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Biomedical subjects

M R Violante

Publications and source records attributed to M R Violante.

11 recordsLinked to original sources

Ultrasound properties of liver with and without particulate contrast agents.

Basic acoustic parameters are examined in rabbit liver with and without a solid contrast agent used for tumor detection. In normal liver, backscatter, attenuation, and sound speed are found to decrease with increasing water content. The addition of micron-sized particles made from iodipamide ethyl ester (IDE) can increase backscatter and attenuation depending on size and concentration. A discrepancy of the increased backscatter from theoretical predictions based on random scatterers is attributed to the particle's biodistribution in the liver.

Absorption

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

Potential of microparticles for diagnostic tracer imaging.

The development of tracer imaging agents with sufficiently high label activity can lead to problems of poor aqueous solubility of the labeled tracer, causing formulation difficulty, inadvertent accumulation by phagocytic cells, or inadequate signal to noise. Our approach to solving these problems is to administer the tracer in the form of monodispersed nanoparticles which can safely be administered intravenously. Since the phagocytosis of these particles can be controlled or avoided in a predictable manner by altering particle size and surface characteristics, imaging tracers can be designed for a variety of intended applications. This paper summarizes the results and ideas for several applications involving computed tomography, ultrasound, magnetic resonance imaging, and radioisotope imaging modalities.

Animals

Ventricular fibrillation from diatrizoate with and without chelating agents.

The toxicity of Renografin 76% was compared with that of Hypaque 76% by selective injection of each into the right coronary artery of dogs. Renografin contains the chelating agents sodium citrate and disodium edetate, while Hypaque contains calcium disodium edetate and no sodium citrate. Ventricular fibrillation occurred significantly more often with Renografin, suggesting that chelating agents contribute to toxicity in coronary angiography.

Angiography

The effect of barium on blood in the gastrointestinal tract.

The effect of various commercial barium sulfate preparations on blood coagulation, flocculation, and hemolysis was studied. There was considerable variation not only among different barium products but also among different concentrations of the same product. There is no good experimental evidence that barium enemas do stop bleeding. It is probably best to avoid the use of any enema in attempting to control major colonic bleeding; but if an enema is given for this purpose, a tap-water enema is better, as it contains no anticoagulants and is more effective in producing clot formation than most barium suspensions.

Barium Sulfate

Iothalamate ethyl ester as hepatolienographic agent.

In search of a hepatolienographic agent, the iothalamate ethyl ester particulate suspension was prepared with the average particle size of 1.5 mu in diameter. When mixed with plasma of different animal species, the physical properties of the particular suspension changed significantly. The nature of this difference is not understood but is probably related to protein-particle interaction in the different species. Doses of 550 mg iodine per kg body weight as a single intravenous infusion of the particulate suspension resulted in satisfactory opacification of liver and spleen in rats, followed by complete loss of radiopacity within three days. Larger doses resulted in the death of the rats within 12-14 hours. In general, the mice tolerated larger doses than rats, but there was very poor opacification of the liver, despite good opacification of spleen. Further work is being carried out to improve the suspension and to better understand the difference in behavior of the particulate suspension in different animal species.

Animals

Cerebral water content, blood flow and EEG changes after cardiac arrest in the dog.

Changes of cerebral water content, blood flow and cortical EEG following cardiac arrest (8-14 minutes) were studied in 14 mongrel dogs. With five hours of maintenance, changes in the water content both in grey and white matter were found to be insignificant. (Grey matter: control 78.68 +/- 2.62%; arrest 79.91 +/- 1.76%. White matter: control 66.66 +/- 4.10%; arrest 67.76 +/- 1.88%). Blood flow was measured using 15 micron microspheres labeled with Sr, 85 Ce141 and Yb.169 Flow in grey matter was decreased to 47% at 3 hours and 53% at 5 hours; while in white matter it was 67% at 3 hours and 75% at 5 hours from baseline. Deterioration of the cortical electrical activity was observed in all animals having an arrest of more than 8 minutes. In aminals having arrest of longer than 12 minutes there is either no return (isoelectric) or marked slowing of cortical electrical activity. From this and previous studies, it is concluded that with more than 8 minutes of cardiac arrest and up to 5 hours of maintenance there is impairment of cortical perfusion which is not associated with a significant increase in total water content. The lack of increase in total water content, however, does not mean there is no local swelling or edema such as in endothelial cells.

Animals

Reduction in ventricular fibrillation using calcium-enriched Renografin 76.

Renografin 76 has been shown to have significant calcium-binding properties in vivo and in vitro. Two contrast media solutions were compared by selective injection into the right coronary artery of dogs. One set of injections was made with commercially available Renografin 76 (referred to as stock Renografin) and another set of injections was made with Renografin 76 to which had been added 24 mMols/liter of calcium chloride dihydrate. Ventricular fibrillation occurred significantly more often with the stock Renografin 76. The nature of the calcium binding and its effects are discussed.

Angiography

Protein binding to iothalamate ethyl ester.

A major problem in the development of a particulate hepatolienographic agent is the prevention of particle aggregation upon contact with blood. When iothalamate ethyl ester, a particulate suspension for potential use as an hepatolienographic agent, was mixed with human or animal plasmas, it resulted in moderate to severe flocculation. In a study conducted to define the binding of plasma proteins to the iothalamate ethyl ester particles, plasma was reversibly adsorbed to various particle preparations. Fractions obtained by incubation of the particle-plasma complexes in buffers of increased ionic strength and decreased pH were subjected to polyacrylamide disc gel electrophoresis. The fraction containing the specifically bound proteins produced three distinct bands corresponding to prealbumin, albumin, and fibrinogen. Since the particles flocculated only when mixed with plasma, it is postulated that the fibrinogen-particle interaction is a major factor leading to particle agglutination.

Blood Proteins

Comparison of hepatic VX2-carcinomas after intra-arterial, intraportal and intraparenchymal tumor cell injection. An angiographic and computed tomographic study in the rabbit.

Hepatic VX2-carcinomas were produced in 45 rabbits by injection of approximately 25 x 10(6) tumor cells into the proper hepatic artery, the superior mesenteric vein, or directly into the liver parenchyma. With the intra-arterial and intraportal approaches, survival times (12 +/- 4 and 13 +/- 5 days, respectively), radiographic and autopsy findings revealing a liver with diffuse tumor involvement were very similar. With intraparenchymal tumor cell injection, survival time was significantly longer (18 +/- 14 days) and the hepatic VX2-carcinoma always localized. The tumor appeared hypervascular on angiography and hypodense on computed tography (CT). After intravenous injection of diatrizoate, the attenuation in the tumor increased less than in the surrounding liver so the lesion became relatively less dense and more easily recognized on CT-scans. The apparent discrepancy between angiographic and contrast enhanced CT findings can be explained with the difference in blood supply of hepatic tumors and normal liver parenchyma.

Angiography