Pheochromocytoma and neuroblastoma are distinct tumours, but their biological diagnosis is based on secretion increase of one or several catecholamines. Assays have to be very sensible and specific for an early diagnosis. 24 hours urinary catecholamines and metabolites are currently measured, but technical improvements permit plasma metanephrine assay, an excellent indicator of pheochromocytoma. HPLC coupled to electrochemical detection represents the most efficient methodology. After a review of urinary and plasma assay methods, the authors show usual values of catecholamines, metanephrines, HVA and VMA, according to ages, and give examples of results encountered in classical or not tumours and in falsely positive cases. Urinary metanephrine assay is the most sensible and specific in biological diagnosis of pheochromocytoma, while catecholamines and VMA assays lack of sensibility. Results have to be given by 24 hours and by creatinine ratio. Metanephrine assay can be performed also in plasma and exhibits the same interest. However, in urine as in plasma, in case of renal failure, results cannot be interpreted. Neuroblastoma biological diagnosis is based classically on HVA, VMA, and dopamine assays, nowadays only in 24 hours urine (or in urinary micturition for screening), and results are also expressed as creatinine ratio. But even if several assays are advisable, 5% of the neuroblastoma cases do not produce increased catecholamine values. In some cases, metanephrine assay could be of interest. After the age of 12 months, clinical expression of neuroblastoma is dramatic in 70% of cases. So, a biological screening has been experimented in several countries including France. A French translation of the consensus conference report (1998) is appended, which shows the complexity of neuroblastoma screening. Now, there is no evidence that early tumour detection by screening lessens the mortality rate, but a weak benefit is not excluded.

A pilot study of neuroblastoma mass screening was initiated in January 1990 in the Rhône French district. The expected number of births per year is 26,000. The study is designed for a 5-year period with three major goals: 1) measurement of the compliance rate of a voluntary test at 4 months of age; 2) evaluation of the technical value of high-pressure liquid chromatography (HPLC) as a screening method; and 3) detailed biological characterization of all detected tumors. 61,551 children were screened between May 1, 1990 and December 31, 1993. Participation was 69% in 1990, 81.5% in 1991, and over 83% in 1992. HPLC was a satisfactory assay method. The number of clinical examinations required for positive tests as defined in the protocol is 1 per 3,621 tests. The false positive rate is 1 per 3,583 tests. Eight neuroblastomas were discovered by-screening (one stage I, three stage II, one stage III, three stage IVs). All are alive and well but were good prognosis cases according to the main prognostic factors. Five patients were discovered before screening (so called Halo effect): one stage I, one stage III, three stage IVs. One died of disease and four are alive in complete remission after treatment. Two patients were false negative (one stage III with N-myc amplification, one stage IV with bad prognosis features) and three cases of neuroblastoma were missed because of noncompliance with the screening program. This pilot study concludes on the feasibility of a mass screening program in France. The estimated cumulative incidence of neuroblastoma at 3 years is 1 per 4,375 living births and overdiagnosis is probable. All the detected cases were of good prognosis and the false negative ones were poor prognosis cases.

Interleukin-1 (IL-1) defines two polypeptides, IL-1 alpha and IL-1 beta, that possess a wide spectrum of biological effects. Two natural antagonists of IL-1 action have been characterized: the IL-1 receptor antagonist (IL-1Ra) and a soluble form of the type II IL-1 receptor. Neutralizing autoantibodies to IL-1 alpha have also been detected in sera of healthy individuals and patients with autoimmune or inflammatory diseases. To characterize such antibodies molecularly, we attempted to generate B cell clones producing anti-IL-1 alpha human monoclonal antibody (HuMAb) by combining Epstein-Barr virus-immortalization and CD40-activation of B lymphocytes from individuals with circulating anti-IL-1 alpha. We describe herein the generation and properties of a natural IgG4/kappa anti-IL-1 alpha monoclonal autoantibody, HuMAb X3, that bound specifically to human IL-1 alpha, but not to IL-1 beta and IL-1Ra, with a high affinity (Kd = 1.2 x 10(-10)M). HuMAb X3 inhibited IL-1 alpha binding to IL-1 receptors and neutralized biological activities of both recombinant and natural forms of IL-1 alpha. A recombinant form of HuMAb X3 was found to display identical specific IL-1 alpha antagonism. The presence of somatic mutations within X3 variable regions suggests an antigen-driven affinity maturation. This study extends the demonstration of the presence of high affinity neutralizing anti-IL-1 alpha autoantibodies that can function as a third type of IL-1 antagonist.

Serum neuron-specific enolase (NSE) levels were studied by an enzymo-immunoassay method in 2 groups of patients: a group of epileptic patients, and a group of patients with refractory major depression after electroconvulsive therapy (ECT). In patients without organic neurological disease (n = 274) the mean serum NSE level (± S.D.) was 8.4 ± 3.4 μg/l. No correlation with sex or age was observed. No significant difference was observed between epileptic patients without seizure or major electroencephalogram (EEG) abnormality, and a reference group. Significant increases were observed in 32 samples collected from patients with interictal EEG without spikes and waves before the 7th day after a seizure, in whom mean NSE was 21.5 ± 9.4 μg/l, and in 26 samples from 4 patients without seizures but with spikes and waves in the interictal EEG, whose mean NSE was 20.6 ± 11.5 μg/l. The increases of serum NSE levels in epileptic patients seem therefore to be linked to seizures and/or to EEG abnormalities. The consequences of these observations for the survey of epileptic patients, and for the diagnosis of cerebral tumors (mainly neuroblastoma) or for monitoring treatment after surgical resection, are discussed. In only 1 patient out of 6, an increase in serum NSE levels was observed with a peak about 12 h after ECT. No significant correlation with the ECT features (length of seizures, one- or two-sided electrodes) was observed.

The possible interference of haematocrit was studied in an evaluation of the analytical performance of the NOVA 11 analyzer. For lithium concentrations between 0.56 and 0.68 mmol/L, the within-run imprecision was less than 1.06%, and less than 2.8% in day-to-day imprecision, measured in quality control solutions. Comparison of whole blood with plasma measurement showed satisfactory correlation with deviations up to 0.06 mmol/L for haematocrits from 35-53% (y = 0.73 x + 0.12). Measurement on a blood specimen not containing lithium, whose haematocrit was varied, allowed us to quantify a specific red cell interference. With samples from treated patients, and a sample spiked to various lithium concentrations, we obtained differences dependent on haematocrit and on lithium concentrations. In subtracting the specific red cell effect, we could systematically observe that apparent lithium levels diminish as haematocrit increases. This observation should allow development of an appropriate algorithm for obtaining exact values on whole blood samples.

Introduction: Following the pioneering Japanese experience, several European and North American groups implemented pilot studies on screening infants for neuroblastoma, considering the possibility of demonstrating a decrease in mortality rate. In France, a 5-year (1990–1994) feasibility study on neuroblastoma screening at the age of 4 months was initiated in the Rhône district (1.5 M inhabitants, 26 000 births per year). Methods: Vanillyknandelic (VMA) and homovanillic (HVA) acids were measured by HPLC, and creatinine (Cr) by the Jaffé's kinetic method on Technicon RA-XT(™). VMA and HVA were expressed as μg/mg of Cr. The method was assessed with both a daily intra-laboratory control and a sample of urine obtained from a national quality control organism. Results and discussion: The overall participation rate for the 5-year period was 82.2%. Out of 105 293 infants tested from 128 126 births, 12 NB cases were discovered with screening (screened cases) and 1 case was discovered with a late performed test (at 13 months of age). Six neuroblastomas were found clinically before the age of 4 m. Two cases were missed because the parents did not perform the test. Three children with normal tests at screening were false-negative cases: two of them were found secreting at diagnosis, while one remained non-secretory at diagnosis and later on. Otherwise, thirty five false-positive tests were found. Biochemical observations are discussed. It is too early to reach clinical conclusions from this screening program on neuroblastoma as it is presently being followed up.

Journal of Interferon ResearchVol. 14, No. 5 Human Monoclonal Antibody as an Interleukin-10-Specific AntagonistP. GARONNE, O. DJOSSOU, F. FUSSIEZ, S. AIT-YAHIA, J. REYES, M.J. MAAT, S. HO, T. HAUSER, J.M. DAYER, E. PEYRON, J.F. NICOLAS, P. JOUVENNE, P. MIOSSEC, J. GREFFE, F. ROUSSET, S. LEBECQUE, and J. BANCHEREAUP. GARONNESearch for more papers by this author, O. DJOSSOUSearch for more papers by this author, F. FUSSIEZSearch for more papers by this author, S. AIT-YAHIASearch for more papers by this author, J. REYESSearch for more papers by this author, M.J. MAATSearch for more papers by this author, S. HOSearch for more papers by this author, T. HAUSERSearch for more papers by this author, J.M. DAYERSearch for more papers by this author, E. PEYRONSearch for more papers by this author, J.F. NICOLASSearch for more papers by this author, P. JOUVENNESearch for more papers by this author, P. MIOSSECSearch for more papers by this author, J. GREFFESearch for more papers by this author, F. ROUSSETSearch for more papers by this author, S. LEBECQUESearch for more papers by this author, and J. BANCHEREAUSearch for more papers by this authorPublished Online:5 May 2009https://doi.org/10.1089/jir.1994.14.309AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "Human Monoclonal Antibody as an Interleukin-10-Specific Antagonist." , 14(5), p. 309FiguresReferencesRelatedDetails Volume 14Issue 5Oct 1994 To cite this article:P. GARONNE, O. DJOSSOU, F. FUSSIEZ, S. AIT-YAHIA, J. REYES, M.J. MAAT, S. HO, T. HAUSER, J.M. DAYER, E. PEYRON, J.F. NICOLAS, P. JOUVENNE, P. MIOSSEC, J. GREFFE, F. ROUSSET, S. LEBECQUE, and J. BANCHEREAU.Human Monoclonal Antibody as an Interleukin-10-Specific Antagonist.Journal of Interferon Research.Oct 1994.309-309.http://doi.org/10.1089/jir.1994.14.309Published in Volume: 14 Issue 5: May 5, 2009PDF download

Neuroblastoma is the commonest solid tumour in children under the age of 5 years (50% of cases before 2 years, 90% before 5) and the second cause of death after accidents. Approximately one child in 10 000 develops neuroblastoma by the age of 15 years. The situation in other European and North American countries is similar to that in France. As neuroblastoma is derived from the sympathetic nervous tissues, it is associated with the production of large amounts of catecholamines and their metabolites which are excreted in the urine. Less than 5% of cases do not produce catecholamines. Vanillylmandelic acid (VMA), homovanillic acid (HVA) and dopamine (DA) are the most useful chemical markers for the diagnosis and clinical control of neuroblastoma. They are generally measured using the reliable and sensitive high pressure liquid chromatography (HPLC). Survival is related to stage (the Evan's staging protocol has been superseded by the INNS staging), and age at diagnosis. There is almost 100% survival for stages I and IIa before the age of 12 months, and less than 20% for stage IV when diagnosed after 2 years of age. Multiple copies of the N-myc oncogene, deletions of chromosome 1p, and diploidy in tumour cells are associated with poor prognosis. Neuroblastoma fulfils the criteria of a condition suitable for screening: it is a serious illness associated with a poor outcome; treatment is more effective in the early rather than late disease stages; there is support for the concept that the disease progresses from the early to late stages; even within stages III or IV younger children have a better prognosis; there are chemical markers excreted in the urine. A feasibility study for neuroblastoma screening was carried out in France, in the Rhone district (26 000 births per year) for a period of 5 years: 1990-1994. This screening programme is evaluated, the main result being a reduction in mortality for stage IV neuroblastomas.

Introduction: Following the pioneering Japanese experience, several European and North American groups implemented pilot studies on screening infants for neuroblastoma, considering the possibility of demonstrating a decrease in mortality rate. In France, a 5-year (1990–1994) feasibility study on neuroblastoma screening at the age of 4 months was initiated in the Rhône district (1.5 M inhabitants, 26 000 births per year). Methods: Vanillyknandelic (VMA) and homovanillic (HVA) acids were measured by HPLC, and creatinine (Cr) by the Jaffé's kinetic method on Technicon RA-XT(™). VMA and HVA were expressed as μg/mg of Cr. The method was assessed with both a daily intra-laboratory control and a sample of urine obtained from a national quality control organism. Results and discussion: The overall participation rate for the 5-year period was 82.2%. Out of 105 293 infants tested from 128 126 births, 12 NB cases were discovered with screening (screened cases) and 1 case was discovered with a late performed test (at 13 months of age). Six neuroblastomas were found clinically before the age of 4 m. Two cases were missed because the parents did not perform the test. Three children with normal tests at screening were false-negative cases: two of them were found secreting at diagnosis, while one remained non-secretory at diagnosis and later on. Otherwise, thirty five false-positive tests were found. Biochemical observations are discussed. It is too early to reach clinical conclusions from this screening program on neuroblastoma as it is presently being followed up.

Neuroblastoma is the commonest solid tumour in children under the age of 5 years (50% of cases before 2 years, 90% before 5) and the second cause of death after accidents. Approximately one child in 10,000 develops neuroblastoma by the age of 15 years. The situation in other European and North American countries is similar to that in France. As neuroblastoma is derived from the sympathetic nervous tissues, it is associated with the production of large amounts of catecholamines and their metabolites which are excreted in the urine. Less than 5% of cases do not produce catecholamines. Vanillylmandelic acid (VMA), homovanillic acid (HVA) and dopamine (DA) are the most useful chemical markers for the diagnosis and clinical control of neuroblastoma. They are generally measured using the reliable and sensitive high pressure liquid chromatography (HPLC). Survival is related to stage (the Evan's staging protocol has been superseded by the INNS staging), and age at diagnosis. There is almost 100% survival for stages I and IIa before the age of 12 months, and less than 20% for stage IV when diagnosed after 2 years of age. Multiple copies of the N-myc oncogene, deletions of chromosome 1p, and diploidy in tumour cells are associated with poor prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

An epidemiological study of neuroblastoma in the Rhône-Alpes area was carried out over a 5 year period. The aim was to set up a background for a screening program in order to increase the number of neuroblastoma diagnosed in children before age 1, and decrease or eliminate advanced stage neuroblastomas.

The authors report, as compared to healthy subjects, a higher daily excretion and a higher urinary variations of homovanillic acid (HVA) for schizophrenic chronic paranoid patients (patients with positive symptomatology predominating, CROW,s type I). Inversely, a lower HVA excretion and probably an inversion of the circadian rhythm of urinary HVA were found for schizophrenic chronic undifferentiated patients (patients with negative symptomatology predominating, CROW's type II). These results have to be confirmed by the study of a greater number of patients and the measure, for comparison among themselves, of other precursors and metabolites of monoamines.