Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
Submitted 7 April 2006
; accepted in final form 22 May 2006
We characterized hemodynamics and systolic and ...diastolic right ventricular (RV) function in relation to structural changes in the rat model of monocrotaline (MCT)-induced pulmonary hypertension. Rats were treated with MCT at 30 mg/kg body wt (MCT30, n = 15) and 80 mg/kg body wt (MCT80, n = 16) to induce compensated RV hypertrophy and RV failure, respectively. Saline-treated rats served as control (Cont, n = 13). After 4 wk, a pressure-conductance catheter was introduced into the RV to assess pressure-volume relations. Subsequently, rats were killed, hearts and lungs were rapidly dissected, and RV, left ventricle (LV), and interventricular septum (IVS) were weighed and analyzed histochemically. RV-to-(LV + IVS) weight ratio was 0.29 ± 0.05 in Cont, 0.35 ± 0.05 in MCT30, and 0.49 ± 0.10 in MCT80 ( P < 0.001 vs. Cont and MCT30) rats, confirming MCT-induced RV hypertrophy. RV ejection fraction was 49 ± 6% in Cont, 40 ± 12% in MCT30 ( P < 0.05 vs. Cont), and 26 ± 6% in MCT80 ( P < 0.05 vs. Cont and MCT30) rats. In MCT30 rats, cardiac output was maintained, but RV volumes and filling pressures were significantly increased compared with Cont (all P < 0.05), indicating RV remodeling. In MCT80 rats, RV systolic pressure, volumes, and peak wall stress were further increased, and cardiac output was significantly decreased (all P < 0.05). However, RV end-systolic and end-diastolic stiffness were unchanged, consistent with the absence of interstitial fibrosis. MCT-induced pressure overload was associated with a dose-dependent development of RV hypertrophy. The most pronounced response to MCT was an overload-dependent increase of RV end-systolic and end-diastolic volumes, even under nonfailing conditions.
right ventricular hypertrophy; right ventricular failure; pressure-volume relations
Address for reprint requests and other correspondence: P. Steendijk, Dept. of Cardiology, C5-P, Leiden Univ. Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands (e-mail: p.steendijk{at}lumc.nl )
Vemurafenib/dabrafenib and trametinib Rissmann, Robert; Hessel, Marleen H M; Cohen, Adam F
British journal of clinical pharmacology,
10/2015, Letnik:
80, Številka:
4
Journal Article
Sofosbuvir and daclatasvir Hessel, Marleen H. M.; Cohen, Adam F.; Rissmann, Robert
British journal of clinical pharmacology,
September 2016, Letnik:
82, Številka:
3
Journal Article
Aims
Prescribing errors among junior doctors are common in clinical practice because many lack prescribing competence after graduation. This is in part due to inadequate education in clinical ...pharmacology and therapeutics (CP&T) in the undergraduate medical curriculum. To support CP&T education, it is important to determine which drugs medical undergraduates should be able to prescribe safely and effectively without direct supervision by the time they graduate. Currently, there is no such list with broad‐based consensus. Therefore, the aim was to reach consensus on a list of essential drugs for undergraduate medical education in the Netherlands.
Methods
A two‐round modified Delphi study was conducted among pharmacists, medical specialists, junior doctors and pharmacotherapy teachers from all eight Dutch academic hospitals. Participants were asked to indicate whether it was essential that medical graduates could prescribe specific drugs included on a preliminary list. Drugs for which ≥80% of all respondents agreed or strongly agreed were included in the final list.
Results
In all, 42 (65%) participants completed the two Delphi rounds. A total of 132 drugs (39%) from the preliminary list and two (3%) newly proposed drugs were included.
Conclusions
This is the first Delphi consensus study to identify the drugs that Dutch junior doctors should be able to prescribe safely and effectively without direct supervision. This list can be used to harmonize and support the teaching and assessment of CP&T. Moreover, this study shows that a Delphi method is suitable to reach consensus on such a list, and could be used for a European list.
A Licence to Prescribe Kramers, Cornelis; Janssen, Ben. J.; Knol, Wilma ...
British journal of clinical pharmacology,
August 2017, Letnik:
83, Številka:
8
Journal Article
Background:
In heart failure patients, cardiac resynchronization therapy (CRT) leads to reverse ventricular remodelling.
Aim:
The aim of this study was to evaluate whether changes in levels of ...circulating biomarkers of extracellular matrix metabolism correlate with the response to CRT.
Methods and results:
Clinical parameters, left ventricular (LV) volumes, and circulating levels of tenascin-C (TNC), matrix metalloproteinase-2 (MMP-2), MMP-9, and amino-terminal propeptide of brain natriuretic peptide (NT-proBNP) were assessed in 64 patients at baseline and 6 months follow-up. The majority of patients (72%) showed a >10% reduction in LV end-systolic volume at follow-up, and were classified as responders to CRT. The remaining patients were classified as non-responders. In responders, a significant decrease in circulating levels of TNC (from 60±40ng/mL to 47±30ng/mL, p<0.01), MMP-9 (from 55±30 AU to 44±27 AU, p<0.01), and NT-proBNP (from 2106±1805pg/mL to 1132±1289pg/mL, p<0.001) were observed at follow-up; MMP-2 levels were unchanged. In non-responders TNC, NT-proBNP, MMP-9 and MMP-2 levels remained unchanged.
Conclusion:
At 6months follow-up, CRT was associated with reverse LV remodelling, and a significant decrease in TNC, MMP-9, and NT-proBNP levels. This suggests an important role of ECM modulation in the process of reverse ventricular remodelling in patients responding to CRT.
Inflammatory mediators can serve as biomarkers for the monitoring of the disease progression or prognosis in many conditions. In the present study we introduce an adaptation of a membrane-based ...technique in which the level of up to 40 cytokines and chemokines can be determined in both human and rodent blood in a semi-quantitative way. The planar assay was modified using the LI-COR (R) detection system (fluorescence based) rather than chemiluminescence and semi-quantitative outcomes were achieved by normalizing the outcomes using the automated exposure settings of the Odyssey readout device. The results were compared to the gold standard assay, namely ELISA.
The improved planar assay allowed the detection of a considerably higher number of analytes (n = 30 and n = 5 for fluorescent and chemiluminescent detection, respectively). The improved planar method showed high sensitivity up to 17 pg/ml and a linear correlation of the normalized fluorescence intensity with the results from the ELISA (r = 0.91).
The results show that the membrane-based technique is a semi-quantitative assay that correlates satisfactorily to the gold standard when enhanced by the use of fluorescence and subsequent semi-quantitative analysis. This promising technique can be used to investigate inflammatory profiles in multiple conditions, particularly in studies with constraints in sample sizes and/or budget.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Since 1990, natural hazards have led to over 1.6 million fatalities globally, and economic losses are estimated at an average of around USD 260–310 billion per year. The scientific and policy ...communities recognise the need to reduce these risks. As a result, the last decade has seen a rapid development of global models for assessing risk from natural hazards at the global scale. In this paper, we review the scientific literature on natural hazard risk assessments at the global scale, and we specifically examine whether and how they have examined future projections of hazard, exposure, and/or vulnerability. In doing so, we examine similarities and differences between the approaches taken across the different hazards, and we identify potential ways in which different hazard communities can learn from each other. For example, there are a number of global risk studies focusing on hydrological, climatological, and meteorological hazards that have included future projections and disaster risk reduction measures (in the case of floods), whereas fewer exist in the peer-reviewed literature for global studies related to geological hazards. On the other hand, studies of earthquake and tsunami risk are now using stochastic modelling approaches to allow for a fully probabilistic assessment of risk, which could benefit the modelling of risk from other hazards. Finally, we discuss opportunities for learning from methods and approaches being developed and applied to assess natural hazard risks at more continental or regional scales. Through this paper, we hope to encourage further dialogue on knowledge sharing between disciplines and communities working on different hazards and risk and at different spatial scales.
Background:
In patients with heart failure cardiac resynchronization therapy (CRT) leads to reverse ventricular remodelling.
Aim:
To evaluate whether myocardial collagen metabolism in patients with ...heart failure is implicated in adverse ventricular remodelling and response to CRT.
Methods:
Collagen synthesis and degradation were assessed from the concentrations of aminoterminal propeptides of type I and type III collagen (PINP and PIIINP) and carboxyterminal telopeptide of type I collagen (ICTP), respectively, in serum of 64 patients with heart failure before and after 6 months of CRT. Forty-six patients (72%) showed a > 10% reduction in LV end-systolic volume at follow-up and were classified as responders to CRT, the other 18 patients (28%) were classified as non-responders.
Results:
Responders demonstrated a mean (±SEM) increase of serum PINP and PIIINP during follow-up, from 32.9±2.2 to 46.7±4.0 μg/L (p<0.001) and from 4.59±0.24 to 5.13±0.36 μg/L (p<0.05), respectively. In non-responders, serum PINP and PIIINP remained unchanged during follow-up. At baseline, responders had significantly lower serum PINP than non-responders (32.9±2.2 vs. 41.8±4.3 μg/L; p<0.05).
ICTP levels of responders at baseline tended to be higher than in non-responders (3.54±0.56 vs. 2.08±0.37 μg/L, p=ns), and in both groups ICTP levels did not change upon CRT.
Conclusion:
Reverse LV remodelling following CRT is associated with increased collagen synthesis rate in the first 6 months of follow-up.
Study Type – Symptom prevalence (retrospective cohort) Level of Evidence 2b
OBJECTIVES
To determine the role of treatment‐associated improvement in nocturia in health‐related quality of life (HRQL) ...in patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia, and secondarily to confirm the role of nocturia in HRQL at baseline and to compare the effects of watchful waiting, transurethral microwave treatment (TUMT) and transurethral resection of the prostate (TURP) to those of α1‐adrenoceptor antagonists (α‐blockers) on nocturia.
PATIENTS AND METHODS
We retrospectively analysed using multiple regression a large single‐centre database of patients receiving routine care for treatment‐associated alterations of symptoms and HRQL (assessed at baseline, 2611 men) and 6–12 months after initiation of treatment (1258 men).
RESULTS
Among the symptoms assessed using the International Prostate Symptom Score, nocturia (together with urgency and weak stream) had the strongest correlation with HRQL at baseline and after treatment. Watchful waiting, α‐blockers, TUMT and TURP reduced nocturia episodes by a mean (sd) of 7 (53)%, 17 (40)%, 32 (47)% and 75 (23)%, respectively. The treatment‐associated improvements in nocturia (together with those of weak stream) had the strongest association with those of HRQL.
CONCLUSIONS
We conclude that among all LUTS assessed in the IPSS, nocturia has one of the strongest associations with HRQL, and that treatment‐associated improvements in nocturia contribute considerably to overall improvements in HRQL.
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