Quantitative Evaluation of the Mechanical Risks Caused by Focal Cartilage Defects in the Knee.

Focal cartilage lesions can proceed to severe osteoarthritis or remain unaltered even for years. A method to identify high risk defects would be of utmost importance to guide clinical decision making and to identify the patients that are at the highest risk for the onset and progression of osteoarthritis. Based on cone beam computed tomography arthrography, we present a novel computational model for evaluating changes in local mechanical responses around cartilage defects. Our model, based on data obtained from a human knee in vivo, demonstrated that the most substantial alterations around the defect, as compared to the intact tissue, were observed in minimum principal (compressive) strains and shear strains. Both strain values experienced up to 3-fold increase, exceeding levels previously associated with chondrocyte apoptosis and failure of collagen crosslinks. Furthermore, defects at the central regions of medial tibial cartilage with direct cartilage-cartilage contact were the most vulnerable to loading. Also locations under the meniscus experienced substantially increased minimum principal strains. We suggest that during knee joint loading particularly minimum principal and shear strains are increased above tissue failure limits around cartilage defects which might lead to osteoarthritis. However, this increase in strains is highly location-specific on the joint surface.

Effect of Ioxaglate on the cutaneous microcirculation in patients with coronary artery disease: Randomized, double blind, placebo-controlled study.

Radiographic contrast media (RCM) can initiate microcirculatory disorders. This study was performed to investigate effects of Ioxaglate on the cutaneous microcirculation. The investigation was carried out as prospective randomized double-blind comparison in parallel-group design on two groups of n = 10 patients each who had to undergo a diagnostic coronary angiography.The confirmatory parameter of the study was mean erythrocyte capillary velocity [vRBC in mm/sec]. VRBC in the ipsilateral nail-fold capillaries was recorded continuously for 3 min before and 6 min after injection of RCM or isotonic saline solution in the A. axillaris respectively, and was evaluated off-line.VRBC in nailfold capillaries was found to be decreased by Ioxaglate by 34% 150 seconds after injection, while isotonic NaCl solution immediately induced a slight increase of 14%.

Efficacy of preventive interventions for iodinated contrast-induced acute kidney injury evaluated by intrarenal oxygenation as an early marker.

OBJECTIVE: The objective of this study was to evaluate the effects of potential renoprotective interventions such as the administration of N-acetylcysteine (NAC; antioxidant) and furosemide (diuretic) on intrarenal oxygenation as evaluated by blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in combination with urinary neutrophil gelatinase-associated lipocalin (NGAL) measurements. MATERIALS AND METHODS: Rats received nitric oxide synthase inhibitor L-NAME (10 mg/kg) and cyclooxygenase inhibitor indomethacin (10 mg/kg) to induce the risk for developing iodinated contrast-induced acute kidney injury before receiving one of the interventions: NAC, furosemide, or placebo. One of the 3 iodinated contrast agents (iohexol, ioxaglate, or iodixanol) was then administered (1600-mg organic iodine per kilogram body weight). Fifty-four Sprague-Dawley rats were allocated in a random order into 9 groups on the basis of the intervention and the contrast agent received.Blood-oxygen-level-dependent MRI-weighted images were acquired on a Siemens 3.0-T scanner using a multiple gradient recalled echo sequence at baseline, after L-NAME, indomethacin, interventions or placebo, and iodinated contrast agents. Data acquisition and analysis were performed in a blind fashion. R2* (=1/T2*) maps were generated inline on the scanner. A mixed-effects growth curve model with first-order autoregressive variance-covariance was used to analyze the temporal data. Urinary NGAL, a marker of acute kidney injury, was measured at baseline, 2 and 4 hours after the contrast injection. RESULTS: Compared with the placebo-treated rats, those treated with furosemide showed a significantly lower rate of increase in R2* (P < 0.05) in the renal inner stripe of the outer medulla. The rats treated with NAC showed a lower rate of increase in R2* compared with the controls, but the difference did not reach statistical significance. Urinary NGAL showed little to no increase in R2* after administration of iodixanol in the rats pretreated with furosemide but demonstrated significant increase in the rats pretreated with NAC or placebo (P < 0.05). CONCLUSIONS: This is the first study to evaluate the effects of interventions to mitigate the deleterious effects of contrast media using BOLD MRI. The rate of increase in R2* after administration of iodinated contrast is associated with acute renal injury as evaluated by NGAL. Further studies are warranted to determine the optimum dose of furosemide and NAC for mitigating the ill effects of contrast media. Because NGAL has been shown to be useful in humans to document iodinated contrast-induced acute kidney injury, the method presented in this study using BOLD MRI and NGAL measurements can be translated to humans.

In vivo evaluation of cisplatin-loaded superabsorbent polymer microspheres for use in chemoembolization of VX2 liver tumors.

PURPOSE: To investigate the pharmacokinetics and efficacy of chemoembolization with a cisplatin-loaded superabsorbent polymer (SAP) suspension in a rabbit model with transplanted liver VX2 tumors. MATERIALS AND METHODS: VX2 tumors were implanted into the left lobe of the liver in eight rabbits. Embolization of the proper hepatic artery was performed with cisplatin-loaded or unloaded SAP. In the cisplatin-loaded SAP group (n = 4), 5 mg of SAP (106-150 µm) loading 2.35 mg of cisplatin and 0.5 mL of ionic contrast material (ioxaglic acid 320 mgI/mL) was injected into the proper hepatic artery. In the control group (hepatic arterial infusion [HAI] + SAP; n = 4), 5 mg of SAP loading 0.5 mL of ioxaglic acid alone was injected after a bolus infusion of an equivalent amount of cisplatin. Sequential change of the plasma platinum concentration within the first 24 hours was measured. Blood sampling and histopathologic examination were performed at 1-week follow-up. Magnetic resonance (MR) images were used to calculate the growth rate of the VX2 tumor. RESULTS: All animals underwent successful embolization. Both total and free plasma platinum mean concentrations within the first 24 hours remained lower in the cisplatin-loaded SAP group, although without statistical significance (P > .05). The mean tumor growth rate was significantly lower in the cisplatin-loaded SAP group than the control group (20% vs 116%; P = .049). Histopathologic examination revealed coagulative necrosis to nontumorous liver parenchyma in two rabbits in the cisplatin-loaded SAP group, although no deaths occurred. CONCLUSIONS: These results suggested that chemoembolization with cisplatin-loaded SAP was a safe and tolerable treatment and was more effective in suppressing the tumor growth.

Torsade de pointes induced by ioxaglate intracoronary injection in patients with pre-existent drug-induced QT prolongation: case reports and review of literature.

We report two cases of torsade de pointes directly related to intracoronary contrast media injection in patients without previous history of neither arrhythmia nor syncope but chronically treated with a drug prolonging ventricular repolarization. We discussed the effects of the contrast medium used on repolarization and concluded that three suggestions may be highlighted from the case reports presented and from the literature: (i) a QT prolongation should be systematically searched before coronary angiography; (ii) it seems important to correct QT prolongation when it results from a reversible cause (such as drug-induced) before nonurgent coronary angiography; and (iii) if there is no reversible cause explaining QT prolongation, contrast media should be used cautiously in such patient and nonionic iso-osmolar contrast media should be preferred.

Observation of intravascular changes of superabsorbent polymer microsphere (SAP-MS) with monochromatic X-ray imaging.

This study was designed to evaluate the intravascular transformation behavior of superabsorbent polymer microsphere (SAP-MS) in vivo macroscopically by using monochromatic X-ray imaging and to quantitatively compare the expansion rate of SAP-MS among different kinds of mixtures. Fifteen rabbits were used for our study and transcatheter arterial embolization (TAE) was performed for their auricular arteries using monochromatic X-ray imaging. We used three kinds of SAP-MS (particle diameter 100-150 mum) mixture as embolic spherical particles: SAP-MS(H) absorbed with sodium meglumine ioxaglate (Hexabrix 320), SAP-MS(V) absorbed with isosmolar contrast medium (Visipaque 270), and SAP-MS(S) absorbed with 0.9% sodium saline. The initial volume of SAP-MS particles just after TAE and its final volume 10 minutes after TAE in the vessel were measured to calculate the expansion rate (ER) (n = 30). Intravascular behavior of SAP-MS particles was clearly observed in real time at monochromatic X-ray imaging. Averaged initial volumes of SAP-MS (H) (1.24 x 10(7) microm(3)) were significantly smaller (p < 0.001) than those of SAP-MS (V) (5.99 x 10(7) microm(3)) and SAP-MS (S) (5.85 x 10(7) microm(3)). Averaged final volumes of SAP-MS (H) were significantly larger than averaged initial volumes (4.41 x 10(7) microm(3) vs. 1.24 x 10(7) microm(3); p < 0.0001, ER = 3.55). There were no significant difference between averaged final volumes and averaged initial volumes of SAP-MS (V) and SAP-MS (S). SAP-MS (H), which first travels distally, reaches to small arteries, and then expands to adapt to the vessel lumen, is an effective particle as an embolic agent, causing effective embolization.

Removal of contrast medium from the coronary sinus during coronary angiography: feasibility of a simple and available technique for the prevention of nephropathy.

BACKGROUND: Contrast-induced nephropathy (CIN) is a major complication of percutaneous coronary interventions with currently limited preventive measures. OBJECTIVES: To prevent CIN, we assessed the safety and feasibility of contrast removal from the coronary sinus (CS) during coronary angiography. METHODS: We attempted contrast removal on seven patients undergoing coronary angiography with preexisting renal insufficiency (mean serum creatinine=262+/-56 mg%). RESULTS: In four patients, a balloon catheter could not be successfully deployed in the CS. In three patients, a balloon catheter with distal side holes was positioned in the CS orifice. The balloon was inflated to occlude the CS concurrent with coronary injections, and 12-16 ml of blood was aspirated after each injection. The procedure appeared to be safe, without adverse events and elevations of serum creatinine levels. Contrast media were effectively withdrawn (44%+/-8%) as assessed by fluoroscopy and dilution of blood. The increased venous pressure at the time of injection reduced coronary flow, allowing for small volumes of administered contrast. CONCLUSIONS: Occlusion of the CS during coronary angiography with aspiration of contrast media is safe and effective in reducing contrast load during coronary interventions. This procedure may reduce the risk for CIN in prone patients.

Postmortem diagnosis of fatal anaphylaxis during intravenous administration of therapeutic and diagnostic agents: evaluation of clinical laboratory parameters and immunohistochemistry in three cases.

This report documented three autopsy cases involving fatal shock during intravenous injection of therapeutic and diagnostic agents in a hospital setting. For postmortem diagnosis, clinical laboratory parameters for anaphylaxis, specificity of antibodies for allergens and mast cell numbers in tissue sections were examined. Elevated plasma tryptase levels were evident in the three adult males; two of the three victims displayed elevated IgE levels. However, immunoassay failed to detect antibodies specific to the relevant agent. Double immuno-staining was performed employing anti-tryptase and anti-chymase monoclonal antibodies in order to count mast cells in lung sections. Increased numbers of mast cells were observed in anaphylactic tissues, which was particularly true for chymase-positive cells, in comparison with tissues associated with acute traumatic deaths. In addition to findings at autopsy, positive data obtained by laboratory examinations and immunohistochemical analyses indicated that fatal systemic anaphylaxis occurred during intravenous injection of clinical agents.

Allergic reaction to contrast medium following gastric band adjustment.

Bariatric surgery is increasingly performed for effective weight loss. A morbidly obese 27-year-old woman underwent laparoscopoic adjustable gastric banding. After a postoperative adjustment of the stomal diameter of the band with ioxaglate, she presented an immediate hypersensitivity reaction. With the patient's consent, cutaneous tests to contrast agents used during the procedure and to latex were performed. Allergy to ioxaglate was confirmed by skin-test positivity. This case suggests the need for allergological investigation of drugs/substances administered during the perioperative period, in case of hypersensitivity reaction.

Renal toxicity evaluation and comparison between visipaque (iodixanol) and hexabrix (ioxaglate) in patients with renal insufficiency undergoing coronary angiography: the RECOVER study: a randomized controlled trial.

OBJECTIVES: This study sought to compare the nephrotoxicity of iodixanol and ioxaglate in patients with renal impairment undergoing coronary angiography. BACKGROUND: Iodixanol, a nonionic, dimeric, iso-osmolar contrast medium (IOCM), may be less nephrotoxic than low-osmolar contrast media (LOCM) in high-risk patients. METHODS: In a prospective, randomized trial in 300 adults with creatinine clearance (CrCl) < or =60 ml/min, patients received either iodixanol or ioxaglate and underwent coronary angiography with or without percutaneous coronary intervention. The primary end point was the incidence of contrast-induced nephropathy (CIN) (an increase in serum creatinine [SCr] > or =25% or > or =0.5 mg/dl [> or =44.2 mumol/l]). The incidence of CIN in patients with severe renal impairment at baseline (CrCl <30 ml/min) or diabetes and in those receiving large doses (> or =140 ml) of contrast medium was also determined. RESULTS: The incidence of CIN was significantly lower with iodixanol (7.9%) than with ioxaglate (17.0%; p = 0.021), corresponding to an odds ratio (OR) of CIN of 0.415 (95% confidence interval [CI] 0.194 to 0.889) for iodixanol. The incidence of CIN was also significantly lower with iodixanol in patients with severe renal impairment (p = 0.023) or concomitant diabetes (p = 0.041), or in patients given > or =140 ml of contrast media (p = 0.038). Multivariate analysis identified use of ioxaglate (OR 2.65, 95% CI 1.11 to 6.33, p = 0.028), baseline SCr, mg/dl (OR 2.0, 95% CI 1.04 to 3.85, p = 0.038), and left ventricular ejection fraction, % (OR 0.97, 95% CI 0.94 to 0.99, p = 0.019) as independent risk factors for CIN. CONCLUSIONS: The IOCM iodixanol was significantly less nephrotoxic than ioxaglate, an ionic, dimeric LOCM. (The RECOVER Trial; http://clinicaltrials.gov; NCT00247325).

Renal effects of CO2 and iodinated contrast media in patients undergoing renovascular intervention: a prospective, randomized study.

PURPOSE: CO2 gas has been proposed for use instead of iodinated contrast media in angiographic examinations in patients at risk of developing renal failure from contrast media. The influence of intraarterial injection of CO2 with small added amounts of ioxaglate (200 mgI/mL) or ioxaglate alone on renal function in patients with suspected renal artery stenosis was studied in a prospective, randomized study. MATERIALS AND METHODS: One hundred twenty-three patients underwent renovascular intervention (n = 83) and/or renal angiography (n = 40) for suspected renal artery stenosis. Patients with a serum creatinine concentration less than 200 micromol/L (n = 82) were randomized prospectively to receive CO2 with small added amounts of ioxaglate (n = 37) or only ioxaglate (n = 45). Patients with serum creatinine levels greater than 200 micromol/L (n = 41) were not randomized and initially received CO2. Serum creatinine concentrations were measured within 1 day before and 1 day, 2 days, and 2-3 weeks after the procedure. RESULTS: The amount of injected CO2 did not relate to an increase in serum creatinine level. In the randomized groups, and also when the whole patient sample was considered, the amount of injected iodine was significantly correlated (P = .011) with an increase in serum creatinine level and a decrease in estimated creatinine clearance after 2 days. Among the randomized patients, one in the CO2 group and three in the ioxaglate group had a more than 25% increase in serum creatinine level within the first 2 days after the intervention. CONCLUSION: The risk of impairment of renal function is lower after injection of CO2 with small amounts of added ioxaglate compared with injection of a larger amount of ioxaglate alone. The larger the amount of administered iodinated contrast medium, the greater the risk of development of renal failure.

The ionic contrast medium ioxaglate interferes with thrombin-mediated feedback activation of factor V, factor VIII and platelets.

Clinical observation shows that radiographic contrast media (CM) may influence thrombus formation. In the search for the underlying mechanism, we have shown that the ionic CM ioxaglate is a potent inhibitor of thrombin generation in platelet-poor and platelet-rich plasma, whereas the influence of the non-ionic contrast medium iodixanol is minimal. Ioxaglate boosts the inhibitory effect of the platelet GPIIb/IIIa antagonist abciximab and the effects of ioxaglate and heparin are additive. Ioxaglate inhibits the clotting of fibrinogen and the activation of factors V and VIII, and of platelets by thrombin. It does not inhibit hydrolysis of small chromogenic thrombin substrates, nor does it influence the heparin-catalyzed inactivation of thrombin by antithrombin. We assume therefore that ioxaglate interferes with the binding of macromolecular substrates to the anionic exosite I of thrombin. The biological correlation to the observed antithrombotic effect of ioxaglate is then to be found in the inhibition of thrombin generation via inhibition of thrombin-mediated feedback activations.

Comparative tolerability of contrast media used for coronary interventions.

Radiographic contrast media (CM) are necessary to provide x-ray absorption of the bloodstream; all other observed effects need to be regarded as adverse. Four types of CM are currently used in diagnostic and interventional cardiology: ionic high-osmolar CM (HOCM), either ionic or non-ionic low-osmolar CM (LOCM), and non-ionic iso-osmolar CM (IOCM). Focusing on the potential cardiovascular effects caused by the CM, there is a clear difference between HOCM and the LOCM or IOCM. HOCM have a poorer profile due to a higher incidence of hypotension and electrophysiological effects. To prevent contrast-induced nephropathy, HOCM should be avoided and patients should receive the minimal dose of LOCM or IOCM with intravenous hydration before and after the procedure. Clinical hyperthyroidism has been detected after CM use, but the condition appears, ultimately, to be self-limited and to occur mainly in elderly patients. When assessing the need for a CM in terms of improved patient safety, preventing serious complications should be the major factor determining the choice. CM should not be selected on the basis of minor adverse effects since these are, ultimately, of low clinical relevance. Thrombotic events, in contrast, carry a high clinical relevance and we consider that these should be the main issue governing current choice. Ionic LOCM appear to have better profile than other CM with respect to interaction with platelet function and coagulation. In relation to thrombotic events in randomised clinical studies, ionic CM have been associated, mainly, with favourable and some neutral results compared with non-ionic agents. Only one trial indicated a more pronounced antithrombotic effect of the non-ionic IOCM relative to the ionic LOCM. The antithrombotic advantages of ionic over non-ionic LOCM are, in part, balanced by a greater frequency of minor adverse effects such as nausea, vomiting or cutaneous rashes. A matter of concern is the delayed adverse effects observed with non-ionic IOCM. However, severe and life-threatening reactions are exceptional and there are probably no significant differences between IOCM and LOCM whether ionic or non-ionic. However, in patients with known allergies, non-ionic CM are to be recommended. On the basis of the available pre-clinical and clinical data, the ionic LOCM or the non-ionic IOCM are the agents to be recommended in percutaneous coronary interventions because of their antithrombotic advantages over non-ionic LOCM.

Monte Carlo dose simulation for intracoronary radiation therapy with a rhenium 188 solution-filled balloon with contrast medium.

BACKGROUND: The therapeutic efficacy of percutaneous transluminal coronary angioplasty is limited by the incidence of restenosis. Intracoronary irradiation has shown to be effective in restenosis control by inhibiting the neointimal proliferation. METHODS AND RESULTS: Monte Carlo simulation has been performed to calculate the dose to the vessel wall for intracoronary irradiation with a rhenium 188 solution-filled balloon for restenosis inhibition. With a 3-mm-diameter and 30-mm-long balloon, the radiation dose at 1 mm from the balloon surface was 5.3% lower when the balloon structure was included in geometric modeling of the angioplasty catheter, as compared with that obtained by ignoring the structure. The additional dose reduction due to Hexabrix 320 contrast medium added in 30% of volume ratio was 4.7%. With regard to axial dose distribution, the dose was uniform over the balloon length except near the balloon end, at which the dose was reduced by 35% at a 1-mm-deep layer in the vessel wall. With the Re-188 solution mixed with 30% of Hexabrix 320 in volume ratio, the Re-188 activity to be injected for delivery of 15 Gy to the 1-mm-deep layer by 1-minute irradiation was 27.3 GBq/mL. CONCLUSIONS: Dose estimates produced in this study should be helpful in determining the Re-188 activity to be injected or the irradiation time for a varying situation in terms of length and diameter of the irradiated arterial segment and depth of the target layer.

Serum pancreastatin levels predict response to hepatic artery chemoembolization and somatostatin analogue therapy in metastatic neuroendocrine tumors.

INTRODUCTION: Neuroendocrine tumors often metastasize to the liver and present with disabling hormonal symptoms. Hepatic artery chemoembolization (HACE) combined with somatostatin therapy, pre-embolization, peri-embolization and post-embolization, at doses to control symptoms, is an aggressive approach that can relieve hormonal symptoms with minimal morbidity and mortality. METHODS: Chemoembolization was performed using 30 mg of adriamycin, 50 mg of mitomycin, 12 ml of hexabrix, 10 ml of ethiodol, and 360-500-microm particles. Pancreastatin, a split product of chromogranin A, was measured pre-HACE and post-HACE in all patients. RESULTS: Forty-three chemoebolization procedures were performed in 34 symptomatic patients from December 1995 to August 1999. Seventeen patients had intestinal primaries (50%), seven had pancreatic primaries (20%), five had bronchial primaries (15%), and five had unknown primaries (15%). Systemic pancreastatin levels were improved or stable in 31 patients (78%). Symptoms were improved in these 31 patients (78%). Systemic serotonin levels were improved or stable in 24 patients (60%). Radiographic improvement or stability was seen in 18 patients (45%). Procedural related morbidity included pain, fevers, nausea, vomiting, and transient elevations of liver function studies in 75-100% of patients. There was one procedural related mortality (2%). Less than 20% improvement in pancreastatin levels from baseline was associated with death in five of five patients (100%). This was not observed with serotonin levels. CONCLUSION: Measurement of serum pancreastatin levels is an easy and useful method to predict success in patients who undergo HACE plus somatostatin therapy for metastatic neuroendocrine tumors to the liver. This therapeutic approach is effective in relieving symptoms in 78% of patients, with minimal major morbidity or mortality.

Ultrastructural evaluation of the effects of the contrast media on the rat kidney.

In this study, the ultrastructural observations in rat kidneys were studied 2, 24 and 48 h after intravenous injection of 1, 3 and 9 g iodine per kg body of ioxaglate and iohexol. The effect of the contrast media was mainly on the proximal convoluted tubule cells, the presence of vacuoles containing granular and membranous structures was a striking feature. In the distal convoluted tubular cells, pycnotic nuclei and cytoplasmic bulges toward the lumen were observed. In some glomeruli, membranous structures in cytoplasm of podocytes and thickening of glomerular basal membrane were seen. Values of biochemical analysis were slightly higher especially at high doses in experimental groups when compared to the control. The results suggest that iohexol causes more degeneration than ioxaglate. Not only proximal convoluted tubule cells but also the other parts of the nephron were affected by contrast media.

Nitric oxide protects against contrast media-increased pulmonary vascular permeability in rats.

RATIONALE AND OBJECTIVES: Nitric oxide (NO) regulation of endothelial function is involved in the development of acute lung injury. The role of NO in contrast media-induced increases in pulmonary vascular permeability was investigated in a rat model. METHODS: Nonionic (iohexol) and ionic (ioxaglate) contrast media were intravenously injected at 1.5 mL/min in rats. Pulmonary vascular permeability was evaluated by measuring the amount of Evans blue dye uptake as a quantitative marker of albumin extravasation in lung tissue. RESULTS: Intravenous injections of contrast media at doses of 4 and 6 g I/kg induced a dose-dependent increase in pulmonary vascular permeability. L-Arginine (an NO synthase substrate) and N(G)-nitro-L-arginine (L-NNA) (an NO synthase inhibitor) prevented and aggravated, respectively, the increase in pulmonary vascular permeability induced by the contrast medium. An aggravating action of L-NNA was confirmed by morphological and histological observations, this action being blocked by L-arginine (300 mg/kg) but not by D-arginine. Isosorbide dinitrate (1-20 mg/kg), an NO donor, had a dose-dependent protective effect on ioxaglate-increased vascular permeability. CONCLUSIONS: Our experimental findings suggest that contrast media at high doses produce pulmonary edema by inhibiting endothelial NO production, and nitrovasodilators protect against this adverse effect in rats.

Seasonal variation in the occurrence of late adverse skin reactions to iodine-based contrast media.

PURPOSE: To study the possible seasonal effect in the occurrence of late adverse skin reactions to iodine-based contrast media (CM). MATERIAL AND METHODS: Data on 4,875 adult patients followed for late adverse reactions after i.v. injections of iohexol or iopamidol, or intra-arterial injection of ioxaglate were retrospectively investigated with respect to the amount of global radiation vs. the occurrence of reactions. The information on these reactions was collected from questionnaires that were filled out by the patients (out-patients) or by nurses (in-patients). The follow-up time was 24 h. RESULTS: Fifty-two of 4,875 patients (1.07%) had experienced a late skin reaction (urticaria or rash); this number exceeds the reports on spontaneous occurrence of such reactions by a factor of 300. Most of the reactions in a known location occurred on sun-exposed areas of the body. A 2-month peak in the incidence of reactions (May to June) included 35% of all events (p<0.025) and a 3-month peak (April to June) 46% of all events (p<0.01). There was a significant rank correlation (r = 0.613, p<0.05) between the frequency of reactions and the mean amount of global radiation. CONCLUSION: This study demonstrates a seasonal variation in skin reactions after intravascular injection of iodine-based CM. The possible photosensitising effect of these drugs should be further studied.