Quantum diffusion and localization of positive muons in superconducting aluminum.
Explore the source record for details and available documents.
Journal Article↗
Biomedical subjects
O Hartmann
Publications and source records attributed to O Hartmann.
Morphologic and molecular cytogenetics in neuroblastoma.
BACKGROUND: Some genetic alterations have been shown to have prognostic implication for patients with neuroblastoma: MYCN oncogene amplification, deletion of the short arm of chromosome 1 and di- or tetraploidy. The goal of this study was to analyze these factors in children with neuroblastoma. METHODS: Twenty neuroblastoma samples were analyzed with morphologic cytogenetics, and each of them was compared with MYCN amplification status by Southern blot and fluorescent in situ hybridization (FISH) with a genomic probe. RESULTS: A complete karyotype was obtained for 14 children. A diploid or tetraploid mode and a 1p deletion were found in most children with advanced stages. MYCN amplification status was totally concordant with both methods in all patients, even in a case with low level amplification. A wide intercellular variation in the amplification level in each MYCN amplified sample was shown. CONCLUSION: The use of FISH to assess MYCN amplification rapidly in neuroblastoma is recommended. This method could be very useful in future therapeutic protocols in which treatment is based on MYCN status (and especially for infants and children with localized tumor).
Adolescent↗
Incidence of bone marrow involvement in Ewing's sarcoma: value of extensive investigation of the bone marrow.
PURPOSE: Bone marrow (BM) status is a critical matter when intensified chemotherapy with bone marrow rescue is proposed to improve the survival of patients with poor prognosis Ewing's sarcoma (ES): metastatic or relapsing disease. A systematic bone marrow investigation was performed in all the patients with newly diagnosed ES or relapsing ES to assess their BM status. PATIENTS AND METHODS: From January 1985 to February 1989, 59 untreated patients and five patients at the time of relapse had a bone marrow investigation under general anesthesia: two BM biopsies and two BM aspirates until May 1986, then two BM biopsies and 10 BM aspirates. The classical method of smearing each BM aspirate was compared to cytocentrifugation of the pool of BM samples after gradient density separation. RESULTS: The BM was involved in 13 of 59 untreated patients. BM was the single site of metastatic spread in only one patient but was involved in 52% of the patients with metastatic disease at other sites. This involvement was focal in several patients and frequent discrepancies were noted between the aspirates and biopsies at the various sites explored. The number of positive cases of BM involvement discovered by the two methods is somewhat limited. However preliminary results indicate a superior rate of positive smears with the pool technique which did however fail to detect involvement in some cases. CONCLUSIONS: The present study indicates that 1) BM involvement is a frequent event in metastatic ES (52%); 2) is often multifocal and therefore requires extensive BM investigation; and 3) further investigation of the pool technique to facilitate the BM screening is warranted.
Adolescent↗
Radioiodinated metaiodobenzylguanidine in neuroblastoma: influence of high dose on tumour site detection.
For more than a decade radioiodinated metaiodobenzylguanidine (mIBG) has been commonly used for neuroblastoma imaging. The accuracy of this scintigraphic method in detecting both primary and secondary tumour sites is crucial when evaluating the extent of disease. The aim of our study was to assess the impact of high-activity mIBG scintigraphy on neuroblastoma staging. Eighteen scans (TS) were obtained in 15 children after a therapeutic dose of iodine-131 mIBG and compared to diagnostic mIBG scans (DS) (in eight cases with 131I-mIBG and in ten cases with 123I-mIBG). The superiority of TS over DS was confirmed by the overall results: a total of 220 lesions were disclosed with TS and 171 with DS. However, in only one case did the TS findings, namely skeletal involvement not evidenced on corresponding DS, have an impact on clinical staging. In contrast, neither TS nor DS detected proven bone involvement in four patients. The dose-related sensitivity of mIBG scintigraphy in detecting neuroblastoma tumour sites was confirmed. The ultimate impact of high-dose scans on neuroblastoma management, however, seems limited.
3-Iodobenzylguanidine↗
Fluoride retention of incipient enamel lesions after treatment with a calcium fluoride varnish in vivo.
The aim was to determine the fluoride retention in plaque-covered and clean incipient enamel lesions after topical application of a CaF2/NaF varnish (Bifluorid 12). In 50 specimens of bovine enamel an incipient lesion was produced with acidic hydroxyethylcellulose (pH 4.8; 72 h). 40 specimens were fluoride varnished; the 10 remaining specimens were used for measuring baseline fluoride content. Each six of the fluoridated specimens were recessed in the buccal aspects of an intraoral appliance worn for 5 days. During the experimental period one side of the appliance was kept clean, and plaque growth was allowed on the other. KOH-soluble and structurally bound fluoride were determined immediately, 1 day, 3 days and 5 days after fluoridation, and compared with the baseline fluoride content of the enamel. Immediately after fluoridation, a considerable amount of KOH-soluble fluoride was bound, but after 5 days 80% had been lost. Simultaneously a significant increase of non-KOH-soluble or structurally bound fluoride was detected in both plaque-covered and clean enamel. It is evident that this CaF2/NaF varnish deposits more KOH-soluble fluoride on the surface of demineralized enamel than other varnishes, but after 5 days fluoride retention is similar to that from other varnishes.
Analysis of Variance↗
[Research on bone marrow involvement in the diagnosis of solid tumors in children. Methods, results and interpretation].
The assessment of bone marrow involvement by tumor cells remains an essential problem at diagnosis in pediatric solid tumors. Besides the conventional cytological and histological methods, some modern cell density separation techniques have been described in order to improve the detection of minimal or scattered bone marrow involvement. Immunological or genetical (molecular biology) tools can be used for the recognition of separated cells. In terms of investigations, MRI and MIBG radionucleide scan, although giving no definite proof, have the ability to macroscopically study the scattering of bone marrow invasion in the particular case of neuroblastoma. In some pediatric tumors, especially neuroblastomas and non Hodgkin lymphomas, an extensive bone marrow investigation is mandatory at diagnosis. Such an investigation is only necessary in case of particular criteria at diagnosis of Hodgkin's disease, Ewing' sarcomas, rhabdomyosarcomas and retinoblastomas. All other pediatric solid tumors do not need to be investigated in terms of bone marrow involvement at diagnosis, with the exceptions of advanced disseminated disease or if an autologous bone marrow transplantation is planned.
Bone Marrow Diseases↗
New strategies for the application of high-dose chemotherapy with haematopoietic support in paediatric solid tumours.
Because paediatric solid tumours are usually highly chemosensitive, conventional-dose adjuvant chemotherapy has improved survival rates for the majority of paediatric patients. However, high-dose regimens are being explored for the treatment of tumours not curable by, or resistant to, conventional treatment. The use of high-dose melphalan and the BACT regime have produced encouraging results in neuroblastoma and Ewing's sarcoma, and non-Hodgkin's lymphoma respectively. Haematopoietic growth factors have also emerged as useful adjuncts both to conventional therapy and in megatherapy with bone marrow transplantation (BMT). Thus, granulocyte colony-stimulating factor (G-CSF) (filgrastim) given to children with disseminated neuroblastoma receiving intensive chemotherapy significantly reduced the duration of febrile neutropenia and led to significantly fewer cycles of chemotherapy requiring antibiotic support. Studies are currently underway to compare the use of autologous BMT with that of peripheral blood progenitor cell (PBPC) rescue in children with solid tumours receiving high-dose chemotherapy. The studies will explore the reduction in thrombocytopenia achievable with PBPC and also the effect of filgrastim on the duration of neutropenia and fever. It seems that haematopoietic growth factors have an important supportive role to play in the treatment of paediatric solid tumours.
Child↗
[High dose chemotherapy followed by autologous bone marrow graft in solid tumors in children: arguments for].
Arguments for the use of high-dose chemotherapy followed by autologous bone marrow transplantation in pediatric solid tumors are discussed. The dose effect relationship in pediatric oncology conventional chemotherapy is emphasized. Results of high-dose chemotherapy followed by autologous bone marrow transplantation are encouraging in metastatic neuroblastoma and Ewing's sarcoma. The probability of event free survival is increased of about 30% as compared to that of conventional treatments. This therapeutic approach could be of value in other pediatric solid tumors, particularly in some poor prognosis forms of Wilm's tumors. However, until now, the results remain preliminary. On the other hand, the role of this strategy in chemoresistant tumors, such as malignant gliomas, remains under investigation.
Antineoplastic Combined Chemotherapy Protocols↗
[The European experience with megadose therapy and autologous bone marrow transplantation in solid tumors with poor prognosis Ewing sarcoma, germ cell tumors and brain tumors)].
Since 1984 a total of 2085 patients with solid tumors have been registered in the European Bone Marrow Transplantation Registry for Solid Tumors (EBMT-STR). The major aim of this registry is to supply data by retrospective analysis for the innovation of prospective, randomized studies. 104 Ewing's sarcoma patients received megatherapy followed by autologous bone marrow transplantation (MGT/ABMT). The 2-year overall survival was 31% in 14 patients with multifocal disease in first complete remission (CR1) and was 37% for 15 patients in second CR (CR2). (6 patients with local disease in CR1 have been excluded.) These results are better than observed under conventional dose chemotherapy. 67 patients were grafted with measurable disease showing a response rate of 72%. The 2-year overall survival was 25% during primary treatments and 33% and 10% for sensitive and resistant relapses, respectively. 201 patients with germ cell tumors received MGT (combinations of platinum derivates, VP16, cyclophosphamide, ifosfamide) followed by ABMT. The overall survival at 5 years was 10% in refractory patients and 58% for 113 responding patients not in CR1 (i.e. first partial remission, CR2 and sensitive relapses). Based on these results and a French randomized trial a prospective, randomized study is underway comparing MGT versus conventional chemotherapy in chemosensitive patients. 219 adults with malignant brain gliomas underwent a program consisting of surgery, MGT (BCNU in the majority)/ABMT and radiotherapy. The overall survival at 3 years was 12%, the median survival was 11 months after ABMT. Life quality after ABMT was good, but no major improvement in terms of prolonged survival was achieved.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Phase I-II study of interleukin-2 after high-dose chemotherapy and autologous bone marrow transplantation in poorly responding neuroblastoma.
Despite intensification of treatment with high-dose chemotherapy (HDC) and autologous bone marrow transplantation (AMBT), the prognosis of poorly responding metastatic neuroblastoma remains bad. Recombinant IL-2 (rIL-2) was used after ABMT to enhance the immune response against the tumor and thereby to improve survival of these patients. In this study, five courses of rIL-2 were administered as a continuous intravenous infusion every 2 weeks, the first course lasting 5 days, and the other four 2 days. rIL-2 treatment was to begin within 120 days of BMT. This study demonstrates the feasibility of rIL-2 soon after HDC and ABMT. The maximum tolerated dose (MTD) was 12 x 10(6) U/m2/day. Clinical toxicity was similar to that observed in adults, moderately increased by the proximity of ABMT; in a previous study we demonstrated that the MTD in non-grafted children was 18 x 10(6) U/M2/day. Nevertheless, half of the patients were not able to receive rIL-2 therapy after ABMT, and only 6/12 received 100% of the planned dose, mainly because of thrombocytopenia. If peripheral stem cell transplantation is demonstrated to enhance platelet recovery, more patients could be treated with rIL-2 with the present schedule. Earlier administration of low-dose rIL-2 after BMT associated with ex vivo rIL-2 treatment of the graft could be a more valid way of using rIL-2 to improve survival.
Antineoplastic Combined Chemotherapy Protocols↗
Long-term pulmonary sequelae after autologous bone marrow transplantation in children without total body irradiation.
We investigated the long-term pulmonary sequelae of 38 children surviving 3 to 11.5 years (median 7 years) after high-dose chemotherapy (HDC) and autologous bone marrow transplantation (ABMT) without TBI. This cross-sectional study included patients with neuroblastoma (21), non-Hodgkin's lymphoma (7), Ewing's sarcoma (5), rhabdomyosarcoma (3), medulloblastoma (1) and ALL (1). They were asked and examined for clinical signs and underwent a physical examination with chest X-ray; 33/38 had pulmonary function tests (PFT) performed. No obstructive disease was found. Fifteen out of 32 evaluable PFT (47%) were abnormal with a pulmonary restrictive syndrome in 10, and borderline values in five patients. Four of these 15 patients were symptomatic with exertional dyspnea and two of four had abnormal chest X-rays. The etiology was mainly multifactorial, associating HDC with thoracic radiotherapy +/- scoliosis/kyphosis +/- previous thoracotomy +/- post-ABMT interstitial pneumonitis. Only 3/10 patients with a restrictive syndrome had HDC containing BCNU or busulfan as the only risk factor for lung disease. We conclude that the prevalence of late pulmonary sequelae after ABMT without TBI is moderate and rarely due to HDC alone, since most abnormal PFT can be explained by heavy pretreatment prior to ABMT. As symptoms are scarce even in advanced disease, repeated testing and very long-term follow-up are needed.
Adolescent↗
Upper clavicular and cardiac meta-[123I]iodobenzylguanidine uptake in children.
In order to clarify some of the particularities and pitfalls of the MIBG thoracic scan, we report our experience with 5 children with Stage III or IV neuroblastoma who presented equivocal scans. The physiological thoracic distribution of MIBG in children differs from that in adults and has to be taken in account in the accurate interpretation of the scans.
3-Iodobenzylguanidine↗
Autologous bone marrow transplantation for pediatric Wilms' tumor: the experience of the European Bone Marrow Transplantation Solid Tumor Registry.
This survey includes 25 children with Wilms' tumor undergoing high-dose chemotherapy associated with autologous bone marrow transplantation (ABMT) in the period June 1984-December 1991 and enrolled in the European Bone Marrow Transplantation Registry for Solid Tumors. At diagnosis, 12 children presented stage IV disease, 5 stage III, 3 stage II, and 5 stage I. Before ABMT, 21 children had 1 to 4 relapses (median 1); 13 achieved a second or subsequent complete remission (CR), four stage IV children failed to respond to first line treatment and achieved either CR (3 patients), or partial remission (PR) after second line therapy. At high-dose chemotherapy, 17 children were in CR and 8 had measurable disease. Seven different high-dose regimens were administered, even if 20 children received melphalan mostly associated with vincristine and 8 involved field radiotherapy. Three children died early of pneumonitis; 2 developed an acute transient renal failure, 1 a chronic renal failure. Out of the 8 children with target disease at graft, 2 died of toxicity, 5 achieved CR, 1 obtained PR, and only 1 is presently alive in CCR at 39 months after ABMT. Of the 17 children grafted in CR, 8 are alive event-free at 14-90 months (median 34) from ABMT; 7 relapsed at 3-23 months (median 7 months); 1 died of toxicity and 1 was lost to follow-up in CR at 12 months. A salvage attempt with high-dose chemotherapy in children with resistant or poor prognosis recurrent Wilms' tumor seems to be justified. An international cooperative protocol taking into account the increased risk of lung and renal toxicity is necessary.
Adolescent↗
What is the prognostic value of osteomedullary uptake on MIBG scan in neuroblastoma patients under one year of age?
Twenty-seven infants under one year of age with metastatic neuroblastoma were studied for osteomedullary metastases. They were evaluated by at least two imaging procedures: X-ray films and MIBG scan. Taking into account the results of these investigations, 3 groups were defined: osteomedullary metastases were detected in 8 infants by both X-ray and MIBG scan, no osteomedullary sites were detected by either technique in 13 patients, and 6 had osteomedullary foci with positive MIBG uptake but no radiological abnormality. These three groups were apparently different in terms of median age, response to chemotherapy, and long-term survival. The third group, which has not been previously described, appears to have a better prognosis than patients with radiologically detectable bone lesions. Nevertheless it was necessary to use intensive chemotherapy to obtain remission in these particular patients. It should be mandatory to specify the investigatory technique used to describe osteomedullary metastases in infants and treatment should be adapted according to this grouping system.
3-Iodobenzylguanidine↗
Negative 123-meta-iodobenzyl-guanidine imaging in Ewing's sarcoma of bone.
The role of radiolabeled meta-iodobenzyl-guanidine (mIBG) is established in the detection and the staging of neuroblastoma. We designed a study of mIBG scanning for patients with Ewing's sarcoma, a tumor for which a neuroectodermic origin has been proposed. We explored 15 children with round cell sarcoma of bone by a whole body scan carried out 24 hours after injection of 123-I mIBG. No patient demonstrated significant uptake either at the site of the primary or at the sites of metastases. These results suggest that despite its neural histogenesis Ewing's sarcoma is a member of the nonneuroblastoma neural crest tumors, which does not produce or store adrenergic metabolites.
3-Iodobenzylguanidine↗
Comparison of auto versus allografting as consolidation of primary treatments in advanced neuroblastoma over one year of age at diagnosis: report from the European Group for Bone Marrow Transplantation.
A case control study was performed to investigate the potential advantage of allogeneic bone marrow transplantation in advanced or poorly responding neuroblastoma first remission patients using the European BMT Solid Tumor Registry. Seventeen allogeneic and 34 autologous bone marrow transplantation (BMT) cases were matched based on a number of prognostic factors including age, sex, prior treatment duration, pre-graft response status and bone and BM involvement before BMT. Only single BMT procedures are included. The median age at diagnosis was 47 months (range 18-113 months). The median follow-up time since BMT is 58 months (range 13-133 months). The only significant prognostic factor within the allogeneic BMT (p = 0.012) and autologous BMT groups (p = 0.025) was residual skeletal disease before BMT, detected by mIBG in 86% of the cases. However, the progression-free survival was not significantly different: 35% and 41% at 2 years, respectively. Only half of the allogeneic BMT patients had developed graft-versus-host disease (GVHD): 7 of 9 grade I-II and only 2 of 9 grade IV. The median donor age was very young with 74 months (range 20-240 months) and 10 of 17 were sex matched. Thus absence of GVHD risk factors in young children could be the major obstacle in achieving an anti-tumor effect with allogeneic BMT in neuroblastoma.
Bone Marrow Transplantation↗
[Humoral immunity and infections during bone marrow transplantation in children: study of 127 transplanted patients successively in a same center].
BACKGROUND: Children with malignant diseases are frequently given high dose chemotherapy plus autologous bone marrow transplants. Infectious complications can lead to morbidity and mortality in this type of treatment. This study was designed to determine whether immunoglobulin deficiency is an additional risk factor for infections. PATIENTS AND METHODS: One hundred and twenty seven children with solid malignant tumors were treated between November 1987 and April 1992 in our Department by chemotherapy followed by autologous bone marrow transplantation. Their serum IgA, IgG and IgM concentrations were measured by nephelometry before chemotherapy, on the day of transplantation and every week thereafter. The frequency and severity of infectious episodes in all the children were recorded using a standard scale. The patients were divided into two subgroups, defined according to their serum IgG concentrations before the transplantation and 7 and 21 days later. RESULTS-Ig deficiency during transplantation was not associated with the occurrence of septicemia or focal infections. It was associated with the course of infection (P = 0.003) and with the occurrence of zoster virus infection during the first 6 months after transplantation (P = 0.003). CONCLUSIONS: Immune replacement during bone marrow transplantation may be indicated in children at risk of Ig deficiency. Fifty percent of the children with solid tumors treated in our institution were at risk of this deficiency.
Adolescent↗
Prognostic value of MDR1 gene expression in neuroblastoma: results of a multivariate analysis.
The prognostic value of the MDR1 gene expression in neuroblastoma (NB) was assessed in a multivariate analysis performed in a series of 84 patients (pts) taking into account the main known clinical and biological factors of the disease, i.e., age, stage, MYCN genomic content and DNA ploidy index. Twenty seven children were < 1 year (yr), 13 presented with stage I and II, 7 with stage IV-S, 17 with stage III and 47 (56%) with stage IV. Tumor specimens were obtained from involved bone marrow (n = 12) or surgical primary tumor specimens (n = 72). MDR1 gene expression was measured by Northern hybridization technique and expressed in arbitrary units (a. u.) (Goldstein et al., 1989). Analysis of MYCN genomic content and DNA ploidy index were performed by Southern blot hybridization technique and flow cytometry, respectively. Out of 84 tumor specimens 19 (23%) showed MYCN amplification (> 3 copies/haploid genome). In 24 cases (29%) no detectable MDR1 gene transcript was found (0 a.u.) whereas 42 (50%) had a value in the range 1-30 a.u., and 18 (21%) a value beyond 30 a.u.. High transcript levels were found in localized as well as in metastatic NB (NS). No significant correlation between MDR1 gene expression, age, stage, or MYCN genomic content was found In univariate analysis stage IV, age > 1 yr, MYCN amplification, diploid DNA content and high MDR1 gene transcript levels were significantly related to an increased risk of death. In multivariate analysis only stage IV, MYCN amplification and MDR1 overexpression remained significantly associated with an increased risk of death.(ABSTRACT TRUNCATED AT 250 WORDS)
ATP Binding Cassette Transporter, Subfamily B, Mem↗