Use of autologous 99mTechnetium-labelled neutrophils to quantify lung neutrophil clearance in COPD.

RATIONALE: There is a need to develop imaging protocols which assess neutrophilic inflammation in the lung. AIM: To quantify whole lung neutrophil accumulation in (1) healthy volunteers (HV) following inhaled lipopolysaccharide (LPS) or saline and (2) patients with COPD using radiolabelled autologous neutrophils and single-photon emission computed tomography/CT (SPECT/CT). METHODS: 20 patients with COPD (Global initiative for chronic obstructive lung disease (GOLD) stages 2-3) and 18 HVs were studied. HVs received inhaled saline (n=6) or LPS (50 µg, n=12) prior to the injection of radiolabelled cells. Neutrophils were isolated using dextran sedimentation and Percoll plasma gradients and labelled with 99mTechnetium (Tc)-hexamethylpropyleneamine oxime. SPECT was performed over the thorax/upper abdomen at 45 min, 2 hours, 4 hours and 6 hours. Circulating biomarkers were measured prechallenge and post challenge. Blood neutrophil clearance in the lung was determined using Patlak-Rutland graphical analysis. RESULTS: There was increased accumulation of 99mTc-neutrophils in the lungs of patients with COPD and LPS-challenged subjects compared with saline-challenged subjects (saline: 0.0006±0.0003 mL/min/mL lung blood distribution volume [mean ±1 SD]; COPD: 0.0022±0.0010 mL/min/mL [p<0.001]; LPS: 0.0025±0.0008 mL/min/mL [p<0.001]). The accumulation of labelled neutrophils in 10 patients with COPD who underwent repeat radiolabelling/imaging 7-10 days later was highly reproducible (0.0022±0.0010 mL/min/mL vs 0.0023±0.0009 mL/min/mL). Baseline interleukin (IL)-6 levels in patients with COPD were elevated compared with HVs (1.5±1.06 pg/mL [mean ±1 SD] vs 0.4±0.24 pg/mL). LPS challenge increased the circulating IL-6 levels (7.5±2.72 pg/mL) 9 hours post challenge. CONCLUSIONS: This study shows the ability to quantify 'whole lung' neutrophil accumulation in HVs following LPS inhalation and in subjects with COPD using autologous radiolabelled neutrophils and SPECT/CT imaging. Moreover, the reproducibility observed supports the feasibility of using this approach to determine the efficacy of therapeutic agents aimed at altering neutrophil migration to the lungs.

Remodeling of periorbital, temporal, glabellar, and crow's feet areas with hyaluronic acid and botulinum toxin.

Botulinum toxins are currently used to reduce facial muscle activity, and hyaluronic acid is used to correct volume loss. This study evaluates the combination of abobotulinumtoxinA (Dysport) and hyaluronic acid 20 mg/mL (Perlane) for rejuvenating specific areas of the upper face. Subjects (n = 20) with mild to moderate temporal volume loss as well as glabellar and/or periorbital rhytids were enrolled in this single-center, open-label, nonrandomized pilot study. Subjects were randomly assigned a number and treated with hyaluronic acid, divided between temporal and glabellar region, and abobotulinumtoxinA in the periorbital and glabellar region. A 1-month touch-up was given if needed. Subjects were evaluated by the investigator, and each subject completed a questionnaire at baseline and at 3, 6, and 9 months after treatment. For glabellar lines and crow's feet, median grades decreased from baseline at 1 month and at 3 months, but returned to baseline values at 6 months. For temporal assessments, the median grade decreased from baseline at 1, 3, and 6 months and returned to baseline at 9 months. Similar trends were observed in subjects' perceived age, perceived social and professional limitations, and desire to alter their facial appearance. Among subjects previously treated with botulinum toxin alone, 64% rated the combination treatment said "superior." Adverse effects were mild and transient. The combination of abobotulinumtoxinA and hyaluronic acid appears to rejuvenate the periorbital, temporal, glabellar, and crow's feet areas with minimal adverse effects.

Treatment of eyebrow hypotrichosis using bimatoprost: a randomized, double-blind, vehicle-controlled pilot study.

BACKGROUND: The Food and Drug Administration has approved bimatoprost ophthalmic solution (0.03%) for the treatment of eyelash hypotrichosis. Previous reports of its efficacy in eyebrow hypotrichosis are anecdotal. OBJECTIVE: To assess the efficacy and safety of bimatoprost 0.03% ophthalmic solution applied to the eyebrows in a randomized, double-blind, vehicle-controlled study. METHODS: Subjects (n = 20) with mild to moderate eyebrow hypotrichosis enrolled in the study. One group (Bim) applied bimatoprost to each eyebrow daily for 9 months, and another applied vehicle nightly to each eyebrow for 5 months. Subjects in the latter group were re-randomized to apply bimatoprost (Veh-Bim Group) or vehicle (Veh Group) daily to each eyebrow for 4 months. The primary end point was investigator-assessed eyebrow appearance; secondary end points were subject-reported outcomes. RESULTS: Investigator assessments showed significant improvements from baseline to 6 (p = .002) and 7 (p = .005) months for the eyebrows treated with bimatoprost. p-Values for the Veh-Bim and Veh groups were not significant at any time point. End-of-study subject satisfaction with eyebrow fullness or thickness and darkness or color was greater in the Bim group than in the Veh group. Adverse effects were not observed. CONCLUSION: Bimatoprost 0.03% ophthalmic solution applied daily for 9 months improves the appearance of eyebrows noticeably more than vehicle, without side effects.

Competitive relationships in a fertile grassland community - does size matter?

There is currently much debate about the relative importance of two contrasting mechanisms thought to be involved in regulating plant communities. One of these mechanisms is thought to result from species which possess particular traits, becoming dominant within the community and thus determining the abundance of other species. The second mechanism is thought to result from the complementarity of different species exploiting different resources and thus promoting co-existence. To investigate the relevant importance of these two mechanisms, a series of pot experiments were performed in which the competitive relationships of eight species of grass were estimated in monoculture, in pair-wise comparisons and by the impact of their removal on the remaining community. Although superficially above-ground biomass appeared to be a good predictor of competitive ability, more detailed analysis revealed that size was ineffective as a predictor of a species' impact on a community. In contrast there was evidence that complementarity was important in determining species-species interactions both at the level of pairs of species and even more so at community level. It is argued that complementarity is more important in diverse communities than in pair-wise interactions because complementarity is an emergent property of species diversity.