Contrast-induced nephropathy in patients with chronic kidney disease undergoing computed tomography: a double-blind comparison of iodixanol and iopamidol

BACKGROUND: Based on a single clinical trial, it has been suggested that the contrast agent iodixanol, which is isotonic to human plasma, may be less nephrotoxic than other nonionic contrast agents in renally impaired patients after intra-arterial injection. We compared the effects on renal function of iopamidol-370 injection (796 mOsm/kg) and iodixanol-320 (290 mOsm/kg) in patients with chronic kidney disease undergoing contrast-enhanced multidetector computed tomography (CE-MDCT) examinations using a multicenter, double-blind, randomized, parallel-group design. METHODS: A total of 166 patients with stable moderate-to-severe chronic kidney disease (screening and baseline serum creatinine, SCr, > or =1.5 mg/dL and/or creatinine clearance, CrCl, < or =60 mL/min) who were undergoing CE-MDCT of the liver or peripheral arteries were randomized to receive equi-iodine IV doses (40 gI) of either iopamidol-370 (370 mgI/mL) or iodixanol-320 (320 mgI/mL) at 4 mL/s. SCr and CrCl were obtained at screening, baseline, and at 48-72 +/- 6 hours after dose (mean, 57.4 hours). Contrast-induced nephropathy (CIN) was defined as an absolute increase > or =0.5 mg/dL (44.2 micromol/L) and/or a relative increase in SCr > or =25% from baseline. RESULTS: A total of 153 patients were included in the final analysis (13 patients excluded because of lack of follow-up, hemodialysis to remove contrast, average daily CrCl variation >1% at screening). The 2 study groups were comparable with regard to age, gender distribution, the presence of diabetes, concomitant medications, hydration, and contrast dose. Mean predose SCr was 1.6 +/- 0.4 mg/dL in both groups (P = 0.9). An absolute increase > or =0.5 mg/dL (44.2 micromol/L) in SCr was observed in none of the patients receiving iopamidol-370 and in 2.6% (2/76) of patients receiving iodixanol-320 (95% confidence interval -6.2, 1.0, P = 0.2). A relative increase > or =25% in SCr occurred in 4% (3/77) of patients receiving iopamidol-370 and in 4% (3/76) of the patients receiving iodixanol-320 (95% confidence interval -6.2, 6.1, P = 1.0). CONCLUSION: The rate of CIN was similarly low in risk patients after intravenous administration of iopamidol-370 or iodixanol-320 for CE-MDCT.     

Coronary stent evaluation with coronary computed tomographic angiography: Comparison between low-osmolar,high-iodine concentration iomeprol-400 and iso-osmolar,lower-iodine concentration iodixanol-320

BackgroundReliability of coronary angiography by multidetector row CT (MDCT-CA) for stent evaluation is still a matter for debate, and it is unknown whether contrast medium characteristics may affect diagnostic performance of MDCT-CA.ObjectiveWe compared iomeprol-400 with iodixanol-320 to evaluate coronary stents with MDCT-CA.MethodsWe randomly assigned 254 patients undergoing coronary stent follow-up with the use of MDCT-CA to iomeprol-400 at 5.0 mL/sec flow rate (group 1; n = 83), iodixanol-320 at 6.2 mL/sec flow rate (group 2; n = 87), and iodixanol-320 at 5.0 mL/sec flow rate (group 3; n = 84). Heart rate (HR) immediately before and at the end of scanning, HR variation, premature heart beats, and heat sensation by visual analog scale during scanning were recorded. Mean attenuation was measured in the aortic root and coronary arteries. Image quality score and type of artifacts were assessed.ResultsMean attenuation was significantly lower in group 3 than in the other groups. In group 3, stent evaluability was significantly higher and artifact rate was significantly lower than in group 2 (99% vs 91% and 4% vs 15%) and group 1 (99% vs 92% and 4% vs 17%), respectively, mainly because of a significant lower rate of beam-hardening artifacts (3 cases in group 3 vs 22 and 27 in groups 2 and 3, respectively). In group 3, visual analog scale, HR at the end of imaging, and number of patients with premature heart beats during the scan were significantly lower than in the other groups.ConclusionsIodixanol-320 provides better image quality of coronary stents, allowing higher MDCT-CA evaluability, than iomeprol-400.     

Effect of theophylline on contrast material-nephropathy in patients with chronic renal insufficiency: controlled,randomized, double-blinded study

PURPOSE: To investigate whether the adenosine antagonist theophylline reduces the incidence of contrast material-induced nephropathy (serum creatinine level increase of at least 0.5 mg/dL [44.2 micromol/L] in 48 hours) in high-risk patients who have chronic renal insufficiency and have received at least 100 mL of contrast medium. MATERIALS AND METHODS: One hundred patients with serum creatinine levels of 1.3 mg/dL (114.3 micromol/L) or greater were randomly assigned to intravenously receive 200 mg theophylline or saline 30 minutes before administration of 100 mL or more of low-osmolarity contrast medium arterially (72 [72%] patients) or intravenously (28 [28%] patients). RESULTS: Patients receiving theophylline and control subjects were comparable with regard to risk factors for contrast-induced nephropathy such as mean serum creatinine level before contrast medium administration (2.07 mg/dL +/- 0.94 [SD] [182.9 micromol/L +/- 83.1] vs 1.92 mg/dL +/- 0.76 [169.7 micromol/L +/- 67.2], respectively), amount of contrast medium (196.5 mL +/- 84.1 vs 216.6 mL +/- 95.0, respectively), and diabetes prevalence. Theophylline prophylaxis significantly reduced the incidence of contrast material-induced nephropathy (4% vs 16%; P =.046). With theophylline, the mean serum creatinine level decreased nonsignificantly 12 (1.98 mg/dL +/- 0.77 [175.0 micromol/L +/- 68.1]; P =.09), 24 (1.97 mg/dL +/- 0.75 [174.1 micromol/L +/- 68.1]; P =.99), and 48 (1.94 mg/dL +/- 0.77 [171.5 micromol/L +/- 68.1]; P =.99)(1.94 mg/dL +/- 0.77 [171.5 micromol/L +/- 68.1]; P =.99) hours after contrast medium administration. With a placebo, serum creatinine level significantly increased 24 hours after contrast medium administration (2.01 mg/dL +/- 0.89 [177.7 micromol/L +/- 78.7]; P =.006). Urinary N-acetyl-beta-glucosaminidase level did not change with theophylline administration but significantly (P =.034) increased 24 hours after contrast medium administration with the placebo. CONCLUSION: Prophylactic administration of 200 mg theophylline reduces the incidence of contrast material-induced nephropathy in patients with chronic renal insufficiency.     

A comparison of the efficacy and safety of iopamidol-370 and iodixanol-320 in patients undergoing multidetector-row computed tomography

OBJECTIVES: To prospectively compare the effects on heart rate (HR) and contrast enhancement efficacy of iopamidol-370 and iodixanol-320 in contrast-enhanced, multidetector-row computed tomography (CE-MDCT). METHODS: IMPACT is a multicenter, double-blind study involving 166 patients undergoing CE-MDCT of the liver (n = 121) or peripheral arteries (n = 45) randomized to receive equi-iodine doses (40 gI) of iopamidol-370 or iodixanol-320 intravenous at 4 mL/s. CE-MDCT was performed using 16-MDCT scanners according to predefined imaging protocols. HR was measured with the patient in the supine position before and continuously for 5 minutes after contrast medium administration. Mean and peak increases in HR and the proportion of subjects with predefined HR increases (>5 to <10, 10 to <15, 15 to <20, >20 bpm) were compared in the 2 populations. Liver images were assessed by 2 independent, blinded readers for contrast enhancement [Hounsfield unit (HU)], using predefined regions-of-interest during the arterial and portal-venous phase of enhancement. RESULTS: Effects on HR: Eighty-four subjects received iopamidol-370 whereas 82 received iodixanol-320. Mean age, gender distribution, weight, total iodine dose, dose/body weight, concomitant medications and use of beta-blockers were comparable in the 2 groups. Mean baseline HR was similar in the 2 groups (iopamidol-370: 72.3 +/- 12.5 bpm; iodixanol-320: 74.5 +/- 11.9 bpm). Mean changes from baseline to peak postdose were similar in the 2 groups (8.0 +/- 9.3 bpm after iopamidol-370 and 8.4 +/- 14.7 after iodixanol-320, P = 0.72). The proportion of subjects in each group having increases of <5, >5 to <10, 10 to <15, 15 to <20, or >20 bpm was comparable (P = 0.87). Two subjects experienced postcontrast tachycardia (HR increase >70 bpm, peak HR of 146 and 164 bpm), both in the iodixanol-320 group (2.4%). Contrast Enhancement: Of the 121 patients undergoing liver CT, 60 received iopamidol-370 whereas 61 received iodixanol-320. Mean age, gender distribution, weight, total iodine dose, and dose/body weight were comparable in the 2 groups. Iopamidol-370 provided significantly higher HU values in abdominal aorta during the arterial phase of enhancement for both readers [R1: 301.3 +/- 80.2 vs. 273.6 +/- 65.9 HU, 95% confidence interval (6.1-56.8), P = 0.02; R2: 302.0 +/- 73.6 vs. 275.1 +/- 62.9 HU, 95% confidence interval (2.3-51.3), P = 0.03]. No significant difference was observed between the 2 contrast medium during the portal venous phase of enhancement. CONCLUSIONS: When the same injection rate and iodine dose is used, the effects on HR of bolus intravenous injections of iopamidol-370 and iodixanol-320 were similar. Iopamidol-370 provides significantly greater enhancement during the arterial phase and similar enhancement during the portal venous phase compared with iodixanol-320.     

Use of iso-osmolar nonionic dimeric contrast media in multidetector row computed tomography angiography for patients with renal impairment

OBJECTIVES: We wanted to determine the rate of contrast-induced nephropathy (CIN) caused in patients with renal impairment undergoing multidetector row computed tomography (MDCT) angiography with intravenous administration of iso-osmolar dimeric contrast media (iodixanol). MATERIALS AND METHODS: The first consecutive 100 patients referred to CT with a serum creatinine level (SCr) between 1.5 and 6 mg/dL were enrolled in the study. Serum creatinine also was determined on days 3 and 7 after the intravenous administration of 100 mL of iodixanol 270 with 5 mL/s. A CIN was considered if variation of SCr on day 3 was >0.5 mg/dl above baseline. RESULTS: Nine patients developed a CIN after MDCT angiography; 7 of them recovered completely by day 7, and the remaining 2 showed elevated SCr on day 7 but did not develop renal failure during their hospital stay. CONCLUSIONS: MDCT angiography performed in patients with impaired renal function with iodixanol may result in CIN but complete recovery is probable.     

Nitric oxide biomarkers increase during exercise-induced vasodilation in the forearm

The purpose of the study was to determine if exercise-induced vasodilation was associated with an increase in forearm plasma levels of nitric oxide (NO) biomarkers (NO2- + NO3- and L-citrulline). Twelve healthy subjects (27+/-6 yrs) performed incremental rhythmic forearm exercise with the nondominant hand for 6 min each at 15, 30 and 45% of maximal voluntary contraction (MVC). Forearm blood flow (FBF) was determined in the exercise arm using venous occlusion plethysmography. Blood samples were obtained from the antecubital vein of the exercise and nonexercise arms for the measurement of NO biomarkers. In the exercise arm, FBF increased by a mean of 150%, 335% and 585% above baseline at 15, 30 and 45% of MVC, respectively. (ANOVA, P= 0.0001). Venous plasma NO2- + NO3- levels increased from 24+/-4 micromol/L at baseline, to 29+/-5, 32+/-4 and 3+/-4 micromol/L (ANOVA, P = 0.0001). Venous plasma L-citrulline levels increased from 31+/-5 micromol/L at baseline to 58+/-10, 87+/-7 and 141+/-15 micromol/L (ANOVA, P = 0.0001). There was a linear relationship between FBF and venous plasma NO2- + NO3- (slope= 0.38+/-0.10, P=0.0007) and between L-citrulline, (slope= 5.1 +/-1.3, P = 0.0004). Venous plasma levels of NO2- + NO3- and L-citrulline in the nonexercise arm were unchanged. These results demonstrate that exercise-induced vasodilation in the forearm is associated with forearm plasma levels of NO2- + NO3- and L-citrulline, in vivo markers of NO production.     

Renal arterial stenosis in renal allografts: retrospective study of predisposing factors and outcome after percutaneous transluminal angioplasty

PURPOSE: To determine the predisposing factors to transplant renal arterial stenosis (TRAS) and assess the outcome of percutaneous transluminal angioplasty (PTA) as the primary treatment. MATERIALS AND METHODS: Of 831 renal allograft recipients (584 cadaveric, 247 living related) between January 1991 and December 1998, 72 had hypertension and/or renal dysfunction. All 72 underwent arteriography, and their medical charts were retrospectively reviewed. RESULTS: Prevalence of TRAS was 3.1% (26 of 831). Technical success rate of PTA was 94% (16 of 17), and clinical success rate was 82% (14 of 17). Those with renal dysfunction had a mean pre-PTA creatinine value of 2.6 mg/dL (230 micromol/L) +/- 0.5 (SD) versus a 1-week post-PTA value of 1.7 mg/dL (150 micromol/L) +/- 0.3 (P <.001). Of those with hypertension, all but one had substantial improvement in mean diastolic blood pressure. At 26.9 months mean follow-up in 16 patients with successful PTA, two stenoses reoccurred, and two grafts were lost to chronic rejection. TRAS was present in 14 of 45 end-to-side anastomoses and 12 of 27 end-to-end anastomoses (P =.31), and TRAS was more prevalent in cadaveric grafts (24 of 584) than in living related grafts (two of 247). In cadaveric grafts, the mean cold ischemia time was 29.0 hours +/- 6.9 in those with TRAS (n = 24), as compared with 25.5 hours +/- 8.1 in those with no TRAS (n = 39; P = .35). Seven of 17 patients with acute rejection and six of 35 with chronic rejection had TRAS. CONCLUSION: Primary treatment of TRAS with PTA has good intermediate-term results. TRAS is more prevalent in cadaveric allografts with long cold ischemia time.     

Prophylaxis of contrast material-induced nephropathy in patients in intensive care: acetylcysteine, theophylline, or both? A randomized study

PURPOSE: To prospectively compare the protective effect of acetylcysteine, theophylline, and both agents combined in patients who are admitted to the intensive care unit with at least one risk factor for contrast material-induced nephropathy and who receive at least 100 mL of iodinated contrast medium. MATERIALS AND METHODS: Institutional ethics review board approval and informed consent were obtained. A total of 91 patients (mean age, 58.5 years+/-14.8 [standard deviation]; 31 women, 60 men; 150 examinations) were admitted to the intensive care unit with at least one risk factor for contrast-induced nephropathy and received either (a) 200 mg theophylline 30 minutes before contrast medium administration (group T), (b) 600 mg acetylcysteine twice daily on the day of and (if possible) the day before the examination (group A), or (c) both agents combined (group AT). The primary endpoint for this study was the incidence of contrast-induced nephropathy (chi2 test). RESULTS: Groups T, A, and AT were comparable with regard to baseline creatinine levels and the amount of contrast medium administered. The incidence of contrast-induced nephropathy in groups T, A, and AT was 2%, 12%, and 4%, respectively, and was significantly lower in group T than in group A (P=.047). There was no significant difference in the incidence of contrast-induced nephropathy between groups A and AT (P=.148) or between groups T and AT (P=.53). For group A, serum creatinine did not change after 12, 24, or 48 hours compared with baseline. Creatinine levels in group T decreased 12 hours (1.19 mg/dL+/-0.58; P=.008) and 48 hours (1.16 mg/dL+/-0.55; P=.034) after contrast material injection compared with baseline (1.25 mg/dL+/-0.61). In group AT, creatinine significantly decreased 24 hours (1.21 mg/dL+/-0.74; P=.003) and 48 hours (1.17 mg/dL+/-0.69; P<.001) after contrast material injection compared with baseline (1.28 mg/dL+/-0.74). Group A had significantly higher maximal increases in creatinine than groups T and AT (P=.014). CONCLUSION: For prophylaxis of contrast-induced nephropathy in patients who are admitted to the intensive care unit and who receive 100 mL or more of contrast medium, theophylline is superior to acetylcysteine.     

Radiographic contrast media induced nephropathy: experimental observations and the protective effect of calcium channel blockers.

Combined acute inhibition of the synthesis of nitric oxide with L-nitroarginine methyl ester (L-NAME) and of prostacycline synthesis with indomethacin predisposes rats to severe renal injury from radiographic contrast media. The reliability of this pharmacological manipulation in the study of radiographic contrast medium induced nephropathy (RCMN) was investigated. Adult male Sprague-Dawley rats were injected with iv L-NAME (10 mg kg(-1)) and iv indomethacin (10 mg kg(-1)) 15 min apart and prior to injection of RCM or normal saline (control group). A dose-dependent reduction in renal function was observed after intravascular injection of the high osmolar RCM diatrizoate (Angiografin, 306 mgI ml(-1)). A significant (p<0.01) increase in serum creatinine (Cr) (from 54.66+/-8.39 micromol l(-1) to 171.96+/-24.49 micromol l(-1) and from 80.95+/-6.73 micromol l(-1) to 204.76+/-16.73 micromol (-1), n=5 per group) was observed 24 h after injection of 6 ml and 8 ml of diatrizoate, respectively. The increase in serum Cr after injection of 8 ml of diatrizoate recovered spontaneously to 80.87+/-8.70 micromol l(-1) 7 days after injection. No significant change in renal function was observed in the control group (n=5) receiving 8 ml kg(-1) of normal saline or after injection of 4 ml of diatrizoate (serum Cr 69.84+/-5.5 micromol l(-1) pre contrast injection and 66.67+/-13.47 micromol l(-1) 24 h post contrast injection, n=5). The increase in serum Cr observed with 6 ml of diatrizoate was significantly higher (p<0.01) than the rise induced by equivolume of the low osmolar non-ionic monomer iopromide (Ultravist, 300 mgI ml(-1)) (serum CR 68.47+/-8.39 micromol l(-1) pre contrast injection and 143.59+/-32.03 micromol l(-1) 24 h post contrast injection, n=5). The calcium channel blocker diltiazem (10 mg kg(-1) injected intraperitoneally 30 min prior to RCM injection) prevented the rise in serum Cr observed with 6 ml of diatrizoate (serum Cr pre contrast injection 70.31+/-7.28 micromol(-1) and 78.21+/-17.81 micromol(-1) 24 h post contrast injection in animals pre-treated with diltiazem, n=5). The protective effect against RCM-induced reduction in renal function was less with lower doses of diltiazem. In conclusion, the animal model used is reliable and reproduced previously established observations in the field of RCMN. The protective effect of a calcium channel blocker at the appropriate dose against RCMN has also been shown. The clinical effectiveness of this class of drugs in preventing RCMN requires further evaluation.     

Flufenamic acid: growth modulating effects on human aortic smooth muscle cells in vitro.

PURPOSE: The aim of the study was to examine the effects of flufenamic acid on proliferation, clonogenic activity, migratory ability, cell-cycle distribution, and p44/42-mitogen-activated protein kinase (MAPK) expression on serum-stimulated human aortic smooth muscle cells (haSMCs) in vitro. MATERIALS AND METHODS: HaSMCs were treated with flufenamic acid in three different doses (40 micromol/L, 200 micromol/L, 400 micromol/L) for 4 days, and then flufenamic-acid-free culture medium was supplemented every 4 days until day 20 after initial treatment. The growth kinetics were assessed. Cell-cycle analysis was performed by flow cytometry. The clonogenic activity was evaluated with use of colony formation assays. The migratory ability was investigated by stimulation with platelet derived growth factor (PDGF-BB) in 24 well plates with 8-microm pore membrane inserts. The p44/42 MAPK was detected by Western blot technique. RESULTS: Flufenamic acid inhibited the proliferation (400 micromol/L treatment over 4 d; 179,700 +/- 49,800 vs 747,900 +/- 144,000; P <.001), clonogenic activity (400 micromol/L treatment over 4 d; 1 +/- 0.3 vs 50 +/- 1.4; P <.001) and migratory ability (400 micromol/L treatment over 4 d; 8 cells +/- 2 vs 48 cells +/- 15; P <.001) of haSMCs in a dose-dependent manner. Cell-cycle analysis revealed a G2/M-phase block (400 micromol/L treatment over 4 d; 28.9 +/- 1.5 vs 9.5 +/- 3.2; P <.001). The expression of p44/42 MAPK was reduced for a treatment with 400 micromol/L flufenamic acid (controls, 427 BLU +/- 0.305 vs treatment group, 190 BLU +/- 106; P <.05) CONCLUSION: Flufenamic acid inhibits the proliferation and migration of haSMCs. Further experiments with animal models concerning stenosis and restenosis are necessary to evaluate the potential of this promising drug.     

Troglitazone improves whole-body insulin resistance and skeletal muscle glucose use in type II diabetic patients.

Recently, troglitazone has emerged as an insulin sensitizer for the treatment of type II diabetes. However, its effect on skeletal muscle glucose use (SMGU) has not been studied. METHODS: To investigate the effect of troglitazone on SMGU in patients with type II diabetes, we undertook skeletal muscle (18)F-FDG PET dynamic imaging under insulin clamping before and after administration of SMGU to 20 patients with type II diabetes. Data were compared with those for 12 age-matched healthy volunteers. RESULTS: The whole-body glucose disposal rate (GDR) was significantly lower in patients (29.9 +/- 9.83 micromol/min/kg) than in control subjects (55.6 +/- 16.5 micromol/min/kg, P < 0.01), as was the SMGU (patients, 3.27 +/- 2.17 micromol/min/kg; control subjects, 10.9 +/- 6.4 micromol/min/kg; P < 0.01). After the therapy, GDR significantly improved in patients (29.3 +/- 14.6 micromol/min/kg, P < 0.05), as did SMGU (5.06 +/- 2.11 micromol/min/kg, P < 0.05). When results for patients with and without hypertension were separately analyzed, a significant improvement in SMGU after troglitazone was seen in both normotensive and hypertensive patients (normotensive [n = 10]: baseline, 3.67 +/- 2.89 micromol/min/kg; after therapy, 5.28 +/- 2.61 micromol/min/kg; P < 0.05; hypertensive [n = 10]: baseline, 2.89 +/- 1.22 micromol/min/kg; after therapy, 4.72 +/- 1.39 micromol/min/kg; P < 0.05). GDR in patients with and without hypertension was significantly improved by troglitazone (normotensive: baseline, 17.9 +/- 10.2 micromol/min/kg; after therapy, 31.9 +/- 15.9 micromol/min/kg; P < 0.01; hypertensive: baseline, 39.6 +/- 15.1 micromol/min/kg; after therapy, 47.7 +/- 23.8 micromol/min/kg; P < 0.05). The plasma free fatty acid concentration during insulin clamping was not changed by troglitazone (baseline, 1.1 +/- 0.86 mEq/L; after therapy, 0.93 +/- 0.65 mEq/L; P = not significant). CONCLUSION: Troglitazone can improve whole-body insulin resistance through the improvement of SMGU but not through a decline in plasma free fatty acid concentration in patients with type II diabetes with or without hypertension.     

Haemodialysis for the prevention of contrast-induced nephropathy: outcome of 31 patients with severely impaired renal function,comparison with patients at similar risk and review

RATIONALE AND OBJECTIVES: To investigate whether haemodialysis prevents contrast-induced nephropathy (definition: increase of serum-creatinine of >or= 0.5 mg/dL within 7 days). MATERIALS AND METHODS: Thirty-one patients (mean serum-creatinine 4.01 +/- 1.83 mg/dL) were dialyzed for 4.36 +/- 1.0 hours within one hour after 278.4 +/- 160.5 mL of contrast medium. RESULTS: Dialysis resulted in a significant reduction of serum-creatinine (2.25 +/- 1.46 mg/dL; P< 0.0001) and stable mean serum-creatinine levels 2, 3, 4, and 7 days after contrast medium and at discharge compared with baseline values. However, 19 patients (61%) developed contrast-induced nephropathy within 7 days. Four patients had to be repeatedly dialyzed. A comparison of our patients' 48 hours-incidence of contrast-induced nephropathy (9/31; 29%) versus patients at comparable risk included in seven previous studies demonstrated a prophylactic effect of dialysis only versus a subgroup in one study. CONCLUSIONS: Data provide no hint that haemodialysis prevents contrast-induced nephropathy. Therefore, postprocedural dialysis should be restricted to patients participating in clinical studies.     

Does ethanol enhance cocaine toxicity?

OBJECTIVES: Results of in vitro and animal studies suggest that ethanol enhances cocaine toxicity. If so, then that this implies that in ethanol users, postmortem blood cocaine concentrations should be lower, or anatomic evidence demonstrable. METHODS: Drug concentrations and autopsy findings were compared in a sample of 72 accidental deaths, where only cocaine, cocaine metabolites, and ethanol were detected. Findings in ethanol positive (E+) and negative (E-) deaths were compared using multiple Student's t-tests and chi2 testing for categorical variables. RESULTS: There were 47 E-decedents and 24E+. Mean ages were similar (40.2 +/- 8.7 and 37.5 +/- 11.1 years respectively). Mean E was 0.113 (range 0.030-0.350 g/dL), and less than 0.080 g/dL in 50% of the cases. Concentrations of C and BE were not significantly different in E- and E+ groups (C = 1.40 +/- 3.6 mg/L, and 0.76 +/- 1.93 mg/L respectively, BE = 3.04 +/- 5.36 mg/L and BE 2.09 +/- 3.77 mg/L, P = 0.4621 and 0.4520). Organ weights were pathologically increased in both groups, but not significantly different. Body Mass Index (BMI) was less (23.9 vs 25.5), and heart weight was greater (449 vs 407 g) than predicted. Over half the decedents had demonstrable heart disease, and 11% died of brain haemorrhage, though the rate for both disorders was similar in each group. CONCLUSIONS: In two-thirds of the cocaine-related deaths studied, no ethanol was detected. When ethanol was present, no differences between the two groups were identified. The findings suggest that acute cocaine toxicity is not enhanced by ethanol cocaine interactions. However, ethanol concentrations were generally low, and it is possible that increased toxicity is apparent when much larger quantities of alcohol have been consumed.     

Quantification of protein synthesis in the human brain using L-[1-11C]-leucine PET: incorporation of factors for large neutral amino acids in plasma and for amino acids recycled from tissue.

The rate of incorporation of exogenous amino acids into brain proteins is indicative of the protein synthesis rate (PSR). The objective of this study was to assess the effect of plasma concentrations of leucine and large neutral amino acids (LNAAs) on the unidirectional uptake rate constant (Kcplx) of l-[1-(11)C]-leucine in the brain and to estimate the amino acid pool recycled from tissue. METHODS: Twenty-seven healthy adult volunteers (11 men and 16 women; age range, 20-50 y) underwent dynamic l-[1-(11)C]-leucine PET with arterial blood sampling. Data were analyzed with a standard 2-tissue-compartment model yielding the unidirectional uptake rate of plasma leucine into tissue (Kcplx = K(1)k(3)/(k(2) + k(3))) and the fraction of leucine originating from exogenous sources (lambda = k(2)/(k(2) + k(3))). PSR in brain was calculated as PSR = [Kcplx/lambda] x leucine. RESULTS: The mean plasma concentration of the sum of all LNAAs was 13% higher in men (981 +/- 86 micromol/L) than in women (850 +/- 76 micromol/L, P = 0.012), whereas the plasma leucine concentration was found to be similar in both sexes (men, 64 +/- 20 micromol/L; women, 58 +/- 21 micromol/L, P = 0.57). The whole-brain value for lambda was determined to be 0.64 +/- 0.03 and did not show a sex difference (P = 0.66). Whole-brain Kcplx values were significantly higher in women (0.0162 +/- 0.0024) than in men (0.0121 +/- 0.0031, P = 0.011); however, after normalization of the Kcplx to a standard plasma concentration of the sum of all LNAAs (Kcplx'), the Kcplx' was similar between the sexes (P = 0.21), as was the PSR' (1.24 +/- 0.49 micromol/L/min in men; 1.29 +/- 0.62 micromol/L/min in women, P = 0.87). No relationship between plasma leucine and Kcplx (r = -0.13, P = 0.63) was observed. Finally, there was a significant correlation between the PSR and the Kcplx derived using Patlak graphical analysis (rho = 0.65, P < 0.001). CONCLUSION: We conclude that both the Kcplx macroparameter and the PSR are stable indices of brain protein synthesis and are appropriate measures for testing altered protein synthesis in neurologic disorders.     

MDCT angiography for detection of pulmonary emboli: comparison between equi-iodine doses of iomeprol 400 mgI/mL and iodixanol 320 mgI/mL

Objectives

To compare iomeprol 400 and iodixanol 320 in pulmonary artery MDCTA in subjects with suspected pulmonary embolism.

Methods

Eighty randomized subjects received equi-iodine intravenous doses (48 g) of iomeprol 400 (n = 40) or iodixanol 320 (n = 40), via power injector at 4 mL/s. Four-row (35 subjects) and 64-row (45 subjects) scanners were used. Lumen attenuation was determined on-site and by two off-site blinded readers in the main, lobar, segmental and subsegmental pulmonary arteries. Statistical comparison between groups was performed for demographics and lumen attenuation.

Results

There were no between-group differences (p > 0.05) in demographics. Pulmonary artery attenuation was significantly (p ≤ 0.03) higher with iomeprol 400 for all readers. Attenuation quality was excellent in more patients after iomeprol 400 than after iodixanol-320 (80% vs. 62.5%; 82.5% vs. 77.5%; off-site readers 1 and 2, respectively). No safety concerns were noted.

Conclusion

The greater iodine delivery rate achievable with iomeprol 400 compared to iodixanol-320 at equi-iodine dose and injection rate permits consistently greater attenuation at all levels of the pulmonary arterial tree.     

Muscle glycogen degradation during simulation of a fatiguing soccer match in elite soccer players examined noninvasively by 13C-MRS

PURPOSE: The purpose of this research project was to noninvasively determine individual muscle glycogen [Gly] degradation during a test intended to predict individual fatigue in intense soccer matches. METHODS: The [Gly] of the calf muscles of 17 elite soccer players [age = 17.4 +/- 0.8 (SD)] were measured with 13C-MRS before and after an alternating velocity test to exhaustion. Blood samples were taken before and 3 min after the test for determination of blood metabolites. RESULTS: Average muscle [Gly] was 135 +/- 53 mmol x (kg wet weight)(-1) before and 87 +/- 27 mmol x (kg wet weight)(-1) (P < 0.001) after exhaustion (42 +/- 25 min). There was a high correlation (r = 0.87, P < 0.0001) between muscle [Gly] at rest and net muscle [Gly] utilized. There was also a more moderate correlation (r = 0.62, P < 0.01) between net muscle [Gly] used and time to exhaustion during the soccer-specific test. There was some evidence of correlation (r = 0.42, P = 0.09) between resting [Gly] and time to exhaustion. Plasma lactate increased (P < 0.001) from 0.8 +/- 0.4 before the test to 2.5 +/- 1.0 mmol x L(-1) at exhaustion, whereas ammonia was raised (P < 0.0001) from 44.1 +/- 10.3 to 89.7 +/- 14.9 micromol x L(-1). Similarly, plasma free fatty acids were elevated (P < 0.0001) from 148 +/- 106 to 797 +/- 401 micromol x L(-1), and glycerol was increased (P < 0.0001) from 48.3 +/- 17.7 to 182.2 +/- 61.8 micromol x L(-1). Insulin levels (11.9 +/- 3.7 vs 11.7 +/- 4.8 microU x mL(-1)) remained the same. Creatine kinase levels increased (P < 0.0001) from 486 +/- 501 to 640 +/- 548 micromol x L(-1) after the test. CONCLUSIONS: We conclude that exhaustion during soccer-specific performance is related to the capacity to utilize muscle [Gly]. The results underline the importance of dietary counseling (glycogen loading and resynthesis strategies) and proper training to enhance the glycogen levels and glycogenolytic capacity of the players.     

Renal tolerance of gadolinium-DTPA/dimeglumine in patients with chronic renal failure.

Safety data for renal tolerance of gadolinium-DTPA(Gd-DTPA)/dimeglumine were evaluated in 21 patients (age: mean +/- standard deviation [SD], 58 +/- 12 years) with impaired renal function. The mean +/- SD serum creatinine level at baseline was 213 +/- 101 mumol/L (range, 89.2-551 mumol/L). Creatinine clearance at baseline averaged 34.5 +/- 19.2 mL/minute (range, 7.2-70 mL/minute). Gd-DTPA was injected at a dose of 0.1 mmol/kg body weight. Serum parameters (creatinine, sodium, and potassium) were determined before and 6, 24, 48, and 120 hours after administration of Gd-DTPA. Urinary parameters (N-acetyl-beta-D-glucosaminidase [beta-NAG], protein, and albumin) were determined before (spot urine sample) and after treatment for collection periods 0 to 3, 3 to 6, 6 to 12, 12 to 24, and 24 to 48 hours. A final spot urine sample was taken at 120 hours. There was no significant statistical change of serum creatinine level within the observation period, and there was no single patient matching the criteria of acute renal failure (increase of serum creatinine level of 88.4 mumol/L [1 mg/dL] or more within 48 hours after injection). Serum values of sodium and potassium levels remained unchanged. Beta-NAG was slightly increased 0 to 3 hours after injection, but returned to baseline values during the collection periods up to 120 hours. There was no increase of protein or albumin excretion. These preliminary results suggest Gd-DTPA has good renal tolerance in patients with pre-existing chronic renal failure.     

Percutaneous metallic stents in patients with obstructive jaundice due to hepatocellular carcinoma

PURPOSE: To evaluate the technical success and clinical efficacy of percutaneously placed self-expandable metallic stents in patients with obstructive jaundice due to hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fifteen men (mean age, 59.3 years) with obstructive jaundice resulting from HCC were treated with self-expandable metallic stents (28 stents in 19 sessions). The authors evaluated the technical success, clinical success (decrease of 30% of total serum bilirubin level or <2 mg/dL [34.2 micromol/L]), treatment efficacy according to lowest total serum bilirubin level, complications, and duration of stent patency. RESULTS: Technical success was achieved in all patients. Clinical success was achieved in 11 of the 15 patients (73%). After stent placement, seven patients (47%) had a low bilirubin level (<2 mg/dL [34.2 micromol/L]), three (20%) had an intermediate bilirubin level (2-10 mg/dL [34.2-171 micromol/L]), and five (33%) had a high bilirubin level (>10 mg/dL [171 micromol/L]). A low bilirubin level was achieved in all patients with Child-Pugh A disease and stage T2 or T3 HCC. Major complications such as hemobilia necessitating transfusion (n=1) or abscess formation (n=1) occurred in two of the 19 sessions (10%). The overall mean stent patency was 149.8 days (range, 12-790 days). The mean stent patency in patients with Child-Pugh class A disease (257.8 days) was significantly longer than that of patients with Child-Pugh class B and C disease (123.2 and 63 days, respectively) (P<.05). CONCLUSIONS: The percutaneous placement of a self-expandable metallic stent is a feasible and effective palliative treatment for patients with obstructive jaundice resulting from HCC, especially for those with Child-Pugh class A disease and stage T2 or T3 HCC.     

The use of gadolinium chelates for X-ray digital subtraction angiography

RATIONALE AND OBJECTIVES: To evaluate the feasibility and safety of using gadolinium chelates for x-ray digital subtraction angiography (DSA) in patients with contraindications to iodinated contrast material. METHODS: We performed 30 DSAs in 22 patients (5 females, 17 males; mean age 64.9 years) with contraindications to iodinated contrast media (renal insufficiency: n = 28; hyperthyroidism: n = 1; contrast allergy: n = 2). Gadolinium chelates were administered as 0.5 mol/L solutions (mean volume of gadolinium chelates per patient was 34 +/- 19 mL). Gadolinium chelates were the sole contrast agent in 17 examinations, were used in conjunction with carbon dioxide (CO2) in 8 studies, (mean 212 +/- 226 mL), and were combined with the restricted use of nonionic iodinated contrast (mean 12.8 +/- 4.7 mL) in 6 examinations. We carried out 15 diagnostic angiographies and 15 percutaneous transluminal angioplasties. RESULTS: Use of gadolinium chelates allowed us to obtain diagnostic angiographic images in all cases. However, the quality of angiograms was inferior compared with that obtained with iodinated contrast agents and superior compared with CO2 as the contrast material. Adverse events were not noted. Mean serum creatinine was 2.6 +/- 1.5 mg/dL before and 2.3 +/- 1.0 mg/dL after DSA. No patient developed contrast-induced nephropathy. CONCLUSIONS: Gadolinium chelates produce an x-ray DSA intermediate in image quality between iodinated contrast and CO2. Digital subtraction angiography with intra-arterial gadolinium chelate administration may offer an alternative to iodinated contrast material in patients with contraindications to iodine.     

Risk of contrast-medium-induced nephropathy in high-risk patients undergoing MDCT – A pooled analysis of two randomized trials

The incidence of contrast-medium-induced nephropathy (CIN) following intravenous (IV) CM administration of contrast media to renally impaired patients undergoing multidetector computed tomography (MDCT) is not well characterized. Our objective was to investigate the incidence of CIN in patients with glomerular filtration rate (GFR) <60 ml/min undergoing contrast-enhanced MDCT examinations and to compare the rates of CIN following the IV administration of low-osmolar contrast media (LOCM, iopamidol and iomeprol) and an iso-osmolar contrast medium (IOCM, iodixanol). A total of 301 adult patients with moderate-to-severe renal failure received a similar IV contrast dose (40 gI). Serum creatinine (SCr) was measured at screening, baseline and 48–72?±?6 h after the MDCT examination. Primary CIN outcome was an increase in SCr ≥0.5 mg/dl (≥44.2 μmol/l) from baseline. The CIN rates were 2.3% in the total population, 0.6% when GFR >40 ml/min, 4.6% when GFR <40 ml/min and 7.8% in patients with GFR <30 ml/min. The incidence of CIN was significantly higher after iodixanol than after LOCM (seven patients, 4.7% following IOCM, no CIN cases following the LOCM; p?=?0.007). Significant differences in favor of the LOCM were also observed in patients with GFR <40 ml/min and GFR <30 ml/min. Following the IV administration of nonionic contrast agents in patients with moderate-to-severe renal insufficiency, the risk of significant CIN seems to be low. The IOCM iodixanol caused a higher rate of CIN than the LOCM iopamidol and iomeprol, especially in high-risk patients. Differences in osmolality between these LOCM and iodixanol do not play a role in the genesis of CIN.