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Amyloid-beta 42 (Aβ 42 ), the key biomarker of Alzheimer's disease (AD), aggregates to form neurotoxic amyloid plaques. In this work, we modified two fluorescein isothiocyanate-labeled Aβ 42 -targeting peptides and designed an Aβ 42 -specific ultrasensitive polyvalent-directed peptide polymer (PDPP) to enhance AD diagnosis sensitivity. The dissociation constant of Aβ 42 by PDPP was 10 3 -fold higher than the single-site-directed peptide. The improved binding was due to the ability of PDPP to detect multiple receptors on the target. The power of the PDPP diagnostic probe was verified in its application to detect Aβ 42 in cerebrospinal fluid (CSF), which showed a lower limit of detection (LOD) in the fg mL -1 range that is more sensitive than detection by antibodies or single peptides. In addition, we present a novel ultrasensitive diagnostic system using an array of nanoporous ZnO nanoparticles, which play a role in fluorescence signal amplification, to further improve AD diagnosis sensitivity. We enhanced the signal on the basis of the properties of nanoporous ZnO nanoparticles and measured and quantified an ultralow concentration (ag mL -1 range) of Aβ 42 . This PDPP coupled to the nanoporous ZnO-based system is a novel approach to AD diagnosis that might also be useful for the detection of other target biomarkers and clinical applications.

Although the ultimate goal of administering active pharmaceutical ingredients (APIs) is to save countless lives, the presence of impurities and/or degradation products in APIs or formulations may cause harmful physiological effects. Today, impurity profiling (i.e., the identity as well as the quantity of impurity in a pharmaceutical) is receiving critical attention from regulatory authorities. Despite the predominant use of spectroscopic and chromatographic methods over electrochemical methods for impurity profiling of APIs, this work investigates the opportunities offered by electroanalytical methods, particularly, ion-selective electrodes (ISEs), for profiling degradation-related impurities (DRIs) compared with conventional spectroscopic and chromatographic methods. For a meaningful comparison, diatrizoate sodium (DTA) was chosen as the anionic X-ray contrast agent based on its susceptibility to deacetylation into its cytotoxic and mutagenic degradation product, 3,5-diamino-2,4,6 triiodobenzoic acid (DTB). This cationic diamino compound can be also detected as an impurity in the final product because it is used as a synthetic precursor for the synthesis of DTA. In this study, four novel sensitive and selective sensors for the determination of both DTA and its cytotoxic degradation products are presented. Sensors I and II were developed for the determination of the anionic drug, DTA, and sensors III and IV were developed for the determination of the cationic cytotoxic impurity. The use of these novel sensors not only provides a stability-indicating method for the selective determination of DTA in the presence of its degradation product, but also permits DRI profiling. Moreover, a great advantage of these proposed ISE systems is their higher sensitivity for the quantification of DTB relative to other spectroscopic and chromatographic methods, so it can measure trace amounts of DTB impurities in DTA bulk powder and pharmaceutical formulation without a need for preliminary separation.

This study proposes a new methodology to evaluate the putative consequences of the long-lasting circulation in the blood pool of nanoparticulate systems widely used in nanomedicine, Indeed, the blood pool contrast agent for micro-computed tomography, i.e. iodinated nano-emulsions, have recently been developed, for their great potential in medical applications such as advanced diagnosis, image-guided surgery, personalized medicine or theragnostics. Stealth nanoparticles exhibit a low recognition by the reticuloendothelial system, resulting in a prolonged circulation in the bloodstream and long-lasting contact with the endothelium. Therefore, the aim of the present study is to determine whether this prolonged interaction could induce an alteration of the vascular reactivity in rat aorta. The Iodinated nano-emulsions were intravenously injected in anesthetized rats. After 1h of contrast agent circulation in the blood pool, the thoracic aorta was removed for the study of vascular reactivity. These animals were compared with control (untreated) rats and a third group of rats receiving an injection of phosphate buffered saline (i.e. dispersing phase of the nano-emulsions). Phenylephrine-induced concentration-dependent contractions of the isolated rat thoracic aorta were not modified whatever the group. Sodium nitroprusside (a nitric oxide (NO) donor)-induced relaxations of endothelium-denuded aorta were also unaltered in response to the different administrations. In contrast, in comparison with control animals, endothelium-dependent NO-mediated relaxations to acetylcholine were significantly impaired in thoracic aorta from PBS-treated rats, but not in animals receiving the iodinated nano-emulsion. In addition, neither isoprenaline-induced nor levcromakalim-induced relaxations were modified in the aorta from the three groups of animals. These findings indicate that even with a long-lasting residence time of the iodinated nano-emulsion in the blood flow, these iodinated nano-emulsions do not alter the vascular reactivity and thus can be used as contrast agent for preclinical vascular imaging on small laboratory animals., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Rationale and Objectives: To compare liver perfusion parameters obtained by using an extravascular contrast agent and a blood-pool agent., Materials and Methods: Fifteen rabbits were imaged with a continuous 40-second single-slice computed tomography acquisition after a bolus injection of contrast agent (physiologic bolus duration 4-5 seconds, extravascular iohexol, n = 7; experimental nanoparticulated blood-pool agent WIN8883, n = 8). Time-density curves were generated for the aorta, portal vein, and liver. From the curves, arterial, portal, and total blood flows and hepatic perfusion index (HPI, arterial-to-total perfusion ratio) were determined by using two commonly applied fundamentally different analyzing methods: the single-compartment model and the peak gradient (PG) method. Also, the gamma variate fitting method was used., Results: By using the single-compartment model, the obtained HPI and total blood flow were 0.14 +/- 0.04 and 2.29 +/- 0.40 (mL/min/mL(tissue)) for WIN8883, and 0.15 +/- 0.06 (P = .54) and 4.60 +/- 1.14 (mL/min/mL(tissue)) (P = .0002) for iohexol, respectively. With the PG, HPI and total blood flow were 0.15 +/- 0.08 and 1.27 +/- 0.24 (mL/min/mL(tissue)) for WIN8883, and 0.20 +/- 0.06 (P = .12) and 2.11 +/- 0.25 (mL/min/mL(tissue)) (P = .00002) for iohexol, respectively. With the blood pool agent, similar contrast enhancement to the conventional agent was achieved with about 36% reduced dosage of iodine per body weight (mg I/kg)., Conclusions: HPI was found to be quite insensitive to different contrast agent types and analyzing methods. However, the arterial, portal and total liver blood flow values strongly depend on contrast agent type and modeling method.

Sigmoid diverticulitis is in case of complications like perforation, abscess and peritonitis a life-threatening disease. A diagnostic work up with high sensitivity is mandatory. In a prospective study upon 247 patients with the possible diagnosis of acute diverticulitis ultrasound is a screening method with a high specificity (97 %) and leads in combination with the hydrocolonsonography and the colour flow doppler to a high sensitivity (76 %). Without any typical findings in ultrasound, helical CT scan is the best method in the evaluation of the acute diverticulitis (sensitivity and specificity 100 %), because contrast enema is inferior to CT in the evaluation of abscesses (6 %) and perforation (53 %). CT has in case of perforation and of abscesses a sensitivity of 90 % and 100 %, while ultrasound has a sensitivity of 12 % to perforation and of 39 % to abscesses.

Purpose: To study the effects of formulation variables on the physical stability of a submicron crystal (nanocrystal) suspension under steam sterilization conditions., Methods: Suspensions of ethyl diatrizoate nanocrystals were prepared by wet milling in the presence of the surfactant poloxamine 908. Particle size distribution and zeta potential were measured by photon correlation spectroscopy., Results: On heating, the mean particle size of the nanocrystal suspension remained essentially unchanged up to 110 degrees C, the cloud point of the stabilizing surfactant, but increased significantly above that temperature. The increase in particle size was a result of particle aggregation rather than crystal growth. Adding a cloud point booster to the suspension significantly minimized the particle aggregation at high temperatures. The purity of poloxamine 908 and the tonicity agent and buffer salt used also affected the heat stability of the suspension, the latter agents apparently through altering the surfactant cloud point., Conclusions: The aggregation of the ethyl diatrizoate nanocrystalline suspension under steam sterilization conditions was a result of phase separation of the stabilizing surfactant at its cloud point. When formulated with a cloud point booster to prevent the phase-separation, the suspension maintained its physical stability under steam sterilization without any significant change in particle size distribution.

An LC procedure was developed to separate diatrizoate sodium from three known impurities. These impurities are 2,4- and 2,6-diiodo-3,5-diacetamidobenzoic acid (DDZA), and the free amine (5-acetamido-3-amino-2,4,6-triiodobenzoic acid). The separation was achieved using a Hamilton, PRP-X100, anion exchange column. The retention of diatrizoate sodium and the impurities was dependent on pH, potassium chloride concentration and phosphate concentration. Increasing any of these mobile phase modifiers decreased the retention time of all of the components. The eluent for assay and purity determination of drug product consisted of 0.1 M potassium chloride and 0.05 M potassium phosphate dibasic in water/acetonitrile (900:100). The mean concentration of diatrizoate sodium in Hypaque Sodium 50% determined over 3 days was 102.3% of label claim with an R.S.D. of 1.3. The accuracy of the purity method, determined by spiking known amounts of the impurities at five concentrations ranging from 0.025 to 0.06% (w/w) into drug product, was 100.1% for DDZA and 94.2% for the free amine. The decomposition of diatrizoate sodium in 0.1 N potassium hydroxide at 85 degrees C followed pseudo first-order kinetics. The calculated half-life was 2 days.

Rationale and Objectives: We evaluated liver vascular physiology with a functional spiral computed tomography (CT) technique and an intravascular contrast agent., Methods: Eleven rabbits were studied by means of continuous 40-second single-section data acquisition after bolus injection of an experimental contrast agent. Sequential images were reconstructed at 200-msec intervals. Aortic, portal and hepatic venous, and liver time-HU curves were obtained. From these, hepatic blood volume and flow, tissue transit times, and arterial and portal contributions to total liver blood supply were assessed., Results: The following measures were obtained: hepatic blood volume fraction, 0.33 +/- 0.03 (mean +/- standard error); total flow, 241.1 mL/min +/- 33.6 per 100 g of tissue (arterial component, 11.3 mL/min +/- 3.0 per 100 g of tissue; portal component, 226.4 mL/min +/- 30.7 per 100 g of tissue); arterial transit time, 8.7 seconds +/- 1.6; portal transit time, 8.7 seconds +/- 1.3; arterial to portal perfusion ratio, 0.06 +/- 0.01; and calculated arterial and portal perfusion indexes, 0.05 +/- 0.01 and 0.95 +/- 0.01, respectively., Conclusion: Functional CT is a promising, high-resolution tomographic imaging technique for evaluating liver perfusion.

Rationale and Objectives: We evaluated the imaging characteristics of an iodinated particulate contrast agent for indirect computed tomography (CT) lymphography of normal subdiaphragmatic lymph nodes in dogs., Methods: Four milliliters of a 15% (wt/vol) iodinated nanoparticle suspension was injected into the gastric, colonic, rectal, or cervical submucosa, loose paraprostatic fascia, or metatarsal subcutaneous tissues in 10 healthy beagles. Endoscopic, CT, or ultrasound guidance was used when necessary to facilitate contrast agent delivery. CT and radiographic images were obtained prior to contrast administration and at 4 hr, 24 hr, and 7 days postcontrast injection. Postmortem examinations were then conducted., Results: CT images showed enhancement of regional lymph nodes draining the various injection sites. The mean attenuation of opacified nodes was 678 +/- 463 Hounsfield units 24 hr after injection and remained elevated 7 days later. Lymph node opacification on CT images correlated well with the node location observed on postmortem examinations., Conclusion: Subdiaphragmatic lymph nodes can be effectively opacified using an iodinated nanoparticle contrast agent for indirect CT lymphography.

Rationale and Objectives: We evaluated the imaging characteristics of an interstitially or intraperitoneally delivered iodinated particulate contrast agent for computed tomography (CT) lymphography of the craniocervical and thoracic lymph nodes., Methods: We injected 2-4 ml of 15% wt/vol iodinated nanoparticle suspension subcutaneously, submucosally, or intraperitoneally in eight normal dogs. CT and plain radiographic images were obtained prior to contrast administration and 4 hr, 24 hr, and 7 days after injection. Correlation was made to detailed postmortem assessment., Results: CT images showed enhancement of regional nodes draining injection sites. Mean attenuation of opacified nodes was 313 +/- 297 (mean +/- standard deviation), 536 +/- 453, and 492 +/- 372 Hounsfield units at 4 hr, 24 hr, and 7 days postinjection, respectively. Lymph node opacification on CT images correlated well with node location found at postmortem., Conclusion: Craniocervical and thoracic lymph nodes can be effectively opacified from interstitial or intraperitoneal delivery of this iodinated nanoparticulate contrast agent.

Rationale and Objectives: Surgical lymphangiography is infrequently used in staging cancer because of its inherent limitations. Radiopaque nanoparticulates target lymph nodes draining interstitial tissues and could make percutaneous lymphography feasible., Methods: Experimental nanoparticulate contrast agent formulations were injected subcutaneously in the forepaw or hindpaw of normal rabbits or rabbits with induced reactive nodal hyperplasia. Axillary and popliteal nodes were imaged with thin-section computed tomography (CT) using quantitative methods to measure node enhancement. Dose-response (0.1-2.0 ml) and time course (4 hr to 10 weeks) of enhancement were assessed., Results: Nodal enhancement above 100 Hounsfield units was consistently obtained. Enhancement was significantly related to dose and peaked at 10 hr with slow washout over the observation period. Nodes with reactive hyperplasia were larger and had heterogeneous enhancement patterns distinctly different from normal nodes., Conclusion: Percutaneous CT lymphography effectively depicts the macroscopic intranodal architecture in rabbits.

Computed tomography was performed in two cases of blood-brain barrier (BBB) disruption due to cerebral arteriography. The first case showed diffuse contrast enhancement in the right frontotemporal region in the distribution of the middle cerebral artery; in the second case patchy contrast enhancement in both gray and white matter of both hemispheres was demonstrated. The possible mechanism for BBB disruption in these patients is discussed.

Thirty-four renal transplant recipients received drip infusion urograms from 2-24 days post-transplantation. Twenty-two patients exhibited changes in renal function within 1-4 days of the urogram that were indistinguishable from allograft rejection: a tender, swollen kidney, elevation of serum creatinine, oliguria, decreased urine sodium concentration, weight gain, and hypertension. Two patients developed acute tubular necrosis and required hemodialysis, but renal function in the remaining 20 patients improved after therapy for "graft rejection" with i.v. methyprednisolone sodium succinnate. Kidneys from older-age donors that were functioning suboptimally and kidneys which exhibited subsequent clinical allograft rejection were more at risk for contrast media toxicity. This suggests that occult vascular lesions may have been present in the allograft which were exacerbated when exposed to the irritant vascular effects of contrast media, producing a mild, reversible toxic nephritis. However, several kidneys with normal function and several kidneys which never exhibited rejection activity were also adversely affected by exposure to contrast media. It appears these agents should be used cautiously, if at all, in the early post-transplant period.

Ligandin, a glutathione (GSH) transferase, is a protein found in proximal tubular cells as well as in other tissues. It does not occur in the urine of normal subjects; however, its presence has been detected in the urine of some patients who have undergone renal angiography. This finding suggests renal tubular cell damage due to the procedure.

Direct contrasting of the anterior epidural space with 9-10% verografin solution was conducted in 123 patients (120 with discogenic radiculitis, 2 with tumors, and 1 with injury to the spine). The epidural space was contrasted for a distance of 3-4 intervertebral spaces and no stimulation of the epidural structures occurred. The epidurograms demonstrated convincing information concerning the character of the protrusion and prolapse of the intervertebral discs and the existence of block of the epidural space in tumors. Phenomena of "spinal epilepsy" occurred in 5 cases, which regressed rapidly after a complex of measures was applied. Anterior epidurography with water-soluble contrast media of low concentration is an informative and safe method.

A clinical and an animal study were performed to examine adverse effects when ratio 3 and ratio 1.5 contrast media are injected directly into the heart. In a randomized double-blind clinical trial of 50 patients undergoing cardiac angiography, the safety and efficacy of Hexabrix (ratio 3) and Renografin-76 (ratio 1.5) were compared. Cardiac output increased more significantly in the Renografin-76 group, and there was a significant difference in AV 02 indicating less vasodilatation with Hexabrix. There was dramatically less prolongation in the QT interval for the Hexabrix group. Ventricular fibrillation threshold studies of dogs examined the adverse electrophysiologic effects on the heart. One-ml doses of Hexabrix and Renografin-76 were injected in the left coronary artery and compared. Renografin-76 significantly reduced threshold, whereas Hexabrix was much less toxic. Ratio 3 agents are less hazardous in terms of total adverse effects and are particularly indicated for certain risk groups.

The effects of intravenous injection of an ionic contrast material (Renografin-76 [meglumine sodium diatrizoate]) on left ventricular pressure, internal diameter, and wall thickness, and on coronary and femoral hemodynamics were compared with those of a hydrolytically stable nonionic contrast material (iohexol). Renografin-76 caused drastic biphasic changes in left ventricular pressure and dp/dt (rate of change of left ventricular pressure), and moderate changes in end systolic dimension. Iohexol caused little or no change in left ventricular pressure and dimensions. In addition, Renografin-76 caused marked arterial hypotension and large increases in coronary and femoral blood flows, while iohexol caused no significant change in arterial pressure and coronary blood flow, and a mild increase in femoral blood flow. Based on these findings, it is concluded that iohexol is preferable to standard ionic contrast material for deriving basal physiologic information from computed tomographic and digital vascular studies.

Coronary angiography with Renografin 76 (RG76) occasionally results in ventricular fibrillation (VF). Angiovist 370 (AV370) is a contrast medium similar to RG76 except the calcium-sequestering agents, sodium citrate and EDTA in RG76 have been replaced by calcium EDTA. To determine whether these sequestering agents contribute to contrast medium-induced VF, a comparison was made of the effects of intracoronary injections of RG76, AV370, and saline solutions containing sodium citrate and EDTA (CIT/EDTA) and calcium EDTA (CA EDTA) on myocardial conduction, local QT intervals, and incidence of spontaneous and induced VF in 32 dogs. Four milliliters of RG76 produced a 111 +/- 12-ms increase in local QT intervals, compared with a 73 +/- 8-ms increase with AV370 (p less than 0.001). Spontaneous VF occurred in 12 of 16 six-milliliter injections of RG76, compared with 4 of 16 injections of AV370 (p less than 0.02) An early-cycle premature impulse applied after every fourth beat induced VF in 15 of 16 four-milliliter injections of RG76 compared with 5 of 16 injections of AV370 (p less than 0.01). As the premature beat conducted through the left anterior descending region, conduction slowing and fractionation occurred, which was less with AV370 than with RG76. The CIT/EDTA solution produced a greater increase in QT intervals (77 +/- 5 ms) than the CA EDTA solution (29 +/- 3 ms) or 0.9% saline solution alone (28 +/- 2 ms) (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Fifty-one patients were analyzed after a randomized double-blind study comparing Hexabrix and Renografin 60 in peripheral arteriography. The arteriographic studies and the volumes of contrast material used in both groups were similar. Hexabrix caused significantly less pain and discomfort than Renografin 60, and the diagnostic quality of the radiographs was comparable. A slightly higher incidence of minor side effects was noted in the Hexabrix group, mostly nausea and vomiting and urinary retention.

Concern for side effects of contrast materials limits the volume that can be used for angiocardiography in infants; many of these effects are related to hyperosmolality. The effects of intracardiac injections of ionic (meglumine sodium diatrizoate) and nonionic (metrizamide) contrast agents on the left ventricle and body fluids were compared in an infant model. Immediately after injection, meglumine sodium diatrizoate (MSD) caused increases in left ventricular peak systolic pressure (LVPSP) (+26 +/- 5%) (control (C) = 92 mmHg), LV dp/dt (+21 +/- 6%) (C = 2610 mmHg/sec), left ventricular end-diastolic dimension (LVEDD) (+31 +/- 5%) (C = 10.5 mm), and left ventricular end-systolic dimension (LVESD) (+28 +/- 6%) (C = 7mm). Subsequently, LVPSP and dp/dt decreased to -16 +/- 6% and -23 4 +/- 6% of control, while LVEDD and LVESD rose. Dimension changes resolved by 15 minutes. Metrizamide caused immediate increases in LVPSP (+27 +/- 4%) (C = 86 mmHg) and LV dp/dt(+25 +/- 4%) (C = 2640 mmHg/sec). These parameters never declined significantly below control levels and were at control level at 15 seconds. Initial increases in LVEDD (+17 +/- 3%) (C = 10 mm) and LVESD (+6 less than 4%) (C = 6.5 mm) with metrizamide were significantly less than with MSD (P less than 0.008). MSD caused greater and more persistent elevations of serum osmolalities than metrizamide. Differences between the two agents were accentuated during systemic hypoxemia. Thus, ionic contrast agents appear to have a greater propensity for inducing toxic cardiovascular effects in infants than nonionic agents.

In view of the possible role of prostaglandins (PG) and thromboxane (TX) in the disturbances of renal function and blood flow after the injection of diatrizoate into the renal artery, we have determined the levels of PGE2, 6-keto-PGF1 alpha (a stable metabolite of prostacyclin) and TXB2 in the renal venous blood before, during and after renal arteriography in 12 patients. Radioimmunologically assayed PGE2 was the most abundant prostaglandin in renal venous blood. Lower basal levels of PGs were associated with renal adenocarcinomas or other tumours than non-tumour kidneys. The concentrations of 6-keto-PGF1 alpha and PGF2 alpha rapidly increased after diatrizoate injection and returned to the basal levels within 5 minutes. Slower elevation was noticed in the PGF2 level of 5 tumour kidneys. Renal plasma concentration of TXB2 remained unchanged throughout the study. The rapid elevation of renal venous prostacyclin and PGF2 alpha concentration after the contrast injection may reflect the enhanced intrarenal prostaglandin synthesis or may be secondary to hemodynamic changes in the kidney caused by hypertonic diatrizoate.

Application of large amounts of iodine in the form of amidotricoic acid (Urografin) in 20 patients undergoing coronary angiography led to an increase in serum thyroxine (T4, p less than 0.005), triiodothyronine (T3, p less than 0.005) and plasma thyrotropin (TSH) in the basal state (p less than 0.05) as well as after TRH-stimulation (p less than 0.05), but not of serum 3,3',5'-triiodothyronine (reverse-T3, rT3) three weeks after contrast medium administration. Although TRH induced TSH stimulation had been subnormal prior to contrast medium application in five patients, T4 as well as T3 remained within the normal range in all patients. Neither preexisting iodine excretion nor the amount of contrast medium applied were related with the observed hormonal changes. We conclude, that application of relatively small as well as large amounts of amidotricoic acid leads to an increase of peripheral thyroid hormone concentrations, paralleled by a rise in basal and stimulated TSH secretion. These changes may be interpreted as physiological adaptation to augmented iodine supply in an area of moderate iodine deficiency.

The excretion of iodinated contrast media was studied in 13 immature rabbits after the intravenous injection of 2 ml/kg (approximately 600 mg I/kg) of radio-labelled Renografin-60, a high osmolality agent (1510 mOsm/kg), or Iopamidol-300, a new agent with a much lower osmolality (616 mOsm/kg). Renografin, but not Iopamidol, induced an immediate but transient 40% fall in blood pressure, a marked diuresis that was 3.4 times greater at its maximum than for Iopamidol, and a much lower urinary iodine concentration at the time of maximum diuresis (Renografin: 90.3 +/- 9.2 microgram/ml; Iopamidol: 213 +/- 32.9 microgram/ml). No difference between the two contrast media was found for plasma iodine concentration, renal clearance from the plasma, urinary iodine excretion rate or volume of distribution. In five additional rabbit pups, formal clearance studies made using a constant IV infusion of the agents and timed collections of urine and plasma showed that Iopamidol and Renografin were cleared at the same rate by the kidneys (P greater than 0.9).

A computer algorithm was developed and applied to measure brightness decay rates of myocardial contrast opacification observed with two-dimensional echocardiography (2DE). An agitated mixture of diatrizoate meglumine and saline (Renografin-saline) was injected into the left main coronary artery of 17 closed-chest dogs during the control state as well as after placement of an intracoronary plug to induce 85% stenosis in the left anterior descending coronary artery (LAD) in five dogs. In 12 dogs, injections were also performed distally to complete intracoronary balloon occlusion of the LAD. For each injection, up to 35 electrocardiographic-gated, end-diastolic 2DE frames were digitized into an image-processing computer that determined mean pixel brightness of each of 12 myocardial segments per 2DE short-axis cross-section. Time-activity curves for each segment were generated, and contrast decay half-life (t 1/2) was calculated. Mean t 1/2 for control-state injections was found to be 24.1 +/- 7.7 sec, as opposed to 293.8 +/- 164.5 sec after complete coronary occlusion (p less than .001). In the five dogs in which 85% LAD stenosis was induced, prolongation of contrast t 1/2 from 18.3 +/- 8.9 sec during control to 44.3 +/- 21.0 sec (p less than .001) after plug insertion occurred in myocardial segments subserved by the stenosed vessel. No significant change occurred in segments that were not supplied by the stenosed vessel (21.9 +/- 9.1 sec during control vs 24.9 +/- 11.6 after plug insertion into the LAD). A reproducibility study of injection-to-injection t 1/2 in the control state indicated a correlation coefficient of r = .84 and a standard error of the estimate (SEE) equal to 5.86 sec, while interobserver t 1/2 reproducibility was r = .91 and SEE = 5.21 sec. The t 1/2 measurement derived by computer analysis of myocardial contrast 2DE may serve as an index for characterization of regional myocardial blood flow and may be applicable to evaluate interventions that alter perfusion.

To investigate the mechanisms of ventricular fibrillation (VF) during coronary angiography, we assessed ventricular automaticity, local QT intervals, local conduction characteristics, and the ability to induce arrhythmias with premature ventricular stimulation in 30 dogs after intracoronary injections of 4 to 6 cc of Renografin 76 (RG 76). Ventricular automaticity was measured in six dogs as the idioventricular escape rate following intense vagal stimulation and was unchanged (51 +/- 6 vs 52 +/- 6 bpm, p greater than 0.05) with 6 cc of RG 76. In addition, 8 of 10 injections of 6 cc of RG 76 produced VF at a heart rate of 200 bpm compared to only 2 of 10 injections at a heart rate of 80 bpm (p less than 0.05). Composite and bipolar plunge electrodes were placed in the region perfused by the left anterior descending coronary artery (LAD) and circumflex coronary artery to assess QT intervals and conduction characteristics. RG 76, 4cc, produced a 116 +/- 18 msec increase in the QT intervals recorded from the region perfused by the LAD, resulting in a marked dispersion in repolarization. Both local bipolar and composite electrograms showed minimal conduction delay, which rarely extended beyond the QRS of a lead II ECG during atrial paced rhythm. As premature beats (spontaneous or induced) conducted through the region of QT prolongation, marked conduction delay was recorded from bipolar electrograms, while composite electrograms recorded continuous fractionated electrical activity spanning the diastolic interval at the onset of VF.(ABSTRACT TRUNCATED AT 250 WORDS)

A neonate with hypoxic damage to the brain from a complicated pregnancy and delivery demonstrated a prolonged retention of contrast medium in her cerebral dural veins and brain substance after cardiac catheterization. Myoclonic status epilepticus began during injection of the contrast medium and persisted until its clearance as noted by CT scan. A postmortem examination did not reveal any vascular or congenital abnormalities that would account for these effects.

The effect of 30% Urografin on platelet aggregation induced by adenosine diphosphate (ADP), epinephrine, and arachidonic acid was examined. In vivo and in vitro experiments in 10 nondiabetic subjects and in vitro experiments in 7 diabetic-uremic patients showed a statistically significant decrease in platelet aggregation 20 minutes after in vitro incubation or in vivo infusion with Urografin. Urografin concentration was about 2.4-2.5%. The possibility of bleeding induced by contrast media and the connection with acute renal failure in diabetic-uremic patients are discussed.

Because of relatively low acute toxicity, iosulamide meglumine has been recommended as an improved contrast material for intravenous cholangiography. It has been postulated that high doses of the compound could be given safely with the expectation of achieving greater biliary excretion and improved opacification of the biliary tree. Experiments performed in dogs show that higher rates of infusion of iosulamide result in greater urinary elimination without additional biliary excretion. Consequently, iosulamide is unlikely to have any special advantage as a contrast agent.

Because of the increased use of intravenous injection of contrast material for the evaluation of cardiac structure and function by digital subtraction techniques, a study was done to assess the hemodynamic effects of contrast material when used in this fashion in man. In 10 patients, with each serving as his own control, the effects of intravenous and intraventricular injections of sodium meglumine diatrizoate (Renografin 76) in the same dose were compared. There was no difference between these two methods with respect to changes in pulmonary wedge pressures, systemic pressures, and pulmonary vascular resistance. The elevation of mean pulmonary artery and right atrial pressure was greater after the intraventricular injection (p less than 0.05). The elevated cardiac output and systemic vascular resistance returned to control values somewhat more quickly after the intravenous injection (p less than 0.001 and p less than 0.05, respectively); and the increase in cardiac output was greater after the intravenous injection at 1 min (p less than 0.05), but less than after the intraventricular injection at 2 min (p less than 0.05). Despite the detection of these statistically significant differences, the magnitude and timing of these differences are too small to justify the notion that imaging by intravenous injections of standard ionic contrast media provides any substantial hemodynamic benefits or decreased risk to the patient.

The dose and concentration of an intra-arterially injected contrast medium, when increased approximately fivefold from a slightly hypotonic solution, produced lower tissue distribution volumes and lower extravascular diatrizoate fractions in the rat. A further fivefold increase in dose (to 1 ml/kg) with little change in concentration produced even lower early distribution volumes. Increases of concentration and dose caused a higher percentage of the contrast medium to remain within the vasculature, presumably as a result of extraction of tissue water by the hypertonic medium. Changes in the concentration of the contrast medium affected its distribution volume for a longer time than corresponding changes in the actual dose. The use of the more concentrated contrast media at higher doses should be expected to give better radiologic detail on angiograms.

Intravenous injections of ionic contrast media increase extravascular lung water in patients with elevated left atrial pressure, particularly in the presence of myocardial ischemia. The authors compared bolus injections of sodium methylglucamine diatrizoate and iopamidol on extravascular lung water at several levels of left atrial pressure in dogs. Methylglucamine increased lung water by a maximum of approximately 25-30% above baseline levels at low (less than 3 mm Hg), moderate (approximately equal to 15 mm Hg), and elevated left atrial pressures (greater than or equal to 25 mm Hg). At matched pressures, the peak change in lung water in the dogs given iopamidol was +4%, +7%, and +6%, respectively. In dogs with myocardial ischemia, the differences were even more pronounced (+45%, +60%, and +70%, respectively, for ionic media, and +7%, +12%, and +21% for iopamidol). The authors caution against using ionic contrast media in patients with left ventricular dysfunction, particularly associated with ischemia. In such cases, non-ionic media appear safer.

Iodinated water-soluble compounds have been widely recommended as the most suitable contrast media for diagnosis of gastrointestinal perforations. However, the authors present 6 cases in which mucosal tears and transmural perforations of the upper gastrointestinal tract were either unrecognizable or inadequately shown during initial evaluation with methylglucamine diatrizoate. Re-examination with barium sulfate demonstrated the precise location and extent of the perforations. Reasons for the higher diagnostic yield of barium studies are explained on the basis of experimental and clinical observations.

Various contrast agents with either sodium or meglumine cations and iothalamate and diatrizoate anions are compared in a series of patients with malignant gliomas. There is no difference in the ability of these agents to enhance tumors in cranial computed tomography.

A prospective clinical study was done on 20 patients referred for computed tomography within 28 hr of a cerebral ischemic event. The patients were scanned before, immediately after, and 3 hr after a high dose of intravenous contrast medium was administered to produce prolonged high blood iodine levels. In seven patients the delayed scan demonstrated a heretofore undescribed type of contrast enhancement which represents the early massive vasogenic edema seen in experimental animals before confluent hemorrhagic infarction. Four of the seven patients developed hemorrhagic infarction. None of the remaining 11 patients with cerebral infarctions and conventional postenhancement CT patterns showed hemorrhage on follow-up CT scans or at autopsy. Two patients with transient ischemic attacks had normal CT scans. It may now be possible to predict patients in whom there is high probability of hemorrhagic infarction before blood appears on CT. Treatment of these patients should probably be aimed at preventing the devastating effects of the vasogenic edema. We speculate that heparinization or bypass surgery to reestablish circulation may be contraindicated in this group.

Renografin-76 (RG76) regularly depresses myocardial contractility during coronary angiography. Angiovist-370 (AV370) is a contrast medium similar to RG76 except the calcium sequestering agents sodium citrate and EDTA in RG76 have been replaced by calcium EDTA (an additive that does not bind additional calcium). To determine if the calcium sequestering agents contribute to the mechanical depression produced by ionic contrast media, this study compared the inotropic response of RG76 to that of AV370. Additionally, saline solutions containing sodium citrate + EDTA and calcium EDTA at concentrations found in the respective contrast media were also compared. In 10 open chest dogs the percent change and duration of the inotropic response following intracoronary injections of RG76 and AV370, as well as solutions of sodium citrate + EDTA and calcium EDTA were compared using Walton-Brodie strain gauges. Injections, 2 cc, of RG76 and AV370 produced a biphasic response characterized by an initial negative inotropic response followed by a more prolonged positive inotropic response. The magnitude (67 +/- 3% vs 59 +/- 2%; p less than 0.001) and duration (34 +/- 3 vs 24 +/- 2 sec; p less than 0.001) of the initial negative inotropic response was greater with RG76 than with AV370. The magnitude of the secondary positive inotropic response with RG76 was not different from that obtained with AV370 (31 +/- 12% vs 28 +/- 10%; p greater than 0.3). This positive response was not affected by beta-adrenergic blockage with 0.2 mg/kg of timolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastrografin was used to relieve subacute intestinal obstruction due to Ascaris lumbricoides in children. This hyperosmolar and wetting agent proved to be highly efficient to achieve this goal. Statistical evaluation of the hospital stay and first bowel action showed a significant difference between the treated "gastrografin group' and the untreated by gastrografin "control group,' in favor of the "gastrografin group.' Our data strongly suggest the use of Gastrografin in subacute intestinal obstruction due to Ascaris lumbricoides. This treatment should be instituted provided the patient has been adequately hydrated prior to administration.

The pathophysiology of iodine-enhanced computed tomography (CT) patterns produced by embolic arterial cerebral infarction in the baboon is reported. The appearance of iodine patterns in zones of nonperfusion, blood-brain barrier damage, loss of autoregulation, and neovascularity is demonstrated. The iodine CT patterns were correlated with stable xenon CT flow studies, regional cerebral blood flow studies, clinical course, and pathology.