Disparity between two-dimensional echocardiographic and electroanatomic left and right atrial volumes in patients undergoing catheter ablation for long-standing persistent atrial fibrillation.

Left atrial (LA) volume (LAV) is used for the selection of patients with atrial fibrillation (AF) to rhythm control strategies. Calculation of LAV from the LA diameters and areas by two-dimensional (2D) echocardiography may result in significant error. Accuracy of atrial volume assessment has never been studied in patients with long-standing persistent AF (LSPAF) and significant atrial remodeling. This study investigated correlation and agreement between 2D echocardiographic (Simpson method) and electroanatomic (CARTO, Biosense Webster) left and right atrial (RA) volumes (LAV(ECHO) vs. LAV(CARTO) and RAV(ECHO) vs. RAV(CARTO)) in patients undergoing catheter ablation for LSPAF. The study enrolled 173 consecutive subjects (females: 21 %, age: 59+/-9 years). There was only modest correlation between LAV(ECHO) (92+/-31 ml) and LAV(CARTO) (178+/-37 ml) (R=0.57), and RAV(ECHO) (71+/-29 ml) and RAV(CARTO) (173+/-34 ml) (R=0.42), respectively. LAV(ECHO) and RAV(ECHO) underestimated LAV(CARTO) and RAV(CARTO) with the absolute bias (+/-1.96 standard deviation) of -85 (-148; -22) ml and -102 (-169; -35) ml, respectively, and with the relative bias of -48 (-75; -21) % and -59 (-88; -30) %, respectively (all P<0.000001 for their mutual difference). Significant confounders of this difference were not identified. In patients with LSPAF, 2D echocardiography significantly underestimated both LA and RA volumes as compared with electroanatomic reference. This disagreement was independent of clinical, echocardiographic and mapping characteristics.

Distribution of mean cycle length in cavo-tricuspid isthmus dependent atrial flutter.

Although cycle length (CL) constitutes a fundamental descriptor of any arrhythmia, there is not larger study describing mean CL in electrophysiologically confirmed cavo-tricuspid isthmus (CTI)-dependent atrial flutter (AFL). We analyzed retrospectively digital recordings of 121 patients (98 men; age 64+/-11 years) referred for radiofrequency ablation of persistent CTI-dependent AFL. Median of mean AFL CL was 240 ms (interquartile range (IQR) of 222-258 ms, overall range of 178-399 ms). The distribution of CL was not normal (Shapiro Wilk test, p<0.001). Both counterclockwise and clockwise (14.9 % of all cases) AFLs were comparable in their CL; 240 (IQR 222-258) ms vs. 234 (217-253) ms, respectively. AFL CL<200 ms and AFL CL<190 ms was noticed in 5 (4.1 %) and 3 cases (2.5 %), respectively. In multivariate regression analysis, age (increase by 6+/-3 ms per decade of age, p=0.036), treatment with specific antiarrhythmic drugs (increase by 11+/-6 ms, p=0.052) and the history of cardiac surgery (increase by 26+/-9 ms, p=0.004) were independently associated with AFL CL. In conclusions, the distribution of AFL CL is not normal. The prevalence of AFL with short CL is low. Short CL<200 ms does not rule out the CTI-dependent AFL, especially in young and otherwise healthy patients.

Relation of central and brachial blood pressure to left ventricular hypertrophy. The Czech Post-MONICA Study.

Central blood pressure (BP) has been shown to be a better predictor of target organ damage and cardiovascular events than brachial BP. Whether central BP is a better predictor of left ventricular hypertrophy (LVH) determined by electrocardiography (ECG) is not known. Radial applanation tonometry and ECG were performed in 728 subjects from the Czech Post-MONICA Study (a randomly selected 1% population sample). LVH was determined using the Sokolow-Lyon index and Cornell product; central pressure was derived from radial pulse. Of 657 subjects included in the analysis, 17 (9.4%) below 45 years and 43 (9%) over 45 years had LVH. In multiple linear regression analysis, the Sokolow-Lyon index in younger individuals was only associated with male sex and low BMI, with no association with BP found. In older individuals, LVH was associated with higher central and brachial BP. In separate binary logistic regression analyses adjusted for covariates, the odds ratio for central systolic pressure was higher than those for brachial systolic and pulse pressure in LVH prediction. Noninvasively determined central pressure in subjects over 45 years is more strongly related to ECG LVH than brachial pressure. This further supports a closer association of central pressure with target organ damage. Voltage criteria of LVH are not independently associated with central or brachial BP in younger individuals.

The prevalence of metabolic syndrome and its components in two main types of primary aldosteronism.

Metabolic syndrome (MS) is frequent clinical condition in patients with hypertension. Primary aldosteronism (PA) is a common form of secondary hypertension. This study was aimed at investigating the prevalence of the MS and its components in the two major forms of PA, in unilateral aldosterone-producing adenoma (APA) and bilateral aldosterone overproduction because of idiopathic hyperaldosteronism (IHA). The diagnosis of the particular form of PA was based on adrenal venous sampling and/or successful surgery confirmed by histopathological examination. We analyzed clinical and laboratory data from 100 patients with PA (50 patients with IHA and 50 patients with APA) and from 90 patients with essential hypertension (EH). Metabolic profiles of patients with bilateral form of PA (because of IHA) were similar to EH, but differed from those in patients with unilateral form of PA (APA). The prevalence of the MS (62% in IHA, 34% in APA and 56% in EH), the body mass index value (30±4 kg m(-2) in IHA, 27±5 kg m(-2) in APA and 29±5 kg m(-2) in EH) and triglycerides levels (1.9±0.9 mmol l(-1) in IHA,1.4±0.8 mmol l(-1) in APA and 2.01±1.39 mmol l(-1) in EH) were all significantly (P<0.05) higher in IHA compared with APA patients. Metabolic profile of patients with bilateral form of PA (because of IHA) is similar to EH in contrast to unilateral form of PA (APA).

Increased carotid intima-media thickness in patients with pheochromocytoma in comparison to essential hypertension.

Catecholamines due to various mechanisms may contribute to the accumulation of collagen fibers and extracellular matrix in the arterial wall. The aim of this study was to compare intima-media thickness (IMT) of the common carotid artery (CCA) and carotid bifurcation (CB) in patients with pheochromocytoma, essential hypertension and healthy controls. Carotid ultrasound studies were carried out in 30 patients with pheochromocytoma matched for age and gender with 80 patients with essential hypertension and 40 normotensive controls. Significantly higher IMT was found in patients with pheochromocytoma and essential hypertension compared to controls when measured in the CCA (0.931+/-0.223, 0.825+/-0.146 and 0.738+/-0.113 mm; P<0.001; P<0.05), and only in patients with pheochromocytoma compared to controls in the region of CB (1.359+/-0.593, 1.095+/-0.311 and 0.968+/-0.247 mm; P<0.001; P=0.13). Higher IMT in patients with pheochromocytoma compared to patients with essential hypertension was also statistically significant in both carotid regions (both P<0.01). This difference remained significant after adjustment for all relevant clinical and biochemical covariates in the CCA (P=0.014) but disappeared in the region of CB (P=0.079). In summary, patients with pheochromocytoma have increased common carotid IMT when compared to patients with essential hypertension. This finding could be caused by the deleterious effects of the excess of catecholamines on the vascular wall growth and thickening.

A new approach to automated assessment of fractionation of endocardial electrograms during atrial fibrillation.

Complex fractionated atrial electrograms (CFAEs) may represent the electrophysiological substrate for atrial fibrillation (AF). Progress in signal processing algorithms to identify sites of CFAEs is crucial for the development of AF ablation strategies. A novel algorithm for automated description of fractionation of atrial electrograms (A-EGMs) based on the wavelet transform has been proposed. The algorithm was developed and validated using a representative set of 1.5 s A-EGM (n = 113) ranked by three experts into four categories: 1-organized atrial activity; 2-mild; 3-intermediate; 4-high degree of fractionation. A tight relationship between a fractionation index and expert classification of A-EGMs (Spearman correlation rho = 0.87) was documented with a sensitivity of 82% and specificity of 90% for the identification of highly fractionated A-EGMs. This operator-independent description of A-EGM complexity may be easily incorporated into mapping systems to facilitate CFAE identification and to guide AF substrate ablation.

Relationship between clinical, 24-hour, average day-time and night-time blood pressure and measures of arterial stiffness in essential hypertension.

Arterial wall stiffness is considered an independent cardiovascular risk factor. Aim of this study was to evaluate relationship between clinical, 24-hour, average day-time and night-time blood pressure (BP) and measures of arterial stiffness assessed by pulse wave velocity (PWV) (using SphygmoCor applanation tonometer) in essential hypertension (severe-resistant (RH, n=29) and moderate hypertension (EH, n=35)) and in normotensive control subjects (n-29) (NCS) matched by age. After multiple regression analysis, PWV remains significantly correlated mainly with night-time pulse pressure and to a lesser extent with age. PWV was significantly higher in RH compared to moderate EH and NCS.

[Conventional treatment of atrial fibrillation in the Czech Republic managed by outpatient cardiologists. Overview of diagnostic and treatment procedures, pharmacological treatment and hospitalisation]. / Konvencní lécba fibrilace síní rízená ambulantními kardiology v CR: prehled diagnostických a lécebných výkonu, medikamentózní lécby a hospitalizací.

OBJECTIVE: The aim of the study was to analyse general health data, diagnostic and therapeutic procedures, pharmacological treatment and hospitalization of patients with atrial fibrillation (AF) who did not undergo AF catheter ablation and were in the care of outpatient cardiologists. METHOD: Data concerning 306 patients (of which 94 women, aged 64 +/- 11 years) for the preceding 2 years were acquired through a questionnaire containing a set of standardized questions on a simple form sent out to outpatient cardiologists. RESULTS: AF was paroxysmal, persistent or permanent in 141 (46%), 77 (25%) or 88 (28%) patients, respectively. The higher the age, the lower the proportion of paroxysmal AF and the higher the proportion of the permanent form of AF. AF was asymptomatic in 122 (39%) of patients. The most frequent among cardiovascular diseases was hypertension, detected in 220 patients (72%), IHD was present in 83 patients (27%). The mean LV EF was 55 +/- 11% and was significantly lower in patients with permanent AF than in patients with paroxysmal AF (phi 51 +/- 13% vs. phi 58 +/- 9%, P < 0,001). The mean left atrium transversal diameter was 47 +/- 7 mm and was significantly higher in patients with permanent AF than in those with paroxysmal AF (50 +/- 8 mm vs. 44 +/- 6 mm, P < 0,001). 230 patients (75%) received anticoagulation treatment and 43 patients (14%) received antiaggregation treatment. 274 patients (90%) were taking antiarrhythmic drugs (AA); 93 patients were taking 1, 168 patients 2 and 13 patients 3 AA drugs. 167 patients (55%) underwent electrical cardioversion in 362 procedures, 106 patients (35%) underwent pharmacological cardioversion in 239 procedures. Coronarography was performed in 79 patients (26%) of which 59 (75%) had normal results for coronary arteries. Pacemaker due to concomitant sinus node dysfunction was implanted to 27 patients (9%). Ablation for concomitant atrial flutter of type I was performed in 42 patients (14%). AF and associated conditions caused 250 hospitalisations in 144 patients (47%). The average length of hospitalisation was 4.2 +/- 3.2 days. Cardioembolic event was the cause of hospitalisation of 25 patients (8%) out of 29 hospitalisations with the mean length of hospital stay 8.2 +/- 2.9 days. CONCLUSION: The study has shown, in the first place, very high standards of anticoagulation and antiarrhythmic treatment. It has also shown a relatively frequent indication for coronarography, pacemaker implant for relative sinus node dysfunction or ablation for concomitant atrial flutter of type I, i.e. intervention procedures with limited benefit for AF patients.

Hyperlipidemia is associated with altered levels of insulin-like growth factor-I.

Previous studies revealed altered levels of the circulating insulin-like growth factor-I (IGF-I) and of its binding protein-3 (IGFBP-3) in subjects with coronary atherosclerosis, metabolic syndrome and premature atherosclerosis. Hyperlipidemia is a powerful risk factor of atherosclerosis. We expected IGF-I and IGFBP-3 alterations in subjects with moderate/severe hyperlipidemia but without any clinical manifestation of atherosclerosis. Total IGF-I and IGFBP-3 were assessed in 56 patients with mixed hyperlipidemia (MHL; cholesterol >6.0 mmol/l, triglycerides >2.0 mmol/l), in 33 patients with isolated hypercholesterolemia (IHC; cholesterol >6.0 mmol/l, triglycerides <2.0 mmol/l), and in 29 healthy controls (cholesterol<6.0 mmol/l, triglycerides<2.0 mmol/l). The molar ratio of IGF-I/IGFBP-3 was used as a measure of free IGF-I. IHC subjects differed from controls by lower total IGF-I (164+/-60 vs. 209+/-73 ng/ml, p=0.01) and IGF-I /IGFBP-3 ratio (0.14+/-0.05 vs. 0.17+/-0.04, p=0.04). Compared to controls, MHL subjects had lower total IGF-I (153+/-54 ng/ml, p=0.0002) and IGFBP-3 (2.8+/-0.6 mg/ml, p<0.0001), but higher IGF-I/IGFBP-3 ratio (0.25+/-0.06, p<0.0001). Differences remained significant after the adjustment for clinical and biochemical covariates, except for triglycerides. Patients with both IHC and MHL have lower total IGF-I compared to controls. The mechanism is presumably different in IHC and MHL. Because of prominent reduction of IGFBP-3 in patients with MHL, they have reduced total IGF-I despite the actual elevation IGF-I/IGFBP-3 ratio as a surrogate of free IGF-I.

Impact of essential hypertension and primary aldosteronism on plasma brain natriuretic peptide concentration.

INTRODUCTION: Brain natriuretic peptide (BNP) has important role in the diagnosis and management of heart failure. Data on the impact of blood pressure (BP) on BNP are controversial. In primary aldosteronism (PA), BNP production can be affected by both hypertension and specific endocrine mechanisms. This study was aimed at investigating the impact of hypertension and hyperaldosteronism on plasma BNP levels. METHODS: Plasma BNP concentration, casual and 24-h BP and echocardiographic indices were assessed in 40 patients with moderate to severe essential hypertension (EH), 40 BP-matched patients with PA, and 40 age- and sex-matched healthy controls. RESULTS: BNP levels in PA and EH groups did not differ significantly and were higher compared with those in controls [median and interquartile range 26 (13-48) pg/ml, p = 0.01, and 23 (9-32) pg/ml, n.s., vs 14 (6-26) pg/ml in controls]. Remarkably elevated BNP was observed only in three PA and two EH patients, all having significant left ventricular (LV) hypertrophy. BNP levels in PA and EH groups correlated weakly with casual and 24-h BP, interventricular septal thickness and LV mass index (LVMI). Diastolic BP and LVMI were identified as the strongest independent determinants of BNP (p = 0.002 and p = 0.01, respectively). CONCLUSIONS: Both PA and EH patients had modest and mutually comparable elevation of BNP, which was independently determined by diastolic BP and LVMI. Both subtypes of PA (aldosterone-producing adenoma and bilateral adrenal hyperplasia) had similar effect on BNP production. Specific impact of hyperaldosteronism on BNP was not confirmed.

Second derivative of the finger arterial pressure waveform: an insight into dynamics of the peripheral arterial pressure pulse.

The study investigated second derivative of the finger arterial pressure waveform (SDFAP) in 120 healthy middle-aged subjects and in 24 subjects with essential hypertension. SDFAP consists of 5 sequential waves 'a'-'e'. Their normalized magnitudes (B/A, C/A, D/A, and E/A) were calculated. In multivariate regression analysis, B/A and C/A correlated only with age. D/A independently correlated with age, heart period, mean blood pressure (MBP), body height, and gender. E/A independently correlated with age and MBP. D/A and E/A were higher (0.42+/-0.16 vs. 0.33+/-0.14, p = 0.05 and 0.63+/-0.15 vs. 0.45+/-0.14, p < 0.001), while B/A and C/A were lower (1.04+/-0.16 vs. 1.20+/-0.17, p = 0.002 and 0.09+/-0.15 vs. 0.26+/-0.20, p = 0.001) in hypertensives compared to sex- and age-matched controls. After the adjustment for MBP, heart period, and body mass index (ANCOVA), independent discriminative power was preserved only for indices B/A and C/A (p = 0.001 and 0.021, respectively). Therefore, B/A and C/A provide additional information about simple clinical characteristics and might reflect the structural alteration of the arterial wall in hypertensive subjects.

[Heart rate turbulence--a new ECG predictor for risk of sudden death]. / Turbulence srdecní frekvence--nový EKG prediktor rizika náhlé smrti.

Heart Rate Turbulence (HRT) is a newly described physiological chronotropic response of sinus rhythm following a single ventricular premature beat (VPB) consisting of early acceleration and later deceleration of heart rate. Using two large independent cohorts of postinfarction patients, the absence of HRT was retrospectively validated to be a potent multivariate risk predictor, stronger than a number of currently available risk stratifiers. Although exact pathophysiological mechanism of HRT remains speculative, it is now believed that HRT arises from the haemodynamic changes and baroreceptor reflexes that occur following a VPB. Therefore, HRT descriptors (Turbulence Onset and Turbulence Slope) may serve as very reasonable, Holter--based surrogates of baroreflex sensitivity available in clinical practice. The aim of this review is to summarise the current knowledge on pathophysiological mechanisms of HRT and to discuss practical problem of its detection.

Both fenofibrate and atorvastatin improve vascular reactivity in combined hyperlipidaemia (fenofibrate versus atorvastatin trial--FAT).

OBJECTIVE: It has been repeatedly proven that statins improve endothelial function in isolated hypercholesterolaemia but there is far less evidence in the case of combined hyperlipidaemia. Studies assessing the effects of fibrates on endothelium have been neglected. Therefore, we conducted a trial in which the effects of fenofibrate and atorvastatin monotherapy on both endothelium-dependent vascular reactivity and biochemical parameters were compared in patients with combined hyperlipidaemia. METHODS: 29 otherwise healthy males (aged 47.4+/-7.8 years) with combined hyperlipidaemia (total cholesterol 7.55+/-1.20 mmol/l, triglycerides 5.41+/-4.54 mmol/l) were included into the randomised, single-blind, cross-over study to receive either 200 mg of micronised fenofibrate or 10 mg of atorvastatin daily--each of the drugs for a period of 10 weeks. Analysed biochemical parameters were as follows: serum total-, LDL- and HDL-cholesterol, apolipoproteins A-I and B, triglycerides, fibrinogen, uric acid, C-reactive protein (CRP), insulin, and homocysteine. Endothelial function was investigated by duplex Doppler ultrasonography at the brachial artery. Two indices of endothelial-dependent postischaemic changes were used - the recently introduced index of peak blood flow (PBF) representing the level of reactive hyperaemia and traditional flow-mediated dilatation (FMD). RESULTS: We observed a small improvement in FMD after both fenofibrate and atorvastatin (from 2.26% to 2.98% and 2.87%, respectively; NS). PBF increased from 448 ml/min to 536 ml/min after fenofibrate (P=0.04) and to 570 ml/min after atorvastatin (P=0.03). The effects of both fenofibrate and atorvastatin on endothelial function did not differ significantly (P-values of 0.82 and 0.47 for FMD and PBF, respectively). Significant correlations (P<0.01) between the changes of vascular reactivity and biochemical indices were found between FMD and CRP (r=-0.60) and between both FMD and PBF, and insulinaemia (r=-0.48 and -0.56, respectively) only during treatment with fenofibrate. CONCLUSIONS: Both fenofibrate and atorvastatin significantly improved endothelium-dependent vascular reactivity without mutual difference. The PBF was superior to FMD for the detection of this improvement. The beneficial effect of both drugs did not correlate with the change of lipid profile during therapy. The improvement of vascular reactivity during treatment with fenofibrate (opposed to atorvastatin) was related to the reduction of indirect marker of chronic vessel wall inflammation and of insulin resistance. The PBF was more reproducible than FMD because of considerably lower intra-subject variability.

Cross-spectral analysis of heart rate and blood pressure modulations.

The cross-spectral analysis of heart rate (HR) and blood pressure (BP) variabilities provides "amplitude" and "phase" related measures. Compared to the amplitude measure, that is the baroreflex gain, the phase related measure characterizing the time lag between HR and BP oscillations has been studied to a much lesser extent. A population of 103 patients (73 men, 30 women, aged 53 +/- 12, range 20-82 years) referred for the management of coronary artery disease and/or hypertension were studied. In each subject, electrocardiogram and BP recordings were obtained in the supine and sitting positions of 5 minutes of rest (spontaneous respiration), 3 minutes of controlled respiration at 0.1 Hz (slow-controlled respiration), and 3 minutes of controlled respiration at 0.33 Hz (fast-controlled respiration). The frequency of maximum coherence (above the arbitrary threshold of 0.5) of BP and RR interval variabilities was searched between 0.033-0.133 Hz and 0.200-0.400 Hz to obtain baroreflex gain and phase shift in low and high frequency bands, respectively. Mean phase shifts of -79.1 and -67.0 degrees (-2.4 and -2.1 s) were found during slow-controlled respiration in the supine and sitting body positions, respectively. The mean phase shift between systolic BP and RR interval in the low frequency band was found between 83 and -109 degrees for body positions and respiration regimes. The actual baroreflex related time lag between systolic BP and RR variations was found between 3.5 and 5.1 seconds. The study concludes that the appropriate, and not always easy, selection of the frequency of maximum coherence between BP and HR oscillation is crucial for an accurate cross-spectral assessment of baroreflex sensitivity.

[Function and dysfunction of the endothelium]. / Funkce a dysfunkce endotelu.

Endothelium is a multi-functional barrier separating blood from interstitium. It plays a role in coagulation, inflammation, angiogenesis and it has vasomotor functions. The endothelial dysfunction can be considered as an initial stage of atherosclerosis. Using morphological and biochemical methods it is possible to study the influence of cardiovascular risk factors on the vessels and the effect of therapeutic interventions. A short review of endothelial functions, endothelial dysfunction and its quantification methods is presented in this article.

Stability of the noninvasive baroreflex sensitivity assessment using cross-spectral analysis of heart rate and arterial blood pressure variabilities.

BACKGROUND: Depressed baroreflex sensitivity (BRS), usually estimated using the invasive phenylephrine method or the nitroprusside test, is significantly and independently associated with an increased risk of malignant ventricular arrhythmias and sudden cardiac death in patients surviving acute myocardial infarction. Several investigators have compared the standard phenylephrine test and different noninvasive methods. HYPOTHESIS: This study evaluated the influence of different body positions with different breathing regimes on cross-spectral baroreflex indices (coherence between the spectral densities of blood pressure and cardiac cycle variabilities) in both low- and high-frequency bands. METHODS: The data were obtained in 103 patients (73 males, aged 53 +/- 12 years) with coronary artery disease and/or hypertension. Simultaneous electrocardiographic and noninvasive blood pressure recordings were obtained in each subject in both supine and sitting positions during both spontaneous and slow and fast controlled respiration (0.1 and 0.33 Hz). RESULTS: The results show a significant bias and disagreement between noninvasive baroreflex sensitivity (BRS) indices. The mean values of the baroreflex in low frequency ranged from 5.0 +/- 5.3 to 10.1 +/- 7.9 ms/mmHg, while in high frequency, the mean values ranged from 6.6 +/- 6.1 to 10.1 +/- 7.9 ms/mmHg. The limits of agreement ranged from +/-1.7 to +/-4.1 ms/mmHg with bias from -1.0 to +0.7 ms/mmHg. CONCLUSION: A comprehensive comparison of different methods shows that BRS estimated in low-frequency band in sitting position during spontaneous respiration is the most representative part of the global baroreflex gain.

[Familial hyperlipoproteinemias--correlations between phenotypes and genotypes]. / Familiární hyperlipoproteinémie--korelace nálezu ve fenotypu s genotypem.

Within the grant project patients with familial hyperlipoproteinaemias have been examined. The examination was performed in the oldest lipid clinic and research laboratory in the world. The classification of lipid metabolism disorders was based upon a detailed biochemical analysis of plasma lipids including electrophoresis and assessment of apolipoprotein levels. Then optimal treatment regimen could be established. The project was aimed to evaluate the efficacy of different treatment regimens in different types of hyperlipoproteinaemias. Biochemical parameters and mainly the impact of treatment of hyperlipoproteinaemia on morphology and function of the vessel wall was monitored. The non-invasive ultrasound measurement of the intima thickness of carotid arteries was used. For more precise diagnosis of genetically determined disorders of lipid metabolism a large scale of methods of molecular biology was introduced. These methods enable confirmation of familial hypercholesterolaemia, familial defective apolipoprotein B-100 or studying polymorphism of apolipoprotein E. The effort of the authors of the project was to maximally utilise the results of basic and applied research in formulating recommendations for everyday practice of physicians.

[Anti-insulin antibodies and insulin resistance]. / Antiinzulinové protilátky a inzulinorezistence.

The submitted review deals with the phenomenon of immunological insulin resistance in insulin dependent diabetics which develops as a result of the presence of circulating anti-insulin antibodies as a response of the organism to administered insulin. This phenomenon is a liminal situation when anti-insulin antibodies exceed as to their concentration and affinity a certain arbitrary limit and the increasingly impaired pharmacokinetics of insulin cause a clinically manifest metabolic decompensation of the disease with the necessity of large daily doses of exogenous insulin. The authors discuss factors ensuing from the type of the administered insulin preparation, as well as the biological predisposition of the patient which potentiates the production of anti-insulin antibodies. Some laboratory methods are discussed which are used for the assessment of anti-insulin antibodies in vitro and the authors summarize individual physical variables which characterize the antibody system and which can be extracted by special mathematical procedures from experimental radioimmunoanalytical data. Only a detailed characterization of the antibody system makes it possible to evaluate the influence of this system on the pharmacokinetics of insulin.

[The effect of Proglicem in patients with an organic hyperinsulinism syndrome]. / Efekt Proglicemu u nemocných se syndromem organického hyperinzulinismu.

BACKGROUND: Organic hyperinsulinism is treated as a rule conservatively with diazoxide (Proglicem) which has a hyperglycaemic effect. In some patients, however, treatment fails and severe hypoglycaemia persists. The objective of the present investigation was to find simple criteria for evaluation of the aptness (effectiveness) of this treatment. METHODS AND RESULTS: In 11 patients with a confirmed insulinoma Proglicem was administered for five days (3 mg/kg body weight) and serum insulin and the blood sugar level as well as their ratio (IRI:G) were followed-up. In eight patients the IRI/G coefficient declined from 10.5 +/- 7.7 to 5.8 +/- 2.9 (p < 0.001); only in three patients the coefficient increased from 4.6 +/- 2.9 to 14.9 +/- 12.3 (p < 0.001). Coefficient "k" from the modified Bergman model for the intravenous glucose tolerance test had identical results; there was statistically significant agreement between the two examinations. CONCLUSIONS: To assess the effectiveness of diazoxide treatment (Proglicem) on hypoglycaemia in nesidiomas it is sufficient to evaluate the IRI/G coefficient (on fasting) before and during diazoxide treatment (Proglicem, Schering Corp.).