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Unlabelled: Thiazolidindione derivates (glitazones) make a very promising group of peroral antidiabetic drugs. They are represented by rosiglitazon which is available on our market to type II diabetics. As far as sugar metabolism is concerned, rosiglitazon can reduce glycaemia and insulin level both when fasting and postprandially., Goal: The goal of the authors' work was to gain their own experience with rosiglitazon treatment in type II diabetics in the Czech Republic., Sample: The monitored sample consisted of 388 patients with insufficiently compensated type II diabetes when treated by sulphonylurea compounds or metformine., Methods: 95 diabetologists from diabetology medical offices started a 6-month-long treatment with rosiglitazon (Avandia) dose of 4 mg a day as stated in European recommendations. In order to assess changes in sugar metabolism (compensation of diabetes) glycaemia and C peptide were monitored when fasting and postpradially and HbA1c was monitored in 2-month-long intervals., Results: Weight, waist-hip ratio (WHR) and C-peptide levels remained unchanged. Statistically significant (p < 0.0001) was a HbA1c decrease over 6 month from 9.61% to 8.48%. Fasting glycaemia decreased by 2.49 and postprandial glycaemia by 2.71 mmol/l. No significant side effects were identified., Conclusion: Rosiglitazon administration combined with administration of sulphonylurea compounds or metformine significantly improved compensation of diabetes compared to initial therapy.

Plant sterols occur naturally in plants and vegetable oils. Sitosterol and campesterol are markers of cholesterol absorption. The ratio of cholesterol endogenous synthesis to its absorption may be assessed by sitosterol, campesterol and other non-cholesterol sterols (lathosterol and squalen) serum concentration measurements. In 38 Type 2 diabetics (59.9 years, BMI 29.8 kg/m2, HbA1c 7.6%, C-peptid 0.82 nmol/l) and in 40 non-diabetics (37.2 years, BMI 25.4 kg/m2, HbA1c 5.2%, C-peptid 0.85 nmol/l) plant sterols serum concentration were measured: lathosterol (diabetics 10.64, non-diabetics 6.04 mumol/l, p = 0.09), squalen (diabetics 3.42, non-diabetics 1.78 mumol/l, p < 0.01), sitosterol (diabetics 3.91, non-diabetics 3.80 mumol/l, p = 0.60) and campesterol (diabetics 7.91, non-diabetics 8.85 mmol/l, p = 0.09). In non-diabetics squalen positive correlates with C-peptid, lathosterol with triacylglycerols and campesterol with HbA1c. In diabetics correlates diabetes compensation with plant sterols value negative. It seems that plant sterols and probably also cholesterol absorption can be influenced negative by higher value HbA1c.

Background and Aim: System of insulin-like growth factor-I (IGF-I) and its binding proteins (IGFBP) may be involved in the pathogenesis of vascular damage in Type 2 diabetes. Aim of the study was to analyse the relationship between this system and microvascular reactivity in Type 2 diabetes as measured by laser-Doppler flowmetry., Methods and Results: Thirteen Type 2 diabetic patients (8 women and 5 men) with microangiopathy and fifteen healthy subjects (8 women and 7 men) were examined clinically, underwent laser-Doppler flowmetry and intima-media thickness measurements. Fasting serum levels of IGF-I, IGFBP and lipids were examined. Percentage perfusion increase in the test with postocclusive reactive hyperaemia (PORH) as well as in that with thermal hyperaemia (TH) were significantly decreased in Type 2 diabetic patients (p < 0.05). Maximal perfusion after heating (THmax) was lower in Type 2 diabetic patients. Reaction of microcirculation after heating (THmax/t) was slower in Type 2 diabetic patients (p < 0.001). The changes in microvascular reactivity didn't significantly correlate with any of measured parameters of IGF-I/IGFBP system., Conclusions: Microvascular reactivity is impaired in Type 2 diabetic patients. The function of microcirculation is not significantly related to the particular parameters of the IGF-I/IGFBP system.

The ethical responsibility to the randomized study participants demands that the results be monitored during the course of the trial. The interim evaluation of the trial results may lead to the premature stopping. However, the repeated statistical testing inflates the probability of false positive error. Hence statistical adjustments are necessary. The probabilistic rules for the random allocation of patients may be changed during the course of the trial according to the observed responses.

Background: Intima-media thickness of the common carotid artery (IMT ACC) and flow-mediated vasodilatation (FMD) of the brachial artery is considered an early marker of atherosclerosis. This study was undertaken to elucidate whether endothelial dysfunction in the popliteal artery, pronoun to atherosclerosis, is related to IMT ACC., Methods and Results: Twenty-nine control subjects, 29 asymptomatic patients with hyperlipoproteinemia (without therapy) and 26 patients with coronary artery disease were examined. Using ultrasound with a linear-array probe (7.5 MHz), we measured IMT ACC and diameter of the popliteal artery (PA) at rest and during reactive hyperaemia after release of 5-minute arterial occlusion. In control subjects we found thicker IMT ACC and greater FMD than did the patients (p<0.001, ANOVA test). A significant negative correlation between the IMT ACC and percent FMD was found in all of the subjects (p<0.001). On multiple regression analysis, percent FMD showed a significant negative correlation with the IMT ACC, total cholesterol, triacylglyceroles, body mass index, age, and diastolic blood pressure., Conclusion: We found significant negative correlation between IMT common carotid artery and FMD popliteal artery.

Non-invasive measurement of the intima-media thickness (IMT) of the carotid artery and flow-mediated dilatation (FMD) of the brachial artery are increasingly used as surrogate markers of vascular disease. Using ultrasound, we measured the diameter of the popliteal artery at rest and during reactive hyperaemia after release of 5-minute arterial occlusion. We also measured IMT of the common carotid artery. In 29 control subjects (average age 35 years) we demonstrated an increase in the diameter by 6.0 +/- 3.3% (p < 0.05), in 29 asymptomatic patients with hyperlipidemia (without therapy, average age 46 years) only by 0.9 +/- 3.0% and in patients with coronary heart disease (average age 50 years) only by 0.2 +/- 2.7%. The difference between patients and control subjects was highly significant (p < 0.001). IMT was 0.58 +/- 0.10 mm, 0.78 +/- 0.17 mm and 1.03 +/- 0.25 mm respectively (p < 0.001). We conclude that in patients FMD of the popliteal artery is smaller and IMT of the common carotid artery is thicker than in controls.

Randomized clinical trial is currently thought to be the most reliable method for comparing therapeutic effects. The article tries to answer the question whether chance allocation of patients into various therapeutic arms is acceptable from the ethical point of view. It deals with the conflict between two concepts: of individual ethics mostly defending interests of individual participants of each trial, and collective ethics based on well-designed experiments that are the sole source of reliable estimation of therapeutic effect and their conclusions can change clinical practice and help patients in the future. The article suggests this possible solution: providing there is no prevailing consensus as for superiority of one of the compared therapies, the offer to participate in randomized clinical trial is not only acceptable but necessary in view of individual patients' right and respect of their autonomy. If an informed consent is obtained the principles of medical ethics have not been violated. Finally, a few alternative trial designs are presented.

We carried out analysis of the influence of long-term weight reduction on individual parameters of metabolic syndrome X. We enrolled the total of 30 obese patients (22 with, 8 without syndrome X). During weight reduction, the mean BMI decreased by 4.08 +/- 3.00 kg/m2 leading to significant (p < 0.001) decrease in insulinaemia from 33.4 +/- 25.9 to 21.2 +/- 19.625 mu j/ml. In patients with syndrome X, the decrease in BMI of 3.50 +/- 2.76 kg/m2 was coupled with significant (p < 0.001) decrease in insulinaemia from 39.7 +/- 27.7 to 24.0 +/- 21.725 mu j/ml. Using cluster analysis of cases syndrome X patients formed two distinctive groups with different behaviour. It seems, that diagnosis of metabolic syndrome, based on arbitrary criteria, encompasses stable patients, in our study characterized by higher age and presence of hypertension, and volatile patients, who form somewhat transition stage between simple obesity and fully developed syndrome X. Moreover, relationships between individual parameters at the beginning of the study can elucidate the environmental influences (relationship between insulinaemia and hypertension), whereas those at the end of the study represent true pathogenetic relationships (insulinaemia and glycaemia) and relationships between syndrome X constituents (hypertension, hypertriglyceridaemia and decrease in HDL cholesterol).

Background: Relationship between dehydroepiandrosterone (DHEA), its sulphate (DHEAS) and various components of metabolic syndrome X have been recently discussed in several papers. Originally only DHEA or DHEAS have been considered to be responsible for all of the effects. At present mainly DHEA hydroxyderivatives (particularly 7-hydroxyisometers) are assumed to be responsible for those effects., Methods and Results: 68 obese subjects (28 males) aged 42.6 +/- 11.1 years, with average BMI 35.7 +/- 11.6 kg/m2 were examined. Relationship between 7-alpha and 7-beta-(OH)-DHEA and various components of metabolic syndrome X have been followed in a pilot epidemiological study. Fluctuations of the hydroxyderivates level during one-day starvation test were investigated in a group of 11 obese females and compared with that of the control group (12 lean subjects with BMI 23.1 +/- 2.4 kg/m2). From the view of the metabolic syndrome X, the negative correlation between the serum levels of 7-beta-(OH)-DHEA and insulinemia (r = -0.28; p = 0.23), glycemia (r = -0.48; p < 0.001), serum level of uric acid (r = -0.35; p = 0.02) and opposite the positive correlation between the serum level of HDL-cholesterol (r = 0.42; p < 0.01) should be pointed out. The negative correlation between 7-alpha-(OH)-DHEA and age and BMI was noticed (correlation for 7-beta-(OH)-DHEA was similar). No other statistically significant correlation was found among the other monitored parameters. In 11 obese females the dynamic changes of the above-mentioned DHEA hydroxyderivatives during one-day starvation test were monitored. Changes were compared with the control group (12 lean females). Significant increases in DHEAS, 7-beta-(OH)-DHEA, and sex hormone binding globulin (SHBG) levels were observed during this test. Significant differences in dynamic changes (before and after the test) between obese and lean group have been found only in DHEAS and SHBG., Conclusion: We suppose that 7-beta-(OH)-DHEA (more than 7-alpha-(OH)-DHEA) is specifically related to the metabolic syndrome X and that its claimed anti-glucocorticoid effect in the immune response can play some role in its metabolic effects.

Irbesartan (Aprovel) belongs into the new group drugs for the cardiovascular system which exert an antagonistic effect at the level of angiotensin II, but experimental pilot studies as well as clinical studies draw also attention to the possible therapeutic potential of AT1 receptor blockers in the treatment of chronic heart failure. Irbesartan has a marked antihypertensive effect as is apparent from a recent clinical study in 139 patients with mild and moderate hypertension--implemented in the Czech Republic. Twelve-week treatment with Irbesartan led to a marked drop of the systolic and diastolic blood pressure (159.2 +/- 14 vs. 137 +/- 13 mmHg/99.2 +/- 7 vs. 85.3 +/- 7 mmHg, p < 0.01). A very favourable therapeutic effect was recorded in this investigation also in 24-hour monitoring of the blood pressure. The use of irbesartan in patients with arterial hypertension has according to other studies also a favourable effect on organ complications of hypertension and diabetes (regression of left ventricular hypertrophy, reduction of albuminuria). Irbesartan may prove due to its favourable effect a suitable alternative in conditions associated with intolerance of ACE-inhibitors in patients with moderate and severe forms of arterial hypertension, in chronic heart failure and in diabetic nephropathy.

A total of 633 patients with combined hyperlipoproteinaemia from 23 centres in the Czech Republic met the criteria for assessment of the effectiveness of 3-month administration of 100 mg ciprofibrate (Lipanor) per day. The cholesterol concentration declined from the original values of 6.94 mmol/l by 13%. The drop of triglycerides was even more significant from 3.03 mmol/l by more than 41%. The relatively low HDL cholesterol at the beginning, 1.14 mmol/l, increased by 15%, while LDL-cholesterol dropped significantly by almost 12%. The classical atherogenic index expressed by the ratio of total/HDL cholesterol declined by 25%. Treatment was very well tolerated by the patients and was associated with a minimum of undesirable side-effects. Treatment with ciprofibrate is effective and safe treatment in patients with combined hyperlipoproteinaemia.

The objective of the paper is to draw attention to incorrectness of various statistical approaches to research data. We critically assess the situation when first the decision on the hypothesis to be proved is done and then data are made to fit the hypothesis. We demonstrate that data cannot be satisfactorily interpreted without close attention to the manner of their collection. Finally we criticize opportunistic data torturing when researcher explores the data until a significant result is found and then devises a biologically plausible hypothesis.

Background: Czech facilities for non-acute, continuing care provide care for very heterogeneous group of residents with different clinical characteristics, care needs and resource use. The rate based funding of LTC doesn't reflect patient case-mix. Therefore, a case mix system RUG based on per diem resource use is being used abroad for rational and fair LTC funding., Methods: The validity of RUG-III has been evaluated and its use for financing of LTC and geriatric care in CR examined. In a sample of 1162 residents from 18 institutions patients were assigned to one of 44 RUG-III groups regarding their clinical characteristics. Data were analyzed using analysis of variance with individual care time per patient per day as independent and RUG-III groups as dependent variables. Weighted means for each group (case-mix indexes, CMI) were calculated., Results: The RUG-III system achieved 59% variance explanation of total per diem costs of nursing and therapy/rehabilitation care and meets criteria of clinical validity. The CMIs for individual groups span from 0.39 to 2.70 i.e. differences in resource use between groups were sevenfold. Resource use within groups was relatively homogeneous., Conclusions: The RUG-III represent a suitable case-mix system for nonacute institutional care in the Czech health care. Besides its use for payment incentives, RUG-III can be used in facility management, quality assurance process and for comparative analyses on national and international level.

Initial hormonal and metabolic investigation was performed in a group o 51 patients (mean age 41 years and body mass index--BMI 45.1 kg/m2) referred to gastric banding for morbid obesity. Patients were followed for one year period after surgery. Using multiple linear regression following parameters influencing BMI change were identified. Negative influence on BMI reduction: high insulin, presence of diabetes, low T3/T4 ratio. Positive influence on BMI reduction high triglycerides level, positive family history of diabetes. It is possible to identify patient's prognosis after gastric banding using metabolic and hormonal investigation. This investigation should be performed in every patient.

Erythroid and/or megakaryocytic dysplasia (EMD) was evaluated in diagnostic bone marrow smears of 37 consecutively treated cases with de novo acute myeloid leukemia (AML) M0-M2 and M4-M5 types and three newly diagnosed cases of refractory anaemia with excess of blasts in transformation. This evaluation was possible in 38 of 40 (95%) patients and 17 cases were categorized without EMD and 21 cases with EMD. One or two cycles with 3-4 doses of daunorubicin 45 mg/m2/d and cytosine arabinoside 200 mg/m2/12 h x 14 lead to complete remission in 13 of 16 cases without EMD but only in 4 of 16 cases with EMD (p = 0.004). However, 10 of 13 patients with EMD reached complete remission with 2000 mg/m2/12 h x 10 of cytosine arabinoside plus daunorubicin. After intensive consolidations 20 patients under 65 years with EMD showed significantly worse overall survival (p = 0.017) with a median 11.5 months, while the median survival was estimated 66.8 months in 15 cases under 65 years without EMD. The proposed categorization of de novo AML patients according to the EMD seems to be useful for selection of optimal induction therapy, clinically relevant for survival and might reflect two biologic groups of AML arising in two different stages of differentiation.

The influence of growth hormone upon trabecular bone remodelation is not definitely clear. The authors of this study compared static and dynamic histomorphometric data of bone patterns of 28 numbered group of acromegalics and 35 numbered group of healthy individuals. They correlated also levels of growth hormone, thyroxine, prolactin and testosterone in men with histomorphometric parameters in acromegalic patients. The results showed statistically significant differences between normal and acromegalic trabecular bone, which has comparable trabecular volume, but significantly wider bone trabeculae and lower mean trabecular density. There were no correlations found between growth hormone levels and levels of thyroxine, prolactin, measured testosterone and histomorphometric parameters.

The influence of duration of growth hormone action (length of history of acromegaly) upon acromegalic trabecular bone histology was followed in 28 biopted active acromegalics. The histology of trabecular bone was standardized by histomorphometric parameters. No statistically significant relation between length of acromegalic history and any of measured histomorphometric parameters (trabecular volume, trabecular thickness, absolute osteoid volume and osteoid surface) was found. The reason of this finding is probably consequence of serum growth hormone level, which changes during period of history in each acromegalic patient. With aim to find out if growth hormone influences bone histomorphometry of acromegalics after causal treatment (removal of hypophyseal adenoma causing overproduction of growth hormone), the comparison of histomorphometry from bone bioptic patterns of six active acromegalics with their bone patterns average 9.3 years after hypophyseal operation was done. With the exception of one eugonadal woman, all acromegalics were hypogonadal in time of second biopsy. Nevertheless no statistically significant differences between histomorphometric data (trabecular volume, trabecular thickness, surface and absolute volume of osteoid) were found. With knowledge of fact that there is low number of rebiopted acromegalics, these results could support idea of protective action of growth hormone upon trabecular bone of acromegalics during nine years after treatment.

Background: Concomitant occurrence of carotid atherosclerosis, coronary artery disease (CAD) and peripheral vascular disease (PVD) has been described in a number of studies. The objective of the present trial was to assess the degree of correlation between atherosclerosis of the carotid beds as well as PVD and the extent of CAD., Methods and Results: Carotid morphologies of 170 patients in total (121 men, 49 women), ranging between 23 and 81 years in age were assessed ultrasonographically. Their carotid beds searched for plaques, stenoses and occlusions. In all patients intima-media thickness (IMT) of the common carotid artery (CCA) were measured ultrasonographically. In addition, case histories of PVD were taken. CAD was proved angiographically in 138 patients. Plaques in carotid beds were found in 98 patients, carotid artery stenoses > 75% were found in 4 patients whereas complete carotid occlusion was not detected in any patient. Clinically manifested PVD was found in 20 patients. A significant difference in IMT of the CCA was assessed by t-test between patients having and not having CAD (0.67 +/- 0.16 mm vs. 0.87 +/- 0.24 mm; P < 0.0001). The correlation between the IMT of the CCA and extent of CAD was weak (r = 0.30, p < 0.01). A positive correlation between carotid plaque occurrence and the number of CAD-affected arteries was statistically assessed (Trend test: P = 0.0001). The sensitivity of incidence of plaques on the carotid beds for prediction of CAD was 64%, the specificity 72%, the positive predictive value 91% and the negative predictive value 32%. The sensitivity of clinically manifested PVD for prediction of CAD was 15%, the specificity 100%, the positive predictive value 100% and the negative predictive value 21%., Conclusions: The authors confirmed a statistically significant but weak correlation between IMT of the CCA and severity of CAD. They found a positive trend between the occurrence of carotid plaques and the number of CAD-affected arteries. The presence of carotid plaques and clinically manifested PVD were confirmed as a reliable positive predictive factors for CAD.

Background: Increased mortality of hypopituitary adults with atherosclerotic vascular disease is commonly explained by growth hormone deficiency and forms the main argument for the growth hormone replacement. At the same time it is known that the growth hormone-IGF-I axis stimulates the vessel wall proliferation as an initial step of atherosclerosis. Investigation of the arterial intima thickness in hypopituitary adults with duplex ultrasound system and its follow up during the growth hormone therapy may clarify these effects of growth hormone on the vessel wall., Methods and Results: Luminal diameter, maximal blood flow velocity and arterial intima thickness of common carotid arteries was measured with colour duplex ultrasound system in 15 adults with hypopituitarism before and after one year therapy with recombinant growth hormone. The results were compared with healthy controls matched for gender, age, blood pressure and weight. The luminal diameter did not changed during the therapy with growth hormone and was the same in patients and controls. Maximal blood velocity in hypopituitary patients before the therapy was lower than in control subjects (74.8 +/- 13.9 cm/s vs. 94.0 +/- 21.0 cm/s), but the statistical difference was only borderline. Arterial intima thickness was significantly thinner in hypopituitary patients when compared with controls (0.56 +/- 0.1 mm vs. 0.71 +/- 0.12 mm, p < 0.001) but became thicker after the treatment and was not any more different from the controls (0.56 +/- 0.1 mm vs. 0.66 +/- 0.1 mm, p < 0.001)., Conclusions: In hypopituitary adults the arterial intima thickness of common carotid arteries is less than in healthy controls. The reduced thickness was normalised after one year treatment with growth hormone. Atheromatous plaques were not found either before or after the treatment. Duplex ultrasound measurement may be one of the means of checking of the effects of growth hormone therapy.

Background: Incontinence represents one of the common problems in long-term care geriatric facilities and nursing homes. However, in the Czech Republic data on prevalence, severity and incontinence-associated factors for nursing home residents are not available. The aim of the study was to report the prevalence of urinary (UI) and bowel incontinence (BI) in different geriatric facilities and to identify factors positively associated with incontinence., Methods and Results: In a sample of 1162 residents of 18 long-term care facilities UI has been found in 684 residents (63.3%). Health and social care facilities did not differ significantly (60.7 vs 65.6%). Of the incontinent 294 residents (27.2%) suffered from permanent/daily incontinence, 390 (36.1%) from occasional transitory UI. Prevalence of BI reached 54.4%, as well as double incontinence (45.9%). Cognitive impairment, self-care ADL and/or mobility dependency and bed rest are factors significantly associated with UI (for all P < 0.001). However, age, gender and urinary tract infection did not reach the statistical significance (P = 0.280-0.069). Risk adjustment/stratification for UI revealed the prevalence of 33.0% in the low risk group. In the high risk group (high ADL dependency and severe cognitive impairment) the prevalence came up to 96.0%., Conclusions: Our study presents the first results focused on incontinence problem in long-term care geriatric institutions in the Czech Republic. High prevalence of this condition makes incontinence an important medical, nursing and economical yet neglected problem.

Background: Urinary incontinence (UI) represents a prevalent nursing problem in geriatric facilities. Yet, comparison of the Czech Republic with countries using different chronic care system has not been conducted., Methods and Results: Data from INTERRAI international database from 8 countries: Czech Republic, Denmark, France, Iceland, Italy, Japan, Sweden and USA have been evaluated in the sample of 280,271 nursing home residents. Prevalence of bladder and bowel incontinence and correlates with selected clinical factors have been determined and national samples compared with the results of 1080 patients in the Czech Republic. Prevalence of UI reached from 42.9% in Japan to 65.2% in France. France and CR belong to countries with the highest prevalence of both bladder and bowel incontinence. Cognitive impairment and dependency in ambulation are factors significantly associated with UI in all countries (p < 0.001). Immobility, age, gender and urinary tract infection reached the statistical significance only in some countries., Conclusions: High prevalence of bladder and bowel incontinence has been demonstrated in an extended sample of nursing home residents. Common protocol Resident Assessment Instrument-Minimum Data Set (RAI-MDS) and creation of a large cross-national database are opening up possibilities for a new level of clinical research in geriatrics.

Presented survey summarises insulin-steroid interactions. Beside the well known resistance to insulin induced by steroid hormones, also the central effect of insulin, its influence on the system hypophysis-adrenals, and its stimulatory effect on the generation of steroids in adrenals and ovaries are reviewed. Insulin-steroid interactions are further illustrated by pathogenesis of the polycystic ovary syndrome and by our study on dehydroepiandrosterone regulation. Insulin induced changes in the dehydroepiandrosterone level during the intravenous glucose tolerance test were described.

Dehydroepiandrosterone (DHEA) is a steroid with important effects on the bone tissue. We tried to check up if it influenced also the bone blood flow (similarly as estradiol and testosterone). We administered DHEA (Sigma) dissolved in dimethylsulphoxide s.c. three times weekly for four weeks in the doses of 15-20 mg per rat on 125 mg/kg body weight to female rats--sham-operated or oophorectomized (OOX). In two experiments (A and B) we ascertained the uptake of 85Sr-microspheres, local blood flow, cardiac output, density and ash weight of the burned tibia, in the third experiment (C) 24 hour incorporation of 45Ca and 3H-proline into the bone. The 85Sr-microsphere uptake in the tibia was elevated after OOX in both experiments A and B; this increase was inhibited completely (and statistically significantly versus the OOX group) by the administration of DHEA. Similar and also significant reactions were found in the microsphere uptake values in the distal end of femur. No significant changes could be demonstrated in the diaphysis of femur and calvaria as well as in the cardiac output, output, blood pressure and heart rate. The incorporation of 45Ca and 3H-proline into the tibia (experiment C) was significantly increased after OOX. The administration of DHEA inhibited this increase significantly in the values of 3H-proline. The density of tibia in both experiments A and B and ash weight of tibia in experiment A, suppressed after OOX, were significantly increased after the administration of DHEA to OOX females. The results show that also DHEA--in the experimental conditions used--has similar effect on the bone blood flow as estradiol and testosterone.

Background: The aim of the study was to approve the hypolipidemic potency of the new drug from the group of fibrate derivates Lipanthyl 200 M(R) (micronized fenofibrate, cps a 200 mg, Laboratoires Fournier, France) in patients with familial hyperlipoproteinemias. The drug has been administered in constant dose of 200 mg daily with the evening meal for three months. Clinical examinations and monitoring of safety laboratory have been performed in addition to complete analysis of lipids, lipoproteins and apolipoproteins during the study., Methods and Results: The group of 30 patients consisted from 14 heterozygotes of familial hypercholesterolemia and 16 patients affected by familial combined hyperlipidemia. Levels of total, HDL- and LDL-cholesterol, triglycerides, apolipoproteins A-I and B and Lp(a) have been measured and concentrations of fibrinogen in plasma as well. Concentration of total cholesterol 8.29 +/- 1.3 mmol/l on the beginning of the study decreased after one and three months of the treatment to 6.94 +/- 1.19 resp. 6.98 +/- 1.21 mmol/l, concentration of triglycerides has been reduced from 2.86 +/- 1.29 mmol/l to 1.70 +/- 0.86 and 1.74 +/- 0.99 mmol/l respectively HDL-cholesterol raised from 1.14 +/- 0.32 mmol/l to 1.27 +/- 0.36 and to 1.34 +/- 0.37 mmol/l in contrast to decrease of LDL-cholesterol 5.88 +/- 1.53 mmol/l on the beginning of the study to 4.87 +/- 1.49 and 4.79 +/- 1.60. Apo B in plasma fall after three month period of the treatment from 1.83 +/- 0.43 g/l to 1.46 +/- 0.47 g/l. On the other hand the concentration of apolipoprotein apo A-I1.20 +/- 0.35 g/l increased to 1.40 +/- 0.32 g/l. Fibrinogen in plasma was reduced from 3.63 +/- 0.69 g/l to 2.77 +/- 0.50 g/l. Also this decrease was statistically significant., Conclusions: Micronized fenofibrate is a potent hypolipidemic drug with only rare side effects. It is very good tolerated by the patients. Micronized fenofibrate is particularly prescribed for combined hyperlipidemia, however we can use it also in some patients with familial hypercholesterolemia. For to the treatment very resistant hyperlipoproteinemias we should consider combined drug therapy.

EDRF-NO probably participates-besides the prostaglandins [3, 4]-in local circulatory changes in the bones of female rats with modified level of sex hormones; we could demonstrate it indirectly using methylene blue as a blocking agent [5]. In this paper, we present corresponding results of two experiments with NG-nitro-arginine methyl ester (L-NAME) as a substance blocking the production of endothelium derived relaxing factor, i.e. nitric oxide (EDRF-NO). Circulatory values were estimated by means of 85Sr-microspheres. In experiment A we ascertained whether the duration of L-NAME administration (0.025% in the food) influenced the effect. It could be demonstrated that the effect of one week's, two weeks', or four weeks' administration of L-NAME was the same: 85Sr-microsphere uptake and blood flow throught the tibia of female rats, increased after oophorectomy (OOX, performed four weeks prior to the experiment), was significantly suppressed to the level in sham-operated animals. In the experiment B, L-NAME was administered in the food in concentration of 0.05% for two weeks prior to the experiment. 85Sr-microsphere uptake was decreased significantly after L-NAME in the tibia of sham-operated females, in the tibia and distal femur of OOX animals; no significant changes were found in the diaphysis of femur and in calvaria. Blood flow values were significantly decreased in all bone samples of OOX females and in tibia of sham-operated rats (besides the local reaction also due to the decrease in the cardiac output). In both experiments the cardiac output was decreased and blood pressure elevated after L-NAME. It can be concluded, from the results of both experiments, that the blockade of EDRF-NO production by L-NAME decreases local circulatory values in the bones of female rats-particularly OOX-in a similar way as methylene blue; however, in contrast to methylene blue, L-NAME induces marked increase in the blood pressure and partially decrease in the cardiac output. Thus, as in the case of methylene blue, the effect of L-NAME on the circulation of blood in the rat bones supports the hypothesis of the participation of EDRF-NO in bone blood flow regulations.

In a short communication we demonstrated the inhibitory affect of acetylosalicylic acid (ASA) on the increased bone blood flow and 45Ca and 3H-proline incorporation in oophorectomized (OOX) female rats. This finding suggested probable participation of prostaglandin. The aim of the present work was to confirm and extend the initial observation and to find out, whether the administration of ASA did not affect also the decrease in the bone blood flow after the administration of estradiol benzoate (EB). Local blood flow was determined by means of the uptake of 85Sr-microspheres. In experiment A (females) the local circulatory values were increased after OOX significantly in tibia and distal femur, insignificantly in diaphysis of the femur and calvaria; this increase after OOX was suppressed by simultaneous administration of ASA completely in tibia, partially (and statistically insignificantly) in distal femur and diaphysis of the femur; no effect of ASA could be demonstrated in the calvaria. The blood flow through the kidneys of OOX female rats was decreased after ASA, while no change occurred in muscle and skin. The bone mineral content was significantly lower in both groups of OOX females. In experiment B (males), we observed an increase in local circulatory values after ORX in tibia, distal femur and diaphysis of the femur and suppression of this increase by the administration of ASA. These changes were not demonstrable in the calvaria and soft tissues studied. In experiment C (females), we found that significant decrease in the local circulatory values in the tibia after 4 weeks of administration of EB was not altered by simultaneous administration of ASA. Experiment D (females) proved again that 24 hour incorporation of 45Ca and 3H-proline was markedly suppressed by the administration of ASA not only in OOX females but also in sham operated control rats. Thus, the present results confirm the inhibitory effect of ASA on the increase in bone blood flow after castration, indicating with high probability participation of prostaglandin (PGE2?) (while no effect of ASA could be demonstrated on the decrease in bone blood flow after EB). The described blood flow changes are induced by local vascular reactions and occur in the bones of both female and male rats. Marked suppression by ASA of 45Ca and 3H-proline incorporation supports the circulatory results and indicates an important interconnection between metabolic processes and local circulation in the bone. We conclude that prostaglandin may be one of the factors regulating bone blood flow.

In the experiments on rats, the bone blood flow may be influenced by the deficiency as well by the administration of sex hormones. The aim of this work was to investigate the bone circulation (determined by means of 85Sr-microspheres, experiment A and B) and the incorporation of 45Ca and 3H-proline into the tibia (experiment C) in the last stage of pregnancy (from 18 to 21 days), i.e. in the physiological condition with elevated level of estrogens. In the experiment A and B, the uptake of 85Sr-microspheres and blood flow in pregnant rats was lower in the tibia and distal femur, the blood flow only was significantly lower also in the humerus and the calvaria. In kidneys, liver, muscle and skin, there was no difference in microsphere uptake; the blood flow was in pregnant females lower only in the kidneys. In perirenal fat, the microsphere uptake and blood flow was several times higher in pregnant rats than in controls. 24 hour incorporation of 45Ca and 3H-proline was in pregnant females significantly lower. The bone density and ash weight was higher in pregnant rats in experiment A. Estradiol concentration in plasma was in experiment B in pregnant rats significantly higher (by 24.8%). Thus, in pregnant female rats, we found lower bone blood flow and lower incorporation of 45Ca and 3H-proline along with normal or higher bone mineral content in the condition, where enhanced resorption and formation of the bone had been described. The changes in bone blood flow and possible role of estrogens in this situation remain to be elucidated.

Background: Insulin resistance and hypertriacylglycerolaemia are part of the X syndrome and are supposed to be interrelated. The objective of the present trial was to evaluate the impact of hypolipidaemic treatment on the action of insulin evaluated by means of a so-called hyperinsulimaemic clamp and by examination of insulin receptors., Methods and Results: To eight type 2 diabetics with mild hypertriacylglycerolaemia for three months ethophylline clofibrate (Duolip) was administered and for three months phenofibrate (Lipanthyl). Before and during treatment parameters of diabetes compensation were examined (blood sugar level, fructosamine and glycolysate haemoglobin), insulin sensitivity, using an isoglycaemic hyperinsulinaemic clamp and insulin receptors on red blood cells. Lipanthyl caused a more marked drop of triacylglycerol (by 46%) than Duolip forte (by 20%). Hypolipidaemic treatment did not affect diabetes compensation. As compared with healthy subjects, in diabetics before treatment a reduced insulin sensitivity was found, evaluated either by the index of insulin sensitivity (24.0 +/- 0.8, as compared with 35.5 +/- 4.9 mumol/kg/min per mU/l x 100, p < 0.05) or metabolic glucose clearance (3.7 +/- 0.9, as compared with 6.3 +/- 1.0 ml/kg/min, p < 0.01) and a slightly reduced insulin bond with receptors (p < 0.05). Duolip treatment led to a drop of insulin sensitivity and concurrent rise of affinity of insulin receptors (p < 0.01), while Lipanthyl was not manifested by marked changes. The authors did not find a significant correlation between the drop of triacylglycerol levels and insulin sensitivity in different types of treatment, which obviously is due to the small number of examinations., Conclusions: Therapy with ethophylline clofibrate of fenofibrate was not manifested in type 2 diabetics by a changes in the compensation of the disease. Hypertriacylglycerolaemia exists as an independent factor which is rather the consequence than cause of insulin resistance.

Published "normal" values of some hormones have an excessively wide range and unequal mean values because the material on which these values are based is from subjects suffering from different diseases which only apparently are not associated with the investigated hormone, or else the specimens are obtained under non-standard conditions (malnutrition, stress, alcohol etc.). This wide range of normal values may hide incipient pathological processes and is not suitable even as control group. The investigation is based on the assessment of insulin, growth hormone (GH), cortisol, thyroxine (T4) and triiodothyronine (T3) in a group of blood donors. The assembled results were compared with two other groups of blood donors and a group of obese subjects. The following findings were assembled: We recommend to lower the upper borderline of "normal" insulinaemia from the recommended value of 26 to 20 i.u./l, as the original range may comprise milder forms of hyperinsulinism which is recently assumed to participate in the genesis of type 2 diabetes, hypertension, coronary ischemia and polycystic ovaries. Elevated normal values of serum insulin may be obtained also from blood donors who usually have breakfast before the blood is collected. The wide range of cortisolaemia is due to the diurnal rhythm. The basal value is raised by a declining blood sugar level, alcohol, obesity and of course, varying forms of stress. The upper range of cortisolaemia at 8 a.m. should not be beyond the range of 140-690 nmol/l. GH secretion is governed by an individual 3.5-hour cycle as well as changes of the blood sugar level, e. g. during the OGTT: the declining blood sugar level raises the GH level.(ABSTRACT TRUNCATED AT 250 WORDS)

Using continual Doppler sonography, the authors measured the highest systolic blood flow rate in the extracranial carotid bloodstream in 3 groups of non-cardiac patients of an average age of 22, 76 and 93 years. In each group, the arteria carotis communis showed, with increasing age, a decrease in the highest systolic rate: 0.692 +/- 0.084 - 0.414 +/- 0.073 - 0.297 +/- 0.031 m/s (p less than 0.01 in all the three groups). Equally, a decrease in the highest systolic rate was found in the arteria carotis interna: 0.506 +/- 0.071 - 0.298 +/- 0.064 - 0.211 +/- 0.10 m/s (p less than 0.01 in all 3 groups). The paper shows a statistically significant decrease in the systolic blood rate in the carotid bloodstream related to aging (p less than 0.01) and discusses causes of this phenomenon.