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Biomedical subjects

R C Brasch

Publications and source records attributed to R C Brasch.

212 records · Page 12Linked to original sources
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

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

Evidence supporting an antibody mediation of contrast media reactions.

Despite past doubts of the existence of antibodies to radiographic contrast material, there is now both clinical and experimental data to indicate that such antibodies do exist and that in certain individuals the antibodies may lead to severe or even fatal contrast media reactions. This article will detail the accumulated evidence supporting an allergic theory of contrast media toxicity in an attempt to stimulate interest and further investigation into this previously abandoned theory of mediation.

Animals↗
PubMedDate not supplied

Nitroxyl spin label contrast enhancers for magnetic resonance imaging. Studies of acute toxicity and mutagenesis.

Two nitroxyl spin label (NSL) compounds that are used experimentally as in vivo contrast enhancers in magnetic resonance (MR) imaging were tested for acute toxicity in rats and for genotoxic effects in cell cultures. These compounds, 2,2,5,5-tetramethyl-1-pyrrolidinyl-oxy-3-carboxylic acid (PCA) and 2,2,6,6-tetramethyl-1-oxido-4-piperidinyl-1-succinic acid (TES) and their hydroxylamine and amine derivatives did not induce sister chromatid exchanges or mutations in Chinese hamster ovary cells at the HGPRT or Na+/K+ ATPase loci. The acute LD50 doses in rats for PCA and TES are 15.1 mmol/kg or greater, suggesting relatively high tolerance.

Animals↗
PubMedDate not supplied

Relative intensity of abdominal organs in MR images.

Knowledge of the normal relative intensity of organs and tissues is a valuable aid to clinical interpretation of magnetic resonance images. In this study the in vivo spin echo image intensities of normal parenchymal organs and other structures in the upper abdomen were evaluated for eight parameter combinations. The examinations of 40 patients were used. Image intensity and calculated T1, T2, and spin density values were obtained for liver, spleen, pancreas, renal cortex, renal medulla, bone marrow, skeletal muscle, and fat. Repetition times (TR) of 500, 1,000, 1,500, and 2,000 ms and echo times of 28 and 56 ms were used. The T1 and T2 values and relative spin density were calculated using a new algorithm. Liver had the smallest relative standard deviation of T1 of all the tissues studied. For comparison purposes, relative image intensities were calculated by normalizing them to the intensity of liver in the same image. The resulting compiled data show the normal ranks and ranges for relative intensity for the tissues in each of eight types of spin echo images. Although images with short TR and echo time (TE) are known to display the greatest T1 contrast, the mean relative intensities of all tissues except muscle and fat in the TR = 500 and TE = 28 ms images were within 20% of liver. A much larger spread in the normal relative intensities was observed with longer TE and TR.

Abdomen↗
PubMedDate not supplied

Comparison of initial biodistribution patterns of Gd-DTPA and albumin-(Gd-DTPA) using rapid spin echo MR imaging.

The initial biodistribution patterns of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA), an extracellular fluid contrast agent, and human serum albumin, paramagnetically labeled with 19 Gd-DTPA groups and used as an intravascular agent, were compared in the brain, heart, liver, and major mediastinal vessels of rats. Repeated 4 s spin echo images acquired after injection of 0.2 mmol/kg Gd-DTPA demonstrated a maximum enhancement between 15 and 25 s of 57% in brain, 307% in heart, 220% in liver, 83% in subcutaneous tissue, and 380% in slowly flowing blood in mediastinal vascular structures. In the following 55 s there was a continuous decrease (average 45%) in signal intensity in each tissue except brain. Albumin-(Gd-DTPA), injected at a four times lower molar dose (0.045 mmol/kg) with respect to Gd-DTPA, demonstrated maximal enhancement of brain by 34%, heart by 237%, liver by 186%, and blood in mediastinal vessels by 325%. Gadolinium-DTPA, which rapidly diffuses from the small vessels into the interstitial space, was noted to accumulate in solid tissues and subsequently to be partially eliminated within 70 s of administration. Signal enhancement achieved with albumin-(Gd-DTPA) remained at a constant level over the 70 s observation period. These data further support the notion that albumin-(Gd-DTPA), due to its predominantly intravascular distribution, might be applied advantageously for the assessment of perfusion and blood-volume disorders.

Animals↗
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Vascular mapping using albumin-(Gd-DTPA), an intravascular MR contrast agent, and projection MR imaging.

An intravascular magnetic resonance (MR) contrast agent is valuable for vascular mapping of tissues when used in combination with projection spin-echo MR imaging. The primary advantage of using projection imaging lies in its global depiction of anatomy. Also, relatively short echo time values can be readily achieved, reducing flow dephasing signal losses from blood and increasing overall signal-to-noise. These advantages, coupled with the reduction of blood pool T1 values due to the presence of the intravascular contrast agent, allow for detailed spatial mapping of slow-flow vascular structures using MR.

Albumins↗
PubMedDate not supplied

Nonenzymatic bioreduction in rat liver and kidney of nitroxyl spin labels, potential contrast agents in magnetic resonance imaging.

Paramagnetic nitroxyl spin labels have potential clinical utility as contrast agents in proton magnetic resonance imaging. Reduction of the nitroxyl moiety in vivo results in the formation of the diamagnetic hydroxylamine, which lacks contrast-enhancing activity. Bioreduction is therefore an important determinant of the imaging behavior of these agents. Both enzymatic and nonenzymatic reduction mechanisms have been suggested for nitroxyl spin labels. This study examines the nonenzymatic mechanisms in rat liver and kidney, mammalian tissues that demonstrate high reducing activity. Protein-free preparations, obtained by heat precipitation or ultrafiltration of rat liver and kidney homogenates, were used to test piperidine and pyrrolidine nitroxyl spin-label derivatives, for which imaging properties and bioreduction had previously been examined. For the piperidine derivative, the initial reduction rates in ultrafiltrates and supernatant fluids were 25-60% of those in whole liver and kidney homogenates. However, the pyrrolidine derivative was reduced at rates much slower than those in whole tissue homogenates. The reduction in whole tissue homogenates was NADPH-dependent, while reduction in ultrafiltrates was unaffected by the addition of NADPH. Preincubation of the ultrafiltrates and supernatant fluids with ascorbic acid oxidase caused almost complete inhibition of the reduction. The reduction rates of these nitroxyl derivatives were determined in ascorbic acid solution; second order rate constants were 0.45 +/- 0.04 and 0.0042 +/- 0.001 mM-1 min-1 for the piperidine and pyrrolidine derivatives, respectively. The concentrations of ascorbic acid in the supernatant fluids and ultrafiltrates of rat liver and kidney were then predicted from the observed reduction rates and found to be virtually identical with those from spectrophotometric determinations.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMedDate not supplied

Magnetic resonance imaging of local soft tissue inflammation using gadolinium-DTPA.

Chemical inflammation was induced subcutaneously in 10 rats using carrageenan mucopolysaccharide. Dual spin echo (SE) imaging of inflammatory loci was performed employing a 0.35 tesla resistive magnet. In addition, gadolinium-DTPA was administrated intravenously into 5 rats to evaluate the potential benefits of paramagnetic contrast medium for the detection and characterization of inflammatory loci. T2 weighted SE images demonstrated the edematous lesions as zones of high intensity. This was attributed to the increased relaxation times of lesions when compared to the adjacent soft tissue. The inflammation was also delineated on T1 weighted SE images, but only after injection of paramagnetic Gd-DTPA. Carrageenan mucopolysaccharide-induced lesions provide a useful experimental model for in vivo evaluation of soft tissue inflammation using magnetic resonance imaging. No special benefit of paramagnetic contrast enhancement was demonstrated in this model of local edema.

Animals↗
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Comparison of ionic and non-ionic nitroxide spin labels for urographic enhancement in magnetic resonance imaging.

Two nitroxide spin labels (NSL) were compared for in vitro relaxivity and in normal rats for efficiency of urographic enhancement. One of the NSL, PCA, a pyrrolidinyl agent, was ionic and one, NAT, was a non-ionic pyrrolidinyl NSL with multiple hydroxyl substituents for water solubility. Using both NSLs the renal medulla and papilla were noted to show greater contrast enhancement than the cortex, with a maximum enhancing effect between 5 and 15 minutes. Using doses of 1.0 and 2.5 mmol/kg, more than 100 per cent increases in spin echo intensities above the baseline were observed. The lowest tested dose of 0.1 mmol/kg showed an easily detectable enhancing effect for NAT. The good contrast enhancing properties of NAT, considered together with its better acute tolerance, justifies further investigation of this non-ionic compound.

Animals↗
PubMedDate not supplied

Contrast-enhancing properties of Gd-DTPA at 2.0 Tesla.

The contrast enhancing properties of Gd-DTPA in various tissues, including myocardium, liver, brain, skeletal muscle, and subcutis were investigated in vivo at 2.0 Tesla. Employing T1-weighted short pulse sequences (TR = 300 msec, TE = 14 msec) signal intensity of myocardium increased by 88%, brain by 19%, liver by 61%, skeletal muscle by 50%, and subcutis by 52% at 2 min after intravenous injection of 0.2 mmol/kg Gd-DTPA in rats. Signal intensity was highest at 2 min after injection and was relatively decreased at 20 min. Tissue intensities had returned to baseline at 60 min. In a separate experiment, fast (4 sec), repeated spin-echo image acquisitions allowed for assessment of the initial, dynamic distribution pattern of Gd-DTPA between 4 sec and 72 sec after intravenous injection. Tissue signal intensities peaked between eight and 16 seconds after injection and slowly decreased thereafter. This study shows that the contrast-enhancing properties of Gd-DTPA can be effectively assessed using T1-weighted short pulse sequences at 2.0 Tesla.

Adipose Tissue↗
PubMedDate not supplied

NMR imaging of experimental brain abscess: comparison with CT.

An experimental canine model of a brain abscess induced with alpha-streptococcus was imaged in the cerebritis and capsule stages by computed tomography (CT) with intravenous contrast enhancement and by nuclear magnetic resonance (NMR). An NMR imager equipped with a superconducting magnet operating at 3.5 kG was used for several imaging techniques. The NMR images were compared with the CT scans and with gross and microscopic neuropathologic findings. CT showed enhancement of the inflammatory focus at the site of capsule formation while the necrotic center retained its low-density appearance. Spin-echo NMR images demonstrated the presence and extent of abnormal infected brain tissue more accurately than contrast-enhanced CT. Spin-echo images showed the necrotic center, the surrounding inflammatory zone, and peripheral edema without discriminating distinctly between the latter two zones. Inversion-recovery NMR images depicted a lesion of lesser extent, showing the necrotic center circumscribed by the surrounding edematous brain tissue. The inversion-recovery technique was best for demonstrating gray- and white-matter contrast in normal brain and depicted edema as loss of contrast between the gray and white matter. NMR offers some advantages over CT in imaging brain abscess, and the variety of NMR imaging techniques is useful for characterizing the different pathologic areas.

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