• MeSH
• Gastrointestinal Transit drug effects   MeSH
• Imino Acids MeSH
• Humans MeSH
• Morpholines pharmacology   therapeutic use   MeSH
• Common Bile Duct Diseases diagnostic imaging   drug therapy   physiopathology   MeSH
• Sphincter of Oddi diagnostic imaging   drug effects   physiopathology   MeSH
• Organotechnetium Compounds MeSH
• Parasympatholytics pharmacology   therapeutic use   MeSH
• Radionuclide Imaging MeSH
• Technetium Tc 99m Lidofenin MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Imino Acids MeSH
• Morpholines MeSH
• Organotechnetium Compounds MeSH
• Parasympatholytics MeSH
• pinaverium MeSH Browser
• Technetium Tc 99m Lidofenin MeSH

Sunitinib is a broad-spectrum multitargeted tyrosine kinase inhibitor mainly used as second-line therapy for non-resectable gastrointestinal stromal or first-line treatment option of metastatic renal cell carcinoma (mRCC), and as an "off-label" option in pediatric oncology. It has been previously reported that sunitinib elevates the mean corpuscular volume of erythrocytes (MCV) in treated subjects. The aim of this study was to assess time-dependent changes of this effect and evaluate its possible clinical relevance. In this study, 179 adult and 21 pediatric patients with solid tumors treated with sunitinib were retrospectively analyzed. The laboratory and treatment-related data were collected for each treatment period. The regression model with a broken-line relationship was used to fit time dependence of the MCV. In the adult group, the MCV was increasing during the first 21.6 weeks (median) of treatment in a median level of 99.8 fL, where it stabilized. MCV increase was faster in the patients who suffered from treatment-related adverse events (21.3 vs. 24.6 weeks, p = 0.010). In the pediatric cohort, the MCV dynamics were similar to adults. In conclusion, MCV changes during sunitinib treatment in pediatric and adult patients may be of clinical utility in monitoring sunitinib treatment course.

• Keywords
• MCV, mean corpuscular volume, sunitinib, toxicity,
• MeSH
• Child MeSH
• Adult MeSH
• Erythrocyte Indices MeSH
• Indoles adverse effects   MeSH
• Carcinoma, Renal Cell * drug therapy   pathology   MeSH
• Humans MeSH
• Kidney Neoplasms * drug therapy   pathology   MeSH
• Antineoplastic Agents * adverse effects   MeSH
• Pyrroles adverse effects   MeSH
• Retrospective Studies MeSH
• Sunitinib pharmacology   therapeutic use   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Indoles MeSH
• Antineoplastic Agents * MeSH
• Pyrroles MeSH
• Sunitinib MeSH

AIMS: In the IN-TIME trial, automatic daily implant-based multiparameter telemonitoring significantly improved clinical outcomes in patients with chronic systolic heart failure and implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D). We compared IN-TIME results for ICD and CRT-D subgroups. METHODS: Patients with LVEF ≤ 35%, NYHA class II/III, optimized drug treatment, no permanent atrial fibrillation, and a dual-chamber ICD (n = 274) or CRT-D (n = 390) were randomized 1:1 to telemonitoring or no telemonitoring for 12 months. Primary outcome measure was a composite clinical score, classified as worsened if the patient died or had heart failure-related hospitalization, worse NYHA class, or a worse self-reported overall condition. RESULTS: The prevalence of worsened score at study end was higher in CRT-D than ICD patients (26.4% vs. 18.2%; P = 0.014), as was mortality (7.4% vs. 4.1%; P = 0.069). With telemonitoring, odds ratios (OR) for worsened score and hazard ratios (HR) for mortality were similar in the ICD [OR = 0.55 (P = 0.058), HR = 0.39 (P = 0.17)] and CRT-D [OR = 0.68 (P = 0.10), HR = 0.35 (P = 0.018)] subgroups (insignificant interaction, P = 0.58-0.91). CONCLUSION: Daily multiparameter telemonitoring has a potential to reduce clinical endpoints in patients with chronic systolic heart failure both in ICD and CRT-D subgroups. The absolute benefit seems to be higher in higher-risk populations with worse prognosis.

• Keywords
• Remote monitoring of cardiac resynchronization therapy defibrillators, Remote monitoring of implantable cardioverter-defibrillators, Telemonitoring of patients with heart failure,
• MeSH
• Defibrillators, Implantable * MeSH
• Middle Aged MeSH
• Humans MeSH
• Survival Rate trends   MeSH
• Follow-Up Studies MeSH
• Cause of Death trends   MeSH
• Prospective Studies MeSH
• Risk Factors MeSH
• Aged MeSH
• Cardiac Resynchronization Therapy methods   MeSH
• Heart Failure, Systolic mortality   physiopathology   therapy   MeSH
• Telemedicine methods   MeSH
• Stroke Volume physiology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH
• Geographicals
• Germany epidemiology   MeSH

This study aimed to compare the effect of three interset rest intervals (1, 3, and 5 minutes) on (I) mean velocity during a resistance training session conducted in a Smith machine with the squat and bench press exercises, and (II) the pre- and post-exercise force-velocity relationship. Fifteen male university students completed three sessions (i.e., Rest 1', Rest 3', and Rest 5') consisting of three sets of five repetitions against the 10RM load during the squat and bench press exercises. The force-velocity relationship (maximal values of force [F0], velocity [v0], and power [Pmax]) was evaluated at the beginning and at the end of each session with the countermovement jump and bench press throw exercises. During training, mean velocity was slower in sets 2 and 3 of the Rest 1' protocol compared to Rest 3' and Rest 5', but no significant differences were present between Rest 3' and Rest 5'. After training, there was a significant decrease in F0 (p = 0.017) and Pmax (p = 0.010), but not in v0 (p = 0.259). These results support the Rest 3' as the most time-efficient protocol, among those analysed, for the maintenance of high mean velocities during training sessions not leading to failure.

• Keywords
• Force-velocity relationship, linear position transducer, strength training, velocity-based training,
• MeSH
• Biomechanical Phenomena MeSH
• Exercise MeSH
• Muscle, Skeletal * MeSH
• Humans MeSH
• Resistance Training * methods   MeSH
• Muscle Strength MeSH
• Weight Lifting MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH

OBJECTIVE: Mean platelet volume is arousing increasing interest as a new independent cardiovascular risk factor. Large platelets are likely to be more reactive. If mean platelet volume would drop after LDL-lowering therapy, decreased MPV could be one of the markers of successful therapy. Therefore, we investigated mean platelet volume after extracorporeal LDL-cholesterol elimination. METHODS: Mean platelet volume was investigated in patients with severe familial hypercholesterolemia long-term treated (3-12 years) by LDL-apheresis (immunoapheresis) or cascade filtration. Plasma was obtained by centrifugation. Adsorbers Lipopak 400 were used for immunoapheresis and filters Evaflux 4A were used for cascade filtration. 95 pair samples were measured (before and after the procedures) in a group of 12 patients--each patient 8 times in 4 years. RESULTS: Mean platelet volume before the procedures was 10.891 fl, CI 10.25-11.53. Mean platelet volume after the procedures decreased--10.478 fl, CI 09.84-11.11. The difference is statistically significant (p = 0.036). Mean platelet volume did not correlate with age, sex, platelet count, duration of therapy. At the same time, we used rheohemapheresis in the therapy of 40 patients with age-related macular degeneration. But mean platelet volume was not changed. CONCLUSION: Mean platelet volume is easily available and is often disregarded, and sometimes may suggest the need for a careful assessment in patients with familial hypercholesterolemia. Mean platelet volume could be one of the markers of therapeutic efficacy in patients with familial hypercholesterolemia treated by extracorporeal LDL-cholesterol elimination that is simple and inexpensive.

• MeSH
• Biomarkers blood   MeSH
• Time Factors MeSH
• Adult MeSH
• Hyperlipoproteinemia Type II blood   diagnosis   therapy   MeSH
• Cholesterol, LDL blood   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Predictive Value of Tests MeSH
• Blood Component Removal * MeSH
• Blood Platelets pathology   MeSH
• Cell Size * MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Biomarkers MeSH
• Cholesterol, LDL MeSH

BACKGROUND: An increasing number of patients with heart failure receive implantable cardioverter-defibrillators (ICDs) or cardiac resynchronisation defibrillators (CRT-Ds) with telemonitoring function. Early detection of worsening heart failure, or upstream factors predisposing to worsening heart failure, by implant-based telemonitoring might enable pre-emptive intervention and improve outcomes, but the evidence is weak. We investigated this possibility in IN-TIME, a clinical trial. METHODS: We did this randomised, controlled trial at 36 tertiary clinical centres and hospitals in Australia, Europe, and Israel. We enrolled patients with chronic heart failure, NYHA class II-III symptoms, ejection fraction of no more than 35%, optimal drug treatment, no permanent atrial fibrillation, and a recent dual-chamber ICD or CRT-D implantation. After a 1 month run-in phase, patients were randomly assigned (1:1) to either automatic, daily, implant-based, multiparameter telemonitoring in addition to standard care or standard care without telemonitoring. Investigators were not masked to treatment allocation. Patients were masked to allocation unless they were contacted because of telemonitoring findings. Follow-up was 1 year. The primary outcome measure was a composite clinical score combining all-cause death, overnight hospital admission for heart failure, change in NYHA class, and change in patient global self-assessment, for the intention-to-treat population. The trial is registered with ClinicalTrials.gov, number NCT00538356. FINDINGS: We enrolled 716 patients, of whom 664 were randomly assigned (333 to telemonitoring, 331 to control). Mean age was 65·5 years and mean ejection fraction was 26%. 285 (43%) of patients had NYHA functional class II and 378 (57%) had NYHA class III. Most patients received CRT-Ds (390; 58·7%). At 1 year, 63 (18·9%) of 333 patients in the telemonitoring group versus 90 (27·2%) of 331 in the control group (p=0·013) had worsened composite score (odds ratio 0·63, 95% CI 0·43-0·90). Ten versus 27 patients died during follow-up. INTERPRETATION: Automatic, daily, implant-based, multiparameter telemonitoring can significantly improve clinical outcomes for patients with heart failure. Such telemonitoring is feasible and should be used in clinical practice. FUNDING: Biotronik SE & Co. KG.

• MeSH
• Monitoring, Ambulatory instrumentation   MeSH
• Defibrillators, Implantable * MeSH
• Humans MeSH
• Aged MeSH
• Heart Failure physiopathology   therapy   MeSH
• Telemedicine methods   MeSH
• Treatment Outcome MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH
• Geographicals
• Australia MeSH
• Europe MeSH
• Israel MeSH

Experimental and computational studies emphasize the role of the millisecond precision of neuronal spike times as an important coding mechanism for transmitting and representing information in the central nervous system. We investigate the spike time precision of a multicompartmental pyramidal neuron model of the CA3 region of the hippocampus under the influence of various sources of neuronal noise. We describe differences in the contribution to noise originating from voltage-gated ion channels, synaptic vesicle release, and vesicle quantal size. We analyze the effect of interspike intervals and the voltage course preceding the firing of spikes on the spike-timing jitter. The main finding of this study is the ranking of different noise sources according to their contribution to spike time precision. The most influential is synaptic vesicle release noise, causing the spike jitter to vary from 1 ms to 7 ms of a mean value 2.5 ms. Of second importance was the noise incurred by vesicle quantal size variation causing the spike time jitter to vary from 0.03 ms to 0.6 ms. Least influential was the voltage-gated channel noise generating spike jitter from 0.02 ms to 0.15 ms.

• MeSH
• Action Potentials physiology   MeSH
• Time Factors MeSH
• Hippocampus physiology   MeSH
• Noise MeSH
• Rats MeSH
• Humans MeSH
• Models, Neurological MeSH
• Synaptic Transmission MeSH
• Neurons metabolism   physiology   MeSH
• Computer Simulation MeSH
• Pyramidal Cells physiology   MeSH
• Software MeSH
• Models, Theoretical MeSH
• Calcium Channels metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Calcium Channels MeSH

Radon is recognized as a public health concern for indoor exposure. Precise quantification derived from occupational exposure in miners is still needed for estimating the risk and the factors that modify the dependence on cumulated exposure. The present paper reports on relationship between radon exposure and lung cancer risk in French and Czech cohorts of uranium miners (n = 10,100). Miners from these two cohorts are characterized by low levels of exposure (average cumulated exposure of less than 60 WLM) protracted over a long period (mean duration of exposure of 10 years) and by a good quality of individual exposure estimates (95% of annual exposures based on radon measurements). The modifying effect of the quality of exposure on the risk is analyzed. A total of 574 lung cancer deaths were observed, which is 187% higher than expected from the national statistics. This significantly elevated risk is strongly associated with cumulated radon exposure. The estimated overall excess relative risk per WLM is 0.027 (95% CI: 0.017-0.043, related to measured exposures). For age at exposure of 30 and 20 years since exposure, the ERR/WLM is 0.042, and this value decreases by approximately 50% for each 10-year increase in age at exposure and time since exposure. The present study emphasizes that the quality of exposure estimates is an important factor that may substantially influence results. Time since exposure and simultaneously age at exposure were the most important effect modifiers. No inverse exposure-rate effect below 4 WL was observed. The results are consistent with estimates of the BEIR VI report using the concentration model at an exposure rate below 0.5 WL.

• MeSH
• Survival Analysis MeSH
• Time Factors MeSH
• Radiation Dosage MeSH
• Adult MeSH
• Risk Assessment methods   MeSH
• Mining statistics & numerical data   MeSH
• Middle Aged MeSH
• Humans MeSH
• Survival Rate MeSH
• Lung Neoplasms mortality   MeSH
• Neoplasms, Radiation-Induced mortality   MeSH
• Body Burden MeSH
• Occupational Exposure statistics & numerical data   MeSH
• Radon analysis   MeSH
• Relative Biological Effectiveness MeSH
• Risk Factors MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Uranium analysis   MeSH
• Age of Onset MeSH
• Age Distribution MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic epidemiology   MeSH
• France epidemiology   MeSH
• Names of Substances
• Radon MeSH
• Uranium MeSH

Identifying haemophilia patients with inhibitors for clinical trials is difficult due to the limited number of patients available. Registries are therefore being established as an additional means of data collection. The aim of this study was to investigate the effect of different recombinant activated factor VII (rFVIIa; NovoSeven dose ranges and dosing schedules on the incidence of re-bleeding in haemophilia patients with inhibitors. In this retrospective, uncontrolled study, data on the bleeding patterns of adult haemophilia patients with high responding inhibitors were analysed. Only data from the Czech Republic, obtained by the HemoRec registry, were used. This study analysed 'real-life' clinical data and focused on the collection of the same parameters in different patients: time from bleeding onset to first injection, effect of first injection, number of re-bleedings, total number of injections and total amount of haemostatic drug used. Fifteen patients met the inclusion criteria and were included into the study (128 bleeding episodes). Patients treated within 2 h of bleeding onset experienced less re-bleeding than patients treated after 2 h of bleeding onset (5.2% vs. 13.7%, respectively). In addition, patients who were treated after 2 h of bleeding onset experienced fewer re-bleedings when high-dose rFVIIa was used (15.8% and 0%; <120 microg kg(-1) and >250 microg kg(-1), respectively). Initial high-dose rFVIIa was also associated with a decline in total rFVIIa consumption. This registry has provided a unique insight into the bleeding patterns of inhibitor patients, highlighting the importance of early treatment initiation and appropriate starting dose.

• MeSH
• Time Factors MeSH
• Adult MeSH
• Factor VIIa administration & dosage   MeSH
• Hemarthrosis drug therapy   MeSH
• Hemophilia A complications   drug therapy   MeSH
• Hemostatics administration & dosage   MeSH
• Blood Coagulation Factor Inhibitors administration & dosage   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Registries statistics & numerical data   MeSH
• Recombinant Proteins administration & dosage   MeSH
• Retrospective Studies MeSH
• Drug Administration Schedule MeSH
• Treatment Outcome MeSH
• Dose-Response Relationship, Drug MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Geographicals
• Czech Republic MeSH
• Names of Substances
• Factor VIIa MeSH
• Hemostatics MeSH
• Blood Coagulation Factor Inhibitors MeSH
• recombinant FVIIa MeSH Browser
• Recombinant Proteins MeSH

AIM: To evaluate the safety and efficacy of multimodal endovascular treatment (EVT) of acute basilar artery occlusion (BAO), including bridging therapy [intravenous thrombolysis (IVT) with subsequent EVT], to compare particular EVT techniques and identify predictors of clinical outcome. MATERIALS AND METHODS: This retrospective, multi-centre study comprised 72 acute ischaemic stroke patients (51 males; mean age 59.1 ± 13.3 years) with radiologically confirmed BAO. The following data were collected: baseline characteristics, risk factors, pre-event antithrombotic treatment, neurological deficit at time of treatment, localization of occlusion, time to therapy, recanalization rate, post-treatment imaging findings. Thirty- and 90-day outcomes were evaluated using the modified Rankin scale with a good clinical outcome defined as 0-3 points. RESULTS: Successful recanalization was achieved in 94.4% patients. Stepwise binary logistic regression analysis identified the presence of arterial hypertension (OR = 0.073 and OR = 0.067, respectively), National Institutes of Health Stroke Scale (NIHSS) at the time of treatment (OR = 0,829 and OR = 0.864, respectively), and time to treatment (OR = 0.556 and OR = 0.502, respectively) as significant independent predictors of 30- and 90-day clinical outcomes. CONCLUSION: Data from this multicentre study showed that multimodal EVT was an effective recanalization method in acute BAO. Bridging therapy shortens the time to treatment, which was identified as the only modifiable outcome predictor.

• MeSH
• Basilar Artery * MeSH
• Arterial Occlusive Diseases diagnosis   therapy   MeSH
• Time Factors MeSH
• Diagnostic Imaging MeSH
• Endovascular Procedures * MeSH
• Combined Modality Therapy MeSH
• Middle Aged MeSH
• Humans MeSH
• Retrospective Studies MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH