Neutrophil trafficking into inflamed joints in patients with rheumatoid arthritis, and the effects of methylprednisolone.

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-99 hexametazime (99mTc-HMPAO) and reinjected intravenously. Synovial fluid neutrophils were labeled from 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.

The effect of intracarotid nonionic contrast media on the blood-brain barrier in acute hypertension.

PURPOSE: To determine whether acute hypertension (HT) is a risk factor for damage to the blood-brain barrier in carotid angiography with nonionic contrast media. METHODS: Anesthetized rats received intravenous injections of technetium-99m-pertechnetate and horseradish peroxidase. Two groups of rats received metaraminol to raise their blood pressure to between 165 and 190 mmHg peak systolic and then received intracarotid injections of saline or iopamidol. Two other groups remained normotensive and received intracarotid injections of saline or iopamidol. Animals were perfused with a fixative solution and their brains removed. Activity of extravasated Tc-99m-pertechnetate was determined to assess blood-brain barrier breakdown. Brains were then sectioned, treated histochemically to visualize extravasated horseradish peroxidase, and ranked visually according to horseradish peroxidase staining. RESULTS: Extravasation of both tracers was significantly greater in the hypertensive group that received contrast media than in the other three groups. CONCLUSIONS: Acute hypertension potentiates the blood-brain barrier-damaging effects of nonionic contrast media during carotid angiography in rats.

Effects of nonionic contrast media on the blood-brain barrier. Osmolality versus chemotoxicity.

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.

Effect of additional cations on the twitching reaction to intracarotid, nonionic contrast media in rabbits.

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.

Factors affecting the precision of bone mineral measurements. Part 1: Review of experimentally derived results obtained from single photon absorptiometry.

An evaluation of the factors which influence the precision of bone mineral measurements using single photon absorptiometry (SPA) is presented. This incorporates several techniques which have been developed over the past few years to improve the reliability of such measurements. As such, the figures obtained should provide an objective and up-to-date basis for critical comparison with other modalities such as quantitative computerized tomography (QCT), dual photon absorptiometry (DPA) using Gd-153, and quantitative digital radiography (QDR). Under optimum conditions, a precision of 0.3% was achievable for in vitro phantom measurements. Under realistic working conditions, however, a precision of 1.0% for phantoms and 1.4% for clinical studies was found to be more typical for bone mineral content (BMC) measurements. Derived parameters such as bone mineral density (BMD) were generally less reliable, with a precision of 4.7%. It is unlikely that these values can be improved upon substantially with current SPA technology.

Factors affecting the precision of bone mineral measurements. Part 2: Some statistical notes relating to photon counting statistics and rates of bone loss.

This paper discusses some statistical aspects of absorptiometric bone mineral measurements. In particular, the contribution of photon counting statistics to overall precision is estimated, and methods available for carrying out statistical comparisons of bone loss and determining their precision are reviewed. The use of replicate measurements as a means of improving measurement precision is also discussed.

Muscular and CNS effects of carotid artery administration of contrast media in rabbits.

Facial muscle twitching during intracarotid injections of nonionic contrast media has been observed in rabbits. To investigate the cause of this reaction, cortical EEG and facial EMG recordings were made from rabbits receiving selective internal and external carotid artery injections of control solutions (normal saline, mannitol), an ionic contrast medium (meglumine iothalamate), and three nonionic contrast media (iohexol, iopromide, and iotrolan). Internal carotid artery injections with all contrast media, both ionic and nonionic, produced ipsilateral EEG changes in 24 of 28 animals; however, ipsilateral EMG changes and visible twitching were observed only in animals injected with nonionic contrast media. Internal carotid artery injections with control ionic and nonionic solutions (physiological saline and mannitol, respectively) produced no EEG changes in any animals. Mannitol produced only ipsilateral EMG changes and visible twitching in most animals. The severity of the reaction to mannitol was generally less than that to the nonionic contrast media, and this difference was statistically significant when comparing mannitol with iohexol and iotrolan but not with iopromide. External carotid artery injections with nonionic solutions (contrast media and mannitol) produced significantly more severe ipsilateral EMG changes and visible twitching than were recorded with the internal carotid artery injections. Ionic solutions (contrast media and saline) had no effect. EEG changes were not observed after external carotid artery injection of any solution, with the exception of two of the seven animals injected with iotrolan. Angiography demonstrated retrograde filling of the external carotid arterial system from internal carotid artery injection via functioning orbital anastamoses. In contrast, internal carotid arterial vessels were not seen angiographically after external carotid artery injection.(ABSTRACT TRUNCATED AT 250 WORDS)

A randomized double-blind trial of ioversol and iopamidol in contrast-enhanced computed body tomography.

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.

The effect of contrast medium viscosity on the blood-brain barrier after intracarotid injection in the rabbit.

This study was undertaken to investigate the role of contrast medium viscosity in blood-brain barrier disruption after carotid angiography. Test solutions were injected into the carotid arteries of rabbits, and the degree of disruption was assessed by using 99mTc-pertechnetate and Evans blue as quantitative and qualitative markers, respectively. The seven test solutions consisted of basic solutions of physiological saline, iopromide, or methylglucamine iothalamate plus solutions derived from these by the addition of sufficient gelatin to augment their viscosities considerably. The solutions were injected over a 30-sec period, resulting in doses that varied inversely with viscosity. One of the high-viscosity solutions was also injected as a fixed dose, equal to the mean injection volume of its low-viscosity counterpart, without regard to the time used. Statistical comparison between the effects of the solutions showed that, under the conditions of the study, contrast medium viscosity, either by itself or as a consequence of its association with hyperosmolality, has no significant effect on the blood-brain barrier. However, under conditions of constant injection volume, higher viscosity solutions may require increased injection times, and this may lead to increased disruption of the blood-brain barrier.

Examination of the nephrographic potential of iotrol by computed tomography.

The x-ray attenuation of the renal cortex of dogs, as determined by computed tomographic (CT) scanning, was measured over a three-day period after an intravenous bolus of 600 mg I/kg of iotrol or iopamidol. A slightly higher density observed 24 hours after injection of iotrol was not considered significant, and was not considered sufficient to warrant clinical application of iotrol for specific, prolonged renal enhancement.

A comparison of blood-brain barrier disruption by intracarotid iohexol and iodixanol in the rabbit.

A rabbit model was used to compare the effect on the blood-brain barrier of the intracarotid injection of two new contrast media: iohexol, a nonionic monomer, and iodixanol, a nonionic dimer. It was hypothesized that the low osmolality of iodixanol (272 mOsm/kg at 300 mgl/ml) would cause less disruption of the blood-brain barrier than the relatively higher osmolality of iohexol (690 mOsm/kg at 300 mgl/ml). The degree of blood-brain barrier disruption was assessed qualitatively, by observing the degree of cortical staining with Evans' Blue dye, and quantitatively, by calculating the difference in uptake of 99mTc-pertechnetate between injected and noninjected hemispheres. Statistical analysis of the results showed that both iodixanol and iohexol had a significantly greater effect on blood-brain barrier disruption than did isotonic saline (0.005 greater than p greater than .001), but that the effect of iodixanol was not significantly different from that of iohexol with respect to either Evans' Blue staining (p greater than .05) or pertechnetate uptake (.75 less than p less than .90). Thus, the low-osmolality iodixanol has no significant advantage over iohexol in terms of blood-brain barrier disruption after experimental carotid angiography.