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Biomedical subjects

J L Bernard

Publications and source records attributed to J L Bernard.

At least 37 records · Page 2Linked to original sources

An open-label, multicentre, randomised phase 2 study of recombinant human granulocyte colony-stimulating factor (filgrastim) as an adjunct to combination chemotherapy in paediatric patients with metastatic neuroblastoma.

Administration of combination chemotherapy to children with metastatic neuroblastoma induces profound myelosuppression resulting in chemotherapy treatment delays and febrile neutropenic episodes. The objective of this randomised multicentre study was to assess the incidence, duration and severity of neutropenia when filgrastim is added to induction chemotherapy administered to patients with metastatic neuroblastoma. In this study, 59 patients with metastatic neuroblastoma were randomised to receive chemotherapy (control group, n = 28) or chemotherapy plus filgrastim (filgrastim group, n = 31). Chemotherapy consisted of four cycles of cyclophosphamide, vincristine and doxorubicin (CADO) alternating at 21-day intervals with cisplatin and etoposide (CDDP-VP16). Filgrastim was administered subcutaneously at a dose of 5 micrograms/kg/day from day 7 for up to 14 days. The incidence of neutropenia (absolute neutrophil count [ANC] < 0.5 x 10(9)/l) in the filgrastim group was not reduced after the first CADO course. However, significant reductions were observed after courses 2, 3 and 4. The duration of neutropenia and of intravenous antibiotic use were significantly reduced in the filgrastim group over the whole study period (9 days versus 26 days, P < 0.001; 12 days versus 20 days, P = 0.04, respectively). However, the duration of hospitalisation and the incidence of febrile neutropenia were not significantly reduced. Compliance to treatment was good and the ability to administer chemotherapy without treatment delays was significantly better in the filgrastim group (P < 0.05). Event-free survival was greater in the filgrastim than in the control group (2.4 years versus 1.3 years; P = 0.072). Filgrastim is a beneficial adjunct to combination induction chemotherapy used in the treatment of metastatic neuroblastoma.

Antineoplastic Combined Chemotherapy Protocols↗

Improving survival in recurrent medulloblastoma: earlier detection, better treatment or still an impasse?

Early detection of relapse has been advocated to improve survival in children with recurrent medulloblastoma. However, the prognostic factors and the longer term outcome of these patients remains unclear. Pattern of recurrences were analysed in three consecutive protocols of the Société Française d'Oncologie Pédiatrique (1985-91). A uniform surveillance programme including repeated lumbar puncture combined with computerized tomography (CT) or magnetic resonance imaging (MRI) scan was applied for all registered patients. Forty-six out of 116 patients had progressive or recurrent disease. The median time from diagnosis to recurrence was 10.5 months and 76% relapses occurred during the first 2 years. Seventeen patients had asymptomatic relapses that were detected by the surveillance protocol. Forty-one patients were treated at time of progression. Twenty-three responded to salvage therapy and 11 achieved a second complete remission. The median survival time after progression was 5 months (<1-41 months), and only two patients remained alive at time of follow-up. Length of survival is primarily related to some specific patterns of relapse (time from diagnosis to recurrence, circumstances of relapse, extent of relapse) and to the response to salvage therapy. No evidence of long-term benefit appeared from any form of treatment.

Adolescent↗

Impact of the TOP-FORUM hypermedia system in a pediatric oncology care unit.

This paper describes our approach in analyzing the impact of the TOP-FORUM hypermedia in a pediatric oncology care unit. The impact of this technology is realized through the study of accommodation and assimilation adoption. Accommodation refers to the technological adoption and Assimilation refers to the professional adoption. Results show that accommodation depends on information and formation of the users. Assimilation is more difficult to evaluate because it depends on human, social and organizational problems.

Attitude of Health Personnel↗

Translocation 1;19 in two brain tumors.

We report two-cases of brain tumors, one childhood medulloblastoma and one adult glioblastoma with an unusual chromosomal abnormality: a t(1;19)(q23;q13). We analyzed these karyotypes using fluorescence in situ hybridization (FISH) and wonder if this chromosomal aberration could represent a particular entity in these brain tumors like t(1;19) in ALL.

Brain Neoplasms↗

Ifosfamide and etoposide in childhood osteosarcoma. A phase II study of the French Society of Paediatric Oncology.

The aim of this phase II study was to determine the efficacy of high-dose ifosfamide with moderate dose etoposide in childhood osteosarcoma. From January 1992 to January 1995, 27 children (15 male, 12 female) with relapsed or refractory evaluable osteosarcoma were included in a phase II study of two courses of ifosfamide 3g/m2/day and etoposide 75 mg/m2/day for 4 days. Median age was 14 years (7-19 years). All but one had received high-dose methotrexate and doxorubicin as first-line treatment. 22 patients had previously received ifosfamide. This regimen was given as first-line in 1 patient, second-line in 23 and third-line in 3. Evaluable disease was lung metastases in 21 patients, local relapse in 5 and adenopathy in 1. There were six complete responses, seven partial responses, three minor responses, six stable disease and five progressive disease (including one mixed response). Response rate was 48% (95% confidence interval, 29-67%). Duration of response was not available (10 responding patients had other treatments). Response rate was equivalent in the subgroup of 22 patients who had previously received ifosfamide (4 CR, 6 PR). Among 3 patients who received the phase II regimen as third-line chemotherapy, there was 1 PR. All but 4 patients had a well tolerated grade 4 neutropenia. Transient mild confusion or seizures were each observed once. 5 patients are alive 15-31 months after the beginning of chemotherapy. This combination of drugs at this dosage has tolerable toxicity, is efficient and deserves evaluation in phase III studies.

Adolescent↗

1070 myeloablative megatherapy procedures followed by stem cell rescue for neuroblastoma: 17 years of European experience and conclusions. European Group for Blood and Marrow Transplant Registry Solid Tumour Working Party.

1070 myeloablative procedures followed by stem cell rescue for neuroblastoma are reviewed. These 1070 procedures are part of the European Group for Blood and Marrow Transplant (EBMTG) registry from the last 17 years (in 4536 patients). In 1070 neuroblastoma patients, survival at 2 years was 49%, at 5 years, 33% and relapses were observed as late as 7 years post-BMT (bone marrow transplant). However, 5-year survivors after megatherapy with BMT for stage 4 disease do have an 80% chance of becoming a long-term survivor. When BMT had been used in first complete response (CR1) no salvage was possible, whereas 15% survivors may be seen if BMT is used for the first time at relapse. Infants with stage 4 neuroblastoma had a 17% toxic death rate and indication in this group is exceptional and not recommended. In a matched cohort (17 allogeneic and 34 autologous), autologous stem cell rescue (SCR) was shown to be at least equal to allogeneic SCR. Multivariate analysis of clinical prognostic factors in children with stage 4 disease over 1 year showed that event-free survival was mainly influenced by two adverse factors before the megatherapy procedure: persisting skeleton lesions (99Tc and/or mIBG scan positive) as well as persisting bone marrow (BM) involvement.

Adolescent↗

Phenotyping of intrahepatic and peripheral blood lymphocytes in patients with chronic hepatitis C.

The host immune responses have been suggested to play a role in liver injury occurring in patients with chronic hepatitis C. In order to explore the relationship between the relative proportions of intrahepatic and peripheral blood lymphocytes (IHL, PBL), the levels of viremia, and the histological hepatitis activity score, three-color fluorescence-activated cytometric analysis was performed for 36 patients with chronic hepatitis C and six control subjects without chronic hepatitis. The liver biopsy was performed before any antiviral therapy. Each liver specimen was divided into two parts: one for histological examination and one for immunological analysis. Tricolor CD45 was used to improve "lymphogating." Fluorescein isothiocyanate- or phycoerythrin-conjugated monoclonal antibodies with specificity for CD3, CD4, CD8, and CD20 (lymphocyte subpopulations), for CD69 (activated lymphocytes), and for CD16/56 (natural killer cells) were used. The livers of patients with chronic hepatitis C contained a greater proportion of CD4+ lymphocytes that exhibited marked expression of CD69 than in control subjects (20.7 +/- 7.3% vs 10.2 +/- 4.6%, P = 0.027). Moreover, in patients with chronic hepatitis C, the proportion of CD4+ IHL correlated with the histological hepatitis activity evaluated by the Knodell score (r = 0.48, P = 0.004). No correlation was found between the percentage of CD4+ IHL and the level of viremia or transaminase activities. Our findings clearly indicate that a cellular immune response does take place in HCV-infected livers and could thus contribute to the outcome of hepatitis C virus infection.

Adult↗

NB87 induction protocol for stage 4 neuroblastoma in children over 1 year of age: a report from the French Society of Pediatric Oncology.

PURPOSE: NB87 was designed to test the efficacy of a short, non cross-resistant, induction protocol for unselected patients over 1 year of age with stage 4 neuroblastoma. A secondary objective was to compare in a randomized study the toxicity of two modalities of cisplatin administration. PATIENTS AND METHODS: A total of 183 patients received two cycles of alternating sequences: cyclophosphamide 300 mg/m2/d on days 1 to 5, vincristine 1.5 mg/m2/d on days 1 and 5, and doxorubicin 60 mg/m2/d on day 5 (CADO); and cisplatin 40 mg/m2/d and etoposide 100 mg/m2/d on days 1 to 5 (CVP), followed by surgery of the primary tumor (126 patients). Ninety-one were randomized to receive cisplatin either as bolus (BO; n = 48) or continuous infusion (CI; n = 43). International Neuroblastoma Staging System (INSS) and Response Criteria (INRC) were used with emphasis on skeletal evaluation by meta-iodobenzylguanidine (MIBG). RESULTS: Hematotoxicity was predominant, with a higher incidence of neutropenia (P = .01) for CADO and of thrombocytopenia for CVP (P < .001). Severe infections, as well as nonhematologic toxicities, occurred more often after the first sequence. Gastrointestinal complications were predominant during both courses of CVP. The toxic death rate, including surgery, was 3%. Complete remissions (CRs) were less frequent on MIBG (45%) compared with marrow (66%) or other metastases (61%). Combining all metastatic sites resulted in a 39% CR rate. After surgery, the final CR rate was 42%. Nephrotoxicity was minimal in both arms (92% normal clearance for CI v 82% for BO). Hearing loss greater than 40 dB at 6,000 to 8,000 Hz was reported equally in both arms (n = 6 for CI v n = 5 for BO). CONCLUSION: Intensified chemotherapy using CADO/CVP increases CR rates despite a shorter induction duration. However, the rate of MIBG normalization remains unsatisfactory and could be raised through the dose-intensive use of agents such as cyclophosphamide.

Adolescent↗

[Atypical mesoblastic nephroma with metastases right away?].

The diagnosis of a metastatic kidney tumor arising in a 2-month infant is discussed between atypical mesoblastic nephroma and clear cell sarcoma. The precocity of distant metastases, their location in bone marrow, liver and thoracic soft tissues, and their association with myelofibrosis set up an original clinical presentation which seems to have never been described elsewhere. Treatment strategy with surgery of the primary followed by a polychemotherapy combining vincristin-etoposide-ifosfamide and the short term follow-up are reported.

Age Factors↗

Childhood leukaemia in Europe after Chernobyl: 5 year follow-up.

The European Childhood Leukaemia - Lymphoma Incidence Study (ECLIS) is designed to address concerns about a possible increase in the risk of cancer in Europe following the nuclear accident in Chernobyle in 1986. This paper reports results of surveillance of childhood leukaemia in cancer registry populations from 1980 up to the end of 1991. There was a slight increase in the incidence of childhood leukaemia in Europe during this period, but the overall geographical pattern of change bears no relation to estimated exposure to radiation resulting from the accident. We conclude that at this stage of follow-up any changes in incidence consequent upon the Chernobyl accident remain undetectable against the usual background rates. Our results are consistent with current estimates of the leukaemogenic risk of radiation exposure, which, outside the immediate vicinity of the accident, was small.

Child↗

[Results of surgical treatment of complicated paraesophageal hernias].

From January 1979 to May 1995, 18 patients (4 men, 14 women) with a mean age of 75.4 +/- 12.5 yr underwent surgery for a complicated paraesophageal hiatus hernia. In 5 patients, the complication was the first sign of the diagnosis. Thirteen patients had a history of digestive, respiratory, or cardiac symptoms (mean duration of symptoms 74 mo.; range 2-240 mo.); 9 of them were aware that they had a hiatus hernia. Ten patients presented with acute obstruction (associated with a perforation in 1 case, jaundice in 1 case, and righy lower lobe pneumonia in 1 case). Hemorrhage occurred in 6 patients (hematemesis 4 cases, melena 2 cases). One patient had a perforation and another had an abscess of the lower right lobe. Surgery was performed via a transabdominal approach in all cases (5 times as an emergency, 12 times as a delayed emergency procedure, and once as an elective procedure). The procedure was delayed in 13 cases because of successful nasogastric decompression. All patients underwent reintegration of the stomach, diaphragmatic repair and gastropexy. An antireflux procedure was performed in 14 cases. Seven patients had an ancillary procedure (including one splenectomy following decapsulation). There were no postoperative deaths. Two patients who underwent emergency surgery developed a benign complication. The outcome of 17 patients is known; none of them developed a recurrence. One patient who did not undergo an antireflux procedure presented with gastroesophageal reflux; another experienced pain during eructation. In conclusion, nearly two-thirds of all patients who present with an acute complication can benefit from medical preparation before surgery, a strategy that improves results.

Aged↗

[Electromagnetic residential fields and childhood cancers: state of epidemiological research].

Thirteen epidemiological studies of the relations between electromagnetic fields and childhood cancers have been published. Eleven have shown some associations between the presumed intensity of exposure to residential magnetic fields and the childhood cancers incidence, either for all cancers or for the 3 most frequent types (leukaemias, brain tumours and lymphomas). These associations are not often significant because of the weak statistical power of these studies in relation with both the low incidence of cancers in childhood, and specially of each particular type, and the little number of subjects considered to be exposed at a high level exposure for residential magnetic fields. All these studies fall in with the same difficulties, particularly for identification and assessment of the exposure to magnetic fields and for the manner to take into account all the potential confounders. So even significant associations do not imply their causality, all the more as the carcinogenicity of extremely low frequency electromagnetic fields, although biologically conceivable, has never been experimentally proven. Today it is impossible to claim or invalidate the influence of residential magnetic fields in the genesis of childhood cancer. Setting up of new epidemiological studies based on large number of cases issued from population based registries and conducted with a best defined methodology seems to be highly desirable.

Electromagnetic Fields↗

[Pneumoblastoma in children. A clinical case and review of the literature].

Pulmonary blastoma is a rare malignant tumor. A new case is reported in a 3 years 6 month-old girl. An apparent clinical remission was first obtained after a surgical treatment followed by a conventional chemotherapy during six months. Afterwards the persistence of a microscopic residual pulmonary disease lead us to deliver successfully an intensive chemotherapy followed by autologous peripheral blood stem cells reinjection. The child remains disease free 12 months after graft. Problems set by the histogenesis of this tumor, its unspecific clinical and paraclinical features and the role of conventional and intensive chemotherapy followed by autologous bone marrow transplantation are discussed on the basis of a review of 50 cases in the literature.

Antineoplastic Combined Chemotherapy Protocols↗

Inspiratory fall in systolic pressure in normal and asthmatic subjects.

We used a noninvasive monitor of arterial pressure to determine whether respiratory changes in arterial pressure were closely correlated with airflow obstruction in asthmatic patients during bronchial challenge with methacholine. To validate the noninvasive measurement of respiratory changes in arterial pressure, a preliminary study in 6 subjects with normal cardiovascular and respiratory systems was done during cardiac catheterization for suspected coronary artery disease. There were no significant differences between inspiratory falls in systolic pressure measured noninvasively and those measured from intraaortic pressure. In 11 otherwise healthy asthmatic patients we measured finger arterial pressure, end-expiratory lung volume (FRC), and forced expired volume (FEV1) during baseline and bronchial challenge in the supine posture. Finger arterial pressure was also measured in 11 normal control subjects seated and supine. Normal subjects had an inspiratory fall in systolic pressure (IFSP) of 3.2 mm Hg supine and 5.1 mm Hg seated (p < 0.01). Asthmatic patients when bronchodilated (seated FEV1 = 83 +/- 7% of predicted) had an IFSP of 5.9 mm Hg supine (p < 0.01 compared with supine normal subjects). During bronchial challenge (average fall in FEV1 = 22%), IFSP increased to 16.1 mm Hg (p < 0.001 compared with baseline). In asthmatic subjects, there was a significant correlation between IFSP and FEV1 (mean r = -0.92 +/- 0.05, p < 0.01), and the average change in IFSP/change in FEV1 was -0.38 mm Hg per percentage change in FEV1. During subsequent bronchodilation, IFSP decreased with a similar time course as relaxation of airway smooth muscle, assessed by the breath-to-breath fall in FRC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Para-esophageal hernias. Apropos of 42 cases].

Between 1979 and May 1994, 42 patients (11 males, 31 females, mean age 72.8 +/- 12.4 years) underwent surgery for paraoesophageal hiatal hernia. In 37 cases, clinical signs had been observed for 64 months on the average: digestive (32), respiratory (15), cardiac (9). Nine patients had iron deficiency anaemia. Eighteen patients had a complication (acute obstruction: 10, haemorrhage: 6, perforation: 2, lung infection: 2). In 5 cases, the complication was the inaugural sign. Surgery was performed in a emergency situation in 5 cases and deferred emergency in 12 and surgery was elective in 25. An antireflux procedure was used in 36 cases (Lortat-Jacob (2), Toupet (5), Dor (2), Nissen-Rossetti (27)). Another procedure was also needed in 12 patients. There were no postoperative deaths and complications occurred in 6 patients (14.9%). Outcome was known in 40 patients with a mean follow-up of 40.5 months (range 3 to 140 months). Functional results was very good in 35 patients (87.5%), good in 3 (7.5%) and poor in 2 (5%). The most satisfactory immediate results were obtained for patients who had elective surgery and in those with a deferred emergency. Use of the Nissen-Rossetti procedure did not have any deleterious effect on these results and no long-term inconveniences.

Acute Disease↗

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↗