Během RTG a CT vyšetření je pacient vystaven ionizujícímu radiačnímu záření. Dávka může být měřena a počítána pomocí různých dozimetrických veličin. Efektivní dávka umožňuje porovnávat radiační zátěž pacientů při použití různých zobrazovacích metod. Autoři uvádějí velikost efektivní dávky pro CT vyšetření čelistí na spirálním CT skeneru Marconi Mx8000. Autoři dále ukazují, že je možné nastavit hodnoty vyšetřovacího protokolu tak, aby efektivní dávka byla menší než pro panoramatický RTG snímek čelistí a přitom byla zachována dostatečná kvalita zobrazení.

The patient subjected to X-ray or CT examination is exposed to ionizing radiation. The dose can be measured and calculated by means of various dosimetric units. The effective dose makes it possible to compare radiation load in patients under the use of various imaging methods. The authors present the size of effective dose for CT examination of jaws on spiral CT scanner Marconi Mx8000. The authors also show that there is a possibility to set the values of the examination protocol so as to make the effective dose lower than for the panoramic Xray picture of the jaws and simultaneously keep sufficient quality of the imaging.

• MeSH
• dávka záření MeSH
• diagnóza stomatologická metody   MeSH
• lidé MeSH
• počítačová rentgenová tomografie metody   využití   MeSH
• radiografie metody   využití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Warfarin treatment is commonly started with a fixed loading dose that might be associated with an increased risk of bleeding. An individual maintenance dose can then be estimated based on a pharmacogenetic algorithm. Starting treatment with the estimated dose implies a longer time to reach the therapeutic range. Our goal was to compare the safety and efficacy of initiating warfarin treatment with a loading dose guided by pharmacogenetics versus a maintenance dose. The primary endpoint was time in the therapeutic range (TTR) in the first 10 days of treatment. Secondary endpoints were time to the first international normalized ratio (INR) in therapeutic range (2.0-3.0) and occurrence of serious adverse events. Consenting cardioembolic stroke patients were genotyped for CYP2C9 (cytochrome P450 2C9 gene) and VKORC1 (vitamin K epoxide reductase complex, subunit 1 gene) polymorphisms and a maintenance warfarin dose was estimated. Patients were randomized into two groups. The loading dose group (LDG) patients received twice the estimated dose in the first 2 days of treatment. The maintenance dose group (MDG) patients received the estimated dose directly from day one. The TTR in the first 10 days was significantly higher in the LDG than in the MDG (50.5% vs. 38.3%, p = 0.003). The time to the first INR in this range was significantly shorter in the LDG (5.24 vs. 7.3 days). There were no significant differences in the INR above this range or serious adverse events. Warfarin loading dose guided by pharmacogenetics after recent cardioembolic stroke improved the efficacy of warfarin initiation without increasing the risk of adverse events.

• MeSH
• antikoagulancia aplikace a dávkování   MeSH
• cévní mozková příhoda farmakoterapie   MeSH
• farmakogenetika MeSH
• INR MeSH
• ischemie mozku farmakoterapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prospektivní studie MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• warfarin aplikace a dávkování   škodlivé účinky   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH

Súhrn Aktivácia a následná agregácia trombocytov hrá kľúčovú úlohu pri vzniku arteriálnej trombózy, a je teda hlavným terapeutickým cieľom v liečbe akútnych koronárnych syndrómov. Duálna antiagregačná liečba kyselinou acetylsalicylovou a antagonistom receptorov P2Y12 pre ADP tvorí v súčasnosti základ farmakologickej liečby akútneho infarktu myokardu s eleváciami segmentu ST (STEMI). Existuje však široká variabilita vo farmakodynamickej odpovedi na klopidogrel, ktorý je najpoužívanejším antagonistom receptorov P2Y12 pre ADP. Vysoká reaktivita trombocytov po podaní klopidogrelu je spojená so zvýšeným rizikom trombózy stentu a poukazuje na vhodnosť laboratórneho monitorovania antiagregačnej liečby v klinickej praxi. Laboratórne monitorovanie antiagregačnej liečby pomocou ex vivo testov funkcie trombocytov môže pomôcť identifikovať jedincov so slabou antiagregačnou odpoveďou. V súčasnosti tiež existuje narastajúce množstvo informácií o nedostatočnej antiagregačnej odpovedi na klopidogrel, ktorá je špecificky spojená s inzulínovou rezistenciou a diabetes mellitus. Prasugrel, nový, potentný antagonista receptorov P2Y12 pre ADP, dosahuje rýchlejšiu a konzistentnejšiu inhibíciu funkcie trombocytov v porovnaní s klopidogrelom. Liečba prasugrelom bola opakovane popísaná ako efektívna metóda na preklenutie klopidogrelovej rezistencie, pričom rezistencia na prasugrel nebola doteraz spoľahlivo popísaná. V práci popisujeme dva prípady pacientov s diabetes mellitus 2. typu v štádiu orgánových komplikácií, u ktorých 60mg nasýcovacia dávka prasugrelu nedosiahla dostatočnú antiagregačnú odpoveď po 60 minútach od jeho podania. Antiagregačná odpoveď bola meraná pomocou optickej agregometrie a stanovenia fosforylácie proteínu VASP (vasodilator-stimulated phosphoprotein).

The activation and subsequent platelet aggregation plays a key role in the formation of arterial thrombosis and therefore is the key therapeutic target in the treatment of acute coronary syndromes. Dual antiplatelet therapy containing aspirin and P2Y12 ADP receptor antagonist forms currently the basis in acute ST-elevation myocardial infarction (STEMI) pharmacological treatment. Nevertheless, there is a wide variability in pharmacodynamic response to administration of clopidogrel, the most frequently used P2Y12 ADP receptor antagonist. High platelet reactivity after clopidogrel administration is associated with increased risk of stent thrombosis and points to the suitability of laboratory monitoring of antiplatelet therapy efficacy in clinical practice. Laboratory monitoring of antiplatelet therapy by ex vivo platelet function tests may help to identify individuals with poor antiplatelet response. Recently, there is a growing number of data reporting a failure in antiplatelet response following clopidogrel administration, which is specifically associated with insulin resistance and diabetes mellitus. Prasugrel, a new, potent P2Y12 ADP receptor antagonist, provides faster and more consistent inhibition of platelet function compared with clopidogrel. Prasugrel therapy was repeatedly described as an effective method to overcome clopidogrel resistance and prasugrel resistance has not yet been reliably described. We report two cases of patients with diabetes mellitus type 2 at the stage of organ complications, in whom a prasugrel loading dose of 60 mg did not reach adequate antiplatelet response in 60 minutes after prasugrel administration. The antiplatelet response was measured by light transmission aggregometry and by VASP protein phosphorylation assessment.

• MeSH
• agregace trombocytů účinky léků   MeSH
• akutní koronární syndrom farmakoterapie   komplikace   MeSH
• Aspirin terapeutické užití   MeSH
• diabetické angiopatie komplikace   MeSH
• infarkt myokardu etiologie   chirurgie   MeSH
• inhibitory agregace trombocytů aplikace a dávkování   MeSH
• koronární angioplastika metody   MeSH
• koronární trombóza farmakoterapie   prevence a kontrola   MeSH
• léková rezistence MeSH
• lidé MeSH
• piperaziny terapeutické užití   MeSH
• senioři MeSH
• thiofeny terapeutické užití   MeSH
• tiklopidin terapeutické užití   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• kazuistiky MeSH
• práce podpořená grantem MeSH

This study aimed to develop a vancomycin population pharmacokinetic model in obese adult patients treated with intermittent haemodialysis and propose a model-based loading dose strategy ensuring attainment of newly recommended AUC-based PK/PD target. Retrospective cross-sectional analysis was performed among obese haemodialysis dependent adult patients treated with intravenous vancomycin. A pharmacokinetic population model was developed using a nonlinear mixed-effects modelling approach and Monte Carlo simulations were used to identify the optimal loading dose for PK/PD target attainment during the first 48 h of treatment. Therapeutic drug monitoring data from 27 patients with a BMI of 30.2-52.9 kg/m2 were analysed. Among all tested variables, only LBM as a covariate of vancomycin Vd significantly improved the model, while vancomycin CL did not correlate with any of the tested variables. The median (IQR) value from the conditional mean of individual estimates of Vd and CL was 68.4 (56.6-84.2) L and 0.86 (0.79-0.90) L/h, respectively. To ensure optimal vancomycin exposure during the first 48 h of therapy, the vancomycin loading dose of 1500, 1750, 2000, 2250, 2500 and 2750 mg should be administered to obese patients with a lean body mass of ˂50, 50-60, 60-70, 70-80, 80-85 and >85 kg, respectively.

• MeSH
• antibakteriální látky * farmakokinetika   aplikace a dávkování   MeSH
• biologické modely MeSH
• dialýza ledvin * MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• metoda Monte Carlo MeSH
• monitorování léčiv MeSH
• obezita * komplikace   MeSH
• průřezové studie MeSH
• retrospektivní studie MeSH
• senioři MeSH
• vankomycin * farmakokinetika   aplikace a dávkování   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Clopidogrel loading has mostly been studied in clopidogrel-naive patients. Whether clopidogrel-treated patients readmitted for an acute coronary syndrome or percutaneous coronary intervention can benefit from a new load of clopidogrel and at what dose remain unknown. Our aim was to evaluate the impact of 3 different strategies of administration of a loading dose of 900 mg clopidogrel in patients already treated with a maintenance dose of 75 mg clopidogrel for at least 7 days on residual platelet aggregation. METHODS AND RESULTS: Patients treated long term by clopidogrel 75 mg/d were assigned to receive a first loading dose of 300, 600, or 900 mg clopidogrel and 4 hours later a second loading dose of 600, 300, or 0 mg, respectively, to achieve a total loading dose of 900 mg in all patients. Platelet aggregation was evaluated at baseline, at 4 hours after the initial load (and before second load), and at 24 hours using light transmission aggregometry with 20 micromol ADP and the point-of-care assay VerifyNow P2Y(12). The primary objective of the study was to evaluate the inhibition (relative change) of residual platelet aggregation (percentage of IRPA) between 600- and 900-mg first loading at 4 hours. IRPA at 24 hours also was evaluated as a secondary objective, as well as the rate of suboptimal response at 4 hours defined as IRPA <10%. We included 166 consecutive patients with acute coronary syndromes (n=80, 48%) or stable coronary artery disease (n=86, 52%). Baseline characteristics were similar in the 3 dose groups. A significant stepwise increase was found in percentage IRPA assessed at 4 hours in patients initially assigned to 300 versus 600 versus 900 mg (30.7% versus 40.3% versus 64.0%, respectively; P=0.0024). The difference in percentage IRPA at 4 hours was not significant between 300 and 600 mg but was significant between 600 and 900 mg and between 300 and 900 mg. Percentage IRPA assessed at 24 hours when all patients had received 900 mg did not differ between the 3 loading regimens. The rates of suboptimal response (IRPA <10% at 4 hours) were 23.6%, 20.4%, and 5.3% with 300, 600, and 900 mg, respectively (P=0.02 for all). CONCLUSIONS: In patients treated long term with 75 mg clopidogrel, a new loading dose of 900 mg improves IRPA and reduces poor and/or slow response to clopidogrel significantly more than that obtained with 300 or 600 mg.

• MeSH
• agregace trombocytů fyziologie   účinky léků   MeSH
• balónková koronární angioplastika metody   MeSH
• čas MeSH
• inhibitory agregace trombocytů aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• tiklopidin analogy a deriváty   aplikace a dávkování   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH

BACKGROUND: Delayed achievement of target vancomycin serum concentrations may adversely affect clinical outcomes. The objective of this retrospective study was to compare the prediction accuracy of different body weight descriptors for volume of distribution and to propose an optimal loading dose (LD) for continuous infusion regimens in adults. METHODS: Pharmacokinetic variables were computed using one-compartmental analysis. Simulated LDs of vancomycin were evaluated for each patient. RESULTS: Volume of distribution, clearance, and half-life median values (interquartile range) for vancomycin in the study population (n = 30) were 0.45 (0.39-0.61) L.kg-1, 0.026 (0.015-0.040) L.h-1.kg-1, and 10.3 (7.7-21.3) h, respectively. The observed volume of distribution was better predicted by total body weight (TBW) than by the ideal body weight or the adjusted body weight. CONCLUSIONS: An LD of 10.7 mg per kg TBW was optimal in our study population. Using this LD, 17.9% of simulated vancomycin serum levels were just below the therapeutic range, only 10.7% concentrations exceeded the target range and no concentration was toxic. The use of a LD would lead to reduced median time to reach target concentrations from 17 to 1 h.

• MeSH
• intravenózní infuze MeSH
• lidé středního věku MeSH
• lidé MeSH
• obezita MeSH
• péče o pacienty v kritickém stavu metody   MeSH
• počítačová simulace MeSH
• poločas MeSH
• retrospektivní studie MeSH
• senioři MeSH
• tělesná hmotnost MeSH
• vankomycin aplikace a dávkování   krev   terapeutické užití   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

• MeSH
• pacienti MeSH
• radiometrie MeSH
• rentgendiagnostika zubní škodlivé účinky   MeSH

BACKGROUND AND AIMS: Moderate alcohol consumption provides protection against cardiovascular disease primarily due to increase of HDL-cholesterol. However, it also has some adverse effects on metabolism of triglycerides (TG). Therefore, we addressed the question how a single dose of alcohol affects postprandial lipemia and activities of two enzymes playing a critical role in regulation of triglyceridemia, lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL). METHODS AND RESULTS: Eight healthy volunteers were given a single dose of alcohol (vodka; 0.6 g of ethanol/kg of body weight) together with a fat load (0.7 g of fat/kg of body weight) in an experimental breakfast or together with dinner 12 h before the experimental breakfast. In comparison to control experiment, alcohol given with breakfast induced increased and prolonged postprandial response of triglyceride-rich lipoproteins (TRL; d < 1.006 g/ml). At the same time TG accumulated also in intermediate density lipoproteins (IDL; d 1.006-1.019 g/ml). Alcohol given in the evening before the experiment increased fasting TG concentration but did not affect changes in TRL and IDL concentrations. LPL activity measured both in vivo using intravenous fat tolerance test and in vitro and HTGL activity were determined at the end of experiments (after 7.5 h of postprandial lipemia study). Neither was affected by a single dose of alcohol. CONCLUSIONS: Single dose of alcohol induces immediate and profound changes in metabolism of TRL and IDL. The same dose of alcohol given 12 h before meal does affect baseline TG concentration but not the postprandial changes of triglyceridemia.

• MeSH
• alkoholické nápoje MeSH
• apolipoproteiny E krev   MeSH
• dietní tuky aplikace a dávkování   MeSH
• dospělí MeSH
• ethanol aplikace a dávkování   MeSH
• HDL-cholesterol krev   MeSH
• hypertriglyceridemie farmakoterapie   MeSH
• inzulin krev   MeSH
• kyseliny mastné neesterifikované krev   MeSH
• lidé MeSH
• lipoproteinlipasa krev   MeSH
• lipoproteiny krev   MeSH
• mladý dospělý MeSH
• omezení příjmu potravy MeSH
• postprandiální období * MeSH
• triglyceridy krev   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

PURPOSE: Delayed achievement of target vancomycin serum concentrations may adversely affect clinical outcomes. The objective of this retrospective study was to explore the real frequency of loading dose use and to evaluate the impact of loading dose for the achievement of vancomycin PK/PD target in adult patients treated with intermittent vancomycin. As a secondary aim we determined optimal vancomycin loading dose based on individual pharmacokinetic calculations. METHODS: Vancomycin pharmacokinetic models were computed using two-compartmental analysis. Based on these models AUC24 were calculated. Unpaired t-test was used to compare AUC24 achieved in patients treated with and without vancomycin loading dose. RESULTS: Vancomycin loading dose was administered only in 17.8% patients. Volume of distribution and clearance median values (interquartile range) for vancomycin in whole study population (n = 45) were 0.69 (0.55-0.87) L/kg and 0.0304 (0.0217-0.0501) L/h/kg, respectively. The AUC24 was significantly higher in patients taking loading dose compared with the group without loading dose: mean (SD) AUC24 was 496 (101) vs. 341 (77) mg h/L. Proportion of patients reaching PK/PD goal was 87.5% and 24.3% with and without loading dose administration, respectively. Considering individual pharmacokinetic parameters optimal vancomycin loading dose was 27.5 mg/kg of body weight. CONCLUSIONS: Loading dose administration plays crucial part in rapid attainment of vancomycin PK/PD target in adult patient treated with intermittent vancomycin, although it is not frequently used in clinical practise. The optimal loading dose of 25-30 mg/kg of body weight should be routinely administered to adult patients treated with intermittent vancomycin.

• MeSH
• antibakteriální látky aplikace a dávkování   krev   farmakokinetika   farmakologie   MeSH
• infuzní pumpy MeSH
• kreatinin krev   MeSH
• lidé MeSH
• monitorování léčiv metody   MeSH
• plocha pod křivkou MeSH
• počítačová simulace MeSH
• retrospektivní studie MeSH
• senioři MeSH
• vankomycin aplikace a dávkování   krev   farmakokinetika   farmakologie   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH

BACKGROUND AND PURPOSE: The present study was performed to evaluate the feasibility of a new, 5-week regimen of 70-75 Gy hyperfractionated accelerated radiotherapy with concomitant integrated boost (HARTCIB) for locally advanced, inoperable head and neck cancer. METHODS AND MATERIALS: A total of 39 patients with very advanced, stage IV nonmetastatic head and neck squamous cell carcinoma (median gross tumor volume 72 ml) were included in this phase I dose escalation study. A total of 50 fractions intensity-modulated radiotherapy (IMRT) were administered twice daily over 5 weeks. Prescribed total dose/dose per fraction for planning target volume (PTV(tumor)) were 70 Gy in 1.4 Gy fractions, 72.5 Gy in 1.45 Gy fractions, and 75 Gy in 1.5 Gy fractions for 10, 13, and 16 patients, respectively. Uninvolved lymphatic nodes (PTV(uninvolved)) were irradiated with 55 Gy in 1.1 Gy fractions using the concomitant integrated boost. RESULTS: Acute toxicity was evaluated according to the RTOG/EORTC scale; the incidence of grade 3 mucositis was 51% in the oral cavity/pharynx and 0% in skin and the recovery time was ≤ 9 weeks for all patients. Late toxicity was evaluated in patients in complete remission according to the RTOG/EORTC scale. No grade 3/4 late toxicity was observed. The 1-year locoregional progression-free survival was 50% and overall survival was 55%. CONCLUSION: HARTCIB (75 Gy in 5 weeks) is feasible for patients deemed unsuitable for chemoradiation. Acute toxicity was lower than predicted from radiobiological models; duration of dysphagia and confluent mucositis were particularly short. Better conformity of radiotherapy allows the use of more intensive altered fractionation schedules compared with older studies. These results suggest that further dose escalation might be possible when highly conformal techniques (e.g., stereotactic radiotherapy) are used.

• MeSH
• celková dávka radioterapie MeSH
• dospělí MeSH
• frakcionace dávky záření MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory hlavy a krku patologie   radioterapie   MeSH
• otorinolaryngologické nádory patologie   radioterapie   MeSH
• plánování radioterapie pomocí počítače metody   MeSH
• přežití bez známek nemoci MeSH
• radiační poranění etiologie   MeSH
• radioterapie s modulovanou intenzitou metody   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• spinocelulární karcinom patologie   radioterapie   MeSH
• staging nádorů MeSH
• tumor burden MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze I MeSH