Mark E. Mullins

Adverse vascular effects of homocysteine are modulated by endothelium-derived relaxing factor and related oxides of nitrogen.

Elevated levels of homocysteine are associated with an increased risk of atherosclerosis and thrombosis. The reactivity of the sulfhydryl group of homocysteine has been implicated in molecular mechanisms underlying this increased risk. There is also increasingly compelling evidence that thiols react in the presence of nitric oxide (NO) and endothelium-derived relaxing factor (EDRF) to form S-nitrosothiols, compounds with potent vasodilatory and antiplatelet effects. We, therefore, hypothesized that S-nitrosation of homocysteine would confer these beneficial bioactivities to the thiol, and at the same time attenuate its pathogenicity. We found that prolonged (> 3 h) exposure of endothelial cells to homocysteine results in impaired EDRF responses. By contrast, brief (15 min) exposure of endothelial cells, stimulated to secrete EDRF, to homocysteine results in the formation of S-NO-homocysteine, a potent antiplatelet agent and vasodilator. In contrast to homocysteine, S-NO-homocysteine does not support H2O2 generation and does not undergo conversion to homocysteine thiolactone, reaction products believed to contribute to endothelial toxicity. These results suggest that the normal endothelium modulates the potential, adverse effects of homocysteine by releasing EDRF and forming the adduct S-NO-homocysteine. The adverse vascular properties of homocysteine may result from an inability to sustain S-NO formation owing to a progressive imbalance between the production of NO by progressively dysfunctional endothelial cells and the levels of homocysteine.

Peroxynitrite-induced rat colitis—A new model of colonic inflammation

BACKGROUND Excessive production of nitric oxide, characteristic of inflamed states, may have deleterious effects through its facile conversion (in the presence of O2) to peroxynitrite, which promotes lipid and sulfhydryl oxidation. This study assessed the effect of peroxynitrite on the rat colon. METHODS Peroxynitrite was administered intrarectally to rats. One, 3, 7, and 21 days after treatment, a distal colonic segment was isolated and tissue was obtained for histological evaluation and determination of myeloperoxidase activity and NOX, and eicosanoids generation. RESULTS Within 24 hours, the exposed segment was edematous and congested with occasional hemorrhagic mucosal ulceration. On day 7, the lumen was narrow; at day 21, there were signs of stenosis. Histological analysis showed transmucosal necrosis, acute inflammation, and exudative edema 24 hours after treatment. Surface re-epithelization and infiltration of granulation tissue were present at 1 week. Resolution of edema, mucin repletion, thickening of muscularis mucosa and propria, and fibrosis were observed at 3 weeks. Significant increase in NOX generation and myeloperoxidase and NO synthase activities were observed at 24 hours, whereas enhanced leukotriene generation was observed only at 21 days. CONCLUSIONS Peroxynitrite-induced colonic inflammation provides a novel model of NO-related tissue injury and offers the opportunity to further explore the potential role of NO in the pathogenesis of inflammatory bowel disease.

Glioma recurrence versus radiation necrosis? A pilot comparison of arterial spin-labeled, dynamic susceptibility contrast enhanced MRI, and FDG-PET imaging.

RATIONALE AND OBJECTIVES Distinguishing recurrent glial tumor from radiation necrosis can be challenging. The purpose of this pilot study was to preliminarily compare unenhanced arterial spin-labeled (ASL) imaging, dynamic susceptibility contrast-enhanced cerebral blood volume (DSCE-CBV) magnetic resonance imaging, and positron emission tomographic (PET) imaging in distinguishing predominant glioma recurrence or progression from predominant radiation necrosis in postoperative patients treated with proton-beam therapy. METHODS Patients with grade II to IV glioma previously treated with surgery and proton-beam therapy were enrolled on the basis of new enhancing nodules or masses with primary differential diagnoses of predominant tumor recurrence or progression versus radiation necrosis. ASL, DSCE-CBV, and PET examinations were assessed by visual qualitative and quantitative analysis for the detection of predominant tumor recurrence. Imaging results were correlated with a clinical-pathologic reference standard. RESULTS Thirty patients were studied, resulting in 33 ASL, 32 DSCE-CBV, and 26 PET examinations. On the basis of visual inspection, the sensitivities of PET, ASL, and DSCE-CBV examinations for detecting high-grade tumor foci were 81%, 88%, and 86%, respectively. The highest sensitivity values for quantitative ASL imaging were obtained using a normalized cutoff ratio of 1.3, resulting in sensitivity of 94% for ASL imaging and 71% for DSCE-CBV imaging. When predominant high-grade tumors with superimposed regions of predominant mixed radiation necrosis were excluded, DSCE-CBV sensitivity improved to 90%, but ASL sensitivity remained unchanged. CONCLUSIONS Compared with DSCE-CBV imaging, ASL imaging may more accurately distinguish predominant recurrent high-grade glioma from radiation necrosis, especially in regions with mixed radiation necrosis, for which DSCE-CBV imaging may underestimate true blood volume because of leakage artifacts.

Improved Detection of Skull Metastasis with Diffusion-Weighted MR Imaging

BACKGROUND AND PURPOSE: Metastasis to the skull is clinically important, but routine MR imaging offers moderate sensitivity for skull-metastasis detection in our experience. We sought to determine if diffusion-weighted MR imaging (DWI) could improve the detection of skull metastasis in patients with primary carcinomas that metastasized to bone compared with conventional MR imaging. MATERIALS AND METHODS: Seventy-five patients from the tumor registry of our institution with extracranial primary malignancy who had brain MR imaging with DWI and radionuclide bone scanning (RNBS, gold standard) within a 6-week interval were evaluated. Thirty-eight patients demonstrated increased radiopharmaceutical uptake on RNBS, consistent with skull metastasis of any size, and the remaining 37 were control subjects. Two readers correlated the DWI and conventional MR imaging with RNBS. RESULTS: The overall sensitivity of DWI for detection of skull metastases was 68.4%–71.1% (κ = 0.68) versus 42.1%–55.3% (κ = 0.65) for conventional MR imaging. Breast cancer (n = 20) was detected with greatest sensitivity of 86.7%–93.3% (κ = 0.80) for DWI versus 60%–80% (κ = 0.5) for conventional MR imaging. Lung cancer (n = 32) was detected with 63.6%–72.7% sensitivity (κ = 0.56), and prostate cancer (n = 8) with 14.3% sensitivity (κ = 0.5) for DWI versus 27.3%–36.4% (κ = 0.81) and 14.3–42.9% (κ = 0), respectively, for conventional MR imaging. CONCLUSIONS: DWI is a useful sequence for identifying focal skull metastases for breast and lung malignancies and, compared with conventional MR imaging, provides improved detection of these lesions. DWI is insensitive for detecting skull metastases from prostate carcinoma.

Potential Influence of Acute CT on Inpatient Costs in Patients with Ischemic Stroke

RATIONALE AND OBJECTIVES Patients presenting with ischemic brain symptoms have widely variable outcomes dependent to some degree on the pathologic basis of their stroke syndrome. The purpose of this study was to determine the cost implications of the emergency use of a computed tomographic (CT) protocol comprising unenhanced CT, head and neck CT angiography, and whole-brain CT perfusion. MATERIALS AND METHODS By using a retrospective patient database from a tertiary care facility and publicly available cost data, the authors derived the potential savings from the use of CT angiography. CT perfusion, or both at hospital arrival by means of a cost model. The cost of the CT angiography-CT perfusion protocol was determined from Medicare reimbursement rates and compared with that of traditional imaging protocols. Cost savings were estimated as a decrease in the length of stay for most stroke patients, whereas the most benign (lacunar) strokes were assumed to be managed in a non-acute setting. Misdiagnosis cost (erroneously not admitting a patient with nonlacunar stroke) was calculated as the cost of a severe complication. Sensitivity testing included varying the percentage of misdiagnosed patients and admitting patients with lacunar stroke. RESULTS The nationwide net savings that would result from the adoption of the CT angiography-CT perfusion protocol are in the

Can chest and abdominal trauma CT eliminate the need for plain films of the spine? – Experience with 329 multiple trauma patients

1.2 billion range (-

Evaluating medical students on radiology clerkships in a filmless environment: use of an electronic test prepared from PACS and digital teaching collection images.

154 million to

Impact of PACS and Voice-Recognition Reporting on the Education of Radiology Residents

2.1 billion) when patients with lacunar strokes are treated nonacutely and

How Much Do Common Imaging Studies Cost? A Nationwide Survey of Radiology Trainees.

1.8 billion when those patients are admitted for acute care. CONCLUSION The results demonstrate the potential effect of implementing a CT angiography-CT perfusion protocol. In particular, prompt CT angiography-CT perfusion imaging could have an effect on the cost of acute care in the treatment of stroke.

Persistence of gadolinium contrast enhancement in CSF: a possible harbinger of gadolinium neurotoxicity?

Purpose: To compare the accuracy of spine plain films with chest and abdominal trauma CT in detection of spine fractures. Methods: The study prospectively enrolled 329 multiple trauma patients. Of these, 38 patients had both chest CT for trauma and thoracic spine plain films, and 87 patients had both abdominal CT for trauma and lumbar spine plain films. Results: Of the fractures visible at either chest trauma CT or thoracic spine plain film examination, all were diagnosed on CT and 62 % on plain films. Of fractures visible at either abdominal trauma CT or lumbar spine plain films, 94 % were diagnosed on CT and 67 % on plain films. The one false negative CT involved an articular process fracture, which was visible but not mentioned, in a patient with a sacral fracture. Conclusion: Evaluation of the digital scout images and bone windows when a patient has chest and abdominal trauma CT appears to be as accurate as thoracic and lumbar spine plain films in the evaluation of spinal trauma.