Objective This study evaluated the efficacy and safety of flecainide in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT) on top of conventional drug therapy. Background CPVT is an inherited arrhythmia syndrome caused by gene mutations that destabilize cardiac ryanodine receptor Ca2+ release channels. Sudden death is incompletely prevented by conventional drug therapy with β-blockers +/− Ca2+ channel blockers. The anti-arrhythmic agent flecainide directly targets the molecular defect in CPVT by inhibiting premature Ca2+ release and triggered beats in vitro. Methods We collected data from every consecutive genotype-positive CPVT patient started on flecainide at eight international centers before November 13, 2009. The primary outcome measure was the reduction of ventricular arrhythmias during exercise testing. Results Thirty-three patients received flecainide because of exercise-induced ventricular arrhythmias despite conventional, for different reasons not always optimal, therapy (median age of 25 years, range 7 to 68; 70% female). Exercise tests comparing flecainide with conventional therapy alone were available in 29 patients. Twenty-two (76%) patients had either a partial (n=8) or complete (n=14) suppression of exercise-induced ventricular arrhythmias by flecainide (p<0.001). No patient experienced worsening of exercise-induced ventricular arrhythmias. Median daily flecainide dose in responders was 150 mg (range 100 to 300 mg). During a median follow-up of 20 months (range 12 to 40) one patient experienced ICD shocks for polymorphic ventricular arrhythmias, which was associated with low flecainide levels. In one patient, flecainide successfully suppressed exerciseinduced ventricular arrhythmias for 29 years. Conclusions Flecainide reduced exercise-induced ventricular arrhythmias patients with CPVT uncontrolled by conventional drug therapy.

No abstract

No abstract

The findings in this study point to a role of TH2-lymphocyte responses in the development of the allergen-induced LAR. In allergic asthmatic patients, allergen-specific responsiveness of peripheral T-lymphocytes in vitro may serve as a model to determine the individual capacity to develop a LAR after allergen inhalation.

To assess the feasibility of intra-arterial tissue ablation by Holmium:YSGG laser pulses (2.1 microns) in a noncontact mode, the transmission of the laser pulses through saline and blood was measured. The temporal interaction between the 500 microseconds laser pulse and saline at the fiber tip was investigated with time-resolved flash photography. The penetration depth in blood, and saline depended on the fiber output energy. In blood at 37 degrees C, the penetration depth varied from 1.2 to 2.1 mm for intensities of 3.1 to 12.4 J/mm2 per pulse, respectively, whereas its theoretical value for water is 0.33 mm, which is based on the measured absorption coefficient of 3.0 +/- 0.1/mm. The large penetration depth was due to the development of a transparent vapour cavity around the fiber tip. In saline, its maximum length was 4.7 mm. Its maximum width was 2.8 mm. The lifetime of the cavity was 450 microseconds. In blood, ablation of porcine aorta was feasible at a distance of 3 mm. Large fissures observed in adjacent tissue are likely to be caused by the expansion of the vapour cavity. We conclude that, due to a "Moses effect in the microsecond region," Holmium:YSGG tissue ablation is possible through at least 2.7 mm of blood.

No abstract

No abstract

This study was designed to investigate whether methotrexate (MTX), used in the treatment of rheumatoid arthritis (RA), affects proliferation and differentiation of human osteoblasts in culture. The effects of MTX were assessed by analyzing markers of proliferation and differentiation of human trabecular bone-derived osteoblast-like cells cultured in the presence or absence of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3). Treatment of the osteoblastic cells with MTX resulted in a strong dose-dependent inhibition of cell proliferation with half maximal response at a dose of 30 nM. MTX did not interfere with cellular alkaline phosphatase (AP) activity, the number of cells expressing cytochemical AP, or basal osteocalcin production. Addition of 1,25(OH)2D3 to the cultures caused an enhanced AP expression and osteocalcin production coinciding with a decreased osteoblast proliferation. Coincubation of 1,25(OH)2D3 with MTX in doses > or = 100 nM further inhibited osteoblast growth and induced a significant stimulation of AP expression and activity, and production of osteocalcin above the values reached in the 1,25(OH)2D3 cultures. In conclusion, MTX proved to be a potent inhibitor of osteoblast proliferation but did not affect basal osteoblastic phenotypic expression. In the presence of the osteoblast differentiation-promoter, 1,25(OH)2D3, MTX further inhibited cell growth which was associated with enhanced AP activity and osteocalcin production. Thus, MTX may have profound effects on bone metabolism and remodeling by interfering with bone cell turnover.