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N L Carlsen

Publications and source records attributed to N L Carlsen.

At least 19 recordsLinked to original sources
PubMed1998

A lack of neuroblastoma in Down syndrome: a study from 11 European countries.

An epidemiological investigation in 11 European countries comprising a total childhood population of 54.1 million children and using 8 separate data sources was conducted to evaluate the occurrence of neuroblastoma in Down syndrome (DS). No cases of DS were detected among 6724 infants and children with neuroblastoma, although more than five were expected. This highly significant result (P = 0.0045 according to the Poisson test) is consistent with data in the literature, which contains only two poorly detailed cases in epidemiological studies and one ganglioneuroma in a DS mosaic patient. Like other tumors, such as leukemias, testicular germ cell tumors and lymphomas are in excess in DS patients; the lack of neuroblastomas does not reflect a general decreased incidence of cancer but rather a specific underrepresentation of this precise tumor. S-100 b protein, the gene for which maps to the long arm of chromosome 21, (a) is overproduced in DS patients, (b) produces growth inhibition and differentiation of neural cells in vitro, (c) is abundant in good-prognosis neuroblastomas, and (d) has been shown to induce growth inhibition and differentiation and cell death in several human and murine neuroblastoma cell lines and could be responsible for this variation. Additional epidemiological and experimental studies are warranted to confirm our interpretation of these data.

Adolescent↗
PubMed1996

Serum neuron specific enolase (S-NSE) reference interval evaluation by time-resolved immunofluorometry compared with a radioimmunoassay.

The serum neuron specific enolase (S-NSE; EC 4.2.1.11) reference interval was evaluated by DELFIA (Wallac) in 161 healthy blood donors and the method compared with the S-NSE RIA assay (Pharmacia). The DELFIA assay total analytical variation coefficient (CV%) was between 3.7% and 6.6%., the RIA CV% 7.6% to 13.1%. Late centrifugation (after hours) increased the variation as a result of contamination with blood cells. Log transformation into a gaussian distribution was selected by Box-Cox analysis and tested by two models: the gauss-distribution and the Refval transformation. The 95% reference intervals and corresponding 90% confidence intervals were: female 2.9-9.6 micrograms/l (2.6-3.2 and 8.5-10.7) micrograms/l and male 3.4-11.7 micrograms/l (3.0-3.8 and 10.2-13.2 micrograms/l). Mean values were significantly different (P < 0.001), female 5.3 (4.9-5.6), male 6.3 (5.8-6.7) micrograms/l. The serum NSE levels were analysed with both methods in a population of 110 patients. The results were significantly correlated (coefficient, 0.9896; r, 0.99; P < 0.0001-two tailed). For high S-NSE values (> 150.0 micrograms/l) differences between the methods exceeded the mean difference + 2S.D., while low concentrations were interconvertible. Maximal diagnostic efficacy was 0.91 for both assays, in DELFIA 17.2-23.9 micrograms/l and for RIA 17.2-21.9 micrograms/l. Identical sensitivity, specificity, discriminative power score, and likelihood ratio were found. The two methods are consequently interconvertible.

Adolescent↗
PubMed1996

Neuroblastomas presenting in the first year of life: epidemiological differences from those presenting at older ages.

In a population-based study comparing neuroblastomas presenting in the first year of life with those presenting at older ages, the following aggregate associations were found: Presentation of the disease before 1 year of age was associated with (i) multiorigin of primary tumors, (ii) young parental age, (iii) lower socioeconomic circumstances, and (iv) complications during pregnancy. Presentation after the first year of life was associated with (i) unifocal disease, (ii) a higher frequency of hereditary diseases in the family, and (iii) parental age above 34 years. Maternal occupation in medical services appeared to be associated with multiorigin of tumors; otherwise, the occupations held by the parents at the time of the child's birth did not differ between the two groups of patients. We hypothesized that differences between the two groups of patients might point to (i) risk factors for germ line mutations and (ii) genomic imprinting. An alternative explanation of the differences could, however, be that neuroblastoma represents at least two distinct disease entities.

Adolescent↗
PubMed1994

Neuroblastomas in Denmark 1943-80. Epidemiological and clinical studies.

Two-hundred-and-fifty patients were registered in a population-based study of neuroblastomas in Denmark in the period 1943-80. The major epidemiological findings were an increased incidence with an unchanged mortality rate during the study period. The increase in incidence related solely to children 0-4 years of age and was most pronounced in infants under 1 year of age. Several reasons for the observed epidemiological rates include (i) changes in the composition of the population, (ii) improved diagnostic procedures, (iii) a shift in the diagnostic criteria, and (iv) an increase in environmental carcinogens of importance in the induction of neuroblastoma. Associated with an increased risk were lower socio-economic levels and young or advanced parental age, suggesting the importance of environmental as well as genetic factors for the induction of neuroblastoma. The epidemiological findings of an increased incidence with an unchanged mortality rate, which suggests the inclusion of borderline lesions in recent years, are of major importance in interpreting the results of mass screening for the disease. The clinical findings in 253 patients treated in Denmark from 1943 to 1980 (including 5 patients resident outside Denmark and excluding 2 patients without available hospital records) were analysed. The major finding was a zero-time shift, that is, earlier diagnosis of the disease during the study period, with increasing survival rates from decade to decade mostly due to a better age and stage distribution, a zero-time shift which was also apparent in the changes of the symptomatology. Independent prognostic variables were age, stage, and treatment with chemotherapy for children over 1 year of age with stage II disease, and for infants with stages III-IV disease. Analysis of data from a subset of the 253 children suggested that high proliferative activity detected by flow cytometry may be an important prognostic variable. The study also suggests that the pattern of metastatic spread might have changed as a consequence of prolonged survival obtained by improved treatment modalities, stressing the importance of a high frequency of autopsy among cancer patients. Hypotheses generated by the study included (i) that most neuroblastomas might be congenital, (ii) that the age influence on prognosis might be explained in terms of growth rate, cell cycle transit time, and duration of the disease, and (iii) that some neuroblastomas might be borderline lesions.

Adolescent↗
PubMed1993

Revisions of the international criteria for neuroblastoma diagnosis, staging, and response to treatment.

PURPOSE AND METHODS: Based on preliminary experience, there was a need for modifications and clarifications in the International Neuroblastoma Staging System (INSS) and International Neuroblastoma Response Criteria (INRC). In 1988, a proposal was made to establish an internationally accepted staging system for neuroblastoma, as well as consistent criteria for confirming the diagnosis and determining response to therapy (Brodeur GM, et al: J Clin Oncol 6:1874-1881, 1988). A meeting was held to review experience with the INSS and INRC and to revise or clarify the language and intent of the originally proposed criteria. Substantial changes included a redefinition of the midline, restrictions on age and bone marrow involvement for stage 4S, and the recommendation that meta-iodobenzylguanidine (MIBG) scanning be implemented for evaluating the extent of disease. Other modifications and clarifications of the INSS and INRC are presented. In addition, the criteria for the diagnosis of neuroblastoma were modified. Finally, proposals were made for the development of risk groups that incorporate both clinical and biologic features in the prediction of prognosis. The biologic features that were deemed important to evaluate prospectively included serum ferritin, neuron-specific enolase (NSE), and lactic dehydrogenase (LDH); tumor histology; tumor-cell DNA content; assessment of N-myc copy number; assessment of 1p deletion by cytogenetic or molecular methods; and TRK-A expression. RESULTS AND CONCLUSION: Modifications of the INSS and INRC made at this conference are presented. In addition, proposals are made for future modifications in these criteria and for the development of International Neuroblastoma Risk Groups.

Humans↗
PubMed1992

Prognostic importance of DNA flow cytometrical, histopathological and immunohistochemical parameters in neuroblastomas.

In 42 tumour samples of human neuroblastoma, histological classification by differentiation (Shimada) was significantly correlated with strong positivity for neuron-specific enolase (NSE) and inversely correlated with rosette formation. Most ganglioneuroblastomas were positive for S-100 protein and reacted strongly with NSE antibody. Histological signs of high proliferative activity included intermediate or high mitosis-karyorrhexis index, necrosis and lack of calcification, which were significantly correlated with each other. Flow cytometric DNA analysis demonstrated that 88% of the tumour samples had DNA aneuploid stem lines. High S phase fraction (greater than or equal to 0.20) was significantly correlated with necrosis and lack of calcification. Univariate analysis of prognosis for 26 patients whose tumour samples were obtained before adjuvant treatment showed that five factors were significantly related to a better outcome: early stage of the disease (stages I, II, IV-S), S phase fraction less than 0.20, favourable Shimada histology, positivity for S-100 protein, and strong positivity for NSE. In multivariate analysis, only S phase fraction or stage of disease remained significantly associated with prognosis. DNA index did not correlate with prognosis in this study.

Adolescent↗
PubMed1992

Neuroblastoma: epidemiology and pattern of regression. Problems in interpreting results of mass screening.

Neuroblastomas are malignant, embryonic tumors, and most are probably congenital in origin. Neuroblastoma is a heterogeneous neoplastic disease with respect to response to treatment and prognosis. Some of its clinical behavior is ascribed to the ability of the tumor to regress spontaneously. Spontaneous regression of neuroblastoma is occasionally observed in young infants, but occurs extremely rarely in older children. This feature is in accordance with the concept that tumors develop by a series of changes, progressing from a dependent state to an autonomous state. Spontaneous regression was documented in less than 2% of Danish neuroblastoma patients. However, the "true" incidence of regression may be higher. Epidemiological data suggest that, in recent decades, borderline lesions may be included among truly malignant neuroblastomas. The recent birth cohorts compiled in Denmark show that 1 in 7,000 live births will develop neuroblastoma before 15 years of age. If 65% of all childhood neuroblastomas could be detected at or before the age of 6 months, then the expected prevalence by screening would be 1/11,000. One can speculate that 1/18,000 live births might possibly benefit from screening at age 6 months, since 59% of these children had tumors in stages III and IV diagnosed after the age of 6 months. However, the proof that screening can only detect lesions that would have progressed to become malignant tumors depends on observing an appropriate fall in the incidence of the malignant tumors in older children and a decline in mortality. Therefore, it is of some concern that the incidence of neuroblastomas appears to actually increase with screening while mortality has been little effected.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

How frequent is spontaneous remission of neuroblastomas? Implications for screening.

The 'true' incidence of spontaneous regression of neuroblastomas is uncertain. However, the frequency of spontaneous regression is important when the benefits of screening procedures are considered. In the population-based Danish neuroblastoma survey 1943-80, spontaneous regression was documented in less than 2% of cases. However, the 'true' incidence may be higher. The epidemiological findings of increased incidence and survival rates with an unchanged mortality rate may suggest the inclusion of borderline lesions among 'truly' malignant neuroblastomas in recent decades in Denmark. However, it is more likely to be a result of improved diagnosis, changes in the social composition of the population and possibly unidentified environmental agents. However, if some premalignant lesions in fact had been included, they are most likely to be stages I-II tumours of infancy. In this study we describe cases of spontaneous regression of neuroblastoma from the Danish population-based survey 1943-80.

Child, Preschool↗
PubMed1990

Late effects on pulmonary function of mantle-field irradiation, chemotherapy or combined modality therapy for Hodgkin's disease.

The aim of the present study was to assess late pulmonary sequelae after treatment for Hodgkin's disease with various treatment modalities. Pulmonary function was studied in 142 patients per median 8 years after treatment for Hodgkin's disease with mantle-field irradiation (54 patients), chemotherapy (26 patients) or mantle-field irradiation followed by chemotherapy (62 patients). Mantle-field irradiation was associated with a primary obstructive and minor restrictive lung function impairment, whereas chemotherapy and combined modality therapy were associated with a restrictive lung function impairment. The number of patients with impaired lung function and the number of patients with complaints of dyspnea, however, were almost the same in the three treatment groups. 5% of the 142 patients had a pathologically low total lung capacity, i.e. values less than 2 standard deviations below predicted values. Pathologically low values of forced vital capacity and forced expiratory volume in 1 second were seen in 33% and 27% of the patients. 33% of the smokers (n = 80) had a pathologically low diffusion capacity in contrast to 8% of the non-smokers (n = 62). Dyspnea on exertion was present in 24% of the 142 patients and was more frequent among patients with pulmonary functional abnormalities. In conclusion, late pulmonary sequelae after treatment for Hodgkin's disease do not provide a basis for choice between otherwise equally effective treatment regimes.

Adult↗
PubMed1990

Influence of age and duration of follow-up on lung function after combined chemotherapy for Hodgkin's disease.

Pulmonary function was studied in 48 patients 4-13 yrs after treatment for Hodgkin's disease with mantle-field irradiation followed by standard mechlorethamine, Oncovin, procarbazine and prednisone (MOPP) chemotherapy. The patients were found to have a restrictive lung disease suggestive of pulmonary fibrosis. Low age at therapy (less than or equal to 30 yrs, median 24 yrs) was associated with a significantly more pronounced restrictive lung function impairment than older age (greater than 30 yrs, median 40 yrs) suggesting a higher susceptibility to the pulmonary side-effects of therapy. In addition younger smokers had a significantly greater reduction in diffusion capacity and forced expiratory volume in one second than older smokers, suggesting a higher susceptibility to the additional adverse effect of smoking. With longer follow-up nonsmokers had an increase in static lung volumes. It is suggested that this may be the result of more frequent pulmonary infections in such patients as compared with the general population. However, the duration of follow-up was not associated with changes in other indices of lung function.

Adult↗