Citations

AbstractThe assessment of the influence of many rare BRCA2 missense mutations on cancer risk has proved difficult. A multifactorial likelihood model that predicts the odds of cancer causality for missense variants is effective, but is limited by the availability of family data. As an alternative, we developed functional assays that measure the influence of missense mutations on the ability of BRCA2 to repair DNA damage by homologous recombination and to control centriole amplification. We evaluated 22 missense mutations from the BRCA2 DNA binding domain (DBD) that were identified in multiple breast cancer families using these assays and compared the results with those from the likelihood model. Thirteen variants inactivated BRCA2 function in at least one assay; two others truncated BRCA2 by aberrant splicing; and seven had no effect on BRCA2 function. Of 10 variants with odds in favor of causality in the likelihood model of 50:1 or more and a posterior probability of pathogenicity of 0.99, eight inactivated BRCA2 function and the other two caused splicing defects. Four variants and four controls displaying odds in favor of neutrality of 50:1 and posterior probabilities of pathogenicity of at least 1 × 10−3 had no effect on function in either assay. The strong correlation between the functional assays and likelihood model data suggests that these functional assays are an excellent method for identifying inactivating missense mutations in the BRCA2 DBD and that the assays may be a useful addition to models that predict the likelihood of cancer in carriers of missense mutations. [Cancer Res 2008;68(9):3523–31]

Background— Multiple factors create discrepancies between electroanatomic maps and merged, preacquired computed tomographic images used in guiding atrial fibrillation ablation. Therefore, a Carto-based 3D ultrasound image system (Biosense Webster Inc) was validated in an animal model and tested in 15 atrial fibrillation patients. Methods and Results— Twelve dogs underwent evaluation using a newly developed Carto-based 3D ultrasound system. After fiducial clip markers were percutaneously implanted at critical locations in each cardiac chamber, 3D ultrasound geometries, derived from a family of 2D intracardiac echocardiographic images, were constructed. Point-source error of 3D ultrasound-derived geometries, assessed by actual real-time 2D intracardiac echocardiographic clip sites, was 2.1�1.1 mm for atrial and 2.4�1.2 mm for ventricular sites. These errors were significantly less than the variance on CartoMerge computed tomographic images (atria: 3.3�1.6 mm; ventricles: 4.8�2.0 mm; P< 0.001 for both). Target ablation at each clip, guided only by 3D ultrasound-derived geometry, resulted in lesions within 1.1�1.1 mm of the actual clips. Pulmonary vein ablation guided by 3D ultrasound-derived geometry resulted in circumferential ablative lesions. Mapping in 15 patients produced modestly smaller 3D ultrasound versus electroanatomic map left atrial volumes (98�24 cm 3 versus 109�25 cm 3 , P< 0.05). Three-dimensional ultrasound-guided pulmonary vein isolation and linear ablation in these patients were successfully performed with confirmation of pulmonary vein entrance/exit block. Conclusions— These data demonstrate that 3D ultrasound images seamlessly yield anatomically accurate chamber geometries. Image volumes from the ultrasound system are more accurate than possible with CartoMerge computed tomographic imaging. This clinical study also demonstrates the initial feasibility of this guidance system for ablation in patients with atrial fibrillation.

Abstract There is a great need for a screening test that results in the detection of asymptomatic lung cancer, at a time when there is a substantially better chance for curative treatment. Based on the significant limitations in the results reported to date from nonrandomized, observational screening trials, the authors do not recommend computed tomography screening for lung cancer at this time. Results of two major randomized controlled trials will soon be available.

The aim of this study was to define the outcome and complications following open reduction and internal fixed-angle plating of distal radius fractures for patients on chronic immunosuppression medications. A retrospective study identified 11 patients with distal radius fractures that had been on chronic immunosuppressive medication. The mean patient age was 59.9 years (40–82 years). According to the Orthopedic Trauma Association classification, there was one 23A3, one 23B3, and nine 23C type fractures. There were two open fractures. All patients received preoperative antibiotics and underwent reduction and fixation with a volar, fixed-angle plate. Postoperative measurements included postoperative and final radiographic indices, wrist flexion and extension, forearm rotation, and grip strength. Clinical follow-up averaged 13 months, and radiographic follow-up averaged 14.9 months. Statistical analysis was performed comparing means of various parameters with a two-sided t test with an alpha value ≤0.05. All fractures healed, and there were no infections. The final mean ulnar variance, volar tilt, and radial inclination were –0.1 mm (ulnar negative; –2.0 to +2.5 mm), 13° (5–23°), and 21° (15–27°), respectively. The mean articular gap or step was 0.4 mm. There was a small but significant decrease between the final and postoperative mean ulnar variance ( p=0.03). Mean wrist flexion was 47°, extension 47°, pronation 77°, and supination was 76°. Grip strength averaged 16.3 kg versus 25.1 kg for the opposite extremity. The one major complication included a postoperative carpal tunnel syndrome. Fixed-angle volar plate fixation for distal radius fractures in patients with chronic immunosuppression was associated with union (with acceptable radiographic alignment), no wound-healing problems or infections, and with functional wrist and forearm motion and grip strength.