Characterisation of very low frequency oscillations in laser Doppler perfusion signals with a singular spectrum analysis.

Laser Doppler (LD) perfusion signals consist of a number of superimposed frequencies that span a wide range. Singular spectrum analysis (SSA) was used to characterise the very low frequency (VLF) components as this method can extract frequencies of interest from the time domain. Its utility is demonstrated on a sex health clinical data set where the focus was on VLF oscillations. A significant change in this frequency range can be measured with SSA when the subject is undergoing erotic stimulation.

Translational research in the pharmaceutical industry: from theory to reality.

Translational research is the collaboration between scientists and clinicians to identify novel targets and develop biomarkers that increase confidence in rationale and therefore help select the mechanisms that are most likely to lead to breakthrough therapies. Here, we describe examples of the utility of linked preclinical and clinical biomarkers to measure pharmacological effects, to estimate clinical dose range, to determine efficacy, and to determine differentiation compared with existing therapies. The use of pharmacogenomics to identify novel drug targets and define enriched patient subpopulations is also discussed. We illustrate how biomarkers and a deep understanding of disease biology are used to discover additional indications for licensed drugs.

Duration of action of sildenafil citrate in men with erectile dysfunction.

INTRODUCTION: Viagra (sildenafil citrate) has a rapid onset of action for the treatment of erectile dysfunction (ED). However, its duration of action has not been thoroughly investigated. Practical knowledge of the time window available for sexual intercourse would be valuable for couples planning sexual activity. AIM: We investigated the duration of action of sildenafil in men with ED. METHODS: This was a double-blind, randomized, placebo-controlled, four-way crossover study of 16 men, mean age of 55 years (range, 36-68 years) with ED of no known organic cause. Participants received oral sildenafil (100 mg) or placebo 1, 8, or 12 hours before visual sexual stimulation (VSS). Measurements included the duration of erections of >or= 60% rigidity, assessed by penile plethysmography (RigiScan), and the proportion of sildenafil responders, defined as patients with erections of >or= 60% rigidity for >or= 4 minutes and >or= 50% improvement over erections achieved in their placebo arm. Self-assessed duration of grade 3 (hard enough for penetration) or grade 4 (fully hard) erections was also recorded. RESULTS: At 1, 8, and 12 hours after dosing with sildenafil, the mean duration of erections with >or= 60% rigidity was 26, 11, and 8 minutes, respectively, compared with only 3 minutes after placebo dosing (P < 0.05). However, the mean duration of self-assessed erections was 33, 23, and 16 minutes, respectively, compared with 7 minutes after placebo dosing (P < 0.05), and was greater than that assessed by RigiScan. Of the 69% sildenafil responders at 1 hour, 82% responded at 8 hours and 45% responded at 12 hours after sildenafil administration. CONCLUSION: Sildenafil improved objective and self-assessed erectile function in men with ED, and the duration of action of sildenafil was longer than that previously reported. These data suggest that sildenafil may be effective in a significant proportion of men with ED up to 12 hours after being taken.