Extracorporeal immunoglobulin elimination for the treatment of severe myasthenia gravis.

Myasthenia gravis (MG) is a neuromuscular disorder leading to fluctuating muscle weakness and fatigue. Rarely, long-term stabilization is not possible through the use of thymectomy or any known drug therapy. We present our experience with extracorporeal immunoglobulin (Ig) elimination by immunoadsorption (adsorbers with human Ig antibodies). Acetylcholine receptor antibodies (AChRAs) were measured during long-term monitoring (4.7 +/- 2.9 years; range 1.1-8.0). A total of 474 samples (232 pairs) were analyzed, and a drop in AChRA levels was observed (P = .025). The clinical status of patients improved and stabilized. Roughly 6.8% of patients experienced clinically irrelevant side effects. The method of Ig elimination by extracorporeal immunoadsorption (IA) is a clinical application of the recent biotechnological advances. It offers an effective and safe therapy for severe MG even when the disease is resistant to standard therapy.

[Disadvantages of unilateral videothoracoscopic thymectomy]. / Nevýhody jednostranné videotorakoskopické tymektomie.

The authors highlight disadvantages of the unilateral videothoracic approach in thymectomy procedures. They present a case-review of a young female patient, indicated for the procedure for myastenia gravis. In these patients, the primary objective is to remove all the thymus tissue and the surrounding adipose tissue within the anterior mediastinum, which, using the above approach cannot always be guaranteed. Considering the number of patients indicated for the procedure based on the above diagnosis, it is inevitable to perform the procedures in specialized centres, experienced with these conditions.

[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.

[CRP--a marker of a pro-inflammatory state and cardiovascular risk]. / CRP--marker proinflamacního stavu a kardiovaskulárního rizika.

The importance of elevated basal levels C-reactive protein (CRP) measured by a highly sensitive test has been known for over 10 years. Increased hsCRP concentration correlates with most of the classical risk factors in cardiovascular disease, however. This seriously complicates the interpretation of the elevated concentration. Concentrations of hsCRP are partly genetically determined and can easily be affected positively by lifestyle changes. These two factors lead us to conclude that the setting of hsCRP should not be used routinely at present in assessing the individual risk of complications for atherosclerosis.

[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.

[CD14 (C-159-->T) polymorphism and levels of C-reactive protein]. / CD14 (C-159-->T) polymorfizmus a hladina C-reaktivního proteinu.

BACKGROUND: High plasma levels of C-reactive protein (involved in unspecific host defence) have been described as independent risk factor of atherosclerosis. The possible association has been analysed between the CD14C-159-->T polymorphism and plasma level of CRP. METHODS AND RESULTS: With the PCR and subsequent restriction analysis we have evaluated C-159-->T polymorphism in the CD14 gene of 166 representatively selected male Caucasians with known plasma level of CRP. The CRP was measured immunologically. A significantly higher (p < 0.01) frequency of the CD14-159TT homozygotes between the individuals with the plasma level of CRP > 2.19 mg/l (31.9%, 15 out of 47) has been detected when compared to the group with plasma level of CRP lower than 2.18 mg/l (11.9%, 5 out of 42). CONCLUSIONS: CD14 C-159-->T polymorphism could be the first described genetic marker associated with plasma level of C-reactive protein.

[Simvor in the treatment of hyperlipoproteinaemia]. / Simvor v lécbe hyperlipoproteinémie.

BACKGROUND: Treatment of hyperlipoproteinaemias (HLP) is a basic step in prevention and treatment of atherosclerosis and its complications. Simvastatin is among hypolipidaemic agents a preparation for which at present there is most evidence from intervention trials. On the Czech market are at present in addition to the original one also some other preparations of simvastatin. In the submitted paper the authors present results achieved with the preparation Simvor (Rambaxy, distribution in CR Interchemia), tablets containing 20 mg simvastatin. CHARACTERISTIC OF GROUP AND METHODS: In 15 departments in the CR a total of 185 patients with HLP were examined, 98 men and 87 women, mean age 55.8 years. The patients were treated after a minimal 4-week period of non-pharmacological treatment with simvastatin 20 mg for a period of 6 weeks. The patients were subjected at the onset and end of treatment to a complete medical examination, basic parameters of lipid metabolism were assessed and a safety laboratory was involved. Facultatively in some departments additional examinations were made. RESULTS: The total cholesterol level 7.26 +/- 1.01 mmol/l declined on average by 1.64 mmol/l i.e. to 5.62 mmol/l, LDL-cholesterol declined from the original value of almost 5 mmol/l to 3.55 mmol/l. The baseline triglyceride concentration 3.07 declined by 1 mmol/l to 2.09 mmol/l, and HDL-cholesterol which was in a normal range already at the onset of treatment did not change significantly, i.e. its slight increase did not reach statistical significance. Treatment was well tolerated and in the safety laboratory no significant deviations from normal were recorded. DISCUSSION: The results achieved in our patients are as far as the investigated parameters are concerned, comparable with or even better than the results presented in the ample literature. The safety and tolerance of treatment of the investigated preparation is also very good. Unfortunately we did not have an opportunity during our short-term follow up to evaluate the influence of the investigated preparation on the incidence of cardiovascular diseases or mortality. In this respect we can only refer to positive results assembled with simvastatin in large statin intervention "megatrials". CONCLUSION: Treatment with decline of total and LDL-cholesterol and triglycerides. Treatment was well tolerated by the patients, in the safety laboratory no significant deviations were detected.

Blood pressure, endothelial function and circulating endothelin concentrations in liver transplant recipients.

OBJECTIVES: To study candidates for liver transplant before and 6 weeks after transplant, and to elucidate the role of endothelial dysfunction and plasma endothelin concentrations in the development of hypertension. DESIGN PROSPECTIVE: follow-up study. SETTING: Institutional, outpatient. PATIENTS: and controls Fifteen patients (11 men, four women, mean age 46.7+/-13.2 years) with end-stage liver disease (ESLD) and healthy volunteers of comparable age and sex. METHODS: We performed office blood pressure readings and 24 h ambulatory blood pressure monitoring (ABPM), measurements of endothelial-dependent vasodilatation using high-resolution ultrasound in the brachial artery at rest and during reactive hyperemia, and plasma endothelin-1 assays 3 months before and 6 weeks after the transplant. RESULTS: Office systolic and diastolic blood pressures increased significantly 6 weeks after liver transplantation (from 116.6+/-14.1 to 139.9+/-19.5 mmHg and from 68.6+/-9.5 to 84.1+/-9.8 mmHg, respectively; both P < 0.001). Hypertension based on office blood pressure readings increased from 6.7 to 40% (P < 0.05). Mean 24 h systolic blood pressure increased from 118.7+/-10.3 to 140.0+/-19.0 mmHg (P < 0.001), mean 24 h diastolic blood pressure increased from 86.0+/-7.7 to 104.8+/-13.9 mmHg (P < 0.001) and heart rate increased from 74.8+/-10.2 to 80.2+/-8.2 beats/min (P < 0.05). Brachial artery flow-mediated dilatation did not change throughout the study (before transplant: 4.2+/-4.0%; after transplant: 6.3+/-5.4%; NS) and did not differ from that in controls (5.2+/-3.8%). Plasma endothelin-1 was increased in patients with ESLD (15.3+/-2.6 pg/ml) compared with controls (5.6+/-0.4 pg/ ml; P < 0.001) and remained unchanged 6 weeks after liver transplantation (14.1+/-3.7 pg/ml). CONCLUSION: Our results show increased blood pressure with suppressed circadian blood pressure variability in liver graft recipients 6 weeks after transplant and no change in endothelial function and plasma endothelin concentrations. Therefore, the blood pressure increase documented in our study cannot be explained by endothelial dysfunction. Twenty-four hour ABPM should be performed routinely in patients who have undergone liver transplant.

[Plasma level of Lp(a) in patients with myocardial infarct is not controlled by the apolipoprotein E gene polymorphism]. / Plazmatická koncentrace Lp(a) u pacientu s infarktem myokardu není ovlivnena polymorfizmem genu pro apolipoprotein E.

BACKGROUND: We evaluated a two risk factors of atherosclerosis development, apolipoprotein E genotype and plasma level of Lp(a), and their association in Czech population. PATIENTS AND CONTROLS: Apo E and Lp(a) have been determined in the group of 109 men with premature myocardial infarction and compared with the population samples (301 men for apo E polymorphism and 112 men for Lp(a) evaluation). METHODS AND RESULTS: Apo E gene polymorphism was analysed by PCR with subsequent restriction analysis of the PCR product. Lp(a) concentration was measured enzymatically using the IMMUNO set. The frequency of alleles of apo E genotype in myocardial infarction patients did not significantly differ from that found in the control group. The distribution of the Lp(a) concentrations in MI patients was shifted to higher levels than in population sample (p < 0.0001). CONCLUSIONS: We have not found correlation between this two risk factors of myocardial infarction. High concentration of Lp(a) is on apo E polymorphism independent risk factor of development of myocardial infarction.

[Development of smoking habits in the population of the Czech Republic from 1985 to 1997/98]. / Vývoj kuráckých zvyklostí obyvatelstva Ceské republiky v období 1985-1997/98.

BACKGROUND: Tobacco smoking belongs to high risk factors for the circulation diseases. Aim of the present study is to identify and describe smoking habits of the population in nine districts in Czech republic in years 1997/98 and in six of these districts to analyze smoking trends during the period of 1985-1997/98. METHODS AND RESULTS: Information on the smoking habits were collected in years 1985, 1988, and 1992 in six districts which took part in the international project WHO MONICA. In 1997/98 data collection was extended into three other districts. New randomly selected samples of 1% of the population were explored each time. 5293 males and 5610 females 25-64 years old were questioned during a controlled talk with a health-officer. In 1997/98 in nine districts the prevalence of actual smokers was 38%, that of former smokers was 24% and 38% of non-smokers. The group of females consisted of 27% of actual smokers, 10% of former smokers, and 63% of non-smokers. The average daily consumption was 16.4% (+/- 8.6) cigarettes per day in males and 11.3 (+/- 7.0) cigarettes per day in females. In 1985-1997/98 the smoking prevalence of males aged 25-64 years decreased in six districts from 49% to 37% (p < 0.001). No changes were detected in females of the same age group (28% in 1985, 26% in 1997/98). Decreasing tendency was observed in both males and females up to 45 years old, in males also in the age group 55-64 years. In females older than 45 years the smoking prevalence increased. Significant changes in the smoking prevalence were found when samples were analyzed according to the education level. In males with basic education and among skilled workers the smoking prevalence decreased in years 1985-1997 from 53% to 42% (p < 0.05), among males with secondary education smoking prevalence decreased from 45% to 33% (p < 0.01) and in graduates from 34% to 23% (p < 0.01). In females with basic education the smoking prevalence increased from 25% to 31% (p < 0.05), among females with secondary education it decreased from 34% to 21% (p < 0.001), in graduate females it decreased from 31% to 18% (p < 0.05). CONCLUSIONS: Present situation and 13 years long development of smoking habits differs in males and females. Higher prevalence was found in males as well as the daily consumption of cigarettes. Since 1985 the male smoking prevalence has decreased in age groups 25-64 years and in age and education level subgroups. Only partial decrease of the female smoking prevalence was observed in age group till 45 years and in subgroups with secondary education and graduates. Significant increase in the smoking prevalence among females with basic education as well as the finding that women do not quit smoking with increasing age my become an important information for preventive programmes.

High-dose immunosuppressive therapy with PBPC support in the treatment of poor risk multiple sclerosis.

High-dose immunoablative chemotherapy with autologous haematopoietic cell support might be beneficial in the treatment of intractable forms of MS. We mobilised PBPC in 11 patients with secondary progressive MS and finally eight patients were grafted after high-dose BEAM chemotherapy with either in vitro or in vivo T cell depletion. Median EDSS and SNRS scores at the time of inclusion were 6.5 (6.5-7.5) and 56 (44-65), respectively. PBPC mobilisation was safe with no serious adverse effects, and without significant aggravation of disability. One patient improved significantly (by 1.0 point on EDSS) after the mobilisation. Two mobilisation failures were observed. No life-threatening events occurred during the transplantation. All grafted patients, except one, at least stabilised their disability status. One patient improved significantly (by 1.5 points on EDSS), two patients improved slightly (by 0.5 points on EDSS), one patient worsened by 1.0 point on the EDSS in 10 months. Improvement occurred with a delay of 2-4 months. Median EDSS and SNRS of grafted patients at the last follow up were 6.5 (5.5-8.5) and 64 (39-73), respectively with median follow-up of 8.5 months. Further follow-up is needed to determine the disease course after complete immune reconstitution. Bone Marrow Transplantation (2000) 25, 525-531.

C(-260)-->T polymorphism in the promoter of the CD14 monocyte receptor gene as a risk factor for myocardial infarction.

BACKGROUND: The CD14 receptor of monocytes is an important mediator for the activation of monocytes/macrophages by endotoxins from the envelope of Gram-negative bacteria (lipopolysaccharides). We identified a polymorphism in the CD14 receptor and examined whether this genetic marker influenced the expression of the CD14 receptor on monocytes and affected the predisposition to myocardial infarction. METHODS AND RESULTS: We identified a C(-260)-->T nucleotide change, creating a HaeIII polymorphism in the promoter of the CD14 gene. The polymorphism was determined in 178 male patients <65 years old (cases; average age, 55.9+/-6.3 years) at the time of their first myocardial infarction and in 135 representative selected male control subjects (controls; average age, 55.2+/-11.5 years). The frequency of the T allele (absence of the cutting site) was 0.49 in cases and 0.35 in controls (P=0.0005; OR, 1.781; 95% CI, 1.286 to 2.465). Subsequently, we measured the expression of monocyte CD14 by flow cytometry in 18 volunteers with different CD14 genotypes. A significantly higher density of the CD14 receptor was shown in the T/T homozygotes than in the others (P=0.0028). CONCLUSIONS: A higher frequency of allele T(-260) in the promoter of the CD14 receptor gene was found in myocardial infarction survivors than in controls. At the same time, this variation was associated with a higher density of CD14 receptors in healthy volunteers. Therefore, we can conclude that in addition to the well-established risk factors, a genetically determined reaction of monocytes/macrophages to infectious stimuli could play an important role in the process of atherosclerosis.

Intima-media thickness of carotid arteries in borderline hypertensives.

The purpose of this study was to assess the effect of the main risk factors for cardiovascular disease on the process of subclinical atherosclerosis in originally borderline hypertensives. The relation of far wall common carotid artery intima-media thickness (IMT CCA) measured by B-mode ultrasound to smoking, body mass index (BMI), blood pressure, lipids, and angiotensin-converting enzyme (ACE) gene polymorphism was analyzed. In 48 subjects examined (mean age, 61.9 +/- 2.54 years), median IMT CCA was 0.708 mm. Statistically significant differences in BMI (26.5 vs. 29.2 kg/m2, p < 0.025) and HDL-cholesterol level (1.42 vs. 1.1 mmol/l, p < 0.025) between the first and third tertile of IMT CCA were found. No differences were observed between "controls" and "cases" in blood pressure, total cholesterol, and triacylglycerols. No significant differences in IMT CCA were found between smokers and nonsmokers and among different alleles of the ACE gene. These data reflect the importance of HDL-cholesterol and BMI on the process of atherosclerosis within an otherwise homogeneous group of patients.

[Vasoneuroses]. / Vazoneurózy.

The term vasoneuroses comprises functional disorders of peripheral vessels, in particular arterioles, manifested by vasospasms on the periphery of the upper and lower extremities, more rarely the nose and ears. The main representant of these diseases is a disorder manifested by episodic attacks of ischaemia of the fingers, in particular of the upper extremities--Raynaud's phenomenon (RP) which has two forms: primary RP (Raynaud's disease) where no other basic disease is diagnoses during a two-year period. secondary RP (Raynaud's phenomenon) as an associated symptom of other, in particular systemic diseases. The etiology and pathology of Raynaud's phenomenon has not been elucidated satisfactorily so far. With regard to the variety and scope of detected functional and morphological abnormalities RP is rather multifactorial, caused by an unbalanced action of local and systemic factors affecting the sensitivity of the vascular wall to spastic stimuli. Treatment therefore remains symptomatic. It is restricted to administration of vasodilatating agents, in more severe cases sympathectomy is considered; it is important to rule out another basic disease. Vasoneuroses include also acrocyanosis, livedo reticularis and erythromelalgia. In the case of erythromelalgia it is important to rule out secondary causes (hypertension and polycythemia vera), otherwise it is not necessary to use pharmacological means to influence these diseases because of their relatively harmless course.

[Correlation of computer tomography findings with surgical findings in patients with myasthenia gravis]. / Korelace nálezu výpocetní tomografie (CT) s operacním nálezem u pacientu s myasthenia gravis.

A group of patients with myasthenia gravis operated at the Third Surgical Clinic, Faculty Hospital had in 20.5% a thymoma. Before operation CT did not detect the thymoma in 13.8% of the thymomas detected during operation and verified by histological examination. This fact must be taken into account when indicating conservative treatment in a myasthenic patient.

[An unusual cause of recurrent septic states]. / Neobvyklá prícina opakovaných septických stavu.

The authors describe the septic sequelae of an unobserved embolization of a central venous catheter into right-sided cardiac compartments. The finding of an embolized fragment of a catheter which was in the patient's circulation for 89 days was quite incidental. The previous period was associated with diagnostic doubts in various departments. The most frequent diagnosis of repeated septicaemia was bacterial endocarditis, although repeated echocardiographic examinations did not confirm it. Similarly, repeated X-rays did not contribute to the diagnosis--this can be explained by dilatation of the heart of the patient. Extraction of the embolized fragment by means of a catheter resolved the problem. The fragment was colonized by the causal agent of the febrile conditions--Staphylococcus aureus.