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Objective. To investigate the trafficking of circulating blood neutrophils and synovial fluid neutrophils in rheumatoid arthritis (RA) patients and the influence of a 1,000-mg intravenous pulse of methylprednisolone succinate (MP). Methods. Neutrophils were isolated from the circulation and from the knee synovial compartments of subjects with RA. Circulating neutrophils were labeled with technetium-99m hexametazime (99mTc-HMPAO) and reinjected intravenously. Synovial fluid neutrophils were labeled with indium-111 oxine and reinjected into the knee from which they were isolated. Gamma camera images were obtained at intervals up to 24 hours post MP. Each patient had a baseline study (no MP) and a study in which MP was administered either 4 hours before (2 patients), 10 minutes before (1 patient), or 30 minutes to 1.5 hours after (6 patients) injection of the radiolabeled neutrophils. Subsequent analysis allowed quantitation of the neutrophil uptake into and clearance from the knee as a function of time. Results. Nine patients who had not received glucocorticoids in the previous 3 months were studied. MP significantly decreased neutrophil ingress in 13 of the 16 knees studied (almost total inhibition in 5 knees), and this occurred within 1.5 hours of MP administration in all except 1 knee. At 24 hours after MP administration, there was a significant increase in visual analog scale (VAS) scores for well-being and significant decreases in scores on the modified Health Assessment Questionnaire (P < 0.05), tender joints (P < 0.005), VAS for pain (P < 0.005), and generalized stiffness (P < 0.005), as well as a decrease in the C-reactive protein level (P < 0.05). MP had no effect on neutrophil egress (2 patients). Two additional patients who were receiving oral glucocorticoids were studied. One of them was clinically unresponsive to oral prednisolone, and MP had no effect on neutrophil ingress. The other patient showed no neutrophil ingress during the baseline study. This was confirmed by the presence of a noninflammatory synovial fluid at arthrocentesis. Conclusion. Neutrophil ingress into and egress from inflamed joints can be accurately monitored using radiolabeled neutrophils and quantitative gamma camera imaging. MP rapidly and substantially decreases neutrophil ingress into inflamed joints. In contrast, MP has no effect on neutrophil egress from the joint.

This study was performed to assess the relative contributions of contrast medium osmolality and chemotoxicity to contrast-induced blood-brain barrier (BBB) damage. Experimental carotid angiography was carried out in rabbits with mannitol at an osmolality of 714 mOsm/kg, with the nonionic, monomeric contrast media iohexol and ioversol at similar osmolalities, and with the nonionic, dimeric contrast media iodixanol and iotrolan at osmolalities less than half that of the mannitol. The amount of damage caused by the procedure was assessed by determining the amount of intracerebral extravasation of intravascularly injected technetium-99m-pertechnetate. Mannitol caused no detectable BBB damage, but all four contrast media caused BBB damage that was significantly more severe than that caused by mannitol. The BBB damage caused by carotid angiography with iohexol, ioversol, iodixanol, and iotrolan was not attributable to their osmolalities, but due to some other physical and/or chemical effects of these media on the BBB.

Whisson CC, Evill CA, Sage MR, Wilson AJ. Effect of additional cations on the twitching reaction to intracarotid, nonionic contrast media in rabbits. Invest Radiol 1990;25:1004–1009. Previous investigations in this laboratory have confirmed the observation of facial muscle twitching during intracarotid injections of nonionic contrast media (CM) in rabbits. The reaction appears to be a locally mediated effect. To further investigate this reaction, cortical electroencephalogram (EEG) and facial electromyogram (EMG) recordings were made from rabbits receiving selective internal carotid artery (ICA) and external carotid artery (ECA) injections of CM. The effects of iopromide and iohexol were compared with and without the addition of sodium (Na) and calcium (Ca) ions at different concentrations. External carotid injections of iopromide also were performed in some animals paralyzed with D. tubocurarine to exclude the possibility that the reaction is due to an effect on peripheral nerves. The addition of between 5 and 20 mM Ca ions to both CM prevented the reaction but while the addition of Na ions (up to 150 mM) to iopromide had some preventative effect, it did not totally abolish the reaction. In those animals paralyzed with D-tubocurarine, the reaction to iopromide, as observed and recorded by EMG, was the same as that occurring in nonparalyzed animals. This finding is consistent with this reaction being independent of the peripheral nervous system.

The effect of intracarotid injections of methylglucamine iothalamate has been compared with that of mannitol solution of similar osmotic strength. The degree and distribution of blood-brain barrier disruption was assessed using Evans' Blue dye as a visual marker and by contrast enhancement measured by computer tomography (CT) scanner. Evans' Blue staining was found to match CT enhancement closely. It was also found that methylglucamine iothalamate injections resulted in significantly greater blood-brain barrier permeability. The relevance of these findings to chemotherapy of brain tumours is discussed briefly.

A rabbit model was used to assess the effects of intracarotid injections of ionic monomer (meglumine iothalamate), non-ionic monomer (iohexol, iopromide), and non-ionic dimer (iotrol) contrast materials on the blood-brain barrier. The degree of blood-brain barrier damage was assessed qualitatively using Evans' blue dye, and quantitatively by calculating the difference in pertechnetate uptake between injected and non-injected hemispheres. The results showed that the non-ionic dimer, iotrol, had the least effect on the blood-brain barrier, and that although iopromide and iohexol produced greater damage than iotrol, the ionic compound, meglumine iothalamate, caused the greatest disruption to the blood-brain barrier. The implications of these findings are discussed.

The incidence of post-myelographic side-effects has been significantly reduced since the advent of the new generation of water-soluble, non-ionic, contrast media (CM). One of these CM, iopamidol, has recently been released for clinical intrathecal use in Australia. Clinical evaluations have shown iopamidol to give excellent diagnostic results. However, many adverse side-effects have been cited in the literature. Reactions to iopamidol following myelography are thought to be due to the lack of a physiologic barrier between the extracellular fluid of the brain parenchyma and the CSF, thereby allowing CM to penetrate the brain parenchyma tissue, following subarachnoid injection. This study investigates the rate of clearance of intrathecal iopamidol from the brain in dogs by performing coronal CT scans at intervals over a 48 h, post-injection period. Analysis of similar regions of interest (ROI) for each time period indicate that iopamidol can be detected in canine brains for at least 48 h following intrathecal injection (P less than 0.05). Furthermore, the disappearance of iopamidol from the brain parenchyma is approximately logarithmic in form, with a half-life of approximately 22 h.

The authors compared iopamidol and ioversol in a double-blind study conducted on 81 patients (ioversol in 40 patients; iopamidol in 41 patients) undergoing computed body tomography (CT) for a variety of indications at the Flinders Medical Centre in South Australia. Each study was assessed for image quality and rated as diagnostic or nondiagnostic. Patients were monitored for blood pressure measurement, pulse rate, and respiration rate before and after contrast administration and were observed for the occurrence of side effects. Subjective assessments of heat and pain sensations also were obtained from the patients. With the exception of one patient studied with iopamidol, all investigations were rated as either good or excellent. In all cases, the examination was considered diagnostic. No adverse reactions were noted after administration of either contrast material, except in one patient who felt nauseated. Because the patient had reported feeling nauseated before the examination, this side effect was considered to be coincidental. One patient experienced mild pain from injection of iopamidol. In no cases were any drug-related or clinically significant changes in vital signs noted. In this study, both iopamidol and ioversol were well tolerated and effective, with few side effects after intravenous administration for contrast enhancement during whole-body CT.