Posthumanist Education

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Philosophy of education in a critical position. La filosofía de la educación en una posición crítica

Bajo Palabra, Revista de Filosofí

Low expression of bcl-2 in Brca1-associated breast cancers

Little data are available concerning the molecular mechanisms of action of Brca1 and Brca2 in breast oncogenesis. Recent experimental results suggest that Brca1 plays a role in the regulation of apoptosis. In order to determine whether the analysis of human tumours would provide data supporting this hypothesis, we have assessed the expression of the antiapoptotic bcl-2 and of the proapoptotic p53 genes in Brca1- and Brca2-associated breast carcinomas. The levels of expression of these genes were compared to those observed in controls and to the mitotic and the apoptotic indexes. Our series were composed of 16 cases of breast carcinoma in women with a germline Brca1 gene mutation, and of four cases with Brca2 mutation. A group of 39 patients aged under 36 years and for whom the search for Brca1 gene mutations was negative, and a group of 36 cases of sporadic cancers without data on their Brca status were used as controls. Immunohistochemistry was used to detect p53 and bcl-2 gene products. Mitotic and apoptotic indexes were higher in Brca1-associated tumours than in controls. No significant difference in p53 immunostaining was observed between the four groups of patients. In contrast, the rate of bcl-2-positive tumours was lower (31%) in Brca1-carcinomas than in carcinomas without Brca1 mutation (90%) (P< 10–3). A strong Bcl-2 expression was found in the four cases of Brca2-associated carcinomas. No significant correlation was observed between p53 and Bcl-2 immunostainings, either in cases or in controls. The association between Brca1 status and Bcl-2 expression remained significant after adjustment for the oestrogen receptor status. Our study shows that a low expression of bcl-2 characterises most Brca1-associated breast carcinomas, a biological trait which seems not to be shared by Brca2-associated tumours nor to be related to oestrogen receptor and/or p53 status.bcl-2 might thus be one of the target genes involved in the oncogenesis related to Brca1 and its down-regulation may account for the increased apoptosis and the high proliferative rate observed in Brca1-associated carcinomas. © 2000 Cancer Research Campaig

Multicentre evaluation of multidisciplinary team meeting agreement on diagnosis in diffuse parenchymal lung disease: a case-cohort study

Background To evaluate inter-multidisciplinary team agreement for the diagnosis of diffuse parenchymal lung disease (DPLD). Methods Seven multidisciplinary meetings (MDTMs) consisting of at least one clinician, radiologist and pathologist, from 7 different countries evaluated 70 cases of diffuse lung disease in a two-stage process. First, the clinician, radiologist and pathologist (when lung biopsy was performed) evaluated each case and chose likelihoods (censored at 5% and summing to 100% in each case) for each of their differential diagnoses, without inter-disciplinary consultation. A full MDTM with review of all clinical, radiologic and pathologic data followed this. Interobserver agreement and inter-MDTM agreement for diagnosis was calculated using Cohen's kappa coefficient or weighted kappa coefficient where appropriate. Findings Inter-MDTM agreement for first choice diagnoses was acceptable (κ = 0.50). Idiopathic pulmonary fibrosis made up 18% of all MDTM first choice diagnoses. Diagnostic likelihoods for MDTM differential diagnoses were converted to a 5-point scale (0 = condition not included in the differential diagnosis, 1 = low probability (5-25%), 2 = intermediate probability (30-65%), 3 = high probability (70-95%), and 4 = pathognomonic (100%)). Inter-MDTM agreement on diagnostic likelihoods was good for idiopathic pulmonary fibrosis (IPF) (κw = 0.71) and connective tissue disease related interstitial lung disease (CTD-ILD) (κw = 0.73), only moderate for non-specific interstitial pneumonia (NSIP) (κw = 0.42) and poor for hypersensitivity pneumonitis (HP) (κw = 0.29). MDTMs, clinicians and radiologists respectively gave high confidence diagnoses of IPF (&gt;65% likelihood) in 77.3%, 64.6% and 66.3% of cases. The prognostic significance of a first choice diagnosis of IPF versus not IPF was evaluated for MDTMs, clinicians and radiologists. Greater prognostic significance was demonstrated for an MDTM diagnosis of IPF as compared to individual clinician's diagnosis of IPF in 5/7 MDTMs, radiologist's diagnosis of IPF in 4/7 MDTMs. Interpretation Agreement between MDTMs for diagnosis in diffuse lung disease is acceptable and good for a diagnosis of IPF. This is validated by the greater prognostic significance of an IPF diagnosis made by MDTMs as compared to individual clinicians or radiologists. Furthermore, MDTMs made the diagnosis of IPF with higher confidence and more frequently than clinicians or radiologists. MDTM agreement for diagnosis of NSIP and hypersensitivity pneumonitis is poor, indicating a need for international consensus on diagnostic criteria for these diseases

La filosofía de la educación en una posición crítica

Bajo Palabra, Revista de Filosofí