The Genuair inhaler is a new multidose dry powder inhaler for the delivery of aclidinium bromide - a novel, long-acting, muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease (COPD). The primary aim of this study was to assess the inspiratory flow characteristics through Genuair in patients with moderate or severe COPD. Using a three-period cross-over design, 48 patients were randomised to inhale placebo powder through Genuair, HandiHaler A (slow, deep inhalation as per manufacturer's instructions) or HandiHaler B (fast, forceful inhalation). Three measurements of peak inspiratory flow (PIF), 10min apart, were recorded for each method of administration. The highest and average PIFs for the three attempts (mean+/-standard deviation) generated through the Genuair inhaler were 97.7+/-15.7 and 92.0+/-15.4L/min, respectively. Furthermore, 97% of inhalations with the Genuair inhaler were successful (activation of trigger threshold mechanism) and optimal (PIF> or =45L/min). The highest and average PIFs generated through HandiHaler A and B were significantly lower than with the Genuair inhaler. In conclusion, patients with moderate or severe COPD were able to generate sufficient inspiratory airflow through the Genuair inhaler to reliably inhale the full dose and reset the inhaler.

Some strains of the protozoan parasite Toxoplasma gondii (such as RH) are virulent in laboratory mice because they are not restricted by the Immunity-Related GTPase (IRG) resistance system in these mouse strains. In some wild-derived Eurasian mice (such as CIM) on the other hand, polymorphic IRG proteins inhibit the replication of such virulent T. gondii strains. Here we show that this resistance is due to direct binding of the IRG protein Irgb2-b1CIM to the T. gondii virulence effector ROP5 isoform B. The Irgb2-b1 interface of this interaction is highly polymorphic and under positive selection. South American T. gondii strains are virulent even in wild-derived Eurasian mice. We were able to demonstrate that this difference in virulence is due to polymorphic ROP5 isoforms that are not targeted by Irgb2-b1CIM, indicating co-adaptation of host cell resistance GTPases and T. gondii virulence effectors.

To investigate the prevalence and type of peripheral neuropathies (PNP) in patients with chronic obstructive pulmonary disease (COPD), we studied lung function and blood gases, clinical signs of PNP, and neurophysiological function in 151 patients with COPD without known risk factors for PNP. Mean (SD) age was 65 (10) years, mean arterial PO2 was 59 (9) mmHg, mean ratio of forced expiratory volume in the first second to vital capacity (FEV1.0/VC) was 42 (12%). Thirty patients (20%) had clinically detectable and 6 (4%) had subclinical PNP of mild degree. Fourteen (9%) of the patients with clinically detectable PNP had symptoms due to PNP. Prevalence of PNP increased with severity of hypoxemia (p less than 0.05) and was more pronounced in the lower than in the upper limbs. Age and the degree of hypoxemia were predictors to differentiate between COPD patients with and without PNP. Although the cause of PNP in COPD patients remains unknown, our observations suggest that chronic hypoxemia may contribute to PNP.

The clinical and radiological findings in an infant with severe cloverleaf skull associated with a Pfeiffer syndrome are presented. The skull anomaly resulted in raised intracranial pressure and proptosis of the right eye within several weeks of birth. The child died at 3 months of age after subtotal craniectomy. At autopsy a detailed macroscopical and histological analysis of the skull base was conducted. The timing and value of surgery are discussed as well as the pathology of the cloverleaf skull anomaly.