Non-invasive assessment of vascular system function and damage induced by anthracycline treatment in the pediatric cancer survivors.

Anthracyclines represent one of the important classes of anti-cancer drugs; however, their major disadvantage is their profound cardiovascular toxicity. This study aimed to evaluate influence of anthracyclines on cardiovascular stiffness parameters estimated from pulse wave (PW). PW was measured in 59 cancer survivors treated with anthracyclines in childhood and in 248 healthy age-matched controls. Both patients and controls were divided into three age groups (13 - 15, 16 - 18 and 19 - 24 years). Central PW augmentation index (C-AI75) and augmentation pressure (C-AP75), both normalized to heart rate 75 bpm, were calculated as parameters of arterial wall stiffness. Central Buckberg sub-endocardial viability ratio (SEVR) was calculated as a parameter of diastolic function. Patients and controls were compared in each age group. C-AI75 and C-AP75 were significantly increased in patients in age groups 16 - 18 and 19 - 24 years. SEVR was decreased in patients in the oldest age group. Our results suggest that although toxic influence of anthracyclines to arterial wall and heart are developing during childhood and puberty, they can be detected rather in the adulthood. These changes are yet subclinical; however, their presence indicates potentially increased cardiovascular risk in childhood cancer survivors treated with anthracyclines during childhood.

Anthracycline therapy and 24-hour blood-pressure profile in long-term survivors of childhood cancer.

In our previous studies, a decreased blood pressure was reported in children treated by anthracycline (AC). The aim of this study was to assess the long-term effects of AC anticancer therapy in 45 subjects aged 13-22 years by repeated 24-hour Holter monitoring of blood pressure. Sixty four aged-matched subjects served as controls. The differences between mean values of systolic (SBP) and diastolic blood pressure (DBP) in each hour of both groups were evaluated by Mann-Whitney test. Also the parameters of the least-squares fit of the sinusoidal curve in each subject were estimated (M - mesor, midline-estimating, a mean value of sinusoidal curve corresponds to 24-hours mean pressure; A - amplitude, double amplitude corresponds to night-day difference; Acr - acrophase is a time of maximal value of a sinusoidal curve). SBP and DBP was significantly lower only during night hours in anthracycline patients 19-22 years old. Also M was lower in this age subgroup of patients comparing to age matched controls (SBP: 112+/-6 mm Hg versus 117+/-7 mm Hg, p<0.05; DBP: 67+/-3 mm Hg versus 69+/-6 mm Hg, p<0.05), A was not different, Acr in patients was shifted one hour earlier (SBP: 2.4 p.m. versus 3.6 p.m., p<0.05; DBP: 2.1 p.m. versus 3.3 p.m., p<0.01). This corresponds to the shift of the morning blood-pressure increase seen on 24-hours blood pressure profiles. M correlated with age in controls (SBP: r=0.374, p<0.01; regression coefficient b=1.34 mm Hg/1 year; DBP: r=0.365, p<0.01; b=0.95 mm Hg/1 year), but not in patients (SBP: r=0.182, DBP: r=0.064). A and Acr were age-independent in all subjects. It is concluded that blood pressure in 19-22 years old AC patients is lower during night hours, the age-dependent increase of blood pressure seen in healthy controls between 13 and 22 years of age does not occur in patients. This finding is consistent with the long-lasting impairment of the sympathetic nervous system caused by anthracyclines.

Wilson's disease: monocentric experiences over a period of 10 years [corrected].

BACKGROUND: Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism. The objective of this study is to present diagnostic pitfalls and long time follow-up data in Wilson disease. PATIENTS/METHODS: We studied 21 WD patients and 14 heterozygote carriers aged 2-43 years, retrospectively. 18 WD patients presented liver disease, three had mixed neurological and hepatic involvement and 9 patients underwent orthotopic liver transplantation (OLT). RESULTS: The median age at diagnosis of WD children without OLT was 10.16+/-3.8 (range, 5-16). All of females and younger age categories of patients prevailed in acute liver failure group. Serum ceruloplasmine levels were below 0.2 g/l in about (1/3) of WD carriers (X =0.27+/-0.09 g/l) and nearly (2/3) of children with WD (X = 0.21+/-0.13 g/l). A statistically significant difference (p<0.05) in the 24-h excretion of copper in urine was noticed between healthy controls, children with WD and WD heterozygote carriers. As diagnostic important proved the copper content of more than 250 microg/g hepatic dry weight. The Kayser-Fleischer?s ring was not observed in children. Ceruloplasmine, haemoglobin, ALT, ALP and plasma albumin were significantly different between fulminant and non-fulminant WD and could be used as indirect markers in evaluation of urgent OLT. CONCLUSION: Detection of WD in children remains very difficult. The most important investigation is liver biopsy with the assessment of liver copper. Genetic analysis may help in doubtful cases.

[Early feeding in infancy and atopic dermatitis - a prospective observational study]. / Säuglingsernährung und atopische Dermatitis - eine prospektive Beobachtungsstudie.

BACKGROUND: Recommendations for primary prevention of allergic diseases in high-risk children include hypoallergenic infant formulas (HA) if breastfeeding is insufficient. The primary objective of our study was to investigate the atopic dermatitis (AD) preventive effect of breastfeeding and HA-nutrition in the first 2 years of life and to follow the increase in weight. PATIENTS AND METHODS: Altogether 174 newborns with a hereditary risk for atopy were enrolled in the study, 121 children were investigated at the age of 2 months, 111 at the age of 4 and 106 at the age of 6 months. A total of 45 infants were in the first half-year of life exclusively breastfed and 61 infants were mainly fed with HA. RESULTS: The body weight of initially HA-fed children was 7870G (SD 949) significantly higher as the one of breastfed children (7508 G, SD 912, p=0.0571), in addition the weight increase was also significantly higher in HA-fed infants at the age of 6 months (p=0.0042). The frequency of AD as well as SCORAD score at the age of 6 to 24 months was comparable in both groups. Neither the milk-specific IgE antibodies nor the proliferation of peripheral blood mononuclear cells (PBMC) to bovine beta-Lactoglobulin (BLG) at the age of 6 months had a prognostic value for development of atopic dermatitis. CONCLUSION: The likelihood to develop AD in the first 2 years of life was comparable in exclusively breastfed as in HA-fed infants with hereditary risk for atopy. The initially HA-fed children demonstrated at the age of 6 months higher body weight and weight increase as the exclusively breastfed infants. The efficacy of nutritional intervention on the incidence of AD in high-risk children for atopy could not be predicted by milk-specific IgE antibodies or BLG-specific proliferation of PBMC.

Haemolytic anaemia and acute liver failure--the initial manifestations of Wilson's disease.

We describe a case of a 16-year-old girl with Wilson disease, which was initially presented as Coombs-negative haemolytic anaemia and acute liver failure. The diagnosis was based on the findings of low ceruloplasmin serum level and high copper levels both in serum and 24-hour urinary excretion. The patient underwent orthotopic liver transplantation. A DNA-based diagnostic tool confirmed Wilson's disease: the patient was p.H1069Q homozygote. Based on further molecular-genetic examinations in the family, Wilson disease was diagnosed seven days later in one of the patient's asymptomatic brothers. The proband's cousin was confirmed as a carrier of the p.H1069Q mutation (Fig. 1, Ref. 24).

Overweight and decreased baroreflex sensitivity as independent risk factors for hypertension in children, adolescents, and young adults.

We studied the relationship between blood pressure (BP), body mass index (BMI, kg/m(2)) and baroreflex sensitivity (BRS, ms/mmHg) in adolescents. We examined 34 subjects aged 16.2+/-2.4 years who had repeatedly high causal BP (H) and 52 controls (C) aged 16.4+/-2.2 years. Forty-four C and 22 H were of normal weight (BMI between 19-23.9), and 8 C and 12 H were overweight (BMI between 24-30). Systolic BP was recorded beat-to-beat for 5 min (Finapres, controlled breathing 0.33 Hz). BRS was determined by the cross-spectral method. The predicting power of BMI and BRS for hypertension was evaluated by sensitivity, specificity, and receiver operating curve (ROC - plot of sensitivity versus specificity). H compared with C had lower BRS (p<0.01) and higher BMI (p<0.05). Multiple logistic regression analysis (p<0.001) revealed that a decreased BRS (p<0.05) and an increased BMI (p<0.01) were independently associated with an increased risk of hypertension. No correlation between BMI and BRS was found either in H or in C. Following optimal critical values by ROC, the sensitivity, specificity and area under ROC were determined for: BMI - 22.2 kg/m(2), 61.8 %, 69.2 %, 66.0 %; BRS - 7.1 ms/mmHg, 67.7 %, 69.2 %, 70.0 %; BMI and BRS - 0.439 a.u., 73.5 %, 82.7 %, and 77.3 %. Decreased BRS and overweight were found to be independent risk factors for hypertension.

Arterial blood pressure and baroreflex sensitivity 1-18 years after completing anthracycline therapy.

UNLABELLED: The analysis of short-term blood pressure regulation in children, adolescents and young adults 1 to 18 years after the treatment with anthracyclines known to have cardiotoxic side effects for oncological diseases was the aim of the present study. Thirty-one subjects treated with anthracyclines (PA) and 11 subjects treated with different antitumour drugs (P0) were investigated twice (the interval between two investigations 1-9 years). Three hundred and thirty-nine healthy subjects served as controls (C). Systolic (SBP), diastolic blood pressures (DBP) in the finger arteries and inter-beat interval (IBI) were recorded beat-to-beat (FINAPRES, Ohmeda, metronome controlled breathing, 5 minute recording); the values were corrected by auscultatory blood pressure measurements. Baroreflex sensitivity (BRS, ms/mmHg) was determined by a spectral method. As the investigated subjects were of different ages, the measured values were standardised on the age of 16 years by linear regression, and only standardised values (IBI16, SBP16, DBP16 and BRS16) were further analysed. No differences were found between PA, P0 and C in BRS16 and IBI16. SBP16 and DBP16 were significantly lower in PA (102.1+/-8.3/59.7+/-7.1 versus C: 114.1+/-12.4/69.0+/-9.5 mmHg; p<0.001/p<0.001; mean from two investigations). SBP16 but not DBP16 was also lower in P0 (102.7+/-12.6/64.5+/-9.7 mmHg; p<0.01/no significant) than in C. The correlation coefficient between SBP16 and period after treatment in PA was -0.11 (no significant) and -0.06 in DBP16 (no significant). Thus, there is not seen a trend to normalisation. CONCLUSION: The anthracycline antitumour therapy in children decreases blood pressure and within 18 years after the treatment there is not observed a trend toward normal values. BRS was not influenced by the anthracycline therapy.

Baroreflex sensitivity in children, adolescents, and young adults with essential and white-coat hypertension.

UNLABELLED: Hypertension, which is a common cardiovascular disease in adults, could originate in childhood. The aim of the study was to show differences in baroreflex sensitivity and short-term blood-pressure variability between healthy and hypertensive children, adolescents and young adults, and those with white-coat effect with respect to obesity. We examined 54 subjects (11-21 years) who had repeatedly high causal blood pressure. Basing on 24-hour blood pressure monitoring, the subjects were divided into groups: 24 subjects with hypertension (Hy) and 30 subjects with white-coat effect (WhC). Hy and WhC subjects were compared with age-matched healthy controls in a ratio of 1 : 2 for both groups: 48 controls for hypertensive subjects (CoHy) and 60 for subjects with white-coat effect (CoWhC). Totally, 162 subjects were studied. Systolic blood pressure (SBP) and inter-beat intervals (IBI) were recorded in all subjects for 5 min (Finapres, metronome controlled breathing at a frequency of 0.33 Hz). The power spectra of SBP and IBI were calculated. Indices of baroreflex sensitivity (BRS [ms/mmHg] and BRSf [mHz/mmHg]) were determined by the cross-spectral method. The SBP variability was determined as SBP spectral power in the range of 10-second rhythm (SBP (0.1Hz)). The body mass index (BMI) was significantly higher in both Hy and WhC compared with their controls (Hy vs. CoHy; WhC vs. CoWhC: 24.6 +/- 6.0 kg/m (2) vs. 20.4 +/- 2.8 kg/m (2), p < 0.001; 23.2 +/- 5.9 kg/m (2) vs. 20.3 +/- 2.6 kg/m (2), p < 0.05). BRS was significantly decreased in both groups (Hy vs. CoHy; WhC vs. CoWhC: 6.0 +/- 2.7 ms/mmHg vs. 9.5 +/- 3.9 ms/mmHg, p < 0.001; 7.2 +/- 3.1 ms/mmHg vs. 10.9 +/- 6.2 ms/mmHg, p < 0.01), and BRSf as well (Hy vs. CoHy; WhC vs. CoWhC: 10.8 +/- 4.6 mHz/mmHg vs. 16.2 +/- 6.1 mHz/mmHg, p < 0.001; 13.0 +/- 4.9 mHz/mmHg vs. 18.3 +/- 8.7 mHz/mmHg, p < 0.01). The decrease of baroreflex sensitivity was linked with the increase in the variability of SBP (0.1Hz), which was significant in hypertensives only (Hy vs. CoHy; WhC vs. CoWhC: 142 +/- 96 mmHg (2)/Hz vs. 94 +/- 83 mmHg (2)/Hz, p < 0.01; 121 +/- 131 mmHg (2)/Hz vs. 107 +/- 98 mmHg (2)/Hz). CONCLUSION: The mild increase of BMI was associated with white-coat effect and a BRS and BRSf decrease. The greater increase of BMI was associated with hypertension and a deeper BRS and BRSf decrease. This greater decrease of BRS and BRSf in hypertensives was linked with the increased SBP-variability.

[Consolidation of therapy of acute myeloid leukemia with the AML-BFM 93 protocol in children in the Czech Republic]. / Sjednocení lécby detí s akutní myeloidní leukémií v Ceské republice podle protokolu AML-BFM 93.

BACKGROUND: Acute myeloid leukemia (AML) in children is rare. Although more resistant to chemotherapy than acute lymphoblastic leukemia, its responsiveness and survival rates have considerably improved during the last 15 years by virtue of intensification of chemotherapy and due to the better supportive care. Relapses still remain the main cause of treatment failure. Management of children with AML was unified in the Czech Republic in 1993 according to AML-BFM 93 Study protocol. METHODS AND RESULTS: Treatment results were evaluated in 61 patients, of whom 45 (73.8%) achieved complete remission. Five-year event-free-survival (EFS) was found in 42.3%, and overall survival was 45.3%. Prognosis of the standard-risk patients was significantly better than in the high-risk group (EFS 62.5% vs. 29.7%, p = 0.03). The most important prognostic factor was the early treatment response. Compared to chemotherapy, allogeneic stem-cell transplantation did not significantly improve the outcome of high-risk patients. CONCLUSIONS: Treatment results of children with AML in the Czech Republic are comparable to those achieved by leading leukemia study groups in the world. The aim of the next study is to increase the complete-remission rate by reducing early deaths.

[Improved results in children with acute lymphoblastic leukemia treated with the ALL-BFM 90 protocol in the Czech Republic]. / Zlepsení výsledku lécby detí s akutní lymfoblastickou leukémií podle protokolu ALL-BFM 90 v Ceské republice.

BACKGROUND: Prognosis of children with acute lymphoblastic leukaemia (ALL)--the most common cancer in childhood, has improved remarkably over the last 40 years. The authors report the treatment outcome in children with ALL cured according to ALL-BFM 90 Study protocol in the Czech Republic during the first half of nineties. METHODS AND RESULTS: Children aged 0-18 years were included into the study in 10 centers between 1990 to 1996. Patients were classified into standard-risk (SR), medium-risk (MR) and high-risk (HR) group according to initial leukaemic burden, early treatment response, and genotype of leukaemia. Duration of the chemotherapy was two years. Treatment results were evaluated in 352 children. With a median follow-up of 7.3 years, event-free-survival (EFS) was 71.3% and overall survival 76.4%. EFS was 80.3%, 74% and 28.2% in SR, MR and HR group, respectively. Relapse was diagnosed in 17.8% of the patients. CONCLUSIONS: The treatment outcome of children with ALL improved significantly (p = 0.0045) compared to the previous study ALL-BFM 83 (EFS 62%). These results are comparable to those achieved by leading leukaemia study groups in the world.

The evaluation of left ventricular function in childhood cancer survivors by pharmacological stress echocardiography.

Late cardiotoxicity after anthracycline chemotherapy for childhood cancer is well recognized sequelae. Many long-term survivors may have subclinical cardiac dysfunction undetectable at a baseline evaluation. Various tests have been utilized for the diagnosis of left ventricular impairment. Recently, low-dose dobutamine stress echocardiography has been proposed as a more sensitive screening test. We have applied low-dose dobutamine stress echocardiography (5-10 microg/kg/min) in 36 asymptomatic survivors (20 male/16 female aged 14.6+/-4.7 years) treated with a cumulative dose of 226+/-106 mg/m2 of doxorubicin. The median follow-up was 5 years. Control group consisted of 20 sex and age matched volunteers (12 male/8 female aged 12.6+/-4.9 years). We found significant differences in mean velocity of circumferential fibre shortening, myocardial performance index (Tei index), left ventricular posterior wall thickening and endsystolic wall stress at a baseline. The stress response was significantly blunted only in a patient group in the following parameters: endsystolic wall stress, isovolumic relaxation time and myocardial performance index. The threshold response was abnormal (0-5% improvement of a variable only) in 45% of subjects from a control group in one or two parameters. On the contrary, 63% of subjects from a patient group responded pathologically (the worsening of a variable) in one or more parameters. We have not found a good correlation between risk factors of late cardiotoxicity and stress changes of left ventricular function parameters. Low-dose dobutamine stress echocardiography is safe and feasible diagnostic tool in children and adolescents. Dobutamine significantly increases the differences in cardiac variables between healthy population and asymptomatic survivors for childhood cancer. In comparison to the controls, most asymptomatic patients revealed subclinical myocardial damage at test. The predictive value for the development of clinical symptoms and cardiac complications need to be assessed in a large prospective study.

[Retinoblastoma in monozygotic twins]. / Retinoblastom u monozygotních dvojcat.

Retinoblastoma is one of the most frequent ophthalmological tumours in children. It is an embryonic tumour originating in the retina. It is caused by abnormalities in the RB1 gene and deletions in the region 13q14. The authors present a bilateral non-hereditary retinoblastoma in monozygotic twins, associated with deletion in the region 13q14, stigmatization, psychomotor and somatic retardation.

[Dynamic stress echocardiography in asymptomatic patients treated for malignant diseases in childhood]. / Dynamická zátezová echokardiografie u asymptomatických pacientu lécených v detství pro maligní onemocnení.

INTRODUCTION: The authors used echocardiography at rest and dynamic stress echocardiography to assess left ventricular function in asymptomatic patients treated during childhood or adolescence by chemotherapy containing anthracyclines. MATERIAL AND METHODS: 137 patients were examined (81 men, 56 women) aged 16.6 +/- 4.8 years (median 17 years) where at the age of 9.1 +/- 4.8 years (median 9 years) malignant disease was detected and treatment with a cumulative dose of anthracyclines 242 +/- 110 mg/m2 (median 240 mg/m2) was administered. The control group was formed by 30 subjects (14 men, 16 women) aged 19.5 +/- 5.2 years (median 20 years). The echocardiographic examination was made at rest and immediately after a dynamic stress on an ergometer with a load of 25 W/2 mins. RESULTS: In 8% patients (n = 11) a reduction of the fractional shortening (FS) LV < 30% was found. The values of the ejection fraction (EF), the median shortening of the circumferential fibre and endosystolic wall stress, excursion and thickening of the posterior wall of the LV were significantly worse as compared with the group with fractional shortening > or = 30% and the control group. The maximum drop of EF was to 40% and of FS to 20%. The values of the index of the global LV function (according to Teie) were as compared with the control group worse in both sub-groups of patients. No differences were found in the exercise tolerance between groups. Values of the ejection fraction at rest and after a exercise were in the sub-group with FS < 30% significantly lower as compared with the others. The values of the stress increment of EF were elevated in all sub-groups. In none of the subjects the load caused a decline of the EF. CONCLUSIONS: Chemotherapy with anthracyclines leads to a late disorder of several indicators of left ventricular function. Asymptomatic patients with a drop of the EF value to 40% or FS to 20% preserve their load tolerance and contraction reserve of the left ventricle. The finding of a preserved contraction reserve and good exercise tolerance implies a more favourable prognosis of the patient. Echocardiography at rest should be made repeatedly after treatment, in case of a pathological finding a loading test must be indicated to evaluate the contraction reserve and its possible development.

The analysis of the risks for the development of tumour lysis syndrome in children.

BACKGROUND: Acute renal failure (ARF) during the course of cytostatic therapy is a serious complication. ARF can be isolated or became as component of tumour lysis syndrome (TLS). TLS comprises a number of metabolic abnormalities (hyperuricemia, hyperphosphatemia, hyperkalemia, azotemia and hypocalcemia) which are associated with lymphoproliferative malignancies following spontaneous or chemotherapy-induced cytolysis. There exist probably no clear prediction for the development of TLS that could enable early detection of manifestation of this severe condition. SUBJECTIVE: Conventional management with aggressive hydration, alkalization of the urine, administration of allopurinol, and the slow introduction of chemotherapy is often unable to prevent metabolic instability and ARF. Recent studies define a subgroup of patients at higher risk of renal failure during induction chemotherapy. ARF was encountered during initial therapy of patients with a lactate dehydrogenase (LDH) index greater than 3.3. METHODS AND MATERIAL: A retrospective analysis of 10 children (3 girls, 7 boys, average age 9.7 years) with LDII index greater than 3.3 has been done. All children were treated for lymphoproliferative malignancy with conventional preventive measures. RESULTS: Three children needed haemodialysis--2 boys had fully expressed TLS with ARF shortly after starting chemotherapy, in 1 boy the dialysis was indicated because of extreme hyperuricemia and high creatinine level presented before chemotherapy. We consider that LDH index is not specific criterium for prediction of TLS. In conclusion, our cases demonstrate the pathophysiologic spectrum of ARF in TLS between hyperuricemia and hyperphosphatemia. CONCLUSION: The LDH index, urine output, and hyperphosphatemia could be used to identify those paediatric patients who would benefit from the prospective use some of extracorporeal elimination methods. Further investigation of this techniques in a larger number of patients is warranted. (Tab. 5, Ref. 12.)

[Monitoring cardiotoxicity of anthracyclines in children and possibilities of its prevention]. / Sledování kardiotoxicity antracyklinu u detí a moznosti prevence.

UNLABELLED: Chemotherapy is the basic therapeutic method in pediatric oncology. Encouraging results of treatment of tumours in children may be adversely influenced by late side effects of cytostatics. Most serious is the late cardiotoxicity of anthracyclines. The authors analyzed and evaluated in a retrospective study clinical and laboratory findings in patients treated during childhood on account of malignity by chemotherapy containing anthracyclines, and focused their attention on late toxicity and evaluation of the effect of cardioprotection of dexrazoxane (ICRF-187, Cardioxane). The investigation comprised 73 patients aged 15 +/- 4.7 years who were given a cumulative dose of anthracycline (doxorubicin or daunorubicin) 244 +/- 13 mg/m2 and were in long-term remission of the disease. The mean follow up period after terminated chemotherapy was 6.7 +/- 3.4 years. Cardioprotection was administered to 42%, to 58% it was not administered. The authors did not find a significant difference in the results of anthropometric, haematological and biochemical examinations in the two sub-groups. A decrease of the left ventricular ejection fraction below 50% was diagnosed in 4 patients (5% of the group) whereby two developed cardiomyopathies with the clinical picture of heart failure and one patient died due to progressive heart failure. Cardiotoxicity was diagnosed only in the sub-group without cardioprotection (9.5% of the sub-group). In patients without cardiotoxicity in the investigated sub-groups no significant difference was found in the left ventricular ejection fraction at rest or after a stress (in dynamic stress echocardiography), in the tolerance of a stress and circulatory indicators. A significant and relatively close negative relationship was found between the administered cumulative dose of anthracyclines and the left ventricular ejection fraction at rest (r = -0.62, p < 0.001) and after a stress (r = -0.64, p < 0.001). CONCLUSION: The finding of a 5% incidence of cardiac damage of the myocardium in the whole group after a relatively short period after termination of chemotherapy is sufficient reason for long-term cardiological and in particular echocardiographic follow up of patients treated in childhood on account of a malignity with anthracyclines and for a rational approach to the administration of cardioprotection.

[Diagnostic possibilities of late cardiotoxic sequelae of chemotherapy with anthracyclines]. / Diagnostické moznosti pozdních následku kardiotoxické chemoterapie antracykliny.

Anthracyclines areamong the most frequently used cytostatics in the treatment of haematological malignities and some solid tumours in childhood and adult age. They affect cellular proliferation in several ways. One of them is the formation of semiquinone radicals which form with oxygen toxic peroxides which damage the myocyte and lead to cardiotoxicity. Cardiotoxicity of anthracyclines has become a clinical problem as it restricts the administered dose of the cytostatic and has become particularly urgent after discovery of the late toxicity which appears some years after termination of anti-tumourous treatment. Damage of the left ventricle is usually characterized by partial reversible contractile dysfunction (early damage) or progressing contractile dysfunction (late damage). The diagnosis of cardiotoxicity is important during the period of treatment but in particular after completed chemotherapy. The application of diagnostic methods before and in the course of chemotherapy is indicated when large doses of anthracyclines will be administered or when in the patient risk factors cumulate or if he developed signs of cardiotoxicity. The use of diagnostic methods after termination of treatment is valuable for early detection of late cardiotoxicity for timing of further diagnostic methods currently used in cardiology. In the routine diagnosis the authors prefer follow up of the left ventricle by assessment of the ejection fraction by echocardiography or by radionuclide examination. In paediatrics we follow up indicators of systolic left ventricular function in relation to changes of the after load. The authors present also a review of other diagnostic methods and procedures which may prove useful in the diagnosis of cardiotoxicity of anthracyclines.

Baroreflex sensitivity and body growth parameters in children and adolescents.

OBJECTIVE: To determine the difference between baroreflex sensitivity expressed in ms/mmHg (BRS) and in Hz/mmHg (BRSf) in relation to body growth parameters. PATIENTS AND METHODS: Two hundred one children and adolescents aged 10 to 21 years (mean age +/- SD 14.7+/-3.1 years) were examined. This population was analyzed as a whole and subsequently was divided into two groups: group A consisted of normotensive, healthy control subjects (n=154); and group B consisted of children with systolic casual blood pressure on primary diagnosis greater than 140 mmHg, measured three times at least one week apart (n=47). These groups were divided into subgroups according to age. BRS and BRSf were determined by spectral analysis of blood pressure and pulse interval variability (5 min records by Finapres, metronome-controlled breathing at a frequency of 0.33 Hz). Body growth parameters (body height, weight and body mass index [BMI]) were assessed. The Spearman correlation coefficient was calculated between pairs of all parameters (age, pulse interval, BRS, BRSf, height, weight, BMI) for the whole group, for groups A and B, and for age-related subgroups. RESULTS: BRS did not correlate with age; it correlated with pulse interval in the whole population, in groups A and B, and in age-related subgroups. BRS correlated significantly only with weight, height or BMI in the oldest group (age 17 to 19 years), but there was no correlation with groups A or B, or with the whole study population. BRSf correlated significantly (P<0.01) with age, and was pulse interval independent in group A and the age-related subgroups. BRSf correlated with weight, height and BMI in group A and in the whole population, but not in the age-related subgroups. CONCLUSION: BRS (a mean pulse interval-related parameter) does not correlate with age. On the contrary, BRSf (which is mean pulse interval independent) decreases significantly with age. The significant relation between BRSf and parameters of body growth is related to age.

Telomerase activity and expression and telomere analysis in situ in the course of treatment of childhood leukemias.

Samples of blood and marrow from children with leukemia were assayed for telomerase activity and expression on the day of diagnosis and during the course of chemotherapy. A strong correlation between either variables and clinical response was observed in most patients. A unique case was observed in which telomerase activity was only moderately increased on diagnosis; it gradually increased in the course of therapy, and a subsequent decrease occurred only after application of intensified therapy. This patient did not respond to therapy, his disease progressed, and he finally died during intensified therapy. In another patient, analysis of telomere lengths using dideoxy-PRINS revealed a single telomere expansion on a long arm of chromosome 4, suggesting involvement of a telomerase-independent mechanism of telomere elongation.