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Introduction. Familial hypercholesterolemia is a hereditary disorder with autosomal dominant heredity. The underlying cause involves the gene for the LDL-receptor leading to accelerated atherosclerosis. Extracorporeal elimination of cholesterol (CH) is indicated in 3-5% of patients not responding to conservative treatment or in homozygous FH. Two methods are used at our institution: immunoadsorption of LDL- cholesterol and rheohemapheresis. Patients and Methods. We currently have long term follow-up available for 14 patients with familial hypercholesterolemia (8 males, 6 females) aged 28-70 years (median 57 years). 10 patients are treated with immunoadsorption (5 homozygous and 5 heterozygous) and 4 patients are treated with rheohemapheresis (2 males, 2 females). Median follow-up is 8.5 years. During immunoadsorption, plasma is collected by continuous separation and flows through alternating pairs of adsorbers in an automatic adsorbing-desorbing device. In rheohemapheresis, plasma is collected similarly but goes through a "second step" - filter. Procedures are repeated every 2-4 weeks. Cholesterol and LDL- cholesterol values are measured before and after each procedure. Results. 1922 procedures have been performed (immunoadsorption 1590 times, rheohemapheresis 332 times). Average cholesterol and LDL- cholesterol values before the procedure were 5.34 and 3.12 mmol/l in immunoadsorption, 5.07 and 2.86 in rheohemapharesis; after the procedure: 1.73 and 0.72 (a fall of 72% and 85%), resp. 1.96 and 0.97 mmol/l (a drop of 61% and 66% drop). Fibrinogen fell by 22% (from 3.05 to 2.42 g/l) and 64% (from 3.48 to 1.2g/l). There were 3.1% of adverse reactions and no difference was observed between the two methods. Conclusion. Treatment of FH is very effective when indicated. There is a significant decrease in all observed parameters. No patient experienced worsening of atherosclerosis. Both methods are safe with minimum adverse reactions. Immunoadsorption is more effective in CH elimination. RHF can be used in patients with hyperfibrinogenemia as an additional risk factor of atherosclerosis. Care of these patients is costly and requires an experienced team and an interdisciplinary approach. [ABSTRACT FROM AUTHOR]

Sudden hearing loss (sudden idiopathic sensorineural hearing loss, SISHL) is a major medical, social and economic problem. The etiology is not fully understood; the problem is arising presumably by the action of heterogeneous factors (viral infections, immunologic or vascular disorders etc.). Treatment of SISHL is generally not satisfactory, both in terms of corticosteroids or other options. Rheohemapheresis (RHF) offers a possibility of a rescue treatment. It is based on a rapid improvement of rheologic properties of blood that can favorably affect the viscosity and thus the flow of the microcirculation, coagulation or activity of the endothelium. In the years 2012-2013, we treated 16 patients in the age 34-72 years by means of our own modification of RHF, after treatment failure with corticoid infusion therapy. Hearing improvement was achieved significantly in 11 patients according to WHO rating, respectively in 12 diseased according to Fowler counting. 5 patients did not improve significantly, at one patient the hearing worsened. Most patients achieved an improvement at a frequency of 0.5 kHz. Tinnitus disappeared in two patients, and average tinnitus reduction was achieved 15.25 dB. Unfavorable prognostic factor showed to be the severity of hearing loss and age of the patient and the time of the incident. RHF side effects were not significant (two short-term non-serious reactions). RHF in our study showed a beneficial therapeutic effect even after a failed conventional therapy and subsequent initiation of treatment and was not associated with significant adverse risks. Treatment results of our group support the hypothesis that RHF may be an alternative rescue therapy in SISHL, especially in case of a vascular etiology, even after a failure of a standard therapy. [ABSTRACT FROM AUTHOR]

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PCSK9-inhibitors belong to the new class of hypolipidemic agents. They enhance catabolism of low density lipoprotein cholesterol (LDL-C) through inhibiting activity of proprotein convertase subtilisin/kexin type 9 (PCSK9). They are monoclonal antibodies (alirocumab, evolocumab etc). Under clinical development are also other types of PCSK9-inhibitors which act at a subcellular level. The treatment with PCSK9-inhibitors can be beneficially combined with lipoprotein apheresis (LA). If such treatment using PCSK9-inhibitors is possible with regard to an individual patients genotype, the combination of LA and PCSK9-inhibitors leads to slowing the space of LDL-C increase between individual procedures of apheresis and enables attaining of the lowest possible values of LDL-cholesterolemia for the longest possible period of time. Due to high efficiency of PCSK9-inhibitors lowering LDL-C, but also their lower cost as compared to therapeutic LA, PCSK9-inhibitors now take precedence over the use of extracorporeal lipoprotein apheresis which, nonetheless, still remains the final method for hypolipidemic treatment of patients with severe hypercholesterolemia, who are resistant to conventional therapy while not reaching the target lipid values and at high cardiovascular risk. They belong to extracorporeal elimination methodologies which remove low density lipoprotein (LDL) cholesterol from circulating blood. LA in combination with higher doses of statins and ezetimib currently represents the most efficient method of treatment of homozygous and statin-refractory heterozygous familial hypercholesterolemia (FH). Residual cardiovascular risk in these patients still remains high, in particular because, despite the aforementioned treatment, the target values for lipids according to present recommendations cannot be reached. The combination of LA with the new drugs is promising, primarily due to its potential for further lowering of LDL-cholesterolemia between the individual apheresis procedures. Preliminary results of the ongoing studies indicate that the new hypolipidemic drugs in combination with LA, or when used separately, will substantially enrich and improve the treatment of refractory FH.Key words: alirocumab - atherosclerosis - evolocumab - hypercholesterolemia - cardiovascular disease - lipoprotein apheresis.

Introduction: Improvement in any human activity is preconditioned by inspection of results and providing feedback used for modification of the processes applied. Comparison of experts experience in the given field is another indispensable part leading to optimisation and improvement of processes, and optimally to implementation of standards. For the purpose of objective comparison and assessment of the processes, it is always necessary to describe the processes in a parametric way, to obtain representative data, to assess the achieved results, and to provide unquestionable and data-driven feedback based on such analysis. This may lead to a consensus on the definition of standards in the given area of health care., Method: Total mesorectal excision (TME) is a standard procedure of rectal cancer (C20) surgical treatment. However, the quality of performed procedures varies in different health care facilities, which is given, among others, by internal processes and surgeons experience. Assessment of surgical treatment results is therefore of key importance. A pathologist who assesses the resected tissue can provide valuable feedback in this respect., Results: An information system for the parametric assessment of TME performance is described in our article, including technical background in the form of a multicentre clinical registry and the structure of observed parameters., Conclusion: We consider the proposed system of TME parametric assessment as significant for improvement of TME performance, aimed at reducing local recurrences and at improving the overall prognosis of patients., Key Words: rectal cancer total mesorectal excision parametric data clinical registries TME registry.

Introduction: Tumour size and the quality of its complete surgical removal are the main prognostic factors in rectal cancer treatment. The number of postoperative local recurrences depends on whether the mesorectum has been completely removed - total mesorectal excision (TME) - and whether tumour-free resection margins have been achieved. The surgery itself and its quality depend on the accuracy of preoperative diagnosis and detection of risk areas in the rectum and mesorectum, on the surgeons skills, and finally on pathological assessment evaluating whether complete tumour excision has been accomplished including circumferential margins of the tumour, and whether mesorectal excision is complete. The aim of our study was to implement and standardize a new method of evaluation of the quality of the surgical procedure - TME - in rectal cancer treatment using an assessment of its circumferential margins (CRO) and completeness of the excision., Methods: The study consisted of two parts. The first, multi-centre retrospective phase with 288 patients analysed individual partial parameters of the diagnosis, operations and histological examinations of the rectal cancer. Critical points were identified and a unified follow-up protocol was prepared. In the second, prospective part of this study 600 patients were monitored parametrically focusing on the quality of the TME and its effect on the oncological treatment results., Results: The proportion of patients with restaging following neoadjuvant therapy increased from 60.0% to 81.7% based on preoperative diagnosis. The number of specimens missing an assessment of the mesorectal excision quality decreased from 52.9% in the retrospective part of to the study to 22.8% in the prospective part. The proportion of actually complete TMEs rose from 22.6% to 26.0%, and that of nearly complete TMEs from 10.1% to 24.0%., Conclusion: The introduction of parametric monitoring into routine clinical practice improved the quality of pre-treatment and preoperative diagnosis, examination of the tissue specimen, and consequently improved quality of the surgical procedure was achieved., Key Words: rectal cancer TME - parametric monitoring - quality control.

Introduction: High incidence of colorectal cancer in the Czech Republic is an actual and demographically significant health issue. Half of all of the patients is older than 70 years. Both surgical and non-surgical treatment options in this group of patients depend on factors that are difficult to measure only by current oncological and anesthesiological classifications (cTcNcM, ASA). The objective of this paper is to measure the impact of age on the use of various treatment modalities within the protocol and their results, and also to suggest alternative options for therapy tolerance assessment., Methods: Analysis of data over a five-year period from the NOR database prepared by the Institute of Biostatistics and Analyses, Masaryk University., Results: In all parameters a difference was demonstrated between patients below the age of 70 and those above the age of 70 years. Older patients were disadvantaged. Only 11.2% of patients younger than 70 years were not treated, whereas 25.2% over the age of 70 years were not treated., Conclusion: A complex geriatric examination could improve the indication process in various treatment modalities, including surgery., Key Words: colorectal cancer - elderly - treatment - geriatric assesment.

Introduction: Liver metastases are diagnosed in 60% of patients with colorectal cancer, both at the time of diagnosis or later in the course of their management. Surgical treatment is the sole potentially curable method with 5-year overall survival of approximately 50%. However, only less than 20% of patients underwent liver resection. A joint effort of medical oncologists and surgeons is to increase the numbers of resected patients. The "liver first approach" (LFA) is one of approaches aimed at increasing resecability. The authors present their preliminary results using this method., Methods: 102 patients were included in the multicentre study supported by the grant IGA NT 13660 Evaluation of quality of multimodal treatment for patients with colorectal cancer liver metastases - conducted at the Central Military Hospital between September 2012 and January 2015. We used LFA in 12 patients (12%). Patients were indicated for liver resection based on good response to neoadjuvant systemic therapy. Multiple bilobar liver involvement (>4 metastases) was present in 11 cases and one large solitary metastasis in the right liver lobe in one case. The primary tumor was located in the rectum in 9 patients, in the rectosigmoid in 3 patients; 3 patients had a colostomy. Others showed no signs of bowel obstruction., Results: We have performed R0 resections in 11 cases, and two-stage hepatectomy with portal vein embolisation was indicated 3 times (in one case we did not finish the second stage due to quick progression after PVE). We performed major resections 7 times, along with sever extraanatomic resections, incl. 11 RFA (6 times in combination with major resections). Perioperative mortality was 0%, morbidity 33% (Dindo-Clavien >2). Ten patients underwent adjuvant chemotherapy, in 7 cases including radiotherapy of the small pelvis due to a local advanced primary tumor. Resection of the primary tumor was done in 7 patients (58%). Two patients died recently because of disease progression (17%); progression was observed in 6 patients (50%)., Conclusion: We deem the LFA suitable especially for patients with metastatic rectal tumors where adjuvant systemic therapy can be combined with radiotherapy. The timing of the resection of the primary tumor still remains a question: it is necessary to rule out potential recurrence of liver metastases, which affected more than 50% of the patients. The benefit of LFA must be confimed by randomised studies.

Lipoprotein apheresis (LA) is an effective treatment method the patients with severe hypercholesterolemia, resistant to the standard therapy. LA is an extracorporeal elimination technique, which specifically removes low density lipoprotein (LDL) cholesterol from the circulation. At present, lipoprotein apheresis, combined with high-dose statin and ezetimibe therapy, is the best available means of treating patients with homozygous and statin refractory heterozygous familial hypercholesterolaemia (FH). However, the extent of cholesterol-lowering achieved is often insufficient to meet the targets set by current guidelines. The recent advent of new classes of lipid-lowering agents provides new hope that the latter objective may now be achievable. These compounds act either by reducing low density lipoprotein (LDL) cholesterol production by inhibiting apolipoprotein B synthesis with an antisense oligonucleotide (mipomersen), or by inhibiting microsomal triglyceride transfer protein (lomitapid), or by enhancing LDL catabolism via monoclonal antibody-mediated inhibition of the activity of proprotein convertase subtilisin/kexin 9 (PCSK9-alirocumab, evolocumab etc). The promising is the combination of LDL-apheresis with new drugs, namely for its potential to further decrease of LDL-cholesterol between apheresis. Depending on the outcome of current trials, it seems likely that these compounds, used alone or combined with lipoprotein apheresis, will markedly improve the management of refractory FH.

LDL-apheresis is an extracorporeal elimination technique, which specifically removes LDL-cholesterol from the circulation. There are six methods for the selective LDL-cholesterol removal these days. The main indications for LDL-apheresis are the diagnosis of homozygous familial hypercholesterolemia, heterozygous familial hypercholesterolemia which is refractory the standard care and intolerance of routine care, and also patients with lipoprotein(a) increase resistant to the farmacotherapy. There is still debate which LDL-cholesterolemia is indication for LDL-apheresis therapy, and the recommendation differs among various countries. Despite large randomized trials are missing, there are several good quality studies to conclude, that the beneficial cardiovascular effects of LDL-apheresis in severe hypercholesterolemia are important and beneficial.

Assessment of the treatment procedures and their results is increasingly important in current medicine. The emphasis is put on an effective use of the health technologies (HTA). Unlike randomised studies, which involve strictly selected groups of patients who meet inclusion and exclusion criterias, the multicentre clinical registries provide a real-life picture of the treatment safety and effectiveness. Well prepared registries involve both research database and a friendly user interface enabling collection of parametric and easily analyzable data. Although there are some technological aspects aiming to ensure a maximum quality of entered data, cooperation with the users and data managers is essential. Such a registry, otherwise meaningful, must provide answers to previously defined medical hypotheses. Regular feedback to users (so called benchmarking or reporting) is considered to be of key importance. The Czech TAVI Registry (CTR) is a good example of reaching all of the above defined criterias. This registry contains data of approximately 95 % of all transcatheter aortic valve implantations (TAVI) performed in the Czech Republic. It is based on a general system aimed at the design of clinical trials, namely the TrialDB2 (a database system for clinical registries developed by the Institute of Biostatistics and Analyses at the Masaryk University (IBA MU). CTR has been run as an English-language version under the auspices of the Czech Society of Cardiology and represents one of the top-quality registries maintained by IBA MU. This paper presents the currently available database systems and some reports from this particular registry.

Introduction: Patients with serious aortic stenoses treated by conservative therapy have significantly worse life expectancy. Besides the surgical aortic valve replacement (AVR) as the gold standard of therapy, the transcatheter aortic valve implantation (TAVI) is indicated in patients at very high risk or who are contraindicated to AVR. The role of learning-curve in TAVI has to be established., Aim: Assessment of the results of consecutive TAVI procedures based on the experience of the team., Methods: 58 high-risk consecutive patients with the average age of 82.2 years were divided into 3 groups based on the TAVI order ( 20., 21.-40., 41.-58.). After the Edwards SAPIEN implantation via transfemoral or transapical approaches, all patients were followed for minimum 30 days. Data from the national registry (Czech TAVI Registry) were used for the retrospective analysis. Comparison of the groups was done by using the Kruskal-Wallis test, Mann-Whitney U test and χ2 test., Results: Significantly shorter procedural time (p < 0.001), hospitalization (p = 0.033) and a lower amount of contrast medium (p < 0.001) was observed during the time. There was no difference in the rate of clinical complications at 30 days., Conclusions: Increasing experience of the TAVI implantation team is associated with significantly shorter procedural time, hospitalization and a lower amount of contrast medium. Overall very good clinical results during 30 days were not affected by the team experience.

In January 2014, a programme of personalised invitations was launched in the Czech Republic, with the objective of inviting insured persons to cancer screening programmes; namely breast cancer screening and cervical cancer screening in women, and colorectal cancer screening both in women and men. This programme aims at strengthening the current cancer prevention programmes, and to increase the currently inadequate participation of the target population in these programmes; therefore, personalised invitations are sent to citizens who have not participated in these programmes for several years and therefore at risk of developing a serious disease. The project is coordinated by the Czech Ministry of Health in cooperation with the expert medical societies involved (gynaecology, gastroenterology, gastrointestinal oncology, diagnostic radiology, general practice), representatives of health care payers, and other experts nominated by the Minister of Health. All health care payers invite their clients (insured persons) to preventive check-ups, covering all examinations needed. The project has been realised with the assistance of financial resources from EU funds. This article describes the methodology of personalised invitations which has been implemented nationwide, its data background, and the first results of the project in the first half of 2014, when almost 1.3 million Czech citizens were invited.

Czech cancer screening programmes feature a comprehensive multimodal information system which covers all the levels of assessment needed - population-based monitoring (Czech National Cancer Registry), monitoring of results in the diagnostic databases of centres, as well as the quantification of coverage and outputs of primary care according to the administrative data of health care payers. A system of personalised invitations to cancer screening programmes was launched in 2014, based on a stand-alone component of the information system which makes it possible to identify eligible clients in health care payers databases. The system was fully standardised and uniformly implemented in all health insurance companies; its functionalities also involve both continuous and retrospective assessment of the results of personalised invitation. The legislative framework in force will have to be applied and implemented for a more comprehensive and integrated employment of all involved data sources, i.e. cancer registries, screening registries, and administrative data. The system must be able to analyse de-identified individual records on clients participation in screening programmes, and thus to ensure an adequate analysis of performance indicators in compliance with international recommendations.

Background: As a part of the development of a new prospective payment model for radiotherapy we analyzed data on costs of care provided by three comprehensive cancer centers in the Czech Republic. Our aim was to find a combination of variables (predictors) which could be used to sort hospitalization cases into groups according to their costs, with each group having the same reimbursement rate. We tested four variables as possible predictors -  number of fractions, stage of disease, radiotherapy technique and diagnostic group., Methods: We analyzed 7,440 hospitalization cases treated in three comprehensive cancer centers from 2007 to 2011. We acquired data from the I COP database developed by Institute of Biostatistics and Analyses of Masaryk University in cooperation with oncology centers that contains records from the National Oncological Registry along with data supplied by healthcare providers to insurance companies for the purpose of retrospective reimbursement., Results: When comparing the four variables mentioned above we found that number of fractions and radiotherapy technique were much stronger predictors than the other two variables. Stage of disease did not prove to be a relevant indicator of cost distinction. There were significant differences in costs among diagnostic groups but these were mostly driven by the technique of radiotherapy and the number of fractions. Within the diagnostic groups, the distribution of costs was too heterogeneous for the purpose of the new payment model., Conclusion: The combination of number of fractions and radiotherapy technique appears to be the most appropriate cost predictors to be involved in the prospective payment model proposal. Further analysis is planned to test the predictive value of intention of radiotherapy in order to determine differences in costs between palliative and curative treatment.

Background: The aim of our study was to compare healthcare-related costs of treatment with XELOX and FOLFOX4 chemotherapeutic regimens in patients with colorectal cancer. We have evaluated costs claimed to the health insurance by the hospital administering these cancer therapies. This study is a pilot project utilising the new I-COP database developed by the Institute of Biostatistics and Analyses of the Masaryk University in Brno, Czech Republic., Patients and Methods: First, we estimated the costs based on current prices of procedures, medication, and materials from public sources. Using the I-COP database, we then carried out a matched-pair comparison of 26 patients treated with FOLFOX4 or XELOX for colorectal cancer. We evaluated a period of three months of therapy (i.e. 6 cycles of FOLFOX4 or 4 cycles of XELOX). Statistical analysis was done using the Wilcoxon matched pairs test., Results: The estimated cost for three months of therapy was 148,288 Czech crowns (CZK) for FOLFOX4 (including CZK 101,064 for chemotherapy drugs) and CZK 123,756 for XELOX. The overall costs claimed to the insurance companies were CZK 160,158 and CZK 151,176 for FOLFOX4 and XELOX, respectively (p = 0.221). The XELOX regimen had significantly higher costs for chemotherapy drugs (CZK 131,705 versus 114,531, p = 0.023) whereas other costs were lower than those for FOLFOX4., Conclusions: FOLFOX4 and XELOX regimens can be considered as equivalent in terms of costs claimed by the hospital administering cancer treatment.

Introduction: Alcohol and caffeine is intermittently or regularly used by majority of people. These drugs may have acute or chronic effects on patients with traumatic brain injury. Alcohol intoxication increases cerebral blood flow from 8 to 24%. Caffeine decreases cerebral blood flow from 10 to 20%. These facts create a theoretical hypothesis that the decrease of CBF may reduce incranial pressure. The aim of this study was to investigate the effect of caffeine on intracranial pressure in rats following traumatic brain injury., Methods: Ten Wistar male rats underwent weight drop closed head injury. The second stage of the experiment was done 12 to 18 hours later. Intracranial pressure, respiration, heart rate and the mean arterial pressure was monitored. Intraperitoneal injection of caffeine (20 mg/kg) was administered and repetitive measurement of vital signs and intracranial pressure was done., Results: The baseline ICP after head injury was 8.5 +/- 2.9 mm Hg. Ten minutes after intraperitoneal caffeine administration ICP dropped to 7.6 +/- 3.1 mm Hg (p < 0.05). This represents a 11% decrease from baseline value. Mean arterial pressure, respiration and heart rate were stable., Conclusion: Intracranial pressure decrease of 11% from baseline value. This drop was compatible with our hypothesis. The exact dosage of caffeine, its form and rate, should be more precisely specified in further studies.

Introduction: The age related macular degeneration (ARMD) is the most common cause of practical blindness in the population older than 60 years of age. Usually it starts as a dry form with soft drusen.The progression of the dry form is difficult to control-promising seems to be the influence of rheologic factors in the choroid and the retina and thus improvement of their blood flow., Aim: By means of haemorheopheresis to improve blood rheology and thus micocirculation in the choroid and retina. The authors describe the development of the dry form of the ARMD in the sensitive stage with soft drusen and the eventual presence of retinal pigment epithelium detachment (RPED) after haemorheopheresis. The treated patients were compared with a control group (natural course of the ARMD) with the same number of patients., Methods: In a prospective, randomized study, comprising of 16 patients with the dry form of ARMD were treated with haemorheopheresis (cascade filtration) and 16 patients in the control group. Haemorheopheresis treatment comprised of 8 cycles in 10 weeks. Plasma obtained by separator was filtered by the Evaflux 4A (Japan) separator, where, the defined spectrum of high molecular proteins was captured. This lead to a decrease in blood and plasma viscosity and thus to improvement of rheologic conditions of the retina., Results: Results show a positive influence on the absorption of soft drusen, reduction of the retinal pigment epithelium detachment, and the possibility to improve the visual acuity of the treated patients., Conclusion: Comparing to the worsening of clinical signs and visual functions in natural course of the ARMD development, the rheopheresis as well tolerated method may cause the retardation or stop of the unfavorable course of the disease.

Background: Molecular biology methods based on reverse transcription and polymerase chain reaction (RT-PCR) are able to detect the presence of BCR-ABL transcripts in chronic myeloid leukemia (CML). In this study we present our experience with monitoring of residual disease using real-time PCR with hybridization probes detection in patients treated with imatinib mesylate and in collected peripheral blood progenitor cells (PBPC)., Methods and Results: We measured the level of BCR-ABL transcripts in peripheral blood cells of 27 subjects before and in the course of the imatinib treatment. The median of relative quantity of BCR-ABL in the blood before imatinib therapy was 2.55%. The number of the transcripts in 23 imatinib-sensitive subjects decreased to 0.02% in 6 months. After 12 months of the treatment the BCR-ABL median was 0.005%. Subsequent levels fluctuated between values below the detection limit (DL, 0.001%) and 0.005%. Three patients were primarily resistant to imatinib with the BCR-ABL range of 0.13%-11.7% during the treatment. One subject showed marks of molecular relapse after 18 months of the treatment. Only two of 16 filgrastim-stimulated patients had BCR-ABL levels in the blood and in collected PBPC below DL. In other subjects BCR-ABL transcripts were determined within the measurable range of RT-PCR., Conclusions: Taking into account prognostic importance, the measurement of BCR-ABL transcripts is an effective approach to monitoring of residual CML kinetics. Evaluation of BCR-ABL levels in collected PBPC can complete information on quality of the cells in potential autotransplants, and choose subsequent therapeutic protocols and patient prognosis.

Background: The interest in aspirin resistance has been increasing during the last few years, with researchers earnestly pursuing alternative anti-platelet therapies and devices for measuring platelet aggregation. The recent studies suggest that 5-45% of patients taking aspirin do not experience adequate anti-platelet effects., Methods and Results: There is scant evidence proving that aspirin resistance has some clinical consequences. To assess the prevalence of aspirin resistance in patients with ischemic heart disease (IHD) two independent methods were used: platelet aggregation in platelet rich plasma (PRP) after induction by propylgallate (CPG), and assessment of platelet function by PFA 100 method. The study population consisted of 424 patients treated for IHD on the 2nd Dept. of Medicine, Teaching Hospital, Hradec Kralove. The age, gender, diagnosis and effect of therapy were characterized in this group of the patients. Daily ASA dose was 100 mg. We used two methods to monitor ASA treatment efficacy: a) thrombocyte aggregation after induction by CPG, b) the assessment of platelet function by PFA 100 method. a) Of the patients studied by CPG platelet aggregation, 51 (12.1%) pts were resistant to ASA dose 100 mg/day, and 32 (7.6%) pts remained resistant even after increasig the dose to 200 mg/day. In 80 (20%) pts, the daily ASA dose of less than 100 mg was sufficient to inhibit platelet function. b) Although the PFA-100 system is not able to detect the difference between low and high ASA dose, we found 53 (15.2%) patients aspirin resistant using this method., Conclusions: In the patients with IHD treated with 100 mg of ASA per day, our study has shown that the prevalence of aspirin resistance was 12.1% using CPG method, and 15.2% using PFA-100 method. Aspirin resistance was dose dependent. Prevalence of ASA resistance in patients treated with 200 mg of ASA per day was only 7.6% using the CPG method.

The surgical anatomy of the temporal branch of the facial nerve was studied in the anatomical laboratory. The temporal branch divides into an anterior, middle (frontal), and a posterior ramus after it pierces the parotid fascia. The anterior ramus innervates orbicularis oculi and corrugator supercilii muscles; the middle branch is for the ipsilateral frontalis muscle. The posterior branch innervates the anterior and superior auricular and tragus muscles. Below the zygomatic arch, the temporal branch of the facial nerve is located in the subcutaneous tissue. Above the arch, it continues in the subgaleal space with the superficial temporal fascia deeply. The terminal twigs of the temporal branch penetrate the galea to reach their target muscles that are all located superficial to the galea. There is a significant variability in the course of the temporal branch of the facial nerve. Occasionally, the terminal twigs of the middle ramus may penetrate superficial layer of superficial temporal fascia and run in the intrafascial fat pad before entering the frontalis muscle. There are four available operative techniques in this anatomical location. The subgaleal dissection of a temporofrontal scalp flap is associated with a high incidence of postoperative palsy of the temporal branch of the facial nerve and cosmetically bothersome results. Reflecting the scalp and temporalis muscle together as a single layer is the safest procedure. Unfortunately, this technique can not be used for the transzygomatic approaches and the bulky temporalis muscle may compromise basal exposure in the pterional route. Third technique was described and propagated by Yasargil. He proposed a subgaleal dissection up to the anterior one-fourth of the temporalis muscle where the dissection has to be deepened between the two layers of the superficial temporal fascia (in the interfascial fat pad). This approach may also infrequently injure the temporal branch in case of anatomical variation. The last available operative technique raises the superficial temporal fascia together with the scalp.

We report here the case report of patient with empyema of the thorax and sternal osteomyelitis, which undertool removal of ectopic mediastinal parathyroid adenoma with omentoplasty of sternal defect. Osteomyelitis was cured; though empyema persisted for several months and it's healing was complicated with central venous catheter sepsis.

Currently there are three major surgical approaches into the sphenoid sinus during transsphenoidal microsurgery. The first approach is the sublabial incision with submucous resection along the nasal septum. It is particularly advantageous in patients with small nasal apertures, in pediatric patients, and for large tumors extending into the cavernous sinuses or into the clivus. The second approach, the transnasal submucous tunnel, is presently the most frequent technique used, although it provides the narrowest operation field. The third technique is the direct transnasal approach. This method is less destructive to structures in the nasal cavity and less time-consuming. In the period of 20 months the authors performed 81 transsphenoidal microsurgical operations in 44 women and 37 men. Visual field defect was the most frequent indication for surgery in 42 cases, followed by hormonal abnormality in 24 patients. The sublabial approach was used in 69 cases, the technique of transnasal submucous tunnel in 10 patients, and the direct transnasal approach in 2 cases. The authors encountered no short-term or long-term complications related to various surgical approaches to the sphenoid sinus.

Tumourous diseases are associated with haemorrhagic as well as thrombotic complications. The most frequent cause of haemorrhagic states in tumourous diseases is thrombocytopenic haemorrhage, consumption coagulopathy and activated fibrinolysis. Trousseau described in 1865 a mutual association between tumourous diseases and venous thromboembolism. As many as 15-20% patients with venous thromboembolism have an undetected malignity which is a prevalence of 2-3% in the population. From this ensues the relative risk of a newly diagnosed malignity which is higher during the first year after venous thromboembolism. The prevalence varies between 2% and 6%. Migrating thrombophlebitiis (saltans and migrans) are a relatively specific sign in tumours, in particular in pancreatic tumours. In the pathogenesis of venous thromboembolisms in tumourous diseases in particular the following factors play a part: elevated coagulation parameters, reduced fibrinolysis, frequent immobilization, surgical operations in the case-history, chemotherapy, hormonal therapy and central venous catheters. The authors present a brief review of changes of haemostasis in tumourous diseases, their possible diagnosis and possible pharmacological prevention and treatment of thromboembolisms.

LDL (low density lipoprotein) - apheresis has been established as an alternative management of severe hypercholesterolaemia after failure of conventional diet and drug therapy. General indication criteria for LDL-apheresis have yet been established. Indication guidelines in USA, Europe and japan are based on whether coronary heart disease is present and on the degree of lDL cholesterol elevation after treatment with diet and maximal drug therapy. It is reasonable to consider LDL apheresis therapy for: 1. patient with coronary heart disease and LDL cholesterol 4.9 mmol/l (190 mg/dl); 2. patients without coronary heart disease, but at high risk for disease (due to an LDL cholesterol above 6.4 mmol/l (250 mg/dl), a first-degree relative with premature coronary heart disease, and the presence of one or more additional risk factor. The therapeutical goal with present coronary heart disease is lDL cholesterol less than 3.4 mmol/l (130 mg/dl), with asymptomatic coronary heart less than 5.2 mmol/l (200 mg/dl). In addition, LDL apheresis is recommended for the management of all patients with homozygous familial hypercholesterolaemia due to the very high risk of coronary heart disease and the poor response to usual lipid-lowering treatments. In the end present two typical cases, treated by LDL-apheresis.

In a group of 993 patients with serious medical diseases an important deficiency of antithrombin III was found in patients with hepatic insufficiency, pulmonary embolism and with disseminated intravascular coagulation. Acquired antithrombin III deficiency in these conditions develops when the antithrombin production in the liver is low and also in patients with shock syndrome and disseminated intravascular coagulation. Assessment of antithrombin III is of diagnostic and prognostic value in thrombotic and prethrombotic conditions and its results is decisive for adequate substitution. Adequate AT III substitution without concurrent heparin administration in patients with septicaemia and manifestations of DIC improves the prognosis of patients with an increased endothelial resistance.

The authors revealed some changes in the platelet activity in patients with invasive cardiological procedures. Changes of the platelet function were manifested by an enhanced aggregation of platelets in vivo, an increased secretion from alpha granules and increased release of prostaglandin metabolites from platelets and from the vascular wall. Acetylsalicylic acid (ASA) suppressed the formation of circulating platelet aggregates in vivo, but the platelet activity was manifested by another mechanism, independent on ASA. The authors recorded therefore an increase of prostaglandin metabolites and PF4 even in patients who were treated with ASA before the invasive examination.

Extracorporeal elimination of LDL-cholesterol is at present an important part of comprehensive treatment of patients with very high cholesterol levels. An absolute indication for their use are patients with the homozygous form of familial hypercholesterolaemia. Treatment is, after individual consideration, indicated also patient with severe heterozygous familial hypercholesterolaemia, with a positive family history of IHD, if it is not possible to reduce LDL-cholesterol by diet and hypolipidaemic agents below 5.2 mmol/l; also patients with severe IHD and severe hypercholesterolaemia, included in secondary prevention where it is not possible to reduce LDL-cholesterol by diet and pharmacotherapy below 3,4 mmol/l. Another indication for treatment by LDL apheresis are patients where cardiosurgery cannot be performed because of angiosclerosis. These are patients with severe hypercholesterolaemia which does not respond to drugs and with diffuse changes of the coronary circulation in young age, which cannot be treated by angioplasty or coronary bypass, and also patients after a coronary bypass with a refractory disorder of the lipid metabolism. LDL apheresis is furthermore indicated in patients with severe hyperlipidaemic crises which eventually develop into necrosis of the pancreas. Long-term LDL-apheresis leads to regression of manifestations of xanthomatosis of the skin and tendons, it prevents progression and starts regression of atherosclerosis in patients with severe hypercholesterolaemia. In homozygotes with familial hypercholesterolaemia treatment by LDL-apheresis leads to prolongation of life and improves the quality of life. In heterozygotes neither prolongation of the life span nor a lower incidence of IHD is observed, while the quality of life improves and regression of atherosclerosis occurs. A combination of LDL-apheresis, dietary provisions and hypolipidaemic treatment in heterozygotes is the most effective method to reduce the LDL-cholesterol level. Extracorporeal elimination of LDL-cholesterol can be done by non-selective centrifuging or membrane plasmapheresis. More recent methods of LDL-apheresis are more selective and effective. They use active columns or capsules to remove atherogenic particles from plasma. These methods include cascade filtration, immunoadsorption heparin-induced LDL precipitation, thermofiltration and dextran-induced LDL precipitation.

The authors examined some indicators of platelet activity in patients with hypertension stage II (according to WHO). They revealed an increased platelet activity which was manifested by an increased concentration of platelet factor 4 (50.2 +/- 28.2 ng/ml) and thromboxane B2 (49.9 +/- 20.1 pg/ml) in plasma. The increase of indicators of platelet activation associated with hypertension is a molecular marker of activation of haemostasis and according to data in the literature it is an indicator of vascular complications in hypertension. It is not clear whether the increased platelet functions in hypertension is primary or an induced change.

The authors used the Simplate test (Organon Teknika) to examine the bleeding time from an incision in 15 healthy blood donors and found normal values of 3.45 +/- 0.90 min. The authors proved a close correlation between the improvement of the number of platelets in 10 patients with thrombocytopenia, treated with thrombocyte infusions and the improvement of the bleeding time when using the Simplate R test after one hour and after 24 hours following thrombocyte administration. Examination of the bleeding time by means of the Simplate R test (Organon Teknika) was well tolerated by the authors' patients and the test does not produce any side-effects.

The syndrome of disseminated intravascular coagulation (DIC) is an acquired coagulation disorder which is characterized by a significant activation of haemostasis and the formation of intravascular microthrombi, the consumption of coagulation factors and activation of fibrinolysis. DIC has similar clinical stages and a similar laboratory picture, regardless of the causal factor. The diagnosis of DIC should be based on anamnestic, clinical and laboratory data. The laboratory diagnosis of DIC is possible by using relatively simple tests, which have the character of statim examinations. DIC treatment is based on the principle of treatment of the cause, discontinued consumption of haemostatic material, substitution of lacking factors and restoration of the microcirculation. The possible development of DIC must be taken into account in a number of acute conditions, in particular the development of shock syndrome. The presented article summarizes some views on causes, diagnosis and possible treatment of DIC.

The authors draw attention to the leukostasis syndrome which develops in haematological patients in case of enormous leucocyte proliferation. It occurs most frequently in chronic myelosis but may occur also in other types of leukaemia. The diagnosis is not easy. Most frequently disorders of the microcirculation develop in the lungs and brain. These are frequently very urgent clinical situations which can be resolved by leukapheresis. The authors described a patient where during chronic lymphadenosis proliferation of lymphocytes occurred to values of 1432 x 10(9)/l. After leukapheresis and cytostatic treatment rapid improvement of the condition occurred and the leucocyte values were approximately 30 x 10(9)/l. The patient's condition improved for a long period of time and became stabilized.

Authors document with the aid of fluorescent angiography of the retina pathological changes on the retina resulting from hyperviscous syndrome of Waldenstrom macroglobulinemia and their regulation after combined treatment with plasmapheresis and cytostatics.

Thrombocyte concentrates are vitally important in thrombocytopenic types of haemorrhage. If repeated transfusions are necessary, they are associated with immunological reactions, which cause side-effects in the recipient and the transfusion is ineffective. Donors should be selected according to the HLA system. The authors prepared a programme in the Redap language for selection of donors according to HLA antigens (loci A and B) which respects cross reactions and split antigens. The donor is selected by the grade of agreement with the recipient. The authors differentiate between nine possibilities from complete agreement to complete disagreement between donor and recipient. The initial experience revealed that the programme is feasible for the user and is sufficiently quick.

The authors made 184 thrombocytaphereses for the preparation of thrombocyte concentrates on a Travenol CS-3000 separator. They evaluate indicators on which the thrombocyte yield depends: it was found that the yield is higher in donors with a higher number of platelets and that it increases with the period of separation. The mean thrombocyte yield was 2.91 +/- 0.84 x 10(11). It corresponded to the average lower platelet number of donors--182 x 10(9)/L. In those donors where the number of platelets was higher than 180 x 10(9)/L, the yield was 3.21 x 10(9)/L. The undesirable presence of leucocytes (in 98% lymphocytes) increases in relation to the number of leucocytes in the donor and their decline after separation. It was lower in longer separations. The authors discuss the possibility to increase the thrombocyte yield without contamination with leucocytes.

Of a series of 300 patients with histologically verified Hodgkin's lymphoma, six cases of familial occurrence of the disease involving three families were reported from two clinical centers. In two families the affected patients were next of kin (daughter and father in the first family and two brothers in the third one). The interval between the onset of the disease was 6 years in the first and 4 months in the third family. In the second family an aunt and her niece were affected with an 18 year interval in the onset of the disease. The histological type was identical within the families involved (1 x LP and 2 x NS). Deficiency of cellular immunity was established in all the members of the two Prague families and the expression of HLA-A and B antigens of the MHC was determined in the first family. The involvement of environmental and genetic factors in familial Hodgkin's disease was analyzed also in the light of findings reported in the literature.

The authors assessed the test of platelet aggregation for the selection of a compatible donor. The test was compared with the hitherto used microlymphocytotoxic test. Consistent with data published abroad, the authors confirmed that the aggregation test improves the accuracy of selection of a suitable donor. The test can be performed in a shorter time than the microlymphocytotoxic test, this being important in particular in case of acute haemorrhage.