Low-osmolar Media Research Articles

Quantitative contrast media dose evaluation for cranial computed tomography

The goal of this study was to quantitatively evaluate the CT enhancement characteristics of selected intracranial blood vessels using four different volumes of a contrast medium under otherwise identical conditions in order to help determine a cost-effective dose. In a double blind, prospective manner, 100 patients referred for contrast-enhanced cranial CT were randomly assigned to receive one of four different volumes (50, 75, 100 or 120 ml) of ioversol 320 mg I/ml which was subsequently administered intravenously at a rate of 1 ml/s via a power injector. Unenhanced images were also obtained. Scanning times, slice thickness and other parameters were identical in all patients. Scanning was initiated immediately following delivery of the full volume of contrast. Region of interest Hounsfield unit measurements were acquired in a standardized manner using a 1 mm diameter circle on the pre- and post-contrast scans of the supraclinoid left internal carotid artery (LICA), supraclinoid right internal carotid artery (RICA), basilar artery (BA), and torcular region (TR). The mean enhancement value (in Hounsfield units) for the 50 ml, 75 ml, 100 ml and 120 ml dose groups respectively were as follows for each vessel: LICA 29.9, 41.5, 63.9, 64.6; RICA 30.1, 39.4, 62.6, 65.1; BA 30.0, 41.7, 66.0, 71.9; TR 31.7, 46.8, 68.9, 74.3. There was no statistically significant ( p > 0.05) difference in enhancement in any of the four vessels when the 120 ml volume was delivered compared to the 100 ml volume. However, there was a statistically significant ( p < 0.05) improvement in enhancement in all four vessels when 100 ml of contrast was administered compared to 75 ml. One hundred milliliters of ioversol 320 mg I/ml appears to be an optimal dose of contrast media for vascular enhancement in cranial CT. This may have cost savings advantages when low osmolality media are used.

F184. Effects of low osmolar contrast media, ioxaglate and iopamidol, on the erythrocyte membrane elasticity

A prospective double blind randomised trial using 25 ml of Hexabrix 320 (ioxaglate, May and Baker), Niopam 370 (iopamidol, Merck) or Omnipaque 350 (iohexol, Nycomed) intravenous urography was carried out. The results showed no perceptible difference in the diagnostic quality of urograms with each of the media. An additional 25 ml of contrast medium was required by 4% of patients in order to obtain a satisfactory examination. We recommend that a dose of 25 ml of low-osmolar medium be used for all patients with the exception of the obese, those taking diuretics or those who have renal impairment.

Iodixanol in intravenous urography: A comparison of iodixanol 270 mgI/ml, iodixanol 320 mgI/ml and iopamidol 300 mgI/ml (NIOPAM ™)

The first European trial of iodixanol (Nycomed Imaging AS) in adult intravenous urography is reported. Iodixanol is a new non-ionic, dimeric contrast medium of low osmolality. A double-blind, randomized, three group parallel study comparing iodixanol 270 mgI/ml, iodixanol 320 mgI/ml and iopamidol 300 mgI/ml (Niopam) was undertaken. A total of 173 of 180 patients entered completed the trial. Efficacy was evaluated with regard to overall diagnostic information and pyelographic density 5 min after contrast medium administration. Efficacy was found to increase with increasing iodine concentration, with no significant difference between the three contrast media. The incidence of adverse events was low, with no significant difference between the groups. Discomfort occurred less frequently with iodixanol than with iopamidol. We conclude that iodixanol is a safe and efficacious contrast medium for use in intravenous urography.

Naturally-occurring, osmo-remedial variants of Escherichia coli.

Two clones of Escherichia coli O27:K1:H31 and O2:H7, isolated from patients with urinary tract infection or bacteraemia, failed to grow in a synthetic minimal medium (MM) of low osmolality. They were considered to be osmo-remedial because they grew well when sufficient amounts of NaCl, mannitol or sucrose were added to raise the osmolality of the medium to > 300 mOsm/kg. The defect could also be corrected by nicotinamide or its precursors quinolinic and aspartic acids. Each clone had a unique DNA restriction enzyme profile, fimbriae and antibiotic susceptibility patterns. The osmo-remedial variants were unstable and underwent phenotypic modulation to form mixtures with osmo-tolerant forms when grown in MM. They tended to form satellites of small colonies around large colonies of osmo-tolerant cells on MM agar plates. The penicillin method of Davis was used to separate the two forms. Nicotinamide induced the expression of ompF when the osmo-remedial strains were grown under conditions of low osmolality. It is possible that the variants are defective in the synthesis of membrane-derived oligosaccharides or outer-membrane proteins, but this has yet to be determined.

In Vivo Fluorescence Microscopy of Microcirculation in the Renal Cortex of Mice

In vivo fluorescence microscopy was used for experimental studies of renal cortical microcirculation in 46 mice. The cortical circulation was studied after i.v. infusions of mannitol of various osmolalities as well as nonionic low osmolar (iohexol) and ionic high osmolar (metrizoate) contrast media. All infusions produced an increase in the number of capillaries with increased blood flow, significantly more pronounced after the infusion of iohexol, metrizoate and mannitol 1.46 mol/l than after the infusion of mannitol 0.3 mol/l. However, the renal cortical blood flow was inhomogeneous with respect to different capillaries. While the blood flow was increased in some capillaries it was to some extent simultaneously decreased in others, significantly more after infusion of metrizoate than after infusion of mannitol 0.3 mol/l.

Nephrotoxicity of nonionic low-osmolality versus ionic high-osmolality contrast media: a prospective double-blind randomized comparison in human beings.

To test whether a nonionic, low-osmolality contrast medium (iopamidol) administered for coronary angiography was less harmful to renal function than ionic, high-osmolality medium (sodium diatrizoate), a prospective, double-blind randomized study of 70 patients with normal or mildly depressed renal function (serum creatinine < or = 2.0 mg/dL (175 mumol/L) was performed. Creatinine clearance was determined before coronary angiography and 24 and 48 hours after. There were no significant differences between the low- and high-osmolality groups with regard to age, baseline creatinine clearance, or dose of contrast medium given. In patients receiving low-osmolality medium (n = 35), creatinine clearance decreased by 19% +/- 13 (1 standard deviation) at 24 hours and recovered by 48 hours. In patients receiving high-osmolality medium (n = 35), creatinine clearance decreased by 40% +/- 16 at 24 hours and remained depressed by 47% +/- 14 at 48 hours. In patients with normal or mildly depressed renal function, use of a non-ionic, low-osmolality contrast medium minimized nephrotoxicity as measured by reductions in creatinine clearance after coronary angiography.

A transcriptional silencer downstream of the promoter in the osmotically controlled proU operon of Salmonella typhimurium.

The proU operon of Salmonella typhimurium is induced by conditions of high osmolality. The cis-acting sequences that mediate osmotic control of transcription were characterized by deletion analysis. The nucleotide sequence between -60 and +274 (relative to the transcription start point) is sufficient for normal osmotic control. Deletions that removed sequences upstream of position +274 but left the promoter intact resulted in greatly increased expression from the proU promoter in the absence of osmotic stress. Thus, the transcription control region of the proU operon consists of two discrete components: (i) the promoter and (ii) a negatively acting site that overlaps the coding sequence of the first structural gene of the operon, proV. That this negative regulatory element is a transcriptional terminator or mRNA processing site was ruled out. Our results suggest that the negative regulatory element behaves as a transcriptional silencer that inhibits transcription initiation at the proU promoter in medium of low osmolality by some action at a distance. We propose several possible mechanisms for the function of this regulatory site.

Decision analysis to assess cost-effectiveness of low-osmolality contrast medium for intravenous urography

Decision analysis was used to compare the cost-effectiveness of a conventional ionic high-osmolality contrast medium with that of a nonionic low-osmolality contrast medium when used for i.v. urography. The patient populations considered in the model were those with a low risk and those with a high risk of contrast medium-associated adverse effects. Mean toxicity rates for the contrast media were obtained from the literature. To estimate the average cost of adverse effects, the probability of a patient in each population developing a mild, moderate, or severe reaction was multiplied by the respective estimated cost for each level of severity, and the products were summed. The incremental cost of the low-osmolality medium per case of adverse effects prevented was calculated by dividing the difference between the average costs of the two media by the difference between the frequencies of toxicity associated with the agents. According to the 1990 cost data used, combined mean drug and toxicity costs were $68 and $13 for the low- and high-osmolality contrast media, respectively, per high-risk patient and $67 and $10 per low-risk patient. The incremental costs of the low-osmolality medium per case of severe adverse effects prevented was $17,974 in the high-risk population and $77,027 in the low-risk population. Sensitivity analysis showed the results to be stable over a range of data used in the model.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of the Osmotic Environment on K+and Mg2+Release from the Seed Coat and Cotyledons of Developing Seeds ofVicia fabaandPisum sativum. Evidence for a Stimulation of Efflux from the Vacuole at High Cell Turgor

After removal of the embryo from developing seeds of Vicia faba L. and Pisum sativum L., the 'empty' ovules were filled with a substitute medium (pH 5-5) and the effect of the osmolality of the medium on K+ and Mg2 + release from the seed coat was examined. In long-term experiments (12 h or longer), with both attached and detached seed coats, the rate of K+ and Mg2 + release from seed coats filled with a solution without osmoticum was enhanced, in comparison with release from seed coats filled with a solution containing 400 mol m3 mannitol. In relatively short experiments (2-5 h) with excised seed-coat halves and cotyledons of pea, the stimulatory effect of a low osmolality of the medium on K+ and Mg2+ efflux into the bathing medium could also be observed in cotyledons. Quantitatively, efflux stimulation was most important in experiments with seed coats and cotyledons from ovules in an early stage of development. In experiments of 7 h, compartmental analysis was used for a more detailed analysis of efflux stimulation. Half-times for exchange (i}) of K+ and Mg2+ from the slowest exchanging compartment (the vacuole) were much lower in tissues incubated in a low-osmolality medium than in tissues incubated in a high-osmolality medium. There was no evidence for an effect on the permeability of the plasmalemma. An increase in the tonoplast permeability at high cell turgor, for all solutes measured (K+, Mg2 + , sucrose, amino acids), will help to maintain high solute concentrations in the seed apoplast.

Intravenous contrast media: use and associated mortality

To determine the extent of use and mortality associated with peripheral intravenous injections of radiocontrast media. A retrospective study of injection data was made for the three and a half year period from January 1987 to June 1990 using the Health Insurance Commission database and the records of public hospital x-ray departments. Information about deaths associated with the injections was obtained from a survey of all radiologists and from other relevant sources. The study related to the entire population of New South Wales and the Australian Capital Territory, approximately 6 million people. Intravenous injections of radiographic contrast medium for computed tomographic scans, intravenous pyelograms and venograms. A comprehensive record of intravenous contrast usage and associated mortality in a large community. Between January 1987 and June 1990, 613 581 intravenous injections of radiocontrast media were administered in New South Wales and the Australian Capital Territory. The overall annual incidence of use was estimated to be 2.9% and was markedly age dependent being more than 7% in subjects over 65 years. Eight deaths were documented, representing an overall mortality of 13 per million injections (95% confidence interval [CI], 5.6-25.7). Mortality appeared to be age related being 35 per million (95% CI, 12.7-75.6) in those over 65 years compared with 4.5 per million (95% CI, 0.6-16.4) in those under 65 years. Two of the deaths involved low osmolar contrast media. Death after injection of intravenous contrast medium is a rare event. There was no evidence that mortality was lower with the newer, low osmolar media than with the older, high osmolar media.

The risks of death and of severe nonfatal reactions with high- vs low-osmolality contrast media: a meta-analysis.

Estimates of the risks associated with the use of radiologic contrast agents frequently are based on a subjective review of some of the numerous articles that have been published on the subject. We have chosen instead to synthesize the existing evidence in an objective, quantitative way by statistically combining the data from individual studies through meta-analysis. Although meta-analysis is subject to whatever biases may exist in the underlying data, and may inappropriately pool data from studies with significant differences, the estimates draw proportionately from each original study and, in addition, gain considerable precision owing to the increased amounts of data considered. Using this technique, we analyzed the data from all available original reports appearing since 1980. Crude rates derived from all reports were used to estimate risks with high-osmolality media. Weighted rate differences based on comparative studies only were used in the estimation of the reductions in risk obtainable with low-osmolality media. The risk of death with high-osmolality media was 0.9 per 100,000 uses (95% confidence interval, 0.3-2.6 per 100,000). The difference in risk produced by using low-osmolality media was 0 (95% confidence interval, -1.1 to 1.1 per 100,000). The risk of severe reactions associated with high-osmolality media was 157 per 100,000 uses (95% confidence interval, 144-172 per 100,000). The reduction in risk that can be obtained by the use of low-osmolality media was estimated to be 126 per 100,000 (95% confidence interval, 110-142 per 100,000). This meta-analysis shows that the risk of death is very low with either type of contrast material and that there is no difference between them. Severe nonfatal reactions with high-osmolality media, although more frequent, are still rare; approximately 80% of them can be prevented by using low-osmolality media.

Glycine betaine biosynthesis and catabolism in bacteroids of Rhizobium meliloti: effect of salt stress

Summary: In medium of low or high osmolality, bacteroids isolated from Medicago sativa nodules induced by Rhizobium meliloti 102F34 rapidly catabolized [14C]choline. Trimethylamine was never detected and glycine betaine was the predominant product within the ethanol-soluble fraction of bacteroids subjected to salt stress (0·4 M-NaCl). Both choline oxidase and glycine betaine aldehyde dehydrogenase activities were characterized; the apparent K m values for choline and glycine betaine aldehyde were 2·0 and 0·4 mM, respectively. A 3 h incubation of the bacteroids in medium of high osmolarity, supplemented or not with choline, did not significantly modify the specific activity of the two enzymes. Similarly, salinization of the host plants for 2 weeks with 0·15 M-NaCl had only a slight effect on both enzymic activities. Thus, the choline—glycine betaine biosynthetic pathway was not modulated by the external osmotic pressure. Glycine betaine itself was actively degraded by bacteroids suspended in low-osmolarity medium, but the demethylation process producing sarcosine and glycine was extremely slow in bacteroids subjected to salt stress. Thus, high concentration of glycine betaine can be maintained in salt-stressed bacteroids.

Prevention and dispersion of contrast media induced red cell aggregates

Red cell aggregation was observed microscopically when human blood and contrast media were mixed on glass slides. Aggregation was more frequent in low-osmolal media: mainly rouleaux were formed in ioxaglate but irregular aggregates in non-ionic media. Aggregation was similar at concentrations of 150 and 300 mg I/ml. Pre-treatment of glass slides with heparinized saline reduced red cell aggregation but saline alone was almost as effective. Most of the irregular aggregates dispersed when saline or heparinized saline was applied to them. Saline and heparinized saline had an identical dispersing effect. After incubation of the aggregates in iopamidol in plastic tubes for one or five minutes, saline was injected into the tubes, and after mixing the solution was poured onto glass slides and examined under the microscope. Only a few small irregular aggregates were detected in 6/60 specimens. It is concluded that ionicity of a flushing medium and shear of the injection are able to disperse red cell aggregates dur...

Prevention and Dispersion of Contrast Media Induced Red Cell Aggregates

Red cell aggregation was observed microscopically when human blood and contrast media were mixed on glass slides. Aggregation was more frequent in low-osmolal media: mainly rouleaux were formed in ioxaglate but irregular aggregates in non-ionic media. Aggregation was similar at concentrations of 150 and 300 mg I/ml. Pre-treatment of glass slides with heparinized saline reduced red cell aggregation but saline alone was almost as effective. Most of the irregular aggregates dispersed when saline or heparinized saline was applied to them. Saline and heparinized saline had an identical dispersing effect. After incubation of the aggregates in iopamidol in plastic tubes for one or five minutes, saline was injected into the tubes, and after mixing the solution was poured onto glass slides and examined under the microscope. Only a few small irregular aggregates were detected in 6/60 specimens. It is concluded that ionicity of a flushing medium and shear of the injection are able to disperse red cell aggregates during angiography.

Ionic and non-ionic contrast media: current practice in the major hospitals of Australia and New Zealand.

Major hospitals in Australia and New Zealand were surveyed to estimate the extent of conversion to non-ionic and/or low-osmolar media. The results indicate that conventional ionic media now comprise only approximately one-third of the total usage.

Iotrolan in selective bronchography via the fibreoptic bronchoscope.

The standard technique of selective bronchography via the fibreoptic bronchoscope using Dionosil aqueous suspension (Glaxo) as described by Flower and Shneerson (1984) has disadvantages. The medium is a thick suspension and is extremely difficult to inject. Direct injection into the suction channel may cause blockage if the channel is not adequately cleaned. Furthermore, Dionosil may induce chemical pneumonia, lung collapse and compromise of lung function if a large volume is used (Flower &amp; Armstrong, 1986). It also augments the adverse effect of bronchoscopy on arterial oxygen saturation (Goldman et al, 1987). These difficulties have prompted the idea of using a different type of contrast medium that can be injected directly into the suction channel of the bronchoscope without the attendant complications. The physicochemical properties of iotrolan, a non-ionic dimer, suggest that it could be useful in selective bronchography. It is iso-osmolar with blood at a concentration of 240mgIml−1 with a viscosity of 3.9 cP at 37°C. At a concentration of 300 mgl ml−1 it is slightly hyperosmolar (320 m osm kg−1) and the viscosity is 8.1 cP at 37°C. Animal work and clinical evaluation have indicated that this medium is comparable in safety to the other low-osmolar media that are currently in wide clinical use, possibly with better neural tolerance (Hammer &amp; Deisenhammer, 1985). The aim of this study was to assess the safety and efficacy of iotrolan 240 in a group of patients requiring selective bronchography.

Loss of OmpC porin in a strain of Salmonella typhimurium causes increased resistance to cephalosporins during therapy.

Minimal inhibitory concentrations of cephalosporins for a strain of Salmonella typhimurium from one patient increased severalfold after starting therapy with cephalexin. The first isolate with increased resistance (S20323) and an earlier, less resistant isolate (S17069) each had a TEM-1 beta-lactamase with similar Vmax and Km values. Intact cells of S20323 grown in a high osmolality medium hydrolyzed cephalosporin substrates much more slowly than did intact cells of S17069 at low substrate concentrations, a result indicating slower diffusion of cephalosporins into S20323. In low osmolality media, S17069 produced both OmpF and OmpC porins; S20323 produced only OmpF porin. In high osmolality media with osmotic activity similar to that in the patient's tissues, synthesis of the OmpF porin was repressed in both strains and left S20323 with undetectably low levels of any porin. The increased beta-lactam resistance in S20323 is apparently a consequence of the loss of the OmpC porin.

Iohexol and Ioxaglate in Peripheral Angiography

A double-blind, cross-over trial of the non-ionic, low-osmolar contrast medium iohexol (Omnipaque) and the ionic, low-osmolar medium ioxaglate (Hexabrix) at concentrations of 300 mg I/ml was carried out in 107 consecutive patients with arterial insufficiency of the lower limbs. The purpose of the study was to observe possible 'carry-over' effects from any of the contrast media, and to evaluate patient discomfort such as pain, adverse reactions, or effect on peripheral blood pressure. No carry-over effect was seen. Ioxaglate caused less injection pain and heat sensations than iohexol, and showed less effect on the systemic blood pressure.

A comparison of the incidence of cardiac arrhythmias produced by two intravenous contrast media in coronary artery disease

The incidence of cardiac arrhythmias in patients with coronary artery disease receiving intravenous contrast medium has been studied and comparison made between a conventional ionic medium (meglumine iothalamate) and a low osmolar medium (sodium meglumine ioxaglate). Occasional ventricular and atrial ectopics were frequently observed both before and during administration of the contrast medium and were regarded as insignificant. Significant arrhythmias occurred in five cases. Three of these however, were in the presence of acute myocardial ischaemia or recent infarction. There was no significant difference in the incidence of arrhythmias between the two contrast media. These results show that, in the absence of acute myocardial ischaemia, the incidence of life threatening arrhythmias in patients with proven coronary artery disease receiving intravenous contrast media is much lower than previously suspected.

Low dose low osmolar intravenous urography

A prospective double blind randomised trial using 25 ml of Hexabrix 320 (ioxaglate, May and Baker), Niopam 370 (iopamidol, Merck) or Omnipaque 350 (iohexol, Nycomed) intravenous urography was carried out. The results showed no perceptible difference in the diagnostic quality of urograms with each of the media. An additional 25 ml of contrast medium was required by 4% of patients in order to obtain a satisfactory examination. We recommend that a dose of 25 ml of low-osmolar medium be used for all patients with the exception of the obese, those taking diuretics or those who have renal impairment.