[Nephroblastoma -  30-years period of its treatment in the University Hospital Motol, Prague]. / Nefroblastom -  30 let lécby ve Fakultní nemocnici v Motole.

INTRODUCTION: Nephroblastoma (Wilms tumor - WT) is the most common solid tumor of kidney in children. We present treatment development of WT at the Department of Pediatric Hematology and Oncology, Charles University in Prague, 2nd Faculty of Medicine and University Hospital Motol (KDHO) in the Czech Republic over 30 years. Patients that were treated prior to access to the International Society of Pediatric Oncology (SIOP) protocols are considered to be the historical group, then we have patients treated according to SIOP 9, SIOP 93-01 and SIOP 2001 protocols as full participants of SIOP studies. PATIENTS AND METHODS: Between January 1980 and April 2009, we treated 330 patients with WT at KDHO: 91 patients in historical group (1980-1988), 94 pts in SIOP 9 (1988-1993), 80 pts in SIOP 93-01 (1994-2001) and 65 pts in SIOP 2001 (2002-2009). Overall survival (OS) and event-free survival (EFS) were analyzed by Kaplan-Meier test. RESULTS: The overall ten-year EFS was 81.2% and OS 87.6%. Fifty-eight patients from the 330 (17.6%) had metastases at diagnosis, EFS without metastatic process was 84.6% compared to 65.4% with metastasis presented at diagnosis (p = 0.0003), OS was 70.7% compared to 91.2% (p < 0.0001). One hundred and seventy patients (51.5%) were treated with preoperative chemotherapy and/or radiotherapy, whereas 158 patients (47.5%) underwent primary nephrectomy; EFS and OS did not differ: neoadjuvant vs primary nephrectomy EFS was 81.2% vs 80.9% (p = 0.85), OS 89.4% vs 85.4% (p = 0.38). Sixty (18%) patients experienced disease recurrence; OS after relapse was 33%. In the historical group, EFS and OS were 85.7% and 91.2%. In patients treated according to the SIOP 9 protocol, EFS and OS were 68.1% and 74.5%, resp. In patients treated according to SIOP 93-01, it was 83.6% and 93.7%, resp. and in patients treated according to 87 SIOP 2001, it was 7% and 95.4% (p = 0.001 and p = 0.0008), resp. CONCLUSION: WT is a well treatable disease. The aim for the future is to maintain the current very good survival while minimizing the treatment intensity.

[Treatment results in patients treated from 1980 to 2004 for Wilms' tumour in a single centre]. / Lécebné výsledky pacientu lécených v letech 1980-2004 na jediném pracovisti pro nefroblastom.

BACKGROUNDS: The principle behind the treatment of nephroblastoma has been similar for at least 4 decades, based on vincristine and dactinomycine, radiotherapy in selected stages. The last three decades have been characterised by the aim to reduce the intensity and length of treatment. DESIGN: To retrospectively compare survival rates and treatment success in a cohort of patients aged under 19 years, treated from 1980 to 2004 at a single centre by five consecutive treatment protocols. MATERIALS AND METHODS: The outcome was evaluated in patients treated consecutively by two protocols established at the centre before 1980 and modified in 1986, and from 1988 consecutively by three accepted protocols, SIOP9, SIOP93 and SIOP2001. RESULTS: Overall survival as well as event-free survival rates were evaluated by Kaplan-Meier functions in 315 patients (52.7% women). The average age at diagnosis was 3.9 +/- 2.9 years, median 3.3, range 0.01-17.2 years. Age over 12 years in 2.2% patients. The average follow-up time was 13.1 +/- 7.8, median 13.6, range 0.2-27.8 years. The original 104 weeks of protocol KDO86 treatment had a 10-year overall survival rate of 91.9 +/- 3.2%. Overall survival significantly fell with radiotherapy reduction in lower clinical stages and treatment diversification in protocols with substantial treatment length reduction. Overall survival returned to the original value of KDO86 only in 1994, when SIOP93 was accepted with a 10-year overall survival rate of 92.47 +/- 3.0% and event-free survival 85%, with similar trends in the latest protocol, SIOP2001. In the entire cohort two coincident malignancies (tumour duplicities) were found: one B-lymphoma, one neuroblastoma. A second malignancy occurred in one patient--superficial spreading melanoma. CONCLUSION: from the retrospective view the accepted SIOP9 protocol has a significantly worse outcome in both the overall survival and in event-free survival rate compared with the original therapy. Only the SIOP93 and SIOP2001 protocols accepted after 2003 have an acceptable 10-year overall survival rate (around 92%) as well as event-free survival (85%) with substantially reduced length and intensity of treatment, lowering the risk of late effects.

[Late effect of treatment of nephroblastoma in patients treated in 1980-2001 in a single centre]. / Pozdní následky Wilmsova tumoru a jeho lécby u pacientu lécených v letech 1980-2001 na jediném pracovisti.

BACKGROUNDS: The aim of the study was to describe the late effects in a cohort of patients in long-term remission (> 5 years from end of treatment) diagnosed and treated for nephroblastoma at the single paediatric centre during 1980- 2001. PATIENTS AND METHODS: 151 patients were examined for renal function, lipid profile, sonography, echocardiography, exercise capacity and postural status. Age at diagnosis was 3.7 +/- 2.7 years, median 3.1, range 0.01-17.2 years. The cohort included 55% of women. Age in the study 19.4 +/- 5.8, median 19.6 years, range 7.8-36 years. Anthracyclines (ATC) were administered to 25.9% of the cohort. Abdominal radiotherapy (RTA) was required in 34.2%. RESULTS: Creatinine clearance was on average 1.56 +/- 0.56 ml/s/1.73m2, (median 1.49 ml/s/1.73m2). Proteinuria was 0.18 +/- 0.30 g/24 h/m2, median 0.13 mg/24 h/m2. Three patients had proteinuria above 1 g/24 h with a normal glomerular filtration rate and s-albumin. Hypertension was treated in 8.6% of patients (6% by pharmacotherapy). Increased diastolic blood pressure (DBP) and systolic blood pressure (SBP) was found in adolescents: DBP > 90 Torr was found in 10.2% of patients and SBP > 135 Torr in 8.3%, all of them above the age of 15 years. ECHO did not reveal any pathology even in patients treated by ATC. Plasma cholesterol, LDL, HDL, triglycerides were outside the recommended range in two or more parameters in 28.9% of the cohort. Lipoprotein Lp(a) > 500 mg.l(-1) (more than 200% higher than the upper limit) was found in 15.2%. Low peak oxygen consumption (VO2peak) was found in 40% of the cohort. Scoliosis (Sc) was anamnestically found in 46%. Prevalence of Sc according to the age of treatment has a similar trend as the reduced use of the RTA. Pulmonary function test showed a moderate increase in the functional residual capacity (the average Z-score of 1.35). VO2 peak correlates positively with the inspiratory capacity (p < 0.05). CONCLUSION: Based on the found pathologies and known risks, a schedule of late effect prevention and monitoring of patients in long-term NFB remission was established. It should include clinical examination, kidney function and blood pressure monitoring, sonographic and echocardiography examination, long-term physiotherapeutic care and prevention of cardiovascular diseases.

[Locomotive activity in prevention blood-vessel complication and diabetes]. / Pohybová aktivita v prevenci cévních komplikací a diabetes.

Adequate, gradual, regular and locomotive diversified physical activities and training is at present a substantial part of treatment virtually in all patients with both type 1 and type 2 diabetes mellitus (T1DM and T2DM). In postgraduate conceived lecture authors explained meaning and indications of physical activities in primary and secondary prevention of metabolic syndrome and its complications. The lecture is focused also on relative contraindications of physical activities and sports in patients with T1DM and T2DM.

Changes of blood count, lymphocyte subpopulations and immunoglobulin levels in nephroblastoma long term survivors.

The aim of this study was to investigate the frequency of blood count, lymphocyte subpopulations, and immunoglobulin levels alterations in a group of healthy nephroblastoma long-term survivors. The group included 122 nephroblastoma longterm survivors who were at least five years post anticancer therapy and free of any sign of recurrence The proportion of lymphocyte subpopulations was analyzed by flow cytometry using antibodies anti CD45 FITC/CD14 PE, anti CD3 FITC/ CD16+CD56 PE, anti CD4 FITC/ CD8 PE and anti CD20 FITC. Immunoglobulin G, A, and M levels were evaluated by immunoturbidimetry. Total blood count was also examined. The occurrence of decreased immunoglobulin levels, leukocytes, lymphocytes, and granulocytes count, proportion of T lymphocytes and their CD4+ subpopulation are not frequent. The most frequently decreased lymphocyte subpopulation was CD8 (15.5%). The most frequent abnormal findings were increased proportion of NK cells (38.5 %), B lymphocytes (38,52 %), decreased number of erythrocytes (25.2 %), hemoglobin levels (41.7 %) and hematocrit (13.9 %). The only significant differences between results of immunological examination and course of the disease were more frequently decreased proportion of CD4+ lymphocytes in recurrent disease survivors and lower IgA levels in survivors after radiotherapy. We found decreased at least one immunological parameter in one fifth of the survivors. The most frequently altered parameter was hemoglobin, which was decreased in 41.7 % of survivors. Decraesed hemoglobin may worsen quality of survivors life. Key words: nephroblastoma long-term survivors, blood count, lymphocyte subpopulations, immunoglobulin G, A, M serum levels.

[Is prescription of physical activity a part of health care in civilization disorders? Results of questionnaire study in medical doctors]. / Je preskripce pohybové aktivity soucásti lécebne-preventivní péce civilizacních chorob? Výsledky dotazníkového setrení lékaru.

BACKGROUND: Low level of physical activity is an independent risk factor of civilization disorders. Intervention for increasing physical activity has been for generations mentioned in health care. Because of low adherence of the population to those general appeals it is necessary to improve radically the knowledge of health professionals about individual exercise prescription. The aim of this study was to analyze approach of medical doctors in this particular dilemma. METHODS AND RESULTS: A questionnaire was distributed at postgraduate courses for medical doctors. Data from doctors of different specializations were summarized (N=657, from which 458 were females, i.e. 69,7 %, mean age=38,8+/-9,74). 96,4 % of doctors stated that they recommend exercise to their patients though only up to 23,4 % of them are regularly asked by their patients about the exercise. Concrete (type, intensity, duration and frequency) or individually tailored recommendation give 66,2 %, or 62,6 % of doctors respectively. Most respondents (56,0 %) also recommend a consultation of another specialist (mostly rehabilitation doctor and physiotherapist). Majority of addressed professionals shows that current medical education structure does not enable adequate prescription of physical activity without the help of specialist. CONCLUSIONS: Study showed a positive attitude of medical doctors to exercise prescription. However, information about the need of individualized prescription and knowledge about possibilities of exercise therapy in particular regions should be increased.

Bacteria in gene therapy: bactofection versus alternative gene therapy.

Recent advances in gene therapy can be attributed to improvements of gene delivery vectors. New viral and nonviral transport vehicles that considerably increase the efficiency of transfection have been prepared. However, these vectors still have many disadvantages that are difficult to overcome, thus, a new approach is needed. The approach of bacterial delivery could in the future be important for gene therapy applications. In this article we try to summarize the most important modifications that are used for the preparation of applied strains, difficulties that are related with bacterial gene delivery and the current use of bactofection in animal experiments and clinical trials. Important differences to the alternative gene therapy (AGT) are discussed. AGT resembles bacteria-mediated protein delivery, as the therapeutical proteins are produced not by host cells but by the bacteria in situ and the expression can be regulated exogenously. Although the procedure of bacterial gene delivery is far from being definitely solved, bactofection remains a promising technique for transfection in human gene therapy.

Lymphocyte subpopulations and immunoglobulin levels in Hodgkin's disease survivors.

We investigated the frequency of lymphocyte populations (CD3+ /T lymphocytes/, CD4+ /helpers/, CD8+ /suppressor and cytotoxic/, CD3- CD16+ /NK cells/, CD3+ HLA-DR+ /activated T lymphocytes/, and CD20+ /B lymphocytes/) and immunoglobulin G, A, M, and E levels in a group of two hundred twenty nine Hodgkins disease long term survivors. The most frequent pathological findings were increased IgE levels, decreased CD3+ and CD4+ proportions, an increased CD20+ proportion and especially a low CD4/CD8 proportion. Decreased CD3+ and CD4+ and increased CD20+ proportions were more frequently found in the group with recurrent infections. IgM and IgA levels were positively correlated with plasmatic cholesterol and triacylglycerols levels. We suppose that immunological defects (increase of IgE levels, decreased T and helper lymphocytes) in Hodgkins disease survivors are inherent and are not related to atopy. Examination of lymphocyte subpopulations may be helpful in the prediction of an increased risk of recurrent infections.

Procedural memory trace for increased tidal volume can be demonstrated in healthy volunteers.

The minority of healthy subjects can (without previous learning) breathe at exactly double of their resting tidal volume on demand. The aim of the present study was to find whether this estimate of tidal volume value can be learned and at what speed. Basic spirometric values were measured by Oxycon B in 20 healthy volunteers. They learned in one day to breathe at double of the resting tidal volume twice for 3 min. The existence and duration of the memory trace was ascertained four times (three times on the same day, once three weeks later). This engram can be demonstrated on the day of learning after 1 or 2 trials of 3 min each. Three weeks later the memory trace is weak but still present. This fact means that a new breathing pattern can be learned. During learning and tests the subjects hyperventilate but no correlation was seen between learning ability and intensity of hyperventilation.

Good exercise tolerance and impaired lung function after atrial repair of transposition.

OBJECTIVE: Evaluation of long-term results of atrial correction of transposition of the great arteries (TGA), focusing on the relationship between pulmonary function and exercise tolerance. METHODS: A prospective population-based study-56 out of 60 survivors of Mustard/Senning repair, born in Bohemia in 1980-1984 (median age at surgery 0.85 years) were followed up over 13.4 +/- 1.2 years and studied by complete lung function and bicycle exercise testing. RESULTS: Maximum heart rate on exercise reached 181 +/- 14 bpm (Z-score: -1.06 +/- 1.66, range -6.7 to +1.6); VO2max: 40.6 +/- 6.7 ml/kg per min (Z-score: -0.97 +/- 1.4, range -5 to +1.8). A total of 73.6% had abnormal lung function, most frequently features of stiff lung (39.6%) and lung restriction (32.1%). Static recoil pressure of the lungs measured at 100, 90 and 60% of total lung capacity reached 137, 126 and 130%, respectively (Z-score: 1.93 +/- 2.33, 1.64 +/- 1.96, and 1.14 +/- 1.95, respectively). There was an inverse relationship between static recoil pressure of the lungs and VO2max (r = -0.306, P = 0.043), indicating the impact of lung function abnormalities on exercise tolerance. Comparison with lung function study of the group of 'pioneer' Mustard patients operated at the mean age of 4.4 years revealed a similar pattern and frequency (73.6% in current series vs. 88%, NS). CONCLUSIONS: Long-term follow-up has shown good exercise tolerance in the majority of patients after atrial correction of TGA performed in infancy. Many of them, however, have impaired lung function, especially stiff lung, although less frequently than original patients operated at a later age. The stiff lung can impair the exercise tolerance.

[The dead space in volitional changes in respiratory volume]. / Mrtvý prostor pri volních zmenách dechového objemu.

The objective of the investigation was to assess changes of the dead space under conditions of volitional changes of the respiratory volume. The authors assessed therefore in repeated experiments in 11 healthy volunteers basic respiratory variables and the effective dead space using a Mijnhardt spirometer at rest and during cortically conditioned changes of the tidal volume. When the breath deepens the effective dead space reaches higher absolute values, but the relative values decline. When the breathing is more shallow, the reverse occurs. Thus e. g. in men of the investigated group a mean value of the respiratory volume at rest was assessed which amounted to 0.74 +/- 0.10 l, the relative dead space declined to 19 +/- 7%, when breathing was shallow it rose to 37 +/- 10%.

Calcitonin gene-related peptide (CGRP) and leg vascular resistance during head-up tilt induced hypovolaemic shock in man.

Calcitonin gene-related peptide is a potent vasodilator and its distribution in perivascular nerves suggests a role in the regulation of vascular tone. We evaluated leg vascular resistance together with total peripheral resistance and the arterial plasma concentrations of calcitonin gene-related peptide and catecholamines during 50 degrees head-up tilt induced hypotension in 7 males. During tilt mean arterial pressure, heart rate, total peripheral resistance, leg vascular resistance and plasma noradrenaline increased, while cardiac output and leg blood flow decreased. After 45 +/- 9 min (mean +/- SE) presyncopal symptoms appeared together with decreases in mean arterial pressure (81 +/- 6 to 56 +/- 9 mmHg), heart rate (97 +/- 6 to 73 +/- 8 beats min-1), leg vascular resistance (158 +/- 9 to 109 +/- 8 mmHg min l-1) and total peripheral resistance (17 +/- 3 to 10 +/- 2 mmHg min l-1) (P less than 0.01). Plasma calcitonin gene-related peptide increased from 32 +/- 3 to 35 +/- 3 pmol l-1 (P less than 0.01) and adrenaline from 1.1 +/- 0.2 to 1.7 +/- 0.3 nmol l-1 (P less than 0.01), while noradrenaline did not change. The results indicate that presyncopal symptoms induced by head-up tilt are associated with regional as well as total decreases in vascular resistance accompanied by moderate increases in arterial plasma concentrations of calcitonin gene-related peptide and adrenaline.

[Anomalous origin of the right coronary artery from the pulmonary artery. Preoperative diagnostic finding in the aortopulmonary window]. / Anomální odstup pravé koronární artérie z plícnice. Predoperacne diagnostikovaný nález u aortopulmonálního okna.

A rare case of the abnormal origin of the right coronary artery is demonstrated in a two-year-old boy with an aortopulmonary window and subvalvular membranous aortal stenosis. The diagnosis was established by angiography before operation by injection of contrast substance into both great arteries. Surgical repair of the complicated defect comprised also derivation of the orifice of the right coronary artery into the aorta. The long-term postoperative follow-up indicates relatively favourable results with signs of impaired myocardial perfusion in the area supplied by the right coronary artery.

[Comparison of the physical fitness of the young population of Czechoslovakia with similar data from other European countries]. / Srovnání telesné zdatnosti nasí mladé populace se stejnými údaji nekterých evropských státu.

In order to analyze the relationship between VO2 max and height, body mass and lean body mass a multi-longitudinal survey was conducted on three different age groups of randomly selected children from a small Czech community. Beginning at the initial ages of 8, 12 and 16 years subjects were subsequently retested three times at two year intervals. At overlapping ages there were no differences in the various age groups between height and VO2 max. By utilizing mean values for the various parameters at specific calendar ages a growth curve was constructed for each sex for the age range 8 to 20 years. The values were compared with longitudinal studies of various countries and no substantial differences were found. When VO2 max was then compared to height, body mass and lean body mass it was apparent that the almost linear relationship with height was the most precise. In addition the children remained, generally speaking, in their same rank order for VO2 max for the three different age groupings.

The relationship between changing body height and growth related changes in maximal aerobic power.

In order to analyse the relationship between maximal aerobic power (VO2max) and height, body mass and lean body mass a multi-longitudinal survey was conducted on three different age groups of randomly selected children from a small Czech community. Beginning at the initial ages of 8, 12 and 16 years subjects were subsequently retested three times at 2-year intervals. At overlapping ages there were no differences in the various age groups between height and VO2max. By utilizing mean values for the various parameters at specific calendar ages a growth curve was constructed for each sex for the age range 8-20 years. The values were compared with longitudinal studies in various countries and no substantial differences were found. When VO2max was then compared to height, body mass and lean body mass it was apparent that the almost linear relationship with height was the most precise. In addition the children remained, generally speaking, in their same rank order for VO2max for the three different age groupings.

[Cardiac arrhythmia following total correction of tetralogy of Fallot]. / Herzrhythmusstörungen nach Totalkorrektur der Fallotschen Tetralogie.

41 patients after surgical correction of the tetralogy of Fall of aged 2-24 years (mean 11.2 y.) were followed for 12-65 months (mean 39.5 m.) for known or suspected dysrhythmias. 24-hour ambulatory ECG and exercise testing demonstrated nonsignificant ventricular ectopy (grade 0-1 according to a modified Lown classification) in 28 patients (group I) and significant (grade 2-5) ventricular dysrhythmias in the remaining 13 patients (group II). There were 2 cases of sudden late death in group II, whereas all patients in group I are alive. The victims of sudden death had no, other serious dysrhythmias and received no antiarrhythmic treatment. Ejection fraction of the functional part of the right ventricle estimated by radionuclide angiocardiography was not different in both groups whereas, global right ventricular ejection fraction differed nearly significantly (group I: 39.6 +/- 8.3%, group II: 31.9 +/- 10.4%, p = 0.052). Thus, a diminished global right ventricular ejection fraction caused by an extensive resection and large patch in the right ventricular outflow tract may be connected with the occurrence of higher grades of ventricular ectopy. These may lead to sudden late death.