A PALB2 mutation associated with high risk of breast cancer

Introduction: As a group, women who carry germline mutations in partner and localizer of breast cancer 2 susceptibility protein (PALB2) are at increased risk of breast cancer. Little is known about by how much or whether risk differs by mutation or family history, owing to the paucity of studies of cases unselected for family history.Methods: We screened 1,403 case probands for PALB2 mutations in a population-based study of Australian women with invasive breast cancer stratified by age at onset. The age-specific risk of breast cancer was estimated from the cancer histories of first- and second-degree relatives of mutation-carrying probands using a modified segregation analysis that included a polygenic modifier and was conditioned on the carrier case proband. Further screening for PALB2 c.3113G > A (W1038X) was conducted for 779 families with multiple cases of breast cancer ascertained through family cancer clinics in Australia and New Zealand and 764 population-based controls.Results: We found five independent case probands in the population-based sample with the protein-truncating mutation PALB2 c.3113G > A (W1038X); 2 of 695 were diagnosed before age 40 years and 3 of 708 were diagnosed when between ages 40 and 59 years. Both of the two early-onset carrier case probands had very strong family histories of breast cancer. Further testing found that the mutation segregated with breast cancer in these families. No c.3113G > A (W1038X) carriers were found in 764 population-based unaffected controls. The hazard ratio was estimated to be 30.1 (95% confidence interval (CI), 7.5 to 120; P A mutation appears to be associated with substantial risks of breast cancer that are of clinical relevance. © 2010 Southey et al.; licensee BioMed Central Ltd

Coronary vein defibrillator coil placement in patients with high defibrillation thresholds

Background: Elevated defibrillation threshold (DFT) occurs in 2%-6% of patients undergoing implantable cardioverter defibrillator (ICD) implantation. Adding a defibrillation coil in the coronary sinus (CS) or its branches can result in substantial reductions in the mean DFT. However, data regarding acute success and long-term stability remain lacking. We report our experience with this bailout strategy. Methods: Patients with elevated DFT at implantation (safety margin at implantation <10 J) and those with failed ICD shocks for ventricular arrhythmias (VA) referred for high DFT underwent placement of an additional defibrillation coil in the CS. DFT testing was performed at the completion of the implantation procedure. External potentially reversible factors were excluded. High-output devices were systematically used. Results: Four patients with high DFT at implantation and two with several failed shock attempts underwent placement of a defibrillation coil in the CS. Mean age was 41.8 (23-78). They presented a mean LVEF of 21% (15-30), QRS-complex duration of 109.8 milliseconds (87-168), body surface area of 1.96 m(2) (1.45-2.58), and a mean R wave of 16.3 mV (8-27). Defibrillation coil implantation in the CS (final shocking configuration of right ventricle as anode and left ventricle (LV) plus can as cathode) was associated with successful DFT testing in all. Three patients had a concomitant LV lead for biventricular pacing. During a mean follow-up of 54.67 months (10-118), two patients experienced successful ICD shocks for VA (one of them also presented inappropriate shocks because of the fast conducting atrial fibrillation). Conclusions: Positioning of a defibrillation coil in the CS can result in a substantial reduction in mean DFT and associates with optimal long-term stability

Mechanisms of pain associated with internal defibrillation shocks: results of a randomized study of shock waveform.

BACKGROUND: Shock pain has limited the acceptance of the implantable atrial cardioverter and is a complication of ventricular implantable cardioverter-defibrillator therapy. Rounding off of the peak of a shock waveform reduces pain. Whether the pain reduction results from reduction in the peak voltage or from the rounding has not been established. In other words, does reducing the extreme dV/dt (voltage derivative) of the conventional truncated exponential capacitive discharge waveform reduce pain? OBJECTIVES: The purpose of this study was to compare the relative contributions of peak voltage and waveform shape to pain. METHODS: We compared rounded and conventional waveforms with equal peak voltages. Eighty-five shocks of 50 to 500 V were delivered to 10 patients requiring atrial cardioversion for persistent atrial fibrillation. The patient touched an analog pain scale (0-15 cm) and orally reported a pain score on a scale from 0 to 5. An observer scored thoracic contractions on a scale from 0 to 5. RESULTS: No differences between the rounded and conventional waveform on any scale were noted for either univariate or multivariate analyses. However, all three response scales were strongly predicted by voltage with r(2) = 0.77 (oral), r(2) = 0.86 (analog), and r(2) = 0.85 (contraction) after correcting for patient variability and including a log voltage term. CONCLUSIONS: Patient pain perception was determined primarily by waveform peak voltage and not by the rounding, per se

Mechanisms of pain associated with internal defibrillation shocks: results of a randomized study of shock waveform.

Shock pain has limited the acceptance of the implantable atrial cardioverter and is a complication of ventricular implantable cardioverter-defibrillator therapy. Rounding off of the peak of a shock waveform reduces pain. Whether the pain reduction results from reduction in the peak voltage or from the rounding has not been established. In other words, does reducing the extreme dV/dt (voltage derivative) of the conventional truncated exponential capacitive discharge waveform reduce pain