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Biomedical subjects

P Kavan

Publications and source records attributed to P Kavan.

At least 19 recordsLinked to original sources

[Effect of amifostine on reducing acute toxicity of megachemotherapy of tumors in children].

BACKGROUND: Amifostine (WR-2721, Ethyol) is a chemoprotective agent. There is little experiences with amifostine application in megachemotherapy in children. We evaluated amifostine effect on the reduction of the acute toxicity. METHODS AND RESULTS: Retrospective comparison of patients who received amifostine with the control group (72 vs. 72). Amifostine 750 mg/m2 was given 15 minute before cytostatic dose and regularly each eight hours if we administered cytostatics continuously. Megachemotherapy schedule included melfalan, carboplatin, cyklophosphamid, vepesid, busulfan, thiotepa and karmustin. Type of graft: peripheral stem cells 56 vs. 29, bone marrow 8 vs. 30, combination 8 vs. 13. Nonhematological toxicity: mucositis p = 0.047, hepatotoxicity p < 0.001, nephrotoxicity p = 0.005. Hematological toxicity: engraftment D + 12 vs. D + 15 (p < 0.001), amount of erythrocyte transfusions 3 vs. 6 (p < 0.001), platelet transfusions 7 vs. 9 (p = 0.06), days when number of platelets reaches 20,000 without substitution D + 15 vs. D + 22 (p < 0.001). The only statistically difference was in the in total amount of platelets (p = 0.032), when we calculated patients, who received peripheral stem cells. Number of hospitalization days 14 vs. 18 (p = 0.016), days with antibiotics 14 vs. 18 (p = 0.016), number of febrile days 6 vs. 7 (p = 0.51). CONCLUSIONS: Amifostine reduces mucosal, liver and kidney damage. The graft type could affect hematological results.

Adolescent↗

[131I meta-iodobenzylguanidine in combination with hyperbaric oxygen therapy in the treatment of prognostically high-risk forms of neuroblastoma].

BACKGROUND: Despite of improving diagnostics, development of new drugs and treatment strategies, patients with biologically unfavourable, advanced or relapsed neuroblastoma remain practically incurable. Treatment related toxicity, requirement for personnel and financial costs have became limiting. Tumor specific therapy represented by 131I-meta-iodobenzylguanidine (MIBG) administration could become an alternative improving the overall survival. In comparison with standard external radiotherapy the targeted therapy enables to achieve radiation 5 to 10 times higher with lower organ toxicity. Data published by European and American colleagues brought evidence of high efficacy of this method. It motivated us to set and develop the method at our department. TYPE OF STUDY: Retrospective analysis of therapeutic results and side effects of the administration of 131I-meta-iodobenzylguanidine in high-risk neuroblastoma patients cured at the Department of Pediatric Oncology in Prague since 1997 till 2000. METHOD AND RESULTS: 131I-meta-iodobenzylguanidine was fourteen times therapeutically administered in seven high-risk relapsed neuroblastoma patients. Four children received a single dose of 131I-meta-iodobenzylguanidine, three patients were treated repeatedly. The first dose represented 5.5 GBq, repeated dose 3.7 GBq, irrespective to the body weight. Each MIBG administration was followed by four days hyperbaric oxygen therapy. The treatment was well tolerated, acute and late side effects were not serious and only rarely reached grade 3 or 4 according to the International North American Children's Cancer Group Classification. Three of the seven children have survived with no evidence of the disease. Four children died of the disease progress. CONCLUSIONS: 131I-meta-iodobenzylguanidine treatment combined with hyperbaric oxygen therapy becomes a well-tolerated therapy for high-risk neuroblastoma patients non-responding to the conventional treatment. Though the 131I-meta-iodobenzylguanidine administration probably cannot cure these patients, the repeated administration can bring long lasting remission.

3-Iodobenzylguanidine↗

[Detection of minimal residual disease in Ewing's sarcoma using RT-PCR].

BACKGROUND: More than 90% of Ewing's sarcomas (ES) contain a fusion of the EWS and FLI-1 genes, due to the t(11;22)(q23;q12) translocation. At the molecular level, the EWS-FLI-1 rearrangement shows great diversity. Specifically, many different combinations of exons from EWS-FLI-1 encode in-frame fusion transcripts and result in differences in length and composition of the chimeric protein, which function as an oncogenic aberrant transcription factor. The finding of this translocation gives evidence for the presence of ES cells. The aim of this prospective study was to verify applicability of the RT-PCR method for the detection of minimal residual disease in patients with ES. METHODS AND RESULTS: Conditions for the detection of Ewing's sarcoma cells by means of the reverse-transcriptase polymerase chain reaction (RT-PCR) at fusion transcripts in peripheral blood, bone marrow (BM) and autologous hematopoietic stem cell grafts in patients with ES were appointed. 31 samples of BM, 5 samples of blood and 7 peripheral blood grafts obtained from 23 patients were investigated. Presence of tumor cells was identified in 7 BM samples from 7 different patients (31 samples from 16 patients), all the peripheral blood and graft samples were negative. CONCLUSIONS: The high sensitivity of RT-PCR method in detection of cells bearing t(11;22)(q23;q12) was demonstrated in the experimental model and clinical samples. Likewise the literary statements, the RT-PCR method was found to be more sensitive than cytology.

Adolescent↗

[High-dose chemotherapy in the treatment of children with malignant lymphoma].

BACKGROUND: Children with primary refractory or recurrent malignant lymphoma have usually poor prognosis. Less than 10% of those, who were treated with conventional-dose regimens had survived for 2 years. In an attempt to improve the outcome for these patients, we explored the role of consolidation high-dose chemotherapy with autografting. METHODS AND RESULTS: Forty-five patients with poor-prognosis lymphoma, of whom 27 were males, underwent megatherapy between January 1992 and December 1999. High-dose chemotherapy was indicated in patients with poor initial response to first-line chemotherapy (14 cases) or in the relapse (31 cases). The group consisted of 27 patients with Hodgkin's disease and 18 patients with non-Hodgkin's lymphoma. The median age was 14.7 years. The conditioning for Hodgkin's disease patients contained cyclophosphamide, etoposide and busulfan or carmustine. Patients with non-Hodgkin's lymphomas received cyclophosphamide, etoposide and busulfan or total body irradiation. Bone marrow was used as the source of haemopoietic stem cells in ten patients, peripheral blood in twenty-eight, and both sources were used in seven patients. After the median follow-up of 47 months, the final survival was 61%. Eleven patients died of the disease progression, four of the infectious complications, one at a car accident. Median time to relapse after the transplantation was 7.5 months. CONCLUSIONS: Further improvement of these results will require earlier transplantation, improved preparative regiments or early posttransplant immunotherapy.

Adolescent↗

Treatment of children and adolescents with non-Hodgkin's lymphoma (results based on the NHL Berlin-Frankfurt-Münster 90 protocols).

BACKGROUND: To determine the feasibility and results of treating children with non-Hodgkin's lymphomas (NHL) according to very intensive protocols based on the German Berlin Frankfurt Münster NHL 90 study. METHODS AND RESULTS: From 1991 until 1995 eighty two patients less than 18 years of age with NHL were admitted to our department. Sixty three of them were eligible for the study. The entire group consisted of 43 males and 20 females (ratio 2.1:1). Median age was 10 2/12 years. Eleven had stage I disease, 4 stage II, 29 stage III and 19 stage IV disease. Histologies represented were: large cell lymphoma 22, lymphoblastic lymphoma 19, and Burkitt lymphoma 10 patients. In 12 cases the immunophenotype was not further classified as to B-cell or T-cell subtype. Patients were stratified into the therapy groups "B" or "non B" according to histopathology, clinical stage and LDH level. Therapy for the B group consisted of 2, 4 or 6 courses of intensive 5 day pulses of 6 drugs. Patients in the non B group received the protocol for acute lymphoblastic leukemia including reinduction and CNS irradiation for advanced stages. At a median follow-up of 35 months the probability of event free survival (pEFS) at 5 years 70% and overall survival 73% for entire group. For therapy group B pEFS was 76%. The non B therapy group had a pEFS 60% (p = 0.22). There was a significantly better outcome for children classified as stage I and II. There was no statistical difference between stage III and IV. Treatment results were comparable between NHL subtypes, except for large cell lymphomas, which did significantly better (pEFS 90%). CONCLUSIONS: The use of protocols based on BFM 90 study in the Czech Republic was feasible. The pEFS are approximately 10% lower than the German study but comparable to some other studies. Outcome for large cell lymphomas was excellent. Reduction of treatment related complication and mortality rate as well as more precise classification are required.

Adolescent↗

[Advances in the diagnosis and treatment of neuroblastoma].

Neuroblastoma is the second most common solid tumor in children. The prognosis is poor for approximately 70% of patients who have widespread disease at the time of diagnosis. The use of new strategies for classification and therapy has raised expectations for cure in advanced neuroblastoma. We summarise results and experiences reached during the last decade.

Child↗

Pseudomembraneous clostridium after autologous bone marrow transplantation.

Clostridium difficile (C. difficile) pseudomembraneous colitis was diagnosed in a 13-year-old boy with Hodgkin's disease 3 months after autologous bone marrow transplantation. Hematopoiesis was fully reconstituted at the time. C. difficile infection occurred after gall bladder empyema had been treated conservatively with i.v. antibiotics and prophylactic 4-week administration of oral amoxicillin. C. difficile colitis was diagnosed early and intensive supportive therapy combined with administration of i.v. and subsequently oral vancomycin therapy failed. It is a phenomenon rarely seen and successful eradication of the clostridium infection was only achieved by a combination of higher dose vancomycin with metronidazole. During the post-colitis recovery the patient experienced a relapse of Hodgkin's disease and died following further surgical intervention 137 days post-transplantation.

Adolescent↗

[Purging of hemopoietic progenitor cells in autologous transplantation].

The authors describe the results of purification of bone marrow and peripheral progenitor cells (PBPC) for clinical transplantations. Vepeside was used to purify in 1990-1995 a total of 41 bone marrows of adults and children. Of these 23 were transplanted. Maphosphamide was used bone marrow purging in two patients; transplantation was performed in one case. By a combination of Vepeside with methylprednisolone haematopoietic cells of 24 patients were purged, transplantations were performed in 10. Three-day cultivation of haematopoietic cells in the presence of Desferal was used for purging cells of 22 patients with neuroblastoma; transplantations were performed in 10 patients. The authors give the values of nucleated cells, haematopoietic colonies of CFU-GM and CD34 positive cells obtained after purification calculated per kg body weight of the patient and the percentage yields.

Adult↗

[N-myc oncogene amplification in tumors of the sympathetic nervous system: preliminary study of methods and clinico-pathologic correlations].

Tumors of the sympathetic nervous system (NT), namely neuroblastoma (NB) and ganglioneuroblastoma (GNB), have a variable clinical course. Prognostic factors include clinical stage, age of the patient, histological grade, and changes at the genomic level, of which amplification of N-myc oncogene is a well recognized phenomenon. The aim of this study was to establish the status of the N-myc oncogene in NT and to compare the results with histopathological grading, with risk groups according to criteria outlined by Joshi et al., and with the clinical stage. To detect the amplification of N-myc oncogene we used differential polymerase chain reaction (D-PCR). Amplified N-myc oncogene was found in 10 out of 31 investigated children with NB (32%). The result of D-PCR could not be interpreted reliably in two patients. Of seven children with GNB the N-myc amplification was found in one case. None of seven children with ganglioneuroma was found to have amplified N-myc oncogene. The tumors with N-myc amplification were histologically poorly differentiated of undifferentiated with a high mitotic activity-8 children were classified as a high risk category; in two we had not enough surgical material to evaluate the histological prognostic factors. The correlation of N-myc status with clinical stage revealed N-myc amplification in two of 9 children classified as clinical stage III, and in eight of 11 children classified as clinical stage IV. The N-myc amplification was not found in any child diagnosed at stage I, II and IV. Five of 10 children with NB and N-myc amplification died of the disease progression. Four children died in the group of 19 children without N-myc amplification. The median of follow-up was 18 months. The patient with GNB and N-myc amplification also died of the disease progression. Although the follow-up period of the investigated group of patients was short, the results showed that the amplification of N-myc oncogene was associated with tumors of patients diagnosed at a late clinical stage (III and IV), and with tumors whose morphology and age were assessed collectively under the term "high risk group".

Child↗

[Allogenic transplantation of bone marrow in childhood].

BACKGROUND: Bone marrow transplantation has become the therapeutic method in some forms of malignant haemotopoietic diseases, malignant tumours, inborn errors of metabolism and immunodeficiency states. The objective of the presented work is the analysis of 40 allogenic bone marrow transplantations in children made in 1989-1994. METHODS AND RESULTS: Bone marrow transplantation was made in 40 children (26 boys and 14 girls), mean age 10.5 years (range 1.5-17.5 years). Indications were acute lymphoblastic leukaemia in 11, acute myeloid leukaemia in 10, chronic myeloid leukaemia in 6, myelodysplastic syndrome in 2, aplastic anaemia and Fanconi's anaemia in 7, non-Hodgkin lymphoma in 2 and inborn errors in 2 children. The donor was in 33 patients in HLA identical sibling and in seven instances a monozygotic twin, HLA non-identical sibling or relative or unrelated matched donor. Bone marrow engraftment was achieved in 35 (87.5%) patients, in one instance the bone marrow was rejected (2.5%) and in four patients (10%) early death occurred before the bone marrow engraftment. On Aug. 15, 1995 20 patients (50%) survived, a relapse developed in 7 (17.5%) and 13 patients died in conjunction with the transplantation (32.5%). The most frequent cause of death were infectious complications (9 children) either in conjunction with the development of graft versus host reaction (6x) or without signs of this reaction (3x). As a prophylaxis of graft versus host disease 24x Cyclosporine A with corticosteroids was used, 16x with methotrexate. A chronic graft versus host disease developed in 6 of 28 children surviving 100 days after transplantation. The greatest problem are infectious (bacterial and mycotic) complications in the phase of bone marrow aplasia before engraftment of the transplanted bone marrow or in conjunction with a graft versus host reaction which cannot be completely avoided by preventive measures. CONCLUSIONS: Bone marrow transplantation is also in children an effective therapeutic method of some forms of malignant haematopoietic diseases, malignant tumours and immunodeficiency states. The correct indication, suitable donor, preventive measures against the graft versus host reaction and protection against infectious complications are essential for the success of this pretentious treatment.

Adolescent↗

[Accuracy of ultrasound measurements of the axial length of the eye].

Ultrasonic assessment of the axial length of the eye provides important baseline data for the calculation of the dioptric power of an artificial intraocular lens. The accuracy of ultrasonic biometry performed by an OPHTASCAN B apparatus is discussed based on evaluation of a group of repeated measurements of the axial length and depth of the anterior chamber in 592 bulbi.

Adult↗

[Comparison of the predicted and actual refraction of the eye after intraocular lens implantation].

After previous assessment of the dioptric potency (by means of a SRK formula) the authors implanted the appropriate intraocular lenses. After 4-18 months following implantation the calculated refraction calculated before the intervention was compared with the postoperative reality. In 85% the difference was not greater than +/- 1.5 Dsf. The calculation of aniseiconia was made only in case of preoperative ametropia greater than +/- 2 Dsf.

Humans↗

[Extraction magnets in ophthalmology].

Magnetic extraction of foreign bodies has been used in the ophthalmologic practice more than one hundred years. The magnetic field of the extractive magnet causes the magnetization of the material present in the foreign intraocular body. Magnetization could be induced only in the ferromagnetic bodies and enables surgeons to perform the extractions. At this time the hand-manipulated and the based magnets are used, without adequate adaptability for the needs of now prevailing ocular microsurgery. Authors explain the use of the new generation of the extraction performed by means of the permanent magnet ORMEX which is based on Czechoslovak invention of the magnetic system ORMAKON characterized by significantly increased effectivity.

Eye Foreign Bodies↗

[Permanent Ormex magnets in clinical practice].

Permanent magnets ORMEX have been successfully used in 14 extractions of the foreign intraocular nodies localized in the anterior and posterior segments of the eye. These magnets proved to be more advantageous than the usually used electromagnets, with respect to their size, weight, easier manipulation and usual mode of sterilization. The ORMEX magnets do not need source of the electric energy and their energetic performance is greater than of the routinely used magnets of the Hirschberg's type. Authors recommend to equip all ophthalmic stationaries with these permanent ORMEX magnets.

Adolescent↗

Clinical ineffectiveness of IL-2 and/or IFN alpha administration after autologous PBSC transplantation in pediatric oncological patients.

Clinical impact of s.c. administration of IL-2 and/or IFN alpha was studied in 23 pediatric patients with Hodgkin lymphoma (IFN alpha group) and sarcoma, non-Hodgkin lymphoma, peripheral neuroepitelioma, neuroblastoma, and embryonic carcinoma (IL-2 + IFN alpha group) after autologous PBSC transplantation. Expression of CD3, CD4, CD8, CD25, CD38, CD56, CD71, CD122, and HLA-DR antigens, serum level of the soluble IL-2R alpha, and NK activity against K562 cell line were evaluated in 11 patients representative for both types of immunotherapy. T and, more markedly, NK cell proliferation, induction of activation markers on the surface of T and NK subsets, and elevation of sIL-2R alpha concentrations were seen in the IL-2 + IFN alpha subgroup. In the IFN alpha subgroup, the total number of lymphocytes and expression of activation markers remained unchanged, but the number of CD8+ T cells increased at the expense of CD4+ T and NK cells during the therapy. Cytotoxic activity against K562 cells was not influenced by the immunotherapy in either subgroup. No significant clinical benefit of the immunotherapy was seen in these patients compared to 27 control patients with relevant diagnoses who did not receive immunotherapy.

Adolescent↗

Treatment of pediatric B-cell non-Hodgkin's lymphomas at the Motol Hospital in Prague, Czech Republic: results based on the NHL BFM 90 protocols.

Malignant non-Hodgkin's lymphomas (NHL) of childhood and adolescence are a heterogeneous group of diseases originating from the lymphoid cells. Unlike adults with non-Hodgkin's lymphoma, children typically have extranodal disseminated disease of high grade (Burkitt's lymphoma, large cell lymphoma, or lymphoblastic lymphoma). This study was conducted to determine the feasibility of treating children in the Czech Republic with B-cell non-Hodgkin's lymphomas according to very intensive protocols based on the German Berlin Frankfurt Munster (BFM) NHL 90 study. Treatments are divided in the BFM studies according to "B" and "non-B" immunophenotypes. The authors report only those treated according to the BFM B-cell protocol. From 1991 through 1997 eighty-two patients less than 18 years with NHL were admitted to the department. Seventy-three of them were classified as B-cell lymphoma and 54 were thus eligible for the BFM B-cell treatment. The entire group consisted of 38 males and 16 females (ratio 2.38). Median age was 11.6 years. Twelve had stage I disease, 3 stage II, 30 stage III, and 9 stage IV lymphoma. There were 21 patients with Burkitt's lymphoma, 29 with large cell lymphoma, of which 5 were patients with MALT lymphoma. In 3 cases B-cell NHL was not further classified and one child had a mediastinal B lymphoma. Patients were further stratified according to clinical stage and lactate dehydrogenase (LDH) level. Therapy consisted of a prephase and short (2, 4, or 6 courses), intensive 5-day therapy with 6 drugs. The probability of event-free survival (pEFS) for the entire group was 74% and overall survival at 5 years was 80%. There was a significantly better outcome for children classified as stage I. No difference was observed between the EFS of stage III and IV patients. Four patients died from treatment-related complications in complete remission. Treatment results were not identical between NHL subtypes, with large cell lymphoma patients doing significantly better (pEFS 90%, p = .008). The use of protocols based on BFM 90 study was feasible at this center. The treatment results are approximately 10% lower than those reported by BFM investigators, but comparable to results from other centers.

Adolescent↗