Biomedical subjects
Publications and source records attributed to E Brambilla.
The anatomical and physiological characteristics of the pulpal and dentinal sensitive system are described. Some different theories about the transmission of the dentinal sensitivity are also explained. Finally, the different desensitizing agents, their main characteristics and mechanisms of action are analyzed.
An unusual case of Niemann-Pick disease type C is reported. The disease was first manifested in utero with hepatomegaly and ascitis. At the age of 3 months, respiratory signs were noted due to diffuse alveolar and interstitial pneumonia. Both bronchoalveolar lavage and blood serologic studies revealed respiratory infection by respiratory syncitial virus and Chlamydia trachomatis. These concomitant infections delayed the diagnosis of Niemann-Pick disease which was finally made by the electronic microscopic studies of liver biopsy and bone marrow specimens. Type C was identified by biochemical characterization of lipid accumulation in hepatocytes and by lipid enzyme profiles obtained from cutaneous fibroblast cultures. The child died at the age of 6 months from respiratory failure. Post mortem examination of the lung showed the presence of numerous overloaded alveolar macrophages in the alveolar spaces and walls. The severity of the lung issue disease is unusual in type C Niemann-Pick disease, in which neurologic involvement is usually the main prognosis factor.
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In order to validate xenografted small cell lung carcinomas (SCLC) for biological studies, the authors established 12 lung neuroendocrine (NE) tumors (eight typical SCLC and four atypical NE tumors [ANE]) by heterotransplantation onto nude mice. Their characterization was performed using serial ultrastructural, enzymatic, and immunohistochemical methods on primary tumors and after xenografts. These were subclassified into epithelial (one), neuroendocrine (three), and multidifferenciated (eight) types. The phenotypic characters (cytokeratins, neurofilaments, neurone-specific enolase) and the proliferative rate (Ki 67 labelling) of original tumor were maintained until the last passage studied. Although further acquisition of subsets of cytokeratin or neurofilaments was observed in some cases, the authors could not detect any morphologic and/or biological spontaneous change comparable to those described in in vitro cell lines. In addition, ANE are not quite identical to variant subclasses described in vitro. The authors conclude that the stability of heterotransplanted SCLC is an advantage in further biological studies.
Neurone specific enolase (NSE); alpha gamma and gamma gamma isoenzymes of the glycolytic enzyme enolase, is found in considerable quantity in serum of patients with small cell lung cancer (SCLC). The spectrophotometric measurement of serum enolase activity, plus the electrophoretic separation of isoenzymes (alpha alpha, alpha gamma and gamma gamma) using an amplification reaction constitute a simple method, the application of which has not yet been demonstrated. In patients, serum values of higher than 25 U/l of total enolase activity, with more than 10% NSE, were considered to be positive. Seventy patients diagnosed as SCLC were classified before treatment as having either limited (LD) or extensive (ED) disease, and after chemotherapy as being in complete (CR) or partial remission (PR), stable state (SS) or in relapse (R). The levels of enolase activity and NSE (M +/- SE) in these patients (enolase: 67 +/- 7 U/l, NSE 27 +/- 2%) were different from those in a control group of 19 patients with non-small cell lung cancer (enolase: 29 +/- 2 U/l, NSE: 7 +/- 1%) (p less than 0.001) at the time of diagnosis. Mean enolase and NSE levels in patients with SCLC were seen to differ significantly according to the clinical stage. The results of those patients with ED differed from those of patients with LD (p less than 0.001). The results of the group of patients that achieved remission differed from that of patients during relapse (p less than 0.0001). Serial measurements demonstrated a good correlation between enolase and NSE serum levels and the progression of the disease. The usefulness of this method in the early assessment of treatment was also demonstrated. The clinical usefulness of the dosage of NSE with that of two other tumour markers CKBB and mitochondrial CK was compared.
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Malignant cells can be distinguished from their normal counterpart at the DNA level: they carry molecular changes which are characteristic of the tumor type or which might have some prognostic value. Amplifications and mutations of oncogenes and loss of alleles have been reported to occur in lung cancers, but their prognostic value has not yet been estimated, mainly for technical reasons: primary fresh biopsies are usually too small for molecular investigation. From 79 biopsies (50 of which were obtained by fiberoptic bronchoscopy), DNA hybridization was performed using the Southern blot technique, with myc family genes probes and a polymorphic probe located on the short arm of chromosome 3. Our study indicates that: 1) in 88% cases, enough DNA can be obtained by 3 or 4 fiberoptic bronchoscopy biopsies: from 5 to 80 micrograms DNA with an average of 25; 2) the quality of DNA is good for analysis by the Southern blot technique; 3) the loss of allele on chromosome 3 (3p 14-23) can be detected both in the small cell and in the non small cell type, but contamination of the specimens by non-tumoral tissue (based on the cytological and histological analysis of each biopsy) remains a problem for this type of study; 4) gene amplifications and rearrangements can be easily evaluated for the genes of the myc family. This pilot study shows that DNA analysis is feasible on perendoscopic biopsies. Collection and analysis of a large series of such biopsies at diagnosis is essential to define the value of DNA markers as prognostic factors in lung cancers.
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Oncogenes are genes for malignant transformation which correspond to changes, by genetic mutation, of genes which are present in all normal eukaryotic cells, called proto-oncogenes. The latter are involved in physiological functions often controlling growth and cell differentiation. Their mechanism of action and the activation of oncogenes are successively anticipated. These oncogenes are implicated in the majority of cancers and in particular in bronchial carcinoma: the myc-oncogenes (c-myc, N myc, L myc) are primarily activated in small cell carcinomas (CPC), the Ras genes (Ki Ras, Ha Ras) in epidermoid and adeno carcinomas. The intervention of growth factors such as bombesin in CPC and of their receptors such as epithelial growth factor (EGF) in non small cell bronchial carcinomas has been shown, as well as the role of cytogenic abnormalities (deletion of the short arm of chromosome 3). Their relation to oncogenes is discussed. The knowledge acquired on oncogenes in bronchial carcinoma should shed light on the pathogenesis of these cancers and find its next application in the diagnostic, prognostic and therapeutic field.
A distinctive form of sarcoidosis is reported. A young woman, without any past medical history, presented with a cannon-ball radiographic appearance and a fever, suggesting an infection or underlying neoplasm. A lung biopsy gave the diagnosis of sarcoidosis after negative fibreoptic bronchoscopy, bronchial lavage and needle biopsy. This macronodular form of sarcoidosis is known but rarely described. There was a favourable clinical and radiological outcome, which occurred spontaneously.
The relation between bronchial cancer and fibrous scars still remains controversial. We report, with regard to a typical case, the histological arguments for this hypothesis in the knowledge that only a clinical history and above all a radiographic progress will evoke the carcinomatous transformation. We report on the diagnostic peculiarities, the evolution, the therapeutic approach and histogenetics of bronchial cancers developing on a scar. This association and the interest of pursuing these investigations in the presence of evocative clinical or radiographic anomalies enable a better understanding of the natural history of bronchial cancer.
Electrophoretic separation of enolase isoenzymes and the measurement of enolase activity were performed in 25 lung tumor extracts. In 13 neuroendocrine (NE) tumors (nine small cell lung carcinoma [SCLC], three atypical NE tumors, and one carcinoid tumor), the NE differentiation was assessed by ultrastructural determination of neurosecretory granule (NSG) density. Twelve non-NE lung tumors also were studied (three adenocarcinomas, four epidermoid, two composite, two large cell undifferentiated carcinomas, and one lymphoma). Four normal lung tissues and 1 human brain were used as controls. The gamma gamma isoenzyme was present at a high level (mean +/- SE, 12 +/- 3%) in all NE carcinomas and consistently absent in all non-NE tumors as well as in normal lung. The alpha gamma isoenzyme was found in significantly higher proportion in NE carcinomas (mean +/- SE, 29 +/- 2%) than in non-NE tumors (mean +/- SE, 8 +/- 1%) (P less than 0.0001), despite an equally high level of total enolase activity in both groups of tumor. The separation of alpha gamma and gamma gamma isoenzymes of enolase allows for the accurate diagnosis of NE tumors and NE components of atypical NE carcinomas, and the gamma gamma isoenzyme, in contrast to gamma chain detection by immunoassay, can be considered to be a specific marker in itself of NE differentiation in lung neoplasms.
Chondromatous hamartomas of the lung are usually intraparenchymal and are rarely located in the bronchial lumen. Mediastinal chondrohamartomas are rare. A case is reported in which the close relationship with the esophagus suggests that this tumor is a choristoma rather than a hamartoma. To our knowledge, such a theory has not been previously proposed.
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A case of primary malignant fibrous histiocytoma of the lung is reported. The clinical course was divided into 2 periods: slow tumoral growth followed by rapid aggravation. The pathological aspects of the first localization and of the relapse are analyzed and discussed. Data from the literature are reviewed, with special attention to diagnostic and prognostic problems.
In order to assess the value of nuclear magnetic imagery NMR in the diagnosis of the extent of bronchial cancers, 61 patients with operable bronchial carcinoma had both a CT scan and an NMR scan pre-operatively. Fifty one mediastinoscopies were performed. Twelve times there were mediastinal glandular enlargement. Ten times the thoracotomy was performed straight away. After pathological studies of the biopsy, 24 patients were N2, 25 N1, 12 N0; the sensibility of NMR to foresee lymph node invasions was 83% (specificity 70%), for CT scanning 75% (specificity 81%). Thirteen patients presented with a direct mediastinal or parietal invasion. The sensibility of detecting these invasions was only 38% for NMR (specificity 94.5%) and for CT scanning 54% (specificity 94.5%). There is little difference in the results and no statistical difference. This leads us to conclude that at present, NMR does not give more information than TDM in the diagnosis of operability in bronchial cancers.
This correlative study concerns the investigation of 22 mediastinal tumors by MRI and CT, subsequently verified by biopsies or surgery. It allows us to better define the technical aspects in the realization of MRI, including an assessment of the use of ECG gating. It also permits an appreciation of the respective performances of these 2 imaging methods: there is a good correlation between the two technics for both the positive and etiologic diagnosis of mediastinal tumors: in etiologic diagnosis, the same limitations were encountered with the two technics. However, MRI offers some advantages in the evaluation of tumoral extension. So, we suggest once a mediastinal mass has been shown using plain films, when available, MRI alone should be performed.
A pulmonary scintigraph of pyrophosphate was performed to assess calcium metabolism in a man of 39 with alveolar microlithiasis, as was histologic study with a mineral analysis of wave-length dispersion and an analysis crossing the microliths enclosed in the resin. Two treatments were tried without success: First with diphosphonates and then alveolar lavage.