Gated myocardial perfusion single photon emission computed tomography in the clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial, Veterans Administration Cooperative study no. 424

Background  Stress gated myocardial perfusion single photon emission computed tomography (gSPECT) is increasingly used before and after intercurrent therapeutic intervention and is the basis for ongoing evaluation in the Department of Veterans Affairs clinical outcomes utilizing revascularization and aggressive drug evaluation (COURAGE) trial. Methods and Results  The COURAGE trial is a North American multicenter randomized clinical trial that enrolled 2287 patients to aggressive medical therapy vs percutaneous coronary intervention plus aggressive medical therapy. Three COURAGE nuclear substudies have been designed. The goals of substudy 0 are to examine the diagnostic accuracy of the extent and severity of inducible ischemia at baseline in COURAGE patients compared with patient symptoms and quantitative coronary angiography and to explore the relationship between inducible ischemia and the benefit from revascularization when added to medical therapy. Substudy 1 will correlate the extent and severity of provocative ischemia with the frequency, quality, and instability of recurrent symptoms in postcatheterization patients. Substudy 2 (n _ 300) will examine the usefulness of sequential gSPECT monitoring 6 to 18 months after therapeutic intervention. Together, these nuclear substudies will evaluate the role of gSPECT to determine the effectiveness of aggressive risk-factor modifications, lifestyle interventions, and anti-ischemic medical therapies with or without revascularization in reducing patients’ ischemic burdens. Conclusions  The unfolding of evidence on the application of gSPECT in trials such as COURAGE defines a new era for nuclear cardiology. We hope the evidence that emerges from the COURAGE trial will further establish the role of nuclear imaging in the evidence-based management of patients with stable coronary disease. The COURAGE trial was supported by the Cooperative Studies Program of the Department of Veterans Affairs Office of Research and Development in collaboration with the Canadian Institutes of Health Research. Unrestricted research grants were obtained from Merck & Co; Pfizer Pharmaceuticals; Bristol-Myers Squibb Medical Imaging; Astellas Pharma; Kos Pharmaceuticals; Data Scope; Astra Zeneca Pharmaceuticals; Astra-Zeneca-Canada; Schering-Plough Coorporation, Ltd; Sanofi-Aventis, Inc; First Horizon; and GE Healthcare. All industrial funding for this trial was directed through the Department of Veterans Affairs. Additional funding for this substudy was provided by grants to the Department of Veterans Affairs and Canadian Institutes of Health Research from Astellas Pharma and Bristol-Myers-Squibb Medical Imaging.     

MBP-annexin V radiolabeled directly with iodine-124 can be used to image apoptosis in vivo using PET

A noninvasive method of measuring programmed cell death in the tumors of cancer patients using positron-emission tomography (PET) would provide valuable information regarding their response to therapeutic intervention. Our strategy is to radiolabel annexin V, a protein that binds to phosphatidylserine moieties that are translocated to the external leaflet of plasma membranes during apoptosis. We developed a phosphatidylserine-ELISA capable of distinguishing wild type from point mutant annexin V that is known to have a lower phosphatidylserine binding affinity. A maltose-binding protein/annexin V chimera was synthesized and purified with high yield using amylose resin. We showed that it bound to phosphatidylserine in the ELISA as well as to that exposed on apoptotic Jurkat cells; therefore, it was used in the development of a method for radiolabeling annexin V using iodine radionuclides. MBP-annexin V retained its phosphatidylserine binding properties on direct iodination, but at high levels of oxidizing agents (iodogen and chloramine T), its specificity for phosphatidylserine was compromised. (124)I-MBP-annexin V was successfully used to image Fas-mediated hepatic cell death in BDF-1 mice using PET. In conclusion, we have shown that MBP-annexin V and the phosphatidylserine ELISA are useful tools for the development of methods for radiolabeling annexin V for PET imaging.     

Myocardial perfusion SPECT reconstruction: Receiver operating characteristic comparison of CAD detection accuracy of filtered backprojection reconstruction with all of the clinical imaging information available to readers and solely stress slices iteratively reconstructed with combined compensation

BACKGROUND: Past receiver operating characteristic (ROC) studies have demonstrated that single photon emission computed tomography (SPECT) perfusion imaging by use of iterative reconstruction with combined compensation for attenuation, scatter, and detector response leads to higher area under the ROC curve (A(z)) values for detection of coronary artery disease (CAD) in comparison to the use of filtered backprojection (FBP) with no compensations. A new ROC study was conducted to investigate whether this improvement still holds for iterative reconstruction when observers have available all of the imaging information normally presented to clinical interpreters when reading FBP SPECT perfusion slices. METHODS AND RESULTS: A total of 87 patient studies including 50 patients referred for angiography and 37 patients with a lower than 5% likelihood for CAD were included in the ROC study. The images from the two methods were read by 4 cardiology fellows and 3 attending nuclear cardiologists. Presented for the FBP readings were the short-axis, horizontal long-axis, and vertical long-axis slices for both the stress and rest images; cine images of both the stress and rest projection data; cine images of selected cardiac-gated slices; the CEQUAL-generated stress and rest polar maps; and an indication of patient gender. This was compared with reading solely the iterative reconstructed stress slices with combined compensation for attenuation, scatter, and resolution. With A(z) as the criterion, a 2-way analysis of variance showed a significant improvement in detection accuracy for CAD for the 7 observers (P = .018) for iterative reconstruction with combined compensation (A(z) of 0.895 +/- 0.016) over FBP even with the additional imaging information provided to the observers when scoring the FBP slices (A(z) of 0.869 +/- 0.030). When the groups of 3 attending physicians or 4 cardiology fellows were compared separately, the iterative technique was not statistically significantly better; however, the A(z) for each of the 7 observers individually was larger for iterative reconstruction than for FBP. Compared with results from our previous studies, the additional imaging information did increase the diagnostic accuracy of FBP for CAD but not enough to undo the statistically significantly higher diagnostic accuracy of iterative reconstruction with combined compensation. CONCLUSIONS: We have determined through an ROC investigation that included two classes of observers (experienced attending physicians and cardiology fellows in training) that iterative reconstruction with combined compensation provides statistically significantly better detection accuracy (larger A(z)) for CAD than FBP reconstructions even when the FBP studies were read with all of the extra clinical nuclear imaging information normally available.     

Gender differences in frontal and sagittal plane biomechanics during drop landings

PURPOSE: To determine gender differences in lower-extremity joint kinematics and kinetics between age- and skill-matched recreational athletes. METHODS: Inverse dynamic solutions estimated the lower-extremity flexion-extension and varus-valgus kinematics and kinetics for 15 females and 15 males performing a 60-cm drop landing. A mixed model, repeated measures analysis of variance (gender (*) joint) was performed on select kinematic and kinetic variables. RESULTS: Peak hip and knee flexion and ankle dorsiflexion angles were greater in females in the sagittal plane (group effect, P < 0.02). Females exhibited greater frontal plane motion (group (*) joint, P = 0.02). Differences were attributed to greater peak knee valgus and peak ankle pronation angles (post hoc tests, P = 0.00). Females exhibited a greater range of motion (ROM) in the sagittal plane (group main effect, P = 0.02) and the frontal plane (group (*) joint, P = 0.01). Differences were attributed to the greater knee varus-valgus ROM, ankle dorsiflexion, and pronation ROM (post hoc tests). Ground reaction forces were different between groups (group (*) direction, P = 0.05). Females exhibited greater peak vertical and posterior (A/P) force than males (post hoc tests). Females exhibited different knee moment profiles (Group main effect, P = 0.01). These differences were attributed to a reduced varus moment in females (post hoc tests). CONCLUSION: The majority of the differences in kinematic and kinetic variables between male and female recreational athletes during landing were observed in the frontal plane not in the sagittal plane. Specifically, females generated a smaller internal knee varus moment at the time of peak valgus knee angulation.     

The Bristol Shared Care Glaucoma Study: reliability of community optometric and hospital eye service test measures.

BACKGROUND/AIMS: Primary open angle glaucoma patients and glaucoma suspects make up a considerable proportion of outpatient ophthalmological attendances and require lifelong review. Community optometrists can be suitably trained for assessment of glaucoma. This randomised controlled trial aims to assess the ability of community optometrists in the monitoring of this group of patients. METHODS: Measures of cup to disc ratio, visual field score, and intraocular pressure were taken by community optometrists, the hospital eye service and a research clinic reference "gold" standard in 405 stable glaucoma patients and ocular hypertensives. Agreement between and within the three centres was assessed using mean differences and intraclass correlation coefficients. Tolerance limits for a change in status at the level of individual pairs of measurements were also calculated. RESULTS: Compared with a research clinic reference standard, measurements made by community optometrists and those made in the routine hospital eye service were similar. Mean measurement differences and variability were similar across all three groups compared for each of the test variables (IOP, cup to disc ratio, and visual field). Overall, the visual field was found to be the most reliable measurement and the cup to disc ratio the least. CONCLUSIONS: Trained community optometrists are able to make reliable measurements of the factors important in the assessment of glaucoma patients and glaucoma suspects. This clinical ability should allow those optometrists with appropriate training to play a role in the monitoring of suitable patients.     

Proximal femur bone marrow blood perfusion indices are reduced in hypertensive rats: A dynamic contrast‐enhanced MRI study

Purpose:

To investigate the differences in proximal femoral bone marrow blood perfusion indices between hypertensive and normotensive rats using perfusion magnetic resonance imaging (MRI).

Materials and Methods:

Six‐month‐old male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were used (12 of each). Dynamic contrast‐enhanced MRI of the right hip was performed after bolus injection of Gd‐DOTA administered through a tail vein cannula. In all, 800 images were acquired at 0.6 sec/image. Regions of interest (ROIs) were drawn comprising the medullary component of proximal femoral shaft and femoral head. MRI maximum enhancement (E^max) and enhancement slope (E^slope) were analyzed.

Results:

The E^max and E^slope of proximal femoral shaft and femoral head of SHR were significantly lower than those of WKY (E^max: 107.4 ± 18.2% vs. 130.6 ± 21.5%, P = 0.009, and 76.0 ± 12.5% vs. 97.9 ± 6.9%, P < 0.001, respectively; E^slope: 3.01 ± 0.63%/sec vs. 3.75 ± 0.74%/sec, P = 0.016, and 1.95 ± 0.33%/sec vs. 2.28 ± 0.28%/sec, P = 0.012, respectively). The E^max and E^slope of femoral head were significantly lower than those of proximal femoral shaft in both SHR and WKY (P < 0.001). In both SHR and WKY, proximal femoral shaft and femoral head had a rather different contrast enhancement pattern.

Conclusion:

Proximal femoral shaft and femoral head bone marrow blood perfusion indices were significantly lower in hypertensive rats than in normotensive rats. Femoral head bone marrow was less perfused than proximal femoral shaft in both rats. J. Magn. Reson. Imaging 2009. © 2009 Wiley‐Liss, Inc.     

Role of Parent Training in the Effective Management of Attention-Deficit/Hyperactivity Disorder

Parent training can be an effective strategy for assisting children and their families to cope with attention-deficit/hyperactivity disorder (ADHD), particularly when it is used as part of a multimodal approach in combination with stimulant medication. The benefits of parent training include: cost effectiveness, particularly when applied in group formats; structured format, enabling the treatment to be applied in a relatively standardized manner across settings and providers; and its generally high degree of acceptability to families. Challenges to implementing parent training programs include: problems with adherence to treatment that may be related to parenting stress; inaccessibility of services; cultural differences between clinicians and families; and the limited financial resources of some families. This article reviews the literature on the effectiveness of parent training as a treatment for ADHD and presents potential benefits as well as barriers to effective interventions. For each barrier, proposed solutions are recommended. Two examples of comprehensive parent training programs used in the treatment of ADHD are provided.