[Planning the care of the sick child].
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Biomedical subjects
Publications and source records attributed to C Raybaud.
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Gangliogliomas and gangliocytomas are rare and benign neuronal tumors which affect young subjects. This study concerns 3 cases of ganglioglioma and 3 cases of gangliocytoma explored by CT and MRI and confirmed by pathological examination. The most typical CT image was that of an often calcified contrast-enhanced cystic tumor. At MRI, each tumor emitted a low-intensity signal on T1-weighted sequences and a high-intensity signal on T2-weighted sequences. Contrast enhancement after gadolinium injection was frequent. Neuroradiology is not specific, and these tumors are usually diagnosed at pathology. However, the diagnosis may be considered in young patients with a history of old, drug-resistant partial epilepsy and having a contrast-enhanced, calcified cystic lesion in the temporal lobe or the cerebellum.
The various treatments currently available for medulloblastoma are reviewed and modifications which have occurred over the last ten years are analyzed. Surgery is the first step of the treatment of a medulloblastoma. Recent advances in neurosurgical anesthesia and intensive care have substantially improved the quality and extent of exeresis and markedly reduced operative mortality (currently under 2%). Radiotherapy of the entire central nervous system should follow surgery in every case. Use of high energy radiations (together with improvements in surgical treatment) have increased survival rates to 50-60%. However, side effects are frequent. The modalities and timing of chemotherapy have also changed considerably over the last ten years; the different modalities currently used are reviewed, as well as the strategies available for reducing toxic effects and hematologic complications. Currently, chemotherapy is "sandwiched" between surgery and radiotherapy. Treatments under evaluation (monoclonal antibodies, immunotoxins, and immunomodulation) are discussed. The purpose of this therapeutic strategy for medulloblastomas is not only to increase survival rates but, above all, to improve the quality of life in survivors. Close cooperation between health care professionals of the different specialties involved and long term multicenter studies are indispensable if this goal is to be achieved.
Twenty-five children or adolescents with relapsed or refractory non-Hodgkin's lymphoma (NHL) were included in this phase II study of the combination of cytarabine (ARA-C) 50 mg/m2/d by 12 hours continuous infusion day 1 to day 5, ARA-C 3 g/m2/d in 3 hours day 1 to day 4, and etoposide (VP 16) 200 mg/m2 daily from day 1 to day 4. Twelve patients had B-cell, 12 T-cell, and one non-T, non-B-cell lymphoma; according to Murphy's staging system, 15 had stage III and nine stage IV disease with bone marrow involvement at diagnosis. All had previously received ARA-C by push or continuous infusion. Two patients had received epipodophyllotoxins. At the time of the study, three children had initial refractory disease, 18 were in first relapse (14 on therapy), two in first refractory relapse, and two in second relapse (on therapy). The overall response rate (RR) was 60%: eight complete responses (CRs), seven partial responses (PRs) (two became CRs after a second course). The RR was 66% (four CRs plus four PRs) in B-cell and 54% (four CRs, three PRs) in non-B-cell NHL. It was 20% (one PR per five patients) in initial or relapsed refractory disease. In four patients with measurable CNS disease, there were three CRs. Duration of response was nonassessable since all the responding patients received high-dose polychemotherapy followed by autologous bone marrow transplantation (ABMT) (five are alive with long follow-up [FU]). Toxicity was marked mostly by pancytopenia for 2 weeks, and half the patients encountered a grade-3 infection. One severe diarrhea was observed. In conclusion, high-dose ARA-C (HD-ARA-C) and VP 16 are an effective regimen in relapsed NHL, especially with CNS disease, and its toxicity is acceptable with regards to the prognosis of the disease.
Between 1984 and 1989, 35 patients with recent arterial or graft occlusions have been treated with intra-arterial infusion using sequential association of Urokinase (U.K.) and Lys-Plasminogen. Occlusion was thrombotic in 68.5% of the cases ans embolic in 31.5%, involving 28 native arteries and 7 bypass grafts. The mean duration was 16 days (2 to 90). Continuous infusion of U.K.: 84,000 U.I./H and bolus of Lys-Plasminogen 15 microKatals every 30 minutes were delivered through a catheter embedded into the clot. Intra-venous heparin was always associated. The mean duration of lytic drug infusion was 8 H. Complementary arterial reconstruction by vascular surgery of percutaneous transluminal angioplasty was performed in 23% of the patients. Patients with recent alimentary tract bleeding, hemorragic stroke in the last six months or severe high blood pressures were contra-indicated. Complete lysis was obtained in 23 cases (66%), partial lysis in 7 (20%) and no lysis in 5 (14%). The clinical result was excellent in 24 cases (68.5%), good in 3 (8.5%) and bad in 8 (23%) in which amputation was always necessary. 5 local hematoma (14%) treated by surgery or transfusion and one death (3%) due to neurological complication occurring 24 hours after the end of the procedure were observed. The literature survey has shown that the results of low doses of Streptokinase (S.K.) local infusions were not better, and that higher doses of S.K. or U.K. delivered during a shorter infusion time increased the efficacy of lysis and decreased the rate of hemorragic complications. We have proposed the local thrombolytic treatment to the limb threatening ischemic cases when the traditional medical or surgical techniques where thought to be associated to a high risk of failure or complication. The specific indications are the acute or sub-acute ischemic situation due to atheromatous artery thrombosis, distal or old embolism where the Fogarty catheter is inefficient, and graft thrombosis. Severe acute ischemia with neurologic involvement are not good indications. Local thrombolysis can be successful on arterial occlusion even after one month duration.
Chromosome analysis was performed in two cases of rhabdomyosarcoma (RMS): one embryonal RMS and one alveolar RMS. Analysis showed number and structural abnormalities of chromosome 2. The relationship between these findings and published reports of karyotypes from RMS is discussed.
A heterogeneous series of 79 children with partial epilepsy was studied by computerized tomography (CT) and magnetic resonance imaging (MRI) to evaluate the contribution of MRI to the aetiological diagnosis of that disease. Both CT and MRI were normal in 13 cases and abnormal in 41 cases showing the same pathology (malformation, atrophy, tumour, scar). In 4 cases of continuous partial epilepsy the lesions observed were either diffuse or focal corresponding to the electrical focus, and they could be due to Rasmussen's encephalitis. In 19 cases where CT gave normal results, MRI showed bilateral high-intensity signal areas of uncertain significance in the white matter of the caudal part of the hemispheres. All considered, it seems that with its greater sensitivity MRI should be the first or only exploratory method to be used in the evaluation of partial epilepsy of childhood.
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The specificity of childhood cancers and the lack of available incidence data in Europe (with the exception of the Manchester and Turin registries) led to the creation of two French regional childhood cancer registries (CCR), in Nancy (1983) and Marseille (1984); both are population based CCR, respectively covering 535,236 and 809,196 children (0 to 14 years). All malignant neoplasms, brain tumours (whatever the grading) and borderline malignancies are included. Data have been collected from medical and administrative sources. Registration is active and each source is recontacted annually. The registries contact all physicians who might include children among their patients (private and hospital practice) and pathology-cytology laboratories. The University Hospital Centers and Anti-Cancer Centers in adjacent regions and in Paris are contacted. Data collected are the following: name, age, sex, address, time and method of diagnosis, histology, anatomical site, stage, treatment and sources of information. We combined our own data with those of a general cancer registry, set up in Strasbourg in 1975 and covering 205,889 children. The reliability of the methodology is attested by the similarity of results to those obtained in other European, US and Australian CCR. This type of registry is needed for organizing studies on the descriptive, analytical and experimental epidemiology in pediatric oncology.
Two cases of veno-occlusive disease (VOD) occurring in metastatic neuroblastoma patients are reported. Treatment included a remission induction by conventional chemotherapy and surgery followed by an early consolidation with massive chemotherapy, total body irradiation and cleared autologous bone marrow transplantation (ABMT). Both patients had multiple halothane anesthesias. Liver complications occurred 10 and 21 days respectively after ABMT. The first patient had a precocious and severe clinical and biological VOD, heparinotherapy and symptomatic treatment were ineffective and he died 12 days after ABMT. The second patient had a moderate and later syndrome which was controlled by heparin therapy (100 U/kg/day) delivered by continuous infusion; he is now alive free of hepatic disturbance 28 months after ABMT. The potential iatrogenic factors are discussed, with special focus on the use of halogenated anesthetic drugs.
Following the well-known European CCRs of Manchester and Turin, 2 regional CCRs have been recently created in France: in Nancy (1983) and Marseille (1984); both are population based CCRs, covering respectively 535,200 and 809,200 children (0-14 yrs). All malignant neoplasms are included, as well as brain tumours (whatever grading) and borderline malignancies. Data are collected from medical and administrative sources. Registration is active and every source is recontacted annually. The registries contact all physicians who might include children among their patients (private and hospital practice), and laboratories of pathology-cytology. The University Hospital Centers and Anti-Cancer Centers in adjacent regions, and in Paris are contacted. Death certificates for children dying of a malignant neoplasm are also sent to the registry. Data collected are as follows: name, age, sex, address, date and method of diagnosis, histological type, anatomical site, stage, treatment and sources of information. We added the data of a general cancer registry, created in Strasbourg in 1975 and covering 205,900 children. reliability of the methodology is attested by the similarity of the results obtained in other European, US and Australian CCRs. In conclusion, this type of registry is needed to organize multicentric epidemiological studies about the role of etiological factors, the survival, and the long term sequelae.
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A pharmacokinetic study was carried out in two infants and two (older) children with high-dose cisplatin (CP) (40 mg/m2/day) by 5-day continuous infusion. Following interruption of the infusion, the decrease in total plasma platinum was biphasic, with a terminal half-life of 155.5-418 h. During administration the urinary concentrations were between 7.66 and 15.2 mg/l. Thirty to thirty five per cent of the administered dose was eliminated within 48 h of discontinuing infusion. Free platinum (FP) levels declined in a biphasic manner, with a mean (+/- S.E.) elimination half-life of 81.25 (+/- 34.9) h. FP was still detectable in the plasma 10 days after the end of infusion with levels above 0.010 micrograms/ml. FP availability, measured as the area under the curves (AUC) of the FP concentration--up to 2 h after ending the infusion--were 768 (+/- 326) micrograms.min/ml. Inter- or intra-individual differences in AUC values were not observed.
Fifteen cases of lissencephaly were studied and the literature reviewed. The authors conclude that the clinical findings of lissencephaly in infancy are non-specific, consisting of developmental delay and hypotonia. While the CT scan establishes the diagnosis, it may also be strongly suggested by an EEG showing 'major fast dysrhythmia', characterized by abnormally rapid, very high-voltage activity, predominantly in the alpha and beta frequency bands. Some possible mechanisms for this highly suggestive EEG pattern are proposed.
Histology of cerebral arteries and veins are reviewed to show variances with extracerebral blood vessels. Muscles fibers even in large cerebral veins are easily overlooked. The thick wall of the vein of Galen grossly and microscopically resembled dura mater fed by microscopic blood vessels and capillaries. The authors reported 4 cases of arteriovenous aneurysms of the great vein of Galen. When compared to the rest of the histological reports on this subject published till now, it is obvious that this new cases bring new facts. First is the presence of an irregular muscle coat in the aneurysmal wall suggesting early hemodynamic troubles. The second and most important data is the association of multiple malformations of the pineal gland, of the vascular elements of the tela choroidea of the third ventricle between which the aneurysm of the great cerebral vein is found. These unusual data suggested complex congenital malformation in the early stages of development.
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Twenty-six children with acute leukemia were treated with allogeneic marrow transplantation from HLA identical siblings after a conditioning regimen with Cyclophosphamide-total body irradiation (19 patients), Melphalan-total body irradiation (6 patients) or Busulfan-cyclophosphamide (1 patient). Eighteen were transplanted in complete remission (4 with acute non lymphoblastic leukemia in first remission, 14 with acute lymphoblastic leukemia: 6 in first, 6 in second and 2 in subsequent remission): 2 died of cytomegalovirus pneumoniae, 1 relapsed and 15 survive in continuous complete remission from 5 to 42 months after transplantation (median = 22 months). Eight were transplanted in relapse, 7 achieve complete remission, 5 of them relapsed, 1 died of G.V.H. and 1 survives in continuous complete remission 46 months after transplantation. Actuarial analysis shows a disease free survival rate at 3 years of 82% for patients transplanted in remission and 12% for patients transplanted in relapse (p less than 0.01).