Acta radiologica. Supplementum最新文献

Absorption and excretion of iodixanol 320 mg I/ml were investigated in rats after intragastric administration of 2.5 g I/kg b.w. Animals were observed for up to 96 hours after treatment, and blood, urine and feces taken at several time-points throughout the experiment. Concentrations of iodixanol in serum and urine were measured by means of reversed-phase high-performance liquid chromatography. Fecal concentrations of iodixanol, based on iodine measurements, were determined by X-ray fluorescence spectrometry. Serial radiographs were obtained and histopathological examination was performed on selected tissues. The results indicate that less than 1% of the intragastric dose of iodixanol is absorbed from the intestine into the blood stream. No adverse clinical signs were observed, and there were no treatment-related histomorphological findings.

A review of the literature on the influence of contrast media (CM) on fibrinolysis showed that information currently available is contradictory, inconclusive and fragmentary. Results of some in vivo studies suggest that both ionic and nonionic CM increase fibrinolytic activity, either by lowering plasma plasminogen activator inhibitor 1 levels, by releasing endogenous tissue plasminogen activator and¿or by altering the fibrin meshwork of thrombi. Most in vitro studies on the subject contain results that are contradictory to those from in vivo studies. The discrepancies are due to obvious differences between systems which are, at best, only comparable under conditions of stagnant flow. Thus, great care should be exercised when extrapolating or interchanging data obtained in vivo and in vitro.

We confirm that the phenomenon of platelet degranulation exists for both iohexol and diatrizoate, as reported earlier. In contrast to previous conclusions, however, we have determined that the degranulation is independent of the nonionic vs. ionic nature of the media per se, since degranulation was neither seen with nonionic iodixanol nor ionic ioxaglate. The degranulation, further, does not significantly augment platelet function, as measured by flowing whole blood platelet aggregometry.

The viscosity of 8 commercially available contrast media (CM) at 2 or 3 concentrations were measured as a function of concentration and temperature, using a rotational viscosmeter. Further on, by use of an automated injector, injection pressures were measured for 3 of the CM at various concentrations, temperatures, catheter lengths, catheter diameters and flow rates. The experiments were performed as fractional factorial designs. The correlation between the injection pressure and the viscosity was found to be log-linear, and an empiric equation was established for this relationship. The relative reduction of viscosity - and therby injection pressure - with increasing injection temperature, was largest for the most concentrated CM. Iodixanol and iotrolan, the 2 nonionic dimers investigated, demonstrated an increased viscosity compared to the nonionic monomers at equal concentrations. However, all CM investigated could be used with an acceptable injection pressure either by relatively small changes in catheter conditions or by adjustment of injection temperature closer to body temperature.

MRI and CT are modalities appropriate for liver imaging. To obtain higher sensitivity in diagnoses of focal lesions in the liver, contrast media (CM) are used. Non-specific extracellular CM are not optimal as they rapidly diffuse into both normal tissue and tumorous tissue. By two different mechanisms, the hepatobiliary route and targeting to the reticuloendothelial system, agents may accumulate in normal liver tissue, thereby giving liver-specific CM. So far no such agents have been approved for clinical use. In the present studies, animal models were used to investigate the imaging efficacy of experimental liver-specific CM and answer the following questions: i) Do these new liver-specific CM result in enhancement of normal liver? ii) If enhancement in normal liver is present, does this result in higher contrast of normal liver to tumorous tissue? iii) If higher contrast of normal liver to tumorous tissue is present, does this result in higher tumour detection-rates? Relative to non-enhanced and contrast-enhanced CT, what tumour detection-rate is obtained using non-enhanced and contrast-enhanced MRI? All the liver-specific CM studies possessed the ability to significantly alter the signal in normal liver tissue. Compared to precontrast values, the liver-specific CM studied in MRI (Mn-DPDP) and CT (IEEC-particles and iodixanol-liposomes) were able to increase significantly the contrast of normal liver tissue to tumorous tissue and the tumour detection-frequency in VX2-carcinoma liver tumour-bearing rabbits. In CT using a non-specific extracellular CM, iohexol, no improvement in contrast or tumour detection-frequency was obtained. As reflected in the values of contrast-to-noise obtained, MRI and CT have the same potential for tumour detection in the liver model used in the present studies. Liver-specific CM have the property of improving the contrast of normal liver tissue to tumorous tissue in MRI and CT, giving higher tumour detection-rates. Permitting intravenous administration and the use of long imaging-windows, liver-specific CM are easy to use.

This paper reviews the basic mechanisms of the thrombohemorrhagic balance and ways in which contrast media (CM) influence these processes. Coagulation and platelet functions are strongly inhibited by ionic CM, but weakly so by nonionic CM, whereas the former are more detrimental to endothelium, and thus thrombogenic in this sense. Some observations indicate a lower rate of thromboembolic events with the ionic CM in percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG), but this purported difference does not effect mortality or frequency of re-PTCA and emergency CABG. Thus, to challenge these events, strong acting antithrombotics, which also, unlike heparin, inactivate fibrin-bound thrombin, are necessary. Aggressive anti-atherogenic prophylaxis may hamper both thrombosis and reocclusion. The ideal antithrombotic in this setting is yet to be found.

Proximal and distal tubular cells in culture have been exposed to various roentgen contrast media (CM) at concentrations of 0 to 100 mg I/ml for 22 hours to study cellular mechanisms that may be involved in CM-induced nephropathy. The effects on cell morphology were assessed by electron microscopy and cell viability was evaluated. Levels of brush border and lysosomal marker enzymes in the culture medium were assayed biochemically. Morphological examination showed that CM induced a concentration-dependent formation of large cytoplasmic vacuoles in both cell lines. Cellular damage was observed more frequently after exposure to low-osmolal rather than the iso-osmolal CM iodixanol; the low-osmolal CM causing more cell death and inhibiting cellular growth to a greater degree than did iodixanol. In cultures of both cell lines the CM produced a concentration-dependent increase in brush border marker enzyme activity. While an increase in lysosomal enzyme activity was seen at low concentrations, a decrease in activity occurred at high concentrations. Earlier investigations have demonstrated that the nonionic CM have less pronounced effects on the cell lines studied than ionic CM. The results presented here indicate that the effects of the iso-osmolal nonionic CM (iodixanol) on both the investigated cell lines are less marked than those of the low-osmolal nonionic CM investigated.

The results are reviewed from 18 European clinical vascular studies in 1950 patients where iodixanol (Visipaque) - a new isotonic, dimeric, nonionic contrast medium (CM) - is compared to other CM. Visipaque gave better patient comfort, i.e., less pain and heat sensation after vascular injections than the comparative CM. Adverse events reported after Visipaque were otherwise similar to nonionic CM but lower than after ioxaglate (Hexabrix) and other ionic CM. Human renal safety of Visipaque has been extensively studied. Only small changes in glomerular filtration rate and serum creatinine were measured with the monomeric nonionic CM as well as with Visipaque. The excretion of marker enzymes for renal tubular cell function was generally lowest for Visipaque. Thus Visipaque was highly tolerable in the kidneys. To study cardiac safety, electrophysiological and hemodynamic changes were recorded. Visipaque had generally no electrophysiological or hemodynamic effects, or less pronounced effects compared to the other CM. Radiograms revealed that Visipaque 320 mg I/ml yielded the same attenuation as 350 to 370 mg I/ml of the other CM and, similarly, 270 mg I/ml of Visipaque gave as good visualization as 300 mg I/ml of comparative CM.

To document the safety of iodixanol and to assess its pharmacokinetic properties, extensive tests have been performed. Iodixanol was rapidly excreted, mainly via the kidneys, with a plasma half-life in rats and monkeys of 25 and 76 mins, respectively. The pharmacokinetic data were consistent with an extracelleular distribution of iodixanol. During the 24 hours post-dosing, the urinary excretion was from 72 to 100% in rats, and 78% in monkeys. Biliary excretion was 1.5% during the first 4 hours in rats. Fecal excretion was about 7% in rats and 0.8% in monkeys over the first 24 hours after injection. Approximately 0.5 and 1% of the dose was found in the kidneys of rats and monkeys, respectively, 24 hours after dosing. Acute toxicity of iodixanol in rats was low, with an LD(50) greater than 21 g I/kg. In mice the LD(50) was 21 g I/kg and the approximated median lethal dose (ADL(50)) was found to range from 15 to 21 g I/kg. A single dose of 1 and 3 g I/kg was well tolerated in monkeys. As for the other roentgen contrast media, a reversible, dose-related, vacuolation of the proximal tubules in the kidneys was seen in the acute and subacute studies in rats and monkeys. No relationship was seen between the vacuolation and kidney function. Local tolerance studies demonstrated a low irritation potential for iodixanol when injected by a variety of intravascular and extravascular routes. The reproductive capacity of male and female rats was unaffected by iodixanol when administered daily at doses up to 2 g I/kg/day. No teratogenic potential in rats and rabbits of iodixanol was observed. Further, no toxic effects on pups were seen when rats were dosed during the lactation period. Each of 4 standard genotoxicity tests was negative. No antigenic potential of iodixanol was observed when assessed by the passive cutaneous anaphylaxis test and the active systemic anaphylaxis test in guinea pigs. The intravascular tolerability of iodixanol is high, and therefore, iodixanol should be considered as a safe roentgen contrast medium for intravascular use.

Mammograms from 12,636 women aged 40-54 years were examined by one screener first as one-view screening and later as two-view screening. With one-view screening, 542 (4.3%) women were recalled and 31 breast cancers were detected. With two-view screening, 349 (2.8%) women were recalled and 32 breast cancers were detected. Mammograms from 11,343 women aged 41-75 years were independently screened by 2 experienced screeners. A total of 76 breast cancers were diagnosed by 131 surgical biopsies. Both screeners detected 56 cancers. One screener detected 14 cancers alone, and the other detected 6 cancers alone. Thus, 15% more cancers were detected because of double reading. Five experienced screeners reviewed 120 sets of mammograms from the first screening round, including 74 women with breast cancer diagnosed in the first round or later. The mean increase in sensitivity by using two views, instead of one, was 2%. The median of the increase in cancer detection because of independent double reading was 14.5% with one-view screening and 12% with two-view screening. We invited 48,517 women aged 40-74 years to mammography screening. 86% participated, of which 4.8% were recalled for further examinations, and 1.0% were referred to surgery. A total of 241 (0.58%) breast cancers were diagnosed. Only 20% of the invasive cancers had lymph node metastasis and the median size was 16 mm. A total of 43,074 women aged 40-69 years were invited to screening. The attendance rate was 87% in the first screening round and 78% in the second screening. The recall rate was 4.6% and 5.7%, respectively. The breast cancer rate was 0.48% in both screening rounds. The rate of stage II or more advanced breast cancers decreased significantly from 0.16% in the first screening round to 0.08% in the second (p = 0.007).