Amiodarone and sotalol are equally efficacious in converting atrial fibrillation to sinus rhythm. Amiodarone is superior for maintaining sinus rhythm, but both drugs have similar efficacy in patients with ischemic heart disease. Sustained sinus rhythm is associated with an improved quality of life and improved exercise performance.

Cyclic nucleotide phosphodiesterases (PDEs) regulate all pathways that use cGMP or cAMP as a second messenger. Five of the 11 PDE families have regulatory segments containing GAF domains, 3 of which are known to bind cGMP. In PDE2 binding of cGMP to the GAF domain causes an activation of the catalytic activity by a mechanism that apparently is shared even in the adenylyl cyclase of Anabaena, an organism separated from mouse by 2 billion years of evolution. The 2.9-Å crystal structure of the mouse PDE2A regulatory segment reported in this paper reveals that the GAF A domain functions as a dimerization locus. The GAF B domain shows a deeply buried cGMP displaying a new cGMP-binding motif and is the first atomic structure of a physiological cGMP receptor with bound cGMP. Moreover, this cGMP site is located well away from the region predicted by previous mutagenesis and structural genomic approaches. C yclic nucleotide phosphodiesterases (PDEs) catalyze the hydrolysis of 3Ј, 5Ј cyclic nucleotides to the inactive 5Ј monophosphates. Five of the 11 PDE families contain regulatory segments consisting of one or two so-called GAF-domain modules (1), which is one of the largest families of small moleculebinding regulatory domains. Among PDEs, cGMP is the only ligand known to bind this domain. The structure of a single GAF domain from a putative protein from yeast (YKG9) has been solved recently (2). However, yeast do not make cGMP, nor does this protein bind cGMP when tested directly (2). cGMP binding to one of two GAF domains (3) in the photoreceptor PDE6 family provides one mechanism for regulating visual signal transduction. cGMP also binds to one or more of the GAF domains of PDE5 (4), the target of the drug, Viagra. The binding and subsequent phosphorylation of an adjacent domain activates the catalytic domain of the enzyme (5). In PDE2A, the catalytic activity is allosterically stimulated by cGMP binding to its GAF domain (6), an event important for several pathways that PDE2A has been shown to regulate (7-12). For example, atrial natriuretic peptide stimulation of cGMP and subsequent activation of PDE2A in the adrenal cortex decreases the secretion of aldosterone and, thereby, mediates much of the effect of this hormone on blood pressure (13). Each PDE2A monomer contains an N-terminal (Ϸ200 residues) domain of unknown function, tandem GAF domains (GAF A and GAF B), and a C-terminal catalytic domain. What seems to be a functionally very similar tandem set of GAF domains is also present in Anabaena adenylyl cyclase. This GAF domain has a preference for cAMP where it functions to confer cAMP activation of cyclase activity (14). Here, we report the 2.9-Å crystal structure of the regulatory segment of murine PDE2A, which reveals the structure of two GAF domains with entirely different functions, dimerization, and binding of cGMP. Amazingly, this binding motif and mechanism has apparently been preserved for over 2 billion years in evolution. Methods and MaterialsCrystallization and Data Collection. Crystals were grown at ...

To evaluate the effectiveness of a lowvision rehabilitation program.Methods: A multicenter randomized clinical trial was conducted from November 2004 to November 2006 with a 4-month follow-up. A total of 126 patients were included, 98% of whom were white and male. The patients were referred from eye or low-vision clinics and blind rehabilitation centers with a visual acuity in the better-seeing eye worse than 20/100 and better than 20/500 and were eligible for Veterans Affairs (VA) services. Telephone interviews of patients were conducted in their homes before and after participation in an outpatient low-vision program at a VA medical care facility or a (waiting list) control group. The interviewer administering questionnaires by telephone was masked to patients' assignments. Interventions included low-vision examination, counseling, and prescription and provision of low-vision devices and 6 weekly sessions provided by a low-vision therapist to teach use of assistive devices and adaptive strategies to perform daily living tasks independently.Main Outcome Measure: Change in patients' visual reading ability estimated from participant responses to the Veterans Affairs Low-Vision Visual Functioning Questionnaire (LV VFQ-48) reading items completed at baseline compared with 4 months after enrollment for the treatment and control groups. The secondary outcomes were changes in other visual ability domains (mobility, visual information processing, visual motor skills) and overall vi-sual ability from baseline to 4 months estimated from VA LV VFQ-48 difficulty ratings for subsets of items.Results: The treatment group demonstrated significant improvement in all aspects of visual function compared with the control group. The difference in mean changes was 2.43 logits (95% confidence interval [CI], 2.07-2.77; P Ͻ.001; effect size, 2.51) for visual reading ability; 0.84 logit (95% CI, 0.58-1.10; P Ͻ .001; effect size, 1.14) for mobility; 1.38 logits (95% CI, 1.15-1.62; PϽ.001; effect size, 2.03) for visual information processing; 1.51 logits (95% CI, 1.22-1.80; P Ͻ .001; effect size, 1.82) for visual motor skills; and 1.63 logits (95% CI, 1.40-1.86; P Ͻ .001; effect size, 2.51) for overall visual function. Conclusion:The program effectively provided lowvision rehabilitation for patients with macular diseases.Applications to Clinical Practice: At least 10 hours of low-vision therapy, including a home visit and assigned homework to encourage practice, is justified for patients with moderate and severe vision loss from macular diseases. Because the waiting-list control patients demonstrated a decline in functional ability, low-vision services should be offered as early as possible.

AE1 protein transports Cl؊ and HCO 3 Ϫ across the erythrocyte membrane by an electroneutral exchange mechanism. Glu 681 of human AE1 may form part of the anion translocation apparatus and the permeability barrier. We have therefore studied the structure of the sequence surrounding Glu 681 , using scanning cysteine mutagenesis.

In patients with persistent AF, restoration and maintenance of SR was associated with improvements in QOL measures and EP. There was a strong correlation between QOL measures and EP.