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Biomedical subjects

A Mussi

Publications and source records attributed to A Mussi.

At least 55 records · Page 3Linked to original sources
PubMed1997

Increased interleukin-7 concentrations in lesional skin and in the sera of patients with plaque-type psoriasis.

Several cytokines have been shown to be increased in psoriasis, mainly at the local and sometimes at the systemic level. At present, no data concerning the relationships between psoriasis and interleukin-7 (IL-7) are available. This biological modifier regulates immune response by means of its pleomorphic activities, including the ability to stimulate different monocyte functions, such as killing of intracellular pathogens, induction of cytokines, and enhancement of some membrane molecule expression. Study groups consisted of nine psoriatic and nine normal subjects. Using a commercially available immune-enzyme method, IL-7 concentrations were determined in various samples: biopsy and scale extracts, peripheral blood mononuclear cells (PBMCs) supernatants, and sera. The results show that IL-7 levels are significantly increased both in biopsy and in scale extracts obtained from lesional skin compared to those obtained from nonlesional and normal skin (P at least < 0.01). In addition, the serum values were higher in psoriatic patients than in the controls (P = 0.003). In contrast, no significant differences were observed in the supernatants of unstimulated PBMCs maintained in culture for 48 hr. These data suggest that IL-7 is involved in some way in the pathomechanisms of psoriasis and that the keratinocyte may be a candidate for psoriatic IL-7 overproduction.

Adult↗
PubMed1997

Interleukin-11 production is increased in organ cultures of lesional skin of patients with active plaque-type psoriasis as compared with nonlesional and normal skin. Similarity to interleukin-1 beta, interleukin-6 and interleukin-8.

Increased levels of several cytokines, mainly proinflammatory mediators, have been reported in psoriatic lesions. Little information, if any, is available concerning other cytokines, especially those initially studied as marrow differentiation agents. Using the experimental approach of measuring cytokines released by skin organ cultures. IL-11 and three other proinflammatory cytokines (IL-1 beta, IL-6 and IL-8) were determined using commercially available ELISA kits in supernatants of ten biopsies from lesional and nonlesional psoriatic skin areas and in supernatants of biopsies from ten normal volunteers. The results obtained showed that the amounts of IL-11 and the other three modulators were significantly increased in the material from the lesional areas (P < 0.01). The amounts of IL-11, which is known to have functional activity similar to the proinflammatory cytokines and to share a receptor component with IL-6, were also correlated with the disease severity index (R = 0.69, P = 0.04). In addition, a nearly significant correlation was noted between the amounts of IL-11 released by the lesional and the nonlesional skin biopsies (R = 0.66, P = 0.05). More detailed studies are needed to clarify whether IL-11 plays a specific functional role in psoriasis, but this study emphasizes the complexity of the pathogenesis of psoriasis and the cytokine network, including activation of proinflammatory and haemopoietic biological response modifiers, in this disease.

Adult↗
PubMed1997

Surgery in the management of small cell lung cancer.

OBJECTIVE: We analyzed our experience in the period January 1975-December 1995 aiming to confirm the role of surgery in the multimodality treatment of small cell lung cancer (SCLC). METHODS: 127 patients (5.28% of the overall lung resections for carcinoma) underwent surgery for SCLC. The median age was 60 years (range 34-73). In 87 patients (68.5%) a pre-operative tissue diagnosis was effected and those patients underwent a complete staging procedure. Fifteen patients received up to six complete courses of neoadjuvant and adjuvant chemotherapy. The surgical procedures included: 50 pneumonectomies, 71 lobectomies and six wedge resections. Two patients experienced a local recurrence and a completion pneumonectomy was performed. RESULTS: The median follow-up is 66 months (range 6-214). The 5-year actuarial survival rate is 22.6% (median 18 months). Twenty-three patients are still alive, 21 of them being disease-free. Considering the most conspicuous group of patients (n = 92) treated by surgery and adjuvant chemotherapy, the survival data were 47.2, 14.8 and 14.4% for Stage I, II and III, respectively (P = 0.001). NO patients had a significantly better survival than N1 and N2 patients (P = 0.035). CONCLUSIONS: Surgery and adjuvant chemotherapy might represent an effective form of treatment of limited SCLC without lymph-node involvement. The role of surgery is yet to be verified as regards N1 and N2 status, where even neoadjuvant chemotherapy has not achieved the hoped-for results (no patient reaching a 2-year survival).

Adult↗
PubMed1997

Tumor angiogenesis and biologic markers in resected stage I NSCLC.

OBJECTIVE: Microvessel count (MC), as a measure of tumor angiogenesis, has been shown to be significantly correlated with metastatic disease in cutaneous, mammary, prostatic, head and neck cancer. We have previously assessed the role of intensity of angiogenesis as predictor of metastasis in surgically resected T1N0M0 NSCLC. We needed to confirm its value, in a prospective larger study on Stage I NSCLC, before its utilization as a prognostic tool for further clinical investigations. METHODS: In the present report we prospectively investigated 227 patients (206 males, 21 females; median age 65 years) with Stage I NSCLC treated only by radical surgery between March 1991 and December 1994 with utmost care for some biological characteristics (proliferative activity, the blood vessel invasion, angiogenesis and the p53 protein expression). RESULTS: The operative procedures consisted of 62 pneumonectomies, 148 lobectomies and 17 segmentectomies or wedge resections. With a median follow-up of 36 months (range 15-60), eighty patients have already experienced a local (n = 22) or systemic (n = 58) relapse. Univariate analysis revealed that T factor (T1 versus T2)(P = 0.008) and angiogenesis count (< or = versus > median, 17) (P = 0.0006) were significant predictors of survival. The same variables were also significant predictors of long Disease Free Survival (P = 0.006 and P = 0.004, respectively). On multivariate analysis, however, only the microvessel count retained its level of prognostic significance as regards both overall (P < 0.01) and disease-free survival (P < 0.01). CONCLUSIONS: The present study corroborates the role of angiogenesis in the metastatic spread of NSCLC and emphasizes its value in the identification of patients in whom surgery should be supplemented by systemic treatment.

Aged↗
PubMed1997

Neoangiogenesis and p53 protein in lung cancer: their prognostic role and their relation with vascular endothelial growth factor (VEGF) expression.

Following up-regulation of an angiogenesis inhibitor by the wild-type p53 protein proven recently, we have analysed on the one hand the prognostic impact of microvessel count (MC) and p53 protein overexpression in non-small-cell lung carcinoma (NSCLC) progression and, on the other hand, the inter-relation between the microvascular pattern and the p53 protein expression. Moreover, we assessed the expression of vascular endothelial growth factor (VEGF), one of the pivotal mediators of tumour angiogenesis, in order to investigate its relation to p53 protein expression and MC. Tumours from 73 patients resected for NSCLC between March 1991 and April 1992 (median follow-up 47 months, range 32-51 months) were analysed using an immunohistochemical method. In univariate analysis, MC and p53 accumulation were shown to affect metastatic nodal involvement, recurrence and death significantly. Multiple logistic regression analysis showed an important prognostic influence of MC and nodal status on overall (P = 0.0009; P = 0.01) and disease-free survival (P = 0.0001; P = 0.03). Interestingly, a strong statistical association was observed between p53 nuclear accumulation and MC (P = 0.0003). The same inter-relationship was found in non-squamous histotype (P = 0.002). When we analysed the concomitant influence of MC and p53 expression on overall survival, we were able to confirm a real predominant role of MC in comparison with p53. With regard to VEGF expression, p53-negative and lowly vascularized tumours showed a mean VEGF expression significantly lower than p53-positive and highly vascularized cancers (P = 0.02). These results underline the prognostic impact of MC and p53 protein accumulation in NSCLC and their reciprocal inter-relationship, supporting the hypothesis of a wild-type p53 regulation on the angiogenetic process through a VEGF up-regulation.

Aged↗
PubMed1997

Effect of data normalization for age on the correlations between corneometric values and serum molecule levels in plaque-type psoriatic patients.

Corneometry has been considered useful both to evaluate disease severity and to monitor psoriatic patients during treatment. However, a limitation of this technique is that the patient's age influences the corneometric determinations, thus reducing their clinical usefulness. The aim of this study was, therefore, to establish whether age normalization of the corneometric results may provide more reliable data for clinical use. Corneometric levels were determined in 10 plaque-type psoriatic patients, under standard conditions. Eight serum variables, including transforming growth factor-beta 1 and seven soluble membrane molecules, were assayed with commercially available immune-enzyme methods in the same patients, whose age and PASI scores were also recorded. The age normalization procedure improved all the correlation coefficients calculated on the lesional or non-lesional corneometric values versus the PASI scores as well as versus the other serum variables. This approach may render corneometric determinations more useful to evaluate disease status or treatment effect in patient groups with plaque-type psoriasis.

Adult↗
PubMed1997

Cytokines in the sera of patients with pemphigus vulgaris: interleukin-6 and tumour necrosis factor-alpha levels are significantly increased as compared to healthy subjects and correlate with disease activity.

Cytokine serum levels, when detectable, are currently measured in many disease states, both to evaluate a possible pathogenetic involvement of such molecules and for clinical purposes. No data are currently available on the cytokine levels in the sera of patients with pemphigus vulgaris (PV), a rare bullous disease of autoimmune origin. This study presents data concerning the levels of 13 different cytokines assayed in the sera of 25 patients affected with PV as compared with 20 healthy subjects using high sensitivity ELISA kits. Of the 13 molecules analyzed, no differences in the levels of most cytokines were observed between pemphigus and control sera, with the exception of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Serum TNF-alpha and IL-6 levels were found to be significantly higher in PV patients than in normal controls (p < 0.001). Furthermore, the levels of the two cytokines decreased after one month of corticosteroid therapy. A significant correlation was found between the serum levels of both TNF-alpha and IL-6 and the number of lesions for each patient (p < 0.001). The data presented support an involvement of at least IL-6 and TNF-alpha in the biological modifications associated with PV manifestations.

Adult↗
PubMed1997

[Current trends in in the treatment of spontaneous pneumothorax].

In agreement with a number of published reports we state that video thoracoscopy is the best means for pnx classification (Vanderschueren RJA) and for the choice of its treatment. Video thoracoscopy and recent innovations in video-assisted thoracic surgery (VATS), together produce a significant improvement in the results. Between February 1992 and September 1994, we treated 143 pnx in 133 patients, 118 males, mean age 34 years (range 14-82); 5 of which undergoing a bilateral treatment and another 5 having to undergo a retreatment. On the basis of the endoscopic classification (Vanderschueren RJA), 26.1% of the cases fell into category I and 67.4% into the higher category, 6.5% presented enlarged bullous emphysema (GBE). Twenty-seven patients (20.3%), classified as category I at the first appearance of pnx, were treated by means of a chest tube thoracostomy. The remaining patients underwent surgical treatment: 106 treatments by VATS (74.1%) and 10 (7%) by an axillary thoracotomy. By VATS we performed: 77 ligature/resections of bullous lesions, 9 resections of pulmonary apex, 9 adhesiolysis, 7 GBE treatment by the "spaghetti technique", 2 coagulations of blebs, 1 suture and 1 parenchymal laceration repair by clips. No patients treated by a chest tube thoracostomy or who underwent thoracotomy presented recurrence at the follow-up (mean 33 months, range 15-46). We had a single complication (0.9%), 2 treatment conversions (1.9%) and in 3 patients (2.8%) a thoracotomy was necessary four days later. In thoracotomy we performed 5 resections of bullous lesions and 2 "capitonages" were effected in those patients treated in the first instance; 2 parenchyma tear repairs and 1 lobectomy in those patients treated after the failure of VATS.

Adolescent↗
PubMed1997

67-Kilodalton laminin receptor expression correlates with worse prognostic indicators in non-small cell lung carcinomas.

Tumor samples obtained from 72 patients resected for non-small cell lung cancer were stained immunohistochemically using an immunoperoxidase method and the MLuC5 monoclonal antibody specific for the 67-kDa laminin receptor. Sixty-one of 72 patients (84.7%) displayed a MLuC5-positive reaction, which was usually localized in both the inner surface of the plasmatic membranes and the cytoplasm of neoplastic cells. When we compared the laminin receptor expression with clinicopathological and biological parameters such as histotype, grading, T status, N status, ploidy, proliferative activity, vessel invasion, and p53 protein accumulation, the following results were observed: (a) the mean expression of the receptor was higher in the group of patients with metastatic nodal involvement than in those with uninvolved lymph nodes (P = 0.02); (b) a high Ki-67 score (>13% of positive cells) was observed in tumors with a higher mean value of laminin receptor (P = 0.004); (c) the tumors harboring neoplastic emboli in their vessels showed a higher laminin receptor immunoreactivity (P = 0.02); and (d) a borderline association was found between the high mean value of laminin receptor immunopositivity and p53 accumulation in neoplastic cell nuclei (P = 0.05). Our observations indicate that detection of high tissue levels of 67-kDa laminin receptor is associated with an invasive phenotype in non-small cell lung cancer and may provide further information in the biological characterization of this type of cancer.

Aged↗
PubMed1997

Vascular endothelial growth factor is associated with neovascularization and influences progression of non-small cell lung carcinoma.

Vascular endothelial growth factor (VEGF) plays a pivotal role in the development of neovascularization in both physiological and pathological processes, e.g., developmental and reproductive angiogenesis, proliferative retinopathies, and cancers. Several solid tumors produce ample amounts of VEGF, which stimulates proliferation and migration of endothelial cells, thereby inducing neovascularization by a paracrine mechanism. Recently, VEGF expression has been shown to significantly affect the prognosis of different kinds of human cancer. Because neoangiogenesis represents an important prognostic indicator of poor prognosis in non-small cell lung cancer (NSCLC), we investigated the influence of VEGF during progression of this type of cancer and its relationship to tumoral neovascularization. VEGF expression was significantly associated with new vessel formation (r = 0.44; P < 0.0001). Moreover, in univariate analysis, VEGF expression significantly affected overall and disease-free survival (P = 0.00003 and P = 0. 0004, respectively). Backward stepwise regression analysis indicated that VEGF expression was an independent prognostic factor in patients with NSCLC. These findings support the hypothesis that VEGF is an important angiogenic factor in primary NSCLC and may help in predicting the outcome of this group of cancers.

Adult↗
PubMed1996

Neoangiogenesis: a putative marker of malignancy in non-small-cell lung cancer (NSCLC) development.

Several studies have documented a relevant prognostic role of microvessel count (MC) in non-small-cell lung carcinomas (NSCLC). However, no evidence has been reported about the involvement of neo-angiogenesis in the development of bronchial cancers. The aim of this study was to analyze microvessel density both in normal and in pathological features of the bronchial tree detected concomitantly with carcinomas. In a group of 34 patients resected for NSCLC, 48 bronchial lesions (hyperplasia, squamous metaplasia, moderate dysplasia and in situ carcinoma) were identified. In addition, 20 samples of normal bronchial epithelium from the same patients were analyzed. A monoclonal antibody was used in order to identify microvessels in the most intense areas of neovascularization from the bronchial specimens. MC was also analyzed in invasive components. An increased number of microvessels was observed from normal to dysplastic epithelium, including in situ carcinoma. Mean MC was significantly lower in normal, hyperplastic and squamous metaplastic epithelium than in dysplastic epithelium and in situ carcinoma. In particular, no differences were observed between normal and hyperplastic/metaplastic components, whereas a statistically significant difference appeared between the latter and dysplastic lesions. Moderate dysplasia and in situ carcinoma showed a number of microvessels in the lamina propria of their mucosa which were not significantly different from the invasive component, whereas hyperplastic/metaplastic lesions presented a much lower number of microvessels than invasive cancer. From these data it appears that normal bronchial epithelium and lesions associated with cancers of the bronchial tree show neovascularization in their stromal component. Hyperplasia and squamous metaplasia, unlike dysplasia and in situ carcinoma, show a low microvessel count, and they cannot represent precursor or incipient changes in the bronchial epithelium before the fully developed in situ stage has also been reached.

Carcinoma in Situ↗
PubMed1996

Prognostic significance of tumoral angiogenesis in completely resected late stage lung carcinoma (stage IIIA-N2). Impact of adjuvant therapies in a subset of patients at high risk of recurrence.

BACKGROUND: Angiogenesis plays a critical role in human tumor growth and metastasis. Microvessel count (MC), as a measure of tumor angiogenesis, has been significantly correlated with metastatic disease in cutaneous, mammary, prostatic, head and neck, and early stage lung carcinoma. METHODS: Ninety-six consecutive patients affected by T1-3N2MO nonsmall cell lung carcinoma (NSCLC), who underwent radical surgery between March 1991 and March 1995 (in many cases followed by adjuvant therapies) were prospectively investigated to assess the prognostic significance of both traditional and new biologic parameters like proliferative activity, blood vessel invasion by tumoral cells, and neovascularization (estimated by the MC). RESULTS: With a median follow-up of 24 months, the projected 3-year survival was 42.1%. Forty-eight of the patients (50%) had already experienced a local (n=14) or systemic (n=34) relapse. The extent of resection (lobectomy vs. pneumonectomy; P=0.0045), the number of mediastinal lymph node levels (single vs. multiple; P=0.014), and the MC (on a X200 field; P=0.015) correlated significantly with metastatic disease. By univariate analysis, significant predictors of survival were: the extent of surgery (P=0.03), adjuvant therapy (P=0.05), and MC (< or = vs. > cut-off; P=0.00076). On multivariate analysis, however, only the MC (P=0.02) retained its level of prognostic significance. CONCLUSIONS: Our results provide evidence that neovascularization, estimated by the MC, can predict metastatic disease and survival in patients with completely resected T1-3N2M0 NSCLC, and may also be useful in patient selection for effective adjuvant treatment.

Actuarial Analysis↗
PubMed1996

Interindividual variability in the rate of salbutamol sulphation in the human lung.

The beta2-adrenergic agonist salbutamol is administered by inhalation to treat lung-obstructive disease. Salbutamol is metabolized by conjugation with sulphate, and the sulphation of salbutamol was investigated in human lung. Specimens of lung were obtained at lobectomy from 11 non-smokers, 39 smokers and 46 ex-smokers, the latter refraining from smoking at least 6 months before surgery. Neither sex nor ageing influenced the activity of sulphotransferase. The rate of salbutamol sulphation (pmol center dot min-1 center dot mg-1) was greater in non-smokers (27.7) than in smokers (21.3), whereas it was similar in smoker and ex-smokers (22.8). The rate of salbutamol sulphation ranged up to six fold and its distribution did not deviate from normality. As the rate of formation of the inactive salbutamol sulphate varied in the lung, the availability of salbutamol and, in turn, the evoked pharmacological effect should vary in parallel. The activities of salbutamol and dopamine sulphotransferase correlated, suggesting that catechol sulphotransferase takes part in the sulphation of salbutamol. The sulphation of salbutamol is stereoselective in the human lung, the kM estimate for (+)- salbutamol (1198 mu M) being greater than those for either (-)-salbutamol (190 mu M) and racemic salbutamol (142 mu M). These results are consistent with the view that (-)-salbutamol is a better substrate than (+)-salbutamol for sulphotransferase.

Adrenergic beta-Agonists↗
PubMed1996

Resection of single brain metastasis in non-small-cell lung cancer: prognostic factors.

Combined resection of primary non-small-cell lung cancer and single brain metastasis is reportedly superior to other treatments in prolonging survival and disease-free interval. To identify prognostic factors that influenced survival we reviewed clinical records and follow-up data of 52 consecutive patients with non-small-cell lung cancer and single brain metastasis who had been evaluated for combined lung and brain operation: 19 had synchronous and 33 metachronous non-small-cell lung cancer and single brain metastasis. Seven patients were excluded from combined operation because of either early brain relapse after craniotomy or single brain metastasis localization in deep brain structures. Forty-one of the 45 patients who underwent combined operation had complete remission of neurologic symptoms. Actuarial 5-year survival from the second surgical intervention was 16% (median 19 months, range 1 to 104 months). N0 status and lobectomy were the only variables associated with longer survival. Actuarial 5-year survivals in patients with synchronous and metachronous presentation were 6.6% and 19%, respectively. In patients with metachronous presentation the length of survival was significantly associated with N0 status, lobectomy, and interval between lung and brain operation equal to or longer than 14.5 months. The subset of patients with N0 status and interval between operations longer than 14.5 months had a 61% 5-year survival. None of the patients with N1-2 disease and shorter interval between operations was alive at 20 months. These data indicate that prognostic factors may help to identify subsets of patients with markedly different outcomes after combined lung and brain operation.

Adult↗
PubMed1996

Recurrence and death in non-small cell lung carcinomas: a prognostic model using pathological parameters, microvessel count, and gene protein products.

The 5-year survival rate of non-small cell lung carcinoma (NSCLC) has only marginally improved during the past two decades, despite advances in surgery and chemoradiotherapy. Major efforts are currently directed toward biological characterization of these tumors to define biomarkers able to add further prognostic information, thus improving new therapeutic protocols. We analyzed the predictive relevance of the microvessel count (MC), bcl-2 and p53 proteins, proliferative activity, and usual postsurgical parameters on recurrence and overall survival in a series of 70 patients with NSCLC. The expression of biological parameters (p53, bcl-2, proliferative activity, and MC) was detected using immunohistochemistry on paraffin-embedded and frozen sections from the tumors treated with surgical resection alone until relapse. In the univariate analysis, the histotype, tumor status, node status, p53, bcl-2, and MC have been shown to significantly affect progression and death. In the multiple logistic regression analysis, the MC (P < 0.000001), tumor status (P < 0.005), and node status (P < 0.0002) influenced the overall survival while prediction of relapse was strongly revealed by tumor status (P < 0.005), nodal metastatic involvement (P < 0.000001), and the assessment of the vascular count (P < 0.0004). These data have allowed the creation of a multivariate model which may add more information on risk of recurrence and death in patients with NSCLC and can form the basis for future randomized clinical trials.

Aged↗
PubMed1995

CD4 Lymphocyte enumeration: comparison between flow cytometry and enzyme immunoassay.

Assessment of the CD4 lymphocyte number, currently performed by flow cytometry, is one of the main laboratory tests for establishing progression to acquired immunodeficiency syndrome (AIDS). An enzyme immunoassay has recently been commercialized which can be very useful for counting CD4 cells in laboratories where flow cytometers are not available. In the present study, a comparative evaluation of CD4 positive lymphocytes with flow cytometry and the enzyme assay was made in healthy subjects (N = 30, R = 0.88, P < 0.0001), human immunodeficiency virus (HIV)-infected individuals (N = 80, R = 0.91, P < 0.0001), and patients with autoimmune diseases (N = 28, R = 0.82, P < 0.001) or psoriasis (N = 18, R = 0.76, P = 0.01). A correlation between the two methodologies was not found in psoriatic patients under treatment with cyclosporin A (N = 7, R = 0.05, not significant). Some differences could be found at low CD4 lymphocyte levels since the influence of CD4 antigen eluted from monocytes or soluble CD4 in the whole blood sample could cause overestimation of CD4 cell numbers by the enzyme assay.

Acquired Immunodeficiency Syndrome↗