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Studies on intrinsic and extrinsic sources of variability in pharmacokinetics and pharmacodynamics

Popular Abstract in Swedish Variabilitet i ett läkemedels farmakokinetiska (hur ett läkemedel omsätts i kroppen) och farmakodynamiska (vilken effekt ett läkemedel har) egenskaper kan resultera i att olika individer som erhållit samma dos av ett läkemedel får olika effekter av läkemedel. Biverkningar eller utebliven effekt kan innebära allvarliga konsekvenser för den enskilda individen. VariabiliteVariability in pharmacokinetic and pharmacodynamic parameters between individuals can be due to intrinsic and extrinsic factors. In this thesis three different areas regarding sources of variability have been investigated. 1. Formulation properties as an extrinsic source of variability. Lipophilic substances often have poor oral bioavailability and high inter- and intraindividual variability. High

Perinatal factors associated with cerebral palsy in children born in Sweden.

OBJECTIVE: To identify perinatal factors associated with cerebral palsy (CP). METHODS: This was a case-control study based on the Swedish Medical Birth Registry and the Swedish Hospital Discharge Registry, including 2,303 infants born in Sweden 1984-1998 with a diagnosis of CP and 1.6 million infants without this diagnosis. Odds ratios (ORs) with 95% confidence intervals (Cis) were calculated. RES

Improved meal-related beta-cell function and insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year.

OBJECTIVE—To examine the effects of dipeptidyl peptidase-IV (DPP-4) inhibition on meal-related β-cell function and insulin sensitivity over 52 weeks in type 2 diabetes. RESEARCH DESIGN AND METHODS—In a 12-week core study, placebo (n = 51) or vildagliptin (n = 56; 50 mg OD) was added to metformin treatment (1.5–3.0 mg/day). A 40-week extension followed in 71 patients. Meal tests were performed at

Results of endosonographic imaging of the anal sphincter 2-7 days after primary repair of third- or fourth-degree obstetric sphincter tears.

Objectives To describe the endosonographic image of the anal sphincter 2-7 days after delivery in women who had undergone a primary repair of an obstetric sphincter tear. Methods Forty-eight women who had suffered a third- or fourth-degree sphincter tear at delivery and had undergone primary sphincter repair were examined with endoanal sonography 2-7 days after delivery. A score from 0 to 16 was

Traditional versus agricultural lifestyle among Shuar women of the Ecuadorian Amazon: Effects on leptin levels

Leptin is a key biological marker related to energy balance and development of diabetes and cardiovascular diseases. Its levels are increased in populations with a high degree of the metabolic syndrome. Life history of evolution has, however, largely taken place under the ecological context of hunting and gathering. In this study, we explored whether the first steps of transition to sedentary agri

Contribution of known and unknown susceptibility genes to early-onset diabetes in scandinavia: evidence for heterogeneity.

In an attempt to identify novel susceptibility genes predisposing to early-onset diabetes (EOD), we performed a genome-wide scan using 433 markers in 222 individuals (119 with diabetes) from 29 Scandinavian families with ≥2 members with onset of diabetes ≤45 years. The highest nonparametric linkage (NPL) score, 2.7 (P < 0.01), was observed on chromosome 1p (D1S473/D1S438). Six other regions on chr

Fibroblast growth factor 23, mineral metabolism and mortality among elderly men (Swedish MrOs)

Background: Fibroblast growth factor 23 (FGF23) is the earliest marker of disturbed mineral metabolism as renal function decreases. Its serum levels are associated with mortality in dialysis patients, persons with chronic kidney disease (CKD) and prevalent cardiovascular disease (CVD), and it is associated with atherosclerosis, endothelial dysfunction and left ventricular hypertrophy in the genera

Mortality risks among heavy-smokers with special reference to women: a long-term follow-up of an urban population

Increased mortality risks associated with smoking are well established among men. There are very few population-based studies comprising a sufficient number of heavily smoking women, measuring the direct effect of smoking on mortality risks. Between 1974 and 1992, 8,499 women and 13,888 men attended a health screening programme including reporting of smoking habits. Individuals were followed for t

Timing and speed of migration in male, female and juvenile Ospreys Pandion haliaetus between Sweden and Africa as revealed by field observations, radar and satellite tracking

Breeding Ospreys were studied in southern Sweden and 13 birds were tracked by satellite telemetry on autumn migration to the African wintering grounds. This was supplemented with studies of migrating birds at Falsterbo and radar trackings From southern Sweden. Females generally left the nest site 2-3 weeks ahead of males and juveniles. Among males, failed bleeders migrated significantly earlier th

Cerebral blood volume (CBV) in humans during normo- and hypocapnia: influence of nitrous oxide (N(2)O)

BACKGROUND: It is generally argued that variations in cerebral blood flow create concomitant changes in the cerebral blood volume (CBV). Because nitrous oxide (N(2)O) inhalation both increases cerebral blood flow and may increase intracranial pressure, it is reasonable to assume that N(2)O acts as a general vasodilatator in cerebral vessels both on the arterial and on the venous side. The aim of t

Pathways through relapses and deaths of children with acute lymphoblastic leukemia: Role of allogeneic stem-cell transplantation in Nordic data

Purpose Our focus was on patients with pediatric acute lymphoblastic leukemia (ALL) who experienced relapse or died without becoming transplantation candidates. The purpose was to outline measures needed to improve the outcome. Patients and Methods We analyzed our population-based 20-year data on 3,385 Nordic children with ALL treated on Nordic Society for Pediatric Hematology and Oncology ALL pro

Efficacy and safety of a new combination of calcipotriol and betamethasone dipropionate (once or twice daily) compared to calcipotriol (twice daily) in the treatment of psoriasis vulgaris: a randomized, double-blind, vehicle-controlled clinical trial.

Background Calcipotriol and betamethasone dipropionate are both widely used, effective treatments for psoriasis. Vitamin D analogues and topical corticosteroids have different mechanisms of action in the treatment of psoriasis. A new vehicle has been developed in order to contain both calcipotriol (50 micro g g-1) and betamethasone dipropionate (0.5 mg g-1) in an ointment form. By using calcipotri

Impact of metformin versus the prandial insulin secretagogue, repaglinide, on fasting and postprandial glucose and lipid responses in non-obese patients with type 2 diabetes

Objective: Non-obese patients with type 2 diabetes (T2DM) are characterized by predominant defective insulin secretion. However, in non-obese T2DM patients, metformin, targeting insulin resistance. is non-inferior to the prandial insulin secretagogue, repaglinide, controlling overall glycaemia (HbA(1c)). Whether the same apply for postprandial glucose and lipid metabolism is unknown. Here. we comp

Atopy is a risk factor for respiratory symptoms in COPD patients: results from the EUROSCOP study

Background: The pathogenesis of COPD is complex and remains poorly understood. The European Respiratory Society Study on Chronic Obstructive Pulmonary Disease (EUROSCOP) investigated long-term effects of budesonide; 18% of the COPD participants were atopic. So far effects of atopy on the long-term course of COPD have not been elucidated. Methods: Factors related to the presence of atopy (positive

Development and validation of a new automatic algorithm for quantification of left ventricular volumes and function in gated myocardial perfusion SPECT using cardiac magnetic resonance as reference standard.

BACKGROUND: By gating image acquisition in myocardial perfusion SPECT (MPS) to ECG, left ventricular (LV) volumes and function can be determined. Several previous studies have shown that existing MPS software packages underestimate LV volumes compared to cardiac magnetic resonance (CMR). The aim of this study was therefore to develop a new LV segmentation algorithm for gated MPS using CMR as refer

A randomized controlled study comparing pain experience between a newly designed needle with a thin tip and a standard needle for oocyte aspiration

Background: Ultrasound-guided transvaginal oocyte retrieval is often performed under local anaesthesia on an outpatient basis. The objective of this study was to compare the overall pain experience of a newly designed reduced needle (RN) compared with a thicker standard needle (SN). Methods: A prospective, randomized, multi-centre study was performed at four different clinics from June to December

Modelling of mineral dust for interglacial and glacial climate conditions with a focus on Antarctica

The mineral dust cycle responds to climate variations and plays an important role in the climate system by affecting the radiative balance of the atmosphere and modifying biogeochemistry. Polar ice cores provide unique information about deposition of aeolian dust particles transported over long distances. These cores are a palaeoclimate proxy archive of climate variability thousands of years ago.

Effects of AZD0837, a Novel Direct Thrombin Inhibitor, on the Electrophysiological Properties of the Human Heart A Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study

Background: AZD0837 is an investigational oral anticoagulant that is bio-converted to its active form, AR-H067637, a selective direct thrombin inhibitor. Objectives: The objectives of the present study were to investigate if there are any clinically relevant adverse effects of intravenous AZD0837 on cardiac conduction, refractoriness and repolarization, and to study its safety and tolerability. Me