Biomedical subjects

Antonio Daponte

Publications and source records attributed to Antonio Daponte.

12 recordsLinked to original sources

PubMed2006

Serial detection of circulating tumour cells by reverse transcriptase-polymerase chain reaction assays is a marker for poor outcome in patients with malignant melanoma.

BACKGROUND: Detection of circulating malignant cells (CMCs) through a reverse transcriptase-polymerase chain reaction (RT-PCR) assay seems to be a demonstration of systemic disease. We here evaluated the prognostic role of RT-PCR assays in serially-taken peripheral blood samples from patients with malignant melanoma (MM). METHODS: One hundred forty-nine melanoma patients with disease stage ranging from I to III were consecutively collected in 1997. A multi-marker RT-PCR assay was used on peripheral blood samples obtained at time of diagnosis and every 6 months during the first two years of follow-up (total: 5 samples). Univariate and multivariate analyses were performed after 83 months of median follow-up. RESULTS: Detection of at least one circulating mRNA marker was considered a signal of the presence of CMC (referred to as PCR-positive assay). A significant correlation was found between the rate of recurrences and the increasing number of PCR-positive assays (P = 0.007). Presence of CMC in a high number (> or =2) of analysed blood samples was significantly correlated with a poor clinical outcome (disease-free survival: P = 0.019; overall survival: P = 0.034). Multivariate analysis revealed that presence of a PCR-positive status does play a role as independent prognostic factors for overall survival in melanoma patients, adding precision to the predictive power of the disease stage. CONCLUSION: Our findings indicated that serial RT-PCR assay may identify a high risk subset of melanoma patients with occult cancer cells constantly detected in blood circulation. Prolonged presence of CMCs seems to act as a surrogate marker of disease progression or a sign of more aggressive disease.

Adolescent↗

PubMed2006

Factors predicting the occurrence of germline mutations in candidate genes among patients with cutaneous malignant melanoma from South Italy.

Clinical predictors for germline mutations of candidate genes in large clinic based population of patients with cutaneous malignant melanoma (CMM) are widely awaited. Using denaturing high-performance liquid chromatography (DHPLC) analysis and DNA sequencing, 557 consecutively-collected CMM patients originating from South Italy were screened for CDKN2A germline mutations; subsets of them were screened for mutations in the BRAF and BRCA2 genes. Seven CDKN2A mutations were detected in 14 (2.5%) CMM patients. Relative risk of carrying a CDKN2A mutation for CMM patients was demonstrated to significantly increase with the presence of familial recurrence of melanoma (risk ratio (RR)=6.31; p=0.0009), multiple primary melanomas (RR=3.43; p=0.0014), and early onset age (RR=4.56; p=0.0026). All CDKN2A mutations were observed in non-Sardinian patients (14/441; 3.2%), whereas BRAF and BRCA2 genes were found mutated in Sardinian patients (3/116; 2.6%). Such indicators of the presence of CDKN2A mutations will be useful in counselling patients about undergoing genetic testing. Our findings strongly suggest that mutation rates of candidate cancer genes may deeply vary among CMM patients from different geographical areas.

Adult↗

PubMed2005

Pegylated arginine deiminase treatment of patients with metastatic melanoma: results from phase I and II studies.

PURPOSE: Individuals with metastatic melanoma have a poor prognosis. Many human melanomas are auxotrophic for arginine, and arginine is not an essential amino acid in humans. We hypothesized that this auxotrophy may be therapeutically exploited. A novel amino acid-degrading enzyme (arginine deiminase) conjugated to polyethylene glycol (ADI-SS PEG 20,000 mw) was used to lower plasma arginine in individuals with metastatic melanoma. PATIENTS AND METHODS: Two cohort dose-escalation studies were performed. A phase I study in the United States enrolled 15 patients, and a phase I to II study in Italy enrolled 24 patients. The Italian patients also received two subsequent cycles of treatment, each consisting of four once-weekly injections of 160 U/m2. The goals of these studies were to determine pharmacokinetics (PK), pharmacodynamics (PD), safety, and the antitumor activity of ADI-SS PEG 20,000 mw. RESULTS: PK and PD studies indicated that a dose of 160 U/m2 lowered plasma arginine from a resting level of approximately 130 micromol/L to less than 2 micromol/L for at least 7 days; nitric oxide levels also were lowered. There were no grade 3 or 4 toxicities directly attributable to the drug. Six of 24 phase I to II patients responded to treatment (five partial responses and one complete response; 25% response rate) and also had prolonged survival. CONCLUSION Elimination of all detectable plasma arginine in patients with metastatic melanoma was well tolerated and may be effective in the treatment of this cancer. Further testing of ADI-SS PEG 20,000 mw in a larger population of individuals with metastatic melanoma is warranted.

Adult↗

PubMed2004

Socio-economic level, farming activities and risk of cancer in small areas of Southern Spain.

An ecological design was used to study the relationship between cancer incidence and both socioeconomic and environmental features in Southern Spain. Twenty-four sites and 26,380 cases diagnosed in 1985--1996 were analysed. Generalised Additive Models were used for data analysis. Except for lip cancer, the urban areas showed an increase in cancer risk for all sites. The relative risks among urban and rural municipalities ranges between 1.09 for skin non-melanoma (95% CI: 1.00-1.18) and 1.64 for cervix cancer (95% CI: 1.28-2.12). The relative risk among areas with high and low unemployment was 1.29 for stomach cancer (95% CI: 1.07-1.57), 1.45 for oral cavity cancer (95% CI: 1.10-1.93) and 1.77 for oesophagus cancer (95% CI: 1.02-3.05). Areas with highest unemployment showed the lowest incidence of melanoma. Risk for leukaemia, gall bladder, breast and prostate cancer showed a significant decreases by approximately 28% in the municipalities with the highest illiteracy score. A high percentage of land under cultivation was related to uterine tumours, larynx, rectum, lung, skin non-melanoma and brain cancers. For these sites, the risk had a significant increase by between 23% (skin non-melanoma) and 70% (rectum). Areas with high intensive farming showed a significant increase in cancer risk for lip, oral cavity, larynx, oesophagus, colon, lung, and bladder cancer. The relative risks ranges between 1.16 for colon cancer (95% CI: 1.04-1.29) and 1.47 for oesophagus cancer (95% CI: 1.15-1.87). The results of this study reveal how important socio-economic and environmental factors are for the analysis of cancer incidence in small areas of Southern Spain.

Agriculture↗

PubMed2004

[The productive sector].

In the last 25 years, the production sector in Spain has undergone important changes. Among these changes, the important growth of the services sector at the expense of the primary sector, the increasing flexibility of the labour market, and the rise in the female workforce could be considered as the most relevant ones. Spanish women have higher rates of unemployment, temporary jobs and part time contracts than Spanish men. Moreover, job access and work conditions are highly related to gender and social class. Because women are forced to compensate for the scarcity of social services for caring for young children and for dependent elderly, they become informal and socially unrecognised caregivers, preventing them from getting or holding a job, and significantly limiting their opportunities for professional development. These social conditions are closely related with the fact that work conditions for women involve higher temporality rates and shorter contracts than those of men, given the sectors and jobs in which they tend to work (due to segregation). Similarly, workers of the less privileged social classes have poorer work conditions. Thus, women of the lower income class are mainly suffering the worst job contracts and the poorest work conditions. More social services are needed to make it possible to attend to family needs and still be able to access and maintain a job contract. Policies tending to conciliate labour and family life are indispensable and should incorporate measures to equally distribute the house keeping activities between women and men.

Family↗

PubMed2003

[Short-term relationship between air pollution and mortality in 13 Spanish cities].

BACKGROUND AND OBJECTIVE: EMECAM is a collaborative project that seeks to evaluate the short-term effects of air pollution on mortality in Spain. MATERIAL AND METHOD: We collected data for air pollutants (particles and gases), daily mortality (total except external, cardiovascular and respiratory causes) and co-variables (temperature, humidity, influenza and calendar variables) in 13 Spanish cities. The magnitude of the association in every city was estimated using GAM under a Poisson distribution. Combined estimates for each cause and pollutant were obtained under 'fixed effects' and 'random effects'models. RESULTS: An increase of 10 (g/m3 in the levels of the average of the concurrent and one day lag for black smoke was associated with a 0.8% (CI: 0.4-1.1) increase in mortality. The same increase in the concentration of SO2 was associated with a 0.5% (CI: 0.1-1.0) increase in daily deaths, and a 0.6% (CI: 0.3-0.8) increase in the case of NO2. An increase of 1 mg/m3 in the levels of CO was associated with an increase of 1.5% (CI: 0.5-2.6) in daily deaths. CONCLUSIONS: There is a short-term association between increases of daily levels of air pollutants and the number of daily deaths in Spanish cities.

Air Pollution↗

PubMed2003

Prognostic value of circulating melanoma cells detected by reverse transcriptase-polymerase chain reaction.

PURPOSE: Factors that are predictive of prognosis in patients who are diagnosed with malignant melanoma (MM) are widely awaited. Detection of circulating melanoma cells (CMCs) by reverse transcriptase-polymerase chain reaction (RT-PCR) has recently been postulated as a possible negative prognostic factor. Two main questions were addressed: first, whether the presence of CMCs, defined as the patient being positive for any of the three markers, had a prognostic role; and second, what the predictive value of each individual marker was. PATIENTS AND METHODS: A consecutive series of 200 melanoma patients observed between January 1997 and December 1997, with stage of disease ranging from I to IV, was analyzed by semiquantitative RT-PCR. Tyrosinase, p97, and MelanA/MART1 were used as markers to CMCs on baseline peripheral blood samples. Progression-free survival (PFS) was used as a unique end point and was described by the product limit method. Multivariable analysis was applied to verify whether the auspicated prognostic value of these markers was independent of the stage of disease, and a subgroup analysis was performed that excluded patients with stage IV disease. RESULTS: Overall, 32% (64 of 200) of patients progressed, and a median PFS of 52 months in the whole series was observed. The presence of CMCs and the markers individually or combined was predictive of prognosis in the univariate analysis but did not provide additional prognostic information to the stage of disease in multivariable models. In the subgroup analysis of stage (ie, I-III subgroup), similar results were observed. CONCLUSION: Detection of CMCs in peripheral blood samples at the time of MM diagnosis by semiquantitative RT-PCR does not add any significant predictive value to the stage of disease. Thus, this approach should not be used in clinical practice, and further studies are required to determine its usefulness.

Adolescent↗

PubMed2003

The public health burden of material deprivation: excess mortality in leading causes of death in Spain.

OBJECTIVE: The aim of the study is to investigate the burden of deprivation-associated excess of deaths by 10 leading causes of death in each gender and two age groups. DESIGN: A small-area ecological study using two indices of material deprivation drawn from 1991 census and mortality data aggregated for 1987-1995 was undertaken. SETTING: 2218 small areas in Spain. Data are presented by region. MAIN OUTCOME MEASURES: The 10 leading causes of death in each gender and two age groups were determined. RESULTS: The deprivation-associated excess mortality in the top 10 leading causes of death was 14.4 and 11% for males and females, respectively. Excess mortality in the 9-year period studied accounted for more than 222,000 deaths. A large proportion of excess deaths was found in causes related to smoking and alcohol consumption among males and diet-related causes of death among females. The most deprived regions within the country showed the highest mortality risk. CONCLUSIONS: Material deprivation appears to be manifested in high mortality rates differently by gender and region. It imposes a significant public health burden that demands urgently attention and action by health policy-makers.

Adolescent↗

PubMed2003

Examining geographic patterns of mortality: the atlas of mortality in small areas in Spain (1987-1995).

BACKGROUND: Small-area mortality atlases have been demonstrated to be a useful tool for both showing general geographical patterns in mortality data and identifying specific high-risk locations. In Spain no study has so far systematically examined geographic patterns of small-area mortality for the main causes of death. This paper presents the main features, contents and potential uses of the Spanish Atlas of Mortality in small areas (1987-1995). METHODS: Population data for 2,218 small areas were drawn from the 1991 Census. Aggregated mortality data for 14 specific causes of death for the period 1987-1995 were obtained for each small area. Empirical Bayes-model-based estimates of age-adjusted relative risk were displayed in small-area maps for each cause/gender/age group (0-64 or 65 and over) combination using the same range of values (i.e. septiles) and colour schemes. RESULTS: The 'Spanish Atlas of Mortality' includes multiple choropleth (area-shaded) small-area maps and graphs to answer different questions about the data. The atlas is divided into three main sections. Section 1 includes the methods and comments on the main maps. Section 2 presents a two-page layout for each leading cause of death by gender including 1) a large map with relative risk estimates, 2) a map that indicates high- and low-risk small areas, 3) a graph with median and interquartile range of relative risk estimates for 17 large regions of Spain, and 4) relative-risk maps for two age groups. Section 3 provides specific information on the geographical units of analysis, statistical methods and other supplemental maps. CONCLUSION: The 'Spanish Atlas of Mortality' is a useful tool for examining geographical patterns of mortality risk and identifying specific high-risk areas. Mortality patterns displayed in the atlas may have important implications for research and social/health policy planning purposes.

Adolescent↗

PubMed2003

Early diagnosis of malignant melanoma: Proposal of a working formulation for the management of cutaneous pigmented lesions from the Melanoma Cooperative Group.

Epiluminescence microscopy (ELM) strongly improves the separation of different types of cutaneous pigmented lesions (CPL) and facilitates the early diagnosis of cutaneous melanoma (CM). ELM alone is not 100% accurate in routine diagnosis, and should not be considered the only criterion in the diagnosis of high-risk skin lesions. We have however, demonstrated close agreement between ELM classification criteria and histology in 2,731 cutaneous lesions. In the past five years, our Melanoma Cooperative Group has evaluated 61,000 skin lesions from 30,000 individuals and identified 478 cutaneous melanomas. Most newly diagnosed patients had very early stage melanoma [299 (62%) were Stage I (203 Stage IA and 96 Stage IB), by the American Joint Committee on Cancer (AJCC) criteria]. We have compared data from the patient histories and clinical evaluations with ELM-based morphological patterns to better characterize skin lesions and minimize interpretative problems. From these comparisons, we propose new guidelines for the management of CPL to provide a standard diagnostic and therapeutic approaches and to foster the early identification of lesions at risk for malignant transformation.

Adolescent↗

PubMedDate not supplied

[The EMECAS Project: Spanish multicentre study on short-term health effects of air pollution].

UNLABELLED: The EMECAM Project demonstrated the short-term effect of air pollution on the death rate in 14 cities in Spain throughout the 1990-1995 period. The Spanish Multicentre Study on Health Effects of Air Pollution (EMECAS) is broadening these objectives by incorporating more recent data, information on hospital disease admissions and totaling 16 Spanish cities. This is an ecological time series study in which the response variables are the daily deaths and the emergency hospitalizations due to circulatory system diseases and respiratory diseases among the residents in each city. Pollutants analyses: suspended particles, SO2, NO2, CO and O3. Control variables: meteorological, calendar, seasonality and influenza trend and incidence. STATISTICAL ANALYSIS: estimate of the association in each city by means of the construction of generalized additive Poisson regression models and metanalysis for obtaining combined estimators. The EMECAS Project began with the creation of three working groups (Exposure, Epidemiology and Analysis Methodology) which defined the protocol. The average levels of pollutants were below those established under the current regulations for sulfur dioxide, carbon monoxide and ozone. The NO2 and PM10 values were around those established under the regulations (40 mg/m3). This is the first study of the relationship between air pollution and disease rate among one group of Spanish cities. The pollution levels studied are moderate for some pollutants, although for others, especially NO2 and particles, these levels could entail a problem with regard to complying with the regulations in force.

Air Pollution↗

PubMedDate not supplied

Temozolomide and cisplatin in avdanced malignant melanoma.

BACKGROUND: Temozolomide (TMZ) is an oral alkylating agent; it produces DNA methyl adducts, which are removed by the DNA repair enzyme AGAT. In vitro studies suggest that CDDP may enhance the antitumor activity of TMZ due to the ability of cisplatin (CDDP) to down-regulate AGAT activity. In a previous phase I study, the combination of TMZ and CDDP was tested, and the recommended dose for each drug was defined. On the basis of these results, we designed a phase II study to evaluate the activity and safety profile of the TMZ-CDDP association in patients with advanced melanoma. PATIENTS AND METHODS: From March 2001 to March 2002, 37 patients with metastatic melanoma, not amenable to surgery, were enrolled in this study. All eligible patients were treated with the combination of CDDP 75 mg/m2 i.v. d 1, TMZ 200 mg/m2 p.o. days 1-5 recycled every 4 weeks. Interferon alpha2b (IFN alpha2b) was administered at the end of chemotherapy to responsive patients at the dose of 5 M.I. U s.c. 3 times a week for 1 year. RESULTS: A total of 174 courses were administered, with a median number of 4 courses/patient (range 1-10). After chemotherapy, 9 CRs and 9 PRs were observed for an overall response rate of 48.6% (95% C.I., 31.9%-65.6%). One of 5 patients with initial brain metastases showed a complete response to the therapy. Five out of 9 CR patients were still with no evidence of recurrence, ranging from 28+ to 82+ weeks. The median survival time was 48 weeks. The schedule was well tolerated, with the most frequent adverse events reported being nausea and vomiting (59%), alopecia (14%) and fatigue (11%), all well controlled by supportive therapy. Haemotological toxicities were mild to moderate. Side-effects attributable to IFN alpha2b were also mild and manageable. CONCLUSION: The combination of TMZ and CDDP seems to be active in untreated patients with advanced melanoma. Absence of recurrence in the majority (5/9; 56%) of CR patients seems to indicate that IFN may act on the duration of the response to chemotherapy. The schedule was well tolerated, with nausea and vomiting as the most frequent adverse events.

Adult↗