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Biomedical subjects

D Sommelet

Publications and source records attributed to D Sommelet.

At least 73 records · Page 4Linked to original sources

Treatment of Langerhans-cell histiocytosis in children. Experience at the Children's Hospital of Nancy.

Forty children who had Langerhans-cell histiocytosis were followed for an average of six years (range, excluding patients who died of the disease, two to fifteen years). The patients were divided into two diagnostic groups: those who had localized disease (involving one bone or more only) and those who had multifocal disease (an osseous lesion and a soft-tissue mass, a skin rash, diabetes insipidus, or generalized disease). Methods of treatment included curettage, bone-grafting, chemotherapy, local or systemic corticosteroids, and radiotherapy. Nineteen of the thirty patients who had localized disease had a complete response to the therapy, four had a partial response, and seven had no response. Twenty-one of these thirty patients had not had a recurrence by the time of the latest follow-up examination; nine had a local recurrence within four years after the initial therapy but had no additional recurrences after treatment of the local recurrence. No recurrence occurred more than four years after the time that the initial diagnosis had been made. Five of the ten patients who had multifocal disease had a complete response to the therapy, two had a partial response, and three had no response. Six patients had a recurrence; four did not. Two patients died of the disease. As a result of this study, we recommend the avoidance of intensive measures of treatment, if possible, and we advise long-term follow-up of these patients.

Child↗

Serum beta-carotene and antioxidant micronutrients in children with cancer. The 'Cancer in Children and Antioxidant Micronutrients' French Study Group.

Serum antioxidant vitamins A (retinol) and E (alpha-tocopherol), beta-carotene, zinc and selenium for 418 children with newly diagnosed malignancy were compared with those of 632 cancer-free controls. Incident cancer cases and controls were 1-16 years old and recruited in 1986-1989. Age- and sex-adjusted serum concentrations of retinol, beta-carotene and alpha-tocopherol were significantly inversely associated with cancer. In similar models, the odds ratio (OR) comparing the highest with the lowest quintile was 2.06 (95% confidence interval [CI] 1.40-3.02) for retinol, 3.87 (95% CI: 2.54-5.90) for beta-carotene, 2.15 (95% CI: 1.48-3.10) for alpha-tocopherol, 1.29 (95% CI: 0.75-2.23) for selenium, and 1.94 (95% CI: 1.17-2.23) for zinc. The cancer sites that were associated with serum beta-carotene were, in general, leukaemia, lymphoma, central nervous system, bone and renal tumours. Moreover, leukaemia was associated with low mean serum levels of retinol, selenium and zinc. Subjects with lymphoma, bone and renal tumours also had lower mean retinol and alpha-tocopherol levels than controls. Brain tumour patients had low vitamin E levels. Low serum values of antioxidant vitamins were associated with childhood neoplasm occurrence. Some site-specific effect was reported. Low peripheral nutrient levels are not considered as cancer promoters but rather as an impairment of the body's defence mechanism occurring during the cancer-related metabolic and nutritional disturbances and inflammation processes.

Adjuvants, Immunologic↗

Etoposide in relapsed or refractory Wilms' tumor: a phase II study by the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group.

PURPOSE: Despite a high cure rate of approximately 85% in Wilms' tumor by multimodality therapy, to date only four drugs are known to be active against such tumors. There is a clear need for new active drugs. PATIENTS AND METHODS: Thirty-one patients with relapsed or refractory Wilms' tumor from three British and 14 French centers were treated with intravenous (IV) etoposide 200 mg/m2 daily for 5 days. Original stage was I (n = 3), II (n = 7), III (n = 9), IV (n = 10), and V (n = 2). Prior chemotherapy, administered initially or at relapse, included vincristine and dactinomycin in all cases, doxorubicin or epirubicin in 30, and ifosfamide in 20. Sites of relapse or resistant disease were lung in 13, abdomen or pelvis in six, liver in one, and multiple in 11. When entered onto the study, 12 patients were in first relapse, 10 in second relapse, and four in third or more relapse. Five had never obtained a complete remission. All but two (progressing) patients received two courses of etoposide, the second course being administered at day 21. RESULTS: A complete response (CR) was documented in two patients, partial response (PR) in 11, stable disease in 10, and progressive disease (PD) in eight. The duration of response could not be evaluated, because all responding patients were subsequently treated with multimodality therapy. The major toxicities observed were neutropenia and thrombocytopenia, but most patients had been heavily pretreated. No toxic death clearly associated with etoposide was noted. CONCLUSION: It is concluded that etoposide in this schedule is an active agent in Wilms' tumor and should be considered for inclusion in regimens for high-risk patients, such as those with metastatic disease at diagnosis and those who relapse after multiagent chemotherapy.

Adolescent↗

[Endocrinal sequela in bone marrow transplantations during childhood and adolescence].

Bone marrow transplants are being increasingly used to treat a broadening spectrum of serious pediatric conditions including hematologic, metabolic, and immune disorders. A common adverse effect is slowing of statural growth which, according to the author's experience, reaches 0.4 SD a year on average in the highest risk group with progressive graft-versus-host disease after whole body irradiation and transplantation of an allograft. Growth was normal in autograft recipients treated by moderate-intensity chemotherapy. High-dose chemotherapy, in particular with busulfan and cyclophosphamide, has been reported to cause growth retardation. The mechanism of failure to gain height is complex. Partial growth hormone deficiency is rare. Relative resistance of growth plates is the most likely mechanism. The role and efficacy of growth hormone replacement therapy is unclear. Conditioning regimens can affect ovarian and testicular function. Peripheral thyroid resistance can occur after whole body irradiation and transplantation of an allograft. The high rate of growth and endocrine disorders warrants close monitoring including full evaluations of growth and pubertal development as well as periodic endocrinologic investigations.

Adolescent↗

Prophylactic use of ganciclovir for allogeneic bone marrow transplant recipients.

Ganciclovir which has proved effective in the treatment of cytomegalovirus (CMV) infection was given prophylactically to 40 bone marrow transplant (BMT) patients pre and post-transplant in seropositive patients and post-transplant in seronegative patients with a seropositive donor. All patients were transfused with screened blood products and 33 received CMV hyperimmune globulin. They were compared with an historical control group consisting of 39 patients who had received significantly more unscreened blood products (p = 0.01) and less HLA-mismatched marrow transplants (p = 0.05). Toxicity of ganciclovir was hematological-neutropenia was responsible for cessation of the drug in seven patients and transfusion requirements were significantly higher in the ganciclovir group. Non-hematological toxicity did not occur in any patient. Only one patient (2.5%) experienced symptomatic CMV infection and no patient developed CMV pneumonitis. In contrast, in the control group, 23 (59%) patients had clinical symptoms of CMV infection (p < 0.0001) and 4 (10%) experienced CMV pneumonitis (p < 0.01). Ganciclovir significantly reduced the incidence of positive CMV antigenemia (7.5% in the treated group vs 72% in the control group; p < 0.01). However, ganciclovir delivery did not result in an improved overall survival due to a higher rate of regimen-related deaths and chronic GVHD mostly in patients transplanted from an HLA-mismatched donor. The prophylactic administration of ganciclovir abrogates CMV pneumonitis and considerably reduces the incidence of CMV infection in BM recipients at high risk of developing this disease after transplantation.

Adolescent↗

[Regressive myelodysplastic syndromes in children. Committee on Childhood Myelodysplasia of the Society of Pediatric Hematology and Immunology].

BACKGROUND: As in adults, myelodysplastic syndromes in children are often preleukemic and their spontaneous remission is exceptional. CASE REPORTS: Case 1. A girl, aged 8 years, developed pancytopenia with macrocytic anemia. The myelogram and bone marrow biopsy showed dyserythropoiesis with macroblastosis, but without sideroblasts. The chromosome configuration was normal and the negative results of other investigations led to the diagnosis of refractory anemia without any known cause. Bone marrow transplantation was considered, but a spontaneous remission intervened and has persisted for 3 years. Case 2. A girl, aged 5 years, was investigated for worsening of a macrocytic anemia that had been present for 3 years, without changes of granulocytes and platelets. The myelogram showed dyserythropoiesis with megaloblastosis and sideroblasts. No known cause could be identified. As for the preceding patient, a spontaneous remission occurred, and has persisted for 3 years. Case 3. A girl, aged 5 months, developed pancytopenia. The myelogram showed dys-megakaryocytopoiesis. All hematologic data spontaneously normalized after 1 year, and have remained so 1 year later. CONCLUSION: The spontaneous remission, that has occurred in our 3 patients, has been reported in one only adult. This possibility precludes considering all the myelodysplastic syndrome in children as preleukemic, and suggests that bone marrow transplantation is not urgent in these situations.

Age Factors↗

[Localizations of histiocytosis X in bone].

Histiocytosis X is still of unknown origin. Its clinical patterns are various and it is above all a bone disease of children, mostly boys. It is a tumoral condition basically benign but with a strong tendency toward dissemination and destruction. Its natural history is unpredictable. The authors have reviewed 37 cases after a 44 months mean follow-up for bringing up a better understanding of the role of orthopedic surgery. The diagnosis was always based on biopsies looking for at least two basic signs out of four possible ones. Scintigraphy was used to detect other locations. MRI was used to evaluate the effect of treatment. In single eosinophilic granuloma, curettage was associated with biopsy. Local injections of corticoids may help in spinal locations. In disseminated forms, surgical treatment should be little aggressive, limited to a biopsy of the most superficial lesion. These forms should be treated by radiotherapy corticotherapy and chemotherapy, as well as the aggressive lesions, the extensive ones, the threatening ones and those which are not accessible.

Adolescent↗

Growth hormone response following growth hormone releasing hormone injection in thalassemia major: influence of pubertal development.

Thirty-five patients with thalassemia major, aged 7 to 21 years, were studied to define the relationship between the pubertal development and the growth-hormone (GH) secretion during sleep, after administration of GH-releasing factor (hpGRF 1-44), and betaxolol-glucagon or arginin-insulin. Pubertal development was classified as being appropriate or delayed for chronological age. GH response to pharmacological stimuli and during sleep was not linked to the pubertal development according to the chronological age. The peak of GH secretion after GHRH injection was significantly delayed in thalassemic patients with retarded puberty. The integrated secretion of GH during the 120-min test was slightly but not significantly reduced in these patients. The prepubertal pattern of GHRH response was restored in the patients receiving substitutive therapy by HCG or testosterone. The alteration of GH response to GHRH in thalassemic patients is likely to be only due to delayed puberty and decreased endogeneous GHRH secretion since it is corrected by androgen or gonadotropin replacement.

Adolescent↗

[Histological and immunohistochemical diagnosis of bone marrow metastases of neuroblastomas].

A retrospective, morphological and immunochemical study was performed on 60 bone marrow biopsies (BOM) and 12 tumor specimens surgically excised, from 9 patients with neuroblastoma (NB). Immunochemistry concerned "neuron-specific enolase" (NSE), chromogranin A (CGA) and synaptophysin (SP). The results of immunochemical stains and the study of reticulin network on the argentic stain were compared to the results of morphological evaluation on the routine stain. NSE, CGA and SP staining of tumor cells (part or all of them) was obtained from all surgical specimens. 17/75 BOM (20%) were discarded because of poor material. NB cells were observed in 24 BOM from 3 patients. Tumor cells formed large strands (1 patient) or nests (2 patients) associated with segregated cells. Diagnosis of metastatic BM involvement was negative or doubtful for 6 BOM (3 obtained at the same time, 2 patients), in which NB cells were clearly demonstrated by immunochemical staining of NSE and/or CGA. Reticulin and/or collagen myelofibrosis was present in 32/35 BOM from the 3 patients metastatic in bone marrow (BM+) even if NB cells could not be demonstrated in these samples.

Biopsy↗

[Role of chemotherapy in the treatment of brain tumors].

Chemotherapy is a treatment of choice for children with brain tumors, since 20% are unresectable (hypothalamic and brainstem), or incompletely removed, and since radiation therapy often induces cognitive and endocrine sequellae. However, tumor cell heterogeneity and blood-brain barrier which play a role in restricting delivery of chemotherapy represent limiting factors to its efficiency. Neuroradiological procedures such as CT scan and magnetic resonance imaging may bring objective criteria in order to evaluate the efficacity of chemotherapy. Chemotherapy is tested in phase II trials to identify the most efficient drugs for each histological tumor type. This provides a rationale to elaborate phase III trials where polychemotherapy is combined to surgery and radiotherapy. Attempts to enhance drug penetration, such a high-dose chemotherapy and blood-brain barrier disruption, are under study. Primary and acquired drug resistance are being studied as well as the means of overcoming them.

Antineoplastic Agents↗