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Biomedical subjects

C Brambilla

Publications and source records attributed to C Brambilla.

At least 145 records · Page 8Linked to original sources
PubMed1991

Medical castration with zoladex: a conservative approach to premenopausal breast cancer.

For almost a century surgical castration represented the initial standard therapy for metastatic breast cancer in premenopausal women with hormone dependent tumors. Today the suppression of ovarian function can also be obtained by the administration of supraphysiologic doses of luteinizing hormone releasing hormone (LHRH) agonists. From April 1987 to February 1989, 23 premenopausal patients with advanced breast cancer (median age 39 years, range 28-52, ER positive 20, unknown 3; prior chemotherapy 17) were treated with the LHRH agonist goserelin depot (Zoladex) at the dose of 3.6 mg. every 4 weeks. Twenty-two patients were evaluable. Serum levels of 17 beta estradiol, progesterone, FSH and LH were suppressed by goserelin and fell to postmenopausal values within 8 weeks of therapy in 77% of cases. Complete response (CR) plus partial response (PR) was documented in 7 of 22 (32%) and occurred in all major sites of disease. Five patients achieved CR (soft tissue 3, viscera 2). Response rate was higher in patients not previously treated with chemotherapy (4/6). In the present series, all responses were seen in women greater than 35 years old, regularly menstruating at the start of treatment. Time to progression for the entire case series was 22 weeks and for responders 64 weeks. Oophorectomy was performed after disease progression in four patients without success. Goserelin was well tolerated. Local cutaneous dyschromia occurred in 45% and hot flushes in 82%. Treatment efficacy of goserelin is comparable to that of oophorectomy, without the psychological trauma and the morbidity related to surgical castration.

Breast Neoplasms↗
PubMed1991

Two simple indexes used to evaluate the impact of therapy on the quality of life of patients receiving primary chemotherapy for operable breast cancer.

The psychometric characteristics of two indexes used to evaluate the subjective morbidity of chemotherapy regimens were analyzed. Both indexes assessed the duration of discomfort as perceived by the patient throughout therapy. The first index asked patients to state the number of days spent with 'discomfort', and the second index asked them which days they would like to eliminate altogether because of the unbearable symptoms experienced on those days. While the first index gives some idea of the duration of suffering, without defining it, the second highlights a specific time when the quality of her life was unacceptable to the patient. We studied these indexes in the form of a questionnaire completed by 168 women who had entered a cancer clinical trial. This trial evaluated the efficacy of primary chemotherapy in rendering conservative surgery feasible in women with operable breast cancer, but whose tumor size was greater than 3 cm. Four different treatment regimens were used: CMF, FAC, FEC, FNC (C = cyclophosphamide, M = methotrexate, F = fluorouracil, A = adriamycin, E = epirubicin, N = mitoxantrone). Seventy-nine patients were interviewed during chemotherapy and 89 during follow-up visits. Initial assessment of the reliability, discriminant and concurrent validity of the two indexes produced satisfactory results. Finally, we analyzed the responses given by 168 patients for a total of 600 treatment cycles. The average value of 'discomfort' was 3 days, whereas the average value of days 'to be eliminated' was 1. The range of subjective morbidity (for every cycle of treatment: 'discomfort = 0-30 days; 'to be eliminated' = 0-20 days) was very broad.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Cytotoxic chemotherapy induces cell differentiation in small-cell lung carcinoma.

Despite the high response rates resulting from chemotherapy, the majority of small-cell lung cancer (SCLC) patients relapse with chemoresistant tumors. To analyze the phenotypic changes that are precursors of chemoresistant status, and to investigate the role of chemotherapy in these changes, tumor samples from 20 patients, taken before chemotherapy (etoposide, doxorubicin, and cyclophosphamide) and again at the onset of chemoresistance (after at least three courses of chemotherapy), were compared. The histologic changes were minor in 10 of 20 patients, as shown by an increase in cell size; they were major in 10 of 20 patients, with the appearance of mixed composite tumors in which neuroendocrine (NE), epidermoid, and glandular components were mixed. Major changes correlated with a good response to chemotherapy (P = .001). Ultrastructural studies showed an increase in neurosecretory granules and desmosomes, and a high frequency of multidirectional differentiation (45%) when comparison was made with pretherapy samples (10%) (P less than .01). Immunohistochemical (IH) analysis showed an increase in cytokeratin (CK) expression in treated patients, with a different labeling pattern and the expression of higher molecular weight CK. The expression of NE lineage markers (Leu 19, Sy 38, SL 11-14) remained stable, while that of NE differentiation markers (Leu 7, chromogranin) increased in the treated patients. The neuron-specific enolase (NSE) activity remained stable in treated SCLC. Large cells with a more differentiated phenotype and proliferative capacity (as shown by Ki 67 labeling), appeared to be characteristic of treated and secondary chemoresistant SCLC. The acquisition of a more complex phenotype, which correlates with primary response to therapy, implies a drug-induced differentiation in SCLC.

Aged↗
PubMed1991

Does oximetry contribute to the detection of apneic events? Mathematical processing of the SaO2 signal.

The purpose of this study was to assess the ability of continuous nocturnal oximetry to detect sleep apnea syndrome (SAS) and to recognize nonapneic oxyhemoglobin desaturations. Oxygen saturation oscillations, related to successive apneas in SAS or to apneic episodes in COPD or restrictive patients, were quantified using a new index: delta = 1/n sigma 1 n magnitude of delta(SaO2)/delta(t)(12-s intervals) Twenty-six patients (15 SAS, 8 COPD, and 3 restrictive patients) were included in a prospective study comparing nocturnal oximetry and polysomnography over 34 nights. In apneic patients, we found a strong correlation (r2 = 0.73, p less than 0.01) between time spent in apnea and the delta index. In COPD, the number of apneas was also correlated to the delta index (r2 = 0.92, p less than 0.01). A lower threshold for delta of 1.5 is accurate enough to detect apneas if initial SaO2 is greater than 93 percent. If initial SaO2 is greater than 93 percent, the delta threshold should be 0.8 (sensitivity 95 percent). Such a method could contribute to the accurate selection of patients for polysomnography.

Blood Gas Monitoring, Transcutaneous↗
PubMed1991

[Tracheo-bronchial granular cell tumors. Apropos of 4 cases].

We have seen four cases of granular cell tumor (Abrikossoff's tumour) and it is recalled that these tumours are most often discovered fortuitously by bronchoscopy in the tracheo-bronchial region because they have a non specific clinical presentation. The cytological and histological characteristics enable an accurate diagnosis but there are problems posed as to the histogenesis of these tumours. With a tumour with a slow progression regular surveillance with regular biopsies seems preferable as in certain cases the tumour regresses spontaneously or disappears after ablation with the forceps. A good alternative approach is destruction of the tumours with a laser in certain complicated forms which enables one to avoid surgical excision.

Adolescent↗
PubMed1991

[The role of new medical imaging technics (TDM and MRI) in the diagnostic strategies of superior vena cava syndrome].

Superior vena caval syndrome (VCS), is easily recognised in the advanced case, however in the early case without clinical signs its detection is much less easy. New techniques of medical imagery such as IRM and above all computer tomography (TDM) have shown an increasing place in the daily clinical practice of the respiratory physician; these enable an early diagnosis to be made and a work up of the aetiology of the syndrome of VCS. With TDM the obstruction of the VCS appears the sign of direct obstruction (thrombosis or extrinsic compression) and of a collateral venous circulation deriving some anastomoses from the brachio-cephalic venous trunk (TVBC) and the azygos system, the VCS and the inferior vena cava (VCI), the two TVBC at the junction of the median line principally by the suprasternal network and finally these portal systemics, by the veins from the anterior wall of the trunk and the accessory portal veins of the round ligament. IRM introduced more recently enables a direct vision of the causal lesion endo or extra luminally, enabling an early detection of the syndrome by showing signs of a slow down of the venous flow. But the detection of a collateral circulation seems more difficult to demonstrate by this method.

Humans↗
PubMed1990

Primary chemotherapy to avoid mastectomy in tumors with diameters of three centimeters or more.

In 165 women with breast cancer who were candidates for mastectomy because the largest diameter of the tumor was 3 cm or more, we administered primary chemotherapy in the attempt to substitute conservative for mutilating surgery. We then systematically quantitated tumor reduction by clinical, radiologic, and histopathologic evaluations. Five consecutive groups of 33 patients received cyclophosphamide, methotrexate, and fluorouracil (CMF); fluorouracil, doxorubicin (Adriamycin), and cyclophosphamide (FAC); or fluorouracil, epirubicin, and cyclophosphamide (FEC). The regimens for the five groups were as follows: group 1, three cycles of CMF; group 2, four cycles of CMF; group 3, three cycles of FAC; group 4, four cycles of FAC; and group 5, three cycles of FEC. In response to primary chemotherapy, 157 of the 161 assessable patients showed measurable tumor shrinkage; progressive disease was documented in four. Tumor shrinkage to less than 3 cm was documented in 127 (81%) of the 157 women subjected to surgery, thus allowing a breast-saving procedure, rather than modified radical mastectomy, in these 127 women. Histopathologic complete remission was documented in seven patients. Tumor response was unrelated to age, menopausal status, DNA content (ploidy), [3H]thymidine-labeling index, drug combination used, or number of treatment cycles in excess of three. The degree of response was inversely proportional to the initial tumor size, and the frequency of response was greater in receptor-negative tumors. Severe vomiting and hair loss were less frequent with CMF than with anthracycline-containing regimens, and the frequency of severe leukopenia and thrombocytopenia was minimal. Our results challenge the classical indication for primary mastectomy by showing that use of full-dose primary chemotherapy, sequentially combined with conservative surgery and radiation, can offer an effective and safe alternative to women concerned about the preservation of body integrity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Analysis of the activation of the myc family oncogene and of its stability over time in xenografted human lung carcinomas.

In order to validate the use of the nude mouse as a model for studying lung cancers, 21 different lung cancers were xenografted onto nude mice and the tumoral DNA and RNA were analyzed for abnormality in the myc family genes (c-myc, L-myc, and N-myc). Six of 14 small cell lung cancers (SCLC) showed a 4-35-fold amplification for L-myc, 5 of 7 non-SCLC a 3-5-fold amplification for c-myc, and 1 of 14 SCLC an 80-fold amplification for N-myc. Of the 7 SCLC with amplified L- or N-myc oncogenes, 4 were of the small and large histological type, while only 5 of the 21 cases studied were of the small and large type. All xenografted tumors with amplification of one of the myc genes showed overexpression of the related mRNA. Overexpression without amplification of the myc genes was observed for 3 SCLC and 2 non-SCLC. These results indicate that the L-myc gene seems to be associated with the small and large phenotype in SCLC, whereas c-myc seems to be implicated in non-SCLC. Of the 21 lung cancers studied 14 were analyzed for myc family gene activation for serial passages into nude mice. No variation of DNA amplification was observed during long-term growth in nude mice for any of the myc oncogenes. Changes in the level of mRNA expression were observed only for c-myc; a beginning of expression in one SCLC and an increase in expression in one non-SCLC were noted in late passages when compared with early ones. The nude mouse is therefore a valuable model for the study of lung cancers "over a 4-year period at least."

Animals↗
PubMed1990

On the estimation of the age at onset distribution in Huntington's chorea using the EM algorithm.

Huntington's chorea is a late onset disease of the nervous system whose mode of inheritance conforms to the autosomal dominant model. The present paper shows how the problem of estimating the distribution of age at onset of the disease can be dealt with as an incomplete data problem via the EM algorithm, both in the parametric and non-parametric setting. In this way it is possible to take into account not only the heterozygotes in the population under study who are manifestly affected, but also those who are apparently unaffected. The estimation of the distribution of age at onset of the disease is required for estimating the posterior probability of heterozygosity of the individual at risk using Bayes' theorem. The proposed approach was applied to data derived from a survey carried out on the population of Latium, Italy.

Adolescent↗
PubMed1990

Pulmonary histiocytosis X with mediastinal lymph node involvement.

In this report, we describe a patient with the classic histology of pulmonary histiocytosis X, who had bilateral reticulonodular densities and mediastinal lymph node involvement. The diagnosis was confirmed by the use of electron microscopy and immunohistochemical markers (PS100, HLA-DR, and CD1), which allowed us to recognize the lymph node infiltration of X histiocytes. An association of mediastinal lymph node enlargement with pulmonary histiocytosis X has been reported but it has never been histologically documented.

Adult↗
PubMed1990

[Immunotherapy of cancer using cytokinins. Use and perspectives in lung oncology].

Progress in genetics now enables the synthesis of molecules acting on the regulation of the immune system which are called cytokines. Currently there are several cytokines, Interferon (IFN), Interleukin 2 (IL2), tumour necrosis factor (TNF) as well as haematopoietic growth factors and these are the object of study in clinical trials. Interferon has already been used in the therapy of hairy cell leukaemia, Kaposi sarcoma associated with AIDS(SIDA) and metastasis of malignant melanoma. Interleukin 2 allows for an increase in the cytotoxic activity of NK cells in producing LAK cells, the lymphocyte infiltrating the tumour (TIL). Therapeutic combinations combining IL2 associated with LAK or of TIL have been evaluated in some private studies. These treatments have shown some interesting response levels on those tumours which are usually resistant, such as malignant melanoma or carcinoma of the kidney. TNF is active in vitro on human tumours; its potential toxicity is important; it is the object of a phase 1 clinical trial. Haematopoietic growth factors, G-CSF and GM-CSF, stimulate the production of leucocytes which will be valuable to correct toxic affects on the marrow during chemotherapy. This will enable chemotherapy to be given at a high dose.

Colony-Stimulating Factors↗
PubMed1990

[Benign pleural fibroma. An anatomo-clinical study of 10 cases].

We present an anatomical-clinical analysis of ten cases of benign pleural fibroma. This tumour was discovered in a systematic fashion in 8 of the 10 cases and fortuitously in one. Recent radiological examinations enabled the diagnosis to be suspected. Computerised tomography most often precisely identified the pleural topography and imagery by nuclear magnetic resonance in one case visualised fibrous tissue (with a zone of low signals on the scale in T2). The final diagnosis was achieved at the same time as the treatment when an exploratory thoracotomy was performed. In all the cases there was a tumour composed of fusiform cells covered by normal epithelium coming from the viscera pleura 8 times out of 10. The ultrastructure examination and immunohistochemistry of the fusiform cells (Vimentin plus, EMA-, KL1-) allowed for a differentiation of these tumours of connective tissue origin from tumours of mesothelial origin. These analyses constitute an argument in favour of the fibroblastic origin of pleural fibromas.

Adult↗
PubMed1990

[Bronchiolitis obliterans with idiopathic organized pneumonia. Anatomoclinical analysis and nosologic discussion apropos of 6 cases].

The clinical, radiological, physiological and pathological features were studied in 6 cases of idiopathic bronchiolitis obliterans organized pneumonia (BOOP). Patients characteristically had a history of exertional dyspnea, cough, fever, weight loss, bilateral radiographic shadowing, elevated ESR and hypoxemia. Corticosteroids were effective; however, one patient died of cytomegalovirus pneumonia. The pathological features, distinguished by the presence of granulation tissue plugs extending from bronchioles into alveolar ducts and alveoli, are described in detail. The place of BOOP within the broad spectrum of bronchiolitis obliterans between small airways disease and usual interstitial pneumonia is discussed.

Aged↗
PubMed1990

[Effect of nebulized salbutamol in 26 patients hospitalized for asthma attack].

Twenty-six asthmatic patients who were hospitalised following an acute asthmatic attack and who had a peak expiratory flow of less than 50% predicted, without hypercapnia, received 5 mg. of salbutamol delivered by a micronebulizer LSA on admission (HO). At H1, 10 mg of additional salbutamol were nebulised in cases where there had been an increase of less than 20% of the PEF. At H2, all the subjects received steroid therapy. Group 1 in which success was defined by an increase of 20% of peak flow judged at H1 and H2, and group II where the increase in peak flow was less than 20%. Group II benefited at H2 by treatment with theophylline or salbutamol intravenously given in a randomised fashion. At H8 the 2 treatments were associated in group II in cases of failures. 15 men, and 11 women aged 40 +/- 17 suffering from severe asthma (65% of Charpin Stage IV) were included. The mean peak flow at HO was 32 +/- 9% of the predicted PEF. 21 subjects, or 81% improved their peak flow by more than 20% at H2. The toleration for salbutamol was very good from the cardiovascular point of view. At HO there was no clinical criteria nor peak flow assessment which would enable one to predict the failures from nebulized salbutamol for a given subject. Nevertheless a level of dyspnoea of greater than 5 on Borg's scale and a peak flow of less than 150 l/min made failure likely.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

[Can oximetry contribute to the detection of apnea? The use of a mathematical analysis of the oximetry signal].

The aim of this study was to test the efficacy of nocturnal oximetry as a means of continuous recording of SaO2 in the identification of apnoeic events in the recognition of non-apnoeic desaturation. The oscillations of SaO2 in relation to successive periods of apnoea during the course of the sleep apnoea syndrome (SAS) or with apnoeic episodes in patients with chronic airflow obstruction (BPCO) or restricted disease, were identified using a new delta index quantifying the variations of SaO2 during the night. 26 successive patients in whom there was an indication for nocturnal oximetry were included in a prospective study comparing nocturnal oximetry and polysomnography during 34 nights. In the apnoeic patients we found a strong correlation (r = .85. p. less than .01) between the apnoeic period and the delta index. In BPCO the number of apnoea was correlated with the delta index (r = .96. p. less than .01). A minimal threshold of the delta index fixed at 1.5 was satisfactory for detecting apnoea if the initial SaO2 was less than 93%. The value of the adequate for affected detection ought to be fixed at .8 (95% sensitivity) when the initial SaO2 was greater than 93%. A detection of apnoeic events thus seems possible by this method.

Apnea↗
PubMed1989

Heterotransplantation of small cell lung carcinoma into nude mice. Stability of the phenotypic characters.

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.

Animals↗
PubMed1989

Mitomycin C and vinblastine in advanced refractory breast cancer.

A combination of mitomycin C and vinblastine was administered as salvage treatment in 44 patients with heavily pretreated refractory breast cancer. Response rate was 23% (10 of 44) including one complete response of lung metastases. The highest response rate was seen in intrathoracic localizations (45%). Median duration of response was 6.5 months (range, 3+-17+). Treatment was generally well tolerated, and only 25% of patients developed nausea and vomiting. Neurologic toxicity was represented by paresthesia (8 patients) and constipation (one patient). Mild leukopenia was observed in 30 of 172 treatment cycles, but it exceeded grade 2 in only 5 patients. Considering the good compliance of this regimen and the poor prognosis of patients with advanced refractory disease, the combination of mitomycin C plus vinblastine appears to be useful as salvage treatment for metastatic breast cancer.

Adult↗