Rapid rest/stress regadenoson ungated perfusion CMR for detection of coronary artery disease in patients with atrial fibrillation.

Cardiovascular magnetic resonance (CMR) perfusion has been established as a useful imaging modality for the detection of coronary artery disease (CAD). However, there are several limitations when applying standard, ECG-gated stress/rest perfusion CMR to patients with atrial fibrillation (AF). In this study we investigate an approach with no ECG gating and a rapid rest/stress perfusion protocol to determine its accuracy for detection of CAD in patients with AF. 26 patients with AF underwent a rapid rest/regadenoson stress CMR perfusion imaging protocol, and all patients had X-ray coronary angiography. An ungated radial myocardial perfusion sequence was used. Imaging protocol included: rest perfusion image acquisition, followed nearly immediately by administration of regadenoson to induce hyperemia, 60 s wait, and stress image acquisition. CMR perfusion images were interpreted by three blinded readers as normal or abnormal. Diagnostic accuracy was evaluated by comparison to X-ray angiography. 21 of the CMR rest/stress perfusion scans were negative, and 5 were positive by angiography criteria. Majority results of the ungated datasets from all of the readers showed a sensitivity, specificity and accuracy of 80, 100 and 96%, respectively, for detection of CAD. An ungated, rapid rest/stress regadenoson perfusion CMR protocol appears to be useful for the diagnosis of obstructive CAD in patients with AF.

Rapid dual-injection single-scan 13N-ammonia PET for quantification of rest and stress myocardial blood flows.

Quantification of myocardial blood flows at rest and stress using 13N-ammonia PET is an established method; however, current techniques require a waiting period of about 1 h between scans. The objective of this study was to test a rapid dual-injection single-scan approach, where 13N-ammonia injections are administered 10 min apart during rest and adenosine stress. Dynamic PET data were acquired in six human subjects using imaging protocols that provided separate single-injection scans as gold standards. Rest and stress data were combined to emulate rapid dual-injection data so that the underlying activity from each injection was known exactly. Regional blood flow estimates were computed from the dual-injection data using two methods: background subtraction and combined modelling. The rapid dual-injection approach provided blood flow estimates very similar to the conventional single-injection standards. Rest blood flow estimates were affected very little by the dual-injection approach, and stress estimates correlated strongly with separate single-injection values (r=0.998, mean absolute difference=0.06 ml min-1 g-1). An actual rapid dual-injection scan was successfully acquired in one subject and further demonstrates feasibility of the method. This study with a limited dataset demonstrates that blood flow quantification can be obtained in only 20 min by the rapid dual-injection approach with accuracy similar to that of conventional separate rest and stress scans. The rapid dual-injection approach merits further development and additional evaluation for potential clinical use.

Psychosocial, Affective, and Behavioral Consequences of Multiple SclerosisTreatment of the "Whole" Patient.

Multiple sclerosis (MS) challenges the individual, the family, and society because (1) it can produce wide-ranging functional losses; (2) it is generally progressive with functional losses increasing over time; and (3) its course is unpredictable. Persons affected by MS respond by (1) experiencing changes in their perception of themselves and their world; (2) altering their social roles; and (3) undergoing a variety of emotional responses, especially depression and grief over the losses caused by the illness. Psychosocial interventions that address MS challenges include (1) educational interventions such as lectures, workshops, and books; (2) supportive interventions such as counseling and support groups; (3) psychoeducational interventions such as communication skills training; and (4) somatic therapies such as antidepressants. The unpredictable and progressive course of MS means that affected individuals face a lifetime of periodic challenge. Comprehensive care in MS must address the psychosocial challenges of the illness on a long-term basis. In this way MS care can address the whole patient.

Mammalian myotube dedifferentiation induced by newt regeneration extract.

Newts are capable of regenerating several anatomical structures and organs, including their limbs. This remarkable regenerative capacity is thought to depend on cellular dedifferentiation. Terminally differentiated mammalian cells, by contrast, are normally incapable of reversing the differentiation process. Several factors could explain the absence of cellular dedifferentiation in mammals: (i) inadequate expression of genes that initiate dedifferentiation; (ii) insufficient intracellular signaling pathways; (iii) irreversible expression of differentiation factors; and (iv) structural characteristics that make dedifferentiation impossible. To investigate the causes underlying the lack of cellular plasticity in mammalian cells, we examined the effect of an extract derived from newt regenerating limbs on terminally differentiated mouse C2C12 myotubes. Approximately 18% of murine myotubes reentered the cell cycle when treated with regeneration extract, whereas 25% of newt myotubes exhibited cell cycle reentry. The muscle differentiation proteins MyoD, myogenin, and troponin T were reduced to undetectable levels in 15-30% of treated murine myotubes. We observed cellular cleavage in 11% of the treated murine myotubes and approximately 50% of these myotubes continued to cleave to produce proliferating mononucleated cells. These data indicate that mammalian myotubes can dedifferentiate when stimulated with the appropriate factors and suggest that one mechanism preventing dedifferentiation of mammalian cells is inadequate spatial or temporal expression of genes that initiate dedifferentiation.

Molecular cloning of SIV from sooty mangabey monkeys.

We derived two infectious molecular clones of SIV from sooty mangabey monkeys (Cercocebus atys) and compared them by restriction enzyme mapping and limited DNA sequencing to other known primate lentiviruses. These analyses show that SIVsmm is closely related to, but distinct from, SIVmac and HIV-2. Our data suggest that SIVmac may have been derived from SIVsmm by cross-species transmission in captivity.

Genetic diversity among simian immunodeficiency virus isolates from African green monkeys.

To characterize isolates further within the SIVagm subtype, we studied four SIVagm isolates by cross-hybridization, molecular cloning, and nucleotide sequencing. Our results indicate an unexpected degree of genetic variation among isolates within the SIVagm subtype comparable to the variation between SIVmac and HIV-2.

Comparison of temporal filtering methods for dynamic contrast MRI myocardial perfusion studies.

Dynamic contrast myocardial perfusion studies may benefit from methods that speed up the acquisition. Unaliasing by Fourier encoding the overlaps using the temporal dimension (UNFOLD), and a similar linear interpolation method have been shown to be effective at reducing the number of phase encodes needed for cardiac wall motion studies by using interleaved sampling and temporal filtering. Here such methods are evaluated in cardiac dynamic contrast studies, with particular regard to the effects of the choice of filter and the interframe motion. Four different filters were evaluated using a motion-free canine study. Full k-space was acquired and then downsampled to allow for a measure of truth. The different filters gave nearly equivalent images and quantitative flow estimates compared to full k-space. The effect of respiratory motion on these schemes was graphically depicted, and the performance of the four temporal filters was evaluated in seven human subjects with respiratory motion present. The four filters provided images of similar quality. However, none of the filters were effective at eliminating motion artifacts. Motion registration methods or motion-free acquisitions may be necessary to make these reduced FOV approaches clinically useful.

Identification of a new subgroup of SIVagm in tantalus monkeys.

Simian immunodeficiency viruses from African green monkeys (SIVagm) can be classified into three subgroups based upon the species from which they were isolated. The most extensively studied subgroup are composed of SIVagm isolated from vervet monkeys (Cercopithicus pygerythrus). Fewer isolates have been characterized from either grivets (Cercopithicus aethiops) or green monkeys (Cercopithicus sabeus). An additional distinct species of African green monkeys, tantalus monkeys (Cercopithicus tantalus), has not been characterized in terms of SIV infection. A high seroprevalence of SIV-specific antibodies was identified in sera collected from Ugandan tantalus monkeys. SIV was isolated from PBMC (SIVagm/tan), the gag region amplified by polymerase chain reaction, cloned, and sequenced. Based upon gag, SIVagm/tan isolates cluster genetically with other previously recognized SIVagm strains. However, SIVagm from tantalus monkeys forms a distinct genetic subgroup. These data confirm earlier observations of species-specific subtypes of SIVagm viruses and support the hypothesis that these viruses may have coevolved with their host during geographic dispersion throughout Africa.