- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: Amikacin monotherapy is recommended for urinary tract infection (UTI) treatment with multi-resistant pathogens. Even though amikacin efficacy in the treatment of UTIs is dependent on its urinary concentration, there are no robust data proving that sufficiently high urinary concentration is reached in patients with reduced glomerular filtration rate (GFR). METHODS: A prospective study to monitor amikacin penetration into urine of 70 patients [40 males, median (interquartile range) age 70 (65-79) years] with different levels of glomerular filtration decline, including patients treated by dialysis, was conducted. The bactericidal efficacy of amikacin in urine samples has been evaluated. RESULTS: Patients with estimated GFR (eGFR) <30 mL/min had significantly lower median amikacin urinary concentration than patients with eGFR >30 mL/min (89.75 vs 186.0 mg/L, P < .0001; 200.5 vs 830.0 mg/L, P < .0001; and 126.0 vs 408.0 mg/L, P < .0001 for minimal, maximal and minimal together with maximal concentrations, respectively). The amount of amikacin eliminated in the first 10-13 h after dose administration was dependent on eGFR (r2 = 0.6144, P < .0001). The urinary concentration of amikacin in patients treated by dialysis was indirectly proportional to pH of urine. The plasma concentrations of amikacin did not correlate with urinary levels in patients in either of the GFR categories. Microbiological evaluation showed that the critical urinary concentration for efficacy of amikacin during UTI monotherapy in patients treated by dialysis is 100 mg/L. We found that 4 out of 11 patients treated by dialysis did not reach this level during the treatment. CONCLUSION: Systemic administration of amikacin monotherapy in patients treated by dialysis is questionable as the concentrations of amikacin in their urine are often below the threshold of effectivity. Amikacin plasma concentrations are not a major determinant of amikacin concentration in urine, therefore pulse dosing is neither necessary nor safe in patients treated by dialysis, and may cause undesirable toxicity.
- Publikační typ
- časopisecké články MeSH
Peritonitis is a limiting complication of peritoneal dialysis, which is treated by intraperitoneal administration of antibiotics. Various dosing strategies are recommended for intraperitoneally administered vancomycin, which leads to large differences in intraperitoneal vancomycin exposure. Based on data from therapeutic drug monitoring, we developed the first-ever population pharmacokinetic model for intraperitoneally administered vancomycin to evaluate intraperitoneal and plasma exposure after dosing schedules recommended by the International Society for Peritoneal Dialysis. According to our model, currently recommended dosing schedules lead to possible underdosing of a large proportion of patients. To prevent this, we suggest avoiding intermittent intraperitoneal vancomycin administration, and for the continuous dosing regimen, we suggest a loading dose of 20 mg/kg followed by maintenance doses of 50 mg/L in each dwell to improve the intraperitoneal exposure. Vancomycin plasma level measurement on the fifth day of treatment with subsequent dose adjustment would prevent it from reaching toxic levels in the few patients who are susceptible to overdose.
- Publikační typ
- časopisecké články MeSH
Determination of renin plasma levels is useful in the diagnosis of hypertension and in the therapeutic follow-up of hypertensive patients. Plasmatic concentration of renin decreases in patients with hypertension due to a primary hyperaldosteronism, contrary to renovascular hypertension where concentrations of renin and aldosterone are both elevated. Blood samples (serum, EDTA plasma) were analysed using two different chemiluminiscent methods CLIA LIAISON® and radioimmunoassay for aldosterone (IMMUNOTECH Beckman Coulter) and renin (Cisbio Bioassay) measurements were compared. We used both methods to ascertain the correlation between serum vs. EDTA plasma levels of aldosterone (RIA, CLIA) and renin (IRMA, CLIA) and to compare aldosterone to renin ratios for CLIA and for radioimmunoassay: serum aldosterone to plasma renin and plasma aldosterone to plasma renin. We compared serum aldosterone CLIA vs. RIA (rP=0.933, P<0.001) and plasma renin determined using CLIA vs. IRMA (rP=0.965, P=0.062). Furthermore, we used both methods to establish the correlation between the serum vs. plasma levels of aldosterone: RIA (rP=0.980, P<0.001); CLIA (rP=0.994, P=0.353) and serum vs. plasma levels of renin: IRMA (rP=0.948, P<0.001); CLIA (rP=0.921, P=0.011). Aldosterone (serum, plasma) to plasmatic renin ratios for CLIA (rP=0.999, P=0.286) and for radioimmunoassay (rP=0.992, P=0.025). Our data demonstrate that renin and aldosterone concentrations obtained using CLIA correlate with renin and aldosterone concentrations using radioimmunoassay methods. Correlation coefficients of pair results ranged from 0.921 to 0.994. Aldosterone (serum, EDTA plasma) to plasmatic renin ratios are comparable and any of them can be used with no significant differences found.
- MeSH
- aldosteron * MeSH
- hyperaldosteronismus * MeSH
- lidé MeSH
- luminiscence MeSH
- radioimunoanalýza MeSH
- renin MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The study presents a novel vancomycin-releasing collagen wound dressing derived from Cyprinus carpio collagen type I cross-linked with carbodiimide which retarded the degradation rate and increased the stability of the sponge. Following lyophilization, the dressings were subjected to gamma sterilization. The structure was evaluated via scanning electron microscopy images, micro-computed tomography, and infrared spectrometry. The structural stability and vancomycin release properties were evaluated in phosphate buffered saline. Microbiological testing and a rat model of a wound infected with methicillin-resistant Staphylococcus aureus (MRSA) were then employed to test the efficacy of the treatment of the infected wound. Following an initial mass loss due to the release of vancomycin, the sponges remained stable. After 7 days of exposure in phosphate buffered saline (37°C), 60% of the material remained with a preserved collagen secondary structure together with a high degree of open porosity (over 80%). The analysis of the release of vancomycin revealed homogeneous distribution of the antibiotic both across and between the sponges. The release of vancomycin was retarded as proved by in vitro testing and further confirmed by the animal model from which measurable concentrations were observed in blood samples 24 hours after the subcutaneous implantation of the sponge, which was more than observed following intraperitoneal administration. The sponge was also highly effective in terms of reducing the number of colony-forming units in biopsies extracted from the infected wounds 4 days following the inoculation of the wounds with the MRSA solution. The presented sponges have ideal properties to serve as wound dressing for prevention of surgical site infection or treatment of already infected wounds.
- MeSH
- antibakteriální látky farmakokinetika MeSH
- hojení ran účinky léků MeSH
- kapři MeSH
- karbodiimidy farmakokinetika MeSH
- kolagen farmakokinetika MeSH
- krysa rodu rattus MeSH
- methicilin rezistentní Staphylococcus aureus účinky léků MeSH
- obvazy MeSH
- vankomycin farmakokinetika MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Úvod: V průběhu let 2014–2015 byla českými odbornými společnostmi postupně přijata nová diagnostická kritéria pro gestační diabetes mellitus (GDM), která vzešla z výsledků velké prospektivní multicentrické studie HAPO (The Hyperglycemia and Adverse Pregnancy Outcome). Přijetí nových kritérií provázely obavy z nárůstu počtu žen se zjištěným GDM. Práce se zabývá epidemiologickými výsledky záchytu GDM v prvních třech letech od zavedení nových kritérií. Název a sídlo pracoviště: Gynekologicko-porodnická klinika 1. LF UK a VFN, Praha; III. interní klinika 1. LF UK a VFN, Praha; Ústav patologické fyziologie 1. LF UK, Praha; Ústav lékařské biochemie a laboratorní diagnos-tiky 1. LF UK a VFN, Praha. Metody a výsledky: V letech 2013–2014 byl v odběrovém centru Všeobecné fakultní nemocnice v Praze proveden screening GDM u 1594 těhotných. Podle tehdy platných diagnostických kritérií (glykémie nalačno ≥ 5,6 mmol/l a/nebo ≥ 8,9 mmol/l v 60. minutě a/nebo ≥ 7,7 mmol/l ve 120. min. 75 g OGTT) byl GDM zjištěn u 324, tj. 20 % žen. V letech 2016–2018 bylo vyšetřeno 2629 těhotných žen. Záchyt GDM byl podle nových kritérií (glykémie nalačno opakovaně ≥ 5,1 mmol/l a/nebo ≥ 10 mmol/l v 60. min. a/nebo ≥ 8,5 mmol/l v 120. min. OGTT) významně nižší – u 375, tj. 14,3 % žen (p < 0,0001). Zjevný diabetes, tj. glykémie nalačno ≥ 7,0 mmol/l a/nebo ≥ 11,1 mmol/l ve 120. min. OGTT, byl nově zjištěn u šesti těhotných žen, tj. u 0,2 %. Gestační diabetes byl v 62 % zjištěn na základě opakovaně vyšší glykémie nalačno a v 38 % na základě vyšší glykémie v 60. min. a/nebo 120. min. OGTT. Záchyt GDM významně stoupal s věkem nad 30 let (p < 0,0001). U žen do 25 let byl GDM přítomen u 9,9 %, ve věku 25–29,9 let u 9,6 %, ve věku od 30–34,9 let u 14,2 % a ve věku ≥ 35 let u 18,6 %. U 2,9 % žen došlo během OGTT k hypoglykémii < 3,5 mmol/l. Pokud by byl screening v letech 2016–2018 vyhodnocen podle předchozích diagnostických kritérií, pak by byl záchyt diabetu u 16,2 % těhotných žen. Výsledek testu by byl falešně negativní u 6 % všech těhotných, tj. tyto ženy měly podle současných kritérií opakovaně vyšší glykémii nalačno (5,1–5,5 mmol/l), která byla po-dle předchozích kritérií hodnocena jako fyziologická. Ve studii HAPO však byly již tyto hodnoty spojeny s významným nárůstem komplikací. Celkem 50 % žen s GDM diagnostikovaným podle předchozích kritérií by mělo naopak falešně pozitivní výsledek OGTT (glykémii 8,9–9,9 mmol/l v 60. min. a/nebo 7,7–8,4 mmol/l ve 120. min. OGTT). Tyto hodnoty nejsou podle nových kritérií považovány za významně rizikové. Závěr: Naše data nepotvrzují nárůst záchytu GDM po zavedení nových diagnostických kritérií, která podle současných poznatků lépe odrážejí reálná rizika komplikací pro dítě a matku. Aplikace předchozích kritérií vedla k řadě falešně negativních i pozitivních výsledků, proto přijetí lépe podložených nových kritérií považujeme za krok správným směrem. Výskyt diabetu byl významný ve všech věkových kategoriích a výrazně stoupal u žen od 30 let věku.
Introduction: During the years 2014-2015 new diagnostic criteria for gestational diabetes mellitus (GDM) were gradually adopted by the Czech professional societies, which emerged from the results of the large prospective multicenter HAPO study (The Hyperglycemia and Adverse Pregnancy Outcome). The adoption of the new criteria was accompanied by concerns about the increase in the number of women with GDM. The paper deals with epidemiological results of GDM incidence in the first three years since the introduction of new criteria. Methods and results: In the years 2013-2014 GDM screening was performed at 1,594 pregnant woman at the General Teaching Hospital in Prague. According to that time valid diagnostic criteria (fasting glucose ≥ 5.6 mmol/g and/or ≥ 8.9 mmol/l in 60 min and/or ≥ 7.7 mmol/l in 120 min 75 g OGTT) GDM was found in 324, i.e. 20 % of women. In the years 2016-2018 were 2,629 pregnant women examined. GDM based on the new criteria (fasting blood glucose ≥ 5.1 mmol/l and/or ≥ 10 mmol/l in 60 min and/or ≥ 8.5 mmol/l in 120 min OGTT) was diagnosed in significantly less women - in 375, i.e. 14.3% (p < 0.0001). Overt diabetes, i.e. fasting glucose ≥ 7.0 mmol/l and/or ≥ 11.1 mmol/l in 120 min OGTT, was newly detected in 6 pregnant women, i.e. 0.2 %. Gestational diabetes was found in 62% cases based on repeated fasting fasting blood glucose and in 38% on the basis of higher blood glucose at 60 min and/or 120 min OGTT. GDM was significantly more prevalent in the age category over 30 years. Among women aged under 25 years GDM was present at 9.9%, aged 25 -29.9 years at 9.6%, aged 30 -34.9 years at 14.2% and aged ≥35 years at 18.6 %. Hypoglycaemia < 3.5 mmol/l experienced 2.9% of women during OGTT. When the screening in 2016-2018 was evaluated according to the previous diagnostic criteria, diabetes would be diagnosed in 16.2% of pregnant women. The result of the test would be falsely negative in 6% of all pregnant women, i.e. these women have repeatedly higher fasting glucose (5.1-5.5 mmol/l) according to the current criteria which was evaluated as physiological according to the previous criteria. However, in the HAPO, these values were already associated with a significant increase of complications. A total of 50% of women with GDM diagnosed according to the previous criteria would have a false positive result of OGTT (8.9-9.9 mmol/l in 60 min and/or 7.7-8.4 mmol/l in 120 min OGTT). These values are not considered to be significantly at risk under the new criteria. Conclusion: Our data do not confirm the increase in GDM incidence following the introduction of new diagnostic criteria which, according to current knowledge, better reflect the real risks of complications for the child and the mother. Applying the previous criteria has led to a number of false negative and positive results, so we consider the adoption of better-funded new criteria a step in the right direction. The incidence of diabetes was significant in all age categories and significantly increased in women over 30 years of age.
- Klíčová slova
- studie HAPO, diagnostická kritéria,
- MeSH
- diagnostické techniky a postupy MeSH
- epidemiologické studie MeSH
- gestační diabetes * diagnóza epidemiologie MeSH
- komplikace těhotenství MeSH
- krevní glukóza analýza MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- plošný screening metody MeSH
- směrnice pro lékařskou praxi jako téma MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
- Publikační typ
- abstrakt z konference MeSH
BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder with a complex pathogenesis and a common occurrence of comorbid diseases such as depression. It is accepted that the presence of the ε4 allele of the gene that encodes apolipoprotein E (APOE) is the strongest genetic risk factor for the development of sporadic AD. Melatonin, cortisol, homocysteine, and prolactin are presumed to be risk factors or biomarkers for stress- and age-related disorders. OBJECTIVE: The interplay between the APOE genotype and plasma biomarkers was examined in patients with AD presenting with or without depression to contribute to understanding the interdependence of various molecular mechanisms in the pathophysiology of AD. METHOD: The APOE genotype and morning plasma melatonin, cortisol, homocysteine, and prolactin concentrations were measured in 85 patients with AD and 44 elderly controls. RESULTS: A significant association between AD and the allele (ε4) or genotype (ε3/ε4 or ε4/ε4) frequencies of APOE was confirmed. Plasma homocysteine and cortisol levels were significantly increased in patients with AD compared to those in controls, independent of the presence of comorbid depressive symptoms or the severity of dementia. Significantly lower plasma melatonin concentration was found in patients with AD but not in controls, who were noncarriers of the APOE ε4 allele, regardless of the presence of depression or the severity of dementia in AD. CONCLUSION: Our findings indicate the existence of a little-known specific APOE-mediated mechanism that increases the plasma melatonin level in a subgroup of patients with AD who are carriers of the APOE ε4 allele.
- MeSH
- Alzheimerova nemoc krev genetika MeSH
- apolipoproteiny E genetika MeSH
- biologické markery krev MeSH
- genotyp MeSH
- homocystein krev MeSH
- hydrokortison krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- melatonin krev MeSH
- prolaktin krev MeSH
- senioři nad 80 let MeSH
- senioři 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
- MeSH
- Alzheimerova nemoc * diagnóza genetika krev MeSH
- biologické markery krev MeSH
- genetické techniky MeSH
- homocystein analýza krev MeSH
- klinická studie jako téma MeSH
- lidé středního věku MeSH
- lidé MeSH
- polymorfismus genetický MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- práce podpořená grantem MeSH
