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PubMedDate not supplied

Antibodies to radiographic contrast agents. Induction and characterization of rabbit antibody.

An allergic, immunologic mechanism for certain adverse reactions to radiocontrast agents has been postulated on the basis of clinical and theoretical considerations. One obstacle to the acceptance of this allergic theory has been the inability to demonstrate significant antibodies with specificity for these agents. We attempted the induction of antibodies in the rabbit using analogues of radiocontrast media. The synthesis of four different analogues of commonly used radiocontrast agents allowed for testing the haptenic potential of various portions of the contrast medium molecule. Each analogue was conjugated to a carrier protein, emulsified in a suitable adjuvant, and repeatedly injected into several rabbits. Optimal immunization conditions were selected to increase the probability of antibody induction. Specific antibody was produced in good titer to each of the four haptens and in all injected rabbits. Antibodies were characterized by means of precipitation assays and radioimmunoassay using contrast agents labeled with 125I. Antibody concentrations ranged from 0.23 to 2.7 mg/ml and varied with interval and frequency of booster injections. In addition to antibodies specific for the contrast media analogues, antibodies to the carrier protein were also detected. Antibodies were of the IgG class and in selected sera were 83-92% precipitable. The induction of antibodies to radiocontrast agents supports the allergic theory of contrast medium toxicity.

Animals↗
PubMedDate not supplied

In vivo measurement of hepatic iodine concentration using fluorescent excitation analysis.

Hepatic iodine concentration was measured in the live dog by external use of fluorescent excitation analysis. The number of characteristic photons produced by interaction of exciting radiation from an americium-241 source with iodine within the tissue is proportional to the tissue iodine concentrations. A correction is made for absorption of radiation by the abdominal wall and other tissues lying between the volume of liver being assayed and the detector collimator. The technique is applicable to the in vivo measurement of iodine concentrations from 0.5 to 40 mg/g. Accuracy of the technique is approximately +/- 10%, which is within the range of variation in iodine concentration at various sites within the liver. Radiation dose is low, and radiolabeled tracer compounds need not be used.

Animals↗
PubMedDate not supplied

The allergic theory of radiocontrast agent toxicity: demonstration of antibody activity in sera of patients suffering major radiocontrast agent reactions.

An allergic, immunologic mechanism for certain adverse reactions to radiocontrast agents has been postulated on the basis of clinical and theoretical considerations. One obstacle to the acceptance of this allergic theory has been the inability to demonstrate significant antibodies with specificity for these agents. In our studies, rabbits were immunized with 4 analogues of radiocontrast agents which induced IgG or IgE antibodies specific for the contrast media analogues. Then, to determine if antibodies to contrast agents were present in man a prospective, one-year surveillance of radiocontrast agent reactions was undertaken. Sera from 27 patients suffering severe reactions and 37 control subjects were analyzed by radioimmunoassay for antibodies reactive with radiocontrast media. Binding of radiolabeled contrast media was significantly elevated (p less than 0.01) by the serum globulin fraction of the patients suffering severe reactions. Demonstration of this antibody activity, although not proof of cause and effect between the presence of antibody activity and clinical symptoms, nonetheless adds support to the hypothesis that some adverse reactions to radiocontrast agents are due to antibodies.

Acetrizoic Acid↗
PubMedDate not supplied

New media. Particulate contrast media.

Particulate contrast agents, when compared to water-soluble media, offer the advantage of allowing the administration of high doses without creating hypertonicity gradients and ionic imbalances. Since these radiopaque particles are accumulated in the reticuloendothelial system, they could be ideal hepatic CT contrast agents. We have developed a method for making particles of 2 +/- 1 microns by precipitating from an organic solvent. Preincubation of these particles in human serum albumin overcomes the very serious problem of in vivo particle aggregation and embolization. The ethyl esters of iothalamic and iodipamic acid have been injected intravenously into mice, rats, and rabbits. Radiopacification of the liver is maximal within 2-3 hours postinfusion, with radiopaque material subsequently clearing through the biliary system. Elimination from the organism seems to be complete within a few days postinfusion. Efforts to decrease the subacute toxicity of these agents are underway.

Animals↗
PubMedDate not supplied

The in vitro activation of complement by radiologic contrast materials and its inhibition with epsilon-aminocaproic acid.

Radiologic contrast materials activate complement by both the classical and alternative pathways. This activation is time, dose, and temperature dependent and is able to proceed with equal facility in either the presence or absence of Ca++ or Mg++ chelating reagents (EGTA, EDTA). All the components examined (C1, C4, C2, Factor B, C3, and C5) were consumed during complement activation. Immune complexes are produced during interaction of serum with contrast materials. The activation of complement by contrast materials appears to be principally initiated by the activation of plasminogen to plasmin. Inhibition of plasminogen activators by epsilon-aminocaproic acid affects complement activation markedly.

Aminocaproates↗
PubMedDate not supplied

The potential of iosulamide meglumine as a contrast material for intravenous cholangiography: an experimental study in dogs.

Because of relatively low acute toxicity, iosulamide meglumine has been recommended as an improved contrast material for intravenous cholangiography. It has been postulated that high doses of the compound could be given safely with the expectation of achieving greater biliary excretion and improved opacification of the biliary tree. Experiments performed in dogs show that higher rates of infusion of iosulamide result in greater urinary elimination without additional biliary excretion. Consequently, iosulamide is unlikely to have any special advantage as a contrast agent.

Animals↗
PubMed1989

Effect of iodinated contrast media on blood clotting.

Recently, blood clot formation in catheters used for the injection of nonionic contrast media (CM) during angiography has been reported as being due to activation of hemostasis in the catheter. However, CM exhibit inhibitory properties regarding coagulation and platelet functions. The effect on blood clotting of iohexol, iopamidol, ioxaglate, diatrizoate, and ioxitalamate at a ratio of 10% v/v with nonanticoagulated human whole blood was evaluated using the kinetics of fibrinopeptide A (FpA) generation. Blood aliquots were taken every 2 minutes until blood clot occurred. Two groups of contrast media were identified: (1) iohexol and iopamidol, which increased the clotting time, and (2) ioxaglate, diatrizoate, and ioxitalamate, for which all clotting times were over 30 minutes and no FpA generation occurred.

Blood Coagulation↗
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↗
PubMed1990

Ultrasound contrast for hepatic tumors using IDE particles.

Iodipimide ethyl ester (IDE) can be formulated as dense spherical particles with narrow diameter distribution. When IDE particles are injected intravenously, the Kupffer cells of the hepatic sinusoids accumulate particles within 10 to 20 minutes, after which the clearance and excretion of IDE takes place. During the uptake phase, the dense particles act as scattering sites, increasing the echogenicity of normal liver tissue. In comparison, tumors and other lesions remain at pre-injection echogenicity, as they lack Kupffer cells and therefore do not retain particles. This report provides initial studies of contrast enhancement in rabbit livers with implanted VX2 tumors, scanned in vivo and evaluated ex vivo using pulse-echo techniques. The distribution of particles within hepatic lobules may explain why the observed echogenicity is greater than that predicted by single-particle backscatter theory. Directions for future improvements are discussed.

Animals↗
PubMed1996

Biochemical characterization of x-ray contrast media.

RATIONALE AND OBJECTIVES: Eleven ionic and nonionic contrast media were compared in parallel regarding their effects on various biochemical parameters in vitro. Partition coefficient, protein binding, release of histamine, hemolysis inhibition and complement activation were determined as well as inhibition of various enzymes. Additionally, incompatibilities between contrast media and intravascular drugs that often are coadministered were determined. METHODS: Partition coefficients were determined in the system n-butanol/water by spectrophotometry. Protein binding was measured by equilibrium dialysis. Histamine release from rat peritoneal mast cells was measured by radioassay. Hemolysis inhibition and complement activation was determined in beagle dog serum using antibody-coated sheep erythrocytes. The inhibition of enzyme systems was measured photometrically. Incompatibility with coadministered drugs was registered by appearance of precipitations. RESULTS: Hydrophilicity as determined by partition coefficients was highest for iotrolan and lowest for iotetrol. Protein binding ranged from practically zero for most substances to 14% for ioxaglate. Histamine release was highest for diatrizoate (77% at 100 mg I/mL) and lowest for iodixanol (1%). Complement activation at 100 mg I/mL ranged from 0% (diatrizoate, iopamidol) to 77% (iopentol). The inhibition of the enzyme systems urokinase, streptokinase, collagenase, tissue plasminogen activator, and lysozyme was lowest for the nonionic dimers. CONCLUSIONS: All compounds influenced the parameters tested. However, the degree of interaction was different. Although there was no significant correlation between hydrophilicity (partition coefficient) or osmolality and the tested parameters, nonionic dimers seemed to be superior to nonionic monomers. The reason might lie in reduced chemotoxicity of this class of contrast media.

1-Butanol↗
PubMed1982

Value of high contrast medium dose in brain CT.

Fifty-five patients with brain lesions were examined by computed tomography (CT) after two doses of contrast medium: a bolus injection of 65% meglumine diatrizoate, 1 ml/kg, and a bolus injection of 65% meglumine diatrizoate, 1.5 ml/kg, in combination with an infusion of 250 ml meglumine iodamide containing 110 mg I/ml. The studies were usually performed 2 days apart and were analyzed by three radiologists. In 25 patients, one or more of the radiologists changed the diagnosis or the number or size of the lesions when the two scans were observed separately. In three patients, the primary tumor or metastases were seen in the study performed after the higher dose only, and, in two other patients having cerebral metastases, a greater number of metastases were detected in the high dose study. The lower dose containing 15 to 31 g iodine (306 mg iodine/kg) seems to be inadequate in CT of the brain.

Brain↗
PubMed2005

Stability of doxorubicin combined with Radioselectan, a contrast agent, for chemoembolization.

OBJECTIVE: To assess the stability of doxorubicin combined with Radioselectan. METHODS: Solutions of doxorubicin 5 mg/mL were prepared from commercially available 50 mg powder with 10 mL of Radioselectan. They were stored in glass syringes at 4, 25 and 45 degrees C. The concentrations of doxorubicin were determined using a stability-indicating high-performance liquid chromatography method. The initial and final pHs of solutions were compared. The times (t90) needed for doxorubicin to fall to 90% of its initial concentration were calculated by a linear regression analysis. RESULTS: The t90 [95% confidence limits] were 79 [75-83], 56 [53-59] and 22 [21-23] hours for the solutions stored at 4, 25 and 40 degrees C respectively. The initial pH of the solutions stored at 4, 25 and 40 degrees C were 6.52, 6.50 and 6.51 respectively. The final pH of solutions stored at 25 and 40 degrees C decreased significantly by 0.3 and 0.9 respectively. No change of pH solution stored at 4 degrees C was observed. CONCLUSION: Doxorubicin combined with Radioselectan stored at room temperature is stable for 48 h.

Antibiotics, Antineoplastic↗