Implementing the clinical nurse specialist role in a regional state psychiatric hospital

Clinical nurse specialists (CNSs) are essential to enhancing psychiatric-mental health nursing within state psychiatric hospital settings. This article presents a project focused on the CNSs in a state psychiatric hospital to expand their clinical role to increase the quality of care to individuals with serious mental illness and their numbers in other state psychiatric hospitals. As the patient population served in these settings becomes more complex, it is critical that advanced practice nurses are provided with appropriate updated state-of-the-art advanced knowledge and skills to collaborate within the interdisciplinary team. Furthermore, because of the complexity of the client and systems characteristics, the CNSs' clinical leadership is critical to promote the best practices in direct care services as well as provide support to various levels of nursing through staff development and training, role modeling, and mentoring of new staff.     

Early identification of relocation risk in older adults with critical illness

One aspect of an evidence-based practice (EBP) guideline on managing relocation in cognitively intact older adults is elaborated upon in this article. The older population is at particular risk for needing to relocate to a new permanent home following hospitalization for a critical illness, but planning for these moves is often done in crisis mode. The purpose of this article is to sensitize nurses to risks for relocation in critically ill older persons and to encourage application of the EBP guideline in practice. Recommendations for risk assessment are made including using existing and supplementary assessment methods and data. Implementing EBP guidelines such as this is one key element in providing quality care to critically ill older adults.     

Detection of upper tract urothelial neoplasms: sensitivity of axial, coronal reformatted, and curved-planar reformatted image-types utilizing 16-row multi-detector CT urography

Background  The purpose of our study was to determine the sensitivity of 16-row multi-detector computed tomography urography (CTU) axial, coronal reformatted, and curved-planar reformatted image-types for upper tract urothelial neoplasm detection. Methods  Twenty-one CTU examinations were identified that contained one or more pathology-proven upper tract urothelial neoplasms during our study period. Two readers independently reviewed 1.25 and 2.5 mm axial, coronal reformatted, and curved-planar reformatted excretory phase CTU images. Each reader then documented the location and appearance of lesions suspicious for upper tract urothelial neoplasm. These results were correlated with relevant endoscopic/surgical procedure notes as well as pathology results. Results  Reader #1 detected 72%, 63%, 75%, and 72% of the known 32 upper tract urothelial neoplasms using 1.25 mm axial, 2.5 mm axial, coronal reformatted, and curved-planar reformatted image-types, respectively. Reader #2 detected 72% of the known neoplasms using each of the four image-types. No significant difference in sensitivity between image-types was identified. After combining the results for all four image-types, readers #1 and #2 had overall sensitivities of 94% and 91%. Conclusions  Axial, coronal reformatted, and curved-planar reformatted image-types have similar sensitivities for the detection of upper tract urothelial neoplasm in 16-row multi-detector CTU. Reviewing multiple image-types increases the sensitivity of urothelial lesion detection.     

N-(4-Hydroxyphenyl)retinamide increases dihydroceramide and synergizes with dimethylsphingosine to enhance cancer cell killing

Fenretinide [N-(4-hydroxyphenyl)retinamide (4-HPR)] is cytotoxic in many cancer cell types. Studies have shown that elevation of ceramide species plays a role in 4-HPR cytotoxicity. To determine 4-HPR activity in a multidrug-resistant cancer cell line as well as to study ceramide metabolism, MCF-7/AdrR cells (redesignated NCI/ADR-RES) were treated with 4-HPR and sphingolipids were analyzed. TLC analysis of cells radiolabeled with [3H]palmitic acid showed that 4-HPR elicited a dose-responsive increase in radioactivity migrating in the ceramide region of the chromatogram and a decrease in cell viability. Results from liquid chromatography/electrospray tandem mass spectrometry revealed large elevations in dihydroceramides (N-acylsphinganines), but not desaturated ceramides, and large increases in complex dihydrosphingolipids (dihydrosphingomyelins, monohexosyldihydroceramides), sphinganine, and sphinganine 1-phosphate. To test the hypothesis that elevation of sphinganine participates in the cytotoxicity of 4-HPR, cells were treated with the sphingosine kinase inhibitor d-erythro-N,N-dimethylsphingosine (DMS), with and without 4-HPR. After 24 h, the 4-HPR/DMS combination caused a 9-fold increase in sphinganine that was sustained through +48 hours, decreased sphinganine 1-phosphate, and increased cytotoxicity. Increased dihydrosphingolipids and sphinganine were also found in HL-60 leukemia cells and HT-29 colon cancer cells treated with 4-HPR. The 4-HPR/DMS combination elicited increased apoptosis in all three cell lines. We propose that a mechanism of 4-HPR-induced cytotoxicity involves increases in dihydrosphingolipids, and that the synergy between 4-HPR and DMS is associated with large increases in cellular sphinganine. These studies suggest that enhanced clinical efficacy of 4-HPR may be realized through regimens containing agents that modulate sphingoid base metabolism.     

SB 234551 selective ET(A) receptor antagonism: perfusion/diffusion MRI used to define treatable stroke model, time to treatment and mechanism of protection

Mismatches between tissue perfusion-weighted imaging (PWI; an index of blood flow deficit) and cellular diffusion-weighted imaging (DWI; an index of tissue injury) provide information on potentially salvageable penumbra tissue in focal stroke and can identify “treatable” stroke patients. The present pre-clinical studies were conducted to: a.) Determine PWI (using perfusion delay) and DWI measurements in two experimental stroke models, b.) Utilize these measurements to characterize selective ET_A receptor antagonism (i.e., determine efficacy, time-to-treatment and susceptibility to treatment in the different stroke models), and c.) Determine if increasing the reduced blood flow following a stroke is a mechanism of protection. Permanent middle cerebral artery occlusion (MCAO) or sham surgeries were produced in Sprague Dawley rats (SD; proximal MCAO; hypothesized to be a model of slowly evolving brain injury with a significant penumbra) and in spontaneously hypertensive rats (SHR; distal MCAO; hypothesized to be a model of rapidly evolving brain injury with little penumbra). Infusions of vehicle or SB 234551 (3, 10, or 30 µg/kg/min) were initiated at 0, 75, and/or 180 min post-surgery and maintained for the remainder of 24 h post-surgery. Hyper-intense areas of perfusion delay (PWI) in the forebrain were measured using Gadolinium (Gd) bolus contrast. DWI hyper-intense areas were also measured, and the degree of forebrain DWI-PWI mismatch was determined. Region specific analyses (ROI) were also conducted in the core ischemic and low perfusion/penumbra areas to provide indices of perfusion and changes in the degree of tissue perfusion due to SB 234551 treatment. At 24 h post-surgery, final infarct volume was measured by DWI and by staining forebrain slices. Following SD proximal MCAO, there was a significant mismatch in the ischemic forebrain PWI compared to DWI (PWI > DWI) at 60 min which was maintained up to 150 min (all p < 0.05). By 24 h post-stroke, infarct volume was identical to the area of early perfusion deficit/PWI, suggesting a slow progression of infarct development that expanded into the significant, earlier cortical penumbra (i.e., model with salvageable tissue with potential for intervention). When SB 234551 was administered within the period of peak mismatch (i.e., at 75 min post-stroke), SB 234551 provided significant dose-related reductions in cortical (penumbral) progression to infarction (p < 0.05). Cortical protection was related to an increased/normalization of the stroke-induced decrease in tissue perfusion in cortical penumbra areas (p < 0.05). No SB 234551-induced changes in reduced tissue perfusion were observed in the striatum core ischemic area. Also, when SB-234551 was administered beyond the time of mismatch, no effect on cortical penumbra progression to infarct was observed. In comparison and strikingly different, following SHR distal MCAO there was no mismatch between PWI and DWI (PWI = DWI) as early as 60 min post-stroke, with this early change in SHR DWI being identical to the final infarct volume at 24 h, suggesting a rapidly occurring brain injury with little cortical penumbra (i.e., model with little salvageable tissue or potential for intervention). In distal MCAO, SB 234551 administered immediately at the time of stroke did not have any effect on infarct volume in SHR. These data demonstrate that selective blockade of ET_A receptors is protective following proximal MCAO in SD (i.e. a model similar to “treatable” clinical patients). The protective mechanism appears to be due to enhanced collateral blood flow and salvage of penumbra. Therefore, the use of PWI-DWI mismatch signatures can identify treatable stroke models characterized by a salvageable penumbra and can define appropriate time to treatment protocols. In addition, tissue perfusion information obtained under these conditions might clarify mechanism of protection in the evaluation of protective compounds for focal stroke.