Q78162021
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Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
Přeruš. str. : il. ; 32 cm
Projekt je zaměřen na komplexní vývoj počítačem řízené soupravy pro měření teplotního profilu biologické tkáně využívající jako čidla miniaturní invazivní sondy s více měřícími body založenými na principu termočlánku.
- MeSH
- elektromagnetická pole MeSH
- nádory terapie MeSH
- počítačem asistovaná terapie přístrojové vybavení metody MeSH
- programovací jazyk MeSH
- terapeutické zahřívání využití přístrojové vybavení metody MeSH
- změny tělesné teploty terapie MeSH
- Konspekt
- Lékařské vědy. Lékařství
- NLK Obory
- technika lékařská, zdravotnický materiál a protetika
- onkologie
- lékařská informatika
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
Přeruš. str. : il. ; 32 cm
Komplexní vývoj a testování miniaturních invazivních snímačů teploty s více měřícími body v jednom snímači založených na bazi termočlánku. Snímače mají univerzální medicinské použití, ale jsou určeny zejména pro účely hypertermie. XXX XXX XXX
- Konspekt
- Farmacie. Farmakologie
- NLK Obory
- technika lékařská, zdravotnický materiál a protetika
- biologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
OBJECTIVES: A stent is a mesh tube inserted into a natural passage in the body to prevent disease induction. Self-expandable esophageal nitinol stents such as SX-ELLA Stent Esophageal HV (HV Stent Plus) can be indicated for palliation of malignant esophageal strictures, for the treatment of benign esophageal strictures that are refractory to standard therapy and for the treatment of esophago-respiratory fistulas. A silicone-stent coating is used for tumor in-growth prevention and esophago-respiratory fistula occlusion. The thickness of the stent and the overall integrity of the silicone coating of all wires indicate the overall mechanical properties of the esophageal stent and the resistance to external adverse events such as corrosion and mechanical and chemical resistance. METHODS: The polymer multicomponent epoxy resin - a mixture of Epon and Durcupan - was used as a method for robust sample stabilization. A cutting system using a thin water beam with a powder (Blue Line) was chosen as the best variant to obtain 6 samples for both-sided measurement (10 measuring sides). The optical microscopic reflective light method was used to examine wire crossing points in the sections. Fifty values were measured on either sample side for the internal, external and mesh thickness of the silicone stent layer. The wire crossing points were selected so that the silicone layer structure could be clearly seen, and the wires approached each other most closely. Only approximately 4 to 8 crossing points in each section could be measured when applying this approach. The resolution of the microscope and calibration (based on the camera used) was 0.677 μm/pixel. RESULTS: Additional data could be obtained on 8 planes. Two boundary samples were destroyed by the cutting process. Whole coating of the stent was around all mesh wires, especially in areas with higher mechanical stress (wire crossing). The minimum detectable and admissible value determined for all 3 measuring areas (internal, external, mesh) on the wire crossings was 6.77 μm, i.e., 10 pixels, based on the microscope resolution and manufacturer's methodology. The results were characterized by p < 0.001 for all 3 parameters. We tested opposite samples in each section to verify the section quality and data consistency. For the 4 areas, the data were significantly different, but the thickness differences were only on the order of units percent, so the measurements were not appreciably affected. We assume that the material cutting loss, making up 1-2 mm, contributed to the differences in the sections. CONCLUSION: We examined the overall integrity of the silicone coating of the esophageal stent. The method of HV stent anchoring in a polymeric bath followed by cutting with a waterjet and sample measurement under an optical microscope proved to be very simple and reliable. Sufficient thicknesses of the silicone layer on the wire cross sections were verified. The coated silicone layer thickness appeared to be significantly different along the stent from the proximal part to the distant part, presumably due to the manufacturing technology.
Účel studie: Zhodnotit nežádoucí účinky léčby septických nedonošených novorozenců v prvním týdnu života aminoglykosidovým antibiotikem gentamicinem (Ge) a analyzovat jejich vztah k farmakokinetice a klinickým charakteristikám. Metody: Novorozenci byli rozděleni do skupin podle gestačního věku na velmi nedonošené (skupina S1, GA = 25–33 týdnů, n = 32) a mírně nedonošené (skupina S2, GA = 34–38 týdnů, n = 22) a dále na podskupiny podle přítomnosti perzistujícího ductus arteriosus (PDA, 18 v S1 a 4 v S2). Před a po zahájení podávání Ge byly vyšetřovány biochemické ukazatele glomerulární a tubulární dysfunkce. Kochleární ototoxicita byla zjišťována metodou tranzientní otoakustické emise a nefrokalcinóza sonografickým vyšetřením ledvin v 1. až 5. roce věku. Výsledky: Výskyt glomerulární dysfunkce byl vyšší ve skupině S1 ve srovnání se skupinou S2 do 7. dne od zahájení léčby (16/32 vs. 4/22; p <0,05). Koncentrace kreatininu a močoviny a frakční exkrece sodíku se zvyšovaly s klesajícím GA (p <0,001), zatímco PDA je neovlivnil. Během podávání Ge došlo ke zvýšení poměru koncentrací vápníku a kreatininu v moči a frakční exkrece hořčíku (2 až 7krát, p <0,01) ve všech skupinách. Korelace mezi sledovanými parametry a koncentrací GE byly netěsné. Nefrokalcinóza byla prokázána pouze u 2 ze 46 vyšetřených dětí a kochleární toxicita se nevyskytla. Závěry: Renální dysfunkce nedonošených novorozenců je většinou relativně mírného stupně a přechodná. Vlivem Ge dochází k vzestupu exkrece vápníku do moči, což se spolu s dalšími faktory podílí na zvýšeném riziku nefrokalcinózy. Periodické vyšetřování parametrů renální funkce je u předčasně narozených dětí důležité, protože u některých se může rozvinout chronické poškození ledvin.
Aim: To evaluate the adverse effects of an aminoglycoside antibiotic gentamicin in the treatment of premature neonates with sepsis during the first postnatal week and their relationship to pharmacokinetics and clinical characteristics of neonates. Methods: Neonates were stratified according to gestational age (GA) into the groups of very preterm (the group S1, GA=25–33 weeks, N=32) and preterm (the group S2, GA=34–38 weeks, N=22). Each of the two groups was further divided in two subgroups of neonates with and without persistent ductus arteriosus (PDA, 18 in S1 a 4 in S2). Biochemical markers of an acute glomerular and tubular dysfunction were evaluated before the initiation of pharmacotherapy with Ge and thereafter. The follow-up investigations performed during the first year and between the 2nd and 5th year of age included the examinations for cochlear ototoxicity using transient otoacoustic emission and nephrocalcinosis with the help of ultrasonography. Results: The proportion of neonates with glomerular dysfunction was higher in the group S1 than S2 (16/32 vs. 4/22; p<0.05). Serum concentrations of creatinine and urea and fractional sodium excretion in urine raised with decreasing GA (P<0.001), whereas PDA exerted no influence. In all four groups, pharmacotherapy with Ge resulted in the elevation of the ratio of calcium to creatinine urinary concentrations and of the fractional urinary excretion of magnesium (2- to7-fold, P<0.01). The correlation between the biochemical parameters under the study and Ge concentrations were weak. Nephrocalcinosis was detected in two out of 46 children undergoing sonography and cochlear toxicity was absent. Conclusions: Acute renal dysfunction is relatively modest and transient in most of premature neonates treated in the intensive care unit. Pharmacotherapy with Ge results, among other effects, in the increase of calcium excretion in urine. This hypercalciuric adverse effect contributes to other risk factors for nephrocalcinosis. Long-term follow-up of kidney function seems warranted because chronic renal dysfunction can develop in a minority of children. Key words: preterm neonate, sepsis, gentamicin, renal dysfunction, nephrocalcinosis, perzistent ductus arteriosus P.
- MeSH
- akutní poškození ledvin diagnóza chemicky indukované terapie MeSH
- analýza moči MeSH
- antibakteriální látky * aplikace a dávkování farmakokinetika škodlivé účinky terapeutické užití MeSH
- biochemická analýza krve MeSH
- chronické selhání ledvin prevence a kontrola MeSH
- diuretika terapeutické užití MeSH
- dopamin terapeutické užití MeSH
- ductus arteriosus patologie MeSH
- hodnoty glomerulární filtrace * účinky léků MeSH
- ibuprofen terapeutické užití MeSH
- inhibitory Na-K-Cl symportérů terapeutické užití MeSH
- inhibitory syntézy proteinů * aplikace a dávkování farmakokinetika škodlivé účinky terapeutické užití MeSH
- kreatinin * moč MeSH
- ledvinové kanálky patologie účinky léků MeSH
- ledviny ultrasonografie MeSH
- lidé MeSH
- močovina MeSH
- nefrokalcinóza etiologie chemicky indukované prevence a kontrola terapie MeSH
- novorozenec nedonošený MeSH
- novorozenec s nízkou porodní hmotností MeSH
- novorozenec s velmi nízkou porodní hmotností MeSH
- novorozenec MeSH
- prospektivní studie MeSH
- retence moči farmakoterapie MeSH
- sluch MeSH
- syndrom systémové zánětlivé reakce * farmakoterapie komplikace MeSH
- vápník * moč MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- práce podpořená grantem MeSH
Účel studie: Cílem je predikce dávkování gentamicinu (Ge) s účinkem závislým na plazmatické koncentraci (Cpl), k navození cílového rozsahu ustálené údolní Cpl Ctrough,3 (0,5–2,0 mg/l) a vrcholové Cpeak4 (5,0–10,0 mg/l), tj. 0,5 hod před čtvrtou a 1 hodinu po startu čtvrté 30minutové i.v. infuze. Cpeak určuje baktericidii, Ctrough snižuje neurotoxicitu a nefrotoxicitu. Metody: Analýza Ge fluorescenční polarizační imunoesejí (TDx Analyzer; Abbott Laboratories, Abbott Park Illinois). Fitováním parametrů 2kompartm. modelu se čtyřmi Cpl Ge byly odhadnuty: distribuční objem (Vd1) a systémová clearance (Cl1) pomocí MW-Pharm 3.15 (Mediware, Groningen, NL). Pokud simulace Cpl při standardním dávkování (4 mg/kg/24–48 hod podle GV a porodní hmotnosti) neprokázala cílové Cpl, dávkování počínaje intervalem po 2. infuzi bylo změněno podle kinetických parametrů. Ctrough,3 a Cpeak4 byly ověřeny analýzou. Výsledky: U 54 novorozenců (32 velmi nedonošených, GV <34. týden a 22 mírně nedonošených, GV <38. týden) Cpeak,1 (po první infuzi) dosáhla cílového rozmezí v 80 %, Ctrough,1 <2 mg/l u všech. Standardní dávkování bylo upraveno v 85 %, zejména snížením rychlosti (65 %). Cílová Cpeak,4 byla dosažena u 69 % velmi nedonošených a 68 % mírně nedonošených, Cpeak,4 <5 mg/l u 31 % velmi nedonošených a 32 % mírně nedonošených, cílová Ctrough,3 byla dosažena u všech s 1 výjimkou. Za příčinu rozdílu Cpeak,4 predikované a ověřené byla označena retence tekutin v čase od první do čtvrté infuze Ge. Při perzistujícím ductus arteriosus nabyla až +374,0 (45,1) ml/kg. Závěr: Kineticky řízená léčba Ge u septických novorozenců v prvním týdnu života na základě Cpl po první infuzi je žádoucí zejména u velmi nedonošených novorozenců. K dosažení baktericidní Cpeak,4 je třeba vycházet z retence tekutin, doprovázející kritický stav.
Objective: The aim of the study was to predict dosing with gentamicin (Ge) of which the effect is dependent on plasma concentrations (Cpl) more than on dosage, to achieve the target range of steady state through Cpl: Ctrough,3 (0.5–2.0 mg/l) and peak Cpeak,4 (5.0–10.0 mg/l), i.e. 0.5 h before the fourth and one h after the start of the fourth dose. Cpeak,4 determines bactericidal effect, Ctrough,3 predicts neurotoxicity and nephrotoxicity. Methods: The analysis was performed by Ge fluorescence polarization immunoassay; Abbott Laboratories, Abbott Park Illinois). Fitting the parameters in a two-compartment model with four Cpl Ge were estimated: volume of distribution (Vd1) and clearance (Cl1) by the MW-Pharm 3.15 (Mediware, Groningen, NL). If the simulation of Cpl with standard dosing (4 mg/kg/24–48 h according to GV and birth weight) did not achieve the target Cpl, the standard dosing after the second dose was changed according to the estimated kinetic parameters, Ctrough,3 and Cpeak,4, and verified by ongoing analysis. Results: In 54 newborns (32 very low preterm, gestational age below 34 weeks and 22 low preterm GA <38 weeks) Cpeak,1 (after the first infusion) reached the target range in 80% Ctrough,1 <2 mg/l in all newborns. The standard dosing was adjusted in 85% of them, mainly by decreasing the rate of infusion or do you mean number of dosages per 24 hours (65%). The target Cpeak,4 was reached in 69% of very low preterm and 68% of low preterm newborns, Cpeak,4 <5 mg/l was reached in 31% of very low preterm and 32% of low preterm newborns. The target Ctrough,3 was obtained in all except one subject. The difference of the predicted and verified Cpeak,4 was caused by retention of fluids between the first and the fourth infusion of Ge. In case of persistent ductus arteriosus it reached up to +374.0 (45.1) ml/kg. Conclusion: Kinetically guided therapy with Ge in septic newborns in the first week of life based on the Cpl after the first infusion is recommended in very low preterm newborns especially. In order to reach bactericidal Cpeak,4 the decision should be based on retention of fluids, accompanying the critical condition.
- Klíčová slova
- kineticky řízené dávkování,
- MeSH
- bakteriální infekce krev MeSH
- bakteriální pneumonie terapie MeSH
- biochemická analýza krve MeSH
- ductus arteriosus MeSH
- gentamiciny * aplikace a dávkování farmakokinetika terapeutické užití MeSH
- gestační stáří MeSH
- jednotky intenzivní péče o novorozence MeSH
- klinické laboratorní techniky MeSH
- kombinovaná farmakoterapie MeSH
- komorbidita MeSH
- krevní plazma účinky léků MeSH
- kritický stav terapie MeSH
- lidé MeSH
- mikrobiální testy citlivosti MeSH
- novorozenec nedonošený * MeSH
- novorozenec MeSH
- porodní hmotnost MeSH
- prospektivní studie MeSH
- sepse * farmakoterapie MeSH
- vankomycin terapeutické užití MeSH
- výběr pacientů MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva * MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- práce podpořená grantem MeSH
INTRODUCTION: The aim of this study was to find out the impact of degradation and regeneration of force over time at NiTi springs on the value and course of the final acting force and to verify the possibility of using these phenomena for a directed transition to the reverse plateau and its maintaining. METHODS: Static and cyclic mechanical loadings were performed. At first unused springs were tested. Afterwards the springs were mechanically stabilized by stress cycling and finally tested again. The difference in shape of the working curves was assessed. For simulation and description of the force degradation the modified Voight model was used. RESULTS: New springs, mainly those with large hysteresis, showed a significant stress-strain curve movement and shape changes during the cycling. The effect of the stress-strain curve course change disappeared fully in the stabilized springs. Multiple loading led to an overall decrease of force value during the measurement. The effect of force degradation and regeneration over time by simple static loading varies in the range of percentage of the nominal force in the plateau area. The transition between stress-strain curve phases caused by the degradation or regeneration of the force wasn't observed in case of mechanically stabilized springs. CONCLUSIONS: Springs should be mechanically stabilized before their application. The degree of force degradation over time is insignificant for mechanically stabilized springs. Degradation or regeneration of force over time, mechanical stabilization or micromovements in the mouth don't cause any transition between individual stress-strain curve phases.
- MeSH
- časové faktory MeSH
- lidé MeSH
- nikl * MeSH
- ortodontické aparáty * MeSH
- pevnost v tahu MeSH
- pevnost v tlaku MeSH
- pružnost * MeSH
- testování materiálů MeSH
- titan * MeSH
- viskozita * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- makrometastázy, submikrometastázy,
- MeSH
- axila MeSH
- biopsie sentinelové lymfatické uzliny MeSH
- lidé MeSH
- lymfadenektomie MeSH
- lymfatické metastázy MeSH
- lymfatické uzliny patologie MeSH
- mikrometastázy MeSH
- nádory prsu patologie MeSH
- prognóza MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- multicentrická studie MeSH
BACKGROUND: Aminoglycosides are bactericidal antibiotics used worldwide for the treatment of serious infections in critically ill patients, including neonates. Critically ill neonates constitute a unique challenge in dosing owing to the pathologic alterations that accompany severe illness and the rapidly changing conditions of these patients. OBJECTIVES: The main objective of this study was to analyze the kinetically guided dosage adjustment of gentamicin in neonates critically ill during the first week of life based on plasma concentrations after the first dose and to identify the impact of covariates (eg, fluid intake, body fluid retention) with respect to gestational age (GA). Tolerability of therapy was also assessed. METHODS: This 10-day, open-label, prospective study included neonates critically ill during the first week of life admitted to the neonatal intensive care unit of a children's hospital between January 2006 and July 2009. Hearing and renal assessments were conducted over a 24-month follow-up period. The patients were treated with gentamicin for suspected sepsis, proven sepsis, or pneumonia as an early sign of sepsis. The first and second doses of gentamicin 4 mg/kg were adjusted according to birth weight and GA: group 1 (GA < 34 weeks), 48-hour interdose intervals; group 2 (GA 34-38 weeks), 36 hours; and group 3 (GA > 38 weeks), 24 or 48 hours. Individual pharmacokinetic parameters were estimated after the first dose (given in 30-minute intravenous infusions) using 4 concentrations. Individual pharmacokinetic parameters were estimated by fitting the parameters of a 2-compartment model into 4 concentrations. The last 2 blood samples were taken 30 minutes before the fourth infusion (C(trough,3)) and 1 hour after its start (C(max,4)). Dosing was individualized to reach target ranges for the C(trough,3) (0.5-2.0 mg/L) and C(max,4) (6-10 mg/L) values. If needed, initial dosing was changed after the second dose by adjusting (reducing or increasing) the third and subsequent doses, or by adjusting (prolonging or shortening) the interdose intervals. C(trough,3) and C(max,4) were assessed to determine differences between predicted and assayed values. Fluid retention was registered as the difference between fluid intake and urine output at different intervals related to the first dose per kilogram of birth weight, and from the start of the first infusion (0 hour) to the day of the fourth infusion. The C(max)/minimum inhibitory concentration (MIC) ratio was determined for assessment of optimal response. Tolerability was evaluated during the 24-month follow-up period using renal sonography to screen for nephrocalcinosis and transient evoked otoacoustic emission recordings to evaluate hearing abnormalities. RESULTS: A total of 84 neonates (all white; 53 males, 31 females; birth weight range, 0.8-4.56 kg; GA range, 24-42 weeks) were enrolled in 3 groups: group 1, GA < 34 weeks, n = 27; group 2, GA 34-38 weeks, n = 22; and group 3, GA > 38 weeks, n = 35. The C(max) value detected 1 hour after the start of the first infusion (C(max,1)) reached the target range of 6-10 mg/L in 66 of the 84 neonates (79%). After the initial dose, C(max,1) was variable (%CV, 29%); the failure rate to reach 6 mg/L was 13%. V(d) decreased with GA (r = -0.30, P < 0.01) and achieved mean (SD) rates of 0.51 (0.10), 0.48 (0.13), and 0.40 (0.15) L/kg in groups 1, 2, and 3, respectively. Neither C(max) nor V(d) was correlated with fluid intake relative to the first infusion. Mean gentamicin clearance measured after dose 1 (0.47 [0.23], 0.66 [0.26], and 0.76 [0.32] mL/min/kg) increased with GA (r = 0.45, P < 0.001). The interdose interval was prolonged after the second and subsequent infusions in 8 of 84 neonates (10%) or by decreasing the third dose and subsequent doses in 51 neonates (61%). The target C(max,4) and C(trough,3) values occurred in 63% (22 of 35) and 83% (29 of 35) of full-term patients (GA >38 weeks), respectively. In preterm neonates, the target range for C(max,4) was reached in 11 of 27 patients (41%) in group 1 and 11 of 22 patients (50%) in group 2; for C(trough,3), the target range was reached in 25 patients (93%) in group 1 and in 16 (73%) in group 2. C(trough,3) >2 mg/L was detected in 1 full-term neonate, and gentamicin was withdrawn. Suspected fluid retention within the time period of 0 hour to the day of the fourth infusion was well correlated with actual body weight (r = 0.58, P < 0.001), but it was negatively correlated with C(max,4) (r = -0.25, P = 0.02). Thirteen of the 84 neonates (15%) had confirmed sepsis. C(max)/MIC was >12 except for 2 resistant staphylococcal infections (C(max)/MIC = 0.4); amikacin and vancomycin were substituted for gentamicin in these cases. Clinical signs and laboratory data indicative of suspected sepsis disappeared in 5 to 10 days in 68 of 71 neonates. In 1 neonate, gentamicin was withdrawn after dose 4 because of a high C(trough,3) value. In the 3 remaining neonates, C-reactive protein was decreased >10 days without changing therapy. Two neonates died, 1 of severe hypoxic-ischemic encephalopathy as a consequence of perinatal asphyxia and another of stage IV intraventricular hemorrhage. Transient renal dysfunction attributable to gentamicin was detected in 1 case. No signs of late toxicity (nephrocalcinosis) were found during the second year of follow-up. Two neonates were diagnosed with unilateral hearing loss, a secondary phenomenon of hypoxic-ischemic encephalopathy thought to be related to the severe perinatal asphyxia. CONCLUSIONS: The initial dose of gentamicin 4 mg/kg for these critically ill premature and mature neonates with sepsis during the first week of life was high enough to reach bactericidal C(max,1) within 6-10 mg/L. C(max,1) <6 mg/L occurred in 13% of neonates. The interdose interval modified according to the recommendation resulted in C(trough) values within the target range of 0.5-2.0 mg/L in all but 2 neonates. The kinetically guided maintenance dosing of gentamicin based on plasma concentrations after the first dose should be optimized, taking into account actual body weight. (EudraCT number: 2005-002723-13).
- MeSH
- antibakteriální látky aplikace a dávkování škodlivé účinky krev terapeutické užití MeSH
- časové faktory MeSH
- gentamiciny aplikace a dávkování škodlivé účinky krev terapeutické užití MeSH
- gestační stáří MeSH
- intenzivní péče o novorozence metody MeSH
- jednotky intenzivní péče o novorozence MeSH
- kritický stav MeSH
- lidé MeSH
- novorozenec MeSH
- porodní hmotnost MeSH
- prospektivní studie MeSH
- rozvrh dávkování léků MeSH
- sepse krev farmakoterapie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- novorozenec MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH