Ca2+ uptake to purified secretory vesicles from bovine neurohypophyses

Purified secretory vesicles isolated from bovine neurohypophyses were found to take up Ca2+ when incubated at 30°C in media containing 10−7 to 10−4 M free Ca2+. At 10−4 free Ca2+ 19 nmol/mg protein were taken up within 30 min. The initial uptake at this Ca2+ concentration was about 2 nmol/mg protein per min. The uptake of Ca2+ to secretory vesicles was not affected by ATP, oligomycin, ruthenium red, trifluoperazine, Mg2+ or K+, but was inhibited by Na+ and Sr2+. From these characteristics it can be concluded that the uptake system does not utilize directly ATP (as the Ca2+-ATPases known to be present in the cell membrane and the endoplasmic reticulum) and is different from the mitochondrial Ca2+ uptake system driven by respiration and/or ATP hydrolysis. However, Ca2+-Na+ exchange may well operate: In experiments using different concentrations of Na+ we found half-maximal inhibition of Ca2+ uptake with 33.3 mM Na+. An analysis of the data in a Hill plot indicated that at least 2 Na+ would be exchanged for 1 Ca2+. Also, it was found that Ca2+ previously taken up could be released again by external Na+ but not by K+

Return to the workforce following first hospitalization for heart failure: a Danish nationwide cohort study

Background: Return to work is important financially, as a marker of functional status and for self-esteem in patients developing chronic illness. We examined return to work after first heart failure (HF) hospitalization. Methods: By individual-level linkage of nationwide Danish registries, we identified 21455 patients of working age (18-60 years) with a first HF hospitalization in the period of 1997-2012. Of these 11880 (55%) were in the workforce prior to HF hospitalization and comprised the study population. We applied logistic regression to estimate odds ratios (OR) for associations between age, sex, length of hospital stay, level of education, income, comorbidity and return to work. Results: One year after first HF hospitalization, 8040 (67.7%) returned to the workforce, 2981 (25.1%) did not, 805 (6.7%) died and 54 (0.5%) emigrated. Predictors of return to work included younger age (18-30 vs. 51-60 years, OR 3.12; 95% CI 2.42-4.03), male sex (OR 1.22 [1.18-1.34]) and level of education (long-higher vs. basic school OR 2.06 [1.63-2.60]). Conversely, hospital stay >7 days (OR 0.56 [0.51-0.62]) and comorbidity including history of stroke (OR 0.55 [0.45-0.69]), chronic kidney disease (OR 0.46 [0.36-0.59]), chronic obstructive pulmonary disease (OR 0.62 [0.52-0.75]), diabetes (OR 0.76 [0.68-0.85]) and cancer (OR 0.49 [0.40-0.61]) were all significantly associated with lower chance of return to work. Conclusions: Patients in the workforce prior to HF hospitalization had low mortality but high risk of detachment from the workforce one year later. Young age, male sex, and higher level of education were predictors of return to work

Influence of heart rate, blood pressure, and beta-blocker dose on outcome and the differences in outcome between carvedilol and metoprolol tartrate in patients with chronic heart failure: results from the COMET trial.

AIMS: We studied the influence of heart rate (HR), systolic blood pressure (SBP), and beta-blocker dose on outcome in the 2599 out of 3029 patients in Carvedilol Or Metoprolol European Trial (COMET) who were alive and on study drug at 4 months after randomization (time of first visit on maintenance therapy). METHODS AND RESULTS: By multivariable analysis, baseline HR, baseline SBP, and their change after 4 months were not independently related to subsequent outcome. In a multivariable analysis including clinical variables, HR above and SBP below the median value achieved at 4 months predicted subsequent increased mortality [relative risk (RR) for HR>68 b.p.m. 1.333; 95% confidence intervals (CI) 1.152-1.542; P120 mmHg 0.78; 95% CI 0.671-0.907; P<0.0013]. Achieving target beta-blocker dose was associated with a better outcome (RR 0.779; 95% CI 0.662-0.916; P<0.0025). The superiority of carvedilol as compared to metoprolol tartrate was maintained in a multivariable model (RR 0.767; 95% CI 0.663-0.887; P=0.0004) and there was no interaction with HR, SBP, or beta-blocker dose. CONCLUSION: Beta-blocker dose, HR, and SBP achieved during beta-blocker therapy have independent prognostic value in heart failure. None of these factors influenced the beneficial effects of carvedilol when compared with metoprolol tartrate at the pre-defined target doses used in COMET

Should beta-blocker therapy be reduced or withdrawn after an episode of decompensated heart failure? Results from COMET.

BACKGROUND: It is unclear whether beta-blocker therapy should be reduced or withdrawn in patients who develop acute decompensated heart failure (HF). We studied the relationship between changes in beta-blocker dose and outcome in patients surviving a HF hospitalisation in COMET. METHODS: Patients hospitalised for HF were subdivided on the basis of the beta-blocker dose administered at the visit following hospitalisation, compared to that administered before. RESULTS: In COMET, 752/3029 patients (25%, 361 carvedilol and 391 metoprolol) had a non-fatal HF hospitalisation while on study treatment. Of these, 61 patients (8%) had beta-blocker treatment withdrawn, 162 (22%) had a dose reduction and 529 (70%) were maintained on the same dose. One-and two-year cumulative mortality rates were 28.7% and 44.6% for patients withdrawn from study medication, 37.4% and 51.4% for those with a reduced dosage (n.s.) and 19.1% and 32.5% for those maintained on the same dose (HR,1.59; 95%CI, 1.28-1.98; p<0.001, compared to the others). The result remained significant in a multivariable model: (HR, 1.30; 95%CI, 1.02-1.66; p=0.0318). No interaction with the beneficial effects of carvedilol, compared to metoprolol, on outcome was observed (p=0.8436). CONCLUSIONS: HF hospitalisations are associated with a high subsequent mortality. The risk of death is higher in patients who discontinue beta-blocker therapy or have their dose reduced. The increase in mortality is only partially explained by the worse prognostic profile of these patients

Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics: nationwide study

Study question What is the effect of proton pump inhibitors (PPIs) on the risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with non-steroidal anti-inflammatory drugs (NSAIDs)? Methods This was a nationwide cohort study based on linked administrative registry data from all hospitals in Denmark between 1997 and 2011. The study included patients aged 30 years and over admitted with a first myocardial infarction who survived at least 30 days after discharge. The association between PPIs and risk of gastrointestinal bleeding according to NSAID plus antithrombotic therapy was estimated using adjusted time dependent Cox regression models. Study answer and limitations The use of PPIs was independently associated with decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with NSAIDs. Of 82 955 post-myocardial infarction patients (mean age 67.4 years, 64% (n=53 070) men), all of whom were taking single or dual antithrombotic therapy, 42.5% (n=35 233) filled at least one prescription for NSAIDs and 45.5% (n=37 771) received PPIs. Over a mean follow-up of 5.1 years, 3229 gastrointestinal bleeds occurred. The crude incidence rates of bleeding (events/100 person years) on NSAID plus antithrombotic therapy were 1.8 for patients taking PPIs and 2.1 for those not taking PPIs. The adjusted risk of bleeding was lower with PPI use (hazard ratio 0.72, 95% confidence interval 0.54 to 0.95) regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used. The main limitation of the study is its observational non-randomised design. The results suggest that PPI treatment probably has a beneficial effect regardless of underlying gastrointestinal risk and that when NSAIDs cannot be avoided in post-myocardial infarction patients, physicians might prescribe a PPI as well. The study does not clarify whether PPIs might be safely omitted in specific subgroups of patients with a low risk of gastrointestinal bleeding. What this study adds In post-myocardial infarction patients, bleeding complications have been associated with both antithrombotic and NSAID treatment. Concurrent use of PPIs was independently associated with a decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and NSAID, regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used. Funding, competing interests, data sharing AMSO has received a grant from the Danish Council of Independent Research (grant 12-132760). GHG is supported by an unrestricted research scholarship from the Novo Nordisk Foundation

Numerical Analysis of Threaded Rods

Denne masteroppgaven er en numerisk analyse av gjengede stag innskrudd i treverk. To modeller ble forsøkt kalibrert basert på eksperimentelle resultater. En modell hadde et gjenget stag utsatt for aksialkraft, i både trykk og strekk, mens en annen modell ble utsatt for en sideveis kraft. For begge modeller ble det gjort forsøk hvor kraften virket på parallelt og normalt på fiberretningen til treverket. Stivheten til modellen hvor staget er utsatt for aksialkraft i strekk viste god overensstemmelse med eksperimentelle resultater, og ikke fullt så god overensstemmelse i trykk. Utdragskraft ble også undersøkt i modellen hvor staget ble utsatt for aksialkraft, og kraften som skulle til for å rive ut staget viste god overensstemmelse med eksperimenter. Basert på resultater fra denne oppgaven, er det sannsynlig at det er mulig å kalibrere en modell som kan gi realistiske resultater, uten for mye kompleksitet.This thesis is a numerical analysis of threaded rods embedded in wood. Two models were calibrated based on experimental results. One had a threaded rod subjected to tension and compression, while the other model was concerned with lateral loading. In the axially loaded model, the stiffness in tension and compression was studied both parallel and perpendicular to the grain. This was also done for the laterally loaded model. The stiffness of the axially loaded model in tension was in general in good agreement with experimental results, while less so for the same model in compression. The author was not able to calibrate the stiffness of the laterally loaded model. Withdrawal failure was also modelled for the axially loaded model, and the withdrawal strength was in general in good agreement with experimental results. A parametric study was conducted parallel to the calibration, and showed good and predictable results. Based on the results of this thesis, it can be possible to successfully calibrate and create a realistic model, that yields accurate results without using too much computational power

Feasibility of a standardized ultrasound examination in patients with rheumatoid arthritis: A quality improvement among rheumatologists cohort.

BACKGROUND: Quality improvement is important to facilitate valid patient outcomes. Standardized examination procedures may improve the validity of US. The aim of this study was to investigate the learning progress for rheumatologists during training of US examination of the hand in patients with rheumatoid arthritis (RA). METHODS: Rheumatologists with varying degrees of experience in US were instructed by skilled tutors. The program consisted of two days with hands-on training followed by personal US examinations performed in their individual clinics. Examinations were sent to the tutors for quality control. The US examinations were evaluated according to a scoring sheet containing 144 items. An acceptable examination was defined as > 80% correct scores. RESULTS: Thirteen rheumatologists participated in the study. They included a total of 104 patients with RA. Only few of the initial examinations were scored below 80%, and as experience increased, the scores improved (p = 0.0004). A few participants displayed decreasing scores. The mean time spent performing the standardized examination procedure decreased from 34 min to less than 10 minutes (p = 0.0001). CONCLUSION: With systematic hands-on training, a rheumatologist can achieve a high level of proficiency in the conduction of US examinations of the joints of the hand in patients with RA. With experience, examination time decreases, while the level of correctness is maintained. The results indicate that US may be applied as a valid measurement tool suitable for clinical practice and in both single- and multi-centre trials

Statin treatment and risk of recurrent venous thromboembolism: a nationwide cohort study

Statins may decrease the risk of primary venous thromboembolism (VTE), that is, deep vein thrombosis (DVT) and pulmonary embolism (PE) but the effect of statins in preventing recurrent VTE is less clear. The aim of this study was therefore to investigate the association between statin therapy and risk of recurrent VTE. A prospective cohort study. All hospitals in Denmark. All patients with a hospital diagnosis of VTE in Denmark during 1997-2009 associated with a warfarin or heparin prescription were identified. Adjusted HR of recurrent hospitalised VTE (ie, fatal or non-fatal DVT or PE) associated with use of statins. 44 330 patients with VTE were included in the study. Of these 3914 were receiving statin therapy at baseline. Patients receiving statins were older (68±11 compared to 62±18 years), had more comorbidity and used more medications. The incidence rate for recurrent VTE was 24.4 (95% CI 22.8 to 26.2) per 1000 person-years among statin users and 48.5 (95% CI 47.4 to 49.7) per 1000 person-years among non-statin users. Statin use was associated with a significantly lower risk of a recurrent VTE, adjusted HR 0.74 (95% CI 0.68 to 0.80), compared with no statin use. The association between statin use and risk of recurrent VTE was significantly affected by age. Among younger individuals (≤80 years), statin use was associated with lower risk of recurrent VTE, HR 0.70 (95% CI 0.65 to 0.76) whereas in older individuals (>80 years) statin use was significantly associated with higher risk of recurrent VTE, HR 1.28 (95% CI 1.02 to 1.60), p for interaction= <0.0001. Statin use was associated with a decreased risk of recurrent VT