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Biomedical subjects

M Navrátil

Publications and source records attributed to M Navrátil.

At least 19 recordsLinked to original sources

[Effect of high-dose chemotherapy with subsequent transplantation of blood-forming cells on left ventricle function in patients with malignant lymphomas treated with doxorubicin in primary chemotherapy].

PURPOSE OF STUDY: The authors examined whether high-dose chemotherapy with hematogenic tissue transplantation might negatively affect function of left ventricle (LV) in oncology patients with malignant lymphomas initially treated with conventional chemotherapy consisting of doxorubicin (DOX) in contrast to patients treated without the transplantation in medium-term follow up. PATIENTS AND METHODOLOGY: The follow up group included 77 patients (39 women/38 men) at the age of 36 +/- 15 (median 30, 16-67 years). All 77 patients were treated with initial chemotherapy with DOX, 22 out of that group later received high-dose chemotherapy with hematogenic tissue transplantation (HTT). 16 (73 %) patients of this subgroup underwent autologous transplantation and 5 (23 %) allogeneic transplantation. One female patient (4 %) underwent both autologous and allogeneic transplantation. The follow up period after completion of initial chemotherapy was 5-10 years (median 6 years). The patients were examined with rest echocardiography before start, after chemotherapy, and during follow-up examination. Spiroergometric test (SET) was only performed at the follow-up examination. RESULTS: Both subgroups showed significant decrease of ejection fraction (EF) after chemotherapy, with further decrease in the control examination period, without mutual difference. While the HTT (HTT+) group showed no EF drop below 50 %, in the non-HTT (HTT-) group EF dropped in two (4 %) patients after chemotherapy and in four (8%) patients at the control examination. Progressing decrease of EF > 10 % was reported with 25 % of the HTT- patients (p < 0.05), but with just 13 % of the HTT+ patients (non-significant). The diastolic insufficiency (DF) was present identically in both groups with 36 % of the patients, which represents a statistically significant increase in comparison to the pre-chemotherapy condition. SET did not show any differences in burden toleration and circulation indicators between the two groups. The drop of pVO2 < 20 ml/kg/min occurred with 22 patients of both groups. Linear regression data analysis revealed existence of a significant relationship between EF change, some diastolic function indicators, pVO2 and cumulative dose of DOX (p < 0.05). The current age significantly and negatively correlated with pVO2 (p < 0.001) and DF indicators (p < 0.001). The follow up period inversely correlates with the changes of EF (p < 0.05) and pVO2 (p < 0.05), not correlating with diastolic function indicators. Multi-variant analysis did not confirm any higher risk of administration of high-dose chemotherapy with HTT for significant drop of EF or its drop down to the pathological zone below 50 % (OR = 0.46; non-significant), for discovery of reduced cardio-pulmonary performance (pVO2 < 20 ml/kg/min) (OR = 0.35; non-significant) or for development of diastolic dysfunction (OR = 1.0; non-significant). CONCLUSIONS: Treatment with high-dose chemotherapy with HTT application within medium-term follow up does not result in any significant systolic or diastolic malfunction of myocardium and deterioration of cardiopulmonary performance in comparison to patients not undergoing this therapy. Treatment with cardiotoxic doxorubicin administered in the context of basic conventional chemotherapy is most likely to be responsible for occurrence of the pathological effects across the followed up group. Length of monitoring is a significant factor correlating with changed ejection fraction. This finding justifies the need for long-term prospective monitoring of ejection fraction of the left ventricle in adult patients treated with cardiotoxic chemotherapy.

Adolescent↗

[Late cardiotoxicity in patients with malignant lymphoma treated with doxorubicin chemotherapy].

AIM OF THE STUDY: Chronic cardiotoxicity of doxorubicin occurs at least one year after the chemotherapy is finished. As such, it is a serious late complication in patients with malignant lymphomas. The aim of the study was to identify the incidence of late clinical and subclinical doxorubicin cardiotoxicity and cardiopulmonary performance of patients being in remission for five and more years from the initial therapy. GROUP OF PATIENTS: We worked with 96 patients (47 men and 49 women) aged 43 +/- 15 (median 41, 23-79) years. Average period of monitoring was 6.2 +/- 1.5 (median 6.5-10) years. On the basis of therapy protocol, the patients were administered a maximum doxorubicin cumulative dose (CD DOX) of 377 +/- 147 (median 300, 50-880) mg/m2. Additional treatment after initial conventional therapy was performed in 32 patients (33%) due to high risk, progression or relapse of tumour. EXAMINATION METHODS: Patients were examined by resting echocardiography before and after initial therapy, and during follow-up examination after 5 years. Also, dynamic stress echocardiography and spiroergometry were performed during follow-up examination. Left ventricle ejection fraction (LVEF) decrease below 50 %, progressive decrease of LVEF > 10 % as compared with initial value, and decreased peak oxygen intake pVO2 < 20 ml/kg/min were considered as pathological. We also evaluated systolic function and index of myocardial performance (Tei-index). RESULTS: Clinical cardiotoxicity was observed in 4 % of patients, subclinical in 31% of patients. Diastolic dysfunction was found in 38 % of patients; pathological values of Tei-index were noted in 31% of patients. Value of stress increment of LVEF was 13 +/- 4 % (median 12; 5-25). Decreased pVO2 was observed in 15 % of patients. Cardiovascular disease and age > 60 years represent a higher risk of left ventricular dysfunction. Additional treatment after initial therapy represents a higher risk only if diastolic dysfunction is found (OR = 2.37, p < 0.05). Multi-dimensional regression analysis proved the relationship between pathological EF, CD DOX > or = 300 mg/m2, age > 60 years and cardiovascular disease (for CD DOX p < 0.05; age p < 0.01; concomitant cardiovascular disease p < 0.01, with r = 0.57 and p < 0.02 values for the overall model). CONCLUSIONS: The above-mentioned findings should positively influence the approach of oncologists and haematologists to long-term cardiological monitoring (at least with the help of resting echocardiography) in adult patients treated with antracyclines during initial chemotherapy.

Adult↗

[Histiocytosis from Langerhans cell in adults--experience of one department and review of treatment alternatives].

Thirteen patients with Langerhans cell histiocytosis (LCH) have been treated in hospital Brno Masaryk University during the last 15 years. In 4 cases of this total amount, the diagnosis was made in childhood and these young adults were referred to our department from Pediatric cancer center. In 9 cases, the diagnosis has been made in people elder than 18 years. The disease recidived in 3 patients with LCH diagnosed in childhood, in one case with neurodegenerative impairment of brain. In 4 patients from the total of 9 with LCH diagnosed in age over 18 years, the disease had aggressive course with several recidives. In one case it was pulmonal and multifocal osseal manifestation, in two cases multifocal osseal disease. Isolated pulmonal form of LCH was diagnosed only in one patient. By the first patient, high dose melphalan and etoposide with peripheral blood stem cell transplantation was performed after failure ofvincristin and prednison therapy and failure of etoposide therapy. The first remission after this high dose therapy lasted only 2.5 years. For relapse second cycle of the same high dose therapy was administered, but the next remission was much shorter. By the two patients with multifocal recidives in bones 2-chlordeoxyadenosine was administered as initial therapy. These patients are followed up for more then 24 months and they are without relapse of this disease. The 2-chlordeoxyadenosine is very efficient in multifocal bone form of LCH and has potential to reach long remission. Therefore in a case of aggressive multifocal disease we would prefer 2-chlordeoxyadenosine therapy as therapy of the first choice.

Adult↗

[Comparison of plasmatic levels of B-natriuretic peptide with echocardiographic indicators of left ventricle function after doxorubicin therapy].

THE STUDY OBJECTIVE: The aim of the study was to find out the relationship between plasmatic levels of brain natriuretic peptide (BNP) and echocardiographic indicators of left ventricle (LV) function in patients who were in a long-term remission after the therapy of hematological malignity and examined in order to diagnose the late cardiotoxicity of doxorubicin. METHODS AND PATIENT SAMPLE: We enrolled 55 patients (31 men/24 women) aged 43 +/- 16 (median 41; 21-79) who were treated for historically diagnosed malignant lymphoma. At the time of examination, all patients were in a long-term remission and, at the same time, they completed their initial therapy 6.2 +/- 1.5 (median 5; 5-10) years ago. Patients were examined via resting echocardiography before and after the therapy and during the follow-up examination. We determined the left ventricle ejection fraction (LV EF), parameters of diastolic function and the Doppler parameters of systolic and diastolic function (MPI-Tei index). During the follow-up examination, we measured plasmatic levels of BNP (standard levels were between 0 and 29 pmol/1). RESULTS: Follow-up examination showed that EF of five patients (9 %) decreased below 50% and three patients had symptoms of heart failure. Although EF of another eleven patients (20%) was in the physiological range, it decreased by more than 10% as compared with their pre-treatment EF values. Seventeen patients (30 %) showed higher MPI > 0.55 and twenty patients (36%) demonstrated diastolic dysfunction (impaired relaxation). BNP > 29 pmol/l was observed only in patients with EF < 50% and heart failure symptoms. BNP values significantly correlated only with endsystolic (r = 0.82; p < 0.0001) and enddiastolic (r = 0.72; p < 0.0001) volume of LV. On the other hand, BNP of 11.4 pmol/l showed negative predictive value for the following parameters: 80% for decrease of EF by more than 10%; 72% for detection of MPI > 0.55; and 70% for detection of relaxation disorder, i.e. the diagnostics of subclinical cardiotoxicity. CONCLUSIONS: The present study highlights the practical importance of measuring BNP levels when diagnosing the late changes of LV functions after doxorubicin chemotherapy. Standard cut-off BNP (29 pmol/1) used in diagnostics of heart failures identifies patients with pathological EF and heart failure symptoms. Cut-off BNP of 11.4 pmol/l has sufficient negative predictive value to exclude subclinical damage to the myocardium.

Antibiotics, Antineoplastic↗

Molecular characterization of Czech and Chinese leek yellow stripe virus isolates from garlic.

Using an RT-PCR specific for nuclear inclusion b (NIb) and coat protein (CP) genes of Leek yellow stripe virus (LYSV) we detected two Czech (LYSV-5CZ and LYSV-22CZ) and one Chinese (LYSV-16) isolate of LYSV in garlic plants. The RT-PCR products were cloned and sequenced. Phylogenetic analysis based on deduced amino acid sequence of NIb-CP region placed the Czech isolates in the group I and the Chinese isolate in the group II of LYSV.

Capsid Proteins↗

Daphne mosaic virus (DapMV), a new potyvirus from Daphne mezereum in the Czech Republic.

Daphne shrubs with light green rings and mosaic on leaves contained flexuous filamentous virions (696 x 13 nm) and cylindrical inclusions typical of the subdivision III of Edwardson's classification for inclusions induced by members of the family Potyviridae. Decoration tests using antisera to 67 potyviruses revealed distant serological relations among chilli veinal mottle virus, Colombian datura virus, papaya ringspot virus, tobacco vein mottling virus and yam mosaic virus. The 3' terminal region of the virus genome was amplified by RT-PCR using primers specific for cloned and sequenced members of the family Potyviridae. The most similar sequences in the GenBank were those of isolates of wild potato mosaic virus (WPMV) and yam mild mosaic virus (YMMV), originating from Peru and Guadeloupe, respectively. The new sequence had 63.2% and 61.9% nucleotide identity to WPMV and YMMV in the coat protein gene. The results suggest that the Czech isolate from daphne should be regarded as a new member of the genus Potyvirus. The name daphne mosaic virus (DapMV) is suggested for this virus.

Capsid Proteins↗

[Evaluation of the clinical effectivity and toxicity of the FDN regimen (fludarabin, mitoxantron, dexamethason) in patients with follicular lymphoma].

BACKGROUND: One of the perspective therapeutic possibilities in follicular lymphomas (FL) is the fludarabine-based regimen FND (fludarabine, mitoxantron, dexamethason). However serious signs of myelotoxicity and significant immunosuppression with appearance of the opportunistic infections were described after the fludarabine treatment. METHODS AND RESULTS: Follicular lymphoma patients with advanced disease grade I-II were treated with FND (6-8 cycles). The immunotoxicity was evaluated by measuring of immunoglobuline levels (IgA, IgG, IgM) and that of lymphocytes subpopulations (CD3+, CD4+, CD8+, CD20+, CD56+) in peripheral blood. The myelotoxicity was evaluated by cultures of progenitor cells (CFC and LTC-IC). Totally 34 patients (median age 55.5 years) were evaluated, the overall response was 72% (CR 61%, PR 11%, progression 28%). 73% patients of 11 after 6-8 FND show persisting CR (27% relapsed) with median follow-up about 15 months. The dominating toxicity was myelotoxicity. The leucopenia grade III-IV occurred in about 30% cycles. Because of toxicity it was necessary to reduce doses of FND in 10% cycles and this treatment had to be finished ahead of schedule in 29% patients. The significant immunotoxicity was found only in the decrease of whole lymphocyte population (p < 0.05) and of IgG level (p < 0.05). The decrease of lymphocyte subpopulations did not reach any statistical significance. The long-term myelotoxicity caused the decrease of LTC-IC that had a clinical correlation with the very difficult mobilization of PBSC. CONCLUSIONS: FND is efficient in treatment of follicular lymphoma. However myelotoxicity seems to be limiting. Myelotoxicity doesn't allow administering scheduled dose of FND in substantial amount of patients, long-term myelotoxicity complicates PBSC-mobilization. Lymphotoxicity is apparent, but seems not to be clinically important.

Adult↗

The development of antenna complexes of barley (Hordeum vulgare cv. Akcent) under different light conditions as judged from the analysis of 77 K chlorophyll a fluorescence spectra.

Using 77 K chlorophyll a (Chl a) fluorescence spectra in vivo, the development was studied of Photosystems II (PS II) and I (PS I) during greening of barley under intermittent light followed by continuous light at low (LI, 50 mumol m(-2) s(-1)) and high (HI, 1000 mumol m(-2) s(-1)) irradiances. The greening at HI intermittent light was accompanied with significantly reduced fluorescence intensity from Chl b excitation for both PS II (F685) and PS I (F743), in comparison with LI plants, indicating that assembly of light-harvesting complexes (LHC) of both photosystems was affected to a similar degree. During greening at continuous HI, a slower increase of emission from Chl b excitation in PS II as compared with PS I was observed, indicating a preferred reduction in the accumulation of LHC II. The following characteristics of 77 K Chl a fluorescence spectra documented the photoprotective function of an elevated content of carotenoids in HI leaves: (1) a pronounced suppression of Soret region of excitation spectra (410-450 nm) in comparison with the red region (670-690 nm) during the early stage of greening indicated a strongly reduced excitation energy transfer from carotenoids to the Chl a fluorescing forms within PS I and PS II; (2) changes in the shape of the excitation band of Chl b and carotenoids (460-490 nm) during greening under continuous light confirmed that the energy transfer from carotenoids to Chl a within PS II remained lower as compared with the LI plants.

Journal Article↗

Monitoring of dihydroxyacetone production during oxidation of glycerol by immobilized Gluconobacter oxydans cells with an enzyme biosensor.

A bi-enzymatic biosensor for monitoring of dihydroxyacetone production during oxidation of glycerol by bacterial cells of Gluconobacter oxydans is presented. Galactose oxidase oxidizes dihydroxyacetone efficiently producing hydrogen peroxide, which reacts with co-immobilized peroxidase and ferrocene pre-adsorbed on graphite electrode. This mediator-based bi-enzymatic biosensor possesses very high sensitivity (4.7 µA/mM in phosphate buffer), low detection limit (0.8 µM, signal/noise = 3), short response time (22 s, 95% of steady-state) and broad linear range (0.002-0.55 mM in phosphate buffer). The effect of pH, temperature, type of buffer, as well as different stabilizers (combinations of a polyelectrolyte and a polyol) on the sensor performance were carefully optimized and discussed. Dihydroxyacetone produced during a batch conversion of glycerol by the pectate-immobilized bacteria in an air-lift reactor was determined by the biosensor and by reference spectrophotometric method. Both methods were compared and were in a very good correlation. The main advantage of the biosensor is a very short time needed for sample analysis (less than 1 min).

Journal Article↗

Ifosfamide- and etoposide-based chemotherapy as salvage and mobilizing regimens for poor prognosis lymphoma.

Treatment of early relapsing or resistant non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) remains problematic. High-dose chemotherapy followed by autologous peripheral blood stem cell (PBSC) transplantation improves the prognosis for patients in response following standard dose regimens. We adopted the strategy of using salvage chemotherapy to debulk disease and simultaneously mobilize stem cells. We used regimens based on ifosfamide and etoposide because these drugs are not usually used as the front-line treatment. Twenty-seven patients with NHL received MINE chemotherapy (mesna and ifosfamide 1330 mg/m2 and etoposide 65 mg/m2 i.v. days 1-3, and mitoxantrone 8 mg/m2 i.v. day 1). The same schedule, but higher doses were used for PBSC stimulation (mesna, ifosfamide 1700 mg/m2, etoposide 175 mg/m2, mitoxantrone 10 mg/m2). Forty-six patients with HD received VIM chemotherapy (mesna, ifosfamide 1200 mg/m2 i.v. days 1-5, etoposide 90 mg/m2 i.v. days 1, 3, and 5, methotrexate 30 mg/m2 i.v. days 1 and 5). After both VIM and high dose MINE, chemotherapy for mobilization was followed by G-CSF administered at a dose 5-16 micrograms/kg/day depending on the clinicians judgement of the patient's pretreatment. Complete response after VIM and MINE were 39% and 38%, respectively; partial response (PR) rates were 17% and 29%, and stable disease (SD) 25% and 4%, respectively. In both groups, patients with relapsing disease had better responses than did those with primary progressive disease. Both regimens exhibited excellent mobilizing capacity. We performed 213 aphereses with a median 3 per patient starting on either day 13 as a median for VIM, or on day 12 as a median for MINE. In the majority of patients, the collection started in the time interval median +/- 1 day (n = 62, 85%). The median yields were 10.6 x 10(6) CD34+ cells/kg and 53.1 x 10(4) CFU-GM/kg for VIM, and 13.3 x 10(6) CD34+ cells/kg and 54.5 x 10(4) CFU-GM/kg for MINE. We collected at least 2.5 x 10(6) CD34+ cells/kg in all but six patients (8%), and the harvested amount of CD34+ cells was less than 1.0 x 10(6)/kg in only two patients (3%). The toxicity of VIM and MINE was minimal and chemotherapy-induced trombocytopenia did not occur with PBSC collection.

Adolescent↗

[Non-cytostatic treatment of malignancies. Anti-CD20 monoclonal antibody (Rituximab, Mabthera) in the treatment of non-Hodgkin's lymphoma].

Some types of non-Hodgkin lymphomas cannot be treated by contemporary preparations. After repeated relapses and chemotherapy moreover damage of bone marrow occurs and further intense cytostatic treatment is not possible. Monoclonal antibodies against structures on tumour cells are an interesting alternative of cytostatic treatment. In 2000 the authors administered anti CD20 monoclonal antibody (rituximab, Mabthera Roche), 375 mg/m2, on the 1st, 8th, 15th and 22nd day i.v. to a total of 24 patients with relapsing non-Hodgkin lymphoma. In five patients the relapse developed after high dosage chemotherapy and autologous transplantation of peripheral stem cells. Treatment was well tolerated with minimal side-effects. Favourable therapeutic results were recorded in patients with follicular lymphoma (70% of the therapeutic responses), small lymphocyte lymphomas (64% of therapeutic responses) and in patients with a relapse after autologous transplantations (80% of therapeutic responses). Anti CD20 monoclonal antibody is a new effective alternative of cytostatic treatment. Its position in the therapeutic strategy in patients with non-Hodgkin lymphoma awaits elaboration.

Adult↗

Use of bioluminometry for determination of active yeast biomass immobilized in ionotropic hydrogels.

The technique of bioluminometry was used to determine the biomass concentration of yeast cells immobilized in ionotropic hydrogel beads, including alginate, pectate, and kappa-carrageenan. The method uses determination of ATP extracted from viable cells, the concentration of which is then expressed as the active biomass concentration. Seven yeast strains divided into three categories (brewing, wine-making, and ethanol-producing yeasts) were tested, and different biomass concentrations were determined in all three immobilization materials. The described method is characterized by a good correlation (up to 99%) to classical dry biomass determination. The method is quicker, easier, and not so laborious, providing sufficient determination accuracy, and can be used for a rapid estimation of viable biomass in most biotechnological processes using immobilized living cells.

Biomass↗

[Haematopoietic stem cell mobilization in patients with multiple myeloma--comparison of 3 variations of the stimulating regime].

In the literature various regimes are described for successful collection of haematopoietic stem cells in patients with multiple myeloma. Most frequently cyclophosphamide is used, 5 g/m2 combined with different doses of haematopoietic growth factors. In our group the yields and tolerance of three stimulating regimes are compared: 1. cyclophosphamide 5 g/m2 and filgrastim (G-CSF) 5 micrograms/kg 2. cyclophosphamide 5 mg/m2 and filgrastim 10 micrograms/kg 3. cyclophosphamide 5 g/m2 and figrastim 5 micrograms/kg along with erythropoitin 50 IU/kg. Cyclophsphamide is administered always on the first day and the haematopoietic growth factors then from the third day till the end of collection of haematopoitic cells. In patients with multiple myeloma where only four cycles of VAD chemotherapy preceded and where radiotherapy of the axial skeleton was not used, optimal collection of haematopoietic stem cells was achieved after administration of cyclohosphamide 5 g/m2 with subsequent administration of 5 micrograms/kg G-CSF. By increasing the dose of G-CSF to 10 micrograms/kg or adding 50 IU/kg erthropoietin did not lead to a significant improvement of the tolerance and yield of this procedure.

Cyclophosphamide↗

[Effect of high-dose chemotherapy in patients with relapsing or resistant Hodgkin's disease].

The authors evaluated a group of 48 patients with relapsing or resistant Hodgkin's disease. The patients were treated by life-saving chemotherapy followed by large doses of chemotherapy and autologous transplantation of haematopoietic cells. For life-saving chemotherapy they used most frequently a combination of VIM in 40 patients and combinations of DHAP, MINE, MiniDexaBEAM. In 11 patients they changed the regime of life-saving chemotherapy because of a poor response. After completed life-saving chemotherapy 18 (37.5%) patients were in CR, 27 (56.2%) in PR and in 3 (6.3%) the disease progressed. For large dose chemotherapy the authors used BEAM in 32 patients, CBV in 2, Busulfan with Cyclophosphamide in 13 patients and Busulfan with Melfalan in one patient. After completion of large dose chemotherapy and subsequent autologous transplantation of bone marrow 31 (64.6%) patients were in CR, 8 (16.7%) in PR and the disease progressed in 9 (18.7%). In August 1999 a total of 44.9% patients in CR survive, the median period of follow up after autologous transplantation was 23 months. Life-saving chemotherapy with subsequent large dose chemotherapy led in the investigated group to induction of CR in 64.6% patients which is the basic prerequisite of long-term survival.

Adult↗

[Damage of left ventricular function after treatment with doxorubicin in patients with malignant lymphomas].

The authors evaluated using clinical and echocardiographic examination the effect of chemotherapy involving bolus administration of doxorubicin on the heart muscle in 90 patients with non-Hodgkin lymphoma and with Hodgkin lymphoma. In 18% of patients they found an asymptomatic decrease of the left ventricular ejection fraction during chemotherapy, chronic cardiotoxicity was recorded in 5% patients, in 2% of the patients one year after termination of chemotherapy a clinically latent myocardial infarction was found. The diastolic function was impaired (impaired relaxation) in 44% patients after terminated chemotherapy and in 50% after one year. Echocardiographic examination provided evidence that the impaired systolic and diastolic function persists even after one year following termination of chemotherapy. High-dose chemotherapy with administration of peripheral stem cells did not lead to marked deterioration of left ventricular function as compared with patients who did not undergo this treatment. The main clinical complications--death, cardiotoxicity, relapse of the malignant disease, cardiovascular complications--were present in the course of a 18.5-month follow up after establishment of the diagnosis in 32% of the patients.

Adolescent↗

[Kinetics of hematopoiesis after high-dose chemotherapy and autologous peripheral stem cell transplantation].

BACKGROUND: Autologous peripheral blood stem cell transplantation (APBSCT) is gradually replacing autologous bone marrow transplantation in many clinical settings. The key question is how to evaluate the quality of grafts. We analyzed the relationship between hematopoietic reconstitution and characteristics of patients and grafts. METHODS AND RESULTS: Data from 95 APBSCTs were analyzed. Peripheral stem cells were obtained after mobilization using anti-neoplastic chemotherapy followed by Neupogen (G-CSF). After high dose chemotherapy and APBSCT, patients received Leucomax (GM-CSF). Patients were reinfused with a median of 6.1 x 10(6) (range 0.83-29.3) CD34+ cells/kg, and 25.1 x 10(4) (range 1.0-167.0) CFU-GM/kg of body weight. The median time to engraftment was 12 days (both for granulocytes 1 x 10(9)/l and platelets 50 x 10(9)/l). We found a significant correlation between the number of CD34+ cells and CFU-GM reinfused and also between their respective graft sizes and time to leukocytes, platelets, and granulocytes recovery. We did not find a significant correlation between the number of mononuclear cells reinfused and any analyzed parameter (time to engraftment, age, diagnosis, number of previous chemotherapies, type of mobilization or high-dose regimen). However, administration of preparative high-dose chemotherapy consisted of busulphan and cyclophosphamide was associated with the risk of a transient secondary graft failure. CONCLUSIONS: We conclude that the content of progenitors in PBSC grafts and time to booth leukocyte and platelet recovery are best estimated by the number of CD34+ cells (not less than 1 x 10(6)/kg) and CFU-GM (not less than 1 x 10(4)/kg). The number of mononuclear cells in an autologous PBSC graft is not suitable and useful for prediction of engraftment rate. There is probably no additional benefit of reinfusion of more than 8-10 x 10(6) CD34+ cells/kg and/or 50 x 10(4) CFU-GM/kg, because hematopoietic recovery is not more rapid.

Adolescent↗

[Warning signs preceding the development of septic shock in patients with neutropenia treated for hematologic malignancies].

BACKGROUND: In patients with haematological malignities infectious complications take a very rapid course, and in particular during the period of neutropenia, they are not necessarily manifested by a clear symptomatology. Frequently they may be manifested only by an elevated temperature and general deterioration of the condition. The onset of shock then can be rapid and surprising. The objective of the work was to identify clinical and laboratory signs warning against the possible development of septic shock. METHODS AND RESULTS: The investigation comprised a total of 38 patients hospitalised due to infectious complications at the intensive care unit because of general deterioration of the condition. 18 developed septic shock (group S), the remaining 20 (group N) achieved during hospitalisation at the ICU a stabilised condition. In both groups the laboratory values and clinical condition were followed up for 2-3 days prior to deterioration of the condition. Risk factors for development of septic shock in the group of investigated patients were: unusual weakness, heart rate above 95/min. beyond the temperature peak, hypoalbuminaemia, mucositis, hypokalaemia, presence of a central venous catheter and administration of parenteral nutrition.

Adult↗

[Changes in left ventricular function during chemotherapy with doxorubicin].

The authors investigated by echocardiography changes of left ventricular function in 79 patients with non-Hodgkin lymphoma or Hodgkin's disease who were treated by chemotherapy containing doxorubicin. In 22% patients they diagnosed during treatment a significant gradual decline of the left ventricular ejection fraction (change > 10% or a drop of EF below 50%) after a cumulative dose of 185 +/- 52 mg/m2 doxorubicin (median 200 mg/m2). Changes of the ejection fraction were at the expense of an increasing endsystolic left ventricular volume. These changes correlated closely with the increase of endsystolic stress of the left ventricular wall (r = -0.87). After administration of a cumulative doxorubicin dose of 100 mg/m2 a significant deterioration of indicators of diastolic filling of the left ventricle occurred--of the isovolumic relaxation period (IRP) and deceleration time (DT). The contribution of these early changes of diastolic function of the left ventricle for assessment of the risk of development of systolic dysfunction is not unequivocal. Prolongation of IRP > 12% as compared with the baseline value and at the same time above 95 ms had a 50% sensitivity, 50% specificity, a 26% positive prediction value a 74% negative prediction value and 50% diagnostic accuracy, change of DT > 13%, and at the same time prolongation above 200 ms had a 47% sensitivity 55% specificity, a 22% positive prediction value, a 78% negative prediction value and a 53% diagnostic accuracy. The authors found a significant relationship between the assessed changes of left ventricular function and clinical and haemodynamic indicators. Only the patients' age correlated significantly with IRP and DT values. Changes of the left ventricular ejection fraction were not associated with clinical signs of cardiac failure, they did not call for cardiological intervention and did not affect the course of chemotherapy. Contrary to some statements in the literature, the authors did not consider the described functional changes as sufficient to justify interference with chemotherapy. On the other hand, their importance for the development of late sequelae of chemotherapy with anthracyclines in adult patients must be based on long-term prospective follow-up.

Adolescent↗