Background: In placebo-controlled clinical trials, reboxetine, a selective noradrenaline reuptake inhibitor, increases urethral pressure and relieves stress urinary incontinence symptoms in women. Considering the close connection in neural regulation of the external urethral and anal sphincters, we hypothesized that reboxetine may also enhance anal sphincter pressure. Conversely, it is believed that selective serotonin reuptake inhibitors may contribute to fecal incontinence by reducing anal sphincter pressure.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2024
Tropical mountains are global biodiversity hotspots, owing to a combination of high local species richness and turnover in species composition. Typically, the highest local richness and turnover levels are implicitly assumed to converge in the same mountain regions, resulting in extraordinary species richness at regional to global scales. We investigated this untested assumption using high-resolution distribution data for all 9,788 bird species found in 134 mountain regions worldwide.
View Article and Find Full Text PDFThe immense concentrations of vertebrate species in tropical mountains remain a prominent but unexplained pattern in biogeography. A long-standing hypothesis suggests that montane biodiversity hotspots result from endemic species aggregating within ecologically stable localities. Here, the persistence of ancient lineages coincides with frequent speciation events, making such areas both 'cradles' (where new species arise) and 'museums' (where old species survive).
View Article and Find Full Text PDFAims: Urethral closure function is essential for urinary continence in women and decreased urethral pressure is associated with stress urinary incontinence (SUI). For decades, the effects of serotonergic drugs on central neural control of urethral closure have been investigated and discussed. Epidemiological studies suggest that the use of selective serotonin reuptake inhibitors (SSRIs), such as citalopram, is associated with SUI.
View Article and Find Full Text PDFClimate-driven range shifts may cause local extinctions, while the accompanying loss of biotic interactions may trigger secondary coextinctions. At the same time, climate change may facilitate colonizations from regional source pools, balancing out local species loss. At present, how these extinction-coextinction-colonization dynamics affect biological communities under climate change is poorly understood.
View Article and Find Full Text PDFBackground: Coronavirus disease 19 (COVID-19) is spreading globally and treatment options remain limited. A formulation of niclosamide, a potent anti-SARS-CoV-2 agent and a broad-spectrum antiviral treatment candidate, optimized for inhalation and intranasal administration (UNI91104) was developed.
Methods: We conducted a randomized, placebo-controlled, double-blind, single-centre, dose-ascending Phase 1 trial to assess the safety of UNI91104 in Denmark (NCT04576312).
Background: Peptide-based vaccination is a rational option for immunotherapy of prostate cancer. In this first-in-man phase I/II study, we assessed the safety, tolerability and immunological impact of a synthetic long peptide vaccine targeting Ras homolog gene family member C (RhoC) in patients with prostate cancer. RhoC is a small GTPase overexpressed in advanced solid cancers, metastases and cancer stem cells.
View Article and Find Full Text PDFInteractions between species are influenced by different ecological mechanisms, such as morphological matching, phenological overlap and species abundances. How these mechanisms explain interaction frequencies across environmental gradients remains poorly understood. Consequently, we also know little about the mechanisms that drive the geographical patterns in network structure, such as complementary specialization and modularity.
View Article and Find Full Text PDFBackground: Midazolam is a first-line drug for the treatment of status epilepticus, both by buccal and intravenous administration. In children and adolescents with obesity, midazolam pharmacokinetics may be altered, and the current dosing guidelines may therefore be insufficient.
Objective: The objective of this study was to investigate the pharmacokinetics of midazolam, after intravenous administration, in obese and non-obese adolescents aged 11-18 years.
Aims: In two open-label trials, imipramine alleviated symptoms in patients with stress urinary incontinence and is therefore used off-label for this indication. However, it has never been confirmed that imipramine increases urethral pressure in a placebo-controlled setting. The purpose of this study was to investigate whether imipramine increases the opening urethral pressure compared to placebo in healthy women using urethral pressure reflectometry.
View Article and Find Full Text PDFBasic Clin Pharmacol Toxicol
February 2018
In some hospitals, clinical pharmacists review the medication to find drug-related problems (DRPs) in acutely admitted patients. We aimed to identify the nature of identified DRPs and investigate factors of potential importance for the clinical implementation of pharmacist suggestions. In 100 randomly selected medication review (MR) notes, we retrospectively evaluated the clinical implementation and classified (1) timing and communication of the review; (2) DRPs and related suggestions for the physician; and (3) DRPs' potential clinical relevance to patients as 'beneficial', 'somewhat beneficial', 'no relevance' or 'other relevance'.
View Article and Find Full Text PDFThe Danish Society of Clinical Pharmacology was founded in 1976, and mainly thanks to the persistent efforts of the society, clinical pharmacology became an independent medical speciality in Denmark in 1996. Since then, clinical pharmacology has gone from strength to strength. In the Danish healthcare system, clinical pharmacology has established itself as an indispensible part of the efforts to promote the rational, safe and economic use of drugs.
View Article and Find Full Text PDFObjective: We investigated the health-related effect of systematic medication review performed by a clinical pharmacist and a clinical pharmacologist on nonelective elderly orthopedic patients.
Methods: This is a nonblinded randomized controlled study of 108 patients 65 years or older treated with at least 4 drugs. For the intervention, the clinical pharmacist reviewed the participants' medication after completion of the usual medication routine.
Island biogeography has greatly contributed to our understanding of the processes determining species' distributions. Previous research has focused on the effects of island geography (i.e.
View Article and Find Full Text PDFMacrolides have been proposed to have a positive effect in patients with inflammatory lung diseases, including patients with chronic obstructive pulmonary disease (COPD), who suffer from acute exacerbations. Increased use of macrolides for long-term treatment of patients with COPD has been observed. The evidence of a treatment effect of macrolides in this area is sparse, but some studies suggest that it might be beneficial on the number of exacerbations and the length between them.
View Article and Find Full Text PDFBackground: The CC-chemokine receptor-1 (CCR1) is thought to be involved in recruitment of inflammatory cells in allergic contact dermatitis (ACD). CP-481715 is a specific antagonist of CCR1.
Objectives: To determine the inhibitory effects of CP-418 715 in ACD by evaluating the clinical signs and cellular infiltration in skin biopsies following epicutaneous nickel challenge in allergic subjects.
Objective: To describe the prevalence of inappropriate prescribing in primary care in Copenhagen County, according to the Medication Appropriateness Index (MAI) and to identify the therapeutic areas most commonly involved.
Setting: A cross-sectional study was conducted among 212 elderly ( >65 years) polypharmacy patients (five or more different medications) listed to 41 general practitioners (GPs) in the County of Copenhagen.
Method: Patients exposed to polypharmacy were identified via the database recording the drug subsidy system of Danish pharmacies.
Eur J Clin Pharmacol
November 2005
Objective: To evaluate the inter-group and intra-group reliability of a modified Medication Appropriateness Index (MAI) for use in primary care.
Methods: Elderly (>65 years) polypharmacy (> or =5 drugs) patients in Copenhagen County participated in the study. Information concerning their medical history and information regarding each drug taken by them was provided by their own general practitioners.
The pathogenesis of chronic hepatitis C (HCV) infection is not fully known, but oxidative stress may play a role. The aim of this study was to assess the relationship between HCV load and antioxidant status among patients with chronic HCV infection. Among 23 patients, HCV load, as well as plasma beta-carotene, retinol, ascorbic acid and alpha-tocopherol were measured.
View Article and Find Full Text PDFObjective: In chronic renal failure, clearance of enalapril is reduced. Hence, a renoprotective effect may be achieved with lower doses than conventionally used. Since marked inter-patient variation in concentrations of enalaprilat has been shown in patients with renal failure despite equivalent dosage of enalapril, a direct comparison of the effect of high versus low plasma concentrations of enalaprilat on the progression of renal failure was undertaken.
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