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The relationship between inspiratory lung function parameters and airway hyper-responsiveness in subjects with mild to moderate COPD

Background: The aim of this study was to evaluate the effects of increasing doses of inhaled histamine on the forced expiratory volume in one second (FEV 1), inspiratory lung function parameters (ILPs) and dyspnea in subjects with mild to moderate chronic obstructive pulmonary disease (COPD). Methods. Thirty-nine (27 males and 12 females) stable COPD patients (GOLD stages I and II) inhaled a maximum of six sequential doses of histamine according to ERS standards until one of these provocative doses produced a 20% decrease in FEV 1 (PD 20). The effects on the FEV 1, the forced inspiratory volume in one second (FIV 1), inspiratory capacity (IC), forced inspiratory flow at 50% of the vital capacity (FIF50), peak inspiratory flow (PIF) and dyspnea score by a visual analogue scale (VAS) were measured and investigated after each dose step. Results: After each dose of histamine, declines in all of the lung function parameters were detected; the largest decrease was observed in the FEV 1. At the PD 20 endpoint, more FEV 1 responders than ILP responders were found. Among the ILPs, the FIV 1 and IC best predicted which patients would reach the PD 20 endpoint. No significant correlations were found between any of the lung function parameters and the VAS results. Conclusions: In COPD patients, the FEV 1 and ILPs declined after each dose of inhaled histamine. FEV 1 was more sensitive to histamine than the ILPs. Of the ILPs, FIV 1 and IC were the best predictors of reaching the PD 20 endpoint. No statistically significant correlations were found between the lung function parameters and the degree of dyspnea

Dissertatio Iuridica De Regressu Indemnitatis

Quam ... In Illustri Academia Ienensi, Praeside ... Dn. Adriano Beiero ... ad diem 30. Sept. Examini publico submittit Christophorus Staffhorst/ Disena-Osnab

Intravenous Lidocaine for Treatment of Chronic Pain:A Retrospective Cohort Study

Introduction: Neuropathic pain is a widespread problem with a big impact on quality of life. The currently used drug regimens are often insufficiently effective or cause – sometimes unacceptable – side effects. Intravenous lidocaine could be an alternative treatment, by blocking spontaneous depolarization and hyperexcitability in upregulated sodium channels in nociceptors. Research so far has shown varying results but the treatment protocols differed a lot and follow-up was usually short. In our hospital, lidocaine infusions have been applied for many years in a unique treatment protocol consisting of a relatively high dose of lidocaine (1000 mg) administered over 25 hours. Our aim is to share information on both the efficacy and safety of this treatment schedule. Methods: We conducted a retrospective cohort study in all patients who received a lidocaine infusion between January 2014 and January 2018. The standard infusion protocol consists of a total of 1000 mg lidocaine administered intravenously during 25 hours (40 mg/hour). Pain diagnoses were stratified into 15 groups, in agreement with diagnoses used in daily practice. Effectiveness of the treatment was classified as effect or no effect based on the description found in the chart. Results: We included 282 patients, with a median age of 58 years and 64% of whom were female. Patients with myofascial pain syndrome, peripheral (mono)neuropathy, small fiber neuropathy and vascular disease benefited most. Patients with cancer pain, postherpetic neuralgia, chemotherapy-induced neuropathy and radicular pain showed the least pain improvement. There were no serious adverse events. Conclusion: In selected patients, lidocaine infusions may be a safe and efficacious treatment for chronic neuropathic pain. More prospective research is needed to further determine the optimal dosing, duration and interval of lidocaine infusion therapy, and to better understand in which specific patient categories this treatment is most beneficial

Transport of the anti-cancer drug doxorubicin across cytoplasmic membranes and membranes composed of phospholipids derived from Escherichia coli occurs via a similar mechanism

AbstractAn assay was developed to measure and directly compare transport of doxorubicin across right-side-out cytoplasmic membrane vesicles (ROV) and across model membranes (LUVET) composed of pure phospholipids, isolated from the corresponding cells. Escherichia coli was used as a model organism, since mutants are available which differ in phospholipid composition. Both in LUVET and ROV only passive diffusion across the bilayer is involved, because effects of drug concentration, pH, divalent cations, the phospholipid composition, and the active transport inhibitor verapamil were comparable. Permeability coefficients were about 2–3-times higher in ROV compared to LUVET. Furthermore, in LUVET an average activation energy of 87 kJ/mol and in ROV of 50 kJ/mol was observed. These differences are suggested to result from differences in membrane order between LUVET and ROV and differences in the temperature dependence of membrane order in LUVET and ROV, respectively. Because no background carrier-facilitated doxorubicin transport seems to be present, ROV are an excellent model system to study the effect of phospholipid composition on drug transport after expression of a multidrug resistance-conferring protein. Furthermore, data of passive diffusion of doxorubicin obtained with LUVET are representative for more complex, biologically relevant membrane systems