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Biomedical subjects

H Gadner

Publications and source records attributed to H Gadner.

At least 55 records · Page 3Linked to original sources
PubMed2001

Pediatric visceral leishmaniasis in Austria: diagnostic difficulties in a non-endemic region.

Visceral leishmaniasis is usually fatal if left untreated. In Europe it is mainly caused by Leishmania infantum which is endemic in the whole Mediterranean region. While visceral leishmaniasis classically affects children, adults increasingly suffer infections in regions which are known to be endemic for HIV. Nowadays up to 70% of the patients with visceral leishmaniasis in southern Europe are HIV-infected adults. The diagnosis is known to be especially difficult to establish in this group of patients because of a frequently atypical clinical presentation, but even in non-HIV-infected patients visceral leishmaniasis often represents a diagnostic challenge particularly when the patient is living in a non-endemic region. We report on four children with visceral leishmaniasis diagnosed at St. Anna Children's Hospital, Vienna, in the last decade. Diagnostic difficulties arose (1) from inexperience with this rare disease, (2) from a long incubation period (6 to 8 months) and (3) from a travel history apparently unsuspicious for the contraction of what is considered a 'tropical' disease. In one case, specific problems resulted (4) from clinical appearance and laboratory data mimicking hemophagocytic lymphohistiocytosis. Consequently even in regions where leishmaniasis is not endemic, diagnostic efforts should be undertaken to rule out this disease especially in patients with the presumptive diagnosis of hemophagocytic lymphohistiocytosis.

Adult↗
PubMed2001

Neuroblastoma cells provoke Schwann cell proliferation in vitro.

BACKGROUND: A subset of human neuroblastomas (NBs) has the capacity to mature completely, imitating sympathetic ganglia. Previously, we showed that the neuronal population in spontaneously maturing NBs usually has a near-triploid DNA content without 1p deletions, and we concluded that the constantly diploid Schwann cells (SCs) do not belong to the neoplastic component of these tumours. We therefore hypothesised that NB cells are able to stimulate SC proliferation, and that SCs trigger NB differentiation. PROCEDURE: We performed in vitro experiments to test this model and to test whether SCs can also influence the growth of aggressive NBs. Human SCs were co-cultivated with NB tumours and cell lines, and were harvested after defined time intervals. Proliferative activity of the SCs and the NB cells was determined by visualisation of 5-bromo-2'-deoxyuridine (BrdU) incorporation or Ki-67 staining. Neurite outgrowth and neurofilament (NF) expression were analysed immunocytochemically and apoptotic rate was determined by a terminal deoxynucleotidyl transferase-mediated dUTP-X fluorescein nick end labelling (TUNEL) assay. RESULTS: Human NB tumours or cell lines unequivocally increased the proliferation of SCs in vitro. In cocultivated NB cells, the proliferative activity was not altered in the first days of cocultivation, although neurite outgrowth and NF expression were enhanced. However, after 10 days, the mitotic rate of neuroblastic cells decreased and the apoptotic rate showed a marked increase. CONCLUSIONS: The results of the cocultivation experiments provide an experimental hint that the in vivo growth of SCs in NBs is caused by the neoplastic neuroblasts, and they also indicate that cells from peripheral nerves can influence the growth of aggressive NB cells if cocultivated.

Antigens, Neoplasm↗
PubMed2001

Intratumoural heterogeneity of 1p deletions and MYCN amplification in neuroblastomas.

BACKGROUND: At least three genetic hallmarks identify aggressive tumour behaviour in neuroblastomas; amplification of the oncogene MYCN; deletion (loss of heterozygosity [LOH]) at the short arm of chromosome 1 (del1p36), seen in approximately 28% of the cases; and di-tetraploidy. The MYCN oncogene is amplified in approximately 23% of all neuroblastomas and becomes important for the stratification of therapy in localised and 4s tumours. Up to now, it has been believed that the genetic constellation of neuroblastic tumours is stable and does not alter during tumour evolution or during tumour progression. PROCEDURE: Using fluorescence in situ hybridisation techniques (FISH) to investigate different tumour areas on touch preparations and histological sections, we show that genetic heterogeneity can be detected in neuroblastomas, especially in tumours detected by urinary mass screening. CONCLUSION: The identification of such cell clones is important, because the MYCN amplification and/or the deletion at 1p36 appear to be responsible for aggressive local growth and development of metastases.

Chromosomes, Human, Pair 1↗
PubMed2001

Automatic detection and genetic profiling of disseminated neuroblastoma cells.

BACKGROUND: Rare tumor cells circulating in the hematopoietic system can escape identification. On the other hand, the nature of these cells, positive for an immunologiCal tumor marker, cannot be determined without any genetic information. PROCEDURE: To overcome these problems a novel computer assisted scanning system for automatic cell search, analysis, and sequential repositioning was developed. This system allows an exact quantitative analysis of rare tumor cells in the bone marrow and peripheral blood by sequential immunological and molecular cytogenetic characterization. RESULTS AND CONCLUSIONS: In that virtually all tumor cells in a mixing experiment could be recovered unambiguously, we can conclude that the sensitivity of this approach is set by the number of cells available for analysis. Sequential FISH analyses of immunologically positive cells improve both the specificity and the sensitivity of the microscopic minimal residual disease detection.

Biomarkers, Tumor↗
PubMed2001

Prognostic significance of DNA di-tetraploidy in neuroblastoma.

BACKGROUND: Identification of biological factors may provide tools to discriminate poor risk neuroblastoma patients of diagnosis, to ultimately offer risk adapted treatment intensity. PROCEDURES: Tumour cell DNA content, MYCN amplification (NMA), deletion of the short arm of chromosome 1 (del 1p) as well as three serological markers were assessed in 179 children with neuroblastoma. RESULTS: Localised regional disease (stage 1 to 3) was diagnosed in 98 patients, and disseminated disease in 81 patients (65 with stage 4, 16 with stage 4s). Median age at diagnosis was 12 months and the median observation time 4 years. Sixty-seven of 179 patients had near di-tetraploid tumours (37%), with a significantly worse prognosis of 44% overall survival at 4 years in comparison with 88% in near triploid tumours (P < .001). The near di-tetraploid group showed a significant correlation with additional adverse biological factors (NMA, del 1p: P < 0.001), age over 1 year (P< 0.001), clinical stage 4 (P< 0.001), elevated ferritin (P = 0.023), and elevated LDH (P< 0.001). Multivariate analysis based on the overall (OS) and event free survival (EFS) estimations revealed that near di-tetraploidy was the most powerful biological factor, with a P-value of <0.001 for EFS and OS, followed by NMA (P = 0.015) for OS and del 1p (P= 0.047) for EFS. CONCLUSIONS: This analysis underlines the important influence of near di-tetraploidy on prognosis, and suggests that more efforts should be undertaken to implement this factor in future studies.

Adolescent↗
PubMed2001

Collection efficiencies of MNC subpopulations during autologous CD34+ peripheral blood progenitor cell (PBPC) harvests in small children and adolescents.

There is increasing demand for mononuclear cell (MNC) harvests not only for PBPC but also for immune therapies using dendritic cells and donor lymphocytes. We determined the collection efficiencies (CE) of various MNC subpopulations during CD34+ cell harvests using a Fenwal CS 3000 Plus Omnix system in small children and adolescents. The cell content of 140 leukapheresis products (LP) was prospectively evaluated in 45 pretreated patients with solid tumors and hematological malignancies. The median age was 12 years (range 0.8-22), and the median body weight (BW) 43 kg (range 9-92). Depending upon the BW of the patients, the media used for priming were saline (SP) in 86, human albumin (HA, HAP) in 10, and packed red blood cells (BP) in 44 apheresis procedures. The major nucleated cell (NC) fractions collected were monocytes (52% of NC) and CD3+ T cells (26%). The median cell yield for monocytes was 174 * 10(6)/kg (range 24-613) representing a CE of 55%. The median number of CD3(+) T cells was 84 * 10(6)/kg (range 5.6-380; CE = 74%). CD34+ cells represented a very small cell fraction of the LP (1.3% of NC), with a median yield of 4.2 * 10(6)/kg (range 0.2-87) and a CE of 63%. The cell yield of various MNCs was significantly correlated with the cell count in the peripheral blood (PB) and with the blood volume processed (ANOVA, P < 0.0001). No influence on the CE was observed for the priming procedure, the patients' age or sex, or the other adaptations used in the harvesting protocol. In conclusion, the Fenwal CS 3000 Plus OMNIX system with the CD34+ cell program and the described adaptations, is also predictably useful for harvest of monocytes or lymphocytes in pediatric patients. We present regression equations that predict the cell yield of various MNC subpopulations in apheresis products.

Adolescent↗
PubMed2001

Pattern and course of single-system disease in Langerhans cell histiocytosis data from the DAL-HX 83- and 90-study.

BACKGROUND: Single-system (SS) disease is the most common presentation in Langerhans cell histiocytosis (LCH) with a heterogenous clinical picture and course. Mostly bone and rarely skin or lymph nodes are involved. PROCEDURE: One hundred and seventy patients with SS-LCH were registered in the DAL-HX 83/90 studies. They were diagnosed according to uniform diagnostic criteria and followed by a standardised schedule. RESULTS: Single bone lesions were most common (68%), followed by multiple bone lesions (19%), isolated skin disease (11%), and isolated lymph node involvement (4 patients). In the detection of bone lesions radiographic skeletal survey proved to be superior to bone scan (97% vs. 82%). Treatment comprised surgery, irradiation and local instillation of steroids, and standardised chemotherapy for multifocal bone disease. After initial therapy 81% of the patients remained disease free. Reactivations restricted to the skeleton occurred in 18% of both unifocal and multifocal bone disease. Two skin patients had a chronic course. Fatality occurred only in one infant with skin disease who progressed to multi-system disease. Twenty-five percent of all patients developed permanent consequences, which were already present at diagnosis in about half of these patients and comprised mainly orthopedic problems related to lesional sites. Diabetes insipidus occurred in 3% and anterior pituitary dysfunction in 2% of the patients. CONCLUSIONS: The course in SS%LCH was benign. In bone disease reactivations remained restricted to the skeleton and did not influence survival. However, reactivations had an impact on morbidity, as permanent consequences were mostly related to the site of disease activity. Med Pediatr Oncol 2001;37:108-114.

Adolescent↗
PubMed2001

Favorable outcome for children and adolescents with T-cell lymphoblastic lymphoma with an intensive ALL-type therapy without local radiotherapy.

In study NHL-BFM 90 we investigated the efficacy of an ALL-type treatment without local radiotherapy for childhood T-cell lymphoblastic lymphoma (T-LBL). In particular, the prognostic impact of the speed of tumor regression was evaluated. From April 1990 to March 1995, 105 evaluable patients, 1.1-16.4 years of age, with T-LBL were enrolled into study NHL-BFM 90. Patients with stage I and II received an 8-drug induction followed by a consolidation including high-dose-methotrexate (MTX) and maintenance therapy up to a total therapy duration of 24 months. Patients with stage III and IV received an additional reinduction and cranial radiotherapy (CRT) (12 Gy for prophylaxis) between consolidation and maintenance. Residual tumor after completion of induction had to be resected. No local RT was applied. Patients received intensified chemotherapy if tumor regression on day 33 of induction was <70% or when vital residual tumor was present after the induction phase. With a median follow-up of 6.41 years, pEFS at 5 years is 91.4% (SE+/-2.7%). 101 patients were evaluable for the speed of tumor response. Two patients received intensified therapy due to <70% tumor regression on day 33. Of 19 patients with tumor residues after induction, 2 relapsed as compared to 4 of 80 patients with complete tumor regression. Our data demonstrate that, with intensive ALL-type chemotherapy but no local radiotherapy, an event-free survival rate of 90% can be achieved in childhood T-LBL. Providing tumor regression within 5 weeks is sufficient, tumor remnants after induction have weak prognostic impact.

Adolescent↗
PubMed2001

Treatment with all-trans retinoic acid in acute promyelocytic leukemia reduces early deaths in children.

All-trans retinoic acid (ATRA) is a known inducer of differentiation in acute promyelocytic leukemia. To improve the outcome of children with acute promyelocytic leukemia, ATRA has been applied since 1994 as an additional induction element inthe AML-BFM 93 study. In a retrospective study, we compared 22 children treated with ATRA (median age: 9.3 years; range: 1.8-16.3) with 22 patients receiving conventional therapy (median age: 12.3 years; range: 3.2-16.7). Twenty-one of the children achieved complete remission. Only one patient died early from bleeding complications after 3 days administration of ATRA. In the control group, seven early deaths occurred (Fisher exact test; p<0.04). Two children died from intracerebral hemorrhages. Two patients suffered from sepsis during aplasia after induction therapy, and one child did not respond to treatment. The 5-year overall survival (OS) and event-free survival (EFS) of the children who received ATRA followed by chemotherapy were significantly bettercom-pared with conventionally treated children [OS: 0.87 +/- 0.9 vs 0.45 +/- 0.11, p (log rank) <0.003; EFS: 0.76 +/- 0.11 vs 0.43 +/- 0.11 p (log rank) <0.02]; the median observation time was 2.8 years (19-76 months). However, nearly all children suffered from common side effects such as headache, fever, joint, muscle and bone pain, weight gain, or dermatitis. In three patients, a retinoic acid syndrome was observed. Interruption of ATRA treatment and application of dexamethasone, necessary in 12 children, controlled theadverse effects. ATRA treatment could be resumed in 18 patients. In conclusion, ATRA treatment during induction could avoid early deaths in children with acute promyelocytic leukemia with considerable but manageable toxic side effects.

Adolescent↗
PubMed2001

Allogeneic bone marrow transplantation-mediated transfer of specific immunity against Toxocara canis associated with excessive IgE.

A girl with myelodysplastic syndrome (RAEB-T) received HLA-identical bone marrow from her younger brother after myeloablative treatment with busulfan and cyclophosphamide. After bone marrow transplantation, fever, exanthema, pruritus, and a pulmonary infiltrate were treated symptomatically. Bacterial cultures remained negative. Leukocyte engraftment began on day 10, and all blood cell populations proved to be of donor origin on FISH analysis. Increasing IgE levels (21 000 U/ml) on day 14 after BMT, positive RAST, specific IgG-antibodies, and missing Toxocara (T.) canis antigens in the recipient indicated donor-derived seroconversion. Before BMT, the recipient had been negative for T. canis in routine parasitological screening, and the donor proved to be positive for T. canis antibody by ELISA. This report suggests that the transfer of IgE immunity in the absence of detectable antigens may be responsible for IgE-mediated symptoms consistent with toxocara infection and confirms the need for parasite screening in donor medical examinations.

Adoptive Transfer↗
PubMed2001

Influence of transplantation regimen on prognostic significance of high-level minimal residual disease before allogeneic stem cell transplantation in children with ALL.

High MRD levels before transplantation in children receiving T cell-depleted unrelated grafts for relapsed ALL were associated with a 100% relapse risk. We report on two children with relapsed ALL who underwent non T cell-depleted BMT from unrelated donors. Despite a high residual tumor load pre- transplant and the occurrence of only aGVHD grade I, they are still in second complete remission 2.7 and 5.2 years after transplantation, respectively. Thus, we propose that the transplant regimens influence the prognostic significance of high MRD levels pre-BMT.

Burkitt Lymphoma↗
PubMed2001

Idarubicin improves blast cell clearance during induction therapy in children with AML: results of study AML-BFM 93. AML-BFM Study Group.

In the randomized trial AML-BFM 93 we compared 60 mg/m2/day daunorubicin with 12 mg/m2/day idarubicin for 3 days each, combined with cytarabine and etoposide during induction. Results showed a significant better blast cell reduction in the bone marrow on day 15 in patients of the idarubicin arm (25 of 144 = 17% of patients with > or = 5% blasts compared to 46 of 149 = 31% of patients after daunorubicin, Pchi2 = 0.01). This was, however, mainly seen in high risk patients treated with idarubicin (19% vs 38%, Pchi2 = 0.007). Cardiotoxicity, WHO grade 1-3 shortening fraction reduction after induction occurred in 6% patients in both arms. Bone marrow toxicity differed slightly with a median recovery time of neutrophils >500/microl of 25 days (daunorubicin) compared to 27 days (idarubicin), P = 0.05. In the total group of patients probabilities of 5 years event-free survival and disease-free survival were similar for patients treated with daunorubicin or idarubicin (49% +/- 4% vs 55% +/- 4% and 57% +/- 4% vs 64% +/- 4%, P logrank 0.29 and 0.15, respectively). However, in patients presenting with more than 5% blasts on day 15 there was a trend for a better outcome after treatment with idarubicin (P logrank 0.06). Together with the early effect seen for high risk patients these results indicate a better efficacy of idarubicin than of daunorubicin during induction with a similar rate of toxicity.

Antibiotics, Antineoplastic↗
PubMed2001

Management of immune thrombocytopenic purpura in children.

Immune thrombocytopenic purpura (ITP) is the most common acquired bleeding disorder occurring in previously healthy children and can be classified into two major forms. Acute and chronic ITP are benign conditions with a high probability of spontaneous recovery with or without therapy. Rates of 80-90% complete remission can be achieved irrespective of the treatment given. In only 10-20% of children thrombocytopenia persists for more than six months, showing a chronic course, which also has a high probability of remitting over time (up to 80% or more). The variability of the clinical course, and the lack of consistent clinical features, make the decision on whether and how to treat difficult. Most physicians are driven to treat all children with symptoms by concern over life-threatening hemorrhage, although the risk of intracranial hemorrhage (ICH) is only 0.1-0.9%. The commonly used treatment regimens for acute ITP are corticosteroids, intravenous immunoglobulins (IVIgG), or intravenous anti-D immunoglobulin (anti-D). So far, there is no evidence that initial therapy can prevent ICH or a chronic course of the disease. In chronic ITP the same drugs are generally used and it seems that pulses with steroids may be just as effective as IVIgG. Anti-D may also be considered a reliable and cheap alternative for chronic disease. A major problem in the management of chronic ITP is the question of whether repeated infusions of Ig (IVIgG or anti-D) and/or corticosteroids can postpone or ultimately preclude splenectomy, which must be considered only for a small proportion of patients resistant to therapy. In these cases, a laparoscopic approach should be preferred. Children who fail to respond to splenectomy (< 20% of cases) warrant second line treatment with other drugs, like cyclophosphamide or azathioprine and deserve a revisit of diagnosis for exclusion of secondary ITP.

Child↗
PubMed2001

A randomized trial of treatment for multisystem Langerhans' cell histiocytosis.

OBJECTIVE: To compare 2 active agents, vinblastine and etoposide, in the treatment of multisystem Langerhans' cell histiocytosis (LCH) in an international randomized study. STUDY DESIGN: One hundred forty-three untreated patients were randomly assigned to receive 24 weeks of vinblastine (6 mg/m(2), given intravenously every week) or etoposide (150 mg/m(2)/d, given intravenously for 3 days every 3 weeks), and a single initial dose of corticosteroids. RESULTS: Vinblastine and etoposide were equivalent (P > or = .2) in all respects: response at week 6 (57% and 49%); response at the last evaluation (58% and 69%); toxicity (47% and 58%); and probability of survival (76% and 83%) [corrected], of disease reactivation (61% and 55%), and of developing permanent consequences (39% and 51%) including diabetes insipidus (22% and 23%). LCH reactivations were usually mild, as was toxicity. All children > or = 2 years old without risk organ involvement (liver, lungs, hematopoietic system, or spleen) survived. With such involvement, lack of rapid (within 6 weeks) response was identified as a new prognostic indicator, predicting a high (66%) mortality rate. CONCLUSIONS: Vinblastine and etoposide, with one dose of corticosteroids, are equally effective treatments for multisystem LCH, but patients who do not respond within 6 weeks are at increased risk for treatment failure and may require different therapy.

Adolescent↗
PubMed2001

And the sun keeps shining.

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Antineoplastic Combined Chemotherapy Protocols↗