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Biomedical subjects

R Moncada

Publications and source records attributed to R Moncada.

At least 37 records · Page 2Linked to original sources

Contrast media-induced chromosomal damage in human lymphocyte cultures.

Ionic (diatrizoate, ioxaglate) and nonionic (iohexol, iosimide, iopromide, and iotrolan) contrast media (CM) were evaluated for their cytogenetic effects in lymphocytes. Heparinized blood was mixed with culture medium RPMI-1640 supplemented with phytohemagglutinin, fetal calf serum, and antibiotics. Plastic tubes containing blood samples were incubated at 37 degrees C in 5% CO2 humidified air for 48 hours. To these cultures, increasing amounts of CM were added and cells incubated for an additional 24 hours. After this exposure, red blood cells were lysed with hypotonic KC1, lymphocyte smears fixed on glass slides and stained with May-Grünwald Giemsa. Chromosomal damage was analyzed by a micronucleus test. All CM tested induced micronuclei in lymphocytes quite significantly (P less than .001) when compared with the frequency of micronuclei in controls. These observations on the genotoxic potential of nonionic CM suggest that factors other than ionic composition and osmolality are involved in clastogenesis; further studies are needed to establish the molecular mechanisms in CM induced chromosomal damage.

Cell Nucleus

Nonionic contrast medium: effects on blood coagulation and complement activation in vitro.

A nonionic contrast medium was evaluated in vitro for its effects on coagulation and complement activation in comparison to a low osmolal contrast agent. In clotting assays each contrast medium was mixed with blood and clotting parameters were analyzed by using a thromboelastographic machine. Platelet function was studied by incubating platelet-rich plasma with individual contrast medium, and the subsequent challenge of a platelet aggregating agent. Complement activation was assessed by the hydrolysis of C3 protein into C3c fragment in contrast medium-incubated serum. Immunoelectrophoresis was used to detect C3c protein. Both the nonionic contrast medium and the low osmolal contrast agent acted as anticoagulant and antiplatelet agents, however, results with the low osmolal contrast agent were more pronounced compared to the nonionic contrast medium. Even at nonphysiologic concentration of contrast medium, no significant conversion at C3 to C3c was seen. Since these two agents caused hypocoagulable states in vitro, it is likely that patients with thrombocytopenia, severe liver disease and with clotting factor deficiencies may present hemostatic complications during angiographic procedures.

Blood Coagulation

Multimodality approach to pericardial imaging.

In this chapter, three modalities--computed tomography, nuclear magnetic resonance imaging, and echocardiography--have been discussed. Each of these techniques offers unique advantages in the diagnosis of pericardial disease. Although echocardiography is the least expensive, most sensitive, and least invasive technique for the identification of pericardial effusion, false-positive and negative studies may be encountered. These are often resolved with the use of computed tomography and may be resolved with magnetic resonance imaging. Plain film radiography still has the advantage of identifying pericardial calcifications and will suggest the diagnosis of large pleural effusions at low cost and radiation dose. Exquisite portrayal of cross section anatomy using CT will aid in the diagnosis of multiple small tumor deposits and will clearly identify pericardial thickening. The value of magnetic resonance imaging awaits carefully controlled blinded studies, but its role in characterization of the content of pericardial effusions appears especially promising.

Cardiomyopathy, Restrictive

Normal excretory urography in patients with primary kidney neoplasms.

The records of 65 consecutive patients discharged from the hospital with a diagnosis of primary parenchymal neoplasm of the kidney were reviewed. Four of the 65 patients had neoplasms which were not detected by excretory urography. The 4 undetected lesions included 3 renal cell carcinomas and 1 oncocytoma. All of these lesions projected from the anterior or posterior surface of the kidney, and all 4 were clearly demonstrated by computed tomography. Normal findings on an excretory urogram do not completely exclude a neoplasm of the kidney. When there is strong clinical suspicion of a renal neoplasm, computed tomography should be the initial examination or should be done even if the urogram has shown normal findings.

Adenoma

Complement abnormalities during contrast media procedures.

Complement changes following the administration of the two most commonly used intravascular contrast media (CM) diatrizoate and iothalmate were studied in 26 patients by measuring complement component C3 levels and the total hemolytic function. Blood from these patients was obtained in plastic tubes containing 10 mM ethylene diamine tetra-acetic acid (EDTA) prior to and 15 min after contrast media infusion. In thirteen patients who received iothalamate a 28% drop in C3 concentration and a 19% change in total hemolytic complement was seen. In the second group of thirteen patients diatrizoate caused a 20% C3 decrease and a 15% reduction in total hemolytic complement. Since iothalamate is a hyperosmolar and hyperviscous solution compared to diatrizoate, it is likely that these factors are responsible for changes in complement level which may present potential risk to patients with depressed immunologic status. This study suggests that screening of patients for their total complement profile may provide useful information in minimizing adverse reactions to contrast material.

Adult

Ultrastructural changes in rat aortic endothelium during contrast media infusion.

A rat model was employed to investigate contrast media (CM) induced ultrastructural changes in the vascular endothelium. Ionic contrast materials such as Renografin-76 (diatrizoate meglumine diatrizoate sodium), MD-76 (diatrizoate meglumine diatrizoate sodium), and Angiovist (meglumine diatrizoate) were injected into the femoral vein of anesthetized male Wistar rats (240-260 g) and allowed to circulate. Control animals were similarly injected with equiosmolar sucrose and physiologic saline. The thorax was opened 15 minutes, 1 hour, and 4 hours postinjection and cardiac perfusion performed using Karnovsky's fixative; the thoracic aorta was then surgically removed, and processed for transmission electron microscopy. All CM produced shrinkage in cell cytoplasm and nuclear structures thereby causing distortions in cell morphology. In control tissues, however, no such ultrastructural damages were noted. Within 15 minutes of CM infusion, electron dense granules were seen on the luminal surface of endothelial cells, in pinocytotic vesicles, as well as in the gap junctions between cells. These observations indicate that contrast media intake occurs via vesicular transport, and through the cell junction.

Animals

Molecular markers of contrast media-induced adverse reactions.

Currently used routine laboratory screening methods are not reliable in the prediction of contrast media-related adverse reactions. Cost-effective laboratory methods for various molecular markers of pathophysiologic activation have now become available. In vitro activation tests in high-risk patients may prove to be useful in the prediction of contrast-induced activation of various adverse reactions. If prior clinical evaluation of a patient suggests an ongoing pathologic process, profiling of the following molecular markers may prove to be useful and helpful in avoiding contrast-induced adverse reactions: Fibrinopeptide A, platelet factor 4, thromboxane B2, 5-HETE, physiologic inhibitors of proteases, B beta 15-42 related peptides, bradykinin/kininogen, and anaphylactozins. In patients suspected of reacting to contrast agents, a small dose of 1 to 5 ml can be injected as a bolus and molecular marker profiling on blood drawn after the infusion may prove to be useful screening tests. Additional clinical studies are needed to prove this. However, this screening test should be performed with extreme caution, since some of the patients are known to react to as little as 1 ml dose. The safety of newly developed nonionic contrast agents can be readily assessed by profiling various molecular markers of adverse reactions, which provide a more reliable and quantitative assessment of contrast-induced adverse reactions. Based on molecular marker profiling, various prophylactic agents can be given to high-risk patients to avoid contrast-induced adverse reactions.

Angiocardiography

Evaluation of superior vena cava syndrome by axial CT and CT phlebography.

Transverse axial computed tomography (CT) has been combined with CT digital phlebography to study nine patients with superior vena cava syndrome. Six were due to malignancy, two were secondary to benign disease, and one was a paraneoplastic manifestation. This combined CT approach successfully identified the abnormal morphology of the superior vena cava, demonstrating external compression, encasement, or intraluminal thrombus in all patients and the collateral venous channels in eight. The efficacy and advantages of this technique are discussed. This technique is a rapid, informative, and cost-effective method for the workup of superior vena cava syndrome. The CT digital phlebogram, however, is not successful in regularly and optimally opacifying the normal superior vena cava because of the limited amount of contrast material, dilution effect of the nonopacified incoming flow from the jugular and azygos veins, and the lack of image enhancement from the CT digital scanograms.

Adenocarcinoma

Intravenous contrast bolus in computed tomography investigation of mass lesion.

Using bolus intravenous contrast (25-75 Renografin 60) and 5-second scanning capability, better definition of vascular anatomy as well as the vascular nature of mass lesions in the chest and abdomen could be demonstrated. The immediate higher concentration of iodine in vessels and organs following initial bolus, improves visualization of these structures dramatically when compared to drip-infusion technique. A description of the technique and examples are shown.

Abdominal Neoplasms

Characterization of cell surface antigens of human mammary epithelial cells with monoclonal antibodies prepared against human milk fat globule.

Hybridomas have been prepared that secrete monoclonal antibodies against three different surface antigens of normal human mammary epithelial cells by fusion of mouse myeloma cells with spleen cells from mice and rats immunized with delipidated human milk fat globules. Using a novel method for molecular weight determination, the three different monoclonal antibodies, BLMRL-HMFG-Mc3, BLMRL-HMFG-McR2, and BLMRL-HMFG-Mc5, were found to identify molecules with apparent molecular weights of 46,000, 70,000, and 400,000 daltons, respectively. The latter is a mucin-like glycoprotein with a high sugar content and has not previously been described as a component of the human milk fat globule or of human mammary epithelial cell membranes. Single-cell quantitation of binding of monoclonal BLMRL-HMFG-Mc5 to three breast tumor cell lines using a Microscope Spectrum Analyzer and indirect immunofluorescence revealed a heterogeneous expression. Further, using a competitive radioimmunoassay, it was found that breast tumor cell lines differed by at least 10-fold in the 400,000-molecular-weight antigen content. None of the three antigens are detectable on several nonbreast cell lines, including normal breast fibroblasts.

Animals

Chronic stridor in a child: CT diagnosis of pulmonary vascular sling.

A child without chronic stridor and tracheal narrowing was considered to have a primary tracheal abnormality. Computed tomography (CT) identified an aberrant left pulmonary artery originating from the right pulmonary as the cause of the tracheal abnormality. The advantages of CT over conventional studies are discussed.

Child

Ionic and non-ionic contrast media interaction with anticoagulant drugs.

Normal and pathologic human plasmas were incubated with radiographic contrast media, heparin, Dextran-40 and saline. Renografin-60 produced a strong anticoagulant effect and the clotting times were significantly prolonged; the addition of heparin resulted in greatly elevated thrombin time. No such prolongation was noted with Dextran-40. P-297, ioxaglic and ioxithalamic acids also showed similar anticoagulant properties. When dogs were injected with contrast media and heparin, the overall anticoagulant effect lasted for more than 6 hours, while contrast media or heparin effect remained for a short period of time. Clinical significance of contrast media interactions with anticoagulant drugs is discussed.

Animals

Contrast media induced serotonin release in human blood.

Several contrast media were tested for their ability to release serotonin from whole blood. Renografin-60, Hypaque M-75, Vascoray and Conray were incubated with human blood at 37 degrees C for 60 min. Platelet-poor plasma was analysed for serotonin using a high performance liquid chromatographic technique. Seven non-ionic contrast media were similarly incubated and serotonin levels determined. Ionic contrast media induced a greater release of serotonin compared with non-ionic ones. The amount of serotonin was not proportional to iodine concentration in blood. These results suggest that hypertonic solutions of contrast media produce a physical injury to platelets causing them to release their granular contents.

Adult

Diagnosis of dissecting aortic aneurysm by computed tomography.

Computed tomography (CT) of the torso combined with simultaneous intravenous bolus injection of contrast media was used in sixteen patients suspected of having dissected their aorta. All patients had subsequent correlative percutaneous aortography within 24 h of the CT examination. Four patients proved to be normal, one had an aneurysm of the thoracic aorta, and eleven had aortic dissection (five type I, six type III dissection). All eleven patients with aortic dissections were diagnosed by CT and angiography; nine had spontaneous dissections and two had iatrogenic injuries to the aorta. Limitations of this imaging procedure include; inability to detect aortic valvular dysfunction and failure to provide an adequate perspective of aortic branch involvement. Potential benefits include: avoidance of aortogram in some cases, relative non-invasiveness, rapidity and ease of procedure, and less expense, radiation, contrast media, and discomfort to the patient. Early experience with CT-enhancement technique has reliably demonstrated normal as well as abnormal aortic wall morphology. It may have a place as an alternative to the conventional aortogram.

Adult