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Biomedical subjects

C Brambilla

Publications and source records attributed to C Brambilla.

At least 19 recordsLinked to original sources
PubMed1992

Cefuroxime and cefuroxime axetil versus amoxicillin plus clavulanic acid in the treatment of lower respiratory tract infections.

In a large multinational study, the clinical and bacteriological efficacy of intravenous cefuroxime 750 mg t.i.d. followed by oral cefuroxime axetil 500 mg b.i.d. was compared to that of amoxicillin plus clavulanic acid (CA) administered as 1.2 g intravenously t.i.d. followed by 625 mg orally t.i.d. in the treatment of lower respiratory tract infections in hospitalised patients. A total of 512 patients were entered (256 in each treatment group). All were suffering from pneumonia or acute exacerbations of chronic bronchitis or bronchiectasis and required initial parenteral antibiotic therapy. Parenteral therapy lasted 48 to 72 h and was followed by five days of oral therapy. The clinical responses in the two treatment groups were very similar: 223 of 256 (87.1%) patients were cured or improved with cefuroxime/cefuroxime axetil compared to 220 of 256 (85.9%) with amoxicillin/CA. Positive pre-treatment sputum samples were obtained from 44% of the patients. Clearance rates obtained were again similar: 72.8% with cefuroxime/cefuroxime axetil and 70% with amoxicillin/CA. Ten percent of the isolates were beta-lactamase producers, similar numbers of which were cleared in both groups. Both regimens were generally well tolerated, with only 5% of patients treated with the cefuroxime regimen and 4.3% of patients treated with amoxicillin/CA experiencing drug-related adverse events. Cefuroxime/cefuroxime axetil "follow-on" therapy produces clinical and bacteriological efficacy equivalent to that of amoxicillin/CA, with the advantage of twice daily oral administration.

Administration, Oral↗
PubMed1992

Basal cell (basaloid) carcinoma of the lung: a new morphologic and phenotypic entity with separate prognostic significance.

On review of 115 poorly or undifferentiated lung cancers from 671 lung tumors resected over a 7-year period, we have found 38 cases of basaloid carcinoma. The cardinal histopathologic features distinguishing this tumor from other non-small cell lung cancers are a lobular growth pattern of small cells with moderately hyperchromatic nuclei, with no prominent nucleoli, and with scant cytoplasm, a high mitotic rate, and peripheral palisading. Basaloid carcinoma was present in a pure form in 19 cases and the other 19 tumors were of a mixed, but prominent, basaloid type associated with squamous cell carcinoma, large cell carcinoma, or adenocarcinoma. The immunophenotype of basaloid cancers was close to that of basal bronchial epithelial cells, with a low level of expression of low molecular weight cytokeratins. Staining for neuroendocrine markers was infrequent and inconsistent. Ultrastructural study showed an absence of neurosecretory granules and the presence of some squamous and/or glandular differentiation. This morphologic and immunologic phenotype suggests that basaloid carcinoma is derived from a pluripotent reserve cell or a basal bronchial epithelial stem cell. This unique histologic form of lung tumor has a poor prognosis, with a median survival rate of 22 months for stage I and II disease. This justifies classification of basaloid carcinoma as a distinct form of lung cancer, separate from small cell lung carcinoma.

Adult↗
PubMed1992

Combination of 5-FU cisplatinum and hypofractionated irradiation followed by split-course radiotherapy in 47 patients with unresectable non small cell lung cancer.

Forty-seven patients with unresectable non small cell lung carcinoma, 15 stage IIIA, 31 stage IIIB, 1 stage IV (cervical lymphadenopathy) were treated with a combination of three courses of chemotherapy and hypofractionated irradiation followed after 3 weeks by split course radiotherapy. Each course was repeated every 3 weeks with the following sequence: Cisplatinum (CDDP) (20 mg/m2) was given in a 20-min infusion, followed by a 2-h infusion of 5-fluorouracil (5-FU) (400 mg/m2) on days 1, 2, 5 and 6. Radiation with a dose of 3 Gy on the target volume was given on days 3 and 4--in one fraction for the former 27 patients, in 2 fractions of 1.5 Gy for the latter 20 patients with a 6-h interval--after a 2-h infusion of 5-FU (400 mg/m2). The results remain disappointing: the objective response rate was 53%, the median survival was 10 months for the series, and the one-year survival 47%. The median survival was 14 months for IIIA, 10 months for IIIB and IV. Regarding the therapeutic regimen there seems to be less morbidity with 2 fractions per day for which the median survival is nearly the same at 10 months (1 fraction/day) versus 12 months (2 fractions/day).

Aged↗
PubMed1992

Neuroendocrine phenotype in lung cancers. Comparison of immunohistochemistry with biochemical determination of enolase isoenzymes.

The authors evaluated methods of recognition of neuroendocrine differentiation in lung cancer because this is thought to bear prognostic value. One hundred forty lung tumors were divided by immunohistochemical analysis using neuroendocrine markers (neuron-specific enolase, Leu7, chromogranin, neural cell adhesion molecules, SL11/14, and Leu19) into two groups of 51 neuroendocrine tumors positive for three neuroendocrine markers and 89 non-neuroendocrine tumors. Biochemical determination of enolase activity and isoenzyme distribution showed that the level of total enolase activity was similar between neuroendocrine and non-neuroendocrine tumors. alpha gamma and gamma gamma enolase isoenzyme percentages were higher in neuroendocrine tumors. A cut-off of gamma enolase % (alpha gamma/2 + gamma gamma) at 14% gave a sensitivity rate of 84% and specificity rate of 97% in separating neuroendocrine and non-neuroendocrine tumors, whereas immunohistochemical analysis using anti-gamma enolase had low specificity (68%) and immunohistochemical analysis with Leu 7 and chromogranin had high specificity (97%) and low sensitivity (37% and 60%) levels for neuroendocrine tumors. The best prediction of neuroendocrine differentiation was obtained using immunohistochemical analysis against neural cell adhesion molecules combined with biochemical estimation of enolase using gamma enolase of 14% and a gamma gamma isoenzyme more than 3%.

Antibodies, Monoclonal↗
PubMed1992

Treatment of pre-menopausal advanced breast cancer with goserelin--a long-acting luteinizing hormone releasing hormone agonist.

Twenty-two pre-menopausal evaluable patients with advanced breast cancer (median age 39 years; ER positive 19, unknown three; prior adjuvant chemotherapy 16) were treated with the LHRH agonist goserelin depot (Zoladex). Serum levels of 17 beta-estradiol and progesterone were suppressed by goserelin within 3-4 weeks of therapy, while serum leuteinizing hormone and follicle stimulating hormone titers remained in the low level of the normal range. Complete or partial response was documented in seven of 22 cases (32%) and occurred in all major sites of disease. Tumor response was documented in women regularly menstruating at the start of therapy. Median time to disease progression was 23 weeks; median duration of response was 64 weeks; overall survival was 141 weeks. Zoladex was well tolerated: only hot flushes in 82% and reversible cutaneous pigmentation in the site of injection in 45% of the patients were observed. In our experience the activity of Zoladex was comparable to that of oophorectomy, without the psychological trauma and the morbidity related to surgical castration.

Adult↗
PubMed1992

Somnofluoroscopy, computed tomography, and cephalometry in the assessment of the airway in obstructive sleep apnoea.

BACKGROUND: Assessments of the upper airways in patients with the obstructive sleep apnoea syndrome are usually carried out on awake patients who are upright. The dynamics of the airway in a patient who is asleep and lying down may be different. METHODS: Somnofluoroscopy, computed tomography of the upper airway, and cephalometry were carried out in 11 patients with the obstructive sleep apnoea syndrome (10 male; mean (SD) age 53 (10) years) to examine the airway while they were awake and asleep. RESULTS: At somnofluoroscopy 10 patients were in stage 2 sleep and only one in REM sleep. At least five obstructive events were visualised by lateral fluoroscopy in each patient. Imaging allowed observation of the dynamics of airway collapse, which began in the oropharynx in all cases, progressing to the hypopharynx in 10 cases and to the laryngopharynx in five. At fluoroscopy the soft palate was seen to hook up during airway occlusion in 10 patients, thereby increasing its cross sectional area. It was then sucked down into the hypopharynx. Somnofluoroscopic and cephalometric findings agreed, eight of the 10 patients with hypopharyngeal collapse shown by somnofluoroscopy having an inferiorly placed hyoid bone according to cephalometry (distance from the mandibular plane to the hyoid bone (MP-H distance) increased); the one patient with no hypopharyngeal collapse had a normal MP-H. By contrast, six of the 11 patients had a normal or supranormal hypopharyngeal cross sectional area of the airway on the computed tomogram. CONCLUSIONS: Somnofluoroscopy allows examination of the dynamics of airway closure in this disorder and shows the important role of the soft palate in acting as a plug in the oropharynx. Dynamic studies are required to determine the pattern of pharyngeal obstruction in obstructive sleep apnoea.

Adult↗
PubMed1992

[Respiratory infection and bronchial cancer].

Respiratory infections are very frequent in the course of lung cancer. The diagnosis is often difficult because of the existence of a chronic inflammatory process and of radiologic abnormalities related to lung cancer. Clinical symptomatology is atypical: no clear distinction between fever due to inflammation or infection, productive cough linked with chronic bronchitis often associated.... Radiological abnormalities are difficult to interpret: infectious lobar infiltrate or atelectasis, nature of a pleural effusion.... Biological data bear little interest because of their lack of specificity. Depending on their evolution, respiratory infections have particular characteristics. Before treatment, the problem is more often related to a fever and/or a radiological abnormality. During the post-operative period, fever generally corresponds to infectious phenomena, not necessarily originating from the lung. Among patients treated by radiotherapy and/or chemotherapy, it is sometimes difficult to conclude among several diagnosis possibilities: infectious lung condition, secondary infectious sites, iatrogenic interventions. The various possibilities that can be encountered can be divided into three main categories: in the case of lung infection in a non-neutropenic patient the organisms are those of a common community-acquired respiratory infection and it is logical to suggest a treatment based on penicillin A possibly associated with an inhibitor of beta-lactamases. In the case of a localised lung infection in a neutropenic subject, it is essential to cover gram negative bacilli by adding a beta-lactam and an aminoside. Finally, in the case of interstitial lung involvement, opportunistic bacteria are likely and it is essential to propose an endoscopic examination before initiating a therapeutic scheme.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗
PubMed1992

[Prolonged effect against exercise-induced bronchospasm: salmeterol versus sodium cromoglycate].

Nineteen subjects with isolated exercise-induced asthma (FEV1, FEF25-75%, PEFR, FVC greater than 95% predicted values, fall in FEV1 of at least 15% after exercise, typical recent symptoms of exercise-induced asthma, no other treatment) were entered in a multicenter trial carried out in a double blind, double placebo, cross-over manner. After a one-month baseline period, subjects underwent an exercise after inhaling 100 micrograms of salmeterol (n = 12) or 40 mg of sodium cromoglycate (n = 7). Treatments were alternated before the second exercise which took place at least 2 days after the first. Efficacy was assessed by examining changes in FEV1, FEF25-75% after exercise carried out 30 minutes and 7 hours after administering the treatment by comparison with baseline values (assessments done 1, 10 and 30 minutes after exercise, lowest of three values kept for the analysis of each parameter). FEV1 and FEF25-75% were significantly higher 30 minutes after taking salmeterol. Salmeterol was found to be superior to sodium cromoglycate for all parameters 7 hours after administering the drug. Both treatments were well tolerated. This study confirms that the longer duration of effect of salmeterol and its superiority by comparison with the standard treatments of exercise-induced asthma.

Adrenergic beta-Agonists↗
PubMed1992

[Diffuse infiltrative lung diseases: histological support of elementary lesions observed on tomodensitometry].

High resolution computed tomography (TDM-HR) is now the technique of choice in the diagnosis and management of diffuse infiltrative lung disease (PID). After a brief review of the technique the authors describe the normal appearance; anatomical observations and the in vivo findings have shown that TDM-HR allow for the exploration of details of structure down to the second pulmonary lobule. Thus, through the alterations that are transmitted in the lobular area, and from its contents and its limits, PID has led to the elaboration of a new semeiology. The authors review the basic computed tomographic images and correlate these in each case with the histological evidence. The spatial distribution and the time sequence of the elementary images are the two other terms in the diagnostic equation of PID. The spatial distribution of several elementary images presents in TDM-HR a superior aetiological pointer to that which is furnished by thoracic radiographs; and the time sequence may furnish a useful indication as to the progress of the treated disease. Sarcoidosis, histiocytosis X, idiopathic interstitial fibrosis and lymphangitis carcinomatosis would serve as examples. Nevertheless, the authors point out that it would be dangerous during the period of evaluation to prematurely extend to all cases of PID conclusions which are only possible to make at present in a restricted number of disorders.

Histiocytosis, Langerhans-Cell↗
PubMed1992

[Long-term tolerance of inhaled corticosteroids].

The effect of inhaled steroids on adrenal glands of asthmatic subjects are often difficult to assess because subjects may have received oral steroids before. Moreover, even if the Synacthen test is abnormal, it does not necessarily mean that the adrenals are clinically inefficient. Adrenal insufficiency can certainly occur at high doses of inhaled steroids. Possible long term effects on bone are under study. Ecchymosis has been described. Oropharyngeal candidiasis is frequent but rarely symptomatic and responds well to treatment. Hoarseness is rare but troublesome. In children, inhaled steroids, even taken at low dose, can induce growth impairment. After cessation of inhaled steroids, adrenal insufficiency is only theoretical. Asthmatic flare-ups are more of a threat. Although inhaled steroids are of remarkable efficacy and tolerance, one should not exclude the possibility of long-term negative effects, especially in children.

Administration, Inhalation↗
PubMed1992

[Value of high resolution tomodensitometry in pulmonary histiocytosis X. Radiological, clinical and functional correlations].

Histiocytosis is a rare cause of diffuse interstitial pneumonia. Its aetiology is not known and the outcome is often unsatisfactory. In 10 subjects in whom the diagnosis of histiocytosis X was established at CHU in Grenoble, 7 could be followed up. We report the clinical, functional, radiological and high resolution tomographic data on these 7 subjects suffering from histiocytosis X and followed up for a period between 3 and 13 years (8 +/- 3 years). All the subjects were symptomatic at the time of diagnosis. The clinical outcome amongst the 10 subjects included 2 patients who died, 2 who stabilised, 1 worsened and there were 4 clinical cures, 1 patient was lost to follow up. The respiratory function tests of the 7 subjects who were followed up was characterised by the appearance of airflow obstruction and a significant fall in the DLCO/VA (KCO) of 68 +/- 17% of the predicted value to 43 +/- 13%. An analysis comparing the initial pulmonary radiography to the current films showed that the reticular nodular lesions tended to progress to a diminution in size, while there was an increase in the reticulation. The high resolution computed tomography was confirmed as better technique than pulmonary radiography in detailing the cystic and nodular lesions. This was the only examination which correlated with DLCO/VA (R: 0.8; p: 0.018). A progressive model for computed tomographic lesions is proposed. Computed tomography appears to be the key examination, orientating the diagnosis based on the association of the nodules and cysts and enabling a better appreciation of the severity of the pulmonary disease taking account of its excellent correlation with diffusion.

Adult↗
PubMed1991

Activation of myc gene family in human lung carcinomas and during heterotransplantation into nude mice.

myc gene family activation (c-myc, L-myc, and N-myc) was examined in 26 human lung carcinomas and in their corresponding xenografts in nude mice. Of the 16 neuroendocrine (NE) carcinomas studied, amplification was observed in 4 with a c-myc probe and in 1 with both L- and N-myc probes. Overexpression was found in 1 of 7 cases studied for c-myc mRNA, in 1 of 7 cases for N-myc, and in 2 of 7 cases for L-myc. Of the 10 non-small cell lung carcinomas studied, only c-myc was amplified in 1 case and overexpressed in 5 of 7 cases. These results suggest that L- and N-myc gene activation are restricted to NE carcinomas. Over-expression of the myc gene without amplification was detected in 36% of cases. During heterotransplantation, there was a 27% change in myc gene abnormality and a 57% increase in myc expression levels, mostly in NE carcinomas (5 of 7; 71%). In a total of 42 xenografted lung carcinomas studied, 45% amplification and 77% overexpression of one of the myc genes were detected with a high prevalence of L-myc overexpression in NE carcinomas (50%) and of c-myc overexpression in non-small cell lung carcinomas (66%). Finally, 19 of 26 (73%) tumors are growing in nude mice with no myc gene amplification and 43% with no myc mRNA overexpression. Thus myc gene activation is not strictly required for heterotransplantation but seems to be a favorable factor in the maintenance and progression of lung carcinomas in vivo.

Animals↗
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↗