measuring the rate of conversion of prekallikrein to kallikrein under certain standard conditions. In a preliminary retrospective study, the test could be used to identify such patients with a sensitivity of 88%, a specificity of 82%, and a predictive value of 79%.

Anaphylaxis↗

Complement and contrast material reactors.

Patients showing systemic reactions to intravascular contrast media and patients receiving contrast media without reaction have significantly different mean values (p is less than 0.05) for functionally determined serum C1-esterase inhibitor (C1 INH) and total hemolytic complement (CH50). The lower concentration of these components in reactors appears in baseline serum samples (as well as after injection), and suggests that many anaphylactoid reactions to contrast media are conditioned by earlier complement consumption, and result directly from contrast-induced activation of complement, and other activation system components in the presence of inhibitor depression.

Complement C1 Inactivator Proteins↗

Comparison of radiopaque perfluorocarbon and Ethiodol in lymphography.

Lymphangiography was performed on 40 adult cats, 39 dogs, 20 rabbits, and 12 rats of mixed sex using Ethiodol or radiopaque perfluorocarbon (BPC). Ethiodol was more radiodense than RPC, but imaging of lymph channels and nodes was satisfactory with the latter. RPC could be infused rapidly, while Ethiodol infusion was time consuming. RPC was biologically inert; Ethiodol produced both local and systemic inflammatory reactions. The lymph node distribution with RPC was more uniform and persisted for longer periods. It was concluded that RPC was an improvement over Ethiodol for lymphangiography.

Animals↗

Complement and coagulation: causative considerations in contrast catastrophies.

Earlier studies suggest that adverse reactions to injected radiographic contrast media are idiosyncratic. In an attempt to gain a better understanding of pathophysiologic events underlying these reactions, rabbit models injected with lethal dose ranges of a cholangiographic contrast material were studied. These animals showed activation of both the complement and coagulation systems. Externally applied heat potentiated complement consumption and increased mortality. Depleting complement components C3-C9 by cobra venom factor did not prevent activation of coagulation or diminish mortality. However, depleting fibrinogen diminished complement activation and markedly diminished mortality. Heparin, administered at several hourly intervals after contrast challenge, also diminished mortality. These studies suggest that the adverse effects of contrast media in this model system are mediated chiefly by the coagulation system, and that complement, if it participates deleteriously, must involve components up to, but not including, C3. A logical role for the inhibitor of C1 esterase in adverse contrast reactions is considered.

Ancrod↗

Nonimmunologic complement activation in normal human serum induced by radiographic contrast media.

Two different radiographic contrast media (RCM), iothalamate and iodipamide, induced the activation of several complement (C) components in normal, genetically C2-deficient and agammaglobulinemic human sera in vitro. This activation was dose dependent and demonstrable by a reduction in whole C as well as C4, C2, C3, and C5 hemolytic activities. C6, C8, and C9 hemolytic activities were unaffected. Concommitant with the loss of C3 hemolytic activity was the appearance of C3 proteolytic cleavage products that were identified by immunoelectrophoresis. Both the loss of C3 hemolytic activity and the production of C3 fragments occurred in the presence of 10 mM EDTA, indicating RCM-induced C3 cleavage occurred without participation of the multicomponent C3/C5 convertases of either the classical or alternative C pathways. Furthermore, loss of C3 hemolytic activity was not due to the direct alteration of the C3 molecule by RCM because purified C3 was unaffected upon incubation with RCM at a concentration that induced 80% reduction in the C3 hemolytic activity in normal human serum. Serum samples obtained from 40 patients, before and 30 min after undergoing i.v. pyelography, revealed no significant change in total hemolytic C activity; 34 patients received sodium and methylglucamine diatrizoate and six received sodium iothalamate. Hemolytic C3 levels were also determined for the six patients before and 30 min after administration of sodium iothalamate and no significant change in activity was detectable.

Agammaglobulinemia↗

Tumor imaging with x-rays using macrophage uptake of radiopaque fluorocarbon emulsions.

Radiopaque fluorocarbon (RFC) emulsions were prepared with small particle size and high concentration of the fluorocarbon. When RFC emulsions were injected intravenously in hamsters, rats, and mice with eight types of malignant tumors, the tumors became radiopaque, except in the mice with spontaneous teratoma of the ovaries. Tumors as small as 3 to 4 mm could be defined radiographically using routine x-ray techniques. The tumors remained radiopaque for days to weeks after injection. Light and electron microscopy revealed characteristic fluorocarbon vacuoles primarily in the tumor macrophages. Thus RFC emulsions may be useful in detection of malignant tumors.

Animals↗

Steroids: theoretical and experimental basis for utilization in prevention of contrast media reactions.

In vitro and in vivo studies were done to examine the effects of methylprednisolone on the adverse reactions induced by contrast media. At very high concentrations, the steroid potentiated the complement-activating effect produced in vitro by iodipamide, but inhibited the immune and nonimmune mechanisms of hemolysis. Rabbits pretreated for 3 days with intramuscular methylprednisolone (at high or low dosages) were significantly protected against an LD47 challenging dose of iodipamide. Those treated once with a low intravenous dose immediately prior to iodipamide challenge were protected to a lesser degree. Rabbits treated once with a very high intravenous dose of steroid evidenced no protection. A hyper-responsive dog was consistently protected against adverse reactions to injected sodium iothalamate by a 3-day steroid pretreatment.

Animals↗

Development of contrast media idiosyncrasy in the dog.

A laboratory dog exhibited an altered response to injections of sodium iothalamate. This idiosyncratic response may have been predicated on an earlier series of iothalamate injections. The overt manifestations of the reactions in this dog were vomiting, hypotension, and hyperreflexia. Significant changes in several electrolyte components and serum complement levels were noted when the dog reacted to the contrast material.

Animals↗