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Biomedical subjects

A Mussi

Publications and source records attributed to A Mussi.

At least 37 records · Page 2Linked to original sources
PubMed2000

Combined Nd-YAG laser/HDR brachytherapy versus Nd-YAG laser only in malignant central airway involvement: a prospective randomized study.

BACKGROUND: Laser debulking and prosthetic stents are useful modalities in the palliative treatment of initial inoperable or recurrent lung cancer. Recently, endobrochial brachytherapy was introduced to extend the duration of palliation and reduce the number of endoscopic treatments. This trial compares Nd-YAG laser alone and associated to high dose rated (HDR)-brachytherapy. PATIENTS AND METHODS: From 1995 to 1998, 29 consecutive patients, with non-small cell lung cancer (NSCLC) and central airway involvement, were randomized in two groups: group 1 (15 patients) received Nd-YAG laser only; group 2 (14 patients) underwent a combined Nd-YAG laser/ HDR brachytherapy treatment. RESULTS: There was no mortality or morbidity related to the treatment. The period free from symptoms was 2.8 months for group 1 and increased to 8.5 months in group 2 (P<0.05). The disease's progression free period grew from 2.2 months of group 1 to 7.5 months of group 2 (P<0.05) and the number of further endoscopic treatment reduced from 15 to 3 (P<0.05). CONCLUSION: The results confirm the potential of brachytherapy to prolong relief from symptoms, lessen disease progression and reduce costs of treatment. A detailed analysis is presented of both groups.

Aged↗
PubMed2000

Tumour necrosis factor-alpha and transforming growth factor-beta are significantly associated with better prognosis in non-small cell lung carcinoma: putative relation with BCL-2-mediated neovascularization.

Recent in vivo and in vitro studies have demonstrated a wide spectrum of biologic activities of cytokines in the pathogenesis and progression of malignancy. Tumour necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) have emerged as two of the many host-derived mediators that seem to interfere with both antiproliferative and tumorigenic effects in malignant tumours including lung cancer. However, their association with tumour prognosis or prognostic factors has not yet been completely clarified. In this study, we assessed TNF-alpha and TGF-beta mRNA expression by RT-PCR technique in 61 NSCLC samples, demonstrating the presence of TNF-alpha and TGF-beta mRNA in 55.74% and 45.9% of cases, respectively. We also evaluated the expression of the two distinct transmembrane TNF receptors. TNFR-I and TNFR-II, with a PCR-positive signal in 70.49% and 65.57% of cases, respectively. In 49 of the 61 cases, we evaluated the prognostic impact of the two growth-inhibiting factors using the Kaplan-Meier analysis. In the univariate analysis patients without nodal metastatic involvement (P = 0.02), less advanced tumour stage (P = 0.02) or TNF-alpha and TGF-beta positive cancers (P = 0.01 and P = 0.03) showed a favourable prognosis in terms of overall survival. Since our previous studies demonstrated a significant association between NSCLC behaviour, neoangiogenesis and bcl-2 expression, we investigated the putative relation between TNF-alpha and TGF-beta on the one hand, and vascular count (as a measure of tumour angiogenesis) and bcl-2 protein expression, on the other hand. Our results showed a significant direct association between TNF-alpha and bcl-2 (P = 0.05) and an inverse association between TNF-alpha and microvessel count (P = 0.03). Moreover, as previously demonstrated, we observed a significant inverse correlation between bcl-2 protein expression and vascular count (P = 0.05), suggesting that the favourable effect of TNF-alpha on clinical outcome may be related to a bcl-2-mediated low neovascular development.

Adult↗
PubMed2000

Surgical approaches to membranous tracheal wall lacerations.

BACKGROUND: Smaller postintubation tracheal tears are often misdiagnosed and, when recognized, they are effectively managed in a conservative fashion. Large membranous lacerations, especially if associated with important manifestations, require immediate surgical repair. We report our experience over the past 7 years. METHODS: From 1993 to 1999, 11 patients with a postintubation posterior tracheal wall laceration were treated in our institution. One patient was male and 10 were female, with a mean age of 68 years. Ten patients underwent orotracheal intubation under general anesthesia for elective surgery, 4 of whom were treated with a double-lumen selective tube. One patient underwent emergency intubation because of anaphylactic shock. In 9 cases the tracheal tear was promptly repaired, by way of a thoracotomy in 4 and by way of a cervicotomy and longitudinal tracheotomy in 5. In 2 cases the tear was small and was consequently managed conservatively. RESULTS: All surgical procedures proved effective in repairing the laceration, and there was no mortality or morbidity in the perioperative period. Early and late endoscopic follow-up showed no signs of tracheobronchial stenosis. CONCLUSIONS: When repair of membranous tracheal laceration is required, the surgical approach should be through a thoracotomy if the tear involves the distal trachea, a main stem, or both, and through a cervicotomy when the laceration is located in the proximal two thirds of the trachea. Performing a longitudinal tracheotomy to reach and suture the posterior tracheal wall is a reliable, quick, and safe procedure, and it avoids lateral and posterior dissection of the trachea.

Adult↗
PubMed2000

Gastropleural fistula as complication of postpneumonectomy empyema.

A 54-year-old woman underwent a left pneumonectomy for monolateral congenital pulmonary cysts, complicated by a pleural empyema without bronchial fistula, in the late postoperative period. The pleural empyema was evacuated and managed by means of a small thoracic drainage. Three months after discharge the patient noticed the presence of ingesta in the pleural washing fluid. Diagnostic and operative procedures in this rare case of non malignant, non traumatic gastropleural fistula are described.

Empyema, Pleural↗
PubMed1999

Aortobronchial fistula after coarctation repair and blunt chest trauma.

A 34-year-old man had development of an aortobronchial fistula 17 years after patch aortoplasty for correction of aortic coarctation and 5 years after blunt chest trauma, an unusual combination of predisposing factors. The clinical presentation, characterized by dysphonia and recurrent hemoptysis, and the surgical findings suggested the posttraumatic origin of the fistula, which was successfully managed by aortic resection and graft interposition under simple aortic cross-clamping, associated with partial pulmonary lobectomy. When hemoptysis occurs in a patient with a history of an aortic thoracic procedure, the presence of an aortobronchial fistula should be suspected. Early diagnosis offers the only possibility of recovery through a lifesaving surgical procedure.

Adult↗
PubMed1999

Expression of vascular endothelial growth factor mRNA in non-small-cell lung carcinomas.

The vascular endothelial growth factor (VEGF) has been shown to be strictly related to vascular permeability and endothelial cell growth under physiological and pathological conditions. In tumour development and progression, VEGF plays a pivotal role in the development of the tumoral vascular network, and useful information in the progression of human cancer can be obtained by analysing the vascular endothelial growth factor expression of the tumours. In this study, we investigated the vascular endothelial growth factor transcript expression in non-small-cell lung carcinomas to evaluate the significance of this factor in a group of cancers in which the vascular pattern has been shown to significantly affect progression. Surgical samples of 42 patients with NSCLC were studied using reverse transcription polymerase chain reaction (PCR) analysis and in situ hybridization. Thirty-three out of 42 cases (78.6%) showed VEGF transcript expression predominantly as transcripts for the secretory forms of VEGF (isoforms 121 and 165). In situ hybridization, performed on 24 out of 42 samples, showed that the VEGF transcript expression was in several cases present in the cytoplasm both of neoplastic and normal cells, even if the VEGF mRNA was less expressed in the corresponding non-tumoral part. The VEGF 121 expression was associated with hilar and/or mediastinal nodal involvement (P = 0.02), and, taken together, the VEGF isoforms were shown to significantly influence overall (P = 0.02) and disease-free survival (P = 0.03). As a regulator of tumour angiogenesis, VEGF may represent a useful indicator of progression and poor prognosis in non-small-cell lung carcinomas.

Adult↗
PubMed1999

Quantitation by competitive PCR assay of vascular endothelial growth factor in non-small cell lung carcinomas.

The vascular endothelial growth factor (VEGF) is known to be one of the most important angiogenic factors under both physiological and pathological conditions. The VEGF overexpression by a wide spectrum of neoplastic diseases has suggested an important role of this cytokine in tumor-neovascularization. A method is described for quantification by reverse transcription-polymerase chain reaction (RT-PCR) of VEGF mRNA in non-small cell lung cancer tissues (NSCLC). The method entails addition to the sample of competitor DNA molecules that share the same primer recognition sites as the amplified target, but which can be easily distinguished by gel electrophoresis because of their different lengths (competitive PCR). We analyzed the VEGF mRNA expression level in 34 cases of lung tumor tissues compared to the respective adjacent normal tissues. In 4 out of 34 (11.7%) analyzed couples there was no VEGF mRNA expression, in 8 out of 34 (23.5%) only normal parenchymal tissue was positive for VEGF mRNA expression; in the remaining 22 cases (64. 7%) both normal and tumor tissues showed PCR products for VEGF. In 17 out of these 22 couples (77.2%) a higher number of VEGF mRNA molecules were present in tumor specimens than in the normal counterpart. According to these results, the competitive PCR-method seems to provide a useful tool for the quantitate VEGF expression in order to identify its role in the development of lung cancer.

Adult↗
PubMed1999

Increased serum IL-6, TNF-alpha and IL-10 levels in patients with bullous pemphigoid: relationships with disease activity.

AIM: The present report analyzes the serum levels of three cytokines, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in 15 patients with bullous pemphigoid (BP) (compared with 20 healthy controls) to evaluate a possible involvement of these biological modulators in the clinical expression of this disease. BACKGROUND: BP is a rare bullous disease of autoimmune origin with evidence of inflammatory processes that cause skin lesions with local increase of various pro-inflammatory mediators. METHODS: Determination of cytokine concentrations were obtained employing commercially available ELISA kits. RESULTS: The sera of BP patients showed increased levels of these three cytokines (P < 0.01). When the number of skin lesions (blisters and/or erosion) of each patient, employed as a marker of disease activity, was correlated with the serum levels of IL-6 and TNF-alpha, significant correlations were found (IL-6: P < 0.01 and TNF-alpha: P < 0.01, respectively), suggesting a possible role of these mediators in the development of BP blisters. The serum levels of IL-6 also correlated (P = 0.01 with those of serum C reactive protein (CRP), an acute-phase protein induced by IL-6 in hepatocytes. In addition, serum TNF-alpha and sE-selectin (an adhesion molecule previously reported to be increased by this cytokine) levels were also correlated (P < 0.05). CONCLUSIONS: On the basis of these data, it may be indicated that at least IL-6 and TNF-alpha are associated with the clinical expression of BP and that the endothelial activation (possibly induced by the TNF-alpha activity), seems to be an important phase of this dermatosis.

Adult↗
PubMed1999

Thrombospondins I and II messenger RNA expression in lung carcinoma: relationship with p53 alterations, angiogenic growth factors, and vascular density.

Thrombospondin (TSP) is a Mr 450,000 multifunctional matrix glycoprotein that interferes with tumor growth, angiogenesis, and metastasis. It has recently been shown that TSP expression is enhanced by the product of the p53 gene and that a down-regulation of TSP may be observed when alterations of the p53 protein occur. Moreover, a number of studies have demonstrated a regulatory activity of p53 on human vascular endothelial growth factor (VEGF), although additional investigations will be necessary to understand their relationship. In non-small cell lung carcinoma (NSCLC), neoangiogenesis, p53 alterations, and VEGF expression seem to have meaningful implications in the development and progression of this type of cancer. The aim of this study is to identify and quantitate TSP I and TSP II mRNA in NSCLCs with respect to p53 alterations, angiogenic growth factor expression, and microvascular density. A series of 24 cases of NSCLC were analyzed. Eleven of 24 of the cases were positive for TSP II mRNA, whereas 8 of 24 showed TSP I mRNA expression. A significant inverse association was found between TSP I mRNA and fibroblast growth factor (FGF) protein expression (P = 0.00001). Tumors with low FGF protein expression (< or = 40% of positive cells) presented a number of TSP I cDNA molecules, significantly higher than tumors expressing high levels of FGF protein. No association was found between TSP mRNA expression and other angiogenic growth factors (i.e., VEGF) or tumoral neovascularization. On the contrary, tumors with high levels of FGF showed a higher number of microvessels (P = 0.05). By PCR-single-strand conformational polymorphism analysis, we observed aberrations of the p53 gene in 19 of the 24 tumor samples. No association was found between p53 alterations and TSP mRNA expression. Instead, an interestingly significant association was found between the presence of p53 mutations and high VEGF protein expression (P = 0.01) and neovascularization (P = 0.03). Highly vascularized tumors showed higher VEGF protein expression (r = 0.45; P = 0.02). These data support the concept that in NSCLC, p53 exerts an important role in the control of neoangiogenesis. This influence is probably mediated by VEGF. The inverse association we found between TSP I and basic FGF suggests a different role of TSP I and TSP II in the angiogenic "switch," supporting the hypothesis that especially TSP I may have a significant function in tumor angiogenesis.

Adult↗
PubMed1998

Bcl2 and p53 regulate vascular endothelial growth factor (VEGF)-mediated angiogenesis in non-small cell lung carcinoma.

The aim of this study was to investigate the expression of p53 and bcl2 proteins in a series of 107 non-small cell lung cancers (NSCLC), and to relate such protein expression to neovascularisation and the expression of vascular endothelial growth factor (VEGF). Moreover, we analysed the prognostic impact of these biological parameters on overall survival, both in univariate and multivariate analyses. An inverse association was found between bcl2 expression and microvessel count (MVC; P = 0.0004) and bcl2 and VEGF (P = 0.007). In contrast, a significant association was found between p53 expression and MVC (P = 0.03) and p53 and VEGF expression (P = 0.04). In univariate analysis, nodal status (P < 0.000001), MVC (P < 0.000001), bcl2 (P = 0.002), p53 (P = 0.03) and VEGF expression (P < 0.000001) significantly affected overall survival, but in multivariate analysis only MVC and VEGF expression retained their prognostic influence. Our results suggest that bcl2 and p53 possibly control the development of tumour angiogenesis in NSCLC, with putative mediation by VEGF. Moreover, the important influence of angiogenesis in the progression of NSCLC is further highlighted.

Aged↗
PubMed1998

Treatment by VATS of giant bullous emphysema: results.

OBJECTIVE: In selected patients with giant bullous emphysema GBE and in those with specific complications, surgery may be the treatment of choice. METHODS: In the period January 1993-February 1996 we performed 34 VATS treatments in 29 patients affected by GBE. There were 22 (76%) males and 7 (24%) females, with a mean age of 54 years (range 24 74). In 23 cases, a pneumothorax (PNX) was present at admission, while 6 patients were treated by choice. Altogether. we performed 23 resections of sessile bullae (type 2 of Reid) by using a linear endoscopic stapling device (Endo-path 35 and 45 mm) and 11 ligatures of pedicled bullae (type 1 of Reid) by loop (Endo-loop 'PDS'). The mean number of charges for every treatment was 8 (range 4-21). The largest bullae were perforated and deprived of incarcerated air. They were then twisted on the axis perpendicular to the base in order to improve the manoeuvrability of the lesion and favour the correct placement of the Endo-path or Endo-loop. GBE was bilateral in 7 cases: one of these was treated bilaterally in the same surgical stage, other 4 were treated by staged operations. RESULTS: We experienced two conversions to open thoracotomy (one sessile giant bulla inside the fissura; 1 case of strong tuberculous pleural adhesions). Two patients, underwent a second operation by open thoracotomy because of a prolonged air leak. We have two peri-operative deaths, both to respiratory failure. Altogether, in 23 out of 29 (79%) cases VATS was effective and the mean hospital stay was 6 days (range 3-16). At a mean follow up of 16 months (range 1-36) no recurrence of PNX was observed. CONCLUSIONS: VATS may be considered as a suitable surgical technique to approach GBE and, in most cases, it is effective.

Adult↗
PubMed1998

Endothelin-1 levels are increased in sera and lesional skin extracts of psoriatic patients and correlate with disease severity.

Endothelins (ETs), in addition to their systematical activities, exert important functions at the skin level, such as increase of keratinocyte proliferation, neo-angiogenesis and leukocyte chemotaxis, which are among the main characteristics of psoriasis. To assess a possible ET-1 involvement in plaque-type psoriasis, ET-1 determinations were carried out in 15 sera and 8 lesional and non-lesional biopsy skin extracts from psoriatic patients and in 15 sera and 5 biopsy skin extracts from healthy volunteers, sex- and age-matched, using commercially available ELISA kits. A statistical analysis of the results showed that ET-1 levels were increased in sera of psoriatic patients, as compared to normal subjects (p = 0.04). In addition, there was a significant correlation between both serum (r = 0.60, p = 0.02) and lesional skin (r = 0.80, p = 0.03) ET-1 values versus the Psoriasis Area and Severity Index scores. Significant increases of the lesional versus the non-lesional (p = 0.01) and versus the normal (p = 0.04) ET-1 skin extract values were observed, together with a significant correlation between lesional and non-lesional ET-1 skin levels (r = 0.79, p = 0.03). These findings were also confirmed at the mRNA level, using RT-PCR analysis, where increased ET-1 mRNA levels, densitometrically measured, were found in the lesional samples versus non-lesional and normal skin. Since interleukin-8 is involved in psoriasis and shares some biological properties with ET-1, we further evaluated the levels of this cytokine in skin extracts. The behaviour of interleukin-8 paralleled that of ET-1, and a significant correlation between these two molecules was observed in the lesional skin (r = 0.76, p = 0.05). Taken together, these data stress that, as previously described for interleukin-8, ET-1 may be involved in inflammatory processes associated with psoriasis.

Adult↗
PubMed1998

Decreased interleukin-7 and transforming growth factor-beta1 levels in blister fluids as compared to the respective serum levels in patients with bullous pemphigoid. Opposite behavior of TNF-alpha, interleukin-4 and interleukin-10.

This study analyzes both the blister fluid (BF) and serum levels of IL-7 and TGF-beta1 in samples from 18 patients affected with bullous pemphigoid (BP). These cytokines clearly present lower concentrations (P<0.001) in BFs than in the sera (1/20 and 1/2, respectively). In contrast, TNF-alpha, IL-10 and IL-4 present increased amounts in BFs that were 12, 12 and 17-fold, respectively. Eighteen sera (and 10 suction BF) from normal individuals were also employed as control. Normal sera presented significantly lower serum IL-7 concentrations than BP, while no significant TGF-beta1 variations were observed between normal and pathologic serum samples. In addition, the serum levels detected in BP patients were significantly correlated with disease intensity (r=0.64, P=0.003, evaluated as the number of blisters/erosions for each patient) as well as with the peripheral B-lymphocyte counts (r=0.80, P<0.001) and antibodies directed against the basement membrane zone (r=0.65, P<0.005). Although a clear explanation of this phenomenon is lacking, the data presented in this report agree with a strong decrease of IL-7 production at the local level (keratinocyte is known to produce IL-7 and the latter is known to be down-regulated by IL-10, and in other models also by TGF-beta1 and IL-4, whose levels are elevated in BP BFs) as opposed to an increased peripheral release of the same modulator. The IL-7 reduction may have a biological relevance in controlling a chronic, progressive disease.

Adult↗
PubMed1998

Recognition and treatment of psoriasis. Special considerations in elderly patients.

Psoriasis is a chronic dermatological disorder that affects 1 to 2% of the general population. Although its aetiology is still unknown, the importance of genetic factors has been confirmed by many studies, mainly in young individuals. With respect to clinical features, plaque-type psoriasis (localised or generalised) is the most common form. At present, there is no cure for psoriasis and the available treatments can only temporarily clear the skin manifestations. The choice of treatment regimen for psoriasis is based on the severity of the disease, the patient's gender, age, treatment history and level of compliance, and the physician's personal experience. All therapies for psoriasis have different and potentially toxic effects. Therefore, a good knowledge of their relative and absolute contraindications, adverse effects and interactions with other drugs is mandatory. The elderly represent a significant proportion of patients with psoriasis because its prevalence increases with age. Physicians, particularly general practitioners, dermatologists and gerontologists, must be aware of the problems that the treatment of psoriasis in the elderly can present. This is especially important because of the increased risk of adverse drug reactions in the elderly.

Aged↗
PubMed1998

Evaluation of epidermal growth factor-related growth factors and receptors and of neoangiogenesis in completely resected stage I-IIIA non-small-cell lung cancer: amphiregulin and microvessel count are independent prognostic indicators of survival.

We have determined the expression of transforming growth factor alpha (TGF alpha), amphiregulin (AR), CRIPTO, the epidermal growth factor receptor (EGFR), erbB-2, erbB-3, and tumor angiogenesis in a series of 195 patients with stage I-IIIA non-small cell lung cancer (NSCLC) treated with radical surgery to define their usefulness as prognostic indicators of survival. A variable degree of specific staining in cancer cells was observed for the three growth factors and for the three growth factor receptors in the majority of NSCLC patients. A statistically significant association between overexpression of TGF alpha, AR, and CRIPTO was observed. Enhanced expression of AR was significantly correlated with enhanced expression of erbB-2 and advanced T-stage. A direct association was also detected for overexpression of TGF alpha and of erbB-2 or erbB-3, respectively. Sex, tumor size, nodal status, stage, microvessel count, as a measure of neovascularization, and AR overexpression significantly correlated with overall survival at univariate analysis. In a Cox multivariate analysis, the only characteristics with an independent prognostic effect on OAS were microvessel count [relative hazard (RH), 6.61; P < 0.00001), nodal status (RH, 1.59; P = 0.0013), and AR overexpression (RH, 1.72; P = 0.02). These results suggest that evaluation of neoangiogenesis and of certain growth factors, such as AR, can be useful in addition to conventional pathological staging to select high-risk NSCLC patients who may benefit from post-surgical systemic therapies.

Adult↗
PubMed1997

Angiogenesis as a prognostic indicator of survival in non-small-cell lung carcinoma: a prospective study.

BACKGROUND: Tumors acquire nutrients that are essential for continued growth and an avenue for dissemination to the rest of the body by inducing angiogenesis (i.e., the formation of new blood vessels). Preliminary studies involving a number of different kinds of cancer have indicated that an assessment of tumor angiogenesis may be useful in predicting disease outcome. PURPOSE: In a prospective study, we evaluated the relationship between tumor angiogenesis and survival for 407 patients with non-small-cell lung carcinoma who were treated with potentially curative surgery. METHODS: The study population consisted of 360 male and 47 female patients who underwent surgery consecutively at the Department of Surgery, University of Pisa, Italy, from March 1991 through December 1994. Follow-up lasted through February 1996, with a median follow-up for living patients of 29 months (range, 15-60 months). An anti-CD34 monoclonal antibody, which is specific for endothelial cells, and standard immunohistochemical techniques were used to measure angiogenesis in tumor samples. Angiogenesis was quantified in terms of microvessel counts; the counts for single, high-power microscopic fields (magnification x250) in the three most intense areas of blood vessel growth for each sample were averaged. The median microvessel count in this series was 20, and the counts were categorized as follows: 1) low versus high (< or =20 versus >20 microvessels) or 2) in five categories (1-10, 11-20, 21-30, 31-40, and > or =41 microvessels). Disease-free and overall survival during follow-up were assessed. Kaplan-Meier survival curves were modeled in a univariate analysis of patient and tumor characteristics; the Cox proportional hazards model was used in multivariate analysis. Reported P values are two-sided. RESULTS AND CONCLUSIONS: In the univariate analysis, patients with larger tumors (P for trend <.00001), a more advanced tumor stage (P for trend <.00001), a greater degree of regional lymph node involvement (P for trend <.00001), or more vascularized tumors (high versus low microvessel count, P<.00001) experienced significantly reduced overall survival. When microvessel counts were analyzed in five categories, a highly significant trend (P<.00001) toward worse prognosis was observed with increasing tumor vascularity. In multivariate analysis, tumor microvessel count (P<.00001), tumor size (P = .0006), and regional lymph node status (P<.00001) retained independent prognostic value with respect to overall survival; among these variables, tumor microvessel count, considered as a continuous variable, was the most important, with a relative hazard of death of 8.38 (95% confidence interval = 4.19-16.78) associated with the highest microvessel counts. IMPLICATIONS: An evaluation of tumor angiogenesis may be useful in the postsurgical staging of patients with non-small-cell lung carcinoma and in identifying subsets of patients who may benefit from different postsurgical treatments.

Adult↗