Biomarkers of cardiometabolic risk in obese/overweight children: effect of lifestyle intervention.

Obesity is a strong cardiometabolic (CM) risk factor in children. We tested potential CM risk in obese/overweight children and the effect of an intensive lifestyle intervention using newer CM markers: atherogenic index of plasma AIP [Log(TG/HDL-C)], apoB/apoAI ratio and a marker of insulin resistance HOMA-IR. The participants (194 girls, 115 boys, average age 13) were enrolled in an intensive, one-month, inpatient weight reduction program. The program consisted of individualised dietary changes and the exercise program comprised aerobic and resistance training. Anthropometrical and biochemical parameters in plasma and CM risk biomarkers - (AIP, apoB/apoAI ratio and HOMA-IR) were examined before and after the intervention. AIP and HOMA-IR significantly correlated with BMI while apoB/apoAI ratio did not. Only AIP and HOMA-IR showed systematic increases according to the level of obesity by BMI quartiles. Lifestyle intervention significantly improved anthropometrical and biochemical values and the biomarkers too. The response of lipid parameters to the intervention was considerably higher in boys than in girls. The children were stratified into three risk categories according to AIP, where 13.8 % of boys and 5.3 % of girls fell into high risk category. The monitored biomarkers may complement each other in the prognosis of CM risk. AIP was strongly related to obesity and to lipid and glycid metabolism, while the relationship of the apoB/apoAI ratio to obesity and glycid metabolism was not significant. The obese children benefited from the intensive lifestyle intervention which improved the anthropometrical and biochemical parameters and CM risk biomarkers.

[Opinion of the Czech Atherosclerosis Society's committee (CSAT) on the ESC/EAS guidelines related to the diagnostics and treatment of dyslipidemias issued in 2011]. / Stanovisko výboru CSAT k doporucením ESC/EAS pro diagnostiku a lécbu dyslipidemií z roku 2011.

This position statement of the Executive Committee of the Czech Society for Atherosclerosis (CSAT) summarizes the most important aspects and novelties of the latest European guidelines for the management of dyslipidemia. In particular the position statement comments on: cardiovascular risk stratification, indications for plasma lipid and lipoprotein levels assessment as well as target lipid values, evaluation of current options for both lifestyle and pharmacological treatment of lipid metabolism disorders and, also, recommendation for laboratory monitoring of patients treated with lipid lowering agents. The statement deals with actual concepts of management of dyslipiemia in everyday practice, e.g. therapy of dyslipidemia in special patients´ groups. This statement does not replace the latest guidelines but focuses on the changes from the former guidelines for dyslipidemia management, published by CSAT in 2007.

[Czech atherosclerosis society guidelines for the diagnosis and treatment of dyslipidemia in adults]. / Doporucení pro diagnostiku a lécbu dyslipidémií v dospelosti, vypracované výborem Ceské spolecnosti pro aterosklerózu.

The present guidelines are based on the recommendations published in 2005 entitled "Prevention of Cardiovascular Diseases in Adulthood" summarizing the conclusions of nine Czech medical societies and agree with them in the assessment of individual risk of mortality from cardiovascular disease (CVD) according to SCORE tables. They reflect new research data in pathophysiology of dyslipidemias (DLP) and particularly the results of recent clinical trials of lipid-lowering therapy and their meta-analyses. They establish priorities for the screening and management of DLP, present suitable diagnostic methods, additional investigations of potential use in risk assessment, including some emerging risk factors and detection of sub-clinical atherosclerosis in persons in a moderate-risk category. Major changes include a lower LDL-cholesterol treatment target (< 2.0 mmol/L for all CVD individuals) and a possible use of apolipoprotein B as a secondary target in selected persons (< 0.9 g/L in high risk without CVD, < 0.8 g/L for CVD patients) and nonHDL-cholesterol (< 3.3 mmol/L in high risk without CVD, < 2.8 mmol/L for CVD patients). Therapy of individual DLP phenotypes (monotherapy and combination therapy) as well as basic principles for control examination at lipid-lowering medication are described. Recommended therapeutic lifestyle changes are shown. Enclosed are five annexes: DLP diagnosis; causes of secondary DLP; additional investiga- tions of potential use in risk stratification; familial hypercholesterolemia; list of recommended foods; two variants of SCORE tables for risk assessment for the Czech Republic; the scheme of recommended procedures and treatment algorithm in DLP asymptomatic individuals.

[Czech Atherosclerosis Society Guidelines for the diagnosis and treatment of dyslipidemias in adults]. / Doporulení pro diagnostiku a lécbu dyslipidemlí v dospelosti, vypracované výborem Ceské spolecnosti pro aterosklerózu.

The present guidelines are based on the recommendations published in 2005 entitled "Prevention of Cardiovascular Diseases in Adulthood" summarizing the conclusions of nine Czech medical societies and agree with them in the assessment of individual risks of mortality from cardiovascular disease (CVD) according to SCORE tables. They reflect new research data in pathophysiology of dyslipidemias (DLP) and particularly the results of recent clinical trials of lipid-lowering therapy and their meta-analyses. They establish priorities for the screening and management of DLP, present suitable diagnostic methods, additional investigations of potential use in risk assessment, including some emerging risk factors and detection of sub-clinical atherosclerosis in persons in a moderate-risk category. Major changes include a lower LDL-cholesterol treatment target (< 2.0 mmol/L for all CVD individuals) and a possible use of apolipoprotein B as a secondary target in selected persons (< 0.9 g/L in high risk without CVD, < 0.8 g/L for CVD patients) and nonHDL-cholesterol (< 3.3 mmol/L in high risk without CVD, < 2.8 mmol/L for CVD patients). Therapy of individual DLP phenotypes (monotherapy and combination therapy) as well as basic principles for control examination at lipid-lowering medication are described. Recommended therapeutic lifestyle changes are shown. Enclosed are five annexes: DLP diagnosis; causes of secondary DLP; additional investigations of potential use in risk stratification; familial hypercholesterolemia; list of recommended foods; two variants of SCORE tables for risk assessment for the Czech Republic; the scheme of recommended procedures and treatment algorithm in DLP asymptomatic individuals.

Relations between particle size of HDL and LDL lipoproteins and cholesterol esterification rate.

Particle size of low density (LDL) and high density (HDL) lipoproteins and cholesterol esterification rate in HDL plasma (FER(HDL)) are important independent predictors of coronary artery diseases (CAD). In this study we assessed the interrelations between these indicators and routinely examined plasma lipid parameters and plasma glucose concentrations. In 141 men, healthy volunteers, we examined plasma total cholesterol (TC), triglycerides (TG), HDL and LDL cholesterol (HDL-C, LDL-C) and HDL unesterified cholesterol (HDL-UC). Particle size distribution in HDL and LDL was assessed by gradient gel electrophoresis and FER(HDL) was estimated by radioassay. An effect of particle size and FER(HDL) on atherogenic indexes as the Log(TG/HDL-C) and TC/HDL-C was evaluated. Subjects in the study had plasma concentrations (mean +/- S.D.) of TC 5.2+/-0.9 mmol/l, HDL-C 1.2+/-0.3 mmol/l, TG 2.1+/-1.7 mmol/l, glucose 5+/-0.8 mmol/l. Relative concentration of HDL(2b) was 17.6+/-11.5 % and 14.6+/-11.8 % of HDL(3b,c). The mean diameter of LDL particles was 25.8+/-1.5 nm. The increase in FER(HDL) significantly correlated with the decrease in HDL(2b) and LDL particle size (r = -0.537 and -0.583, respectively, P<0.01) and the increase in HDL(3b,c) (0.473, P<0.01). Strong interrelations among TG and HDL-C or HDL-UC and FER(HDL) and particle size were found, but TC or LDL-C did not have such an effect. Atherogenic indexes Log(TG/HDL-C) and TC/HDL-C correlated with FER(HDL) (0.827 and 0.750, respectively, P<0.0001) and with HDL and LDL particle size.

[Consumption of white wine retards development of atherosclerosis and affects anticoagulation]. / Pití bílého vína k veceri oddaluje aterosklerózu a pusobí antikoagulacne.

BACKGROUND: An inverse relationship between moderate alcohol use and coronary heart disease was found in various countries. Aims of the study were to find out whether drinking of moravian white wine will have the same effect on lipoproteins and fibrinogen as described in foreign wines. Blood pressure, body mass, blood glucose and a hepatic enzyme were also measured before and after drinking. METHODS AND RESULTS: Drinking of the Moravian white wine (vintage 1999; alcohol 11.48 vol %) was studied in 50 men aged 44.4 (SD 9.25) years. Drinking of 350 ml (40.2 g of alcohol) every evening for four weeks without any change of dietary factors followed in 45 men by statistically significant increase in HDL cholesterol from 1.17 to 1.25 mmol/l (p < 0.001) and free HDL cholesterol from 0.17 to 0.20 mmol/l (p < 0.0001) and highly significant (p < 0.00001) decrease in plasma fibrinogen level from 3.77 to 3.35 g/l. Nor triglycerides, or blood glucose and BMI were changed after increasing source of carbohydrates in wine. Mean systolic blood pressure of 123.4 mmHg did not change and diastolic blood pressure decreased insignificantly from 78.0 to 76.7 mmHg. Minimal decrease of ALT from 0.60 to 0.59 mukat/l disproved any hepatic disturbance. CONCLUSIONS: Everynight moderate drinking of Moravian white wine has similar beneficial effect as consumption of foreign alcohol drinks.

A 5-year randomized controlled, double-blind study of glycosaminoglycan polysulphuric acid complex (Rumalon) as a structure modifying therapy in osteoarthritis of the hip and knee.

OBJECTIVE: To determine the structure (disease) modifying effect of a glycosaminoglycan polypeptide association complex (GP-C; Rumalon) in patients with knee and hip osteoarthritis (OA). METHODS: Double-blind, randomized, placebo-controlled five-year study. Primary assessment criterion was change in radiographic joint space width between baseline and follow-up at 5 years. Secondary outcome criteria included Lequesne algofunctional index (LAI), pain on passive motion and consumption of non-steroidal antiinflammatory drugs (NSAIDs). The patients received 10 courses of injections of placebo or GP-C 2 ml intramuscularly in 5 years (two courses each year). Each course included 15 injections administered twice weekly. RESULTS: There were 277 patients with knee OA and 117 patients with hip OA. Control and GP-C treated groups were comparable as to sex, age, duration of disease, body weight, X-ray stage and value of LAI at the baseline. Knee joint space at 5 years decreased 0.37+/-0.08 (mean+/-standard deviation) mm for GP-C and 0.42+/-0.08 mm for placebo groups (P=0.68). Hip joint space at 5 years decreased 0.21+/-0.08 mm for GP-C and 0.22+/-0.08 mm for placebo groups (P=0.53). In a subset of patients with hip OA, Kellgren-Lawrence> or =2 and JSW> or =1 mm, there was a trend in favor of GPC for lower joint space narrowing in 5 years (P=0.11). In addition, there were no statistical differences between the treatment groups in LAI, pain on passive motion and consumption of NSAIDs. Side-effects after GP-C (14.5%) were rare, mild and not more frequent than in the placebo group (15%). CONCLUSION: We were not able to demonstrate a structure modifying effect of GP-C in OA of the hip or knee. Radiographic progression of OA in both knee and hip OA was lower than expected in both study groups.

[Total hip replacement in patients with ankylosing spondylitis.]. / Totální náhrada kycelního kloubu u pacientu s ankylozující spondylitidou.

The authors present their experience with total hip replacement in patients with ankylosing spondylitis. In the period of 1985-1997 they performed in total 66 total hip replacements in 41 patients. Of the total number of the used implants 24 were fully cemented (the average follow-up - 13 years), 3 were hybrid and 39 cementless (the average follow-up - 6 years). The results of total hip replacements were assessed on the basis of Harris score (HS). The outcomes of the two subgroups, i. e. cemented and cementless implants, were statistically evaluated and compared. The group of hybrid implants was not statistically evaluated due to a small size of the subgroup. In both evaluated groups of implants the results were very favourable (the average HS value in cemented: 86,2 in cementless: 86,4). The occurrence of periarticular ossifications was minimal in both groups. Of the post-operative complications we recorded one case of displacement of the implant which was solved by closed reduction under general anesthesia. Two cases required re-operation of the loosened cementless cup. There occurred no infect. On the basis of the evaluation of the average 13-year results of cemented implants the use of this type of total hip replacement in patients with M. Bechterev is recommended. The question remains whether the same positive values will be produced after the same time interval also by cementless implants as we still do not have results from a 10-year follow-up. Key words: ankylosing spondylitis, total hip replacement.

Nabumetone induces less gastrointestinal mucosal changes than diclofenac retard.

The aim of the study was to compare the efficacy and the effects on the mucosa of the gastrointestinal tract (GIT) of nabumetone and diclofenac retard in patients with osteoarthritis (OA). An open, multicentre, randomised, comparative, endoscopy-blind parallel group study included 201 patients with nabumetone and 193 patients with diclofenac retard suffering from moderate to severe OA of the knee or hip joint. Twelve clinical efficacy variables were assessed and a portion of the population underwent gastroduodenoscopy. All patients exhibited significant improvement in pain severity and pain relief (p < 0.001 and p < 0.0001, respectively) but there were no differences between the groups for all the efficacy variables. Eleven per cent of patients on nabumetone and 19% on diclofenac experienced GIT side-effects. Sixty-nine patients with nabumetone and 61 with diclofenac underwent gastroduodenoscopy. The differences in the mucosal grade for the oesophagus, stomach and duodenum at baseline were not significant. In the oesophagus there were significantly less changes after treatment with nabumetone (p = 0.007) than with diclofenac; there were similar findings in the stomach (p < 0.001) but the difference in the duodenum was not significant. This study indicates that nabumetone and diclofenac retard have similar efficacy in the treatment of OA, but nabumetone has significantly fewer GIT side-effects.

High-density lipoprotein subclasses and esterification rate of cholesterol in children: effect of gender and age.

Since the development of coronary heart disease (CAD) is affected by a specific pattern of plasma high density lipoprotein (HDL) effects it may be useful to know whether this occurs already in childhood. In this study we evaluated particle size distribution of HDL by gradient gel electrophoresis and the determination of cholesterol esterification rate (FER(HDL)) in plasma depleted of apo B lipoproteins in 221 children (108 boys and 113 girls) aged 4 months to 20 years. Total plasma- (TC), low-density lipoprotein- (LDL-C) and HDL- (HDL-C) cholesterol, HDL unesterified cholesterol (HDL-UC) and plasma triglycerides (TG) were also measured. There were no significant gender and age differences with respect to the plasma TC, LDL-TC and TG but concentration of HDL-TC increased with age. Post-pubertal girls had significantly higher relative concentrations of HDL2b compared to boys (30.4% vs 17.2%), while HDL3b,c was lower in post-pubertal girls (8.7% vs. 16.5%). FER(HDL) correlated inversely with HDL2b and positively with HDL3b,c particles and was significantly higher in boys of the post-pubertal group compared to girls (16.9%/h vs 12.5%/h). While in girls there was a positive correlation between age and HDL-C, HDL-UC and the relative concentration of HDL2b no significant correlation were observed in boys. In girls the increase in TC showed a significant correlation with a simultaneous increase in HDL-C, HDL-UC and HDL2b. In boys TC correlated significantly with changes in TG only. When HDL2b and HDL3b,c cholesterol levels are calculated from HDL-C concentration and per cent distribution the differences between males and females are further emphasized. These data indicate that HDL particle size distribution is age- and gender-dependent.

[What was not included in the recommendations for the diagnosis and therapy of hyperlipoproteinemia in childhood]. / Co se neveslo do doporucení pro diagnostiku a lécbu hyperlipoproteinémií v detství.

Screening and treatment of hyperlipidaemia should be the concern of paediatricians. This is suggested by the finding of fatty streaks and other atheromatic changes in children. The authors prefer selective to nationwide screening in children who have close relatives with coronary heart disease or cerebral haemorrhage before the age of 55 years in men and 65 years in women or elevated total cholesterol levels. In case of repeated total cholesterol levels of 4.4-5.2 mmol/l the authors recommend annual, in case of levels above 5.2 mmol/l 3-6 month intervals between examinations. The authors found values above 5.2 mmol/l in one quarter of otherwise healthy children. In addition to the hyperlipidaemic theory there is the infectious theory of development of atherosclerosis and the theory of programming of coronary heart disease during pregnancy. By dietary and lifestyle provisions it is possible to reduce hyperlipidaemia in the great majority of children. In boys above 10 years and girls above 20 years resins are indicated if the total cholesterol level is above 8 mmol/l.

[Cholesterol and triglyceride levels and their development from 2 to 17 years of age]. / Hodnoty cholesterolu a triglyceridu a jejich vývoj mezi druhým a sedmnáctým rokem.

BACKGROUND: High blood cholesterol levels is important risk factor of an early atherosclerosis and ischemic heart disease. Information on cholesterol level in children in essential for grading the risk and following its trends in the Czech population and for starting an effective prevention already in childhood. METHODS AND RESULTS: Fasting venous cholesterol and triglyceride levels were measured in 1378 children and adolescents, 707 boys and 671 girls aged 1-17 years. Children with familiar hypercholesterolemia or with another illness influencing the measured data were excluded. The mean total cholesterol (TC) level was 4.46 +/- 0.92 mmol/l. It increased from the youngest age, culminated at the age of 13 and decreased afterwards. Mean HDL cholesterol value was 1.23 mmol/l. The lowest value was measured in the youngest age group. The highest values were reached at the age of 11 years and later. TC/HDL ratio was higher than 4.0 only between the age of 3 and 5. LDL cholesterol mean value was 2.70 +/- 0.92 mmol/l. The lowest values were found between 1 and 3 and 13 to 17 years. Triglyceride mean value was 1.22 +/- 0.79 mmol/l. It ranged from 1.53 mmol/l in the youngest age group to 1.03 mmol/l at the age of 7 to 9 years. The values in boys did not differ from those in girls. TC was higher in children with an increased body mass than in children with normal body weight. We did not prove any regional difference in the measured values. CONCLUSIONS: The desired TC value (< 4.41 mmol/l) was found in only 52% of children. In total 18% of all probands, but 26% of school age children belong into high risk category with TC above 5.20 mmol/l.

Correlation between knee roentgenogram changes and clinical symptoms in osteoarthritis.

The main purpose of this study was to analyze the relationship between clinical symptoms and roentgenographic changes in patients with incipient osteoarthritis of the knees (OA). One hundred and sixty-two patients (126 women, 36 men, mean age 59 years) with established osteoarthritis of the knee were examined. Patients performed subjective self-assessment using Lequesne's questionnaire (index of severity for OA of the knee) and had frontal and lateral roentgenograms of both knees. Validity of the indices as reflections of individual symptoms was documented. A statistically significant correlation was found between clinical and patient indices (r = 0.327, p < 0.0001) as well as a very weak correlation between the clinical and roentgenogram indices (r = 0.196, p = 0.286). However, there was no correlation between the patient index and roentgenogram index (r = 0.065, p = 0.47). For the assessment of severity and progression of the disease, items reflecting acute irritation (swelling, effusion, increased joint temperature, pain during passive motion) were more reliable than items reflecting chronicity (muscular atrophy, decreased range of motion, crepitus). This study confirmed that Lequesne's questionnaire is a suitable tool for assessing subjective symptoms as well as for generating a condensed measure of disease severity. In addition, sclerosis, narrowing and osteophytes were proved to be important features characterizing the OA process.

[Replacement of hip joints with total endoprostheses in patients with ankylosing spondylitis]. / Náhrady kycelních kloubu totální endoprotézou u nemocných s ankylozující spondylitidou.

In the Rheumatological Institute in Prague the authors made a retrospective investigation in patients with ankylosing spondylitis affecting the hip joints where one or two endoprostheses of the hip joints were made. In all these patients they evaluated the subjective complaints of the operated extremity, they made a clinical examination of the extent of mobility and evaluated X-ray pictures. The group of 20 patients was examined in this retrospective investigation approximately five years after operation. From the total of 32 endoprostheses 20 were cemented and 12 were without cement. From the total number of patients only four reported slight pain in the area of the operated hip joint without signs of loosening on the X-ray picture. The extent of mobility of all endoprostheses was very satisfactory, the mean abduction in men was 27.6 degrees, in women 30.7 degrees, flexion 84 degrees in men and 97 degrees in women. As revealed by X-ray, the hip joints were affected most frequently by coxitis, osteoplastic changes were detected in six patients. Enthesopathies of a small or medium extent were found in almost all patients. Heteroplastic bone was evaluated according to Brooker's criteria, in the investigated group only type I was found. It may be stated that the submitted group of results of endoprostheses in ankylosing spondylitis is a very satisfactory solution which improves the patient's mobility and thus restores the quality of life.

[Pneumococcal infectious endocarditis in an infant (case report)]. / Pneumokoková infekcní endokarditida u kojence (kasuistika).

In a 10-month-old infant with purulent pneumococcal meningitis without structural heart disease acute infectious endocarditis developed. Echocardiographic examination revealed vegetations on both cusps of the mitral valve. With regard to the age and critical condition of the infant, in the acute stage surgical removal of the vegetations, was not indicated. During long-term intravenous antibiotic therapy the vegetations on the mitral valve and clinical and laboratory manifestations of endocarditis disappeared. The valve was, however, devastated and the child developed severe mitral insufficiency. Because of progressive cardiac failure which could not be controlled by drugs, at the age of 19 months a plastic operation of the mitral valve had to be performed after which the haemodynamics and clinical condition improved markedly.

The effects of peptidoglycan, a pyrogenic constituent of gram-positive microorganisms, on the pharmacokinetics of rifampicin.

Pharmacokinetics of rifampicin (20 mg/kg orally or i.v.) was determined in calves and rabbits. Seven days later a model pyrogen was administered i.v. to the same animals and 1 hr later the rifampicin administration was repeated. The pharmacokinetic analysis of oral rifampicin was performed using a one-compartment open model with absorption. Intravenously administered rifampicin was analysed by a two-compartment intravascular model. Injection of peptidoglycan in pyrogenic doses led to a significant increase of orally applied rifampicin serum levels in both animal species. The i.v. administration of rifampicin had the same parameters in the control and peptidoglycan experiments. Daily pretreatment of rabbits with small doses of peptidoglycan induced tolerance to the pyrogenic effect. In tolerant animals we did not observe any changes of rifampicin serum levels. Elevated temperature alone was not responsible for observed pharmacokinetic changes leading to the increase of bioavailability of oral rifampicin since another pyrogenic substance (endotoxin) had an opposite effect on pharmacokinetics of previously tested drugs.

Bacterial pyrogens of different origin and pharmacokinetics of rifampicin.

Changes of pharmacokinetics of rifampicin (RFP, Rifadin were investigated on endotoxin pretreated still not ruminant calves. The animals served as their own controls and drug administration twice in a 1-week interval gave the same results. Endotoxin 0.02 micrograms kg-1 given intravenously 1 h prior to the oral administration of RFP (20 mg kg-1) induced considerable pharmacokinetic changes. The serum levels of the total drug were significantly lower after the endotoxin administration. The pharmacokinetic analysis revealed significant changes mainly in the distribution phase. When both toxin and drug were administered intravenously, the drug levels were higher. The results are discussed with reference to the pathophysiological endotoxin changes. After the toxin administration the bioavailability of oral RFP was 4-fold lower.