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Biomedical subjects

Y Benoit

Publications and source records attributed to Y Benoit.

At least 37 records · Page 2Linked to original sources

[Biological diagnosis of immediate drug allergy. Comparative study of histamine liberation tests and CD63 expression by flow cytometry (preliminary results)].

The diagnosis of drug allergy is mainly based upon a detailed clinical history, positive skin tests (ST) and detection of specific IgE. In case of discrepant results, in vitro investigations to identify the responsible drug are needed. The histamine release test (HR) is usually performed. Nevertheless, its clinical benefit remains controversial. Flow cytometric methods (FCM) for the study of allergen induced basophil activation have been recently described. We assessed their usefulness in the diagnosis of drug allergy in comparison to HR results. Eighteen patients were included and 24 drugs (mainly antibiotics and muscle relaxant drugs) were tested. On the basis of clinical signs, 15 patients were classified as allergic (18 drugs). Sensitivity of biological investigations were found as follows: 71% (ST), 71% (FCM) and 24% (HR). This suggests performing FCM rather than HR. In addition, HR is more costly in terms of both reagents and laboratory technician time. Thus, CD63 detection by FCM seems to be a more reliable method in the clinical immunology laboratory. Additional data are needed to validate these preliminary results (sensitivity and specificity, especially in atopic patients) and to assess the interest of the method to investigate drug allergy due to other types of molecules.

Antigens, CD↗

Coexistence of an adrenocortical carcinoma with an abdominal ganglioneuroma in a child.

We report a 3-year, 5-month-old boy with an adrenocortical carcinoma. These tumours are rare and highly malignant in childhood. In most cases they are functional, secreting adrenocortical hormones. In this case there was a misleading coexistence with a second abdominal neoplasm, which was a ganglioneuroma; this is a rare benign tumour arising from the sympathetic nervous system. The imaging investigations and their findings are discussed and correlated with pathology.

Abdominal Neoplasms↗

Haematopoietic stem cell transplantation for sickle cell anaemia: the first 50 patients transplanted in Belgium.

Fifty patients affected by sickle cell anaemia underwent transplantation of HLA-identical haematopoietic stem cells (bone marrow, 48; cord blood, 2). Two groups of patients were considered for transplantation. Group 1 included 36 permanent residents of a European country who, retrospectively, met the inclusion criteria accepted at a consensus conference held in Seattle in 1990, wherein children were selected because they already had evidence of a morbid course. Group 2 included 14 patients who were transplanted earlier, had not received more than three blood transfusions and were transplanted because they had decided to return to their country of origin. Kaplan-Meier estimates of overall survival, event-free survival and disease-free survival at 11 years of the whole grafted population are 93, 82 and 85%, respectively. In group 1, overall survival, EFS and DFS were 88, 76 and 80% and in group 2, 100, 93 and 93%, respectively. Clinical manifestations of the disease, as well as disease associated haemolytic anaemia, disappeared in all successfully treated patients. Recovery of spleen function was present in seven out of 10 evaluated patients. Adverse events (death, absence of engraftment, mixed chimerism and relapse) occurred more frequently in group 1 than in group 2 (25% vs 7%, P< 0.001). Acute graft-versus-host disease (GVHD) was present in 20 patients (grade I or II, 19; grade III, 1), chronic GVHD in 10 (limited, 7; extensive, 3). One patient developed an acute myeloid leukaemia. Gonadal dysfunction was present in all patients (six boys and eight girls) transplanted close to or after puberty, although transient in one adolescent girl.

Adolescent↗

Pulmonary and mediastinal lesions in children with Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is an uncommon group of disorders affecting mainly children and young adults. In children, pulmonary involvement occurs mostly in the disseminated forms; isolated pulmonary lesions are unusual. A retrospective study was undertaken on a group of 42 children diagnosed with LCH over a 19-year period. Eight children (19 %) had radiological evidence of pulmonary involvement. The lung lesions were either present at the time of diagnosis or, when appearing during the course of the disease, always coinciding with exacerbation or recurrence of the disease in other sites. Lung involvement did not appear to be an unfavourable prognostic factor. However, the toxic effects of treatment on the lungs might lead to important pulmonary sequelae.

Adolescent↗

Sensitive and reliable detection of genomic imbalances in human neuroblastomas using comparative genomic hybridisation analysis.

Deletions of the short arm of chromosome 1, extra copies of chromosome 17q and MYCN amplification are the most frequently encountered genetic changes in neuroblastomas. Standard techniques for detection of one or more of these genetic changes are karyotyping, FISH analysis and LOH analysis by Southern blot or PCR. Each of these techniques has its own particular limitations. More recently, comparative genomic hybridisation (CGH) was introduced for detection of genomic imbalances including deletions, duplications and gene amplification. We evaluated the sensitivity and reliability of CGH for detection of the most frequently encountered genetic changes in neuroblastoma. For this purpose a panel of well-characterised neuroblastoma cell lines as well as a series of 11 primary neuroblastomas was analysed. Our results show that CGH is a valuable tool for the genetic characterisation of neuroblastomas, both for the detection of frequently occurring genomic imbalances and for the identification of previously unnoticed genetic changes.

Child, Preschool↗

Systemic effect of intrathecal methotrexate during the initial phase of treatment of childhood acute lymphoblastic leukemia. The European Organization for Research and Treatment of Cancer Children's Leukemia Cooperative Group.

PURPOSE: The in vivo response to prephase corticosteroid therapy for 1 week has been described as a major prognostic factor in childhood acute lymphoblastic leukemia (ALL). Patients with less than 1,000 blasts/microL at day 8 are considered responders and have a better prognosis. This prephase therapy is usually considered as an evaluation of glucocorticoid sensitivity. In fact, it also includes one intrathecal (IT) injection of methotrexate (MTX). In this study, we try to clarify the influence of this injection of IT MTX on the response to the prephase therapy. PATIENTS AND METHODS: This retrospective study analyzed the response to prephase therapy in 1,044 children with ALL entered onto the European Organization for Research and Treatment of Cancer (EORTC) trial 58881 of the Children's Leukemia Cooperative Group (CLCG). Analysis was restricted to 732 cases with an initial blast count greater than 1,000/microL. The following variables were tested to analyze response to prephase therapy: age, sex, evaluated risk factor (RF), blast count on day 0, actual dose of prednisolone administered, immunophenotype (T v non-T), and day of IT MTX. For statistical analysis, the variable day of IT MTX (D) was stratified into three groups: group 1 if D less than 2, group 2 if D > or = 2 but < or = 6, and group 3 if D greater than 6. RESULTS: All variables tested had a significant influence on response to the prephase therapy. This was especially true for IT MTX: 90.4% responders in group 1, 76.9% in group 2, and 70% in group 3 (P < .001). Immunophenotype was also a major predictor of response to the prephase: 88% responders in B-lineage ALL versus 56.2% in T-lineage ALL. IT MTX had a significant influence in B-lineage ALL (96% responders in group 1, 90% in group 2, and 79% in group 3; P < .001), whereas the influence could not be detected in T-lineage ALL. CONCLUSION: These results clearly demonstrate a therapeutic systemic effect of low doses of IT MTX in childhood ALL, and response to prephase therapy should not be considered as an in vivo test for cortico-sensitivity only. Earlier use of IT MTX leads to a higher percentage of responders.

Antimetabolites, Antineoplastic↗

Mitoxantrone-containing regimen for treatment of childhood acute leukemia (AML) and analysis of prognostic factors: results of the EORTC Children Leukemia Cooperative Study 58872.

The objective of this study was to evaluate the feasibility, the toxicity and the efficiency of a BFM-like treatment protocol for acute nonlymphoblastic leukemia (ANLL) of children in which mitoxantrone was substituted for conventional anthracycline. The chemotherapy called for induction (mitoxantrone, cytosine arabinoside, etoposide), consolidation (mitoxantrone, cytosine arabinoside, 6 thioguanine), followed by two intensification courses with cytosine arabinoside plus, respectively, mitoxantrone during the first and etoposide during the second courses. Maintenance therapy consisted of daily 6 thioguanine, four-weekly courses of cytosine arabinoside (s.c. daily during 4 days) and eight-weekly courses of mitoxantrone. The latter drug was pursued up to a total cumulative dose of 150 mg/sqm. Maintenance therapy was stopped at 2 years of diagnosis. Out of 108 patients, 84 (77%) achieved a complete remission, 10 died during induction of hemorrhage, sepsis or pulmonary infiltration by leukemic cells. A total of 32 relapses occurred. The median follow-up was 3.5 years. Actuarial event-free survival, disease-free survival and overall survival at 3 years as 41%, 52%, 56%, respectively. These results compare favorably with most reported data, and cytogenetic findings appear to be the most important prognostic factor.

Adolescent↗

Dobutamine stress echocardiography in the evaluation of late anthracycline cardiotoxicity in childhood cancer survivors.

Late anthracycline cardiotoxicity has been of increasing concern to pediatric oncologists. An increasing number of patients with cardiac dysfunction has been reported without a good correlation between cardiac function or symptoms and routine echocardiographic follow-up. We studied dobutamine stress echocardiography in patients who had received moderate doses of anthracyclines years before. Twenty-three patients (14 male, 9 female; 7-25 y) who completed chemotherapy with moderate doses of anthracyclines (180-380 mg/m2) more than 2 y previously underwent dobutamine stress echocardiography and were compared with a control group of 26 healthy young people (15 male, 11 female; 6-26 y) matched for age and weight. Dobutamine was administered in three periods up to a rate of 5 micro g/kg/min. Eighty-five percent of the patients showed an abnormal response to dobutamine. Both systolic and diastolic functions were affected. The systolic dysfunction was not related to diminished contractility but to an elevated systolic wall stress due to inadequate cardiac muscle thickening. The diminished wall thickening was related to the length of follow-up. Dobutamine proved to be a very sensitive method to detect clinical and subclinical cardiac dysfunction in patients post anthracycline chemotherapy and questions the concept of a safe dose.

Adolescent↗

Tropisetron in the prevention of nausea and vomiting in 131 children receiving cytotoxic chemotherapy.

Tropisetron (Navoban, Sandoz Pharma Ltd., Basel, Switzerland), a selective antagonist of the serotonin receptor (5-HT3) dosed once-daily at 0.2 mg/kg (with a maximum of 5 mg daily), was evaluated in the prevention of chemotherapy-induced nausea and vomiting in 131 children with a median age of 5 years (age 10 weeks to 21 years). Acute lymphocytic leukemia was the most common malignancy (49%). Most children (82%) had received cytotoxic chemotherapy before enrollment. Patients received tropisetron during one or more courses of chemotherapy (455 courses in total). Tropisetron was administered slowly intravenously as a single dose before the start of chemotherapy on day 1 and intravenously or by mouth the subsequent days as a single daily dose (median treatment duration: 5 days). Response to tropisetron per 24 hour period on the first 5 days of each chemotherapy course was graded as complete (absence of both nausea and vomiting), partial (one to four vomits and/or less than 5 hours of nausea), or failure. Overall complete response on day 1 was observed in 305 out of 455 chemotherapy courses (67%). The patients receiving intravenous chemotherapy (N = 92) had a 70% complete response rate and a 26% partial response rate on day 1, both for course 1 and course 2. The percentage of complete responders increased the subsequent days of the course. Emesis after day 1 was observed primarily during courses with the most emetogenic chemotherapy. No side-effects of tropisetron other than a single case of diarrhoea were documented in this study.

Adolescent↗

Control of nausea and vomiting by Navoban (tropisetron) in 131 children receiving cytotoxic chemotherapy.

One hundred and thirty-one children with a median age of 5 years were administered Navoban (tropisetron), a selective antagonist of the serotonin receptor (5-HT3), dosed once daily at 0.2 mg/kg (with a maximum of 5 mg daily) in a study aimed at evaluating the prevention of nausea and vomiting induced by anti-cancer chemotherapy. The most common malignancy (in 49% of patients) was acute lymphocytic leukaemia. Patients received Navoban during one or more courses of emetogenic chemotherapy for a total of 455 courses administered intravenously or intravenously and intrathecally (IV + IT). Most patients (89%) had already received cytotoxic chemotherapy before enrollment for the trial. On Day 1, Navoban was administered slowly and intravenously as a single dose before the start of chemotherapy, or by mouth as a single daily dose on subsequent days (median treatment duration = 5 days). On the first 5 days of each course of chemotherapy, response to Navoban per 24-hour period was graded as: complete (absence of both nausea and vomiting), partial (1-4 vomits and/or less than 5 hours of nausea), or failure (more than 4 vomits and/or at least 5 hours of nausea). Ninety-six per cent of the intravenous chemotherapy group and 97% of the IV + IT chemotherapy group had a complete (70% and 55% respectively) or partial (26% and 42% respectively) response during the first 24-hour period of the first course in which Navoban was used. The second and subsequent courses yielded similar percentages. Delayed emesis was observed mainly during those courses employing the most emetogenic chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Intracranial germ cell tumors: a comprehensive update of the European data.

Intracranial germ cell tumors are rare tumor entities in childhood and adolescents. Extra- and intracranial germ cell tumors are identical in their histologic pattern and occur in preferential midline localizations such as the pineal and the suprasellar region. Germ cell neoplasms show increasing incidence rates over the last 30 years. The majority of intracranial germ cell neoplasms are germinomas. About 90% of the patients with pure germinomas can be salvaged by radiotherapy alone according to modern protocols. Non-germinomatous malignant CNS-germ cell tumors are considered to have a poor prognosis. In order to improve the survival of patients affected by these tumors different treatment approaches adding chemotherapy to conventional surgery and radiotherapy have been initiated by various study groups throughout the world. Due to the rarity of these neoplasms only a very limited number of patients has been enrolled in each study. In 1993 an international working group on these tumors was established by the International Society of Pediatric Oncology (SIOP).

Brain↗

Improved survival for acute lymphoblastic leukaemia in infancy: the experience of EORTC-Childhood Leukaemia Cooperative Group.

Out of 744 newly diagnosed ALL children under the age of 18 years treated according to the EORTC-CLCG protocols 58831 and 58832, 28 (4%) were infants less than 1 year of age. An elevated risk factor, which takes into account the sizes of the liver and spleen and the number of circulating blasts, was present in 25 cases. Most patients had non-common ALL. Among 15 patients studied by cytogenetics, nine present chromosomal abnormalities, six of them having a t(4;11) translocation. Complete remission was achieved in 86% of cases. One patient died in complete remission of therapy-related infection. The overall EFS is 43%. It is not statistically different in very young infants as compared to infants older than 6 months. Except for patients with AUL or with t(4;11) translocation, a continuous complete remission rate above 50% can be achieved with a median follow-up of 4 years. The results obtained in infant ALL with EORTC-CLCG protocols are currently better than those obtained with some other protocols, but remains inferior when compared to the ones obtained in older children. Thus, further improvements are needed and should be evaluated in large cooperative trials.

Age Factors↗

Performance of the Coulter STKS and the Sysmex NE-1500 in a paediatric population.

The Coulter STKS and the Sysmex NE-1500 were evaluated for their performance in paediatric samples. Special attention was paid to the ability of both instruments to detect white blood cell morphology abnormalities. Therefore a population with a high frequency of pathologies was selected. The studied population included children aged between 1 month and 14 years, 45% of which suffered from oncological and/or haematological diseases. Two hundred and forty blood samples were analysed. The leukocyte differentiation results from the Coulter STKS and the Sysmex NE-1500 were compared with the manual microscopic method. The differentials compared very well for neutrophils, lymphocytes and eosinophils. Sensitivity and specificity for the detection of blasts, immature granulocytes, left shift and atypical lymphocytes were examined. While specific morphology flagging showed a rather low sensitivity, blasts and immature granulocytes were mostly detected by the two systems, taking into account white blood cell alarm flags other than the two mentioned above. The overall sensitivity for the detection of white blood cell abnormalities was better with the Coulter STKS, whereas the Sysmex NE-1500 showed a higher specificity. In an ancillary study which was performed exclusively on neonatal samples, of which 80% originated from preterm infants, we found a limited sensitivity for the detection of low percentages of nucleated red blood cells for both analysers. The high frequency of abnormalities, together with the limited sensitivity mentioned above, prompted us to review all neonatal samples in the future.

Adolescent↗

A comparison of iodine-123 meta-iodobenzylguanidine scintigraphy and single bone marrow aspiration biopsy in the diagnosis and follow-up of 26 children with neuroblastoma.

In staging neuroblastomas, the demonstration of tumoural invasion of the bone marrow is an important criterion with regard to the therapeutic prospects and the prognosis. Iliac crest aspiration sampling has been used routinely for the detection of bone marrow metastases in neuroblastoma. However, due to the limited character of the sampling, it sometimes leads to false-negative results. Another procedure which is used to determine the extent of neuroblastoma is metaiodobenzylguanidine (mIBG) scintigraphy. In order to establish the respective merits of both diagnostic techniques retrospectively, 148 iodine-123 mIBG scans of 26 children with neuroblastoma have been re-evaluated and compared with the results of routine bone marrow samples obtained within a 4-week period before or after scanning. Three types of mIBG uptake in the bone/bone marrow could be differentiated: (1) no visualization of the skeleton; (2) diffuse uptake in the skeleton with or without focally increased uptake, which indicates massive, diffuse bone marrow invasion by the tumour; and (3) focal tracer accumulation in one or several bones. No tracer uptake was observed in the skeleton in 91 scans. In 89 of the 91 the bone marrow biopsy was negative. Twenty-four scans showed diffuse skeletal uptake with or without foci. The bone marrow biopsies were negative for eight of those 24 scans. Hyperactive foci in one or more bones without diffuse tracer accumulation in the skeleton were detected in 33 scans. In only 7 of these 33 scans did bone marrow biopsy specimens from the iliac MDP crest contain neuroblastoma cells.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Iodobenzylguanidine↗

Gender difference in aerobic capacity in adolescents after cure from malignant disease in childhood.

The aim of this study was to document gender difference in aerobic capacity after cure from malignant disease in childhood. We studied 18 males and 17 females aged 11-19 years and 10-18 years, respectively. They had all completed their treatment at least two years previously. Twelve males and 11 females received anthracyclines in comparable doses (range 150-500 mg/m2). Maximal exercise tests were performed on a cycle ergometer. Maximal oxygen consumption (ml/min/kg) was significantly (p < 0.001) lower only in females when compared to their controls. We postulate two causes: girls are smaller than their controls, possibly related to their higher vulnerability to cranial irradiation than boys; and girls were less involved than boys in sports. The influence of anthracycline treatment on aerobic capacity was only observed in males and not in females. This could be related to the higher exercise level in boys than in girls.

Adolescent↗

Detection of subtle reciprocal translocations by fluorescence in situ hybridization.

Three different subtle reciprocal translocations were detected on long, well-banded chromosomes. The same translocations were examined using fluorescence in situ hybridization (FISH) with chromosome-specific libraries and unique DNA sequences. Our findings show that FISH allows rapid and unequivocal detection and characterization of this type of chromosome rearrangement. This approach is especially useful for prenatal diagnosis when one of the parents is a balanced carrier of such small fragment translocations.

Adult↗