Onset and duration of action of formoterol and tiotropium in patients with moderate to severe COPD

BACKGROUND: Chronic obstructive pulmonary disease (COPD) management guidelines recommend regular treatment with one or more long-acting bronchodilators for patients with moderate to severe COPD. OBJECTIVE: To compare the onset and duration of action of formoterol and tiotropium in patients with COPD. METHODS: This randomized, multicentre, open-label crossover study in 38 patients with COPD (mean age 64 years; mean FEV(1) 55% predicted) assessed the effect of 7 days of treatment with formoterol (12 microg b.i.d. via Foradil Aerolizer) vs. tiotropium (18 microg o.d. via Spiriva HandiHaler) on lung function measured over a period of 12 h after the first dose on day 1 and the last dose on day 8. RESULTS: The primary efficacy variable, FEV(1)-AUC during the first 2 h post-dose (FEV(1)-AUC(10-120 min)), was significantly higher for formoterol compared with tiotropium, with between-treatment differences of 124 ml (p = 0.016) after the first dose and 80 ml (p = 0.036) after 7 days' treatment in favour of formoterol. FEV(1) measured 12 h after inhalation did not differ statistically significantly between treatments. Adverse events occurred in 2 (5%) patients after treatment with formoterol and in 5 (12%) patients after treatment with tiotropium. CONCLUSION: This study demonstrates faster onset of action and greater bronchodilation of formoterol vs. tiotropium for bronchodilation within the first 2 h of inhalation (FEV(1)-AUC(10-120 min)) and comparable bronchodilation 12 h post-inhalation in patients with moderate to severe COPD.     

The immunological synapse: kinases in T cell signalling as potential drug targets

This international workshop on key signalling molecules in lymphocyte activation and immune regulation was held in Grossziethen, Germany from November 02-04, 2005 and brought together molecular, cellular, and clinical immunologists whose common goal is to develop ways of manipulating the immune response in order to avert T cell effector functions that are of significant relevance for pathogenesis in different diseases, including dermatological (psoriasis, atopic dermatitis and allergic contact allergy) and other indications (e.g. asthma, rheumatoid arthritis, multiple sclerosis and transplant rejection).     

Dissociable networks for the expectancy and perception of emotional stimuli in the human brain

William James posited that comparable brain regions were implicated in the anticipation and perception of a stimulus; however, dissociable networks (at least in part) may also underlie these processes. Recent functional neuroimaging studies have addressed this issue by comparing brain systems associated with the expectancy and perception of visual, tactile, nociceptive, and reward stimuli. In the present fMRI study, we addressed this issue in the domain of pictorial emotional stimuli (IAPS). Our paradigm involved the experimental conditions emotional expectancy, neutral expectancy, emotional picture perception, and neutral picture perception. Specifically, the emotional expectancy cue was uncertain in that it did not provide additional information regarding the positive or negative valence of the subsequent picture. Neutral expectancy and neutral picture perception served as control conditions, allowing the identification of expectancy and perception effects specific for emotion processing. To avoid contamination of the perception conditions by the preceding expectancy periods, 50% of the pictorial stimuli were presented without preceding expectancy cues. We found that the emotional expectancy cue specifically produced activation in the supracallosal anterior cingulate, cingulate motor area, and parieto-occipital sulcus. These regions were not significantly activated by emotional picture perception which recruited a different neuronal network, including the amygdala, insula, medial and lateral prefrontal cortex, cerebellum, and occipitotemporal areas. This dissociation may reflect a distinction between anticipatory and perceptive components of emotional stimulus processing.     

An open-label randomized trial comparing itraconazole oral solution with fluconazole oral solution for primary prophylaxis of fungal infections in patients with haematological malignancy and profound neutropenia

OBJECTIVES: This trial studied the efficacy and safety of itraconazole and fluconazole in the prevention of invasive fungal infections in neutropenic patients with haematological malignancies. PATIENTS AND METHODS: An 8 week, open-label, randomized, parallel-group, multicentre trial comparing itraconazole oral solution (2.5 mg/kg twice daily; N=248) with fluconazole oral solution or capsules (400 mg daily; N=246) in 494 patients with anticipated profound neutropenia (i.e. neutrophil count expected to be <500 cells/mm3 for at least 10 days) from tertiary care centres. RESULTS: Invasive fungal infections were reported for 4 out of 248 patients (1.6%) in the itraconazole group and 5 out of 246 patients (2.0%) in the fluconazole group. Invasive Aspergillus infections were proven for 2 out of 248 patients (0.8%) in the itraconazole group and 3 out of 246 patients (1.2%) in the fluconazole group. For both the ITT and profoundly neutropenic populations, no differences were detected between treatment groups in proven or suspected invasive fungal infections or other endpoints. The mortality rates owing to proven invasive fungal infections were 2 out of 248 patients (0.8%) for the itraconazole group and 3 out of 246 patients (1.2%) for the fluconazole group. There was also no difference between treatment groups in the number of patients who recovered from neutropenia or in the duration of neutropenia. More discontinuation of drug intake owing to nausea and more hypokalaemia occurred in the itraconazole group, other adverse events and the total number of adverse events were similar in both groups. CONCLUSIONS: In this study there were no differences in the efficacy and safety of itraconazole and fluconazole prophylaxis in neutropenic patients with haematological malignancies.     

Polymerization efficiency of different photocuring units through ceramic discs

This study compared the ability of a variety of light sources and exposure modes to polymerize a dual-cured resin composite through ceramic discs of different thicknesses by depth of cure and Vickers microhardness (VHN). Ceramic specimens (360) (Empress 2 [Ivoclar Vivadent], color 300, diameter 4 mm, height 1 or 2 mm) were prepared and inserted into steel molds according to ISO 4049, after which a dual-cured composite resin luting material (Variolink II [Ivoclar Vivadent]) with and without self-curing catalyst was placed. The light curing units used were either a conventional halogen curing unit (Elipar TriLight [3M/ESPE] for 40 seconds), a high-power halogen curing unit (Astralis 10 [Ivoclar Vivadent] for 20 seconds), a plasma arc curing unit (Aurys [Degré K] for 10 seconds or 20 seconds) or different light emitting diode (LED) curing units (Elipar FreeLight I [3M/ESPE] for 40 seconds, Elipar FreeLight II [3M/ESPE] for 20 seconds, LuxOmax [Akeda] for 40 seconds, e-Light [GC] for 12 seconds or 40 seconds). Depth of cure under the ceramic discs was assessed according to ISO 4049, and VHN at 0.5 and 1.0 mm distance from the ceramic disc bottom was determined (ISO 6507-1). Medians and the 25th and 75th percentiles were determined for each group (n=10), and statistical analysis was performed using the Mann-Whitney-U-test (p < or = 0.05). The results showed that increasing ceramic disc thickness had a negative effect on the curing depth and hardness of all light curing units, with hardness decreasing dramatically under the 2-mm thick discs using LuxOmax, e-Light (12 seconds) or Aurys (10 seconds or 20 seconds). The use of a self-curing catalyst is recommended over the light-curable portion only, because it produced an equivalent or greater hardness and depth of cure with all light polymerization modes.     

Two-year clinical performance of cast gold vs ceramic partial crowns

Cast gold partial crowns (CGPC) are an accepted means of restoring posterior teeth with extended lesions. However, for esthetic reasons, CGPC are being increasingly substituted with partial ceramic crowns (PCC). The aim of the present prospective split-mouth study was to compare the clinical performance of PCC and CGPC. There were 29 patients (male 12, female 17) who participated in the investigation for a total of 58 restorations. In each patient, one CGPC (Degulor C) and one PCC (Vita MarkII/Cerec III) were placed. CGPC were inserted using conventional zinc-phosphate cement (Harvard); PCC were adhesively luted to the cavities (Variolink II/Excite). The restorations were clinically rated using modified United States Public Health Service (USPHS) criteria at baseline and 1 and 2 years after placement. The median patient age was 38 years (range 25–54). There were 29 of the CGPC and 14 PCC placed in molars, while 15 PCC were placed in premolars. All patients were available for the 1- and the 2-year recall. One PCC (1.7%) failed and had to be replaced after 2 years in situ. The rest of the restorations were functional without need of replacement. The evaluation using USPHS criteria revealed no statistically significant differences between CGPC and PCC with the exception of anatomic form: PCC showed occlusal chipping in two cases without need of replacement. From these data, it can be concluded that PCC may provide an esthetic and tissue-conservative alternative to CGPC. However, long-term studies comparing the clinical performance and longevity of cast gold and ceramic partial crowns for posterior teeth are desirable.