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Vascular endothelial injuries induced by intravascular administration of radiographic contrast agents may be clinically relevant to the development of thrombosis and platelet activation. In this connection, we investigated the in vitro effects induced by iodamide, iopamidol, and ioxaglate on vascular endothelial ADPase activity and tissue plasminogen activator (t-PA) release in bovine aortic endothelium, in order to extend knowledge required to evaluate endothelial compatibility of radiographic contrast media. Undiluted and Tris-diluted contrast agent formulations were employed, and mannitol and sucrose hyperosmolar solutions were used as comparison. Results demonstrated that the high-osmolar ionic contrast agent iodamide, and to a lesser extent, the low-osmolar nonionic agent iopamidol, stimulated endothelial ADPase activity of the aortic endothelium; the low-osmolar ionic agent ioxaglate left endothelial ADPase activity unchanged. Furthermore, the diluted formulations of iodamide and iopamidol, as well as high-osmolar mannitol and sucrose solutions, were devoid of activity in ADPase. This suggests that the endothelial ADPase stimulation induced by both radiographic contrast media was a hyperosmolar-independent pharmacodynamic activity. Iopamidol and ioxaglate reduced endogenous t-PA release from bovine aortic endothelium only in undiluted formulation, while iodamide showed this inhibiting action in both diluted and undiluted formulations. No effect was observed when using mannitol solutions at different osmolarity values. Our in vitro findings agree with published data on the different thrombotic tendency attributed to the contrast agents used, suggesting endothelial enzymatic activities (ADPase and t-PA release) as suitable tools for evaluating endothelial vessel wall compatibility with radiographic contrast media.

Dynamic contrast-enhanced magnetic resonance imaging (MRI) is a technique used to study and track contrast kinetics in an area of interest in the body over time. Reconstruction of images with high contrast and sharp edges from undersampled data is a challenge. While good results have been reported using a radial acquisition and a spatiotemporal constrained reconstruction (STCR) method, we propose improvements from using spatially adaptive weighting and an additional edge-based constraint. The new method uses intensity gradients from a sliding window reference image to improve the sharpness of edges in the reconstructed image. The method was tested on eight radial cardiac perfusion data sets with 24 rays and compared to the STCR method. The reconstructions showed that the new method, termed edge-enhanced spatiotemporal constrained reconstruction, was able to reconstruct images with sharper edges, and there were a 36%±13.7% increase in contrast-to-noise ratio and a 24%±11% increase in contrast near the edges when compared to STCR. The novelty of this paper is the combination of spatially adaptive weighting for spatial total variation (TV) constraint along with a gradient matching term to improve the sharpness of edges. The edge map from a reference image allows the reconstruction to trade-off between TV and edge enhancement, depending on the spatially varying weighting provided by the edge map.

The consequences of the inadvertent administration, by the intrathecal route, of ionic contrast media instead of iopamidol in seven subjects are reported. The ionic compounds were diatrizoate, iodamide and ioxitalamate. The outcome was fatal in three out of seven subjects, and it depended on the type and the dose of the administered contrast agent. The serious or fatal reactions observed are a tragic confirmation of the predictive power of neurotoxicity data obtained in animal studies with various iodinated water-soluble compounds. The margin of safety, represented by the ratio of LD50 i.ce. in mice to clinical dose in humans, both normalized to bodyweight, appears to reliably reflect the risk of toxic reactions after intrathecal administration of iodinated contrast agents.

OBJECTIVE To compare the diagnostic image quality between three different water soluble iodinated contrast media in hysterosalpingography (HSG). MATERIAL AND METHOD In a prospective randomised study of 204 patients, the diagnostic quality of images obtained after hysterosalpingography were evaluated using Iopramide (106 patients) and Ioxaglate (98 patients). 114 patients who had undergone HSG examination using Iodamide were analysed retrospectively. Image quality was assessed by three radiologists independently based on an objective set of criteria. The obtained results were statistically analysed using Kruskal-Wallis and Mann-Whitney U test. RESULTS Visualisation of fimbrial rugae was significantly better with Iopramide and Ioxaglate than Iodamide. All contrast media provided acceptable diagnostic image quality with regard to uterine, fallopian tubes outline and peritoneal spill. Uterine opacification was noted to be too dense in all three contrast media and not optimal for the assessment of intrauterine pathology. Higher incidence of contrast intravasation was noted in the Iodamide group. Similarly, the numbers of patients diagnosed with bilateral blocked fallopian tubes were also higher in the Iodamide group. CONCLUSION HSG using low osmolar contrast media (Iopramide and Ioxaglate) demonstrated diagnostic image qualities similar to HSG using conventional high osmolar contrast media (Iodamide). However, all three contrast media were found to be too dense for the detection of intrauterine pathology. Better visualisation of the fimbrial outline using Ioxaglate and Iopramide were attributed to their low contrast viscosity. The increased incidence of contrast media intravasation and bilateral tubal blockage using Iodamide are probably related to the high viscosity.

Chemotoxicity and osmotoxicity of contrast media (CM) are determined by chemical structure. The lower the chemotoxicity and osmotoxicity of the CM, the less animal toxicity and higher clinical tolerance in humans will be achieved. Nonionic monomers such as iohexol and iopamidol in iodine-equivalent concentrations have approximately half the osmolality and therefore half the osmotoxicity of ionic monomers such as diatrizoate, iodamide, iothalamate and metrizoate. Absence of carboxyl groups in nonionic CM, as opposed to the presence of carboxyl groups in ionic CM, results in a lower chemotoxicity in nonionic CM. Similarly, a larger number of hydroxyl groups in nonionic CM than in ionic CM result in a lower chemotoxicity. The lower chemotoxicity of nonionic CM is reflected as a higher subarachnoid and intravenous tolerance both in animals and in the clinical setting.

The study comparesin vitro effect of different contrast media on complement activity and eicosanoid content. Ionic agents (Bilignost>Iodamide>Triombrast>Hexabrix) exert pronounced complement-activating effect, while nonionic agents markedly increase blood content of arachidonic acid metabolites. The complement-activating effect of contrast media did not correlate with their ability to elevate blood content of prostaglandin F2α and leukotrienes C4 and B4.

The aim of this study was to determine the influence of radiographic contrast media (CM) on endothelial cells in order to compare the effects of non-ionic (Iomeron and Visipaque) and ionic (Hexabrix and Uromiro) CM on the endothelial cells (EC). Human and murine cells were exposed for 2, 4 and 24 h to increasing concentrations (12.5, 25, 50 and 100 mg/mL) of test compounds. Controls were incubated with complete growth medium or mannitol solution (osmotic control). MTT assay was used to evaluate the cell viability, LDH assay was used to evaluate the membrane damage. The results demonstrate a difference between non-ionic and ionic compounds in the effect on endothelium. Ionic CM show to strongly affect endothelial cells viability under all tested conditions, while non-ionic CM show effects only after prolonged exposure at 50 and 100 mg/mL, which represent instant concentrations lasting just minutes after intravascular injection of CM. Taken together, these results confirm that the currently employed non-ionic contrast media are well tolerated by the vascular endothelium and have wide margins of safety.

To prospectively assess contrast material-enhanced voiding ultrasonography (US) for grading of vesicoureteral reflux (VUR) and to compare results with those of voiding cystourethrography (VCUG) in adult patients undergoing antireflux ureteral implantation.Thirty-seven consecutive adult patients who had undergone renal transplantation with Politano-Leadbetter (18 patients) or Lich-Gregoire (19 patients) technique were included on the basis of previous urinary tract infections (UTIs) and time elapsed after renal transplantation. Exclusion criterion was current UTI. US was performed by one of two sonologists with injection of saline and microbubble suspension and was recorded on videotape. Sonologists assigned VUR diagnosis in consensus after videotape review. VCUG was performed by one of two radiologists immediately after US. Radiologists were blinded to US findings and assigned VCUG diagnoses in consensus. Contingency table was used to compare US and VCUG. Agreement between US and VCUG was determined with kappa statistics.With VCUG, VUR was diagnosed in 15 patients and not diagnosed in 22 patients. US and VCUG results were in agreement in 14 patients with VUR and 21 patients without VUR. US sensitivity and specificity for detection of VUR were 93% (14 true-positive results in 15 abnormal cases) and 95% (21 true-negative results in 22 normal cases), respectively. Agreement between US and VCUG was 95% (kappa = 0.89, P.001). In 11 of 14 patients, VUR grades were in agreement for US and VCUG. In three of 14 patients, US indicated a higher grade than did VCUG. VUR was diagnosed in seven of 18 Politano-Leadbetter cases and eight of 19 Lich-Gregoire cases.A high rate of agreement was seen between voiding US and VCUG.

Despite enormous advancements in the area of high performance liquid chromatography (HPLC) in recent years, method development remains a major challenge. This is primarily due to the unknown nature of the matrix material which sometimes is difficult to characterize (e.g. biological matrices). To improve the efficiency of method development a multidimensional screening approach was presented. This approach was based on two major steps: (1) a matrix spiked with drug was eluted from a large number of columns, each under different mobile phase compositions, to provide the preliminary selectivity-separation information; (2) this information was then used to compose column switching pairs (each pair consisted of a preparatory column followed by an analytical column) and the elution profile was evaluated to determine the suitable clean up and quantitation conditions. An example was provided using ethyl 3,5-bis(acetylamino)-2,4,6-triiodobenzoate (EEDA), an X-ray enhancement agent, in human plasma. Since the HPLC system was fully automated the data generation time, and consequently the method development time, can be significantly reduced.

epsilon-Aminocaproic acid and prednisolone in concentration of 3.0 x 10(-5) M are proven to reduce or even completely prevent activation of the alternative pathway of the component which has been induced by iod-amide adipiodone and triombrast in concentrations 2.5 x 10(-2) M in the serum of "sensitive" rats. The preventive effect of the glucocorticoid appeared less pronounced. There exists direct positive correlation between the degree of the component activation with radiopaque compounds and preventive effect of the drugs studied.

It was demonstrated in rat experiments that a positive direct correlation exists between the decrease in the amount of histamine in rat peritoneal must cells after intravenous infusion of radiopaque agents (ROA) in a dose of 2 ml/kg and the amount of these penetrating from the blood into the peritoneal cavity. The degree of penetration is determined by the chemical structure and/or physiochemical properties of the ROA.

Restorative proctocolectomy with ileal pouch has become the surgical treatment of choice for patients with ulcerative colitis and familial polyposis of the colon. Defecography is the radiologic technique commonly used to obtain detailed information on function and morphology of the ileal pouch, but it fails to depict the pelvis. Computed Tomography (CT), with coronal images only was used to examine 10 patients with ulcerative colitis, submitted to restorative proctocolectomy. Coronal CT, yielding a panoramic view of the pelvis, represent an effective alternative technique to defecography. In fact, the two techniques provide comparable information relative to the ileal pouch; coronal CT also depicts the possible thickening of pouch walls and of pelvic fat tissue. Coronal CT also depicts the continence of ileo-anal and ileo-ileal anastomoses and the functional changes of the perineal muscles at rest and during squeezing. Coronal CT images allow easy and clear detection of such major postoperative complications as pelvic inflammation and fistulae (less frequently stenosis or dehiscences of the anastomosis).

The intravenous injection of cimetidine in a dose of 20 mg/kg enhanced verografine and iodamide excretion in chronic canine experiments. The higher verografine and iodamide excretion was due to their increased renal tubular secretion. In dogs, cimetidine unchanged the secretion of cardiotrast, a test agent for anionic transport. Possible extrarenal mechanisms of action of cimetidine on verografine and iodamide transport were also examined.

The purpose of this study was to verify and compare the different types of reactions to iodinated contrast media available at the Social Security Metropolitan Hospital Complex: Conray 60%, Vascoray and Uromiron. These are ionic, high osmolality compounds. The authors found that, in 400 patients not only the osmolality had an important role in the reactions observed, but that the intrinsic nature of the molecule of the contrast medium used was the determining factor.

The authors analyze the results of iodamide use for galactography. 434 females with discharge from the nipples were examined making use of galactography, and 136 women were selected for surgical treatment; the local processes in the mamma were previously unpalpated, nor were they confirmed by the laboratory findings. Clinical and morphologic analysis of the preparations resected in surgery has lead the authors to a conclusion that galactograms made with use of iodamide are sufficiently contrast and informative. The authors recommend this agent for the diagnosis of unpalpated mammary tumors.

The in vivo and in vitro effects of radioopaque agents such as bilignost, iodamide, and triombrast on blood thromboxane B2 (TxB2) and prostacyclin levels were studied in man and rats. These radioopaque agents were demonstrated to increase prostacyclin levels and to decrease TxB2 in the plasma by 40%, as evidenced by urography when given in vivo (1-2 g/kg) and in vitro (2.5.10(-2) M and 2.5.10(-3) M).

Perineal sonography and urethrocystography were performed on 45 patients in the same sitting to evaluate the sonographical method with regard to its applicability as a routine examination method. Corresponding results were obtained 14 times (= 30%). In 31 patients (= 70%) urethrocystographic and ultrasonic measurements diverged. The urethrocystogram must therefore remain an integral part in the work-up of urinary incontinence.

On the 3rd day after the last administration of phenobarbital (50 mg/kg orally, 4 days), benzonal (35 mg/kg orally, 4 days), zixorine (200 mg/kg orally, 4 days) and 3-methylcholanthrene (20 mg/kg subcutaneously, 2 days) the rats exhibited a decrease of iodamide secretion in the kidneys. The administration of zixorine to the dog (200 mg orally, 6 days) led to a significant decrease of iodamide transport in the first two weeks after discontinuation of the drug administration.

The authors analyzed data from two recent articles in Radiology in which the quality and results of randomized control trials (RCTs) comparing the efficacy or safety of the low-osmolality contrast media (LOM) iopamidol, iohexol, and ioxaglate with that of the high-osmolarity contrast media (HOM) diatrizoate, iodamide, iopamide, iothalamate, and metrizoate were assessed. One conclusion in the source articles was that no differences were seen between the two groups of contrast media in frequency of nausea, vomiting, and urticaria. However, the LOM group included both nonionic LOM (NIM) and the ionic contrast medium ioxaglate. The authors found that various complications associated with the use of contrast media were much less common with NIM than with HOM; statistically this lower frequency is highly significant. This difference was obscured in the previous studies by the pooling of RCTs in which the less toxic NIM were used and RCTs in which the more toxic ionic contrast medium ioxaglate was used.

To investigate whether the endogenous vasoactive substrate, leukotriene B4 (LTB4), was induced in adverse reactions observed after intravenous injection of iodinated contrast media (CM), the authors measured the in vitro production and metabolism of LTB4 by human polymorphonuclear leukocytes (PMNs) after stimulation with different doses of commercial CM preparations: iopamidol, 300 mg I/mL; iodamide, 300 mg I/mL; iohexol, 300 mg I/mL; ioxaglate, 320 mg I/mL; and the experimental preparation, iomeprolo. This study showed that the CM studied do not stimulate the production or metabolism of LTB4 by isolated human blood PMNs. All of the CM studied except iodamide do not inhibit the production or metabolism of LTB4 in PMNs stimulated by A23187. The in vitro hepatic microsomal oxidation of exogenous LTB4 to (omega-1)OH LTB4 and omega-OH LTB4 was inhibited by all the CM studied. LTB4 production by PMNs seems not to play a major role in anaphylactoid reactions observed after iodinated CM. However, a transient blockade by CM of LTB4 metabolism, leading to an increase of steady-state concentrations of LTB4, could not be excluded by these experiments.

Bilignost, iodamide and triombrast were shown to increase the concentration and to decrease the size of the rat blood serum immune complexes in vivo and in vitro. A decrease of the size of immune complexes was also observed during angiography with the use of triombrast in humans. According to the relation to the action of roentgen contrast media on the concentration and size of immune complexes humans and rats can be divided in "sensitive" and "tolerant" ones.

Hemolytic complement activity and a C3a radioimmunoassay (RIA) were investigated for their ability to characterize contrast media (CM) with respect to complement activation. The CM tested were commercial formulations of diatrizoate, iodamide, iothalamate, ioxaglate, iohexol, and iopamidol. When plasma was exposed to CM, the hemolytic complement activity decreased and the C3a concentration increased. The C3a assay had a larger dynamic range and therefore more ability to discriminate among the CM. Using C3a data from pooled plasma or from individual donors' plasma, nonionic iopamidol (as Isovue 300) had lower complement-activating potential (P less than .005 and P greater than .05, respectively) than all of the ionic media based on diatrizoate, iothalamate, iodamide, and ioxaglate. The ranges of mean C3a values generated by saline, nonionic CM, and ionic CM were 48 to 60, 65 to 173, and 807 to 3272 ng C3a/50 microL, respectively. Complement activation was found to correlate with osmolality (r = 0.945, all media) and with molarity (r = 0.994, diatrizoates).

Ultrasonography and intravenous pyelography (IVP) were compared for their diagnostic value in 65 patients (29 women, 36 men; mean age 57 [19-85] years) thought to have disease of the kidneys or urinary tract (microhaematuria in 16, macrohaematuria in 5, urinary tract infection in 11, suspicion of renovascular hypertension in 6, suspected tumour in 5, suspected nephrolithiasis in 15, and flank pain of uncertain cause in 7). Ultrasound established an abnormal condition in 29, in five of which IVP gave false positive results, false-negative results in three. The false-negative results were an indirect sign of renal artery stenosis in one patient and in one patient each of duplex ureter and cystic ureteritis. Mild hydronephrosis (n = 3), stone in a kidney or the renal calyx system (n = 2) and tumour of the right kidney (n = 1), diagnosed by ultrasound, were not seen by IVP. Concordant results were thus obtained in 70% of cases. Ultrasound examination of the urinary tract gives such reliable results that in many cases an additional IVP is unnecessary.

The results from a hysterographic study on women with bicornuate uterus are discussed. It is established that its frequency is 2.2% of 1623 performed hysterosalpingographies. A detailed analysis is made on the form and dimensions of the cornua [correction of corns], total isthmic part and cervical canal. Some metric parameters (height and width, sizes of the isthmus the an angle between the corns) are given with the purpose of greater precision of roentgenological interpretation.

In the course of 131 coronary angiographies, a non-ionic hyperosmolar contrast medium (Uromiro 75%, Bracco, Milano) provoked transient arrhythmias in 92 cases: 50 marked sinus bradycardias, 11 asystoles, 21 low-rate idiojunctional rhythms, 1 first-degree AV block, 7 third-degree AV blocks and 2 ventricular fibrillations. In 90 cases the rhythm disturbance was stopped by mere repeated cough. In the 2 cases of ventricular fibrillation direct current shock was used. If instructed coughing started within 8 seconds after the onset of arrhythmia, the patient maintained consciousness and the cough, as an internal cardiac massage, proved to be an adequate resuscitation method. In case prodromal signs of artificial bradycardiac arrhythmias were present, immediate cough could usually prevent the loss of consciousness and could also stop the arrhythmia. Therefore it seems logical to apply this method in patients at risk of Adams-Stokes attacks. A certain number of sudden deaths could be avoided.

In chronic experiments on dogs it was shown that verografin and iodamide are excreted from the body not only by filtration but by tubular excretion as well. The maximal transport of verografin and iodamide is significantly lower than that of cardiotrast. In experiments on rats similar results were obtained. Concurrent administration of verografin and iodamide with cardiotrast decreases their excretion in the urine in rats that is probably due to competition for the common transport system in the epithelium of renal tubules.

Active tubular secretion of iodamide, a water-soluble contrast medium, was demonstrated by comparing the clearances of iodamide, iothalamate and inulin. Passive tubular back diffusion was not found. The fraction excreted by tubular secretion was significantly reduced at "clinical" plasma concentrations. The glomerular filtration rate was slightly depressed at these concentrations of iodamide and diatrizoate.

The combined effects of an iodine contrast medium and X-rays on the number of colony forming units (CFUs) in mice bone marrow were examined in vitro and in vivo. No changes were observed in the number of CFUs per 105 nucleated bone marrow cells, when the contrast medium alone was added to bone marrow cell suspensions at concentration of 0.5 and 5.0%. X-irradiation of the suspensions above a dose of 50 R reduced the number of CFUs per 105 cells. The irradiation of the suspensions in the presence of the contrast medium produced further decrease in the number of CFUs per 105 cells, depending on the concentration of the medium used. No enhancement of the X-ray effect was observed when mice were injected with the contrast medium at a dosage 10 times higher than that used in X-ray diagnosis in man and irradiated immediately. Thus, the iodine contrast medium sensitized hematopoietic stem cells to X-rays in vitro but did not in vivo.

The myocardial toxicity of iodamide (Jodomiron 380) in selective coronary angiography was compared with that of metrizoate (Isopaque coronar). Electrocardiographic changes, systolic blood pressure and heart rate were registered and compared in a total of 106 injections. Both contrast media produced transient changes in ST-segment and T-wave, reduced the heart rate and systolic blood pressure. Differences noted were: a more marked hypotensive effect after injection of Jodomiron into the left coronary artery, and a higher frequency of moderate electrocardio graphic changes at injection of Isopaque into the right coronary artery. Because of the small number of registrations, however, these differences were not conclusive. The diagnostic quality of examination with both contrast media was excellent.

The endothelial injury produced by meglumine iodamide was studied in the rat aorta. A mixture of blood and contrast medium was more toxic to the endothelium than the pure contrast agent. This difference disappeared after premedication with antihistamine, which did not affect the injury produced by the pure contrast agent. Meglumine iodamide appears to cause a release of histamine from blood but not from the aortic endothelium nor from surrounding tissues in amounts demonstrable by this method. Leucocytes are a source of histamine after intravascular contrast medium administration.

Furosemide injection was used in a total of 72 guinea pigs to induce a cochlear dysfunction similar to the sensorineural loss associated with sudden deafness. Prior to the furosemide administration, 38 of the animals were treated with an injection of one of four radio-contrast media; methylglucamine and sodium diatrizoate, sodium iothalamate, methylglucamine and sodium iodamide, and methlyglucamine diatrizoate. In the control animals, receiving only furosemide, both endocochlear potential (EP) and cochlear microphonic (CM) underwent a severe depression followed by recovery and subsequent secondary depression. Animals pretreated with one of the first three compounds showed little or no EP or CM depression. Animals pretreated with the fourth, methylglucamine diatrizoate, showed the same EP depression as the control animals. The possible mechanism for this blocking effect and its significance in the clinical treatment of sudden deafness is discussed.

Infusion of dilute contrast agent through an upper extremity vein results in marked opacification of the superior vena cava and the ipsilateral subclavian and brachiocephalic veins in computed tomography of the upper mediastinum. Also, the cranial arteries are well opacified. Images obtained by this method display anatomical relationships to better advantage and permit more accurate interpretation of anatomical relationships of the upper mediastinal masses. Improved anatomical details are obtained as compared to noncontrast scans or scans after bolus injection. In cases of suspected venous occlusion, functional diagnostic information is also achieved.

The pharmacokinetic characteristics of iodamide, a contrast agent for excretion urography, were studied in seven normal subjects and in 15 patients with various degrees of renal impairment. Two different formulations were administered, namely, a 65% solution (iodamide 300) by slow intravenous injection and a 24% solution by slow intravenous (drip) infusion. Both preparations of iodamide exhibited characteristics of an open two-compartment model. In both normal subjects and patients, the contrast agent was excreted almost exlusively in urine. In normal subjects, the pharmacokinetic parameters of both formulations were similar, with a distribution half-life (1/2alpha) of about 3 minutes and a disposition half-life (t1/2beta) of about 69 minutes. An average of 84 per cent of the dose was excreted in urine within 4 hours after administration of iodamide with net renal tubular secretion of about 38 per cent. The binding of iodamide to plasma proteins was negligible, and the extent of biotransformation of iodamide was minimal. In patients with renal impairment, the disposition half-life (t1/2beta) of iodamide ranged from 4.1 to 16.4 hours. Other changes in pharmacokinetic parameters were also seen in patients with renal impairment.

In a comparative urographic study of the methylglucamine salts of iodamide (Uromiro 300) and iothalamate (Conray 280) the following conclusions have been made: (i) In subjects with radiologically normal kidneys and a creatinine clearance greater than 70 ml/min total urogram scores and nephrogram scores were higher with iodamide (not statistically significant). The improvement in performance was more marked in the nephrographic phase. (ii) In patients with radiologically normal kidneys and a spectrum of normal and abnormal renal function, total urogram scores and nephrogram scores showed no significant dependance on creatinine clearance. (iii) No correlations of note were observed between urographic performance and physical or biochemical parameters for either contrast medium. (iv) Side effects encountered in the study were mild and there were no significant differences between the contrast media in either the incidence or severity of the side effects. (v) Post-injection blood pressure profiles showed no significant differences between the media. (vi) Induced electrocardiographic abnormalities were uncommon and mild occurring in seven patients following iothalamate and three patients following iodamide.

Five contrast media, Conray 280 and 420, Urografin 370, Uromiro Sodium 300 and Niopam 370, were compared in a randomised trial involving a total of 482 patients. The best urographic agent was Conray 420 and the worst Conray 280, these control agents defining the ends of the scoring system. Uromiro Sodium 300 was very nearly as good as Conray h1^>. A non-ionic agent, Niopam 370, scored nearly equal with Urografin 370; both were rather better than Conray 280. There was little difference in minor reactions between the media. No reason was found to prefer non-ionic to ionic agents for general use in urography; indeed for a diagnostic examination the sodium salt of an ionic agent is preferable. A new generation of contrast media which do not dissociate in solution and are therefore known as nonionic have been introduced recently. The characteristics of non-ionic contrast media include a low neurotoxicity and a considerably higher LD50 in experimental animals than ionic agents. Non-ionic media are said to produce denser pyelograms because of a lower osmotic diuresis but they opacify the collecting system more slowly. Water restriction is thought to be less important for good quality pyelograms (Cueff& Pinet, 1979). There has been considerable interest in the use of non-ionic agents for urography because they are said to cause fewer side effects, to be safer and to produce better urograms. This study was designed to test these hypotheses. The non-ionic contrast medium chosen for this trial was Niopam 370 (iopamidol). Uromiro Sodium 300 (sodium iodamide), an ionic contrast medium, is said to have an additional pathway of excretion by active tubular transport and so to be a better contrast agent (Bonatti et al, 1983; Bollerup et al, 1975). It was therefore included in the trial as an additional test medium. The control media for the study were Conray 420 (sodium iothalamate) and Conray 280 (meglumine iothalamate). These two contrast media have been used for more than a decade at the City Hospital. Conray 420 had displaced Urografin 370 for urography as it was easier to inject, was thought to give better nephrograms, and the urogram could be completed more quickly because it reliably showed a pyelogram on

In a comparative urographic study of the sodium salts of iodamide (Uromiro 300 Sodium) and iothalamate (Conray 420) the following conclusions have been made. (i) In subjects with radiologically normal kidneys and a creatinine clearance greater than 70 ml/min, nephrogram scores were significantly higher with iodamide (P less than 0.02). There were differences between the media in respect of total urogram scores and pyelogram scores but they were not statistically significant. (ii) In patients with radiologically normal kidneys and a spectrum of normal and abnormal renal function, performance scores for iothalamate showed no significant relationship with creatinine clearance. Results for iodamide, however, showed some relationship with creatinine clearance (nephrogram score r = 0.46, pyelogram score r = 0.38, total urogram score r = 0.49). A possible mechanism for this is proposed. (iii) Side-effects encountered in the study were mild and there were no significant differences between the contrast media in either the incidence or severity of the side-effects. (iv) Blood-pressure and pulse-rate profiles following iodamide were not significantly different from those following iothalamate. (v) Cardiac arrhythmias were mild and uncommon.

Ten patients with normal serum creatinine and no evidence of acute cholecystitis were found to have vicarious excretion of water-soluble contrast media into the gallbladder 20 minutes to 72 hours after injection. Eight of the ten had unilateral renal pathology. Two patients, however, had bilaterally normal kidneys. The patients had been injected with either diatrizoate, iothalamate, or iodamide. The mechanisms and pathophysiology of vicarious contrast excretion are discussed. The vicarious excretion of intravascular contrast in the gallbladder does not in itself indicate renal or hepatobiliary disease. Although commonly associated with unilateral renal pathology, vicarious gallbladder excretion of urographic contrast may be a normal variant in some patients.

N tau-methylhistamine concentrations in plasma and urine were determined using a newly developed simultaneous determination for histamine and N tau-methylhistamine, based on isotope dilution mass fragmentography. Three groups of patients were investigated: patients receiving intravenously-administered iodamide for excretory urography, patients receiving a wasp-sting challenge, and patients treated with an intravenously-administered muscle relaxant. In all patients showing a distinct systemic anaphylactic or anaphylactoid reaction histamine and N tau-methylhistamine concentrations were found to be elevated. From the results of this study it can be concluded that N tau-methylhistamine in plasma and urine is a good parameter for histamine release, and that the determination of this histamine metabolite are less hampered by possible artefacts (due to basophil disrupture, a very short half-life time or bacterial production) than determinations of histamine itself.

All the modern radiographic contrast agents (diatrizoate, iodamide, iothalamate, metrizoate) for use in studies of the blood vessels (angiography) consist of a benzene ring, in which three hydrogen atoms have been replaced by three firmly-bound iodine atoms. In order to provide high water solubility and low toxicity one of the remaining three hydrogen atoms in the benzene ring has been replaced by a salt-forming carboxyl group while two of them have been replaced by other hydrophilic radicals, each containing a chain of one nitrogen and two to three carbon atoms. A high absorption of X-rays requires high iodine concentration and consequently the angiographic contrast agents are very concentrated solutions with osmolalities in the magnitude of 1500 to 2500 mOsm. For fast injection through narrow catheters, an angiographic contrast agent should have a low viscosity. Several of the toxic effects of angiographic contrast agents are related to their high osmolality. There is thus a need for a water-soluble contrast agent for which the ratio osmolality/iodine content is lower than for the contrast agents available today. The ratio osmolality/iodine content could be decreased if oligomers or polymers of the modern contrast agents were synthesized. However, measurements of the viscosity of such agents showed that already oligomers had a high viscosity. A discussion of physico-chemical laws gives the following conclusions. (1) The viscosity of polymeric contrast agents could be kept at a minimum if the axial ratio of the contrast medium molecule is kept as close to one as possible. (2) The synthesis of a non-electrolytic contrast agent, that does not contain any salt-forming radicals, raises the possibility of combining low osmolality with low viscosity in a water soluble contrast agent. A monomer of a non-electrolytic contrast agent could get a lower osmolality than a polymer of an electrolytic contrast agent.

Twenty-two patients with a complaint of sudden deafness were treated with one or the other of two of the radiopaque contrast media, 9 received daily doses of sodium iothalamate, and 13 were treated similarly with methlyglucamine and sodium iodamide. Four of the first group and eight of the second demonstrated either an effective partial or a complete recovery of hearing function. Those failing to respond were generally classified completely deaf at admission and reported nausea, vomiting, or vertigo at onset of sudden deafness. Treatment with sodium salts of triiodobenzoic acid derivatives, i.e., sodium iothalamate and methylglucamine and sodium iodamide, is judged to be effective in selected cases of sudden deafness.

The effect of intravenous administration of ionic contrast media on local release of prostacyclin (PGI2) was investigated in man. Iodamide and ioxaglate, high- and low-osmolality contrast media, respectively, both significantly increased PGI2 levels at the site of injection. Iodamide was the most active, whereas an identical volume of isotonic saline had no effect. This study suggests that local formation of PGI2 may adequately reflect the degree of endothelial irritation that is caused by contrast media and that depends in part on their osmolality.

Fifty apparently healthy individuals undergoing intravenous pyelography had electrocardiographic evaluation before, during, and after the examination. No patient had a major electrocardiographic change after contrast injection. Of the 7 patients with abnormal baseline electrocardiograms, all had a striking (greater than 40 beats per minute) rise in rate. The 43 patients with normal electrocardiograms had a small but significant rise in rate. No ischemic changes or major arrhythmias occurred. Although electrocardiographic aberrations were better correlated with baseline electrocardiograms than history or physical evaluation, our experience and a review of the literature confirms the safety of this examination in healthy people.