Morphologic and functional changes in nontumorous liver tissue after radiofrequency ablation in an in vivo model: comparison of 18F-FDG PET/CT, MRI, ultrasound, and CT.

Rimlike contrast enhancement on morphologic imaging and increased tracer uptake on (18)F-FDG PET in the periphery of the necrosis can hamper differentiation of residual tumor from regenerative tissue after radiofrequency ablation of liver lesions. This study used MRI, CT, ultrasound, and (18)F-FDG PET/CT to assess the typical appearance of lesions in nontumorous animal liver tissue after radiofrequency ablation. METHODS: Lesions were created by radiofrequency ablation of normal liver parenchyma in 21 minipigs. Follow-up was performed by 3 contrast-enhanced morphologic modalities-MRI, CT, and ultrasound-and by (18)F-FDG PET/CT immediately, 3 and 10 d, and 1, 2, 3, and 6 mo after radiofrequency ablation. Images were evaluated qualitatively for areas of increased enhancement and regions of elevated tracer uptake. Furthermore, all images were assessed quantitatively by determination of ratios comparing enhancement/tracer uptake in the periphery of the necrosis with enhancement/tracer uptake in normal liver parenchyma. Imaging findings were compared with histopathology findings. RESULTS: Immediately after radiofrequency ablation, no increase in (18)F-FDG uptake was visible, whereas elevated enhancement was noticed in the periphery of the necrosis on all morphologic imaging procedures. At further follow-up, an area of rimlike increase in (18)F-FDG uptake surrounding the necrosis was detected on PET/CT. The rimlike pattern of increased enhancement in the arterial phase was present for all liver lesions on CT, MRI, and ultrasound, especially between day 3 and month 1 after the radiofrequency ablation. Both elevated glucose metabolism and enhancement persisted for 6 mo postinterventionally. Histologic examination showed a hemorrhagic border converting into a regeneration capsule. CONCLUSION: If performed immediately after radiofrequency ablation, (18)F-FDG PET/CT probably has benefits over those of morphologic imaging procedures when assessing liver tissue for residual tumor. Later follow-up may be hampered by visualization of peripheral hyperperfusion and tissue regeneration. Further studies on a patient population are essential.     

Corticosteroids for multiple sclerosis: II. Application for disease-modifying effects

Physicians who treat multiple sclerosis (MS) face the challenge of patients exhibiting ongoing disease activity, including exacerbations, loss of functional capabilities, intellectual decline, and radiologic progression, despite being on a disease-modifying agent (DMA). After searching for factors that might at least in part explain these changes—such as nonadherent drug-taking behavior, or the presence of interfer-on-neutralizing antibodies—some providers may ultimately decide to switch the patient to another DMA. In most circumstances, patients likely derive only partial effects from these agents, even in the absence of compromising factors. Thus, a number of factors must be considered in order to intensify the treatment regimen in response to disease progression. In the context of an inadequate treatment response to a DMA, some clinicians will convert the patient to an alternative therapy, and others will instead use a second agent in combination with the first (the so-called platform agent). In the first of this two-part series, we explored the use of anti-inflammatory CS and ACTH to treat MS exacerbations. Although we underscored the limited availability of evidence-based studies to support specific regimens for this purpose, there is an even greater paucity of data to support the routine use of these agents in order to achieve chronic disease-modifying effects in those who continue to deteriorate clinically, radiographically, or both. Without doubt, a number of factors influence the formulation of combination treatment plan for MS. Nevertheless, we will focus on the rationale and practical schemes that can be considered for using corticosteroids (CS) (and perhaps even ACTH) in an attempt to modify various domains of ongoing disease activity.     

Gene transfer experiments imply instructive role of major histocompatibility complex class I molecules in cellular peptide processing.

DBA/2-derived mouse tumor cells were transfected with the H-2 Kb gene. Naturally processed minor histocompatibility (H) peptides were extracted from both transfected and non-transfected cells by acid elution, and were separated by high-performance liquid chromatography. Kb-restricted minor H epitopes corresponding to H-4b and mapki, both encoded by non-major histocompatibility complex genes of DBA/2, were readily detected by the respective cytotoxic T lymphocyte in peptides extracted from Kb-transfected, but not from non-transfected or Db-transfected cells. Titration experiments indicated at least 3000-fold less copies of correctly processed Kb-restricted epitopes in cells without Kb as compared to cells with Kb. Since we estimate the copy number of Kb-restricted H-4b epitopes in Kb-expressing transfectants to be less than 1000 per cell, the pool size of H-4b epitopes correctly processed in the absence of Kb should be less than 1/3 copy per cell.     

Entwicklung der Hornhautdicke und -endothelzelldichte nach Kataraktextraktion mittels Phakoemulsifikation

Ziel der vorliegenden Untersuchung war es, das Ausma? der Hornhautsch?digung durch eine Kataraktextraktion im Hinblick auf das Hornhautendothel und die Hornhautdicke zu untersuchen. Patienten und Methode: In einer prospektiven Untersuchung wurde die Entwicklung der Hornhautdicke und der Endothelzelldichte an 48 Patienten untersucht. Die Patienten wurden mittels Phakoemulsifikation operiert. Die Hornhautdicke wurde dabei mit einem Ultraschallpachymeter bei 12 Uhr und im Hornhautzentrum und die Endothelzelldichte mit einer Endothelzellkamera an den gleichen Me?punkten pr?operativ sowie 4 Wochen, 4 Monate und 1 Jahr postoperativ bestimmt. Ergebnisse: Ein Jahr postoperativ nahm die Hornhautdicke nach Phakoemulsifikation an der 12-Uhr-Position um ca. 9% und im Hornhautzentrum um ca. 12% im Vergleich zum pr?operativen Wert zu. Die Endothelzelldichte war 1 Jahr postoperativ an der 12-Uhr-Position um ca. 27% und im Zentrum um ca. 18% reduziert. Das Patientenalter korrelierte signifikant mit dem Zellverlust an beiden Me?punkten. Bezüglich der Dickenzunahme ist keine signifikante Korrelation festzustellen. Schlu?folgerung: Nach einer Kataraktextraktion ist der Hornhautstoffwechsel reduziert. Als Indikator k?nnen der Verlauf der Endothelzelldichte und der Dicke herangezogen werden.      

Disposition of oral and intravenous pravastatin in MRP2-deficient TR- rats.

The aim of this study was to characterize the role of the efflux transporter Mrp2 (Abcc2) in the pharmacokinetics of orally and intravenously administered pravastatin in rats. Eight Mrp2-deficient TR- rats and eight wild-type rats were given an oral dose of 20 mg/kg pravastatin. Four TR- animals and four wild-type animals were studied after intravenous administration of pravastatin (5 mg/kg). The TR(-) rats showed a 6.1-fold higher mean area under the plasma concentration-time curve (AUC) of pravastatin (p < 0.001) after oral administration and a 4.7-fold higher AUC (p < 0.01) after intravenous administration of pravastatin as compared with the wild-type animals. The mean systemic (total) clearance of pravastatin was 4.6-fold higher (39.2 versus 8.50 l/h/kg, p < 0.001) and the mean V 4.3-fold higher (14.1 versus 3.29 l/kg, p < 0.01) in the wild-type rats. The mean renal clearance of pravastatin in the TR(-) rats was 16.5-fold increased as compared with the wild-type animals (0.695 versus 0.042 l/h/kg, p < 0.05). The increased systemic exposure to oral pravastatin in the TR- rats was associated with a greater inhibitory effect on 3-hydroxy-3-methylglutaryl CoA reductase, as shown by smaller lathosterol to cholesterol concentration ratios. These results suggest that the reduced biliary pravastatin excretion in the Mrp2-deficient TR- rats is partly compensated for by increased urinary excretion of pravastatin. Furthermore, intestinal Mrp2 does not appear to play a major role in the oral absorption of pravastatin in normal rats.     

Assessment of the reliability and validity of panoramic imaging for assessment of mandibular condyle morphology using both MRI and clinical examination as the gold standard.

OBJECTIVES: The purpose of this study was to evaluate both reliability and validity of the assessment of the shape of the mandibular condyle in panoramic images of the TMJ. STUDY DESIGN: Forty subjects were included and were examined according to the Research Diagnostic Criteria for Temporomandibular Disorders. Panoramic radiographs (PRs) and magnetic resonance images (MRIs) were completed for all subjects. Both MRIs and PRs were rated by raters blinded to the clinical diagnosis. Kappa statistics were used to compare the results of the raters of the PRs. Additionally, the specificity and the sensitivity of the PRs were calculated for 2 scenarios: one with MRI and the other with clinical findings as the gold standard. RESULTS: The sensitivity was 0.94 (specificity = 0.45) for the assumption that MRI is the gold standard and 0.86 (specificity = 0.49) for the assumption that the clinical examination is the gold standard. For reliability, the results for kappa ranged from 0.06 to 0.327. CONCLUSION: It can be concluded that PRs are not a reliable method of accurately judging the shape of the mandibular condyle.     

Bacterial hydrogen peroxide contributes to cerebral hyperemia during early stages of experimental pneumococcal meningitis.

Alterations of blood flow contribute to major clinical complications in invasive infections such as sepsis and bacterial meningitis. As a unique feature streptococci -- in particular, Streptococcus pneumoniae, the most frequent pathogen in bacterial meningitis -- release hydrogen peroxide (H(2)O(2)) because of the absence of functional catalase. In a 6 h rat model of experimental meningitis, we studied the impact of bacterial H(2)O(2) production on regional cerebral blood flow (rCBF) and intracranial pressure (ICP). Compared to wild-type D39 pneumococci, the increase of rCBF was diminished in meningitis induced by the H(2)O(2) defective SpxB(-) mutant (maximum increase, 135% +/- 17% versus 217% +/- 23% of the individual baseline; P<0.01) or after treatment of D39-induced meningitis with H(2)O(2)-degrading catalase or with tetraethylammonium (TEA), a blocker of calcium-sensitive potassium channels, which mediate H(2)O(2)-induced vasodilation. Catalase did not significantly reduce the remaining rCBF increase caused by SpxB(-), supporting the predominant role of bacterial H(2)O(2). We conclude that in addition to host-sided mediators, bacterial-derived H(2)O(2) acts as a potent vasodilator, which accounts for a certain proportion of the early cerebral hyperperfusion in pneumococcal meningitis.