Biotransformation of 1-nitropyrene to 1-aminopyrene and N-formyl-1-aminopyrene by the human intestinal microbiota

The nitropolycyclic aromatic hydrocarbon 1-nitropyrene (1-NP) is an environmental pollutant, a potent bacterial and mammalian mutagen, and a carcinogen. The metabolism of 1-NP by the human intestinal microbiota was studied using a semicontinuous culture system that simulates the colonic lumen. [3H]-1-Nitropyrene was metabolized by the intestinal microbiota to 1-aminopyrene (1-AP) and N-formyl-1-aminopyrene (FAP) as determined by high-performance liquid chromatography (HPLC) and mass spectrometry. Twenty-four hours after the addition of [3H]-1-NP, the formylated compound and 1-AP accounted for 20 and 80% of the total metabolism, respectively. This percentage increased to 66% for FAP after 24 h following 10 d of chronic exposure to unlabeled 1-NP, suggesting metabolic adaptation to 1-NP by the microbiota. Both 1-AP and FAP have been shown to be nonmutagenic towards Salmonella typhimurium TA98, which indicates that the intestinal microflora may potentially detoxify 1-NP.     

Efficacy and safety of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. Multicenter phase III clinical trials. Efficacy of early imaging

The efficacy of contrast-enhanced magnetic resonance imaging (MRI) for detecting and characterizing, or excluding, hepatic masses was assessed in 404 patients, following the intravenous administration of mangafodipir trisodium (MnDPDP) injection, a hepatic MRI contrast agent. An initial contrast-enhanced computed tomography (CT) examination was followed by unenhanced MRI, injection of MnDPDP (5 micromol/kg IV), and enhanced MRI at 15 minutes post injection. Agreement of the radiologic diagnoses with the patients' final diagnoses was higher for enhanced MRI and for the combined unenhanced and enhanced MRI evaluations than for unenhanced MRI alone or enhanced CT using the clinical diagnosis as the gold standard. Mangafodipir-enhanced MRI uniquely provided additional diagnostic information in 48% of the patients, and patient management was consequently altered in 6% of the patients. MnDPDP-enhanced MRI was comparable or superior to unenhanced MRI and enhanced CT for the detection, classification, and diagnosis of focal liver lesions in patients with known or suspected focal liver disease.     

Safety and efficacy of mangafodipir trisodium (MnDPDP) injection for hepatic MRI in adults: results of the U.S. multicenter phase III clinical trials (safety)

The short-term safety of mangafodipir trisodium (MnDPDP) injection was studied in 546 adults with known or suspected focal liver lesions. An initial contrast-enhanced computed tomography examination was followed by unenhanced magnetic resonance imaging (MRI), injection of MnDPDP (5 micromol/kg), and enhanced MRI. Adverse events were reported for 23% of the patients; most were mild to moderate in intensity, did not require treatment, and were not drug related. The most commonly reported adverse events were nausea (7%) and headache (4%). The incidence of serious adverse events was low (nine events in six patients) and not drug related. Injection-associated discomfort was reported for 69% of the patients, and the most commonly reported discomforts included heat (49%) and flushing (33%). Changes in laboratory values and vital signs were generally transient, were not clinically significant, and did not require treatment. There were no clinically significant short-term risks from exposure to MnDPDP.     

Three-dimensional multislice helical computed tomography with the volume rendering technique in the detection of vascular complications after liver transplantation

BACKGROUND: Hepatic artery stenosis and thrombosis are common complications in liver transplant patients. Digital subtraction angiography (DSA) has served as the gold standard to make this diagnosis. More recently, three-dimensional helical computed tomographic arteriography (3D CTA) with maximum intensity projection and shaded surface display techniques has been compared with DSA. The purpose of this study was to determine whether 3D CTA with the volume rendering technique is a useful and accurate tool in the detection of vascular complications after liver transplantation. METHODS: Thirty-five consecutive liver transplant patients underwent 3D CTA with volume rendering technique. The standard of reference was DSA for 20 patients and imaging and clinical follow-up for 15 patients. Two blinded reviewers evaluated the axial and 3D CTA images in consensus. RESULTS: 3D CTA with volume rendering technique detected 10 hepatic artery stenoses, six hepatic artery thromboses, two hepatic artery pseudoaneurysms, two splenic artery aneurysms, two portal vein stenoses, and four redundant hepatic arteries. In one case computed tomography (CT) detected a moderate hepatic artery stenosis, while conventional angiography showed a normal artery. The sensitivity of CT for detecting vascular lesions was 100%, specificity was 89% (8 of 9), accuracy was 95% (19 of 20), positive predictive value was 92% (11 of 12), and negative predictive value was 100% (8 of 8). CONCLUSIONS: 3D CTA is a useful and accurate noninvasive technique for detection of vascular complications in liver transplant patients.     

Small hypervascular hepatocellular carcinoma revealed by double arterial phase CT performed with single breath-hold scanning and automatic bolus tracking

OBJECTIVE: The purpose of this study was to evaluate the usefulness of double arterial phase CT for the detection of small hypervascular hepatocellular carcinomas, using an automated bolus-tracking technique to initiate the hepatic arterial phase CT. MATERIALS AND METHODS: Double arterial and late phase contrast-enhanced helical CT scans were obtained on 287 consecutive patients suspected of having hepatocellular carcinoma. These included 56 patients with 90 small (< or 3 cm) hepatocellular carcinomas and 50 patients with no hepatocellular carcinomas. CT scans of these patients were interpreted by three reviewers. The first arterial phase scan was initiated automatically 10 sec after the bolus-tracking program detected the threshold enhancement of 50 H in the abdominal aorta. Three reviewers interpreted the late phase CT scans in combination with the first, second, or both hepatic arterial phases. Measures of the reviewers' detection of hepatocellular carcinoma included analysis of interobserver variation, sensitivity, specificity, and area under receiver operating characteristic curve (A(z)). RESULTS: The time elapsed from bolus initiation to threshold aortic enhancement ranged from 10 to 24 sec (mean, 13 sec), resulting in initiation of the first arterial phase CT scan from 20 to 34 sec (mean, 23 sec). The combination of late phase CT and both first and second arterial phase images showed significantly better performance than the combination of the late phase and either the first or second arterial phases, although the difference was most evident in comparison with the combination of second arterial and late phases. CONCLUSION: An automated bolus-tracking program can be used to optimize the timing of hepatic arterial phase CT. Multiphasic CT performed using this technique is useful in detection of small hepatocellular carcinoma.