Adverse reactions following administration of contrast media for diagnostic imaging in anaesthetized dogs and cats: a retrospective study.

PubMed

Scarabelli, Stefania; Cripps, Peter; Rioja, Eva; Alderson, Briony

2016-09-01

To evaluate incidences of adverse reaction after the administration of contrast media. Retrospective observational study. Animals included 356 dogs and 58 cats receiving non-ionic iodinated contrast agents, and 425 dogs and 49 cats receiving gadolinium-based contrast agents. Anaesthesia records of dogs and cats receiving intravenous (IV) gadobutrol for magnetic resonance imaging (MRI) or IV iohexol for computed tomography (CT) were reviewed. Changes in pulse rate, respiratory rate and mean arterial pressure at 5 minutes after administration of the contrast medium were evaluated. Changes of 10-20% were considered mild, those of >20% moderate, and reactions that required immediate treatment were considered severe. Associations of sex, age and weight with contrast reaction were investigated using logistic regression. Differences in the incidences of reactions to CT and MRI contrast media were examined with chi-squared tests. A p-value of <0.05 was considered to indicate statistical significance. Of cats receiving iohexol, eight (13.8%) had mild and 10 (17.2%) had moderate reactions. Of cats receiving gadobutrol, six (12.2%) had mild and six (12.2%) had moderate reactions. No cats had severe reactions and the risk for reaction was not associated with type of medium, age, weight or sex (p > 0.2). Of dogs receiving iohexol, 64 (18.0%) had mild, 65 (18.3%) had moderate and three (0.8%) had severe reactions. Of dogs receiving gadobutrol, 42 (9.9%) had mild, 87 (20.5%) had moderate and one (0.2%) had a severe reaction. When dogs receiving iohexol were compared with those receiving gadobutrol, the odds ratio of a moderate reaction was 2.0 (95% confidence interval 1.34-3.10; p = 0.001). These estimates did not change substantially after adjustment for age, weight and sex. Severe reactions to iohexol and gadobutrol are rare in dogs and cats; moderate reactions are more likely with iohexol than with gadobutrol. © 2015 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Acute compartment syndrome of hand resulting from radiographic contrast iohexol extravasation

PubMed Central

Vinod, Kolar Vishwanath; Shravan, Rampelli; Shrivarthan, Radhakrishnan; Radhakrishna, Pedapati; Dutta, Tarun Kumar

2016-01-01

Intravenous (IV) administration of iodinated contrast agents (ICAs) is frequently employed for image enhancement while performing radiographic studies such as computed tomography and angiography. Complications related to IV administration of ICAs such as immediate hypersensitivity reactions and nephrotoxicity are well-known. However, severe skin and soft tissue injuries and acute compartment syndrome resulting from contrast extravasation are rare. This is especially so with small volume extravasation of a low osmolar, nonionic ICA such as iohexol. Here, we report a 63-year-old woman who developed acute compartment syndrome of left hand following iohexol extravasation and had swelling, blistering, cutaneous and soft tissue necrosis. She underwent fasciotomy for acute compartment syndrome of hand and later surgical debridement of necrotic skin and soft tissues was carried out. Clinical pharmacology of ICAs, extravasation injuries following their IV administration, their management and measures to reduce them are discussed in brief. PMID:27127398

Acute compartment syndrome of hand resulting from radiographic contrast iohexol extravasation.

PubMed

Vinod, Kolar Vishwanath; Shravan, Rampelli; Shrivarthan, Radhakrishnan; Radhakrishna, Pedapati; Dutta, Tarun Kumar

2016-01-01

Intravenous (IV) administration of iodinated contrast agents (ICAs) is frequently employed for image enhancement while performing radiographic studies such as computed tomography and angiography. Complications related to IV administration of ICAs such as immediate hypersensitivity reactions and nephrotoxicity are well-known. However, severe skin and soft tissue injuries and acute compartment syndrome resulting from contrast extravasation are rare. This is especially so with small volume extravasation of a low osmolar, nonionic ICA such as iohexol. Here, we report a 63-year-old woman who developed acute compartment syndrome of left hand following iohexol extravasation and had swelling, blistering, cutaneous and soft tissue necrosis. She underwent fasciotomy for acute compartment syndrome of hand and later surgical debridement of necrotic skin and soft tissues was carried out. Clinical pharmacology of ICAs, extravasation injuries following their IV administration, their management and measures to reduce them are discussed in brief.

X-ray attenuation coefficients of high-atomic-number, hexanuclear transition metal cluster compounds: a new paradigm for radiographic contrast agents.

PubMed

Mullan, B F; Madsen, M T; Messerle, L; Kolesnichenko, V; Kruger, J

2000-04-01

The purpose of this study was to examine the radiologic attenuation properties of the parent cluster compounds, particularly attenuation as a function of discrete photon energy, before investigating ligand substitutions, which are necessary to improve cluster biocompatibility and to impart desirable physicochemical properties. The linear attenuation coefficients for solutions of the cluster compounds Ta6Br14, K8Ta6O19, and (H3O)2W6Cl14 were determined at 60, 80, 103, 122, and 140 keV from gamma-ray transmission measurements with americium-241, xenon-133, gadolinium-153, cobalt-57, and technetium-99m radioactive sources. Transmission measurements were obtained for a fixed time interval that ensured a statistically accurate count distribution exceeding 20,000 counts through the sample for each trial. On a strictly mole per liter basis, a 0.075 mol/L aqueous solution of K8Ta6O19 showed 1.08 times the attenuation of 0.063 mol/L aqueous iohexol at 60 keV and 3.30 times the attenuation at 80 keV. Similarly, a 0.05 mol/L methanolic solution of (H3O)2W6Cl4 showed 0.96 times (96%) the attenuation of 0.063 mol/L aqueous iohexol at 60 keV but 3.09 times the attenuation of the iohexol solution at 80 keV. Attenuations of 0.063 mol/L aqueous iohexol and 0.0125 mol/L Ta6Br14 (ie, at approximately one-fifth the iohexol concentration) were comparable at greater than 60 keV. These results confirm the theoretic potential for use of early transition metal cluster compounds as radiographic contrast agents. At higher x-ray energies, cluster compounds demonstrate multiplied x-ray attenuation relative to iodinated contrast agents.

Quality evaluation of radiographic contrast media in large-volume prefilled syringes and vials.

PubMed

Sendo, T; Hirakawa, M; Yaginuma, M; Aoyama, T; Oishi, R

1998-06-01

The authors compared the particle contaminations of radiographic contrast media packaged in large-volume prefilled syringes and vials. Particle counting was performed for four contrast media packaged in large-volume prefilled syringes (iohexol, ioversol, ioversol for angiography, and ioxaglate) and three contrast media packaged in vials (iohexol, ioversol, and ioxaglate). X-ray emission spectrometry was performed to characterize the individual particles. The amount of silicone oil in the syringe was quantified with infrared spectrophotometry. The particle contamination in syringes containing ioversol was higher than that in syringes containing iohexol or ioxaglate. Particle contamination in the vials was relatively low, except with ioxaglate. X-ray emission spectrometry of the components of the syringe and vial showed that the source of particles was internal material released from the rubber stopper or inner surface. The particle counts for contrast media packaged in syringes and vials varied considerably among the different contrast media and were related to the amount of silicone oil on the inner surface and rubber piston of the syringe.

Astaxanthin attenuates contrast agent-induced acute kidney injury in vitro and in vivo via the regulation of SIRT1/FOXO3a expression.

PubMed

Liu, Nana; Chen, Jing; Gao, Dongmei; Li, Wenhua; Zheng, Di

2018-06-01

The study was processed to investigate the effect of astaxanthin (AST; 3,3-dihydroxybeta, beta-carotene-4,4-dione) on the acute kidney injury induced by iohexol and the relationship with SIRT1/FOXO3a signal pathway. Thirty male Sprague Dawley rats were randomly divided into five groups as follows: control group (CON; olive oil only), contrast media group, astaxanthin control group (100 mg/kg), low astaxanthin dose group (LAG, 50 mg/kg) and high astaxanthin dose group (HAG, 100 mg/kg). As followed, serum creatinine (SCr), blood urea nitrogen (BUN), the oxidative stress markers and apoptosis-related proteins were detected. Human proximal tubular epithelial cells (HK-2) were cultured in DMEM/F12 medium in vitro and then randomly divided into appropriate experimental groups: normal group (N), dimethyl sulfoxide (DMSO), iohexol group (I), iohexol + (1.0, 10.0 μmol/L) astaxanthin group (I + LAST; I + HAST), iohexol + SIRT1 inhibitors (nicotinamide) group (NA) and iohexol + si-RNA FOXO3a group (si-RNA FOXO3a); when cultured for 24 h, cell proliferation ability was tested by cell counting kit (CCK-8), reactive oxygen species (ROS) were detected by flow cytometry and the expression of SIRT1 and FOXO3a were observed using western blot. At the end of the experiment, the levels of SCr, BUN and malondialdehyde (MDA) were all increased in the CM group. The LAG and HAG reduce superoxide anion (SOD) activity, catalase (CAT) activity, glutathione peroxidase (GPx) activity and glutathione (GSH) content, as well as SCr and BUN level. Moreover, apoptosis-associated proteins, caspase 3 p17, bax and bcl-2 were upregulated. In HK-2 cells, after adding iohexol, proliferation and intracellular ROS levels were significantly increased. Using astaxanthin in advance after the intervention, the result is opposite. SIRTl inhibitors NA can reduce the expression of SIRTl and decrease the expression of FOXO3a protein. Si-RNA FOXO3a reduces the expression of FOXO3a but had no significant effect on the expression of SIRT1. Our study demonstrates that the intervention of astaxanthin could attenuate the oxidative stress and apoptosis in contrast-induced acute kidney injury (CI-AKI), and the SIRT1/FOXO3a pathway participates in the contrast-induced apoptosis of HK-2 cells. Finally, astaxanthin reduces CI-AKI by suppression of apoptosis, which may be through inhibition of SIRT1/FOXO3a pathways.

Optical clearing of articular cartilage: a comparison of clearing agents

NASA Astrophysics Data System (ADS)

Bykov, Alexander; Hautala, Tapio; Kinnunen, Matti; Popov, Alexey; Karhula, Sakari; Saarakkala, Simo; Nieminen, Miika T.; Tuchin, Valery

2015-07-01

Optical clearing technique was applied to the problem of OCT imaging of articular cartilage and subchondral bone. We show that optical clearing significantly enhances visualization of articular cartilage and cartilage-bone interface. The effect of different clearing agents was analyzed. For the clearing, iohexol solution and propylene glycol (PG) were used. Clearing was performed in vitro at room temperature by immersion method. Cylindrical osteochondral samples (d=4.8mm) were drilled from bovine lateral femur and stored in phosphate-buffered saline at -20°C until clearing. Monitoring of clearing process was performed using high-speed spectral-domain OCT system providing axial resolution of 5.8μm at 930nm. Total duration of experiment was 90-100min to ensure saturation of clearing. We have shown that iohexol solution and PG are capable to optically clear articular cartilage enabling reliable characterization of cartilagebone interface with OCT. Being a low osmolarity agent, iohexol provides minimal changes to the thickness of cartilage sample. Clearing saturation time for the cartilage sample with the thickness of 0.9 mm measured with OCT is of 50 min. However, less than 15 min is enough to reliably detect the rear cartilage boundary. Alternatively, PG significantly (60%) reduces the cartilage thickness enabling better visualization of subchondral bone. It was observed that PG has higher clearing rate. The clearing saturation time is of 30 min, however less than 5 min is enough to detect cartilage-bone interface. We conclude that iohexol solution is superior for OCT imaging of cartilage and cartilage-bone interface, while PG suits better for subhondral bone visualization.

Fixed drug eruption associated with intravenous contrast media: report in a woman receiving iohexol.

PubMed

Wright, Natalie A; Cohen, Philip R

2011-07-01

Fixed drug eruption, a medication-associated mucocutaneous reaction, rarely presents as a delayed adverse reaction to intravenous non-ionic contrast media. We describe a 57-year-old woman with a history of metastatic renal cell carcinoma who repeatedly developed a sharply demarcated, erythematous patch on her left breast after receiving the iodinated non-ionic contrast media iohexol for staging computed tomography scans. Recurrent fixed drug eruption may be avoided by using another contrast medium. Prophylactic treatment with systemic corticosteroids may prevent repeated fixed drug eruption if an alternative contrast agent cannot be used.

The impact of iodinated X-ray contrast agents on formation and toxicity of disinfection by-products in drinking water.

PubMed

Jeong, Clara H; Machek, Edward J; Shakeri, Morteza; Duirk, Stephen E; Ternes, Thomas A; Richardson, Susan D; Wagner, Elizabeth D; Plewa, Michael J

2017-08-01

The presence of iodinated X-ray contrast media (ICM) in source waters is of high concern to public health because of their potential to generate highly toxic disinfection by-products (DBPs). The objective of this study was to determine the impact of ICM in source waters and the type of disinfectant on the overall toxicity of DBP mixtures and to determine which ICM and reaction conditions give rise to toxic by-products. Source waters collected from Akron, OH were treated with five different ICMs, including iopamidol, iopromide, iohexol, diatrizoate and iomeprol, with or without chlorine or chloramine disinfection. The reaction product mixtures were concentrated with XAD resins and the mammalian cell cytotoxicity and genotoxicity of the reaction mixture concentrates was measured. Water containing iopamidol generated an enhanced level of mammalian cell cytotoxicity and genotoxicity after disinfection. While chlorine disinfection with iopamidol resulted in the highest cytotoxicity overall, the relative iopamidol-mediated increase in toxicity was greater when chloramine was used as the disinfectant compared with chlorine. Four other ICMs (iopromide, iohexol, diatrizoate, and iomeprol) expressed some cytotoxicity over the control without any disinfection, and induced higher cytotoxicity when chlorinated. Only iohexol enhanced genotoxicity compared to the chlorinated source water. Copyright © 2017. Published by Elsevier B.V.

Incompatibility of Contrast Medium and Trisodium Citrate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Delcour, Christian, E-mail: christian.delcour@chu-charleroi.be; Bruninx, Guy

2013-02-15

To test the compatibility of trisodium citrate, a catheter lock solution, with iodinated contrast medium. Iohexol, iobitridol, iodixanol, ioxaglate, ioxithalamate, iomeprol, and iopromide were tested. In all tests, 2 ml of contrast medium were mixed with 2 ml of trisodium citrate solution. Iodixanol and ioxaglate provoked a highly viscous gluelike precipitation when mixed with trisodium citrate. A brief transient precipitate was observed with iohexol, iomeprol, and ioxithalamate. Permanent precipitation occurred with iobitridol and iopromide. One must be aware of the potential for precipitation when contrast medium is mixed with trisodium citrate solution. Before trisodium citrate solution is injected, the cathetermore » should be thoroughly flushed with saline if a contrast medium has previously been injected through it.« less

Implementation of material decomposition using an EMCCD and CMOS-based micro-CT system.

PubMed

Podgorsak, Alexander R; Nagesh, Sv Setlur; Bednarek, Daniel R; Rudin, Stephen; Ionita, Ciprian N

2017-02-11

This project assessed the effectiveness of using two different detectors to obtain dual-energy (DE) micro-CT data for the carrying out of material decomposition. A micro-CT coupled to either a complementary metal-oxide semiconductor (CMOS) or an electron multiplying CCD (EMCCD) detector was used to acquire image data of a 3D-printed phantom with channels filled with different materials. At any instance, materials such as iohexol contrast agent, water, and platinum were selected to make up the scanned object. DE micro-CT data was acquired, and slices of the scanned object were differentiated by material makeup. The success of the decomposition was assessed quantitatively through the computation of percentage normalized root-mean-square error (%NRMSE). Our results indicate a successful decomposition of iohexol for both detectors (%NRMSE values of 1.8 for EMCCD, 2.4 for CMOS), as well as platinum (%NRMSE value of 4.7). The CMOS detector performed material decomposition on air and water on average with 7 times more %NRMSE, possibly due to the decreased sensitivity of the CMOS system. Material decomposition showed the potential to differentiate between materials such as the iohexol and platinum, perhaps opening the door for its use in the neurovascular anatomical region. Work supported by Toshiba America Medical Systems, and partially supported by NIH grant 2R01EB002873.

Implementation of material decomposition using an EMCCD and CMOS-based micro-CT system

NASA Astrophysics Data System (ADS)

Podgorsak, Alexander R.; Nagesh, S. V. Setlur; Bednarek, Daniel R.; Rudin, Stephen; Ionita, Ciprian N.

2017-03-01

This project assessed the effectiveness of using two different detectors to obtain dual-energy (DE) micro-CT data for the carrying out of material decomposition. A micro-CT coupled to either a complementary metal-oxide semiconductor (CMOS) or an electron multiplying CCD (EMCCD) detector was used to acquire image data of a 3D-printed phantom with channels filled with different materials. At any instance, materials such as iohexol contrast agent, water, and platinum were selected to make up the scanned object. DE micro-CT data was acquired, and slices of the scanned object were differentiated by material makeup. The success of the decomposition was assessed quantitatively through the computation of percentage normalized root-mean-square error (%NRMSE). Our results indicate a successful decomposition of iohexol for both detectors (%NRMSE values of 1.8 for EMCCD, 2.4 for CMOS), as well as platinum (%NRMSE value of 4.7). The CMOS detector performed material decomposition on air and water on average with 7 times more %NRMSE, possibly due to the decreased sensitivity of the CMOS system. Material decomposition showed the potential to differentiate between materials such as the iohexol and platinum, perhaps opening the door for its use in the neurovascular anatomical region. Work supported by Toshiba America Medical Systems, and partially supported by NIH grant 2R01EB002873.

Extracellular distribution volumes of hydrophilic solutes used to measure the glomerular filtration rate: comparison between chromium-51-EDTA and iohexol.

PubMed

Bird, Nicholas J; Peters, Christina; Michell, A Robert; Peters, A Michael

2007-02-01

Extracellular fluid volume (ECV) is larger when measured with Tc-99m-DTPA ( approximately 500 Da) than inulin (6 kDa). As part of an assessment of the suitability of the non-radioactive marker, iohexol, against the gold standard tracer, Cr-51-EDTA, for measurement of the glomerular filtration rate (GFR) based on a postal service, we took the opportunity to determine if this volume dependence is present for diffusible markers less disparate in size than inulin and Tc-99m-DTPA. Cr-51-EDTA ( approximately 400 Da) and iohexol ( approximately 900 Da) were administered into the opposite arms of 20 normal volunteers (fasting and non-fasting) and 60 patients (non-fasting), including 36 diabetics, 10 cancer patients and 13 dermatology patients. Blood was obtained from both arms 20, 40, 60, 120, 180 and 240 min after injection and assayed for a marker injected contra-laterally. The glomerular filtration rate (GFR) and mean indicator transit time, T, were measured from the bi-exponential clearance curves. ECV, the product of GFR and T, was subdivided into V(1) (administered indicator divided by the sum of zero-time intercepts of the two exponentials) and V(2) (the difference between V(1) and ECV). Variables were scaled to 1.73 m(2). For all 100 studies, the mean GFR from Cr-51-EDTA was 3 ml min(-1) higher than iohexol (p < 0.01). ECV was 0.41 L higher (p < 0.02) and V(1) 0.65 L higher (p < 0.001) from Cr-51-EDTA but V(2) was 0.33 L lower (p < 0.02). V(1)/ECV was 0.031 higher from Cr-51-EDTA (p < 0.01). ECV and V(2) from Cr-51-EDTA were both higher in diabetics (15.1 [1.7] and 5.0 [0.095] L, respectively) compared with normal non-fasting subjects (13.7 [1.5] and 4.3 [1.0]; p < 0.01). ECV and the volumes of its sub-compartments are different between markers that are less than an order of magnitude different in size.

Simethicone to prevent colonic bubbles during CT colonography performed with polyethylene glycol lavage and iohexol tagging: a randomized clinical trial.

PubMed

Hong, Gil-Sun; Park, Seong Ho; Kim, Bohyun; Lee, Ju Hee; Kim, Jin Cheon; Yu, Chang Sik; Baek, Seunghee; Lee, Jong Seok; Kim, Hyun Jin

2015-04-01

The purpose of this study was to determine whether the occurrence of numerous colonic bubbles during CT colonography (CTC) performed with polyethylene glycol cleansing and oral iohexol fecal/fluid tagging could be prevented by use of simethicone. Adults with suspected colonic neoplasia who had been randomly assigned to control and simethicone intervention groups underwent CTC after cleansing with 4 L of polyethylene glycol, tagging with 50 mL of 350 mg I/mL oral iohexol, and without (control) or with (intervention) oral administration of 200 mg of simethicone. Colonic segments in the control and intervention groups were evaluated for amount of colonic bubbles during CTC. A 6-point grading system was used in which 0 indicated no bubbles and 5 indicated that more than three fourths of the air-distended mucosa was covered with bubbles. The primary endpoint was a per-patient colonic bubble grade, derived as an average of the segmental grades. Eighty adults with suspected colonic neoplasia were randomly assigned to the control (40 patients) and simethicone intervention (40 patients) groups. A total of 659 colonic segments in the control group and 689 segments in the intervention group were evaluated for amount of colonic bubbles during CTC. The per-patient colonic bubble score was significantly lower in the simethicone intervention group than in the control group. The mean score was 0.0±0.1 (SD) versus 1.2±0.8 (p<0.001; 95% CI for the mean difference, -1.4 to -1.0). In the intervention group, 673 (97.7%) segments were grade 0, and 16 (2.3%) were grade 1. In contrast, in the control group, 226 (34.3%) segments were grade 0; 173 (26.3%), grade 1; 175 (26.6%), grade 2; 45 (6.8%), grade 3; 23 (3.5%), grade 4; and 17 (2.6%), grade 5. The colonic bubbles associated with fecal/fluid tagging with iohexol can be successfully prevented by adding simethicone to the colonic preparation.

Quantitation of iothalamate in urine and plasma using liquid chromatography electrospray tandem mass spectrometry (HPLC-ESI-MS/MS).

PubMed

Molinaro, Ross J; Ritchie, James C

2010-01-01

The following chapter describes a method to measure iothalamate in plasma and urine samples using high performance liquid chromatography combined with electrospray positive ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Methanol and water are spiked with the internal standard (IS) iohexol. Iothalamate is isolated from plasma after IS spiked methanol extraction and from urine by IS spiked water addition and quick-spin filtration. The plasma extractions are dried under a stream of nitrogen. The residue is reconstituted in ammonium acetate-formic acid-water. The reconstituted plasma and filtered urine are injected into the HPLC-ESI-MS/MS. Iothalamate and iohexol show similar retention times in plasma and urine. Quantification of iothalamate in the samples is made by multiple reaction monitoring using the hydrogen adduct mass transitions, from a five-point calibration curve.

A Simple Method to Measure Renal Function in Swine by the Plasma Clearance of Iohexol

PubMed Central

Luis-Lima, Sergio; García-Contreras, Consolación; Carrara, Fabiola; Negrín-Mena, Natalia; Jiménez-Sosa, Alejandro; Jiménez-Hernández, Hugo; Porrini, Esteban

2018-01-01

There is no simple method to measure glomerular filtration rate (GFR) in swine, an established model for studying renal disease. We developed a protocol to measure GFR in conscious swine by using the plasma clearance of iohexol. We used two groups, test and validation, with eight animals each. Ten milliliters of iohexol (6.47 g) was injected into the marginal auricular vein and blood samples (3 mL) were collected from the orbital sinus at different points after injection. GFR was determined using two models: two-compartment (CL2: all samples) and one-compartment (CL1: the last six samples). In the test group, CL1 overestimated CL2 by ~30%: CL2 = 245 ± 93 and CL1 = 308 ± 123 mL/min. This error was corrected by a first-order polynomial quadratic equation to CL1, which was considered the simplified method: SM = −47.909 + (1.176xCL1) − (0.00063968xCL12). The SM showed narrow limits of agreement with CL2, a concordance correlation of 0.97, and a total deviation index of 14.73%. Similar results were obtained for the validation group. This protocol is reliable, reproducible, can be performed in conscious animals, uses a single dose of the marker, and requires a reduced number of samples, and avoids urine collection. Finally, it presents a significant improvement in animal welfare conditions and handling necessities in experimental trials. PMID:29329247

Extended Renal Outcomes with Use of Iodixanol versus Iohexol after Coronary Angiography

PubMed Central

Horrigan, Mark; Mcintosh, Elizabeth; Bellomo, Rinaldo

2014-01-01

The impact of isoosmolar versus low-osmolar contrast media (CM) administration on contrast-induced acute kidney injury (CI-AKI) and extended renal dysfunction (ERD) is unclear. We retrospectively examined incidences of CI-AKI and ERD in patients who received iodixanol (isoosmolar) versus iohexol (low-osmolar) during angiography for cardiac indications. Of 713 patients, 560 (cohort A), 190 (cohort B), and 172 (cohort C) had serum creatinine monitored at 3 days, 30 days, and 6 months after angiography, respectively. 18% of cohort A developed CI-AKI, which was more common with iodixanol than iohexol (22% versus 13%, P = 0.006). However, patients given iodixanol were older with lower baseline estimated glomerular filtration rates (eGFR). On multivariate analysis, independent associations with higher CI-AKI risk include age >65 years, female gender, cardiac failure, ST-elevation myocardial infarction, intra-aortic balloon pump, and critical illness, but not CM type, higher CM load, or eGFR < 45 mL/min/1.73 m2. 32% of cohort B and 34% of cohort C had ERD at 30 days and 6 months, while 44% and 41% of subcohorts had ERD at 90 days and 1 year, respectively. CI-AKI, but not CM type, was associated with medium- and longer-term ERD, with 3-fold higher risk. Advanced age, emergent cardiac conditions, and critical illness are stronger predictors of CI-AKI, compared with CM-related factors. CI-AKI predicts longer-term ERD. PMID:25180184

Influence of Contrast Agent Dilution on Ballon Deflation Time and Visibility During Tracheal Balloon Dilation: A 3D Printed Phantom Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Min Tae; Park, Jung-Hoon; Shin, Ji Hoon, E-mail: jhshin@amc.seoul.kr

PurposeTo determine the effect of contrast medium dilution during tracheal balloon dilation on balloon deflation time and visibility using a 3-dimensional (3D) printed airway phantom.Materials and MethodsA comparison study to investigate balloon deflation times and image quality was performed using two contrast agents with different viscosities, i.e., iohexol and ioxithalamate, and six contrast dilutions with a 3D printed airway phantom.ResultsCompared to 1:0 concentration, 3:1, 2:1, 1:1, 1:2, and 1:3, contrast/saline ratios resulted in a 46% (56.2 s), 59.8% (73.1 s), 74.9% (91.6 s), 81.7% (99.8 s), and 83.5% (102 s) reduction for iohexol, respectively, and a 51.8% (54.7 s), 63.8% (67.6 s), 74.7% (79.2 s), 80.5% (85.3 s), andmore » 82.4% (87.4 s) reduction for ioxithalamate, respectively, in the mean balloon deflation time, although at the expense of decreased balloon opacity (3.5, 6.9, 11.1, 12.4, and 13.9%, for iohexol, respectively, and 3.2, 6, 9.6, 10.8, and 12.4%, for ioxithalamate, respectively).ConclusionsUse of a lower viscosity contrast agent and higher contrast dilution is considered to be able to reduce balloon deflation times and then simultaneously decrease visualization of balloons. The rapid balloon deflation time is likely to improve the safe performance of interventional procedures.« less

Universal GFR determination based on two time points during plasma iohexol disappearance.

PubMed

Ng, Derek K S; Schwartz, George J; Jacobson, Lisa P; Palella, Frank J; Margolick, Joseph B; Warady, Bradley A; Furth, Susan L; Muñoz, Alvaro

2011-08-01

An optimal measurement of glomerular filtration rate (GFR) should minimize the number of blood draws, and reduce procedural invasiveness and the burden to study personnel and cost, without sacrificing accuracy. Equations have been proposed to calculate GFR from the slow compartment separately for adults and children. To develop a universal equation, we used 1347 GFR measurements from two diverse groups consisting of 527 men in the Multicenter AIDS Cohort Study and 514 children in the Chronic Kidney Disease in Children cohort. Both studies used nearly identical two-compartment (fast and slow) protocols to measure GFR. To estimate the fast component from markers of body size and of the slow component, we used standard linear regression methods with the log-transformed fast area as the dependent variable. The fast area could be accurately estimated from body surface area by a simple parameter (6.4/body surface area) with no residual dependence on the slow area or other markers of body size. Our equation measures only the slow iohexol plasma disappearance curve with as few as two time points and was normalized to 1.73 m2 body surface area. It is of the form: GFR=slowGFR/[1+0.12(slowGFR/100)]. In a random sample utilizing a third of the patients for validation, there was excellent agreement between the calculated and measured GFR with low root mean square errors being 4.6 and 1.5 ml/min per 1.73 m2 for adults and children, respectively. Thus, our proposed simple equation, developed in a combined patient group with a broad range of GFRs, may be applied universally and is independent of the injected amount of iohexol.

Epidural spread of iohexol following the use of air or saline in the 'loss of resistance' test.

PubMed

Iseri, Toshie; Nishimura, Ryohei; Nagahama, Shotaro; Mochizuki, Manabu; Nakagawa, Takayuki; Fujimoto, Yuka; Zhang, Di; Sasaki, Nobuo

2010-11-01

To compare, using CT epidurography, the cranial distribution of contrast after epidural injection when saline or air is used for the loss of resistance (LOR) technique in identifying the epidural space. Prospective, randomized, cross-over experimental study. Nine healthy adult Beagle dogs. Under general anaesthesia, a spinal needle (22-gauge, 70 mm) was inserted through the lumbosacral space, and the position in the epidural space confirmed using the LOR technique employing either 0.3 mL per dog of saline or of air. Epidurography using CT was performed before and 5, 10 and 20 minutes after epidural injection of 0.2 mL kg(-1) of iohexol. The cranial distribution of iohexol was recorded as the number of vertebral segments reached from the seventh lumbar vertebrae. The median values in vertebral segments of the cranial distribution at 5, 10 and 20 minutes after epidural injection were 19.5, 20.5 and 21.0 respectively with the saline treatment, and 12.0, 15.0 and 16.0 respectively in the air treatment. At all time points spread of contrast was significantly less with the air treatment. All dogs after air treatment had some air bubbles in the epidural space, and in seven, the spinal cord was moderately compressed by the air. No neurological complications were observed after recovery. The use of air for the LOR technique is associated with significantly less spread, uneven cranial distribution of the contrast medium and compression of the spinal cord. It is recommended that saline, and not air, should be used to identify the epidural space by this method. © 2010 The Authors. Veterinary Anaesthesia and Analgesia © 2010 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Cytotoxic Effects of Nonionic Iodinated Contrast Agent on Human Adipose-derived Mesenchymal Stem Cells.

PubMed

Wu, Tao; Nie, Hai; Dietz, Allan B; Salek, David R; Smith, Jay; van Wijnen, Andre J; Qu, Wenchun

2018-05-31

Transplantation of mesenchymal stem cells (MSCs) is a promising therapy for degenerative spine conditions. However, cell therapy for painful spine degeneration presently requires use of contrast agents during fluoroscopy-guided injections and the effects of these agents on MSCs represents a gap in knowledge. To investigate the biological effects of contrast media that are co-injected with MSCs. Prospective observational study. Academic medical center. Patient-derived clinical-grade culture expanded MSCs. Iohexol(Omnipaque300) was reduced to 12.5%, 25%, 50% and 100% of the stock solution and incubated with MSCs for 30 minutes, 4 hours and 48 hours. We also used complete media and 12.5%, 25%, 50%, 100% of phosphate buffered saline (PBS) as control group. We examined cytotoxicity of Iohexol at different concentrations and exposure duration, as well as the potential for recovery over time. Cell counts, mitochondrial activity, and quantitative real time reverse-transcriptase polymerase chain reaction (qRT-PCR) of related genes were analyzed immediately after exposure (day 0) and after two days of exposure (day 2). Human MSCs exhibit a time- and concentration-dependent cytotoxic response to iodinated CM. A brief 30min exposure did not affect MSCs function and viability. However, extended treatment with iohexol for 4 hours at 50% or higher concentration had a significant impact on both viability and gene expression in MSCs. CM (Omnipaque300) is cytotoxic to MSCs in a time-and concentration-dependent manner. Hence, the concentration of CM that accompanies MSC injections should be carefully considered during mesenchymal stem cell therapy for disc degenerative diseases. Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Varied incidence of immediate adverse reactions to low-osmolar non-ionic iodide radiocontrast media used in computed tomography.

PubMed

Kim, S R; Lee, J H; Park, K H; Park, H J; Park, J W

2017-01-01

Low-osmolar non-ionic radiocontrast media (RCMs) are commonly used throughout hospitals. However, the incidence of immediate adverse drug reactions (ADRs) to various low-osmolar non-ionic RCMs is not well studied. We compared the incidence of immediate ADRs among different low-osmolar non-ionic RCMs used in computed tomography (CT). Severance Hospital has collected data for adverse reactions occurring in-hospital using an internally developed system. Using this data, we reviewed 1969 immediate ADRs from 286 087 RCM-contrasted CT examinations of 142 099 patients and compared the immediate ADRs of iobitridol, iohexol, iopamidol, and iopromide. We analysed the incidence of immediate ADRs to different RCMs, as well as the effect of single or multiple CT examinations per day. Iopromide showed the highest incidence of immediate ADRs (1.03%) and was followed by iopamidol (0.67%), iohexol (0.64%), and iobitridol (0.34%). In cases of anaphylaxis, iopromide also showed the highest incidence (0.041%), followed by iopamidol (0.023%), iohexol (0.018%), and iobitridol (0.012%). Risk of immediate ADR due to multiple CT examinations (1.19%) was significantly higher than the risk due to a single CT examination (0.63%). Risk of anaphylaxis was also higher for multiple CT examinations (0.052%) than for a single CT examination (0.020%). The incidence of immediate ADRs varied according to the low-osmolar non-ionic RCM used. Iopromide-induced immediate ADRs were more frequent, while iobitridol was associated with fewer immediate ADRs than other RCMs. Multiple CT examinations per day resulted in a higher incidence of immediate ADRs and anaphylaxis than a single CT examination. Clinicians should consider these risk differences of immediate ADRs when prescribing contrasted CT examinations. © 2016 The Authors. Clinical & Experimental Allergy Published by John Wiley & Sons Ltd.

Effects of two types of medical contrast media on routine chemistry results by three automated chemistry analyzers.

PubMed

Park, Yu Jin; Rim, John Hoon; Yim, Jisook; Lee, Sang-Guk; Kim, Jeong-Ho

2017-08-01

The use of iodinated contrast media has grown in popularity in the past two decades, but relatively little attention has been paid to the possible interferential effects of contrast media on laboratory test results. Herein, we investigate medical contrast media interference with routine chemistry results obtained by three automated chemistry analyzers. Ten levels of pooled serum were used in the study. Two types of medical contrast media [Iopamiro (iopamidol) and Omnipaque (iohexol)] were evaluated. To evaluate the dose-dependent effects of the contrast media, iopamidol and iohexol were spiked separately into aliquots of serum for final concentrations of 1.8%, 3.6%, 5.5%, 7.3%, and 9.1%. The 28 analytes included in the routine chemistry panel were measured by using Hitachi 7600, AU5800, and Cobas c702 analyzers. We calculated the delta percentage difference (DPD) between the samples and the control, and examined dose-dependent trends. When the mean DPD values were compared with the reference cut-off criteria, the only uniformly interferential effect observed for all analyzers was in total protein with iopamidol. Two additional analytes that showed trends toward interferential effects only in few analyzers and exceeded the limits of the allowable error were the serum iron and the total CO 2 . The other combinations of analyzer and contrast showed no consistent dose-dependent propensity for change in any analyte level. Our study suggests that many of the analytes included in routine chemistry results, except total protein and serum iron, are not significantly affected by iopamidol and iohexol. These results suggest that it would be beneficial to apply a flexible medical evaluation process for patients requiring both laboratory tests and imaging studies, minimizing the need for strict regulations for sequential tests. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Successful Graded Dose Challenge to Iodixanol Radiocontrast Media in a Patient With Delayed Anaphylaxis to Iohexol.

PubMed

Soffer, Gary; Cohen, Barrie; Toh, Jennifer; Edelman, Devorah; Garg, Karan; Jariwala, Sunit

2018-01-01

We present a case of an 82-year-old male with known radiocontrast media (RCM) hypersensitivity who was admitted to our hospital with gangrene of his right toe. The plan for revascularization of his lower extremity required an angiogram. This presented a management challenge as the patient had experienced 2 episodes of delayed anaphylaxis to Omnipaque (iohexol) RCM, and based on a literature review, there was no known or established precedent on a safe procedure in these situations. The patient was premedicated and given a graded dose challenge of an alternative RCM (iodixanol) prior to the radiographic study. He was given 1% of the total expected dose 1 hour before to the procedure and an additional 10% for the 30 minutes prior. He was then given the final dose in the operating room. Following angiogram, the patient was monitored for 18 hours in the postanesthesia care unit, with no adverse reactions. He was placed on a prednisone taper for 1 week, with daily diphenhydramine. The patient remained asymptomatic throughout the hospital course. This novel approach to RCM hypersensitivity management lends itself to a hope that graded dose challenges may play a greater role in the management of these patients.

Effect of renal impairment on the pharmacokinetics, pharmacodynamics, and safety of apixaban.

PubMed

Chang, Ming; Yu, Zhigang; Shenker, Andrew; Wang, Jessie; Pursley, Janice; Byon, Wonkyung; Boyd, Rebecca A; LaCreta, Frank; Frost, Charles E

2016-05-01

This open-label study evaluated apixaban pharmacokinetics, pharmacodynamics, and safety in subjects with mild, moderate, or severe renal impairment and in healthy subjects following a single 10-mg oral dose. The primary analysis determined the relationship between apixaban AUC∞ and 24-hour creatinine clearance (CLcr ) as a measure of renal function. The relationships between 24-hour CLcr and iohexol clearance, estimated CLcr (Cockcroft-Gault equation), and estimated glomerular filtration rate (modification of diet in renal disease [MDRD] equation) were also assessed. Secondary objectives included assessment of safety and tolerability as well as international normalized ratio (INR) and anti-factor Xa activity as pharmacodynamic endpoints. The regression analysis showed that decreasing renal function resulted in modestly increased apixaban exposure (AUC∞ increased by 44% in severe impairment with a 24-hour CLcr of 15 mL/min, compared with subjects with normal renal function), but it did not affect Cmax or the direct relationship between apixaban plasma concentration and anti-factor Xa activity or INR. The assessment of renal function measured by iohexol clearance, Cockcroft-Gault, and MDRD was consistent with that determined by 24-hour CLcr . Apixaban was well tolerated in this study. These results suggest that dose adjustment of apixaban is not required on the basis of renal function alone. © 2015, The American College of Clinical Pharmacology.

Nephrotoxicity of high- and low-osmolar contrast media. The protective role of amlodipine in a rat model.

PubMed

Duan, S B; Liu, F Y; Luo, J A; Wu, H W; Liu, R H; Peng, Y M; Yang, X L

2000-09-01

To evaluate the nephrotoxicity of high- and low-osmolar contrast media (HOCM, LOCM) on kidneys in Sprague-Dawley rats. The protective role of amlodipine was studied. Forty rats of both sexes were randomly divided into 5 groups (n=8/group) and glycerine for inducing renal failure was given to all rats except controls. In diatrizoate-injected rats, blood urea nitrogen (BUN) and serum creatinine (SCr) were increased; levels of phospholipase A2 (PLA2), lipid peroxide (LPO) and calcium were also increased in renal tissues. There was no significant difference between LOCM (iohexol) animals and glycerol controls either in the renal levels of PLA2, LPO and calcium or in the levels of BUN and SCr. The histologic changes were milder in the LOCM animals than in the HOCM animals. In the group pretreated with amlodipine, no increase in the levels of BUN or SCr was discovered and the renal content of PLA2, LPO and calcium were significantly lower than in the HOCM group; the renal injuries induced by diatrizoate were alleviated. The HOCM, diatrizoate, was more toxic to rat kidneys than the LOCM iohexol; PLA2, LPO and calcium load played a role in producing renal function impairment induced by diatrizoate meglumine; amlodipine protected the renal tissue from nephrotoxicity induced by diatrizoate.

Comparison of the Safety of Seven Iodinated Contrast Media

PubMed Central

Seong, Jong-Mi; Choi, Nam-Kyong; Lee, Joongyub; Chang, Yoosoo; Kim, Ye-Jee; Yang, Bo Ram; Jin, Xue-Mei; Kim, Ju-Young

2013-01-01

We aimed to determine the characteristic adverse events (AEs) of iodinated contrast media (IOCM) and to compare the safety profiles of different IOCM. This study used the database of AEs reports submitted by healthcare professionals from 15 Regional Pharmacovigilance Centers between June 24, 2009 and December 31, 2010 in Korea. All reports of IOCM, including iopromide, iohexol, iopamidol, iomeprol, ioversol, iobitridol and iodixanol, were analyzed. Safety profiles were compared between different IOCM at the system organ level using the proportional reporting ratio (PRR) and 95% confidence interval (95% CI). Among a total of 48,261 reports, 6,524 (13.5%) reports were related to the use of IOCM. Iopromide (45.5%), iohexol (16.9%), iopamidol (14.3%) and iomeprol (10.3%) were identified as frequently reported media. 'Platelet, bleeding & clotting disorders' (PRR, 29.6; 95%CI, 1.9-472.6) and 'urinary system disorders' (PRR, 22.3; 95% CI, 17.1-29.1) were more frequently reported for iodixanol than the other IOCM. In conclusion, the frequency of AEs by organ class was significantly different between individual media. These differences among different IOCM should be considered when selecting a medium among various IOCM and when monitoring patients during and after its use to ensure optimum usage and patient safety. PMID:24339697

Occurrence of iodinated X-ray contrast media and their biotransformation products in the urban water cycle.

PubMed

Kormos, Jennifer Lynne; Schulz, Manoj; Ternes, Thomas A

2011-10-15

A LC tandem MS method was developed for the simultaneous determination of four iodinated X-ray contrast media (ICM) and 46 ICM biotransformation products (TPs) in raw and treated wastewater, surface water, groundwater, and drinking water. Recoveries ranged from 70% to 130%, and limits of quantification (LOQ) varied between 1 ng/L and 3 ng/L for surface water, groundwater and drinking water, and between 10 ng/L and 30 ng/L for wastewater. In a conventional wastewater treatment plant, iohexol, iomeprol, and iopromide were transformed to >80%, while iopamidol was transformed to 35%. In total, 26 TPs were detected above their LOQ in WWTP effluents. A significant change in the pattern of ICM TPs was observed after bank filtration and groundwater infiltration under aerobic conditions. Predominately, these TPs are formed at the end of the microbial transformation pathways in batch experiments with soil and sediment. These polar ICM TPs, such as iohexol TP599, iomeprol TP643, iopromide TP701A, and iopromide TP643, were not or only partially removed during drinking water treatment. As a consequence, several ICM TPs were detected in drinking water, at concentration levels exceeding 100 ng/L, with a maximum of 500 ng/L for iomeprol TP687.

Contrast Media-Induced Renal Inflammation Is Mediated Through HMGB1 and Its Receptors in Human Tubular Cells.

PubMed

Guan, Xiao-Feng; Chen, Qing-Jie; Zuo, Xiao-Cong; Guo, Ren; Peng, Xiang-Dong; Wang, Jiang-Lin; Yin, Wen-Jun; Li, Dai-Yang

2017-01-01

With the rapid development of imaging diagnosis and interventional therapy, contrast media (CM) are widely used in clinics. However, contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute renal failure accounting for 10-12% of all causes of hospital-acquired renal failure. Recent study found that inflammation may participate in the pathogenesis of CIN, but the role of it remains unclear. HK-2 cells were treated with Iohexol, Urografin, and mannitol. Two types of CM increased the release of HMGB1 in cell supernatant accompanied by increased expression of TLR2 and CXCR4. Iohexol and Urografin also caused a significant increase in NF-κB followed by the release of IL-6 and MCP-1. To clarify the role of HMGB1, TLR2, and CXCR4, glycyrrhizin, anti-TLR2-IgG, and AMD3100 were used to inhibit HMGB1, TLR2, and CXCR4, respectively. Significant decrease in the expression of TLR2, CXCR4, nuclear NF-κB, and the release of IL-6 and MCP-1 were observed. These results indicate that TLR2 and CXCR4 signaling are involved in CM-induced HK-2 cell injury model in an HMGB1-dependent pathway, which may provide a new target for the prevention and the treatment of CIN.

Investigating the fate of iodinated X-ray contrast media iohexol and diatrizoate during microbial degradation in an MBBR system treating urban wastewater.

PubMed

Hapeshi, E; Lambrianides, A; Koutsoftas, P; Kastanos, E; Michael, C; Fatta-Kassinos, D

2013-06-01

The capability of a moving bed biofilm reactor (MBBR) to remove the iodinated contrast media (ICM) iohexol (IOX) and diatrizoate (DTZ) from municipal wastewater was studied. A selected number of clones of microorganisms present in the biofilm were identified. Biotransformation products were tentatively identified and the toxicity of the treated effluent was assessed. Microbial samples were DNA-sequenced and subjected to phylogenetic analysis in order to confirm the identity of the microorganisms present and determine the microbial diversity. The analysis demonstrated that the wastewater was populated by a bacterial consortium related to different members of Proteobacteria, Firmicutes, and Nitrisporae. The optimum removal values of the ICM achieved were 79 % for IOX and 73 % for DTZ, whereas 13 biotransformation products for IOX and 14 for DTZ were identified. Their determination was performed using ultra-performance liquid chromatography-tandem mass spectrometry. The toxicity of the treated effluent tested to Daphnia magna showed no statistical difference compared to that without the addition of the two ICM. The MBBR was proven to be a technology able to remove a significant percentage of the two ICM from urban wastewater without the formation of toxic biodegradation products. A large number of biotransformation products was found to be formed. Even though the amount of clones sequenced in this study does not reveal the entire bacterial diversity present, it provides an indication of the predominating phylotypes inhabiting the study site.

The use of iohexol as oral contrast for computed tomography of the abdomen and pelvis.

PubMed

Horton, Karen M; Fishman, Elliot K; Gayler, Bob

2008-01-01

Positive oral contrast agents (high-osmolar iodinated solutions [high-osmolar contrast medium] or barium sulfate suspensions) are used routinely for abdominal computed tomography. However, these agents are not ideal. Patients complain about the taste and, sometimes, refuse to drink the required quantity. Nausea, vomiting, and diarrhea are frequent. In certain clinical indications, either barium suspensions or high-osmolar contrast mediums may be contraindicated. This technical note describes the potential advantages of using low-osmolar iodinated solutions as an oral contrast agent for computed tomography.

Evaluation of Gentian cystatin C reagent on Abbott Ci8200 and calculation of glomerular filtration rate expressed in mL/min/1.73 m(2) from the cystatin C values in mg/L.

PubMed

Flodin, M; Jonsson, A-S; Hansson, L-O; Danielsson, L-A; Larsson, A

2007-01-01

Estimation of the glomerular filtration rate (GFR) is essential when evaluating patients with kidney disease and treating patients with drugs eliminated from the circulation by the kidneys. Cystatin C has been shown in several studies to be superior to creatinine in the estimation of GFR. At our hospitals, there is an increasing demand for cystatin C and at present we perform approximately 1500 cystatin C analyses a month. We thus need the assay available 24 h/day and to have it on our routine chemistry instrument to minimize handling time per test and time to reported test results. We have evaluated a new cystatin C immunoassay from Gentian (Gentian, Moss, Norway) on Architect ci8200 (Abbott Laboratories, Abbott Park, Ill., USA). A prerequisite at our hospital is that cystatin C results are reported as a calculated GFR in mL/min/1.73 m(2), so we also made a comparison with iohexol clearance. The Gentian cystatin C assay showed good agreement with the corresponding assay from Dade Behring (Deerfield, Ill., USA) and good inter-laboratory concordance. The assay has very low total imprecision, good linearity and strong correlation with iohexol clearance (R (2) = 0.956). The equation for the correlation curve is: y = 79.901x(-1.4389). There was low inter-laboratory variation between the three laboratories involved in the cystatin C evaluation, and thus all three laboratories can use the same equation for calculating the estimated GFR.

Quality by Design approach in the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol and its impurities.

PubMed

Jovanović, Marko; Rakić, Tijana; Tumpa, Anja; Jančić Stojanović, Biljana

2015-06-10

This study presents the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol, its endo-isomer and three impurities following Quality by Design (QbD) approach. The main objective of the method was to identify the conditions where adequate separation quality in minimal analysis duration could be achieved within a robust region that guarantees the stability of method performance. The relationship between critical process parameters (acetonitrile content in the mobile phase, pH of the water phase and ammonium acetate concentration in the water phase) and critical quality attributes is created applying design of experiments methodology. The defined mathematical models and Monte Carlo simulation are used to evaluate the risk of uncertainty in models prediction and incertitude in adjusting the process parameters and to identify the design space. The borders of the design space are experimentally verified and confirmed that the quality of the method is preserved in this region. Moreover, Plackett-Burman design is applied for experimental robustness testing and method is fully validated to verify the adequacy of selected optimal conditions: the analytical column ZIC HILIC (100 mm × 4.6 mm, 5 μm particle size); mobile phase consisted of acetonitrile-water phase (72 mM ammonium acetate, pH adjusted to 6.5 with glacial acetic acid) (86.7:13.3) v/v; column temperature 25 °C, mobile phase flow rate 1 mL min(-1), wavelength of detection 254 nm. Copyright © 2015 Elsevier B.V. All rights reserved.

Iodixanol versus low-osmolar contrast media for prevention of contrast induced nephropathy: meta-analysis of randomized, controlled trials.

PubMed

From, Aaron M; Al Badarin, Firas J; McDonald, Furman S; Bartholmai, Brian J; Cha, Stephen S; Rihal, Charanjit S

2010-08-01

Contrast-induced nephropathy (CIN) is associated with significant morbidity and mortality. The objective of our meta-analysis was to assess the efficacy of iodixanol compared with low-osmolar contrast media (LOCM) for prevention of CIN. We searched MEDLINE, the Cochrane Central Register of Controlled Trials, and internet sources of cardiology trial results for individual and relevant reviews of randomized, controlled trials, for the terms contrast media, contrast nephropathy, renal failure, iodixanol, Visipaque, and low-osmolar contrast media. All studies reported an incidence rate of CIN for each study group; there was no restriction on the definition of CIN. There were no restrictions on journal type or patient population. Overall, 36 trials were identified for analysis of aggregated summary data on 7166 patients; 3672 patients received iodixanol and 3494 patients received LOCM. Overall, iodixanol showed no statistically significant reduction in CIN incidence below that observed with heterogeneous comparator agents (P=0.11). Analysis of patient subgroups revealed that there was a significant benefit of iodixanol when compared with iohexol alone (odds ratio, 0.25; 95% confidence interval, 0.11 to 0.55; P<0.001) but not when compared with LOCM other than iohexol or with other ionic dimers or among patients receiving intra-arterial contrast injections or among patients undergoing coronary angiography with or without percutaneous intervention. Analysis of aggregated summary data from multiple randomized, controlled trials of iodixanol against diverse LOCMs for heterogeneous procedures and definitions of CIN show an iodixanol-associated reduction that is suggestive but statistically nonsignificant.

Efficacy of using an air arthrogram for EUA and injection of the hip joint in adults.

PubMed

Shahid, Mohammad; Shyamsundar, Srinivasan; Bali, Navi; McBryde, Callum; O'Hara, John; Bache, Edward

2014-09-01

Hip arthrography usually requires the injection of iodine based dyes which can cause complications. We wanted to determine the accuracy of using air for hip arthrography. A prospective study was undertaken including all adults who had a hip arthrogram. We initially did an air arthrogram and subsequently injected iohexol to see if we were still in the joint. Forty injections were done. Mean age 32 years. There was a 100% success rate with obtaining a positive air arthrogram. Air arthrogram of the hip offers a safe, cost free and accurate alternative to iodine based arthrograms.

Liquid metal angiography for mega contrast X-ray visualization of vascular network in reconstructing in-vitro organ anatomy.

PubMed

Wang, Qian; Yu, Yang; Pan, Keqin; Liu, Jing

2014-07-01

Visualization on the anatomical vessel networks plays a vital role in the physiological or pathological investigations. However, so far it still remains a big challenge to identify the fine structures of the smallest capillary vessel networks via conventional imaging ways. Here, the room temperature liquid metal angiography was proposed for the first time to generate mega contrast X-ray images for multiscale vasculature mapping. Particularly, gallium was adopted as the room temperature liquid metal contrast agent and infused into the vessels of in vitro pig hearts and kidneys. We scanned the samples under X-ray and compared the angiograms with those obtained via conventional contrast agent--the iohexol. As quantitatively demonstrated by the grayscale histograms and numerical indexes, the contrast of the vessels to the surrounding tissues in the liquid metal angiograms is orders higher than that of the iohexol enhanced images. And the angiogram has reached detailed enough width of 0.1 mm for the tiny vessels, which indicated that the capillaries can be clearly distinguished under the liquid metal enhanced images. Further, with tomography from the micro-CT, we also managed to reconstruct the 3-D structures of the kidney vessels. Tremendous clarity and efficiency of the method over existing approaches have been experimentally clarified. It was disclosed that the usually invisible capillary networks now become distinctively clear in the gallium angiograms. This basic mechanism has generalized purpose and can be extended to a wide spectrum of 3-D computational tomographic areas. It opens a new soft tool for quickly reconstructing high-resolution spatial channel networks for scientific researches as well as engineering practices where complicated and time-consuming resections are no longer a necessity.

Behaviour and fate of nine recycled water trace organics during managed aquifer recharge in an aerobic aquifer

NASA Astrophysics Data System (ADS)

Patterson, B. M.; Shackleton, M.; Furness, A. J.; Bekele, E.; Pearce, J.; Linge, K. L.; Busetti, F.; Spadek, T.; Toze, S.

2011-03-01

The fate of nine trace organic compounds was evaluated during a 12 month large-scale laboratory column experiment. The columns were packed with aquifer sediment and evaluated under natural aerobic and artificial anaerobic geochemical conditions, to assess the potential for natural attenuation of these compounds during aquifer passage associated with managed aquifer recharge (MAR). The nine trace organic compounds were bisphenol A (BPA), 17β-estradiol (E2), 17α-ethynylestradiol (EE2), N-nitrosodimethylamine (NDMA), N-nitrosomorpholine (NMOR), carbamazepine, oxazepam, iohexol and iodipamide. In the low organic carbon content Spearwood sediment, all trace organics were non-retarded with retardation coefficients between 1.0 and 1.2, indicating that these compounds would travel at near groundwater velocities within the aquifer. The natural aerobic geochemical conditions provided a suitable environment for the rapid degradation for BPA, E2, iohexol (half life < 1 day). Lag-times for the start of degradation of these compounds ranged from < 15 to 30 days. While iodipamide was persistent under aerobic conditions, artificial reductive geochemical conditions promoted via the addition of ethanol, resulted in rapid degradation (half life < 1 days). Pharmaceuticals (carbamazepine and oxazepam) and disinfection by-products (NDMA and NMOR) did not degrade under either aerobic or anaerobic aquifer geochemical conditions (half life > 50 days). Field-based validation experiments with carbamazepine and oxazepam also showed no degradation. If persistent trace organics are present in recycled waters at concentrations in excess of their intended use, natural attenuation during aquifer passage alone may not result in extracted water meeting regulatory requirements. Additional pre treatment of the recycled water would therefore be required.

Hemoglobin Decline in Children with Chronic Kidney Disease: Baseline Results from the Chronic Kidney Disease in Children Prospective Cohort Study

PubMed Central

Fadrowski, Jeffrey J.; Pierce, Christopher B.; Cole, Stephen R.; Moxey-Mims, Marva; Warady, Bradley A.; Furth, Susan L.

2008-01-01

Background and objectives: The level of glomerular filtration rate at which hemoglobin declines in chronic kidney disease is poorly described in the pediatric population. Design, setting, participants, & measurements: This cross-sectional study of North American children with chronic kidney disease examined the association of glomerular filtration rate, determined by the plasma disappearance of iohexol, and hemoglobin concentration. Results: Of the 340 patients studied, the mean age was 11 ± 4 yr, the mean glomerular filtration rate was 42 ± 14 ml/min per 1.73 m2, and the mean hemoglobin was 12.5 ± 1.5. Below a glomerular filtration rate of 43, the hemoglobin declined by 0.3 g/dl (95% confidence interval −0.2 to −0.5) for every 5-ml/min per 1.73 m2 decrease in glomerular filtration rate. Above a glomerular filtration rate of 43 ml/min per 1.73 m2, the hemoglobin showed a nonsignificant decline of 0.1 g/dl for every 5-ml/min per 1.73 m2 decrease in glomerular filtration rate. Conclusions: In pediatric patients with chronic kidney disease, hemoglobin declines as an iohexol-determined glomerular filtration rate decreases below 43 ml/min per 1.73 m2. Because serum creatinine–based estimated glomerular filtration rates may overestimate measured glomerular filtration rate in this population, clinicians need to be mindful of the potential for hemoglobin decline and anemia even at early stages of chronic kidney disease, as determined by current Schwartz formula estimates. Future longitudinal analyses will further characterize the relationship between glomerular filtration rate and hemoglobin, including elucidation of reasons for the heterogeneity of this association among individuals. PMID:18235140

Analysis of iodinated X-ray contrast agents in water samples by ion chromatography and inductively-coupled plasma mass spectrometry.

PubMed

Sacher, Frank; Raue, Brigitte; Brauch, Heinz-Jürgen

2005-08-26

In this paper, an analytical method for the determination of six iodinated X-ray contrast agents (amidotrizoic acid, iohexol, iomeprol, iopamidol, iopromide, and ioxitalamic acid), iodide, and iodate in water samples is presented. The method is based on a separation of the analytes by ion chromatography (IC) and a subsequent detection by inductively-coupled plasma mass spectrometry (ICP-MS). The method was optimised with respect to separation conditions (column type and eluent composition) and extensively validated. Without pre-concentration of the samples, limits of detection below 0.2 microg/l could be achieved whereby reproducibility was below 6% for all compounds under investigation.

Occurrence and fate of emerging trace organic chemicals in wastewater plants in Chennai, India.

PubMed

Anumol, Tarun; Vijayanandan, Arya; Park, Minkyu; Philip, Ligy; Snyder, Shane A

2016-01-01

The presence of pharmaceuticals, hormones, pesticides and industrial contaminants collectively termed as trace organic compounds (TOrCs) in wastewater has been well-documented in USA, Europe, China and other regions. However, data from India, the second most populous country in the world is severely lacking. This study investigated the occurrence and concentrations of twenty-two indicator TOrCs at three wastewater treatment plants (WWTPs) in South India serving diverse communities across three sampling campaigns. Samples were collected after each WWTP treatment unit and removal efficiencies for TOrCs were determined. Eleven TOrCs were detected in every sample from every location at all sites, while only five TOrCs were detected consistently in effluent samples. Caffeine was present at greatest concentration in the influent of all three plants with average concentrations ranging between 56 and 65μg/L. In contrast, the x-ray contrast media pharmaceutical, iohexol, was the highest detected compound on average in the effluent at all three WWTPs (2.1-8.7μg/L). TOrCs were not completely removed in the WWTPs with removal efficiencies being compound specific and most of the attenuation being attributed to the biological treatment processes. Caffeine and triclocarban were well removed (>80%), while other compounds were poorly removed (acesulfame, sucralose, iohexol) or maybe even formed (carbamazepine) within the WWTPs. The effluent composition of the 22 TOrCs were similar within the three WWTPs but quite different to those seen in the US, indicating the importance of region-specific monitoring. Diurnal trends indicated that variability is compound specific but trended within certain classes of compounds (artificial sweeteners, and pharmaceuticals). The data collected on TOrCs from this study can be used as a baseline to identify potential remediation and regulatory strategies in this understudied region of India. Copyright © 2016 Elsevier Ltd. All rights reserved.

Estimated and Measured GFR Associate Differently with Retinal Vasculopathy in the General Population.

PubMed

Eriksen, Bjørn Odvar; Løchen, Maja-Lisa; Arntzen, Kjell Arne; Bertelsen, Geir; Winther Eilertsen, Britt-Ann; von Hanno, Therese; Herder, Marit; Jenssen, Trond Geir; Mathisen, Ulla Dorte; Melsom, Toralf; Njølstad, Inger; Solbu, Marit D; Mathiesen, Ellisiv B

2015-01-01

Estimated glomerular filtration rate (eGFR) is used extensively in epidemiological research. Validations of eGFR have demonstrated acceptable performance, but the dependence of creatinine and cystatin C on non-GFR factors could confound associations with disease. Few studies have investigated this issue in direct comparison with measured GFR (mGFR). We compared the associations between eGFR and mGFR and retinal vasculopathy, a marker of systemic microvasculopathy. Iohexol clearance and retinal photography were examined in the Renal Iohexol Clearance Survey in Tromsø 6, which consists of a representative sample of middle-aged persons from the general population. A total of 1,553 persons without self-reported kidney disease, cardiovascular disease or diabetes were investigated. Three eGFR equations based on creatinine and/or cystatin C from the Chronic Kidney Disease Epidemiology Collaboration were studied. Differences between eGFR and mGFR were analyzed with seemingly unrelated regression methods. mGFR in the lowest quartile was associated with an increased multivariable-adjusted odds ratio of retinopathy (OR 1.86, 95% CI 1.16-2.97), but not with retinal artery or vein diameters. eGFR based on cystatin C (eGFRcys) was consistently biased relative to mGFR in its associations with retinal vessel diameters across different models. eGFR based on creatinine (eGFRcrea) and eGFR based on both creatinine and cystatin C were also biased in several of these models (p < 0.05). For retinopathy, the differences between the 3 eGFR and mGFR measurements were not statistically significant. Low mGFR is associated with retinopathy in the general population. eGFR based on creatinine and/or cystatin C are not valid substitutes for mGFR in studies of the relationship between the retina and kidney function in healthy persons. © 2015 S. Karger AG, Basel.

Nephropathy after administration of iso-osmolar and low-osmolar contrast media: evidence from a network meta-analysis.

PubMed

Biondi-Zoccai, Giuseppe; Lotrionte, Marzia; Thomsen, Henrik S; Romagnoli, Enrico; D'Ascenzo, Fabrizio; Giordano, Arturo; Frati, Giacomo

2014-03-15

Contrast-induced nephropathy (CIN) may be a severe complication to the administration of iodine-based contrast media for diagnostic or interventional procedure using radiation exposure. Whether there is a difference in nephrotoxic potential between the various agents is uncertain. We aimed to perform a systematic review and network meta-analysis of randomized trials on iodine-based contrast agents. Randomized trials of low-osmolar or iso-osmolar contrast media were searched in CENTRAL, Google Scholar, MEDLINE/PubMed, and Scopus. Risk of CIN was appraised within a hierarchical Bayesian model computing absolute rates (AR) and odds ratios (OR) with 95% credibility intervals, and probability of being best (Pbest) for each agent. A total of 42 trials (10048 patients) were included focusing on 7 different iodine-based contrast media. Risk of CIN was similarly low with iodixanol (AR=5.7% [2.2%-13.9%], Pbest=18.8%), iomeprol (AR=6.0% [2.2%-15.4%], Pbest=24.8%), iopamidol (AR=6.1% [2.2%-15.5%], Pbest=21.5%), and ioversol (AR=6.0% [2.1%-16.4%], Pbest=31.3%). Conversely, CIN was twice as common with iohexol (AR=11.2% [4.1%-29.5%], Pbest=0.1%) and ioxaglate (AR=11.0% [4.0%-26.9%], Pbest<0.1%), with both proving less safe than iodixanol (respectively OR=2.18 [1.22-3.92] and 2.05 [1.26-3.29]), iomeprol (OR=2.08 [1.04-4.17] and 1.96 [1.06-3.48]) and iopamidol (OR=2.04 [1.15-3.85] and 1.92 [1.06-3.45]). Data on iopromide were less conclusive (AR=6.9% [2.6%-17.1%], Pbest=3.6%). Iodixanol, iomeprol, iopamidol and ioversol are iodine-based contrast media with a similar renal safety profile. Iohexol and ioxaglate have a poorer renal safety profile, whereas further data may be required on iopromide. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Iodinated contrast media and contrast-induced nephropathy: is there a preferred cost-effective agent?

PubMed

Sharma, Samin K

2008-05-01

Over 20 years have passed since the introduction of the tri-iodinated low-osmolar nonionic contrast agents such as iopamidol, iohexol, ioversol and iopromide. During this time, most cardiology practices have switched to these nonionic agents to avoid the nuisance side effects and cardiac adverse events associated with the older ionic contrast agents. Although the improved tolerability of the nonionic agents is generally attributed to their decreased osmolality (approximately half that of the older ionic contrast agents), in fact, these contrast agents also differ from the older agents in their ionicity, viscosity and direct chemotoxicity. The impact of these properties on safety, together with cost differences, should be considered when selecting a contrast agent.

An overview of glomerular filtration rate testing in dogs and cats

PubMed Central

Von Hendy-Willson, Vanessa E.; Pressler, Barrak M.

2010-01-01

Determination of glomerular filtration rate (GFR) is a valuable, yet underused, diagnostic tool for evaluating renal function in dogs and cats. This article first reviews the hormonal and hemodynamic factors which contribute to GFR, followed by a description of considerations when selecting a pharmacokinetic model and methods of animal-to-animal standardization. The best-characterized existing GFR markers, including creatinine, radiolabeled markers, and iohexol, are reviewed in depth, as well as alternative but lesser-used techniques. A weighted means analysis of reported GFR measurements in healthy dogs and cats and a review of selected studies that have examined GFR alterations in animals with naturally-occurring and experimental diseases provide the reader with preliminary guidelines on expected GFR results in these species and disease conditions. PMID:20541957

Temporary organ displacement coupled with image-guided, intensity-modulated radiotherapy for paraspinal tumors

PubMed Central

2013-01-01

Background To investigate the feasibility and dosimetric improvements of a novel technique to temporarily displace critical structures in the pelvis and abdomen from tumor during high-dose radiotherapy. Methods Between 2010 and 2012, 11 patients received high-dose image-guided intensity-modulated radiotherapy with temporary organ displacement (TOD) at our institution. In all cases, imaging revealed tumor abutting critical structures. An all-purpose drainage catheter was introduced between the gross tumor volume (GTV) and critical organs at risk (OAR) and infused with normal saline (NS) containing 5-10% iohexol. Radiation planning was performed with the displaced OARs and positional reproducibility was confirmed with cone-beam CT (CBCT). Patients were treated within 36 hours of catheter placement. Radiation plans were re-optimized using pre-TOD OARs to the same prescription and dosimetrically compared with post-TOD plans. A two-tailed permutation test was performed on each dosimetric measure. Results The bowel/rectum was displaced in six patients and kidney in four patients. One patient was excluded due to poor visualization of the OAR; thus 10 patients were analyzed. A mean of 229 ml (range, 80–1000) of NS 5-10% iohexol infusion resulted in OAR mean displacement of 17.5 mm (range, 7–32). The median dose prescribed was 2400 cGy in one fraction (range, 2100–3000 in 3 fractions). The mean GTV Dmin and PTV Dmin pre- and post-bowel TOD IG-IMRT dosimetry significantly increased from 1473 cGy to 2086 cGy (p=0.015) and 714 cGy to 1214 cGy (p=0.021), respectively. TOD increased mean PTV D95 by 27.14% of prescription (p=0.014) while the PTV D05 decreased by 9.2% (p=0.011). TOD of the bowel resulted in a 39% decrease in mean bowel Dmax (p=0.008) confirmed by CBCT. TOD of the kidney significantly decreased mean kidney dose and Dmax by 25% (0.022). Conclusions TOD was well tolerated, reproducible, and facilitated dose escalation to previously radioresistant tumors abutting critical structures while minimizing dose to OARs. PMID:23800073

Nanoengineered multimodal contrast agent for medical image guidance

NASA Astrophysics Data System (ADS)

Perkins, Gregory J.; Zheng, Jinzi; Brock, Kristy; Allen, Christine; Jaffray, David A.

2005-04-01

Multimodality imaging has gained momentum in radiation therapy planning and image-guided treatment delivery. Specifically, computed tomography (CT) and magnetic resonance (MR) imaging are two complementary imaging modalities often utilized in radiation therapy for visualization of anatomical structures for tumour delineation and accurate registration of image data sets for volumetric dose calculation. The development of a multimodal contrast agent for CT and MR with prolonged in vivo residence time would provide long-lasting spatial and temporal correspondence of the anatomical features of interest, and therefore facilitate multimodal image registration, treatment planning and delivery. The multimodal contrast agent investigated consists of nano-sized stealth liposomes encapsulating conventional iodine and gadolinium-based contrast agents. The average loading achieved was 33.5 +/- 7.1 mg/mL of iodine for iohexol and 9.8 +/- 2.0 mg/mL of gadolinium for gadoteridol. The average liposome diameter was 46.2 +/- 13.5 nm. The system was found to be stable in physiological buffer over a 15-day period, releasing 11.9 +/- 1.1% and 11.2 +/- 0.9% of the total amounts of iohexol and gadoteridol loaded, respectively. 200 minutes following in vivo administration, the contrast agent maintained a relative contrast enhancement of 81.4 +/- 13.05 differential Hounsfield units (ΔHU) in CT (40% decrease from the peak signal value achieved 3 minutes post-injection) and 731.9 +/- 144.2 differential signal intensity (ΔSI) in MR (46% decrease from the peak signal value achieved 3 minutes post-injection) in the blood (aorta), a relative contrast enhancement of 38.0 +/- 5.1 ΔHU (42% decrease from the peak signal value achieved 3 minutes post-injection) and 178.6 +/- 41.4 ΔSI (62% decrease from the peak signal value achieved 3 minutes post-injection) in the liver (parenchyma), a relative contrast enhancement of 9.1 +/- 1.7 ΔHU (94% decrease from the peak signal value achieved 3 minutes post-injection) and 461.7 +/- 78.1 ΔSI (60% decrease from the peak signal value achieved 5 minutes post-injection) in the kidney (cortex) of a New Zealand white rabbit. This multimodal contrast agent, with prolonged in vivo residence time and imaging efficacy, has the potential to bring about improvements in the fields of medical imaging and radiation therapy, particularly for image registration and guidance.

Residual Associations of Inflammatory Markers with eGFR after Accounting for Measured GFR in a Community-Based Cohort without CKD.

PubMed

Schei, Jørgen; Stefansson, Vidar T N; Mathisen, Ulla Dorte; Eriksen, Bjørn O; Solbu, Marit D; Jenssen, Trond G; Melsom, Toralf

2016-02-05

eGFR on the basis of creatinine (eGFRcre) associates differently with cardiovascular disease and mortality than eGFR on the basis of cystatin C (eGFRcys). This may be related to risk factors affecting the level of creatinine and cystatin C along non-GFR pathways, which may confound the association between eGFR and outcome. Nontraditional risk factors are usually not measured in epidemiologic studies of eGFR and cannot be adjusted for to reduce confounding. We examined whether the inflammatory markers soluble TNF receptor type 2 (sTNFR2), C-reactive protein (CRP), and fibrinogen associated differently with eGFR than with measured GFR (mGFR). GFR was measured by iohexol clearance in 1627 middle-aged participants without kidney disease, diabetes, or cardiovascular disease enrolled in the Renal Iohexol Clearance Survey Study from the Sixth Tromsø Study between 2007 and 2009. Generalized estimating equations were used to assess the residual associations between eGFR (eGFRcre, eGFRcys, and eGFR on the basis of creatinine and cystatin C) and the inflammatory markers relative to mGFR. sTNFR2, CRP, and fibrinogen were associated with a higher eGFRcre after accounting for mGFR in multivariable-adjusted models (2.63 ml/min per 1.73 m(2); 95% confidence interval [95% CI], 2.1 to 3.2 per SD increase in sTNFR2, 0.93 ml/min per 1.73 m(2); 95% CI, 0.3 to 1.5 per SD increase in log CRP, and 1.19 ml/min per 1.73 m(2); 95% CI, 0.6 to 1.8 per SD increase in fibrinogen). sTNFR2 and CRP were inversely associated with eGFRcys (-1.4 ml/min per 1.73 m(2); 95% CI, -2.1 to -0.6 per SD increase in sTNFR2, and -0.76 ml/min per 1.73 m(2); 95% CI, -1.4 to -0.1 per SD increase in log CRP). eGFRcre and eGFRcys are associated with inflammatory factors after accounting for mGFR but in opposite directions. These non-GFR-related associations may bias risk estimates by eGFR and, in part, explain the different risks predicted by eGFRcre and eGFRcys in longitudinal studies. Copyright © 2016 by the American Society of Nephrology.

Tungsten Oxide Nanorods: An Efficient Nanoplatform for Tumor CT Imaging and Photothermal Therapy

PubMed Central

Zhou, Zhiguo; Kong, Bin; Yu, Chao; Shi, Xiangyang; Wang, Mingwei; Liu, Wei; Sun, Yanan; Zhang, Yingjian; Yang, Hong; Yang, Shiping

2014-01-01

We report here a facile thermal decomposition approach to creating tungsten oxide nanorods (WO2.9 NRs) with a length of 13.1 ± 3.6 nm and a diameter of 4.4 ± 1.5 nm for tumor theranostic applications. The formed WO2.9 NRs were modified with methoxypoly(ethylene glycol) (PEG) carboxyl acid via ligand exchange to have good water dispersability and biocompatibility. With the high photothermal conversion efficiency irradiated by a 980 nm laser and the better X-ray attenuation property than clinically used computed tomography (CT) contrast agent Iohexol, the formed PEGylated WO2.9 NRs are able to inhibit the growth of the model cancer cells in vitro and the corresponding tumor model in vivo, and enable effective CT imaging of the tumor model in vivo. Our “killing two birds with one stone” strategy could be extended for fabricating other nanoplatforms for efficient tumor theranostic applications. PMID:24413483

Exchange-Mediated Contrast Agents for Spin-Lock Imaging

PubMed Central

Cobb, Jared G.; Xie, Jingping; Li, Ke; Gochberg, Daniel F.; Gore, John C.

2011-01-01

Measurements of relaxation rates in the rotating frame with spin-locking (SL) techniques are sensitive to substances with exchanging protons with appropriate chemical shifts. We develop a novel approach to exchange rate selective imaging based on measured T1ρ dispersion with applied locking field strength, and demonstrate the method on samples containing the X-ray contrast agent Iohexol (IO) with and without cross-linked bovine serum albumin (BSA). T1ρ dispersion of water in the phantoms was measured with a Varian 9.4T magnet by an on-resonance SL pulse with fast spin-echo readout, and the results used to estimate exchange rates. The IO phantom alone gave a fitted exchange rate of ~1 kHz, BSA alone was ~11 kHz, and in combination gave rates in between. By using these estimated rates, we demonstrate how a novel SL imaging method may be used to enhance contrast due to the presence of a contrast agent whose protons have specific exchange rates. PMID:21954094

Drugs of abuse, cytostatic drugs and iodinated contrast media in tap water from the Madrid region (central Spain):A case study to analyse their occurrence and human health risk characterization.

PubMed

Mendoza, A; Zonja, B; Mastroianni, N; Negreira, N; López de Alda, M; Pérez, S; Barceló, D; Gil, A; Valcárcel, Y

2016-01-01

This work analyses the presence of forty-eight emerging pollutants, including twenty-five drugs of abuse and metabolites, seventeen cytostatic drugs and six iodinated contrast media, in tap water from the Madrid Region. Analysis of the target compounds in the tap water was performed by means of (on-line or off-line) solid-phase extraction followed by analysis by liquid chromatography-tandem mass spectrometry. A preliminary human health risk characterization was undertaken for each individual compound and for different groups of compounds with a common mechanism of action found in tap water. The results of the study showed the presence of eight out of the twenty-five drugs of abuse and metabolites analysed, namely, the cocainics cocaine and benzoylecgonine, the amphetamine-type stimulants ephedrine, 3,4-methylenedioxymethamphetamine and methamphetamine, the opioid methadone and its metabolite 2-ethylene-1,5-dimethyl-3,3-diphenylpyrrolidine and, finally caffeine at concentrations ranging from 0.11 to 502 ng L(-1). Four out of the six analysed iodinated contrast media, namely, diatrizoate, iohexol, iomeprol and iopromide, were detected in at least one sample, with concentration values varying between 0.4 and 5 ng L(-1). Cytostatic compounds were not detected in any sample. Caffeine was the substance showing the highest concentrations, up to 502 ng L(-1), mainly in the drinking water sampling point located in Madrid city. Among the other drugs of abuse, the most abundant compounds were cocaine and benzoylecgonine, detected at concentrations ranging from 0.11 to 86 ng L(-1) and from 0.11 to 53 ng L(-1), respectively. Regarding iodinated contrast media, iohexol was the most ubiquitous and abundant compound, with a frequency of detection of 100% and concentrations from 0.5 to 5.0 ng L(-1) in basically the same range in all sampling points. Taking into account the results and types of treatment applied, ozonisation plus granular activated carbon filtration appears to be efficient in the removal of cocaine and benzoylecgonine. For the amphetamine-type stimulants, opioids and caffeine, ozonisation plus granular activated carbon filtration and ultrafiltration plus reverse osmosis showed higher removal efficiency than sand filtration. The human health risk characterization performed indicates that the lifetime consumption of the tap waters analysed has associated a negligible human health concern. Copyright © 2015 Elsevier Ltd. All rights reserved.

Use of a 22-gauge Whitacre needle to reduce the incidence of side effects after lumbar myelography: a prospective randomised study comparing Whitacre and Quincke spinal needles.

PubMed

Pedersen, O N

1996-01-01

In a prospective study lumbar iohexol myelography was performed in 107 consecutive patients, randomised for lumbar puncture with a Quincke or Whitacre spinal needle. All patients answered a questionnaire about possible side effects. Data from 100 patients (58 men, 42 women) were evaluated. In the Quincke group (n = 53), 23 (43%) reported no side effects. In the 30 patients who reported various side effects, post-dural puncture headache (PDPH) occurred in 22 (42%), of whom 9 had mild, 6 moderate and 7 (13%) severe cephalalgia, 18 (34%) reported increased low back pain/sciatica, 5 nausea and 7 dizziness. In the Whitacre group (n = 47), 33 (70%) had no side effects. PDPH was reported by 9 patients (19%), of whom 2 had mild, 6 moderate and only 1 (2%) severe cephalalgia, 4 (9%) reported increased low back pain/sciatica, 5 nausea and 4 dizziness. The conclusion drawn from this study is that lumbar myelography performed with the Whitacre spinal needle reduces postspinal side effects.

Results of the first-in-human clinical trial for MB-102, a novel fluorescent tracer agent for real-time measurement of glomerular filtration rate

NASA Astrophysics Data System (ADS)

Dorshow, Richard B.; Debreczeny, Martin P.; Dowling, Thomas C.

2015-03-01

The fluorescent tracer agent 2,5-bis[N-(1-carboxy-2-hydroxy)]carbamoyl-3,6-diaminopyrazine, designated MB-102, has been developed with properties and attributes necessary for use as a direct measure of glomerular filtration rate (GFR). Comparison to known standard exogenous GFR agents in animal models has demonstrated an excellent correlation. A clinical trial to demonstrate this same correlation in humans is in progress. This clinical trial is the first in a series of trials necessary to obtain regulatory clearance from the FDA. We report herein the comparison of plasma pharmacokinetics between MB-102 and the known standard exogenous GFR agent Iohexol in healthy subjects with normal renal function. Post simultaneous administration of both agents, blood samples over a period of 12 hours were collected from each subject to assess pharmacokinetic parameters including GFR. Urine samples were collected over this same period to assess percent injected dose recovered in the urine. Results indicate MB-102 is a GFR agent in humans from the comparison to the standard agent.

Acceptability of oral iodinated contrast media: a head-to-head comparison of four media.

PubMed

Pollentine, A; Ngan-Soo, E; McCoubrie, P

2013-05-01

To assess the palatability of iodinated oral contrast media commonly used in abdominopelvic CT and CT colonography (CTC). 80 volunteers assessed the palatability of a 20-ml sample of a standard 30 mg ml(-1) dilution of Omnipaque® (iohexol; GE Healthcare, Cork, Ireland), Telebrix® (meglumine ioxithalamate; Guerbet, Aulnay-sous-Bois, France), Gastromiro® (iopamidol; Bracco, High Wycombe, UK) and Gastrografin® (sodium diatrizoate and meglumine diatrizoate; Bayer, Newbury, UK) in a computer-generated random order. Gastrografin is rated significantly less palatable than the remaining media (p<0.005). Omnipaque and Telebrix are significantly more palatable than Gastromiro. No difference existed between Omnipaque and Telebrix. 39% of participants would refuse to consume the quantities of Gastrografin required for a CTC examination compared with Telebrix (7%) and Omnipaque (9%) (p<0.05). Omnipaque and Telebrix are significantly more palatable than both Gastromiro and Gastrografin, with participants more willing to ingest them in larger quantities as well as being less expensive. Omnipaque and Telebrix are significantly more palatable iodinated oral contrast media than both Gastromiro and Gastrografin, which has potential implications in compliance with both abdominopelvic CT and CTC.

Acceptability of oral iodinated contrast media: a head-to-head comparison of four media

PubMed Central

Ngan-Soo, E; McCoubrie, P

2013-01-01

Objective: To assess the palatability of iodinated oral contrast media commonly used in abdominopelvic CT and CT colonography (CTC). Methods: 80 volunteers assessed the palatability of a 20-ml sample of a standard 30 mg ml−1 dilution of Omnipaque® (iohexol; GE Healthcare, Cork, Ireland), Telebrix® (meglumine ioxithalamate; Guerbet, Aulnay-sous-Bois, France), Gastromiro® (iopamidol; Bracco, High Wycombe, UK) and Gastrografin® (sodium diatrizoate and meglumine diatrizoate; Bayer, Newbury, UK) in a computer-generated random order. Results: Gastrografin is rated significantly less palatable than the remaining media (p<0.005). Omnipaque and Telebrix are significantly more palatable than Gastromiro. No difference existed between Omnipaque and Telebrix. 39% of participants would refuse to consume the quantities of Gastrografin required for a CTC examination compared with Telebrix (7%) and Omnipaque (9%) (p<0.05). Conclusion: Omnipaque and Telebrix are significantly more palatable than both Gastromiro and Gastrografin, with participants more willing to ingest them in larger quantities as well as being less expensive. Advances in knowledge: Omnipaque and Telebrix are significantly more palatable iodinated oral contrast media than both Gastromiro and Gastrografin, which has potential implications in compliance with both abdominopelvic CT and CTC. PMID:23564884

Perceived Appetite and Clinical Outcomes in Children with Chronic Kidney Disease

PubMed Central

Ayestaran, Frank W.; Schneider, Michael F.; Kaskel, Frederick J.; Srivaths, Poyyapakkam R.; Seo-Mayer, Patricia W.; Moxey-Mims, Marva; Furth, Susan L.; Warady, Bradley A.; Greenbaum, Larry A.

2017-01-01

Background Children with chronic kidney disease (CKD) may have impaired caloric intake through a variety of mechanisms, with decreased appetite as a putative contributor. In adult CKD, decreased appetite has been associated with poor clinical outcomes. There is limited information about this relationship in pediatric CKD. Methods 879 participants of the Chronic Kidney Disease in Children (CKiD) study were studied. Self-reported appetite was assessed annually and categorized as very good, good, fair, or poor/very poor. The relationship between appetite and iohexol or estimated glomerular filtration rate (ieGFR), annual changes in anthropometrics z-scores, hospitalizations, emergency room visits, and quality of life were assessed. Results An ieGFR< 30 ml/min per 1.73m2 was associated with a 4.46 greater odds (95% confidence interval: 2.80, 7.09) of having a worse appetite than those with ieGFR >90. Appetite did not predict changes in height, weight, or BMI z-scores. Patients not reporting a very good appetite had more hospitalizations over the next year than those with a very good appetite. Worse appetite was significantly associated with lower parental and patient reported quality of life. Conclusions Self-reported appetite in children with CKD worsens with lower ieGFR and is correlated with clinical outcomes, including hospitalizations and quality of life. PMID:26857711

Perceived appetite and clinical outcomes in children with chronic kidney disease.

PubMed

Ayestaran, Frank W; Schneider, Michael F; Kaskel, Frederick J; Srivaths, Poyyapakkam R; Seo-Mayer, Patricia W; Moxey-Mims, Marva; Furth, Susan L; Warady, Bradley A; Greenbaum, Larry A

2016-07-01

Children with chronic kidney disease (CKD) may have impaired caloric intake through a variety of mechanisms, with decreased appetite as a putative contributor. In adult CKD, decreased appetite has been associated with poor clinical outcomes. There is limited information about this relationship in pediatric CKD. A total of 879 participants of the Chronic Kidney Disease in Children (CKiD) study were studied. Self-reported appetite was assessed annually and categorized as very good, good, fair, or poor/very poor. The relationship between appetite and iohexol or estimated glomerular filtration rate (ieGFR), annual changes in anthropometrics z-scores, hospitalizations, emergency room visits, and quality of life were assessed. An ieGFR < 30 ml/min per 1.73 m(2) was associated with a 4.46 greater odds (95 % confidence interval: 2.80, 7.09) of having a worse appetite than those with ieGFR >90. Appetite did not predict changes in height, weight, or BMI z-scores. Patients not reporting a very good appetite had more hospitalizations over the next year than those with a very good appetite. Worse appetite was significantly associated with lower parental and patient reported quality of life. Self-reported appetite in children with CKD worsens with lower ieGFR and is correlated with clinical outcomes, including hospitalizations and quality of life.

Osmolarity: a decisive parameter of bowel agents in intestinal magnetic resonance imaging.

PubMed

Borthne, Arne S; Abdelnoor, Michael; Storaas, Trygve; Pierre-Jerome, Claude; Kløw, Nils-E

2006-06-01

The aim was to evaluate the importance of the osmolarity of different oral agents for bowel distension and the level of related adverse events. The longitudinal design included the exposition of different oral MR agents on two separate occasions. Four groups of volunteers were randomly given 350 ml gastrografin of three different concentrations and water. On the second occasion they received mannitol, iohexol or iodixanol with equivalent osmolarities, but the control group (water) received mannitol. We recorded the outcomes as the degree of bowel distension determined as the mean bowel section area and the total level of discomfort recorded from a visual analogue scale (VAS). The statistical analysis included scatter plots with the best-fitted line with linear regression to study the association between osmolarity and section area and the association between osmolarity and adverse events. A dose-response association was found between increasing osmolarity levels and bowel area in square centimeters (P = 0.00001). A similar dose-response association existed between increasing levels of osmolarity and adverse events (P = 0.001). Osmolarity appears to be more important for bowel distension than the physico-chemical characteristics of the nonabsorbable oral agents. The optimum osmolarity level is determined by the patient's tolerance of the adverse events.

Near-infrared light-triggered theranostics for tumor-specific enhanced multimodal imaging and photothermal therapy

PubMed Central

Wu, Bo; Wan, Bing; Lu, Shu-Ting; Deng, Kai; Li, Xiao-Qi; Wu, Bao-Lin; Li, Yu-Shuang; Liao, Ru-Fang; Huang, Shi-Wen; Xu, Hai-Bo

2017-01-01

The major challenge in current clinic contrast agents (CAs) and chemotherapy is the poor tumor selectivity and response. Based on the self-quench property of IR820 at high concentrations, and different contrast effect ability of Gd-DOTA between inner and outer of liposome, we developed “bomb-like” light-triggered CAs (LTCAs) for enhanced CT/MRI/FI multimodal imaging, which can improve the signal-to-noise ratio of tumor tissue specifically. IR820, Iohexol and Gd-chelates were firstly encapsulated into the thermal-sensitive nanocarrier with a high concentration. This will result in protection and fluorescence quenching. Then, the release of CAs was triggered by near-infrared (NIR) light laser irradiation, which will lead to fluorescence and MRI activation and enable imaging of inflammation. In vitro and in vivo experiments demonstrated that LTCAs with 808 nm laser irradiation have shorter T1 relaxation time in MRI and stronger intensity in FI compared to those without irradiation. Additionally, due to the high photothermal conversion efficiency of IR820, the injection of LTCAs was demonstrated to completely inhibit C6 tumor growth in nude mice up to 17 days after NIR laser irradiation. The results indicate that the LTCAs can serve as a promising platform for NIR-activated multimodal imaging and photothermal therapy. PMID:28670120

Potential influence of tubular dysfunction on the difference between estimated and measured glomerular filtration rate after kidney transplantation.

PubMed

Lezaic, V; Mirkovic, D; Ristic, S; Radivojevic, D; Dajak, M; Naumovic, R; Marinkovic, J; Djukanovic, L J

2013-05-01

Because no consensus exists regarding the most accurate calculation to estimate glomerular filtration rate (GFR) based on serum creatinine concentrations (sCr) after kidney transplantation, this study sought to assess the potential role of tubular dysfunction on GFR estimates using various equations as well as the effect of pharmacologic blockades on tubular secretion of creatinine on creatinine clearance (ClCr). Iohexol GFR (mGFR) was performed in 17 stable kidney transplant recipients(R) at >24 months post-transplantation. Their mean age was 48.3 ± 11.3 years. All R were treated with a calcineurin inhibitor (CNI). At the time of study we measured sCr, 24 hour-ClCr, cystatin C, 24-hour proteinuria, microalbuminuria, FE Na, alfa1-microglobulinuria (alfa1-MG), and CNI concentrations. To block tubular secretion of Cr, recipients were prescribed cimetidine (2400 mg) 2 days before the sCr measurement. Additionally, to exclude dietary influences on sCr, R did not eat meat for 2 days before testing. GFR was estimated using the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Cockroft-Gault (C&G), and Cystatin C (Cyst C) GFR equations. Mean kidney graft function over the previous 6 months was used as the control. Pearson correlation was determined between the differences between mGFR and estimatedGFR: Iohexol minus MDRD, EPI, Cyst C or C&G GFR for paired estimates. The diagnostic accuracy of the eGFRs to detect an mGFR of 60 mL/min/1.73 m(2) was examined by receiver operating characteristic curves. Mean mGFR was 75.2 ± 35.8 mL/min/1.73 m(2). The sCr increased but the 24-hour ClCr, MDRD, EPI, and C&G decreased after vs before cimetidine. The difference was significant for sCr (F = 12.933; P = .002) and MDRD GFR (F = 15.750; P = .001). mGFR was not significantly higher than all pair values of eGFRs, and not significantly lower than 24-hour ClCr before and after cimetidine. However, in comparison to all eGFRs, ClCr after cimetidine most approached mGFR. A significant positive correlation was observed between alfa1-MG and the difference between mGFR and MDRD (before, r = .543 [P = .045]; after cimetidine, 0.568 [P = .034]), EPI (before, r = 0.516 [P = .050]; after cimetidine, r = 0.562 [P = .036]), and ClCr (r = 0.633; P = .016), C&G (P = .581; P = .029) before cimetidine. Accuracy of eGFRs to detect mGFR of 60 mL/min/1.73 m(2) showed EPI GFR before cimetidine to show diagnostic accuracy for patients with GFR >60 mL/min/1.73 m(2) with a sensitivity of 81.8% and a specificity of 71.4%. Because mGFR is unavailable in many transplant centers, determination of ClCr after cimetidine may help to achieve a more accurate diagnosis of CKD among transplant patients. Copyright © 2013 Elsevier Inc. All rights reserved.

Confocal Raman microscopy supported by optical clearing treatment of the skin—influence on collagen hydration

NASA Astrophysics Data System (ADS)

Sdobnov, Anton Yu; Tuchin, Valery V.; Lademann, Juergen; E Darvin, Maxim

2017-07-01

Confocal Raman microscopy (CRM) is employed to study the skin physiology, drug permeation and skin disease monitoring. In order to increase the depth of investigations, the effect of optical clearing was observed on porcine ear skin ex vivo. The optical clearing agents (OCAs) glycerol and iohexol (Omnipaque™) were applied to the porcine ear skin and investigated by CRM after 30 and 60 min of treatment. The extent of optical clearing by utilizing concentrations of 70% glycerol and 100% Omnipaque™ was evaluated. The intensity of the skin-related Raman peaks significantly increased starting from the depth 160 µm for Omnipaque™ and 40 µm for glycerol (p  ⩽  0.05) after 60 min of treatment. The OCAs’ influence on the collagen hydration in the deep-located dermis was investigated. Both OCAs induce skin dehydration, but the effect of glycerol treatment (30 min and 60 min) is stronger. The obtained results demonstrate that with increasing the treatment time, both glycerol and Omnipaque™ solutions improve the optical clearing of porcine skin making the deep-located dermal regions able for investigations. At the used concentrations and time intervals, glycerol is more effective than Omnipaque™. However, Omnipaque™ is more promising than glycerol for future in vivo applications as it is an already approved pharmaceutic substance without any known impact on the skin structure.

The Enhancement of H2O2/UV AOPs for the Removal of Selected Organic Pollutants from Drinking Water with Hydrodynamic Cavitation.

PubMed

Čehovin, Matej; Medic, Alojz; Kompare, Boris; Žgajnar Gotvajn, Andreja

2016-12-01

Drinking water contains organic matter that occasionally needs to be treated to assure its sufficient quality and safety for the consumers. H2O2 and UV advanced oxidation processes (H2O2/UV AOPs) were combined with hydrodynamic cavitation (HC) to assess the effects on the removal of selected organic pollutants. Water samples containing humic acid, methylene blue dye and micropollutants (metaldehyde, diatrizoic acid, iohexol) were treated first by H2O2 (dosages from 1 to 12 mg L-1) and UV (dosages from 300 to 2800 mJ cm-2) AOPs alone and later in combination with HC, generated by nozzles and orifice plates (4, 8, 18 orifices). Using HC, the removal of humic acid was enhanced by 5-15%, methylene blue by 5-20% and metaldehyde by approx. 10%. Under favouring conditions, i.e. high UV absorbance of the matrix (more than 0.050 cm-1 at a wavelength of 254 nm) and a high pollutant to oxidants ratio, HC was found to improve the hydrodynamic conditions in the photolytic reactor, to improve the subjection of the H2O2 to the UV fluence rate distribution and to enhance the removal of the tested organic pollutants, thus showing promising potential of further research in this field.

The Impact of the Glomerular Filtration Rate on the Human Plasma Proteome.

PubMed

Christensson, Anders; Ash, Jessica A; DeLisle, Robert K; Gaspar, Fraser W; Ostroff, Rachel; Grubb, Anders; Lindström, Veronica; Bruun, Laila; Williams, Steve A

2018-05-01

The application of proteomics in chronic kidney disease (CKD) can potentially uncover biomarkers and pathways that are predictive of disease. Within this context, this study examines the relationship between the human plasma proteome and glomerular filtration rate (GFR) as measured by iohexol clearance in a cohort from Sweden (n = 389; GFR range: 8-100 mL min -1 /1.73 m 2 ). A total of 2893 proteins are quantified using a modified aptamer assay. A large proportion of the proteome is associated with GFR, reinforcing the concept that CKD affects multiple physiological systems (individual protein-GFR correlations listed here). Of these, cystatin C shows the most significant correlation with GFR (rho = -0.85, p = 1.2 × 10 -97 ), establishing strong validation for the use of this biomarker in CKD diagnostics. Among the other highly significant protein markers are insulin-like growth factor-binding protein 6, neuroblastoma suppressor of tumorigenicity 1, follistatin-related protein 3, trefoil factor 3, and beta-2 microglobulin. These proteins may indicate an imbalance in homeostasis across a variety of cellular processes, which may be underlying renal dysfunction. Overall, this study represents the most extensive characterization of the plasma proteome and its relation to GFR to date, and suggests the diagnostic and prognostic value of proteomics for CKD across all stages. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Measuring and Estimating GFR and Treatment Effect in ADPKD Patients: Results and Implications of a Longitudinal Cohort Study

PubMed Central

Cannata, Antonio; Carrara, Fabiola; Cella, Claudia; Ferrari, Silvia; Stucchi, Nadia; Prandini, Silvia; Ene-Iordache, Bogdan; Diadei, Olimpia; Perico, Norberto; Ondei, Patrizia; Pisani, Antonio; Buongiorno, Erasmo; Messa, Piergiorgio; Dugo, Mauro; Remuzzi, Giuseppe

2012-01-01

Trials failed to demonstrate protective effects of investigational treatments on glomerular filtration rate (GFR) reduction in Autosomal Dominant Polycystic Kidney Disease (ADPKD). To assess whether above findings were explained by unreliable GFR estimates, in this academic study we compared GFR values centrally measured by iohexol plasma clearance with corresponding values estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) and abbreviated Modification of Diet in Renal Disease (aMDRD) formulas in ADPKD patients retrieved from four clinical trials run by a Clinical Research Center and five Nephrology Units in Italy. Measured baseline GFRs and one-year GFR changes averaged 78.6±26.7 and 8.4±10.3 mL/min/1.73 m2 in 111 and 71 ADPKD patients, respectively. CKD-Epi significantly overestimated and aMDRD underestimated baseline GFRs. Less than half estimates deviated by <10% from measured values. One-year estimated GFR changes did not detect measured changes. Both formulas underestimated GFR changes by 50%. Less than 9% of estimates deviated <10% from measured changes. Extent of deviations even exceeded that of measured one-year GFR changes. In ADPKD, prediction formulas unreliably estimate actual GFR values and fail to detect their changes over time. Direct kidney function measurements by appropriate techniques are needed to adequately evaluate treatment effects in clinics and research. PMID:22393413

Well Preserved Renal Function in Children With Untreated Chronic Liver Disease.

PubMed

Berg, Ulla B; Németh, Antal

2018-04-01

On the basis of studies with hepatorenal syndrome, it is widely regarded that renal function is impacted in chronic liver disease (CLD). Therefore, we investigated renal function in children with CLD. In a retrospective study of 277 children with CLD, renal function was investigated as glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), measured as clearance of inulin and para-amino hippuric acid or clearance of iohexol. The data were analyzed with regard to different subgroups of liver disease and to the grade of damage. Hyperfiltration (>+2 SD of controls) was found in the subgroups of progressive familial intrahepatic cholestasis (44%), glycogenosis (75%), and acute fulminant liver failure (60%). Patients with biliary atresia, most other patients with metabolic disease and intrahepatic cholestasis, and those with vascular anomalies and cryptogenic cirrhosis had normal renal function. Decreased renal function was found in patients with Alagille's syndrome (64% < -2 SD). Increased GFR and ERPF was found in patients with elevated transaminases, low prothrombin level, high bile acid concentration, and high aspartate-aminotransferase-to-platelet ratio. Most children with CLD had surprisingly well preserved renal function and certain groups had even hyperfiltration. The finding that children with decompensated liver disease and ongoing liver failure had stable kidney function suggests that no prognostic markers of threatening hepatorenal syndrome were at hand. Moreover, estimation of GFR based on serum creatinine fails to reveal hyperfiltration.

Removal of APIs and bacteria from hospital wastewater by MBR plus O(3), O(3) + H(2)O(2), PAC or ClO(2).

PubMed

Nielsen, U; Hastrup, C; Klausen, M M; Pedersen, B M; Kristensen, G H; Jansen, J L C; Bak, S N; Tuerk, J

2013-01-01

The objective of this study has been to develop technologies that can reduce the content of active pharmaceutical ingredients (APIs) and bacteria from hospital wastewater. The results from the laboratory- and pilot-scale testings showed that efficient removal of the vast majority of APIs could be achieved by a membrane bioreactor (MBR) followed by ozone, ozone + hydrogen peroxide or powdered activated carbon (PAC). Chlorine dioxide (ClO(2)) was significantly less effective. MBR + PAC (450 mg/l) was the most efficient technology, while the most cost-efficient technology was MBR + ozone (156 mg O(3)/l applied over 20 min). With MBR an efficient removal of Escherichia coli and enterococci was measured, and no antibiotic resistant bacteria were detected in the effluent. With MBR + ozone and MBR + PAC also the measured effluent concentrations of APIs (e.g. ciprofloxacin, sulfamethoxazole and sulfamethizole) were below available predicted no-effect concentrations (PNEC) for the marine environment without dilution. Iodinated contrast media were also reduced significantly (80-99% for iohexol, iopromide and ioversol and 40-99% for amidotrizoateacid). A full-scale MBR treatment plant with ozone at a hospital with 900 beds is estimated to require an investment cost of €1.6 mill. and an operating cost of €1/m(3) of treated water.

Generation of a new cystatin C-based estimating equation for glomerular filtration rate by use of 7 assays standardized to the international calibrator.

PubMed

Grubb, Anders; Horio, Masaru; Hansson, Lars-Olof; Björk, Jonas; Nyman, Ulf; Flodin, Mats; Larsson, Anders; Bökenkamp, Arend; Yasuda, Yoshinari; Blufpand, Hester; Lindström, Veronica; Zegers, Ingrid; Althaus, Harald; Blirup-Jensen, Søren; Itoh, Yoshi; Sjöström, Per; Nordin, Gunnar; Christensson, Anders; Klima, Horst; Sunde, Kathrin; Hjort-Christensen, Per; Armbruster, David; Ferrero, Carlo

2014-07-01

Many different cystatin C-based equations exist for estimating glomerular filtration rate. Major reasons for this are the previous lack of an international cystatin C calibrator and the nonequivalence of results from different cystatin C assays. Use of the recently introduced certified reference material, ERM-DA471/IFCC, and further work to achieve high agreement and equivalence of 7 commercially available cystatin C assays allowed a substantial decrease of the CV of the assays, as defined by their performance in an external quality assessment for clinical laboratory investigations. By use of 2 of these assays and a population of 4690 subjects, with large subpopulations of children and Asian and Caucasian adults, with their GFR determined by either renal or plasma inulin clearance or plasma iohexol clearance, we attempted to produce a virtually assay-independent simple cystatin C-based equation for estimation of GFR. We developed a simple cystatin C-based equation for estimation of GFR comprising only 2 variables, cystatin C concentration and age. No terms for race and sex are required for optimal diagnostic performance. The equation, [Formula: see text] is also biologically oriented, with 1 term for the theoretical renal clearance of small molecules and 1 constant for extrarenal clearance of cystatin C. A virtually assay-independent simple cystatin C-based and biologically oriented equation for estimation of GFR, without terms for sex and race, was produced. © 2014 The American Association for Clinical Chemistry.

Cost-effectiveness of iso- versus low-osmolality contrast media in outpatients with high risk of contrast medium-induced nephropathy.

PubMed

Chicaíza-Becerra, Liliana Alejandra; García-Molina, Mario; Gamboa, Óscar

2012-06-01

Contrast media can cause acute renal failure by direct toxic effects on the tubular cells and kidney ischemia. Diabetics and hospitalized patients have a greater risk of developing contrast-induced nephropathy than the general population. The cost effectiveness of iso and low-osmolality contrast media was assessed in high risk outpatients. The analysis was based on a systematic literature review comparing the nephrotoxic effects of iso- to low-osmolality contrast media. Only direct costs were considered; these were obtained from the official tariff manual. Incremental cost-effectiveness ratios, efficiency curves and acceptability curves were calculated. Univariate sensitivity analyses were performed for costs and effects, as well as probabilistic analyses. Zero and 3% discounts were applied to results. The cost-effectiveness threshold was equal to the per capita GDP per life-year gained. Alternatives with Iopamidol and Iodixanol are preferable to the others, because both reduce risk of contrast-induced nephropathy and are less costly. The incremental cost-effectiveness of the Iodixanol alternative compared to the Iopamidol alternative is US$ 14,660 per additional life year gained; this is more than twice the threshold. The low-osmolality contrast medium, Iopamidol, appears to be cost-effective when compared with Iohexol or other low-osmolality contrast media (Iopromide, Iobitridol, Iomeprol, Iopentol and Ioxilan) in contrast-induced nephropathy, high-risk outpatients. The choice of the iso-osmolality contrast medium, Iodixanol, depends on its cost per vial and on the willingness to pay.

A Radiographic Measurement of the Anterior Epidural Space at L4-5 Disc Level.

PubMed

Xu, Rui-Sheng; Wu, Jie-Shi; Lu, Hai-Dan; Zhu, Hao-Gang; Li, Xia; Dong, Jian; Yuan, Feng-Lai

2017-05-01

To observe the morphology character of the anterior epidural space at the L 4-5 disc level and to provide an anatomical basis for safely and accurately performing a percutaneous endoscopic lumbar discectomy (PELD). Fifty-five cases with L 5 S 1 lumbar disc herniation were included in this study, and cases with L 4-5 disease were excluded. When the puncture needle reached the epidural space at the L 5 S 1 level, iohexol was injected at the pressure of 50 cm H 2 O during the PELD, then C-Arm fluoroscopy was used to obtain standard lumbar frontal and lateral images. The widths of epidural space at the level of the L 4 lower endplate, the L 5 upper endplate, as well as the middle point of the L 4-5 disc were measured from the lumbar lateral X-ray film. Epidural space at the L 4-5 disc plane performs like a trapezium chart with a short side at the head end and a long side at the tail end in the lumbar lateral X-ray radiograph, while the average widths of epidural space were 10.2 ± 2.5, 12.3 ± 2.3, and 13.8 ± 2.6 mm at the upper, middle, and lower level of the L 4-5 disc. Understanding the morphological characteristics of epidural space will contribute to improving the safety of the tranforaminal percutaneous endoscopy technique. © 2017 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

The potential utility of iodinated contrast media (ICM) skin testing in patients with ICM hypersensitivity.

PubMed

Ahn, Young-Hwan; Koh, Young-Il; Kim, Joo-Hee; Ban, Ga-Young; Lee, Yeon-Kyung; Hong, Ga-Na; Jin, U-Ram; Choi, Byung-Joo; Shin, Yoo-Seob; Park, Hae-Sim; Ye, Young-Min

2015-03-01

Both immediate and delayed hypersensitivity reactions to iodinated contrast media (ICM) are relatively common. However, there are few data to determine the clinical utility of immunologic evaluation of ICM. To evaluate the utility of ICM skin testing in patients with ICM hypersensitivity, 23 patients (17 immediate and 6 delayed reactions) were enrolled from 3 university hospitals in Korea. With 6 commonly used ICM including iopromide, iohexol, ioversol, iomeprol, iopamidol and iodixanol, skin prick (SPT), intradermal (IDT) and patch tests were performed. Of 10 patients with anaphylaxis, 3 (30.0%) and 6 (60.0%) were positive respectively on SPTs and IDTs with the culprit ICM. Three of 6 patients with urticaria showed positive IDTs. In total, 11 (64.7%) had positive on either SPT or IDT. Three of 6 patients with delayed rashes had positive response to patch test and/or delayed IDT. Among 5 patients (3 anaphylaxis, 1 urticaria and 1 delayed rash) taken subsequent radiological examinations, 3 patients administered safe alternatives according to the results of skin testing had no adverse reaction. However, anaphylaxis developed in the other 2 patients administered the culprit ICM again. With 64.7% (11/17) and 50% (3/6) of the sensitivities of corresponding allergic skin tests with culprit ICM for immediate and delayed hypersensitivity reactions, the present study suggests that skin tests is useful for the diagnosis of ICM hypersensitivity and for selecting safe ICM and preventing a recurrence of anaphylaxis caused by the same ICM.

Frequency of an accessory popliteal efferent lymphatic pathway in dogs.

PubMed

Mayer, Monique N; Sweet, Katherine A; Patsikas, Michael N; Sukut, Sally L; Waldner, Cheryl L

2018-05-01

Staging and therapeutic planning for dogs with malignant disease in the popliteal lymph node are based on the expected patterns of lymphatic drainage from the lymph node. The medial iliac lymph nodes are known to receive efferent lymph from the popliteal lymph node; however, an accessory popliteal efferent pathway with direct connection to the sacral lymph nodes has also been less frequently reported. The primary objective of this prospective, anatomic study was to describe the frequency of various patterns of lymphatic drainage of the popliteal lymph node. With informed client consent, 50 adult dogs with no known disease of the lymphatic system underwent computed tomographic lymphography after ultrasound-guided, percutaneous injection of 350 mg/ml iohexol into a popliteal lymph node. In all 50 dogs, the popliteal lymph node drained directly to the ipsilateral medial iliac lymph node through multiple lymphatic vessels that coursed along the medial thigh. In 26% (13/50) of dogs, efferent vessels also drained from the popliteal lymph node directly to the internal iliac and/or sacral lymph nodes, coursing laterally through the gluteal region and passing over the dorsal aspect of the pelvis. Lymphatic connections between the right and left medial iliac and right and left internal iliac lymph nodes were found. Based on our findings, the internal iliac and sacral lymph nodes should be considered when staging or planning therapy for dogs with malignant disease in the popliteal lymph node. © 2018 American College of Veterinary Radiology.

CKD-EPI equation: A suitable Glomerular Filtration Rate estimate for drug dosing in HIV-infected patients.

PubMed

Gagneux-Brunon, A; Botelho-Nevers, E; Delanaye, P; Lucht, F; Frésard, A; Cazorla, C; Guglielminotti, C; Fafin, C; Mariat, C; Moranne, O

2017-06-01

To evaluate concordance between glomerular filtration rate (GFR) estimates (Cockcroft and Gault, modification of diet in renal diseases, chronic kidney disease epidemiology study group equations) for drug dosing in HIV-infected patients. We performed a monocentric study. GFR was measured using the gold standard method (plasma clearance of iohexol) in 230 HIV-infected patients. Concordance rate was evaluated between measured GFR (mGFR) and estimated GFR (eGFR) for different GFR categories (GFR>90 mL/min, GFR<90 mL/min, GFR>70 mL/min, and GFR<70 mL/min). MDRD and CKD-EPI were used with and without indexation to body surface area (BSA). Mean age was 48±10 years, mean mGFR was 101±26 mL/min. Concordance between mGFR and eGFR estimated with CG, CKD-EPI (indexed and not indexed to BSA), or MDRD equations (not indexed to BSA) was similar (73%, 73%, 74%, and 73% respectively) for a breakpoint value of 90 mL/min for GFR. At this value, the concordance rate between mGFR and MDRD indexed to BSA was significantly lower (65%, P<0.05). Using 70 mL/min of GFR as the breakpoint value, all equations had similar concordance rates with mGFR (with or without indexation to BSA). CKD-EPI equation has the same concordance with GFR and with CG when used for drug dosing. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chemotherapy-induced gastrointestinal toxicity is associated with changes in serum and urine metabolome and fecal microbiota in male Sprague-Dawley rats.

PubMed

Forsgård, Richard A; Marrachelli, Vannina G; Korpela, Katri; Frias, Rafael; Collado, Maria Carmen; Korpela, Riitta; Monleon, Daniel; Spillmann, Thomas; Österlund, Pia

2017-08-01

Chemotherapy-induced gastrointestinal toxicity (CIGT) is a complex process that involves multiple pathophysiological mechanisms. We have previously shown that commonly used chemotherapeutics 5-fluorouracil, oxaliplatin, and irinotecan damage the intestinal mucosa and increase intestinal permeability to iohexol. We hypothesized that CIGT is associated with alterations in fecal microbiota and metabolome. Our aim was to characterize these changes and examine how they relate to the severity of CIGT. A total of 48 male Sprague-Dawley rats were injected intraperitoneally either with 5-fluorouracil (150 mg/kg), oxaliplatin (15 mg/kg), or irinotecan (200 mg/kg). Body weight change was measured daily after drug administration and the animals were euthanized after 72 h. Blood, urine, and fecal samples were collected at baseline and at the end of the experiment. The changes in the composition of fecal microbiota were analyzed with 16S rRNA gene sequencing. Metabolic changes in serum and urine metabolome were measured with 1 mm proton nuclear magnetic resonance ( 1 H-NMR). Irinotecan increased the relative abundance of Fusobacteria and Proteobacteria, while 5-FU and oxaliplatin caused only minor changes in the composition of fecal microbiota. All chemotherapeutics increased the levels of serum fatty acids and N(CH 3 ) 3 moieties and decreased the levels of Krebs cycle metabolites and free amino acids. Chemotherapeutic drugs, 5-fluorouracil, oxaliplatin, and irinotecan, induce several microbial and metabolic changes which may play a role in the pathophysiology of CIGT. The observed changes in intestinal permeability, fecal microbiota, and metabolome suggest the activation of inflammatory processes.

Sensation of smell and taste during intravenous injection of iodinated contrast media in CT examinations.

PubMed

Yamaguchi, Naoto; Fukushima, Yasuhiro; Yamaguchi, Aiko; Nagasawa, Naoki; Taketomi-Takahashi, Ayako; Suto, Takayuki; Tsushima, Yoshito

2017-01-01

To assess the incidence and types of sensation of smell and taste during i.v. injection of five kinds of contrast media (CM) in CT examinations. 735 patients who underwent contrast-enhanced CT (CE-CT) between 14 March 2016 and 5 April 2016 were enrolled. Medical staff asked patients whether they felt heat sensation and sensation of smell and taste during i.v. injection of CM (one of the following: iopromide, iomeprol, iopamidol, iohexol and ioversol) after their CE-CT. If the patients stated having felt the sensation of smell or taste, they were also asked what kind of smell or taste they sensed. Next, 30 ml of each CM was poured into high-purity pet cups for radiological technologists to smell directly. Radiological technologists were asked whether or not each CM had any smell. The sensations of smell and taste incidence for iopromide were 24.3% and 18.9%, respectively, which were significantly higher than those for other CM (p < 0.05). The highest incidence of the sensation of smell was medicine-ish, and the most frequently noted taste was bitterness. All radiological technologists could directly smell only iopromide, which has an ether group on a side chain and fewer hydroxyl groups. Iopromide showed a higher incidence of sensation of smell and taste than other CM. Advances in knowledge: This was the first investigation of sensation of smell and taste during i.v. injection of CM, and a specific CM showed a higher incidence, which is suspected to be due to its chemical structure.

Sensation of smell and taste during intravenous injection of iodinated contrast media in CT examinations

PubMed Central

Yamaguchi, Naoto; Yamaguchi, Aiko; Nagasawa, Naoki; Taketomi-Takahashi, Ayako; Suto, Takayuki; Tsushima, Yoshito

2017-01-01

Objective: To assess the incidence and types of sensation of smell and taste during i.v. injection of five kinds of contrast media (CM) in CT examinations. Methods: 735 patients who underwent contrast-enhanced CT (CE-CT) between 14 March 2016 and 5 April 2016 were enrolled. Medical staff asked patients whether they felt heat sensation and sensation of smell and taste during i.v. injection of CM (one of the following: iopromide, iomeprol, iopamidol, iohexol and ioversol) after their CE-CT. If the patients stated having felt the sensation of smell or taste, they were also asked what kind of smell or taste they sensed. Next, 30 ml of each CM was poured into high-purity pet cups for radiological technologists to smell directly. Radiological technologists were asked whether or not each CM had any smell. Results: The sensations of smell and taste incidence for iopromide were 24.3% and 18.9%, respectively, which were significantly higher than those for other CM (p < 0.05). The highest incidence of the sensation of smell was medicine-ish, and the most frequently noted taste was bitterness. All radiological technologists could directly smell only iopromide, which has an ether group on a side chain and fewer hydroxyl groups. Conclusion: Iopromide showed a higher incidence of sensation of smell and taste than other CM. Advances in knowledge: This was the first investigation of sensation of smell and taste during i.v. injection of CM, and a specific CM showed a higher incidence, which is suspected to be due to its chemical structure. PMID:27805431

Torsten Almén (1931-2016): the father of non-ionic iodine contrast media.

PubMed

Nyman, Ulf; Ekberg, Olle; Aspelin, Peter

2016-09-01

The Swedish radiologist Torsten Almén is the first clinical radiologist ever to have made a fundamental contribution to intravascular contrast medium design, the development of non-ionic contrast media. He became emotionally triggered by the patients' severe pain each time he injected the ionic "high-osmolar" contrast media when performing peripheral arteriographies in the early 1960s. One day he got a flash of genius that combined the observation of pain, a pathophysiological theory and how to eliminate it with suitable contrast media chemistry. After self-studies in chemistry he developed the concept of iodine contrast media not dissociating into ions in solution to reduce their osmolality and even reach plasma isotonicity. He offered several pharmaceutical companies his concept of mono- and polymeric non-ionic agents but without response, since it was considered against the chemical laws of that time. Contrast media constructed as salts and dissociating into ions in solution was regarded an absolute necessity to achieve high enough water solubility and concentration for diagnostic purposes. Finally a small Norwegian company, Nyegaard & Co., took up his idea 1968 and together they developed the essentially painless "low-osmolar" monomeric non-ionic metrizamide (Amipaque) released in 1974 and iohexol (Omipaque) in 1982 followed by the "iso-osmolar" dimeric non-ionic iodixanol (Visipaque) released in 1993. This has implied a profound paradigm shift with regard to reduction of both hypertonic and chemotoxic side effects, which have been a prerequisite for the today's widespread use of contrast medium-enhanced CT and advanced endovascular interventional techniques even in fragile patients. © The Foundation Acta Radiologica 2016.

Intratympanic Iodine Contrast Injection Diffuses Across the Round Window Membrane Allowing for Perilymphatic CT Volume Acquisition Imaging.

PubMed

Abt, Nicholas B; Lehar, Mohamed; Guajardo, Carolina Trevino; Penninger, Richard T; Ward, Bryan K; Pearl, Monica S; Carey, John P

2016-04-01

Whether the round window membrane (RWM) is permeable to iodine-based contrast agents (IBCA) is unknown; therefore, our goal was to determine if IBCAs could diffuse through the RWM using CT volume acquisition imaging. Imaging of hydrops in the living human ear has attracted recent interest. Intratympanic (IT) injection has shown gadolinium's ability to diffuse through the RWM, enhancing the perilymphatic space. Four unfixed human cadaver temporal bones underwent intratympanic IBCA injection using three sequentially studied methods. The first method was direct IT injection. The second method used direct RWM visualization via tympanomeatal flap for IBCA-soaked absorbable gelatin pledget placement. In the third method, the middle ear was filled with contrast after flap elevation. Volume acquisition CT images were obtained immediately postexposure, and at 1-, 6-, and 24-hour intervals. Postprocessing was accomplished using color ramping and subtraction imaging. After the third method, positive RWM and perilymphatic enhancement were observed with endolymph sparing. Gray scale and color ramp multiplanar reconstructions displayed increased signal within the cochlea compared with precontrast imaging. The cochlea was measured for attenuation differences compared with pure water, revealing a preinjection average of -1,103 HU and a postinjection average of 338 HU. Subtraction imaging shows enhancement remaining within the cochlear space, Eustachian tube, middle ear epithelial lining, and mastoid. Iohexol iodine contrast is able to diffuse across the RWM. Volume acquisition CT imaging was able to detect perilymphatic enhancement at 0.5-mm slice thickness. The clinical application of IBCA IT injection seems promising but requires further safety studies.

Glomerular filtration rate in evaluation of the effect of iodinated contrast media on renal function.

PubMed

Becker, Joshua; Babb, James; Serrano, Manuel

2013-04-01

The purpose of this study was to use measured glomerular filtration rate (GFR), the reference standard of renal function, to assess the deleterious effect of iodinated contrast media on renal function. Such an effect has been traditionally defined as a greater than 0.5-mg/dL increase in serum creatinine concentration or a 25% or greater increase 24-72 hours after the injection of iodinated contrast medium. This pilot investigation was focused on the consequences of clinically indicated IV injection of iodinated contrast media; intraarterial injection was excluded. One hundred thirteen patients with normal serum creatinine concentrations were enrolled in an approved protocol. At random, as chosen by one of the investigators, patients underwent imaging with one of three monomeric agents (iopamidol 300, iopromide 300, iohexol 300) and one dimeric agent (iodixanol 320). Measured GFR was determined immediately before CT and approximately 3 and 72 hours after the contrast injection for the CT examination. Iodinated contrast medium, a glomerular filtrate with no tubular excretion or reabsorption, was the GFR marker. Measured GFR was determined by x-ray fluorescence analysis with nonisotopic iodinated contrast media. Monomeric and dimeric contrast agents in diagnostic CT volumes (based on bodyweight and imaging protocol) did not induce a significant change in measured GFR (95% confidence by Wilcoxon test), suggesting that use of the evaluated contrast media will not lead to more than a 12% variation. The three monomeric agents studied and the one dimeric agent were equivalent in terms of lack of a significant effect on measured GFR when administered to patients with a normal GFR.

Serum creatinine can be used as a surrogate for glomerular filtration rate in single renal unit models.

PubMed

Gofrit, Ofer N; Orvieto, Marcelo A; Zorn, Kevin C; Steinberg, Gary D; Zagaja, Gregory P; Shalhav, Arieh L

2009-02-01

Single renal unit models are invaluable for studies in renal physiology, transplantation and response to ischemic injury. Glomerular filtration rate (GFR) is commonly used for evaluation of renal function. Measuring the GFR involves relatively complicated and expensive systems. In this study we determined whether serum creatinine (Scr) can predict the GFR in this model. Right laparoscopic nephrectomy was performed in 46 female pigs weighing 25 kg-30 kg. Twelve days later the left kidney was exposed to various periods of warm ischemia (30, 60, 90, and 120 minutes). Scr and GFR (using the iohexol clearance method) were determined preoperatively and at postoperative days 1, 3, 8, 15, 22 and 29. A total of 244 pairs of Scr and GFR values were analyzed to determine a formula for predicting GFR (pGFR) from Scr. Scr range was 1.2 mg/dl -29 mg/dl and GFR range was 1.8 ml/min -180.5 ml/min. The empiric formula deduced from the database for calculating pGFR from Scr was: pGFR = (217 divided by Scr) minus 0.2. pGFR correlated well with the actual GFR (R(2) = 0.85). The graphs for pGFR were almost indistinguishable from the graphs for actual GFR in every single animal. The results and conclusions of the experiments using either actual or predicted GFR were identical. We conclude that in a single renal unit porcine model using ischemia as the insult to the kidney, expensive actual measurements of GFR can be reliably replaced by Scr based calculated GFR.

Impact on creatinine renal clearance by the interplay of multiple renal transporters: a case study with INCB039110.

PubMed

Zhang, Yan; Warren, Mark S; Zhang, Xuexiang; Diamond, Sharon; Williams, Bill; Punwani, Naresh; Huang, Jane; Huang, Yong; Yeleswaram, Swamy

2015-04-01

Serum creatinine is commonly used as a marker of renal function, but increases in serum creatinine might not represent changes in glomerular filtration rate (GFR). INCB039110 (2-(3-(4-(7H-pyrrolo[2,3-day]pyrimidin-4-yl)-1H-pyrazol-1-yl)-1-(1-(3-fluoro-2-(trifluoromethyl)isonicotinoyl)piperidin-4-yl)azetidin-3-yl)acetonitrile) is an inhibitor of the Janus kinases (JAKs) with selectivity for JAK1. In a phase 1 study, a modest and reversible increase in serum creatinine was observed after treatment with INCB039110. However, a dedicated renal function study with INCB039110, assessed by iohexol plasma clearance, conducted in healthy volunteers indicated no change in GFR. In vitro studies were therefore conducted to investigate the interaction of INCB039110 with five transporters that are likely involved in the renal clearance of creatinine. Cell systems expressing individual or multiple transporters were used, including a novel quintuple-transporter model OAT2/OCT2/OCT3/MATE1/MATE2-K. INCB039110 potently inhibited OCT2-mediated uptake of creatinine as well as MATE1-/MATE2-K-mediated efflux of creatinine. Given the interactions of INCB039110 with multiple transporters affecting creatinine uptake and efflux, an integrated system expressing all five transporters was sought; in that system, INCB039110 caused a dose-dependent decrease in transcellular transport of creatinine with weaker net inhibition compared with the effects on individual transporters. In summary, a molecular mechanism for the increase in serum creatinine by INCB039110 has been established. These studies also underline the limitations of using serum creatinine as a marker of renal function. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

Blood Pressure in Children with Chronic Kidney Disease: A Report from the Chronic Kidney Disease in Children Study

PubMed Central

Flynn, Joseph T; Mitsnefes, Mark; Pierce, Christopher; Cole, Steven R; Parekh, Rulan S; Furth, Susan L; Warady, Bradley A

2011-01-01

To characterize the distribution of blood pressure (BP), prevalence and risk factors for hypertension in pediatric chronic kidney disease (CKD), we conducted a cross-sectional analysis of baseline BP's in 432 children (mean age 11y; 60% male; mean glomerular filtration rate [GFR] 44 ml/min/1.73m2) enrolled in the Chronic Kidney Disease in Children cohort study. BP's were obtained using an aneroid sphygmomanometer. GFR was measured by iohexol disappearance. Elevated BP was defined as BP≥90th percentile for age, gender and height. Hypertension was defined as BP≥95th percentile or as self-reported hypertension plus current treatment with antihypertensive medications. For systolic BP, 14% were hypertensive and 11% were pre-hypertensive (BP 90-95th percentile); 68% of subjects with elevated SBP were taking antihypertensive medications. For diastolic BP, 14% were hypertensive, and 9% were pre-hypertensive; 53% of subjects with elevated DBP were taking antihypertensive medications. 54% of subjects had either systolic or diastolic BP≥95th percentile or a history of hypertension plus current antihypertensive use. Characteristics associated with elevated BP included black race, shorter duration of CKD, absence of antihypertensive medication use, and elevated serum potassium. Among subjects receiving antihypertensive treatment, uncontrolled BP was associated with male sex, shorter CKD duration and absence of ACE inhibitor or ARB use. 37% of children with CKD had either elevated systolic or diastolic BP, and 39% of these were not receiving antihypertensives, indicating that hypertension in pediatric CKD may be frequently under- or even un-treated. Treatment with ACE inhibitors or ARB's may improve BP control in these patients. PMID:18725579

Association of Proteinuria with Race, Cause of Chronic Kidney Disease, and Glomerular Filtration Rate in the Chronic Kidney Disease in Children Study

PubMed Central

Wong, Craig S.; Pierce, Christopher B.; Cole, Stephen R.; Warady, Bradley A.; Mak, Robert H.K.; Benador, Nadine M.; Kaskel, Fredrick; Furth, Susan L.; Schwartz, George J.

2009-01-01

Background and objectives: Proteinuria is associated with chronic kidney disease (CKD), and heavy proteinuria predicts a rapid decline in kidney function. However, the epidemiologic distribution of this important biomarker study is not well described in the pediatric CKD population. Design, setting, participants & measurements: This cross-sectional study of North American children with CKD examined the association of proteinuria among the baseline clinical variables in the cohort. Urinary protein-to-creatinine ratios (Up/c) were used to measure level of proteinuria. Results: Of the 419 subjects studied, the median GFR as measured by iohexol disappearance (iGFR) was 42 ml/min per 1.73 m2, median duration of CKD was six yr, and glomerular diseases accounted for 22% of the CKD diagnoses. Twenty-four percent of children had normal range (Up/c <0.2), 62% had significant, and 14% had nephrotic-range proteinuria (Up/c >2.0). A decrease in iGFR was associated with an increase in Up/c. At any level of GFR, a higher Up/c was associated with a glomerular cause of CKD and non-Caucasian race. Among subjects with a glomerular cause of CKD, Up/c was lower in subjects reporting utilization of renin-angiotensin system (RAS) antagonists (median Up/c = 0.93) compared with those who did not (median Up/c = 3.78). Conclusions: Proteinuria is associated with level of iGFR, cause of CKD, and race. The longitudinal study design of Chronic Kidney Disease in Children (CKiD) cohort study and the large number of subjects being studied has created an opportunity to better define the association between proteinuria and CKD progression. PMID:19297612

Multi-Modal Imaging in a Mouse Model of Orthotopic Lung Cancer

PubMed Central

Patel, Priya; Kato, Tatsuya; Ujiie, Hideki; Wada, Hironobu; Lee, Daiyoon; Hu, Hsin-pei; Hirohashi, Kentaro; Ahn, Jin Young; Zheng, Jinzi; Yasufuku, Kazuhiro

2016-01-01

Background Investigation of CF800, a novel PEGylated nano-liposomal imaging agent containing indocyanine green (ICG) and iohexol, for real-time near infrared (NIR) fluorescence and computed tomography (CT) image-guided surgery in an orthotopic lung cancer model in nude mice. Methods CF800 was intravenously administered into 13 mice bearing the H460 orthotopic human lung cancer. At 48 h post-injection (peak imaging agent accumulation time point), ex vivo NIR and CT imaging was performed. A clinical NIR imaging system (SPY®, Novadaq) was used to measure fluorescence intensity of tumor and lung. Tumor-to-background-ratios (TBR) were calculated in inflated and deflated states. The mean Hounsfield unit (HU) of lung tumor was quantified using the CT data set and a semi-automated threshold-based method. Histological evaluation using H&E, the macrophage marker F4/80 and the endothelial cell marker CD31, was performed, and compared to the liposomal fluorescence signal obtained from adjacent tissue sections Results The fluorescence TBR measured when the lung is in the inflated state (2.0 ± 0.58) was significantly greater than in the deflated state (1.42 ± 0.380 (n = 7, p<0.003). Mean fluorescent signal in tumor was highly variable across samples, (49.0 ± 18.8 AU). CT image analysis revealed greater contrast enhancement in lung tumors (a mean increase of 110 ± 57 HU) when CF800 is administered compared to the no contrast enhanced tumors (p = 0.0002). Conclusion Preliminary data suggests that the high fluorescence TBR and CT tumor contrast enhancement provided by CF800 may have clinical utility in localization of lung cancer during CT and NIR image-guided surgery. PMID:27584018

Multi-Modal Imaging in a Mouse Model of Orthotopic Lung Cancer.

PubMed

Patel, Priya; Kato, Tatsuya; Ujiie, Hideki; Wada, Hironobu; Lee, Daiyoon; Hu, Hsin-Pei; Hirohashi, Kentaro; Ahn, Jin Young; Zheng, Jinzi; Yasufuku, Kazuhiro

2016-01-01

Investigation of CF800, a novel PEGylated nano-liposomal imaging agent containing indocyanine green (ICG) and iohexol, for real-time near infrared (NIR) fluorescence and computed tomography (CT) image-guided surgery in an orthotopic lung cancer model in nude mice. CF800 was intravenously administered into 13 mice bearing the H460 orthotopic human lung cancer. At 48 h post-injection (peak imaging agent accumulation time point), ex vivo NIR and CT imaging was performed. A clinical NIR imaging system (SPY®, Novadaq) was used to measure fluorescence intensity of tumor and lung. Tumor-to-background-ratios (TBR) were calculated in inflated and deflated states. The mean Hounsfield unit (HU) of lung tumor was quantified using the CT data set and a semi-automated threshold-based method. Histological evaluation using H&E, the macrophage marker F4/80 and the endothelial cell marker CD31, was performed, and compared to the liposomal fluorescence signal obtained from adjacent tissue sections. The fluorescence TBR measured when the lung is in the inflated state (2.0 ± 0.58) was significantly greater than in the deflated state (1.42 ± 0.380 (n = 7, p<0.003). Mean fluorescent signal in tumor was highly variable across samples, (49.0 ± 18.8 AU). CT image analysis revealed greater contrast enhancement in lung tumors (a mean increase of 110 ± 57 HU) when CF800 is administered compared to the no contrast enhanced tumors (p = 0.0002). Preliminary data suggests that the high fluorescence TBR and CT tumor contrast enhancement provided by CF800 may have clinical utility in localization of lung cancer during CT and NIR image-guided surgery.

Using Multidetector Computed Tomography in a Swine Model to Assess the Effects of Sublingual Nitroglycerin and Intravenous Adenosine on Epicardial Coronary Arteries

PubMed Central

Clarkson, Wesley A; Restrepo, Carlos Santiago; Bauch, Terry D; Rubal, Bernard J

2009-01-01

This study examines the effects of intravenous infusion of adenosine and sublingual nitroglycerin on coronary angiograms obtained by current-generation multidetector computed tomography. We assessed coronary vasodilation at baseline and after intravenous adenosine (140 µg/kg/min) or sublingual nitroglycerin spray (800 µg) in 7 female swine (weight, 40.9 ± 1.4 kg) by using electrocardiogram-gated coronary angiography with a 64-detector scanner (rotation time, 400 ms; 120kV; 400 mA) and intravenous contrast (300 mg/mL iohexol, 4.5 mL/s, 2 mL/kg). Cross-sectional areas of segments in the left anterior descending, circumflex, and right coronary arteries were evaluated in oblique orthogonal views. Images were acquired at an average heart rate of 73 ± 11 beats per minute. Changes in aortic pressure were not significant with nitroglycerin but decreased (approximately 10%) with adenosine. Of the 76 segments analyzed (baseline range, 2 to 39 mm2), 1 distal segment could not be assessed after adenosine. Segment cross-sectional area increased by 11.3% with nitroglycerin but decreased by 9.6% during adenosine infusion. The results of the present study are consistent with the practice of using sublingual nitroglycerin to enhance visualization of epicardial vessels and suggest that intravenous adenosine may hinder coronary artery visualization. This study is the first repeated-measures electrocardiogram-gated CT evaluation to use the same imaging technology to assess changes in coronary cross-sectional area before and after treatment with a vasodilator. The nitroglycerin-associated changes in our swine model were modest in comparison with previously reported human studies. PMID:20034433

Cerebrospinal fluid volume measurements in hydrocephalic rats.

PubMed

Basati, Sukhraaj; Desai, Bhargav; Alaraj, Ali; Charbel, Fady; Linninger, Andreas

2012-10-01

Object Experimental data about the evolution of intracranial volume and pressure in cases of hydrocephalus are limited due to the lack of available monitoring techniques. In this study, the authors validate intracranial CSF volume measurements within the lateral ventricle, while simultaneously using impedance sensors and pressure transducers in hydrocephalic animals. Methods A volume sensor was fabricated and connected to a catheter that was used as a shunt to withdraw CSF. In vitro bench-top calibration experiments were created to provide data for the animal experiments and to validate the sensors. To validate the measurement technique in a physiological system, hydrocephalus was induced in weanling rats by kaolin injection into the cisterna magna. At 28 days after induction, the sensor was implanted into the lateral ventricles. After sealing the skull using dental cement, an acute CSF drainage/infusion protocol consisting of 4 sequential phases was performed with a pump. Implant location was confirmed via radiography using intraventricular iohexol contrast administration. Results Controlled CSF shunting in vivo with hydrocephalic rats resulted in precise and accurate sensor measurements (r = 0.98). Shunting resulted in a 17.3% maximum measurement error between measured volume and actual volume as assessed by a Bland-Altman plot. A secondary outcome confirmed that both ventricular volume and intracranial pressure decreased during CSF shunting and increased during infusion. Ventricular enlargement consistent with successful hydrocephalus induction was confirmed using imaging, as well as postmortem. These results indicate that volume monitoring is feasible for clinical cases of hydrocephalus. Conclusions This work marks a departure from traditional shunting systems currently used to treat hydrocephalus. The overall clinical application is to provide alternative monitoring and treatment options for patients. Future work includes development and testing of a chronic (long-term) volume monitoring system.

Low-dose dual-energy electronic cleansing for fecal-tagging CT Colonography

NASA Astrophysics Data System (ADS)

Cai, Wenli; Zhang, Da; Lee, June-Goo; Yoshida, Hiroyuki

2013-03-01

Dual-energy electronic cleansing (DE-EC) provides a promising means for cleansing the tagged fecal materials in fecaltagging CT colonography (CTC). However, the increased radiation dose due to the double exposures in dual-energy CTC (DE-CTC) scanning is a major limitation for the use of DE-EC in clinical practice. The purpose of this study was to develop and evaluate a low-dose DE-EC scheme in fecal-tagging DE-CTC. In this study, a custom-made anthropomorphic colon phantom, which was filled with simulated tagged materials by non-ionic iodinated contrast agent (Omnipaque iohexol, GE Healthcare), was scanned by a dual-source CT scanner (SOMATON Definition Flash, Siemens Healthcare) at two photon energies: 80 kVp and 140 kVp with nine different tube current settings ranging from 12 to 74 mAs for 140 kVp, and then reconstructed by soft-tissue reconstruction kernel (B30f). The DE-CTC images were subjected to a low-dose DE-EC scheme. First, our image-space DE-CTC denoising filter was applied for reduction of image noise. Then, the noise-reduced images were processed by a virtual lumen tagging method for reduction of partial volume effect and tagging inhomogeneity. The results were compared with the registered CTC images of native phantom without fillings. Preliminary results showed that our low-dose DE-EC scheme achieved the cleansing ratios, defined by the proportion of the cleansed voxels in the tagging mask, between 93.18% (12 mAs) and 96.62% (74 mAs). Also, the soft-tissue preservation ratios, defined by the proportion of the persevered voxels in the soft-tissue mask, were maintained in the range between 94.67% and 96.41%.

Blood Pressure and Metabolic Effects of Acetyl-l-Carnitine in Type 2 Diabetes: DIABASI Randomized Controlled Trial.

PubMed

Parvanova, Aneliya; Trillini, Matias; Podestà, Manuel A; Iliev, Ilian P; Aparicio, Carolina; Perna, Annalisa; Peraro, Francesco; Rubis, Nadia; Gaspari, Flavio; Cannata, Antonio; Ferrari, Silvia; Bossi, Antonio C; Trevisan, Roberto; Parameswaran, Sreejith; Chávez-Iñiguez, Jonathan S; Masnic, Fahrudin; Seck, Sidy Mohamed; Jiamjariyaporn, Teerayuth; Cortinovis, Monica; Perico, Luca; Sharma, Kanishka; Remuzzi, Giuseppe; Ruggenenti, Piero; Warnock, David G

2018-05-01

Acetyl-l-carnitine (ALC), a mitochondrial carrier involved in lipid oxidation and glucose metabolism, decreased systolic blood pressure (SBP), and ameliorated insulin sensitivity in hypertensive nondiabetic subjects at high cardiovascular risk. To assess the effects of ALC on SBP and glycemic and lipid control in patients with hypertension, type 2 diabetes mellitus (T2D), and dyslipidemia on background statin therapy. After 4-week run-in period and stratification according to previous statin therapy, patients were randomized to 6-month, double-blind treatment with ALC or placebo added-on simvastatin. Five diabetology units and one clinical research center in Italy. Two hundred twenty-nine patients with hypertension and dyslipidemic T2D >40 years with stable background antihypertensive, hypoglycemic, and statin therapy and serum creatinine <1.5 mg/dL. Oral ALC 1000 mg or placebo twice daily on top of stable simvastatin therapy. Primary outcome was SBP. Secondary outcomes included lipid and glycemic profiles. Total-body glucose disposal rate and glomerular filtration rate were measured in subgroups by hyperinsulinemic-euglycemic clamp and iohexol plasma clearance, respectively. SBP did not significantly change after 6-month treatment with ALC compared with placebo (-2.09 mm Hg vs -3.57 mm Hg, P = 0.9539). Serum cholesterol, triglycerides, and lipoprotein(a), as well as blood glucose, glycated hemoglobin, fasting insulin levels, homeostatic model assessment of insulin resistance index, glucose disposal rate, and glomerular filtration rate did not significantly differ between treatments. Adverse events were comparable between groups. Six-month oral ALC supplementation did not affect blood pressure, lipid and glycemic control, insulin sensitivity and kidney function in hypertensive normoalbuminuric and microalbuminuric T2D patients on background statin therapy.

New insights into the effects of support matrix on the removal of organic micro-pollutants and the microbial community in constructed wetlands.

PubMed

Zhang, Liang; Lyu, Tao; Ramírez Vargas, Carlos Andrés; Arias, Carlos A; Carvalho, Pedro N; Brix, Hans

2018-09-01

Constructed wetlands (CWs) are an eco-friendly and cost-effective technology to remove organic micro-pollutants (OMPs) from wastewater. The support matrix is an important component in CWs as it has a primary role in the growth and development of plants and microbes. However, the roles of the support matrix in CWs in removing OMPs have not been systematically studied. Therefore, in this study, six common materials (sand, zeolite, blast iron slag, petcoke, polonite and crushed autoclaved aerated concrete (CAAC)) as support matrixes were firstly investigated by batch tests to explore their adsorption capacities to selected OMPs (ibuprofen, iohexol, tebuconazole and imazalil). Results showed that the adsorption capacities of the materials were low (at the level of μg/g) compared to well-known sorbents (at the level of mg/g), such as activated carbon and carbon nanotubes. Columns packed with the six materials, respectively, were then built up to study the effects of different materials on microbial community. In the medium-term study (66 days), the removal of four OMPs in all the columns increased by 2-58% from day 25 to day 66, and was mainly attributed to microbial degradation. Furthermore, Community-level physiological profiling (CLPP) analysis indicates that material presence shaped the microbial community metabolic function not only in the interstitial water but also in the biofilm. Overall, all the findings demonstrate that although the adsorption capacities of the common materials are low, they may be a driver to improve the removal of OMPs by altering microbial community function in CWs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Standardization of a Videofluoroscopic Swallow Study Protocol to Investigate Dysphagia in Dogs.

PubMed

Harris, R A; Grobman, M E; Allen, M J; Schachtel, J; Rawson, N E; Bennett, B; Ledyayev, J; Hopewell, B; Coates, J R; Reinero, C R; Lever, T E

2017-03-01

Videofluoroscopic swallow study (VFSS) is the gold standard for diagnosis of dysphagia in veterinary medicine but lacks standardized protocols that emulate physiologic feeding practices. Age impacts swallow function in humans but has not been evaluated by VFSS in dogs. To develop a protocol with custom kennels designed to allow free-feeding of 3 optimized formulations of contrast media and diets that address limitations of current VFSS protocols. We hypothesized that dogs evaluated by a free-feeding VFSS protocol would show differences in objective swallow metrics based on age. Healthy juvenile, adult, and geriatric dogs (n = 24). Prospective, experimental study. Custom kennels were developed to maintain natural feeding behaviors during VFSS. Three food consistencies (thin liquid, pureed food, and dry kibble) were formulated with either iohexol or barium to maximize palatability and voluntary prehension. Dogs were evaluated by 16 swallow metrics and compared across age groups. Development of a standardized VFSS protocol resulted in successful collection of swallow data in healthy dogs. No significant differences in swallow metrics were observed among age groups. Substantial variability was observed in healthy dogs when evaluated under these physiologic conditions. Features typically attributed to pathologic states, such as gastric reflux, were seen in healthy dogs. Development of a VFSS protocol that reflects natural feeding practices may allow emulation of physiology resulting in clinical signs of dysphagia. Age did not result in significant changes in swallow metrics, but additional studies are needed, particularly in light of substantial normal variation. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Oxidation of iopamidol with ferrate (Fe(VI)): Kinetics and formation of toxic iodinated disinfection by-products.

PubMed

Dong, Huiyu; Qiang, Zhimin; Liu, Shaogang; Li, Jin; Yu, Jianwei; Qu, Jiuhui

2018-03-01

Presence of iodinated X-ray contrast media (ICMs) in source water is of high concern, because of their potential to form highly toxic iodinated disinfection by-products (I-DBPs). This study investigated kinetics, mechanisms and products for oxidation of one ICMs, iopamidol (IPM) by ferrate (Fe(VI)). The obtained apparent second-order rate constants for oxidation of IPM by Fe(VI) ranged from 0.7 M -1  s -1 to 74.6 M -1  s -1  at pH 6.0-10.0, which were highly dependent on pH. It was found that the oxidation of IPM by Fe(VI) led to the formation of highly toxic I-DBPs. Iodoform (IF), iodoacetic acid and triiodoacetic acid formations were observed during the oxidation and IF dominated the formed I-DBPs. The formation of I-DBPs was also governed by pH and the maximum formation of I-DBPs occurred at pH 9.0. Transformation pathways of IPM by Fe(VI) oxidation were speculated to proceed through deiodination, amide hydrolysis and oxidation of amine reactions. The deiodination reaction during the oxidation of IPM by Fe(VI) contributed to the formation of I-DBPs. The formation of I-DBPs during the oxidation of IPM by Fe(VI) was significantly higher than those of iohexol, diatrizoate and iopromide, which was consistent with the lowest molecular orbital energy gap of IPM. Although Fe(VI) is considered as a green oxidant, the formation of highly toxic I-DBPs during the oxidation of IPM should receive great attention. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of arterial input functions measured from ultra-fast dynamic contrast enhanced MRI and dynamic contrast enhanced computed tomography in prostate cancer patients

NASA Astrophysics Data System (ADS)

Wang, Shiyang; Lu, Zhengfeng; Fan, Xiaobing; Medved, Milica; Jiang, Xia; Sammet, Steffen; Yousuf, Ambereen; Pineda, Federico; Oto, Aytekin; Karczmar, Gregory S.

2018-02-01

The purpose of this study was to evaluate the accuracy of arterial input functions (AIFs) measured from dynamic contrast enhanced (DCE) MRI following a low dose of contrast media injection. The AIFs measured from DCE computed tomography (CT) were used as ‘gold standard’. A total of twenty patients received CT and MRI scans on the same day. Patients received 120 ml Iohexol in DCE-CT and a low dose of (0.015 mM kg-1) of gadobenate dimeglumine in DCE-MRI. The AIFs were measured in the iliac artery and normalized to the CT and MRI contrast agent doses. To correct for different temporal resolution and sampling periods of CT and MRI, an empirical mathematical model (EMM) was used to fit the AIFs first. Then numerical AIFs (AIFCT and AIFMRI) were calculated based on fitting parameters. The AIFMRI was convolved with a ‘contrast agent injection’ function (AIFMRICON ) to correct for the difference between MRI and CT contrast agent injection times (~1.5 s versus 30 s). The results show that the EMMs accurately fitted AIFs measured from CT and MRI. There was no significant difference (p  >  0.05) between the maximum peak amplitude of AIFs from CT (22.1  ±  4.1 mM/dose) and MRI after convolution (22.3  ±  5.2 mM/dose). The shapes of the AIFCT and AIFMRICON were very similar. Our results demonstrated that AIFs can be accurately measured by MRI following low dose contrast agent injection.

In vivo diffusion characteristics following perineural injection of the deep branch of the lateral plantar nerve with mepivacaine or iohexol in horses.

PubMed

Contino, E K; King, M R; Valdés-Martínez, A; McIlwraith, C W

2015-03-01

Hindlimb proximal suspensory desmopathy is a common injury of sport horses but diagnosis can be difficult because diagnostic analgesia of the region lacks specificity. Perineural analgesia of the deep branch of the lateral plantar nerve (DBLPN) has been proposed as a more specific method of isolating pain of the proximal aspect of the suspensory ligament but the technique has not been evaluated in vivo. To determine the extent of diffusion of contrast medium and mepivacaine following DBLPN analgesia using a single-needle injection technique and to determine if there is inadvertent involvement of the tarsal sheath and/or tarsometatarsal (TMT) joint using this technique. In vivo experimental study. Perineural injection of the DBLPN was performed in 16 limbs with 3 ml of either mepivacaine hydrochloride or positive contrast medium. Contrast medium-injected limbs were radiographed 5, 15, and 30 min post injection and diffusion characteristics were described. In mepivacaine-injected limbs, synovial fluid from the TMT joint was obtained 10 and 20 min post injection and mepivacaine concentrations were analysed. At 5, 15 and 30 min post injection, the contrast medium extended, on average, 19.6, 20.6 and 21.0 mm proximal and 38.0, 43.5 and 51.9 mm distal to the injection site, respectively. Three of 8 (37.5%) limbs had evidence of contrast medium in the tarsal sheath. Two of 8 (25%) limbs had mepivacaine concentrations within the TMT joint sufficient to produce analgesia (>300 mg/l) at 10 min post injection. Contrast medium diffused further in a distal direction than in a proximal direction. Analgesia of the DBLPN can result in inadvertent involvement of the tarsal sheath and/or TMT joint. © 2014 EVJ Ltd.

Performance of Creatinine and Cystatin C GFR Estimating Equations in an HIV-positive population on Antiretrovirals

PubMed Central

INKER, Lesley A; WYATT, Christina; CREAMER, Rebecca; HELLINGER, James; HOTTA, Matthew; LEPPO, Maia; LEVEY, Andrew S; OKPARAVERO, Aghogho; GRAHAM, Hiba; SAVAGE, Karen; SCHMID, Christopher H; TIGHIOUART, Hocine; WALLACH, Fran; KRISHNASAMI, Zipporah

2013-01-01

Objective To evaluate the performance of CKD-EPI creatinine, cystatin C and creatinine-cystatin C estimating equations in HIV-positive patients. Methods We evaluated the performance of the MDRD Study and CKD-EPI creatinine 2009, CKD-EPI cystatin C 2012 and CKD-EPI creatinine-cystatin C 2012 glomerular filtration rate (GFR) estimating equations compared to GFR measured using plasma clearance of iohexol in 200 HIV-positive patients on stable antiretroviral therapy. Creatinine and cystatin C assays were standardized to certified reference materials. Results Of the 200 participants, median (IQR) CD4 count was 536 (421) and 61% had an undetectable HIV-viral load. Mean (SD) measured GFR (mGFR) was 87 (26) ml/min/1.73m2. All CKD-EPI equations performed better than the MDRD Study equation. All three CKD-EPI equations had similar bias and precision. The cystatin C equation was not more accurate than the creatinine equation. The creatinine-cystatin C equation was significantly more accurate than the cystatin C equation and there was a trend toward greater accuracy than the creatinine equation. Accuracy was equal or better in most subgroups with the combined equation compared to either alone. Conclusions The CKD-EPI cystatin C equation does not appear to be more accurate than the CKD-EPI creatinine equation in patients who are HIV-positive, supporting the use of the CKD-EPI creatinine equation for routine clinical care for use in North American populations with HIV. The use of both filtration markers together as a confirmatory test for decreased estimated GFR based on creatinine in individuals who are HIV-positive requires further study. PMID:22842844

Aminoglycoside exposure and renal function before lung transplantation in adult cystic fibrosis patients.

PubMed

Novel-Catin, Etienne; Pelletier, Solenne; Reynaud, Quitterie; Nove-Josserand, Raphaele; Durupt, Stephane; Dubourg, Laurence; Durieu, Isabelle; Fouque, Denis

2018-04-18

Patients with cystic fibrosis (CF) are at risk of kidney injury even before undergoing lung transplantation, because of prolonged exposure to aminoglycosides (AGs), chronic dehydration and complications of diabetes mellitus. The usual equations estimating the glomerular filtration rate (GFR), such as Cockcroft-Gault and Modification of Diet in Renal Disease, are not adapted to the CF population due to patients' low body weight and reduced muscle mass. The aim of this study was to precisely measure GFR in adult CF patients and to see whether repeated AG treatment would impair renal function before lung transplantation. Inulin or iohexol clearances were performed in 25 adult CF patients when they entered the lung transplant waiting list. No patient was treated with AGs at the time of GFR measurement. Body mass index (BMI), history of diabetes mellitus and blood pressure were recorded. Exposure to intravenous (IV) AGs within 5 years prior to the GFR measurement was obtained from the patient's medical files. Urine samples were collected to check for albuminuria and proteinuria. The population was predominantly female (67%). The mean age was 32 years, the mean BMI was 19 kg/m2 and 28% had CF-related diabetes. Median exposure to IV AG within 5 years before GFR measurement was 155 days with a mean dosage of 7.7mg/kg/day. The mean measured GFR was 106 mL/min/1.73 m2 and the mean estimated GFR according to the Chronic Kidney Disease Epidemiology Collaboration formula was 124 mL/min/1.73 m2. Despite prolonged exposure to high-dose IV AG, no decline in GFR was observed in these patients.

Influence of needle position on lumbar segmental nerve root block selectivity.

PubMed

Wolff, André P; Groen, Gerbrand J; Wilder-Smith, Oliver H

2006-01-01

In patients with chronic low back pain radiating to the leg, segmental nerve root blocks (SNRBs) are performed to predict surgical outcome and identify the putative symptomatic spinal nerve. Epidural spread may lead to false interpretation, affecting clinical decision making. Systematic fluoroscopic analysis of epidural local anesthetic spread and its relationship to needle tip location has not been published to date. Study aims include assessment of epidural local anesthetic spread and its relationship to needle position during fluoroscopy-assisted blocks. Patients scheduled for L4, L5, and S1 blocks were included in this prospective observational study. Under fluoroscopy and electrostimulation, they received 0.5 mL of a mixture containing lidocaine 5 mg and iohexol 75 mg. X-rays with needle tip and contrast were scored for no epidural spread (grade 0), local spread epidurally (grade 1), or to adjacent nerve roots (grade 2). Sixty-five patients were analyzed for epidural spread, 62 for needle position. Grade 1 epidural spread occurred in 47% of L4 and 28% of L5 blocks and grade 2 spread in 3 blocks (5%; L5 n = 1, S1 n = 2). For lumbar blocks, the needle was most frequently found in the lateral upper half of the intervertebral foramen. Epidural spread occurred more frequently with medial needle positions (P = .06). The findings suggest (P = .06) that the risk of grade 1 and 2 lumbar epidural spread, which results in decreased SNRB selectivity, is greater with medial needle positions in the intervertebral foramen. The variability in anatomic position of the dorsal root ganglion necessitates electrostimulation to guide SNRB in addition to fluoroscopy.

Measured glomerular filtration rate does not improve prediction of mortality by cystatin C and creatinine.

PubMed

Sundin, Per-Ola; Sjöström, Per; Jones, Ian; Olsson, Lovisa A; Udumyan, Ruzan; Grubb, Anders; Lindström, Veronica; Montgomery, Scott

2017-04-01

Cystatin C may add explanatory power for associations with mortality in combination with other filtration markers, possibly indicating pathways other than glomerular filtration rate (GFR). However, this has not been firmly established since interpretation of associations independent of measured GFR (mGFR) is limited by potential multicollinearity between markers of GFR. The primary aim of this study was to assess associations between cystatin C and mortality, independent of mGFR. A secondary aim was to evaluate the utility of combining cystatin C and creatinine to predict mortality risk. Cox regression was used to assess the associations of cystatin C and creatinine with mortality in 1157 individuals referred for assessment of plasma clearance of iohexol. Since cystatin C and creatinine are inversely related to mGFR, cystatin C - 1 and creatinine - 1 were used. After adjustment for mGFR, lower cystatin C - 1 (higher cystatin C concentration) and higher creatinine - 1 (lower creatinine concentration) were independently associated with increased mortality. When nested models were compared, avoiding the potential influence of multicollinearity, the independence of the associations was supported. Among models combining the markers of GFR, adjusted for demographic factors and comorbidity, cystatin C - 1 and creatinine - 1 combined explained the largest proportion of variance in associations with mortality risk ( R 2  = 0.61). Addition of mGFR did not improve the model. Our results suggest that both creatinine and cystatin C have independent associations with mortality not explained entirely by mGFR and that mGFR does not offer a more precise mortality risk assessment than these endogenous filtration markers combined. © The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Distribution and relevance of iodinated X-ray contrast media and iodinated trihalomethanes in an aquatic environment.

PubMed

Xu, Zhifa; Li, Xia; Hu, Xialin; Yin, Daqiang

2017-10-01

Distribution and relevance of iodinated X-ray contrast media (ICM) and iodinated disinfection byproducts (I-DBPs) in a real aquatic environment have been rarely documented. In this paper, some ICM were proven to be strongly correlated with I-DBPs through investigation of five ICM and five iodinated trihalomethanes (I-THMs) in surface water and two drinking water treatment plants (DWTPs) of the Yangtze River Delta, China. The total ICM concentrations in Taihu Lake and the Huangpu River ranged from 88.7 to 131 ng L -1 and 102-252 ng L -1 , respectively. While the total I-THM concentrations ranged from 128 to 967 ng L -1 in Taihu Lake and 267-680 ng L -1 in the Huangpu River. Iohexol, the dominant ICM, showed significant positive correlation (p < 0.01) with CHClI 2 in Taihu Lake. Iopamidol and iomeprol correlated positively (p < 0.01) with some I-THMs in the Huangpu River. The observed pronounced correlations between ICM and I-THMs indicated that ICM play an important role in the formation of I-THMs in a real aquatic environment. Characteristics of the I-THM species distributions indicated that I-THMs may be transformed by natural conditions. Both DWTPs showed negligible removal efficiencies for total ICM (<20%). Strikingly high concentrations of total I-THMs were observed in the finished water (2848 ng L -1 in conventional DWTP and 356 ng L -1 in advanced DWTP). Obvious transformation of ICM to I-THMs was observed during the chlorination and ozonization processes in DWTPs. We suggest that ICM is an important source for I-DBP formation in the real aquatic environment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Utility of 16-MDCT angiography for comprehensive preoperative vascular evaluation of laparoscopic renal donors.

PubMed

Raman, Steven S; Pojchamarnwiputh, Suwalee; Muangsomboon, Kobkun; Schulam, Peter G; Gritsch, H Albin; Lu, David S K

2006-06-01

Our objective was to determine the efficacy of 16-MDCT angiography in preoperative evaluation of vascular anatomy of laparoscopic renal donors. Fifty-five consecutive renal donors (25 men and 30 women) underwent 16-MDCT angiography followed by donor nephrectomy. In the arterial and nephrographic phases, images were acquired with 60% overlap and 0.6-mm reconstruction in both phases after 120 mL of iohexol was injected at 4 mL/sec. On a 3D workstation, images were evaluated retrospectively by two abdominal imagers blinded to surgical results with respect to number and branching pattern of renal arteries and major and minor renal veins. These CT angiography results were compared with surgical findings. The surgically confirmed sensitivity of both reviewers (1 and 2) using the MDCT data for detection of renal arteries was 98.5% (65 of 66), and accuracies were 97.0% for reviewer 1 and 95.5% for reviewer 2. Sensitivity and accuracy detection of renal veins was 97% (61 of 63) and 98% (62 of 63) for reviewer 1 and reviewer 2, respectively. Sensitivity and accuracy detection of early arterial bifurcation (< 2 cm from aorta) was 100% (14 of 14), and sensitivity in detection of late venous confluence (< 1.5 cm from aorta) was 100% (8 of 8). All major renal venous variants were identified; reviewer 1 identified 78% (18 of 23) minor venous variants, and reviewer 2 identified 83% (19 of 23) minor venous variants. There were no hemorrhagic complications at surgery. Excellent agreement between reviewers (kappa = 0.92-0.97) was achieved for detection of normal and variant anatomy. 16-MDCT angiography enabled excellent preoperative detection of arterial anatomy and venous laparoscopic donor nephrectomy.

Assessing Glomerular Filtration Rate in Hospitalized Patients: A Comparison Between CKD-EPI and Four Cystatin C-Based Equations

PubMed Central

de la Torre, Judith; Ramos, Natalia; Quiroz, Augusto; Garjau, Maria; Torres, Irina; Azancot, M. Antonia; López, Montserrat; Sobrado, Ana

2011-01-01

Summary Background and objectives A specific method is required for estimating glomerular filtration rate GFR in hospitalized patients. Our objective was to validate the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and four cystatin C (CysC)–based equations in this setting. Design, setting, participants, & measurements This was an epidemiologic, cross-sectional study in a random sample of hospitalized patients (n = 3114). We studied the accuracy of the CKD-EPI and four CysC-based equations—based on (1) CysC alone or (2) adjusted by gender; (3) age, gender, and race; and (4) age, gender, race, and creatinine, respectively—compared with GFR measured by iohexol clearance (mGFR). Clinical, biochemical, and nutritional data were also collected. Results The CysC equation 3 significantly overestimated the GFR (bias of 7.4 ml/min per 1.73 m2). Most of the error in creatinine-based equations was attributable to calculated muscle mass, which depended on patient's nutritional status. In patients without malnutrition or reduced body surface area, the CKD-EPI equation adequately estimated GFR. Equations based on CysC gave more precise mGFR estimates when malnutrition, extensive reduction of body surface area, or loss of muscle mass were present (biases of 1 and 1.3 ml/min per 1.73 m2 for equations 2 and 4, respectively, versus 5.9 ml/min per 1.73 m2 for CKD-EPI). Conclusions These results suggest that the use of equations based on CysC and gender, or CysC, age, gender, and race, is more appropriate in hospitalized patients to estimate GFR, since these equations are much less dependent on patient's nutritional status or muscle mass than the CKD-EPI equation. PMID:21852668

Intratympanic Iodine Contrast Injection Diffuses Across the Round Window Membrane Allowing for Perilymphatic CT Volume Acquisition Imaging

PubMed Central

Abt, Nicholas B.; Lehar, Mohamed; Guajardo, Carolina Trevino; Penninger, Richard T.; Ward, Bryan K.; Pearl, Monica S.; Carey, John P.

2016-01-01

Hypothesis Whether the RWM is permeable to iodine-based contrast agents (IBCA) is unknown; therefore, our goal was to determine if IBCAs could diffuse through the RWM using CT volume acquisition imaging. Introduction Imaging of hydrops in the living human ear has attracted recent interest. Intratympanic (IT) injection has shown gadolinium's ability to diffuse through the round window membrane (RWM), enhancing the perilymphatic space. Methods Four unfixed human cadaver temporal bones underwent intratympanic IBCA injection using three sequentially studied methods. The first method was direct IT injection. The second method used direct RWM visualization via tympanomeatal flap for IBCA-soaked absorbable gelatin pledget placement. In the third method, the middle ear was filled with contrast after flap elevation. Volume acquisition CT images were obtained immediately post-exposure, and at 1, 6, and 24 hour intervals. Post-processing was accomplished using color ramping and subtraction imaging. Results Following the third method, positive RWM and perilymphatic enhancement were seen with endolymph sparing. Gray scale and color ramp multiplanar reconstructions displayed increased signal within the cochlea compared to pre-contrast imaging. The cochlea was measured for attenuation differences compared to pure water, revealing a pre-injection average of −1,103 HU and a post-injection average of 338 HU. Subtraction imaging shows enhancement remaining within the cochlear space, Eustachian tube, middle ear epithelial lining, and mastoid. Conclusions Iohexol iodine contrast is able to diffuse across the RWM. Volume acquisition CT imaging was able to detect perilymphatic enhancement at 0.5mm slice thickness. The clinical application of IBCA IT injection appears promising but requires further safety studies. PMID:26859543

A sensitive multi-residue method for the determination of 35 micropollutants including pharmaceuticals, iodinated contrast media and pesticides in water.

PubMed

Valls-Cantenys, Carme; Scheurer, Marco; Iglesias, Mònica; Sacher, Frank; Brauch, Heinz-Jürgen; Salvadó, Victoria

2016-09-01

A sensitive, multi-residue method using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed to determine a representative group of 35 analytes, including corrosion inhibitors, pesticides and pharmaceuticals such as analgesic and anti-inflammatory drugs, five iodinated contrast media, β-blockers and some of their metabolites and transformation products in water samples. Few other methods are capable of determining such a broad range of contrast media together with other analytes. We studied the parameters affecting the extraction of the target analytes, including sorbent selection and extraction conditions, their chromatographic separation (mobile phase composition and column) and detection conditions using two ionisation sources: electrospray ionisation (ESI) and atmospheric pressure chemical ionisation (APCI). In order to correct matrix effects, a total of 20 surrogate/internal standards were used. ESI was found to have better sensitivity than APCI. Recoveries ranging from 79 to 134 % for tap water and 66 to 144 % for surface water were obtained. Intra-day precision, calculated as relative standard deviation, was below 34 % for tap water and below 21 % for surface water, groundwater and effluent wastewater. Method quantification limits (MQL) were in the low ng L(-1) range, except for the contrast agents iomeprol, amidotrizoic acid and iohexol (22, 25.5 and 17.9 ng L(-1), respectively). Finally, the method was applied to the analysis of 56 real water samples as part of the validation procedure. All of the compounds were detected in at least some of the water samples analysed. Graphical Abstract Multi-residue method for the determination of micropollutants including pharmaceuticals, iodinated contrast media and pesticides in waters by LC-MS/MS.

A meta-analysis of the risk of total cardiovascular events of isosmolar iodixanol compared with low-osmolar contrast media.

PubMed

Zhang, Bu-Chun; Wu, Qiang; Wang, Cheng; Li, Dong-Ye; Wang, Zhi-Rong

2014-04-01

The iso-osmolar contrast agent iodixanol may be associated with a lower incidence of cardiac events than low-osmolar contrast media (LOCM), but previous trials have yielded mixed results. To compare the risk of total cardiovascular events of the iso-osmolar contrast medium, iodixanol, to LOCM. Medical literature databases were searched to identify comparisons between iodixanol and LOCM with cardiovascular events as a primary endpoint. A random-effects model was used to obtain pooled odds ratio (OR) for within-hospital and 30-day events. A total of 2 prospective cross-sectional studies and 11 randomized controlled trials (RCTs) (covering 6859 subjects) met our criteria. There was no significant difference in the incidence of within-hospital and 30-day cardiovascular events when iodixanol was compared with LOCM, with pooled OR of 0.72 (95%CI 0.49-1.06, p=0.09) and 1.19 (95%CI 0.70-2.02, p=0.53), respectively. Subgroup analysis showed no relative difference when iodixanol was compared with ioxaglate (OR=0.92, 95%CI 0.50-1.70, p=0.80) and iohexol (OR=0.75, 95%CI 0.48-1.17, p=0.21). However, a reduction in the within-hospital cardiovascular events was observed when iodixanol was compared with LOCM in the RCT subgroup (OR=0.65, 95%CI 0.44-0.96, p=0.03). Sensitivity analyses revealed that three studies had a strong impact on the association of within-hospital cardiovascular events between iodixanol and LOCM. Meta-regression analysis failed to account for heterogeneity. No publication bias was detected. This meta-analysis demonstrates that there is no conclusive evidence that iodixanol is superior to LOCM overall with regard to fewer cardiovascular events. Copyright © 2014. Published by Elsevier Ltd.

Estimating Glomerular Filtration Rate in Kidney Transplant Recipients: Comparing a Novel Equation With Commonly Used Equations in this Population

PubMed Central

Salvador, Cathrin L.; Hartmann, Anders; Åsberg, Anders; Bergan, Stein; Rowe, Alexander D.; Mørkrid, Lars

2017-01-01

Background Assessment of glomerular filtration rate (GFR) is important in kidney transplantation. The aim was to develop a kidney transplant specific equation for estimating GFR and evaluate against published equations commonly used for GFR estimation in these patients. Methods Adult kidney recipients (n = 594) were included, and blood samples were collected 10 weeks posttransplant. GFR was measured by 51Cr-ethylenediaminetetraacetic acid clearance. Patients were randomized into a reference group (n = 297) to generate a new equation and a test group (n = 297) for comparing it with 7 alternative equations. Results Two thirds of the test group were males. The median (2.5-97.5 percentile) age was 52 (23-75) years, cystatin C, 1.63 (1.00-3.04) mg/L; creatinine, 117 (63-220) μmol/L; and measured GFR, 51 (29-78) mL/min per 1.73 m2. We also performed external evaluation in 133 recipients without the use of trimethoprim, using iohexol clearance for measured GFR. The Modification of Diet in Renal Disease equation was the most accurate of the creatinine-equations. The new equation, estimated GFR (eGFR) = 991.15 × (1.120sex/([age0.097] × [cystatin C0.306] × [creatinine0.527]); where sex is denoted: 0, female; 1, male, demonstrating a better accuracy with a low bias as well as good precision compared with reference equations. Trimethoprim did not influence the performance of the new equation. Conclusions The new equation demonstrated superior accuracy, precision, and low bias. The Modification of Diet in Renal Disease equation was the most accurate of the creatinine-based equations. PMID:29536033

Estimating glomerular filtration rate (GFR) in children. The average between a cystatin C- and a creatinine-based equation improves estimation of GFR in both children and adults and enables diagnosing Shrunken Pore Syndrome.

PubMed

Leion, Felicia; Hegbrant, Josefine; den Bakker, Emil; Jonsson, Magnus; Abrahamson, Magnus; Nyman, Ulf; Björk, Jonas; Lindström, Veronica; Larsson, Anders; Bökenkamp, Arend; Grubb, Anders

2017-09-01

Estimating glomerular filtration rate (GFR) in adults by using the average of values obtained by a cystatin C- (eGFR cystatin C ) and a creatinine-based (eGFR creatinine ) equation shows at least the same diagnostic performance as GFR estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparison of eGFR cystatin C and eGFR creatinine plays a pivotal role in the diagnosis of Shrunken Pore Syndrome, where low eGFR cystatin C compared to eGFR creatinine has been associated with higher mortality in adults. The present study was undertaken to elucidate if this concept can also be applied in children. Using iohexol and inulin clearance as gold standard in 702 children, we studied the diagnostic performance of 10 creatinine-based, 5 cystatin C-based and 3 combined cystatin C-creatinine eGFR equations and compared them to the result of the average of 9 pairs of a eGFR cystatin C and a eGFR creatinine estimate. While creatinine-based GFR estimations are unsuitable in children unless calibrated in a pediatric or mixed pediatric-adult population, cystatin C-based estimations in general performed well in children. The average of a suitable creatinine-based and a cystatin C-based equation generally displayed a better diagnostic performance than estimates obtained by equations using only one of these analytes or by complex equations using both analytes. Comparing eGFR cystatin and eGFR creatinine may help identify pediatric patients with Shrunken Pore Syndrome.

Adverse reactions to contrast media: an analysis of spontaneous reports in the database of the pharmacovigilance programme of India.

PubMed

Kalaiselvan, Vivekanandan; Sharma, Surbhi; Singh, Gyanendra Nath

2014-09-01

Contrast media are used widely to improve medical imaging. Like all other pharmaceuticals, these agents are not completely devoid of risk, and continuous monitoring of adverse reactions with these agents is important. Spontaneous reporting is the simplest method for understanding the safety profile of pharmaceutical products after their approval. Our objective was to identify the pattern and characteristics of adverse reactions attributed to contrast media in the Indian population reported to the National Coordination Centre for the Pharmacovigilance Programme of India (NCC-PvPI). Individual case safety reports (ICSRs) attributed to contrast media submitted spontaneously to the NCC-PvPI were extracted from the database for July 2010 to September 2013. We analysed these reports for information related to reporter's professional category, patient's age and sex, reporter's diagnosis of the reaction, seriousness of the reaction, type of contrast media exposure, system organ class (SOC) affected (as described in World Health Organization Adverse Reaction Terminology [WHO-ART]) and outcome. Of the total 59,915 ICSRs in the database, 415 (0.7%) were suspected adverse reactions to contrast media; 44 reports were serious, including three fatal cases. The most affected SOCs were skin and appendage disorders, body as a whole-general disorders, gastrointestinal system disorders and respiratory system disorders. Hypersensitivity reactions were reported in the majority of ICSRs. The contrast media with the highest number of reports were iohexol (40.7%), iomeprol (17.8%), iopamidol (12%) and diatrizoate (12%). Most of the reactions to contrast media were allergic-like, and no previously unrecognised adverse reactions were observed in the Indian population. Further data and increased awareness among healthcare professionals is required to signal and prevent the consequences of adverse reactions attributed to contrast media.

Feasibility of dual-low scheme combined with iterative reconstruction technique in acute cerebral infarction volume CT whole brain perfusion imaging.

PubMed

Wang, Tao; Gong, Yi; Shi, Yibing; Hua, Rong; Zhang, Qingshan

2017-07-01

The feasibility of application of low-concentration contrast agent and low tube voltage combined with iterative reconstruction in whole brain computed tomography perfusion (CTP) imaging of patients with acute cerebral infarction was investigated. Fifty-nine patients who underwent whole brain CTP examination and diagnosed with acute cerebral infarction from September 2014 to March 2016 were selected. Patients were randomly divided into groups A and B. There were 28 cases in group A [tube voltage, 100 kV; contrast agent, iohexol (350 mg I/ml), reconstructed by filtered back projection] and 31 cases in group B [tube voltage, 80 kV; contrast agent, iodixanol (270 mg I/ml), reconstructed by algebraic reconstruction technique]. The artery CT value, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), dose length product, effective dose (ED) of radiation and brain iodine intake of both groups were measured and statistically analyzed. Two physicians carried out kappa (κ) analysis on the consistency of image quality evaluation. The difference in subjective image quality evaluation between the groups was tested by χ 2 . The differences in CT value, SNR, CNR, CTP and CT angiography subjective image quality evaluation between both groups were not statistically significant (P>0.05); the diagnosis rate of the acute infarcts between the two groups was not significantly different; while the ED and iodine intake in group B (dual low-dose group) were lower than group A. In conclusion, combination of low tube voltage and iterative reconstruction technique, and application of low-concentration contrast agent (270 mg I/ml) in whole brain CTP examination reduced ED and iodine intake without compromising image quality, thereby reducing the risk of contrast-induced nephropathy.

Very Low Intravenous Contrast Volume Protocol for Computed Tomography Angiography Providing Comprehensive Cardiac and Vascular Assessment Prior to Transcatheter Aortic Valve Replacement in Patients with Chronic Kidney Disease

PubMed Central

Pulerwitz, Todd C.; Khalique, Omar K.; Nazif, Tamim N.; Rozenshtein, Anna; Pearson, Gregory D.N.; Hahn, Rebecca T.; Vahl, Torsten P.; Kodali, Susheel K.; George, Isaac; Leon, Martin B.; D'Souza, Belinda; Po, Ming Jack; Einstein, Andrew J.

2016-01-01

Background Transcatheter aortic valve replacement (TAVR) is a lifesaving procedure for many patients high risk for surgical aortic valve replacement. The prevalence of chronic kidney disease (CKD) is high in this population, and thus a very low contrast volume (VLCV) computed tomography angiography (CTA) protocol providing comprehensive cardiac and vascular imaging would be valuable. Methods 52 patients with severe, symptomatic aortic valve disease, undergoing pre-TAVR CTA assessment from 2013-4 at Columbia University Medical Center were studied, including all 26 patients with CKD (eGFR<30mL/min) who underwent a novel VLCV protocol (20mL of iohexol at 2.5mL/s), and 26 standard-contrast-volume (SCV) protocol patients. Using a 320-slice volumetric scanner, the protocol included ECG-gated volume scanning of the aortic root followed by medium-pitch helical vascular scanning through the femoral arteries. Two experienced cardiologists performed aortic annulus and root measurements. Vascular image quality was assessed by two radiologists using a 4-point scale. Results VLCV patients had mean(±SD) age 86±6.5, BMI 23.9±3.4 kg/m2 with 54% men; SCV patients age 83±8.8, BMI 28.7±5.3 kg/m2, 65% men. There was excellent intra- and inter-observer agreement for annular and root measurements, and excellent agreement with 3D-transesophageal echocardiographic measurements. Both radiologists found diagnostic-quality vascular imaging in 96% of VLCV and 100% of SCV cases, with excellent inter-observer agreement. Conclusions This study is the first of its kind to report the feasibility and reproducibility of measurements for a VLCV protocol for comprehensive pre-TAVR CTA. There was excellent agreement of cardiac measurements and almost all studies were diagnostic quality for vascular access assessment. PMID:27061253

Blood Lead Level and Measured Glomerular Filtration Rate in Children with Chronic Kidney Disease

PubMed Central

Abraham, Alison G.; Navas-Acien, Ana; Guallar, Eliseo; Weaver, Virginia M.; Furth, Susan L.

2013-01-01

Background: The role of environmental exposure to lead as a risk factor for chronic kidney disease (CKD) and its progression remains controversial, and most studies have been limited by a lack of direct glomerular filtration rate (GFR) measurement. Objective: We evaluated the association between lead exposure and GFR in children with CKD. Methods: In this cross-sectional study, we examined the association between blood lead levels (BLLs) and GFR measured by the plasma disappearance of iohexol among 391 participants in the Chronic Kidney Disease in Children (CKiD) prospective cohort study. Results: Median BLL and GFR were 1.2 µg/dL and 44.4 mL/min per 1.73 m2, respectively. The average percent change in GFR for each 1-µg/dL increase in BLL was –2.1 (95% CI: –6.0, 1.8). In analyses stratified by CKD diagnosis, the association between BLL and GFR was stronger among children with glomerular disease underlying CKD; in this group, each 1-µg/dL increase in BLL was associated with a –12.1 (95% CI: –22.2, –1.9) percent change in GFR. In analyses stratified by anemia status, each 1-µg/dL increase in BLL among those with and without anemia was associated with a –0.3 (95% CI: –7.2, 6.6) and –4.6 (95% CI: –8.9, –0.3) percent change in GFR, respectively. Conclusions: There was no significant association between BLL and directly measured GFR in this relatively large cohort of children with CKD, although associations were observed in some subgroups. Longitudinal analyses are needed to examine the temporal relationship between lead and GFR decline, and to further examine the impact of underlying cause of CKD and anemia/hemoglobin status among patients with CKD. PMID:23694739

Metabolic syndrome but not obesity measures are risk factors for accelerated age-related glomerular filtration rate decline in the general population.

PubMed

Stefansson, Vidar T N; Schei, Jørgen; Solbu, Marit D; Jenssen, Trond G; Melsom, Toralf; Eriksen, Bjørn O

2018-05-01

Rapid age-related glomerular filtration rate (GFR) decline increases the risk of end-stage renal disease, and a low GFR increases the risk of mortality and cardiovascular disease. High body mass index and the metabolic syndrome are well-known risk factors for patients with advanced chronic kidney disease, but their role in accelerating age-related GFR decline independent of cardiovascular disease, hypertension and diabetes is not adequately understood. We studied body mass index, waist circumference, waist-hip ratio and metabolic syndrome as risk factors for accelerated GFR decline in 1261 middle-aged people representative of the general population without diabetes, cardiovascular disease or kidney disease. GFR was measured as iohexol clearance at baseline and repeated after a median of 5.6 years. Metabolic syndrome was defined as fulfilling three out of five criteria, based on waist circumference, blood pressure, glucose, high-density lipoprotein cholesterol and triglycerides. The mean GFR decline rate was 0.95 ml/min/year. Neither the body mass index, waist circumference nor waist-hip ratio predicted statistically significant changes in age-related GFR decline, but individuals with baseline metabolic syndrome had a significant mean of 0.30 ml/min/year faster decline than individuals without metabolic syndrome in a multivariable adjusted linear regression model. This association was mainly driven by the triglyceride criterion of metabolic syndrome, which was associated with a significant 0.36 ml/min/year faster decline when analyzed separately. Results differed significantly when GFR was estimated using creatinine and/or cystatin C. Thus, metabolic syndrome, but not the body mass index, waist circumference or waist-hip ratio, is an independent risk factor for accelerated age-related GFR decline in the general population. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Ubiquitous Detection of Artificial Sweeteners and Iodinated X-ray Contrast Media in Aquatic Environmental and Wastewater Treatment Plant Samples from Vietnam, The Philippines, and Myanmar.

PubMed

Watanabe, Yuta; Bach, Leu Tho; Van Dinh, Pham; Prudente, Maricar; Aguja, Socorro; Phay, Nyunt; Nakata, Haruhiko

2016-05-01

Water samples from Vietnam, The Philippines, and Myanmar were analyzed for artificial sweeteners (ASs) and iodinated X-ray contrast media (ICMs). High concentrations (low micrograms per liter) of ASs, including aspartame, saccharin, and sucralose, were found in wastewater treatment plant (WWTP) influents from Vietnam. Three ICMs, iohexol, iopamidol, and iopromide were detected in Vietnamese WWTP influents and effluents, suggesting that these ICMs are frequently used in Vietnam. ASs and ICMs were found in river water from downtown Hanoi at concentrations comparable to or lower than the concentrations in WWTP influents. The ASs and ICMs concentrations in WWTP influents and adjacent surface water significantly correlated (r (2) = 0.99, p < 0.001), suggesting that household wastewater is discharged directly into rivers in Vietnam. Acesulfame was frequently detected in northern Vietnamese groundwater, but the concentrations varied spatially by one order of magnitude even though the sampling points were very close together. This implies that poorly performing domestic septic tanks sporadically leak household wastewater into groundwater. High acesulfame, cyclamate, saccharin, and sucralose concentrations were found in surface water from Manila, The Philippines. The sucralose concentrations were one order of magnitude higher in the Manila samples than in the Vietnamese samples, indicating that more sucralose is used in The Philippines than in Vietnam. Acesulfame and cyclamate were found in surface water from Pathein (rural) and Yangon (urban) in Myanmar, but no ICMs were found in the samples. The ASs concentrations were two-three orders of magnitude lower in the samples from Myanmar than in the samples from Vietnam and The Philippines, suggesting that different amounts of ASs are used in these countries. We believe this is the first report of persistent ASs and ICMs having ubiquitous distributions in economically emerging South Asian countries.

Measurement of myocardial extracellular volume fraction by using equilibrium contrast-enhanced CT: validation against histologic findings.

PubMed

Bandula, Steve; White, Steven K; Flett, Andrew S; Lawrence, David; Pugliese, Francesca; Ashworth, Michael T; Punwani, Shonit; Taylor, Stuart A; Moon, James C

2013-11-01

To develop and validate equilibrium contrast material-enhanced computed tomography (CT) to measure myocardial extracellular volume (ECV) fraction by using a histologic reference standard and to compare equilibrium CT with equilibrium contrast-enhanced magnetic resonance (MR) imaging. A local ethics committee approved the study, and all subjects gave fully informed written consent. An equilibrium CT protocol was developed using iohexol at 300 mg of iodine per milliliter (bolus of 1 mg per kilogram of body weight administered at a rate of 3 mL/sec, followed immediately by an infusion of 1.88 mL/kg per hour with CT imaging before and at 25 minutes after injection of bolus of contrast agent) and ECV within the myocardial septum measured using both equilibrium CT and equilibrium MR imaging in patients with severe aortic stenosis. Biopsy samples of the myocardial septum collected during valve replacement surgery were used for histologic quantification of extracellular fibrosis with picrosirius red staining. Equilibrium CT- and equilibrium MR imaging-derived ECV measurements were compared with histologically quantified fibrosis by using Pearson correlation. Agreement between equilibrium CT and equilibrium MR imaging was assessed by using Bland-Altman comparison. Twenty-three patients (16 male, seven female; mean age, 70.8 years; standard deviation, 8.3) were recruited. The mean percentage of histologic fibrosis was 18% (intersubject range, 5%-40%). There was a significant correlation between both equilibrium CT- and equilibrium MR imaging-derived ECV and percentage of histologic fibrosis (r = 0.71 [P < .001] and r = 0.84 [P < .0001], respectively). Equilibrium CT-derived ECV was significantly correlated to equilibrium MR imaging-derived ECV (r = 0.73). ECV measured by using equilibrium CT in patients with aortic stenosis correlates with histologic quantification of myocardial fibrosis and with ECV derived by using equilibrium MR imaging. RSNA, 2013

Decline in measured glomerular filtration rate is associated with a decrease in endurance, strength, balance and fine motor skills.

PubMed

Hellberg, Matthias; Höglund, Peter; Svensson, Philippa; Abdulahi, Huda; Clyne, Naomi

2017-07-01

Physical performance in chronic kidney disease affects morbidity and mortality. The aim was to find out which measures of physical performance are important in chronic kidney disease (CKD) and if there are associations with declining measured glomerular filtration rate (GFR). Endurance was assessed by 6 min walk test (6-MWT) and stair climbing, muscular endurance by 30 s sit to stand, heel rises and toe lifts, strength by quadriceps- and handgrip-strength, balance by functional reach and Berg's balance scale, and fine motor skills by Moberg's picking-up test. GFR was measured by Iohexol clearance. The study comprised 101 patients with CKD 3b-5 not started dialysis, 40 women and 61 men, with a mean age of 67 ± 13 (range: 22 - 87) years. All measures of physical performance were impaired. A decrease in GFR of 10 mL/min per 1.73 m 2 corresponded to a 35 metre shorter walking distance in the 6-MWT. Multivariable linear regression analysis showed significant relationships between decline in GFR and the 6-MWT (P = 0.04), isometric quadriceps strength left (P = 0.04), balance measured as functional reach (P = 0.02) and fine motor skills in the left hand as measured by Moberg's picking-up test (P = 0.01), respectively, after sex, age, comorbidity and the interaction between sex and age had been taken into account. Endurance, muscular endurance, strength, balance and fine motor skills were impaired in patients with CKD 3b-5. Walking capacity, isometric quadriceps strength, balance, and fine motor skills were associated with declining GFR. The left extremities were more susceptible to GFR, ageing and comorbidities and seem thus to be more sensitive. © 2016 Asian Pacific Society of Nephrology.

Sonographic evaluation of epidural and intrathecal injections in cats.

PubMed

Otero, Pablo E; Verdier, Natali; Zaccagnini, Andrea S; Fuensalida, Santiago E; Sclocco, Matias; Portela, Diego A; Waxman, Samanta

2016-11-01

To describe the ultrasonographic anatomy of the caudal lumbar spine in cats and to detect ultrasound (US) signs associated with epidural or intrathecal injection. Prospective, clinical study. Twenty-six client-owned cats. Transverse (position 1) and parasagittal (position 2) two-dimensional US scanning was performed over the caudal lumbar spine in all cats. Midline distances between the identified structures were measured. Cats assigned to epidural injection (group E, n = 16) were administered a bupivacaine-morphine combination confirmed by electrical stimulation. Cats assigned to intrathecal injection (group I, n = 10) were administered a morphine-iohexol combination injected at the lumbosacral level and confirmed by lateral radiography. The total volume injected (0.3 mL kg -1 ) was divided into two equal aliquots that were injected without needle repositioning, with the US probe in positions 1 and 2, respectively. The presence or absence of a burst of color [color flow Doppler test (CFDT)], dural sac collapse and epidural space enlargement were registered during and after both injections. US scanning allowed measurement of the distances between the highly visible structures inside the spinal canal. CFDT was positive for all animals in group E. In group I, intrathecal injection was confirmed in only two animals, for which the CFDT was negative; seven cats inadvertently and simultaneously were administered an epidural injection and showed a positive CFDT during the second aliquot injection, and the remaining animal was administered epidural anesthesia and was excluded from the CFDT data analysis. Dural sac collapse and epidural space enlargement were present in all animals in which an epidural injection was confirmed. US examination allowed an anatomical description of the caudal lumbar spine and real-time confirmation of epidural injection by observation of a positive CFDT, dural sac collapse and epidural space enlargement. © 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

Outcome Differences between Intra-Arterial Iso- and Low-Osmolality Iodinated Radiographic Contrast Media in the Interventional Management of Stroke III Trial.

PubMed

Tomsick, T A; Foster, L D; Liebeskind, D S; Hill, M D; Carrozella, J; Goyal, M; von Kummer, R; Demchuk, A M; Dzialowski, I; Puetz, V; Jovin, T; Morales, H; Palesch, Y Y; Broderick, J; Khatri, P; Yeatts, S D

2015-11-01

Intracarotid arterial infusion of nonionic, low-osmolal iohexol contrast medium has been associated with increased intracranial hemorrhage in a rat middle cerebral artery occlusion model compared with saline infusion. Iso-osmolal iodixanol (290 mOsm/kg H2O) infusion demonstrated smaller infarcts and less intracranial hemorrhage compared with low-osmolal iopamidol and saline. No studies comparing iodinated radiographic contrast media in human stroke have been performed, to our knowledge. We hypothesized that low-osmolal contrast media may be associated with worse outcomes compared with iodixanol in the Interventional Management of Stroke III Trial (IMS III). We reviewed prospective iodinated radiographic contrast media data for 133 M1 occlusions treated with endovascular therapy. We compared 5 prespecified efficacy and safety end points (mRS 0-2 outcome, modified TICI 2b-3 reperfusion, asymptomatic and symptomatic intracranial hemorrhage, and mortality) between those receiving iodixanol (n = 31) or low-osmolal contrast media (n = 102). Variables imbalanced between iodinated radiographic contrast media types or associated with outcome were considered potential covariates for the adjusted models. In addition to the iodinated radiographic contrast media type, final covariates were those selected by using the stepwise method in a logistic regression model. Adjusted relative risks were then estimated by using a log-link regression model. Of baseline or endovascular therapy variables potentially linked to outcome, prior antiplatelet agent use was more common and microcatheter iodinated radiographic contrast media injections were fewer with iodixanol. Relative risk point estimates are in favor of iodixanol for the 5 prespecified end points with M1 occlusion. The percentage of risk differences are numerically greater for microcatheter injections with iodixanol. While data favoring the use of iso-osmolal iodixanol for reperfusion of M1 occlusion following IV rtPA are inconclusive, potential pathophysiologic mechanisms suggesting clinical benefit warrant further investigation. © 2015 by American Journal of Neuroradiology.

Concentrations of gatifloxacin in plasma and urine and penetration into prostatic and seminal fluid, ejaculate, and sperm cells after single oral administrations of 400 milligrams to volunteers.

PubMed

Naber, C K; Steghafner, M; Kinzig-Schippers, M; Sauber, C; Sörgel, F; Stahlberg, H J; Naber, K G

2001-01-01

Gatifloxacin (GTX), a new fluoroquinolone with extended antibacterial activity, is an interesting candidate for the treatment of chronic bacterial prostatitis (CBP). Besides the antibacterial spectrum, the concentrations in the target tissues and fluids are crucial for the treatment of CBP. Thus, it was of interest to investigate its penetration into prostatic and seminal fluid. GTX concentrations in plasma, urine, ejaculate, prostatic and seminal fluid, and sperm cells were determined by a high-performance liquid chromatography method after oral intake of a single 400-mg dose in 10 male Caucasian volunteers in the fasting state. Simultaneous application of the renal contrast agent iohexol was used to estimate the maximal possible contamination of ejaculate and prostatic and seminal fluid by urine. GTX was well tolerated. The means (standard deviations) for the following parameters were as indicated: time to maximum concentration of drug in serum, 1.66 (0. 91) h; maximum concentration of drug in serum, 2.90 (0.39) microg/ml; area under the concentration-time curve from 0 to 24 h, 25.65 microg. h/ml; and half life, 7.2 (0.90) h. Within 12 h about 50% of the drug was excreted unchanged into the urine. The mean renal clearance was 169 ml/min. The gatifloxacin concentrations in ejaculate, seminal fluid, and prostatic fluid were in the range of the corresponding plasma concentrations which were 1.92 (0.27) microg/ml at approximately the same time point (4 h after drug intake). The concentrations in sperm cells (0.195, 0.076, and 0.011 microg/ml) could be determined in three subjects. The good penetration into prostatic and seminal fluid, the good tolerance, and the previously reported broad antibacterial spectrum suggest that GTX may be a good alternative for the treatment of chronic bacterial prostatitis. Clinical studies should be performed to confirm this assumption.

Concentrations of Gatifloxacin in Plasma and Urine and Penetration into Prostatic and Seminal Fluid, Ejaculate, and Sperm Cells after Single Oral Administrations of 400 Milligrams to Volunteers

PubMed Central

Naber, Christoph K.; Steghafner, Michaela; Kinzig-Schippers, Martina; Sauber, Christian; Sörgel, Fritz; Stahlberg, Hans-Jürgen; Naber, Kurt G.

2001-01-01

Gatifloxacin (GTX), a new fluoroquinolone with extended antibacterial activity, is an interesting candidate for the treatment of chronic bacterial prostatitis (CBP). Besides the antibacterial spectrum, the concentrations in the target tissues and fluids are crucial for the treatment of CBP. Thus, it was of interest to investigate its penetration into prostatic and seminal fluid. GTX concentrations in plasma, urine, ejaculate, prostatic and seminal fluid, and sperm cells were determined by a high-performance liquid chromatography method after oral intake of a single 400-mg dose in 10 male Caucasian volunteers in the fasting state. Simultaneous application of the renal contrast agent iohexol was used to estimate the maximal possible contamination of ejaculate and prostatic and seminal fluid by urine. GTX was well tolerated. The means (standard deviations) for the following parameters were as indicated: time to maximum concentration of drug in serum, 1.66 (0.91) h; maximum concentration of drug in serum, 2.90 (0.39) μg/ml; area under the concentration-time curve from 0 to 24 h, 25.65 μg · h/ml; and half life, 7.2 (0.90) h. Within 12 h about 50% of the drug was excreted unchanged into the urine. The mean renal clearance was 169 ml/min. The gatifloxacin concentrations in ejaculate, seminal fluid, and prostatic fluid were in the range of the corresponding plasma concentrations which were 1.92 (0.27) μg/ml at approximately the same time point (4 h after drug intake). The concentrations in sperm cells (0.195, 0.076, and 0.011 μg/ml) could be determined in three subjects. The good penetration into prostatic and seminal fluid, the good tolerance, and the previously reported broad antibacterial spectrum suggest that GTX may be a good alternative for the treatment of chronic bacterial prostatitis. Clinical studies should be performed to confirm this assumption. PMID:11120980

Combining Cystatin C and Creatinine Yields a Reliable Glomerular Filtration Rate Estimation in Older Adults in Contrast to β-Trace Protein and β2-Microglobulin.

PubMed

Werner, Karin; Pihlsgård, Mats; Elmståhl, Sölve; Legrand, Helen; Nyman, Ulf; Christensson, Anders

2017-01-01

The glomerular filtration rate (GFR) is the most important measure of kidney function and chronic kidney disease (CKD). This study aims to validate commonly used equations for estimated GFR (eGFR) based on creatinine (cr), cystatin C (cys), β-trace protein (BTP), and β2-microglobulin (B2M) in older adults. We conducted a validation study with 126 participants aged between 72 and 98 with a mean measured GFR (mGFR) by iohexol clearance of 54 mL/min/1.73 m2. The eGFR equations (CKD-Epidemiology collaboration [CKD-EPI], Berlin Initiative Study [BIS], Full Age Spectrum [FAS], Modification of Diet in Renal Disease [MDRD]cr, Caucasian-Asian-Pediatric-Adult [CAPA]cys, Lund-Malmö Revised [LM-REV]cr, and MEAN-LM-CAPAcr-cys), were assessed in terms of bias (median difference: eGFR-mGFR), precision (interquartile range of the differences), and accuracy (P30: percentage of estimates ±30% of mGFR). The equations were compared to a benchmark equation: CKD-EPIcr-cys. All cystatin C-based equations underestimated the GFR compared to mGFR, whereas bias was mixed for the equations based only on creatinine. Accuracy was the highest for CKD-EPIcr-cys (98%) and lowest for MDRD (82%). Below mGFR 45 mL/min/1.73 m2 only equations incorporating cystatin C reached P30 accuracy >90%. CKD-EPIcr-cys was not significantly more accurate than the other cystatin C-based equations. In contrast, CKD-EPIcr-cys was significantly more accurate than all creatinine-based equations except LM-REVcr. This study confirms that it is reasonable to use equations incorporating cystatin C and creatinine in older patients across a wide spectrum of GFR. However, the results call into question the use of creatinine alone below mGFR 45 mL/min/1.73 m2. B2M and BTP do not demonstrate additional value in eGFR determination in older adults. © 2017 S. Karger AG, Basel.

Chronic Kidney Disease.

PubMed

Webster, Angela C; Nagler, Evi V; Morton, Rachael L; Masson, Philip

2017-03-25

The definition and classification of chronic kidney disease (CKD) have evolved over time, but current international guidelines define this condition as decreased kidney function shown by glomerular filtration rate (GFR) of less than 60 mL/min per 1·73 m 2 , or markers of kidney damage, or both, of at least 3 months duration, regardless of the underlying cause. Diabetes and hypertension are the main causes of CKD in all high-income and middle-income countries, and also in many low-income countries. Incidence, prevalence, and progression of CKD also vary within countries by ethnicity and social determinants of health, possibly through epigenetic influence. Many people are asymptomatic or have non-specific symptoms such as lethargy, itch, or loss of appetite. Diagnosis is commonly made after chance findings from screening tests (urinary dipstick or blood tests), or when symptoms become severe. The best available indicator of overall kidney function is GFR, which is measured either via exogenous markers (eg, DTPA, iohexol), or estimated using equations. Presence of proteinuria is associated with increased risk of progression of CKD and death. Kidney biopsy samples can show definitive evidence of CKD, through common changes such as glomerular sclerosis, tubular atrophy, and interstitial fibrosis. Complications include anaemia due to reduced production of erythropoietin by the kidney; reduced red blood cell survival and iron deficiency; and mineral bone disease caused by disturbed vitamin D, calcium, and phosphate metabolism. People with CKD are five to ten times more likely to die prematurely than they are to progress to end stage kidney disease. This increased risk of death rises exponentially as kidney function worsens and is largely attributable to death from cardiovascular disease, although cancer incidence and mortality are also increased. Health-related quality of life is substantially lower for people with CKD than for the general population, and falls as GFR declines. Interventions targeting specific symptoms, or aimed at supporting educational or lifestyle considerations, make a positive difference to people living with CKD. Inequity in access to services for this disease disproportionally affects disadvantaged populations, and health service provision to incentivise early intervention over provision of care only for advanced CKD is still evolving in many countries. Copyright © 2017 Elsevier Ltd. All rights reserved.

MO-AB-BRA-09: Temporally Realistic Manipulation a 4D Biomechanical Lung Phantom for Evaluation of Simultaneous Registration and Segmentation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Markel, D; Levesque, I R.; Larkin, J

Purpose: To produce multi-modality compatible, realistic datasets for the joint evaluation of segmentation and registration with a reliable ground truth using a 4D biomechanical lung phantom. The further development of a computer controlled air flow system for recreation of real patient breathing patterns is incorporated for additional evaluation of motion prediction algorithms. Methods: A pair of preserved porcine lungs was pneumatically manipulated using an in-house computer controlled respirator. The respirator consisted of a set of bellows actuated by a 186 W computer controlled industrial motor. Patient breathing traces were recorded using a respiratory bellows belt during CT simulation and inputmore » into a control program incorporating a proportional-integral-derivative (PID) feedback controller in LabVIEW. Mock tumors were created using dual compartment vacuum sealed sea sponges. 65% iohexol,a gadolinium-based contrast agent and 18F-FDG were used to produce contrast and thus determine a segmentation ground truth. The intensity distributions of the compartments were then digitally matched for the final dataset. A bifurcation tracking pipeline provided a registration ground truth using the bronchi of the lung. The lungs were scanned using a GE Discovery-ST PET/CT scanner and a Phillips Panorama 0.23T MRI using a T1 weighted 3D fast field echo (FFE) protocol. Results: The standard deviation of the error between the patient breathing trace and the encoder feedback from the respirator was found to be ±4.2%. Bifurcation tracking error using CT (0.97×0.97×3.27 mm{sup 3} resolution) was found to be sub-voxel up to 7.8 cm displacement for human lungs and less than 1.32 voxel widths in any axis up to 2.3 cm for the porcine lungs. Conclusion: An MRI/PET/CT compatible anatomically and temporally realistic swine lung phantom was developed for the evaluation of simultaneous registration and segmentation algorithms. With the addition of custom software and mock tumors, the entire package offers ground truths for benchmarking performance with high fidelity.« less

Bilateral Contrast-enhanced Dual-Energy Digital Mammography: Feasibility and Comparison with Conventional Digital Mammography and MR Imaging in Women with Known Breast Carcinoma

PubMed Central

Dershaw, D. David; Sung, Janice S.; Heerdt, Alexandra S.; Thornton, Cynthia; Moskowitz, Chaya S.; Ferrara, Jessica; Morris, Elizabeth A.

2013-01-01

Purpose To determine feasibility of performing bilateral dual-energy (DE) contrast agent–enhanced (CE) digital mammography and to evaluate its performance compared with conventional digital mammography and breast magnetic resonance (MR) imaging in women with known breast cancer. Materials and Methods This study was approved by the institutional review board and was HIPAA compliant. Written informed consent was obtained. Patient accrual began in March 2010 and ended in August 2011. Mean patient age was 49.6 years (range, 25–74 years). Feasibility was evaluated in 10 women with newly diagnosed breast cancer who were injected with 1.5 mL per kilogram of body weight of iohexol and imaged between 2.5 and 10 minutes after injection. Once feasibility was confirmed, 52 women with newly diagnosed cancer who had undergone breast MR imaging gave consent to undergo DE CE digital mammography. Positive findings were confirmed with pathologic findings. Results Feasibility was confirmed with no adverse events. Visualization of tumor enhancement was independent of timing after contrast agent injection for up to 10 minutes. MR imaging and DE CE digital mammography both depicted 50 (96%) of 52 index tumors; conventional mammography depicted 42 (81%). Lesions depicted by using DE CE digital mammography ranged from 4 to 67 mm in size (median, 17 mm). DE CE digital mammography depicted 14 (56%) of 25 additional ipsilateral cancers compared with 22 (88%) of 25 for MR imaging. There were two false-positive findings with DE CE digital mammography and 13 false-positive findings with MR imaging. There was one contralateral cancer, which was not evident with either modality. Conclusion Bilateral DE CE digital mammography was feasible and easily accomplished. It was used to detect known primary tumors at a rate comparable to that of MR imaging and higher than that of conventional digital mammography. DE CE digital mammography had a lower sensitivity for detecting additional ipsilateral cancers than did MR imaging, but the specificity was higher. © RSNA, 2012 PMID:23220903

Comparison of creatinine and cystatin C based eGFR in the estimation of glomerular filtration rate in Indigenous Australians: The eGFR Study.

PubMed

Barr, Elizabeth Lm; Maple-Brown, Louise J; Barzi, Federica; Hughes, Jaquelyne T; Jerums, George; Ekinci, Elif I; Ellis, Andrew G; Jones, Graham Rd; Lawton, Paul D; Sajiv, Cherian; Majoni, Sandawana W; Brown, Alex Dh; Hoy, Wendy E; O'Dea, Kerin; Cass, Alan; MacIsaac, Richard J

2017-04-01

The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation that combines creatinine and cystatin C is superior to equations that include either measure alone in estimating glomerular filtration rate (GFR). However, whether cystatin C can provide any additional benefits in estimating GFR for Indigenous Australians, a population at high risk of end-stage kidney disease (ESKD) is unknown. Using a cross-sectional analysis from the eGFR Study of 654 Indigenous Australians at high risk of ESKD, eGFR was calculated using the CKD-EPI equations for serum creatinine (eGFRcr), cystatin C (eGFRcysC) and combined creatinine and cystatin C (eGFRcysC+cr). Reference GFR (mGFR) was determined using a non-isotopic iohexol plasma disappearance technique over 4h. Performance of each equation to mGFR was assessed by calculating bias, % bias, precision and accuracy for the total population, and according to age, sex, kidney disease, diabetes, obesity and c-reactive protein. Data were available for 542 participants (38% men, mean [sd] age 45 [14] years). Bias was significantly greater for eGFRcysC (15.0mL/min/1.73m 2 ; 95% CI 13.3-16.4, p<0.001) and eGFRcysC+cr (10.3; 8.8-11.5, p<0.001) compared to eGFRcr (5.4; 3.0-7.2). Accuracy was lower for eGFRcysC (80.3%; 76.7-83.5, p<0.001) but not for eGFRcysC+cr (91.9; 89.3-94.0, p=0.29) compared to eGFRcr (90.0; 87.2-92.4). Precision was comparable for all equations. The performance of eGFRcysC deteriorated across increasing levels of c-reactive protein. Cystatin C based eGFR equations may not perform well in populations with high levels of chronic inflammation. CKD-EPI eGFR based on serum creatinine remains the preferred equation in Indigenous Australians. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Determination of the best method to estimate glomerular filtration rate from serum creatinine in adult patients with sickle cell disease: a prospective observational cohort study.

PubMed

Arlet, Jean-Benoît; Ribeil, Jean-Antoine; Chatellier, Gilles; Eladari, Dominique; De Seigneux, Sophie; Souberbielle, Jean-Claude; Friedlander, Gérard; de Montalembert, Marianne; Pouchot, Jacques; Prié, Dominique; Courbebaisse, Marie

2012-08-06

Sickle cell disease (SCD) leads to tissue hypoxia resulting in chronic organ dysfunction including SCD associated nephropathy. The goal of our study was to determine the best equation to estimate glomerular filtration rate (GFR) in SCD adult patients. We conducted a prospective observational cohort study. Since 2007, all adult SCD patients in steady state, followed in two medical departments, have had their GFR measured using iohexol plasma clearance (gold standard). The Cockcroft-Gault, MDRD-v4, CKP-EPI and finally, MDRD and CKD-EPI equations without adjustment for ethnicity were tested to estimate GFR from serum creatinine. Estimated GFRs were compared to measured GFRs according to the graphical Bland and Altman method. Sixty-four SCD patients (16 men, median age 27.5 years [range 18.0-67.5], 41 with SS-genotype were studied. They were Sub-Saharan Africa and French West Indies natives and predominantly lean (median body mass index: 22 kg/m2 [16-33]). Hyperfiltration (defined as measured GFR >110 mL/min/1.73 m2) was detected in 53.1% of patients. Urinary albumin/creatinine ratio was higher in patients with hyperfiltration than in patients with normal GFR (4.05 mg/mmol [0.14-60] versus 0.4 mg/mmol [0.7-81], p = 0.01). The CKD-EPI equation without adjustment for ethnicity had both the lowest bias and the greatest precision. Differences between estimated GFRs using the CKP-EPI equation and measured GFRs decreased with increasing GFR values, whereas it increased with the Cockcroft-Gault and MDRD-v4 equations. We confirm that SCD patients have a high rate of glomerular hyperfiltration, which is frequently associated with microalbuminuria or macroalbuminuria. In non-Afro-American SCD patients, the best method for estimating GFR from serum creatinine is the CKD-EPI equation without adjustment for ethnicity. This equation is particularly accurate to estimate high GFR values, including glomerular hyperfiltration, and thus should be recommended to screen SCD adult patients at high risk for SCD nephropathy.

Very low intravenous contrast volume protocol for computed tomography angiography providing comprehensive cardiac and vascular assessment prior to transcatheter aortic valve replacement in patients with chronic kidney disease.

PubMed

Pulerwitz, Todd C; Khalique, Omar K; Nazif, Tamim N; Rozenshtein, Anna; Pearson, Gregory D N; Hahn, Rebecca T; Vahl, Torsten P; Kodali, Susheel K; George, Isaac; Leon, Martin B; D'Souza, Belinda; Po, Ming Jack; Einstein, Andrew J

2016-01-01

Transcatheter aortic valve replacement (TAVR) is a lifesaving procedure for many patients high risk for surgical aortic valve replacement. The prevalence of chronic kidney disease (CKD) is high in this population, and thus a very low contrast volume (VLCV) computed tomography angiography (CTA) protocol providing comprehensive cardiac and vascular imaging would be valuable. 52 patients with severe, symptomatic aortic valve disease, undergoing pre-TAVR CTA assessment from 2013-4 at Columbia University Medical Center were studied, including all 26 patients with CKD (eGFR<30 mL/min) who underwent a novel VLCV protocol (20 mL of iohexol at 2.5 mL/s), and 26 standard-contrast-volume (SCV) protocol patients. Using a 320-slice volumetric scanner, the protocol included ECG-gated volume scanning of the aortic root followed by medium-pitch helical vascular scanning through the femoral arteries. Two experienced cardiologists performed aortic annulus and root measurements. Vascular image quality was assessed by two radiologists using a 4-point scale. VLCV patients had mean (±SD) age 86 ± 6.5, BMI 23.9 ± 3.4 kg/m(2) with 54% men; SCV patients age 83 ± 8.8, BMI 28.7 ± 5.3 kg/m(2), 65% men. There was excellent intra- and inter-observer agreement for annular and root measurements, and excellent agreement with 3D-transesophageal echocardiographic measurements. Both radiologists found diagnostic-quality vascular imaging in 96% of VLCV and 100% of SCV cases, with excellent inter-observer agreement. This study is the first of its kind to report the feasibility and reproducibility of measurements for a VLCV protocol for comprehensive pre-TAVR CTA. There was excellent agreement of cardiac measurements and almost all studies were diagnostic quality for vascular access assessment. Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.

Effect of benazepril, robenacoxib and their combination on glomerular filtration rate in cats.

PubMed

King, Jonathan N; Panteri, Alessandro; Graille, Melanie; Seewald, Wolfgang; Friton, Gabriele; Desevaux, Cyril

2016-06-23

Combined use of angiotensin-converting enzyme inhibitors and nonsteroidal anti-inflammatory drugs may induce acute kidney injury in humans, especially when combined with diuretics. The objective of this investigation was to evaluate the effects of benazepril, robenacoxib and their combination in healthy cats. In each of two studies (study 1 followed by study 2), 32 healthy cats were randomised to one of four groups (n = 4 male and 4 female cats per group) in a parallel-group design. The groups received orally once daily for 7 days either placebo (control group), benazepril, robenacoxib or benazepril plus robenacoxib. In study 2, all groups received in addition 0.5 mg/kg furosemide twice daily by subcutaneous injection for 7 days. Benazepril, robenacoxib and their combination were well tolerated as evidenced from lack of clinical signs and no negative effects on body weight, feed consumption and clinical chemistry, haematology and urinalysis variables. The primary endpoint of the study was the glomerular filtration rate (GFR), which was estimated from the plasma clearance of iohexol. In the absence of furosemide, GFR was significantly higher in cats receiving the combination of benazepril plus robenacoxib compared to the other three groups, and was also significantly higher in females receiving only benazepril compared to the control. Administration of furosemide induced diuresis, reduced GFR and activated the renin-aldosterone-angiotensin system, evidenced from increased plasma renin activity and plasma aldosterone concentrations. Compared to the control group in cats treated with furosemide, GFR was increased by benazepril (females only) but decreased by robenacoxib (males only). Benazepril, robenacoxib and their combination significantly inhibited the increase in plasma aldosterone induced by furosemide. The combination of benazepril and robenacoxib was well tolerated and either increased or had a neutral effect on GFR in healthy cats without or with concomitant furosemide. The combination of benazepril and robenacoxib reduced plasma aldosterone concentrations increased by furosemide. It is recommended to test the efficacy and safety of the combined use of benazepril and robenacoxib in cats with clinical disease, notably proteinuric chronic kidney disease.

Nephroprotective potential of carnitine against glycerol and contrast-induced kidney injury in rats through modulation of oxidative stress, proinflammatory cytokines, and apoptosis

PubMed Central

Kunak, Celalettin S; Ugan, Rustem A; Karakus, Emre; Polat, Beyzagul; Halici, Zekai; Saritemur, Murat; Atmaca, Hasan T; Karaman, Adem

2016-01-01

Objective: Contrast media (CM) are a major cause of nephropathy in high-risk patients. The aim of this study was to examine the effects of carnitine (CAR) in advanced nephrotoxicity due to CM administration in rats with glycerol-induced renal functional disorder. Methods: 40 rats were divided randomly into five groups (n = 8): (1) healthy group; (2) glycerol only (GLY); (3) glycerol and CM (GLY + CM); (4) glycerol, CM and 200 mg kg−1 carnitine (CAR200, Carnitene®; Sigma-tau/Santa Farma, Istanbul, Turkey); and (5) glycerol, CM and 400 mg kg−1 carnitine (CAR400). Kidney injury was induced with a single-dose, intramuscular injection of 10 ml kg−1 body weight (b.w.) of GLY. CAR was administered intraperitoneally. CM (8 ml kg−1 b.w. iohexol, Omnipaque™; Opakim Medical Products, Istanbul, Turkey) was infused via the tail vein to the rats in Groups 3–5. Results: l-carnitine administration significantly decreased serum creatinine and blood urea nitrogen levels. Superoxide dismutase and glutathione activity increased significantly in the treatment groups compared with the nephrotoxic groups. CAR400 significantly reduced malondialdehyde levels to healthy levels. In the treatment groups, tumour necrosis factor (TNF)-α, transforming growth factor 1β, interleukin 1β and caspase-3 gene expression decreased compared with the nephrotoxic groups. TNF-α and nuclear factor kappa-beta (NF-κB) protein expression increased after CM and CAR administration reduced both TNF-α and NF-κB expressions. Histopathologically, hyaline and haemorrhagic casts and necrosis in proximal tubules increased in the nephrotoxicity groups and decreased in the CAR groups. Conclusion: The results reveal that l-carnitine protects the oxidant/antioxidant balance and decreases proinflammatory cytokines and apoptosis in CM-induced nephrotoxicity in rats with underlying pathology. Advances in knowledge: Depending on the underlying kidney pathologies, the incidence of CM-induced nephropathy (CIN) increases. Therefore, this is the best model to represent clinically observed CIN. PMID:26562095

Tagging-based, electronically cleansed CT colonography: evaluation of patient comfort and image readability.

PubMed

Zalis, Michael E; Perumpillichira, James J; Magee, Cordula; Kohlberg, Gavriel; Hahn, Peter F

2006-04-01

To prospectively compare the homogeneity, adequacy, and patient acceptance of nonionic iodine-based regimens with those of a barium-based regimen for computed tomographic (CT) colonography with electronic subtraction cleansing. After institutional review board approval and informed consent were obtained, 68 subjects (41 men (60%) men, 27 (40%) women; mean age, 60 years +/- 6 [standard deviation]) with average or moderate risk factors for development of colorectal carcinoma were recruited and placed into three study groups. Group 1 (n = 25) ingested 150-mL aliquots of 2% barium sulfate suspension with meals and snacks for 48 hours prior to imaging, without other diet modification or a cathartic. Group 2 (n = 21) ingested 10-mL aliquots of nonionic iodinated contrast material (iopromide) with a concentration of 300 mg per milliliter with meals and snacks for 2 days before imaging, without diet modification or a cathartic. Group 3 (n = 22) ingested nonionic iodinated contrast material (iohexol) with a concentration of 300 mg per milliliter with meals and snacks for 2 days before imaging and ingested 34 g of magnesium citrate the evening prior to imaging. CT colonography was also performed on 10 control subjects who ingested polyethylene glycol electrolyte solution prior to imaging. Subjective and numerical measures of bowel preparation quality, homogeneity, and patient comfort among the noncathartic and cathartic cohorts were compared with nonparametric analysis of variance, the Fisher exact test, and the F test, as appropriate. The study was HIPAA compliant. Study subjects who received tagging preparations reported significantly improved discomfort scores when compared with those of the control subjects (P < .05, each comparison). There was no significant difference in discomfort scores among groups 1, 2, and 3. For each reader, scores of subtracted image readability were highest for group 3. Dichotomized rates of preparation "success" were also greatest for group 3. In this series, the patient discomfort scores were significantly improved with tagging preparations for CT colonography. Nonionic iodinated contrast material in conjunction with a hyperosmotic laxative (magnesium citrate) was associated with the best subjective and numerical indices of readability. (c) RSNA, 2006.

Effect of Intravenous Administration of Contrast Media on Serum Creatinine Levels in Neonates.

PubMed

Bedoya, Maria A; White, Ammie M; Edgar, J Christopher; Pradhan, Madhura; Raab, Elisabeth L; Meyer, James S

2017-08-01

Purpose To assess the effect of intravenous contrast media on renal function in neonates. Materials and Methods Institutional review board approval was obtained with waiver of consent. Electronic health records from January 2011 to April 2013 were reviewed retrospectively. Measures of renal function were obtained in inpatient neonates who underwent magnetic resonance (MR) imaging or computed tomography (CT) and for whom serum creatinine (Cr) levels were obtained within 72 hours before imaging and at least one time after imaging (>1 day after administration of contrast material). A total of 140 neonates who received contrast material (59 who underwent CT with iohexol or iodixanol and 81 who underwent MR imaging with gadopentetate dimeglumine) were identified. These neonates were frequency matched according to sex, gestational and postnatal age, and preimaging serum Cr levels with neonates who underwent unenhanced MR imaging or CT. Cr levels and glomerular filtration rates (GFRs) were grouped according to when they were obtained (before imaging, 1-2 days after imaging, 3-5 days after imaging, 6-9 days after imaging, 10-45 days after imaging, and more than 45 days after imaging). Serum Cr levels and GFRs for each time period were compared between groups by using hierarchic regressions or χ 2 or Fisher exact tests and with repeated-measures analysis of variance to compare groups on the rate of change in serum Cr levels and GFRs from before to after imaging. Results Cr levels decreased and GFRs increased in both groups from before to after imaging (CT group, P ≤ .01; MR imaging group, P ≤ .01). The neonates who underwent contrast material-enhanced imaging and the neonates who underwent unenhanced imaging showed similar serum Cr levels at all examined time periods. Groups also did not differ in the proportion of neonates with serum Cr levels higher than the reference range (>0.4 mg/dL) at any time point (iodine- [P > .12] or gadolinium-based [P > .13] contrast material). Similar findings were observed for GFRs. None of the neonates developed nephrogenic systemic fibrosis. Conclusion In the absence of known renal failure, neonates receiving standard inpatient care do not appear to be at increased risk for developing renal toxicity due to administration of intravenous iodine- and gadolinium-based contrast material. © RSNA, 2017.

Formation of toxic iodinated disinfection by-products from compounds used in medical imaging.

PubMed

Duirk, Stephen E; Lindell, Cristal; Cornelison, Christopher C; Kormos, Jennifer; Ternes, Thomas A; Attene-Ramos, Matias; Osiol, Jennifer; Wagner, Elizabeth D; Plewa, Michael J; Richardson, Susan D

2011-08-15

Iodinated X-ray contrast media (ICM) were investigated as a source of iodine in the formation of iodo-trihalomethane (iodo-THM) and iodo-acid disinfection byproducts (DBPs), both of which are highly genotoxic and/or cytotoxic in mammalian cells. ICM are widely used at medical centers to enable imaging of soft tissues (e.g., organs, veins, blood vessels) and are designed to be inert substances, with 95% eliminated in urine and feces unmetabolized within 24 h. ICM are not well removed in wastewater treatment plants, such that they have been found at elevated concentrations in rivers and streams (up to 100 μg/L). Naturally occurring iodide in source waters is believed to be a primary source of iodine in the formation of iodo-DBPs, but a previous 23-city iodo-DBP occurrence study also revealed appreciable levels of iodo-DBPs in some drinking waters that had very low or no detectable iodide in their source waters. When 10 of the original 23 cities' source waters were resampled, four ICM were found--iopamidol, iopromide, iohexol, and diatrizoate--with iopamidol most frequently detected, in 6 of the 10 plants sampled, with concentrations up to 2700 ng/L. Subsequent controlled laboratory reactions of iopamidol with aqueous chlorine and monochloramine in the absence of natural organic matter (NOM) produced only trace levels of iodo-DBPs; however, when reacted in real source waters (containing NOM), chlorine and monochloramine produced significant levels of iodo-THMs and iodo-acids, up to 212 nM for dichloroiodomethane and 3.0 nM for iodoacetic acid, respectively, for chlorination. The pH behavior was different for chlorine and monochloramine, such that iodo-DBP concentrations maximized at higher pH (8.5) for chlorine, but at lower pH (6.5) for monochloramine. Extracts from chloraminated source waters with and without iopamidol, as well as from chlorinated source waters with iopamidol, were the most cytotoxic samples in mammalian cells. Source waters with iopamidol but no disinfectant added were the least cytotoxic. While extracts from chlorinated and chloraminated source waters were genotoxic, the addition of iopamidol enhanced their genotoxicity. Therefore, while ICM are not toxic in themselves, their presence in source waters may be a source of concern because of the formation of highly toxic iodo-DBPs in chlorinated and chloraminated drinking water.

A novel approach to contrast-induced nephrotoxicity: the melatonergic agent agomelatine

PubMed Central

Karaman, Adem; Diyarbakir, Busra; Kose, Duygu; Özbek-Bilgin, Asli; Topcu, Atilla; Gundogdu, Cemal; Durur-Karakaya, Afak; Bayraktutan, Zafer; Alper, Fatih

2016-01-01

Objective: To study the potential nephroprotective role of agomelatine in rat renal tissue in cases of contrast-induced nephrotoxicity (CIN). The drug's action on the antioxidant system and proinflammatory cytokines, superoxide dismutase (SOD) activity, levels of glutathione (GSH) and malondialdehyde (MDA) and the gene expression of interleukin-6 (IL-6), tumour necrosis factor (TNF)-α and nuclear factor kappa B (NF-κB) was measured. Tubular necrosis and hyaline and haemorrhagic casts were also histopathologically evaluated. Methods: The institutional ethics and local animal care committees approved the study. Eight groups of six rats were put on the following drug regimens: Group 1: healthy controls, Group 2: GLY (glycerol), Group 3: CM (contrast media—iohexol 10 ml kg−1), Group 4: GLY+CM, Group 5: CM+AGO20 (agomelatine 20 mg kg−1), Group 6: GLY+CM+AGO20, Group 7: CM+AGO40 (agomelatine 40 mg kg−1) and Group 8: GLY+CM+AGO40. The groups were evaluated by one-way analysis of variance and Duncan's multiple comparison test. Results: Agomelatine administration significantly improved the serum levels of blood urea nitrogen (BUN) and creatinine, SOD activity, GSH and MDA. The use of agomelatine had substantial downregulatory consequences on TNF-α, NF-κB and IL-6 messenger RNA levels. Mild-to-severe hyaline and haemorrhagic casts and tubular necrosis were observed in all groups, except in the healthy group. The histopathological scores were better in the agomelatine treatment groups. Conclusion: Agomelatine has nephroprotective effects against CIN in rats. This effect can be attributed to its properties of reducing oxidative stress and inhibiting the secretion of proinflammatory cytokines (NF-κB, TNF-α and IL-6). Advances in knowledge: CIN is one of the most important adverse effects of radiological procedures. Renal failure, diabetes, malignancy, old age and non-steroidal anti-inflammatory drug use pose the risk of CIN in patients. Several clinical studies have investigated ways to avoid CIN. Theophylline/aminophylline, statins, ascorbic acid and iloprost have been suggested for this purpose. Agomelatine is one of the melatonin ligands and is used for affective disorders and has antioxidant features. In this study, we hypothesized that agomelatine could have nephroprotective, antioxidant and anti-inflammatory effects against CIN in rats. PMID:26886874

Can computed tomography esophagography reliably diagnose traumatic penetrating upper digestive tract injuries?

PubMed

Conradie, Wilhelmus Jacobus; Gebremariam, Fekade Admassu

2015-01-01

To determine the sensitivity and specificity of computed tomography (CT) esophagography in diagnosing penetrating esophageal and hypopharyngeal injuries in trauma patients and to see if it can be used as the only imaging method in diagnosing these injuries. The confidence of radiologists using only CT esophagography was also measured. A prospective cross-sectional analytic study was done on haemodinamically stable patients requiring multidetector CT after external penetrating neck or chest trauma. Each patient was given oral contrast consisting of 50 ml 50% iohexol solution, within 5 min of commencement of the CT examination and in the supine position. An attempt was made to confirm all CT esophagography findings with at least one secondary method. Images were evaluated separately by two general departmental radiologists who were blinded to the results of the confirmation method. Between December 2012 and November 2014, 102 patients were included, of which 93 (91.2%) were male. Stab wounds were responsible for 85.3% (n=87) of penetrating wounds. Ninety-four patients (92.2%) had CT angiography (CTA) in conjunction with CT esophagography. There were 20 confirmed upper digestive tract injuries; 11 (55.0%) in the hypopharynx and 9 (45.0%) in the esophagus. With the exception of one case, all upper digestive tract injuries were diagnosed using only CT esophagography. No upper digestive tract injuries were correctly identified in 70 and 75 out of 82 true negative cases respectively, suggesting a sensitivity of 95.0% for both radiologists and specificity of 85.4% and 91.5% for CT esophagography. A number of false positive diagnoses were reported when CT esophagography was done in conjunction with CTA, resulting in a positive predictive value of 61.3% and 79.1% for this technique. Reviewers were positive to very confident about the CT esophagography findings in 90.0% and 100% of patients with injuries and 79.0% and 87.0%, respectively, in the no injury group. CT esophagography is reliable in diagnosing penetrating upper digestive tract injuries. In conjunction with CTA, false positive findings may occur. Radiologists were generally positive to very confident about their CT esophagography findings, not needing further imaging in more than 60% of cases. Copyright © 2015 Elsevier Inc. All rights reserved.

Evaluation of the effect of tofacitinib on measured glomerular filtration rate in patients with active rheumatoid arthritis: results from a randomised controlled trial.

PubMed

Kremer, Joel M; Kivitz, Alan J; Simon-Campos, Jesus A; Nasonov, Evgeny L; Tony, Hans-Peter; Lee, Soo-Kon; Vlahos, Bonnie; Hammond, Constance; Bukowski, Jack; Li, Huihua; Schulman, Seth L; Raber, Susan; Zuckerman, Andrea; Isaacs, John D

2015-04-06

Tofacitinib is an oral Janus kinase inhibitor for the treatment of rheumatoid arthritis (RA). During the clinical development programme, increases in mean serum creatinine (SCr) of approximately 0.07 mg/dL and 0.08 mg/dL were observed which plateaued early. This study assessed changes in measured glomerular filtration rate (mGFR) with tofacitinib relative to placebo in patients with active RA. This was a randomised, placebo-controlled, Phase 1 study (NCT01484561). Patients were aged ≥18 years with active RA. Patients were randomised 2:1 to oral tofacitinib 10 mg twice daily (BID) in Period 1 then placebo BID in Period 2 (tofacitinib → placebo); or oral placebo BID in both Periods (placebo → placebo). Change in mGFR was evaluated by iohexol serum clearance at four time points (run-in, pre-dose in Period 1, Period 1 end, and Period 2 end). The primary endpoint was the change in mGFR from baseline to Period 1 end. Secondary endpoints included: change in mGFR at other time points; change in estimated GFR (eGFR; Cockcroft-Gault equation) and SCr; efficacy; and safety. 148 patients were randomised to tofacitinib → placebo (N = 97) or placebo → placebo (N = 51). Baseline characteristics were similar between groups. A reduction of 8% (90% confidence interval [CI]: 2%, 14%) from baseline in adjusted geometric mean mGFR was observed during tofacitinib treatment in Period 1 vs placebo. During Period 2, mean mGFR returned towards baseline during placebo treatment, and there was no difference between the two treatment groups at the end of the study--ratio (tofacitinib → placebo/placebo → placebo) of adjusted geometric mean fold change of mGFR was 1.04 (90% CI: 0.97, 1.11). Post-hoc analyses, focussed on mGFR variability in placebo → placebo patients, were consistent with this conclusion. At study end, similar results were observed for eGFR and SCr. Clinical efficacy and safety were consistent with prior studies. Increases in mean SCr and decreases in eGFR in tofacitinib-treated patients with RA may occur in parallel with decreases in mean mGFR; mGFR returned towards baseline after tofacitinib discontinuation, with no significant difference vs placebo, even after post-hoc analyses. Safety monitoring will continue in ongoing and future clinical studies and routine pharmacovigilance. Clinicaltrials.gov NCT01484561. Registered 30 November 2011.

The eGFR-C study: accuracy of glomerular filtration rate (GFR) estimation using creatinine and cystatin C and albuminuria for monitoring disease progression in patients with stage 3 chronic kidney disease--prospective longitudinal study in a multiethnic population.

PubMed

Lamb, Edmund J; Brettell, Elizabeth A; Cockwell, Paul; Dalton, Neil; Deeks, Jon J; Harris, Kevin; Higgins, Tracy; Kalra, Philip A; Khunti, Kamlesh; Loud, Fiona; Ottridge, Ryan S; Sharpe, Claire C; Sitch, Alice J; Stevens, Paul E; Sutton, Andrew J; Taal, Maarten W

2014-01-14

Uncertainty exists regarding the optimal method to estimate glomerular filtration rate (GFR) for disease detection and monitoring. Widely used GFR estimates have not been validated in British ethnic minority populations. Iohexol measured GFR will be the reference against which each estimating equation will be compared. The estimating equations will be based upon serum creatinine and/or cystatin C. The eGFR-C study has 5 components: 1) A prospective longitudinal cohort study of 1300 adults with stage 3 chronic kidney disease followed for 3 years with reference (measured) GFR and test (estimated GFR [eGFR] and urinary albumin-to-creatinine ratio) measurements at baseline and 3 years. Test measurements will also be undertaken every 6 months. The study population will include a representative sample of South-Asians and African-Caribbeans. People with diabetes and proteinuria (ACR ≥30 mg/mmol) will comprise 20-30% of the study cohort.2) A sub-study of patterns of disease progression of 375 people (125 each of Caucasian, Asian and African-Caribbean origin; in each case containing subjects at high and low risk of renal progression). Additional reference GFR measurements will be undertaken after 1 and 2 years to enable a model of disease progression and error to be built.3) A biological variability study to establish reference change values for reference and test measures.4) A modelling study of the performance of monitoring strategies on detecting progression, utilising estimates of accuracy, patterns of disease progression and estimates of measurement error from studies 1), 2) and 3).5) A comprehensive cost database for each diagnostic approach will be developed to enable cost-effectiveness modelling of the optimal strategy.The performance of the estimating equations will be evaluated by assessing bias, precision and accuracy. Data will be modelled as a linear function of time utilising all available (maximum 7) time points compared with the difference between baseline and final reference values. The percentage of participants demonstrating large error with the respective estimating equations will be compared. Predictive value of GFR estimates and albumin-to-creatinine ratio will be compared amongst subjects that do or do not show progressive kidney function decline. The eGFR-C study will provide evidence to inform the optimal GFR estimate to be used in clinical practice. ISRCTN42955626.

Effect of Sirolimus on Disease Progression in Patients with Autosomal Dominant Polycystic Kidney Disease and CKD Stages 3b-4.

PubMed

Ruggenenti, Piero; Gentile, Giorgio; Perico, Norberto; Perna, Annalisa; Barcella, Luca; Trillini, Matias; Cortinovis, Monica; Ferrer Siles, Claudia Patricia; Reyes Loaeza, Jorge Arturo; Aparicio, Maria Carolina; Fasolini, Giorgio; Gaspari, Flavio; Martinetti, Davide; Carrara, Fabiola; Rubis, Nadia; Prandini, Silvia; Caroli, Anna; Sharma, Kanishka; Antiga, Luca; Remuzzi, Andrea; Remuzzi, Giuseppe

2016-05-06

The effect of mammalian target of rapamycin (mTOR) inhibitors has never been tested in patients with autosomal dominant polycystic kidney disease (ADPKD) and severe renal insufficiency. In this academic, prospective, randomized, open label, blinded end point, parallel group trial (ClinicalTrials.gov no. NCT01223755), 41 adults with ADPKD, CKD stage 3b or 4, and proteinuria ≤0.5 g/24 h were randomized between September of 2010 and March of 2012 to sirolimus (3 mg/d; serum target levels of 5-10 ng/ml) added on to conventional therapy (n=21) or conventional treatment alone (n=20). Primary outcome was GFR (iohexol plasma clearance) change at 1 and 3 years versus baseline. At the 1-year preplanned interim analysis, GFR fell from 26.7±5.8 to 21.3±6.3 ml/min per 1.73 m(2) (P<0.001) and from 29.6±5.6 to 24.9±6.2 ml/min per 1.73 m(2) (P<0.001) in the sirolimus and conventional treatment groups, respectively. Albuminuria (73.8±81.8 versus 154.9±152.9 μg/min; P=0.02) and proteinuria (0.3±0.2 versus 06±0.4 g/24 h; P<0.01) increased with sirolimus. Seven patients on sirolimus versus one control had de novo proteinuria (P=0.04), ten versus three patients doubled proteinuria (P=0.02), 18 versus 11 patients had peripheral edema (P=0.04), and 14 versus six patients had upper respiratory tract infections (P=0.03). Three patients on sirolimus had angioedema, 14 patients had aphthous stomatitis, and seven patients had acne (P<0.01 for both versus controls). Two patients progressed to ESRD, and two patients withdrew because of worsening of proteinuria. These events were not observed in controls. Thus, the independent data and safety monitoring board recommend early trial termination for safety reasons. At 1 year, total kidney volume (assessed by contrast-enhanced computed tomography imaging) increased by 9.0% from 2857.7±1447.3 to 3094.6±1519.5 ml on sirolimus and 4.3% from 3123.4±1695.3 to 3222.6±1651.4 ml on conventional therapy (P=0.12). On follow-up, 37% and 7% of serum sirolimus levels fell below or exceeded the therapeutic range, respectively. Finding that sirolimus was unsafe and ineffective in patients with ADPKD and renal insufficiency suggests that mTOR inhibitor therapy may be contraindicated in this context. Copyright © 2016 by the American Society of Nephrology.

Effect of Sirolimus on Disease Progression in Patients with Autosomal Dominant Polycystic Kidney Disease and CKD Stages 3b-4

PubMed Central

Ruggenenti, Piero; Gentile, Giorgio; Perico, Norberto; Perna, Annalisa; Barcella, Luca; Trillini, Matias; Cortinovis, Monica; Ferrer Siles, Claudia Patricia; Reyes Loaeza, Jorge Arturo; Aparicio, Maria Carolina; Fasolini, Giorgio; Gaspari, Flavio; Martinetti, Davide; Carrara, Fabiola; Rubis, Nadia; Prandini, Silvia; Caroli, Anna; Sharma, Kanishka; Antiga, Luca; Remuzzi, Andrea

2016-01-01

Background and objectives The effect of mammalian target of rapamycin (mTOR) inhibitors has never been tested in patients with autosomal dominant polycystic kidney disease (ADPKD) and severe renal insufficiency. Design, setting, participants, & measurements In this academic, prospective, randomized, open label, blinded end point, parallel group trial (ClinicalTrials.gov no. NCT01223755), 41 adults with ADPKD, CKD stage 3b or 4, and proteinuria ≤0.5 g/24 h were randomized between September of 2010 and March of 2012 to sirolimus (3 mg/d; serum target levels of 5–10 ng/ml) added on to conventional therapy (n=21) or conventional treatment alone (n=20). Primary outcome was GFR (iohexol plasma clearance) change at 1 and 3 years versus baseline. Results At the 1-year preplanned interim analysis, GFR fell from 26.7±5.8 to 21.3±6.3 ml/min per 1.73 m2 (P<0.001) and from 29.6±5.6 to 24.9±6.2 ml/min per 1.73 m2 (P<0.001) in the sirolimus and conventional treatment groups, respectively. Albuminuria (73.8±81.8 versus 154.9±152.9 μg/min; P=0.02) and proteinuria (0.3±0.2 versus 06±0.4 g/24 h; P<0.01) increased with sirolimus. Seven patients on sirolimus versus one control had de novo proteinuria (P=0.04), ten versus three patients doubled proteinuria (P=0.02), 18 versus 11 patients had peripheral edema (P=0.04), and 14 versus six patients had upper respiratory tract infections (P=0.03). Three patients on sirolimus had angioedema, 14 patients had aphthous stomatitis, and seven patients had acne (P<0.01 for both versus controls). Two patients progressed to ESRD, and two patients withdrew because of worsening of proteinuria. These events were not observed in controls. Thus, the independent data and safety monitoring board recommend early trial termination for safety reasons. At 1 year, total kidney volume (assessed by contrast–enhanced computed tomography imaging) increased by 9.0% from 2857.7±1447.3 to 3094.6±1519.5 ml on sirolimus and 4.3% from 3123.4±1695.3 to 3222.6±1651.4 ml on conventional therapy (P=0.12). On follow-up, 37% and 7% of serum sirolimus levels fell below or exceeded the therapeutic range, respectively. Conclusions Finding that sirolimus was unsafe and ineffective in patients with ADPKD and renal insufficiency suggests that mTOR inhibitor therapy may be contraindicated in this context. PMID:26912555