Optimization of opacity function for computed tomography volume rendered images of the prostate using magnetic resonance reference volumes

Objective To enhance the opacity function for computed tomography (CT)-based prostate volume rendered (VR) images using reference magnetic resonance (MR) images. Materials and Methods After simulating on phantoms, ten patients with CT and MR datasets were identified/ registered. Optimal VR images were produced, and intra-modality and cross-modality errors [mean distance in voxel units (VU) from VR partial surface to target] were computed. On the CT VR images, a global transformation was computed to relate the opacity functions obtained using CT reference volumes with those obtained using MR reference volumes. Results The prostate was better visualized on MR than CT, as the intra-modality errors obtained using MR (2.78 ± 1.02 VU) were lower than on CT (3.68 ± 2.15 VU). Despite similar qualitative results as the intra-modality CT images, the cross-modality errors obtained using the individual patient data (2.77 ± 0.99 VU) and using the global transformation (2.89 ± 0.99 VU) were each closer (P = 0.010 and P = 0.011, respectively) to the intra-modality MR errors than were the intra-modality CT errors. Conclusion By optimizing the opacity function using MR reference images, CT VR images of the prostate could closely represent the prostate defined on MR; furthermore, this process can be approximated by a simple transformation. Overall, the errors were reduced to a level (<3 VU) justifying further exploration in CT-based radiotherapy treatment planning. Grant Support: This work was supported by an American Society of Therapeutic Radiology and Oncology (ASTRO) Junior Faculty Research Grant/Award, and was an oral presentation at the annual meeting of ASTRO in Philadelphia, PA in November 2006.     

Determination of dipeptides in urine

The urine of a patient suffering from dermatological purpura was examined for dipeptides by combined gas chromatography—mass spectrometry. Several dipeptides were identified and all were of the general formula, R proline, where R is one of the amino acids, glycine, alanine, leucine, isoleucine, valine, phenylalanine, glutamic acid, aspartic acid. The prevalence of proline and the percentage distributions of the other amino acids, R, strongly suggested a collagen abnormality.     

Initiation of apoptosis by granzyme B requires direct cleavage of bid, but not direct granzyme B-mediated caspase activation

The essential upstream steps in granzyme B-mediated apoptosis remain undefined. Herein, we show that granzyme B triggers the mitochondrial apoptotic pathway through direct cleavage of Bid; however, cleavage of procaspases was stalled when mitochondrial disruption was blocked by Bcl-2. The sensitivity of granzyme B-resistant Bcl-2-overexpressing FDC-P1 cells was restored by coexpression of wild-type Bid, or Bid with a mutation of its caspase-8 cleavage site, and both types of Bid were cleaved. However, Bid with a mutated granzyme B cleavage site remained intact and did not restore apoptosis. Bid with a mutation preventing its interaction with Bcl-2 was cleaved but also failed to restore apoptosis. Rapid Bid cleavage by granzyme B (<2 min) was not delayed by Bcl-2 overexpression. These results clearly placed Bid cleavage upstream of mitochondrial Bcl-2. In granzyme B-treated Jurkat cells, endogenous Bid cleavage and loss of mitochondrial membrane depolarization occurred despite caspase inactivation with z-Val-Ala-Asp-fluoromethylketone or Asp-Glu-Val-Asp-fluoromethylketone. Initial partial processing of procaspase-3 and -8 was observed irrespective of Bcl-2 overexpression; however, later processing was completely abolished by Bcl-2. Overall, our results indicate that mitochondrial perturbation by Bid is necessary to achieve a lethal threshold of caspase activity and cell death due to granzyme B.     

Professional Ethics and Patients'' Rights: Past Realities, Future Imperatives

The nature and application of professional ethics in relation to patients' rights is not always clearly understood by healthcare professionals. As a result, patients' rights are not always respected or upheld in a way that they ought to be. An undersirable consequence of this has been that patients have suffered otherwise avoidable harms. The issue of professional ethics and patients' rights is one of concern to all healthcare professionals. It is of particular concern to nurses since they are the ones who are often caught in situations involving abuses of patients' rights. This paper briefly examines the failure of professional ethics to prevent patients' rights' abuses in healthcare contexts. It also makes recommendations on how the nursing profession could respond to this problem.     

In vivo magnetic resonance imaging of experimental thrombosis in a rabbit model

The process of atherosclerotic plaque disruption has been difficult to monitor because of the lack of an animal model and the limited ability to directly visualize the plaque and overlying thrombus in vivo. Our aim was to validate in vivo magnetic resonance imaging (MRI) of the thrombus formation after pharmacological triggering of plaque disruption in the modified Constantinides animal model of plaque disruption. Atherosclerosis was induced in 9 New Zealand White male rabbits (3 kg) with aortic balloon endothelial injury followed by a high cholesterol (1%) diet for 8 weeks. After baseline (pretrigger) MRI, the rabbits underwent pharmacological triggering with Russell's viper venom and histamine, followed by another MRI 48 hours later. Contiguous cross-sectional T2-weighted fast spin echo images of the abdominal aorta were compared by histopathology. In all animals, aortic wall thickening was present on the pretrigger MRI. On MRIs performed 48 hours after triggering, a histologically confirmed intraluminal thrombus was visualized in 6 (67%) of the 9 animals. MRI data correlated with the histopathology regarding aortic wall thickness (R=0.77, P<0.0005), thrombus size (R=0.82, P<0.0001), thrombus length (R=0.86, P<0.005), and anatomic location (R=0.98, P<0.0001). In vivo, MRI reliably determines the presence, location, and size of the thrombus in this animal model of atherosclerosis and plaque disruption. The combination of in vivo MRI and the modified Constantinides animal model could be an important research tool for our understanding of the pathogenesis of acute coronary syndromes.     

Effect of Variation in Diacylglycerol Kinase Eta (DGKH) Gene on Brain Function in a Cohort at Familial Risk of Bipolar Disorder

Several lines of evidence indicate that the diacylglycerol kinase eta (DGKH) gene is implicated in the etiology of bipolar disorder (BD). However, the functional neural mechanisms of DGKH''s risk association remain unknown. Therefore, we examined the effects of three haplotype-tagging risk variants in DGKH (single nucleotide polymorphisms rs9315885, rs1012053, and rs1170191) on brain activation using a verbal fluency functional magnetic resonance imaging task. The subject groups consisted of young individuals at high familial risk of BD (n=81) and a comparison group of healthy controls (n=75). Individuals were grouped based on risk haplotypes described in previous studies. There was a significant risk haplotype*group interaction in the left medial frontal gyrus (BA10, involving anterior cingulate BA32), left precuneus, and right parahippocampal gyrus. All regions demonstrated greater activation during the baseline condition than sentence completion. Individuals at high familial risk for BD homozygous for the DGKH risk haplotype demonstrated relatively greater activation (poor suppression) of these regions during the task vs the low-risk haplotype subjects. The reverse pattern was seen for the control subjects. These findings suggest that there are differential effects of the DGKH gene in healthy controls vs the bipolar high-risk group, which manifests as a failure to disengage default-mode regions in those at familial risk carrying the risk haplotype.