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Biomedical subjects

Francesco Sera

Publications and source records attributed to Francesco Sera.

At least 19 recordsLinked to original sources
PubMed2006

Dermoscopy improves accuracy of primary care physicians to triage lesions suggestive of skin cancer.

PURPOSE: Primary care physicians (PCPs) constitute an appropriate target for new interventions and educational campaigns designed to increase skin cancer screening and prevention. The aim of this randomized study was to determine whether the adjunct of dermoscopy to the standard clinical examination improves the accuracy of PCPs to triage lesions suggestive of skin cancer. PATIENTS AND METHODS: PCPs in Barcelona, Spain, and Naples, Italy, were given a 1-day training course in skin cancer detection and dermoscopic evaluation, and were randomly assigned to the dermoscopy evaluation arm or naked-eye evaluation arm. During a 16-month period, 73 physicians evaluated 2,522 patients with skin lesions who attended their clinics and scored individual lesions as benign or suggestive of skin cancer. All patients were re-evaluated by expert dermatologists at clinics for pigmented lesions. Referral accuracy of both PCP groups was calculated by their scores, which were compared to those tabulated for dermatologists. RESULTS: Referral sensitivity, specificity, and positive and negative predictive values were 54.1%, 71.3%, 11.3%, and 95.8%, respectively, in the naked-eye arm, and 79.2%, 71.8%, 16.1%, and 98.1%, respectively, in the dermoscopy arm. Significant differences were found in terms of sensitivity and negative predictive value (P = .002 and P = .004, respectively). Histopathologic examination of equivocal lesions revealed 23 malignant skin tumors missed by PCPs performing naked-eye observation and only six by PCPs using dermoscopy (P = .002). CONCLUSION: The use of dermoscopy improves the ability of PCPs to triage lesions suggestive of skin cancer without increasing the number of unnecessary expert consultations.

Adolescent↗
PubMed2006

Daily consumption of a high-phenol extra-virgin olive oil reduces oxidative DNA damage in postmenopausal women.

Extra-virgin olive oils (EVOO), high in phenolic compounds with antioxidant properties, could be partly responsible for the lower mortality and incidence of cancer and CVD in the Mediterranean region. The present study aims to measure oxidative DNA damage in healthy human subjects consuming olive oils with different concentrations of natural phenols. A randomised cross-over trial of high-phenol EVOO (high-EVOO; 592 mg total phenols/kg) v. low-phenol EVOO (low-EVOO; 147 mg/kg) was conducted in ten postmenopausal women in Florence. Subjects were asked to substitute all types of fat and oils habitually consumed with the study oil (50 g/d) for 8 weeks in each period. Oxidative DNA damage was measured by the comet assay in peripheral blood lymphocytes, collected at each visit during the study period. Urine samples over 24 h were collected to measure the excretion of the olive oil phenols. The average of the four measurements of oxidative DNA damage during treatment with high-EVOO was 30 % lower than the average during the low-EVOO treatment (P=0.02). Urinary excretion of hydroxytyrosol and its metabolite homovanillyl alcohol were significantly increased in subjects consuming high-EVOO. Despite the small sample size, the present study showed a reduction of DNA damage by consumption of an EVOO rich in phenols, particularly hydroxytyrosol.

Aged↗
PubMed2006

Survival and prognostic variables of cutaneous melanoma observed between 1995 and 2000 at Istituto Dermopatico Dell'Immacolata (IDI-IRCCS), Rome, Italy.

INTRODUCTION: Melanoma is an increasingly common malignancy of melanocytes, with incidence rates steadily rising over the past several decades. The objective of this study was to evaluate 5-year survival and to investigate the association between melanoma mortality and clinical and histological features. METHODS: We conducted a 5-year cohort study among 1020 patients from the same geographic area (Rome) with a single primary cutaneous melanoma diagnosed between January 1995 and December 2000. Survival probability was determined by Kaplan-Meier estimates, and prognostic factors were evaluated by multivariate analysis (Cox proportional hazards model). RESULTS: Survival decreased with increasing age (P for trend <0.049) and Breslow thickness (P for trend <0.0001). In the multivariate Cox model, Breslow thickness was the only independent prognostic factor for mortality in primary melanoma patients. The risk of death among patients with melanoma increased with increasing tumour thickness 0.76-1.49 mm (relative risk (RR) 2.67, 95% confidence interval (95% CI) 0.63-11.4); 1.50-4.0 mm (RR 6.38, 95% CI 1.75-23.2), >4.0 mm (RR 34.6, 95% CI 8.23-145.7) (P for trend <0.0001). The Years of Life Lost (YLLs) for the Breslow categories < or =0.75 mm, 0.76-1.49 mm, 1.50-4.0 mm and >4.0 mm were 65.4, 153.6, 274.3 and 317.6 years, respectively. CONCLUSION: This study shows the great importance of secondary melanoma prevention and illustrates how many years of life could be saved by early diagnosis.

Adolescent↗
PubMed2006

Placenta growth factor in diabetic wound healing: altered expression and therapeutic potential.

Reduced microcirculation and diminished expression of growth factors contribute to wound healing impairment in diabetes. Placenta growth factor (PlGF), an angiogenic mediator promoting pathophysiological neovascularization, is expressed during cutaneous wound healing and improves wound closure by enhancing angiogenesis. By using streptozotocin-induced diabetic mice, we here demonstrate that PlGF induction is strongly reduced in diabetic wounds. Diabetic transgenic mice overexpressing PlGF in the skin displayed accelerated wound closure compared with diabetic wild-type littermates. Moreover, diabetic wound treatment with an adenovirus vector expressing the human PlGF gene (AdCMV.PlGF) significantly accelerated the healing process compared with wounds treated with a control vector. The analysis of treated wounds showed that PlGF gene transfer improved granulation tissue formation, maturation, and vascularization, as well as monocytes/macrophages local recruitment. Platelet-derived growth factor, fibroblast growth factor-2, and vascular endothelial growth factor mRNA levels were increased in AdCMV.PlGF-treated wounds, possibly enhancing PlGF-mediated effects. Finally, PlGF treatment stimulated cultured dermal fibroblast migration, pointing to a direct role of PlGF in accelerating granulation tissue maturation. In conclusion, our data indicate that reduced PlGF expression contributes to impaired wound healing in diabetes and that PlGF gene transfer to diabetic wounds exerts therapeutic activity by promoting different aspects of the repair process.

Adenoviridae↗
PubMed2005

GSTT1 and GSTM1 gene polymorphisms and gastric cancer in a high-risk italian population.

Glutathione S-Transferases (GSTs) are a family of phase II enzymes involved in the detoxification of potential carcinogens and provided of a strong antioxidant function by neutralizing electrophiles and free radicals. The GSTM1 and GSTT1 isoenzymes exhibit deletion polymorphisms, resulting in a lack of activity, and the null genotypes have been associated with increased cancer risk at several sites, including the stomach, although with contrasting results. We carried out a case-control study to evaluate whether these polymorphisms modulate the risk of developing gastric cancer (GC). Genotypes for GSTM1 and GSTT1 were obtained from a series of 175 histologically confirmed GC patients and a large series of 546 healthy controls randomly sampled from the general population of Tuscany, an area at high GC risk. No difference in the frequency of GSTM1 null genotype was observed between cases and controls, whereas the GSTT1 null genotype was more frequent among cases (p = 0.04). Multivariate single-gene analyses adjusted for possible confounders showed that the GSTT1 null genotype, but not the GSTM1 null genotype, was associated with an increased GC risk. Combined-genotype analyses showed a significantly increased GC risk only for the double null (GSTM1-GSTT1) genotype (OR = 2.27; 95% CI: 1.14-4.53). A statistically significant positive interaction between the 2 null genotypes was observed (p = 0.02). Our findings suggest that only subjects lacking both GSTM1 and GSTT1 activity are at increased GC risk. This study provides further support to the hypothesis that the risk of developing GC is influenced by inter-individual variation in both carcinogen detoxification and antioxidant capacity. (c) 2005 Wiley-Liss, Inc.

Aged↗
PubMed2005

Meta-analysis of risk factors for cutaneous melanoma: I. Common and atypical naevi.

A systematic meta-analysis of observational studies of melanoma and one of the most important risk factors, the number of naevi, was conducted in order to clarify aspects of the aetiology of this disease. Following a systematic literature search, relative risks (RRs) were extracted from 46 studies published before September 2002. Dose-response random effects models were used to obtain pooled estimates. Sub-group analysis and meta-regression were carried out to explore sources of between-study variation and bias. Sensitivity analyses investigated the reliability of the results and any publication bias. Number of common naevi was confirmed an important risk factor with a substantially increased risk associated with the presence of 101-120 naevi compared with <15 (pooled Relative Risk (RR) = 6.89; 95% Confidential Interval (CI): 4.63, 10.25) as was the number of atypical naevi (RR = 6.36 95%; CI: 3.80, 10.33; for 5 versus 0). The type of study and source of cases and controls were two study characteristics that significantly influenced the estimates. Case-control studies, in particular when the hospital was the source for cases or controls, appeared to present much lower and more precise estimates than cohort studies.

Adult↗
PubMed2005

Meta-analysis of risk factors for cutaneous melanoma: II. Sun exposure.

A systematic revision of the literature was conducted in order to undertake a comprehensive meta-analysis of all published observational studies on melanoma. An extensive analysis of the inconsistencies and variability in the estimates was performed to provide some clues about its Epidemiology. Following a systematic literature search, relative risks (RRs) for sun exposure were extracted from 57 studies published before September 2002. Intermittent sun exposure and sunburn history were shown to play considerable roles as risk factors for melanoma, whereas a high occupational sun exposure seemed to be inversely associated to melanoma. The country of study and adjustment of the estimates adjuste for phenotype and photo-type were significantly associated with the variability of the intermittent sun exposure estimates (P = 0.024, 0.003 and 0.030, respectively). For chronic sun exposure, inclusion of controls with dermatological diseases and latitude resulted in significantly different data (P = 0.05 and 0.031, respectively). Latitude was also shown to be important (P = 0.031) for a history of sunburn; studies conducted at higher latitudes presented higher risks for a history of sunburns. Role of country, inclusion of controls with dermatological diseases and other study features seemed to suggest that "well conducted" studies supported the intermittent sun exposure hypothesis: a positive association for intermittent sun exposure and an inverse association with a high continuous pattern of sun exposure.

Adolescent↗
PubMed2005

Meta-analysis of risk factors for cutaneous melanoma: III. Family history, actinic damage and phenotypic factors.

A systematic meta-analysis of observational studies of melanoma and family history, actinic damage and phenotypic factors was conducted as part of a comprehensive meta-analysis of all major risk factors for melanoma. Following a systematic literature search, relative risks were extracted from 60 studies published before September 2002. Fixed and random effects models were used to obtain pooled estimates for family history (RR = 1.74, 1.41-2.14), skin type (I vs. IV: RR = 2.09, 1.67-2.58), high density of freckles (RR = 2.10, 1.80-2.45), skin colour (Fair vs. Dark: RR = 2.06, 1.68-2.52), eye colour (Blue vs. Dark: RR = 1.47, 1.28-1.69) and hair colour (Red vs. Dark: RR = 3.64, 2.56-5.37), pre-malignant and skin cancer lesions (RR = 4.28, 2.80-6.55) and actinic damage indicators (RR = 2.02, 1.24-3.29). Sub-group analysis and meta-regression were carried out to explore sources of between-study variation and bias. Sensitivity analyses investigated reliability of results and publication bias. Latitude and adjustment for phenotype were two study characteristics that significantly influenced the estimates.

Humans↗
PubMed2004

Cyclosporine therapy monitored with abbreviated area under curve in nephrotic syndrome.

Cyclosporin A (CsA) is an effective therapy for children with long-lasting nephrotic syndrome (NS). Long-term treatment can result in chronic CsA nephropathy (CsAN) and there is controversy concerning its incidence and severity. Trough levels are commonly used to monitor the drug concentration. We report a retrospective clinical and histological analysis of 18 children (12 males, 6 females) with steroid-dependent nephrotic syndrome (15 patients) and partially steroid-sensitive nephrotic syndrome (3 patients) treated with CsA for a long-term period (mean 4.9 years, range 2.2-6.9). Before CsA treatment all patients had normal creatinine clearance. CsA was started at a dose of 5 mg/kg per day administered orally in two divided doses and adjusted to maintain the mean CsA blood concentration between 250 and 350 ng/ml obtained from abbreviated area under the curve (AUC). A renal biopsy was performed after a mean period of 3.9 years (range 2.2-6.2) from the start of CsA treatment. Tubular, interstitial, and arteriolar lesions were evaluated in order to assess CsAN. The mean CsA dose and the mean CsA blood concentration were 4.4 mg/kg per day (range 3.6-5.8) and 276.6 ng/ml (range 162-346), respectively. No child had a worsening creatinine clearance during CsA treatment and follow-up after CsA discontinuation. If compared with the year before the start of CsA treatment, NS relapses and prednisone (PDN) dose significantly decreased during CsA treatment, 4/year versus 0.8/year (P <0.0001) and 0.9 mg/kg per day versus 0.2 mg/kg per day (P <0.0001), respectively. Histological analysis showed 15 patients with minimal change disease and 3 with focal segmental glomerulosclerosis. Clear-cut lesions diagnostic of CsAN were never found and only mild lesions were observed in 5 children (suggestive of CsAN in 2 patients and consistent with CsAN in 3 patients). Long-term CsA treatment is confirmed to be effective in preventing NS relapses and reducing PDN dose. Renal function is not a reliable indicator of CsAN. With the mean CsA blood concentrations used in our patients CsAN presented a low incidence (28%) and was generally mild. Renal biopsy should be performed 2-3 years from the start of long-term CsA treatment, especially if the mean CsA blood concentrations are not regularly monitored.

Adolescent↗
PubMed2004

Melanoma computer-aided diagnosis: reliability and feasibility study.

BACKGROUND: Differential diagnosis of melanoma from melanocytic nevi is often not straightforward. Thus, a growing interest has developed in the last decade in the automated analysis of digitized images obtained by epiluminescence microscopy techniques to assist clinicians in differentiating early melanoma from benign skin lesions. PURPOSE: The aim of this study was to evaluate diagnostic accuracy provided by different statistical classifiers on a large set of pigmented skin lesions grabbed by four digital analyzers located in two different dermatological units. EXPERIMENTAL DESIGN: Images of 391 melanomas and 449 melanocytic nevi were included in the study. A linear classifier was built by using the method of receiver operating characteristic curves to identify a threshold value for a fixed sensitivity of 95%. A K-nearest-neighbor classifier, a nonparametric method of pattern recognition, was constructed using all available image features and trained for a sensitivity of 98% on a large exemplar set of lesions. RESULTS: On independent test sets of lesions, the linear classifier and the K-nearest-neighbor classifier produced a mean sensitivity of 95% and 98% and a mean specificity of 78% and of 79%, respectively. CONCLUSIONS: In conclusion, our study suggests that computer-aided differentiation of melanoma from benign pigmented lesions obtained with DB-Mips is feasible and, above all, reliable. In fact, the same instrumentations used in different units provided similar diagnostic accuracy. Whether this would improve early diagnosis of melanoma and/or reducing unnecessary surgery needs to be demonstrated by a randomized clinical trial.

Diagnosis, Computer-Assisted↗
PubMed2004

Vascular structures in skin tumors: a dermoscopy study.

OBJECTIVES: To describe the different vascular structures seen by dermoscopy and to evaluate their association with various melanocytic and nonmelanocytic skin tumors in a large series of cases. DESIGN: Digital dermoscopic images of the lesions were evaluated for the presence of various morphologic types of vessels. SETTING: Specialized university clinic. PATIENTS: From a larger database, 531 excised lesions (from 517 patients) dermoscopically showing any type of vascular structures were included. MAIN OUTCOME MEASURES: The frequency and positive predictive value of the different vascular structures seen in various tumors were calculated, and the differences were evaluated by the chi2 or Fisher exact test. RESULTS: Arborizing vessels were seen in 82.1% of basal cell carcinomas, with a 94.1% positive predictive value (P<.001). Dotted vessels were generally predictive for a melanocytic lesion (90.0%, P<.001), and were especially seen in Spitz nevi (77.8% of lesions). In melanoma, linear-irregular, dotted, and polymorphous/atypical vessels were the most frequent vascular structures, whereas milky-red globules/areas were the most predictive ones (77.8%, P = .003). The presence of erythema was most predictive for Clark nevus, whereas comma, glomerular, crown, and hairpin vessels were significantly associated with dermal/congenital nevi, Bowen disease, sebaceous hyperplasia, and seborrheic keratosis, respectively (P<.001 for all). CONCLUSIONS: Different morphologic types of vessels are associated with different melanocytic or nonmelanocytic skin tumors. Therefore, the recognition of distinctive vascular structures may be helpful for diagnostic purposes, especially when the classic pigmented dermoscopic structures are lacking.

Adult↗
PubMed2004

Bronchial carcinoid tumors: nodal status and long-term survival after resection.

BACKGROUND: Bronchial carcinoid tumors show a favorable outcome. We sought to determinate the variables influencing the long-term survival of patients treated for bronchial carcinoid tumors. METHODS: We conducted a retrospective single institutional review of 163 patients surgically treated from January 1990 to April 2002. According to 1999 World Health Organization criteria, cases were segregated into typical (<2 mitoses per 2 mm, no necrosis) and atypical carcinoids (2 to 10 mitoses per 2 mm or necrosis). RESULTS: There were 86 men and 77 women with a mean age of 49.5 +/- 11 years. Symptoms were present in 89 patients (54.6%). Operations included 145 formal lung resections (89%), 9 wedge resections (5.52%), 8 sleeve lobectomies (4.9%), and 1 segmental resection (0.61%) plus radical mediastinal lymphadenectomy in all cases. No operative mortality was reported. Histologic examination showed 121 (74.2%) typical carcinoids (107 N0 and 14 N1), and 42 (25.8%) atypical carcinoids (15 N0, 18 N1, 9 N2). All patients were included in a follow-up (median, 54 months; mean, 58 months; range, 4 to 150 months), which included total body computed tomographic scan and bronchoscopy every year. Overall 5-year survival was 90.3% with a mean survival time of 139 months (95% confidence interval, 133 to 145). In N0 patients with either typical or atypical carcinoid tumors, no disease-related mortality was reported (100% 5-year survival). In N1 patients, 5-year survival was 90.0% for those with typical carcinoids, and 78.8% for those with atypical carcinoids (p = 0.394). In atypical carcinoids with N2 disease, 5-year survival was 22.2%. CONCLUSIONS: Prognosis in bronchial carcinoid tumors is more related to nodal status than to histologic subtype. In N0 and N1 patients no statistical significant difference has been found between typical and atypical subtype. However, N2 bronchial carcinoid tumors show a dismal prognosis.

Adolescent↗
PubMed2004

A gene-environment interaction between occupation and BRCA1/BRCA2 mutations in male breast cancer?

The association of male breast cancer (MBC) with a positive breast cancer (BC) family history and with BRCA1/2 germ-line mutations points to a genetic component; a relationship with occupation has also been reported. Recently, we identified pathogenetic BRCA1/2 mutations in a population-based series of Italian MBC patients: here in, we investigated interactions between a carrier status for BRCA1/2 mutations and occupation using a case-case design and estimating case-only odds ratios (CORs). Truck-driving was the most frequent occupation (3/4 BRCA-related cases and 2/19 unrelated cases). An interaction between carrier status and working as a truck-driver emerged, when we classified MBC cases as "ever/never-held" this job title (COR 25.5; 95% Confidence Limits (CL): 1.1-1,412.5) or according to truck-driving as the "longest-held" work (COR 54.0; 95% CL: 1.6-2,997.5). The possible modifying effect on MBC risk in subjects carrying BRCA1/2 germ-line mutations of an occupation characterised by exposure to chemicals such as polycyclic aromatic hydrocarbons (PAH) that are capable of inducing DNA damage, may provide clues to the role of environmental exposures in modifying BC risk in mutation carriers in both genders.

Adult↗
PubMed2004

Measures of clinical severity, quality of life, and psychological distress in patients with psoriasis: a cluster analysis.

The impact of psoriasis on patients' quality of life may be quite destructive, and measures of disease status alone seem to have questionable validity in describing the true burden of illness. Our aim was to study, in patients with psoriasis, the relationship between classical measures of clinical status (i.e., PASI and SAPASI) and quality-of-life indexes (i.e., Skindex-29, Dermatology Life Quality Index, Psoriasis Disability Index, Impact of Psoriasis Questionnaire). In addition, two psychological distress indexes (i.e., Psoriasis Life Stress Inventory, 12-item General Health Questionnaire) were assessed. Data were collected between February 2000 and July 2001 at the inpatient wards of the Dermatological Institute IDI-IRCCS, Rome, Italy, in the framework of a large project on clinical, epidemiologic, emotional, and quality-of-life aspects of psoriasis. A cluster analysis of all the above-mentioned instruments was conducted on 786 eligible patients hospitalized with a diagnosis of psoriasis. Correlations between instruments were also analyzed in subsets of patients based on the main variables of interest. The instruments clustered in two distinct groups, one formed by clinical severity measurements and the other grouping all the quality-of-life and psychological indexes. The correlations between instruments observed in the subgroups determined by different sociodemographic and clinical variables showed the same pattern. In conclusion, the dissimilarity between clinical severity assessment and patient-centered measures stresses the need for a more comprehensive assessment of severity of psoriasis.

Adult↗
PubMed2004

Characterization of the anti-BP180 autoantibody reactivity profile and epitope mapping in bullous pemphigoid patients.

Bullous pemphigoid is a subepidermal bullous disease of skin and mucosae associated with autoantibodies to BP180. To characterize the humoral response to BP180, we generated a random BP180 epitope library displayed on lambda bacteriophage. After validation of the library by epitope mapping of three BP180-specific monoclonal antibodies, 15 novel or known BP180 epitopes were identified using 10 bullous pemphigoid serum samples. Fifty-seven bullous pemphigoid and 81 control sera were then assayed against the selected epitopes. Thirty-one out of 57 (54%) bullous pemphigoid sera reacted with at least an additional antigenic site other than the NC16A, within the extracellular (37%) and intracellular (28%) domains of BP180. In addition, the reactivity with extracellular epitopes of BP180 contained within the residue stretches 508-541 and 1331-1404 appeared to be related to the presence of both skin and mucosal involvement. Finally, a preliminary analysis of the epitope pattern in the disease course indicated that bullous pemphigoid patients exhibit a specific reactivity pattern, and that binding to intracellular epitopes of BP180, in addition to NC16A, may be detectable at an early clinical stage. Our findings provide novel insights into the pathophysiology of bullous pemphigoid and show the potential of the utilized approach as a tool for a rapid diagnosis of bullous pemphigoid patients and their management.

Antibodies, Monoclonal↗
PubMed2004

Dermoscopic patterns of cutaneous melanoma metastases.

Although the long experience acquired with the widespread use of dermoscopy has allowed the establishment of criteria for the recognition of benign and malignant skin lesions, very few data are available on cutaneous melanoma metastases. As the characteristic clinical aspects are multiform and even histological evaluation may sometimes be difficult, we have studied and characterized the patterns of cutaneous melanoma metastases in dermoscopy. In this paper, we report dermoscopic data on 130 histologically confirmed metastases observed in 32 patients affected by melanoma, with particular emphasis on dermoscopic features. Nine dermoscopic elements (homogeneous, saccular, amelanotic, polymorphic and vascular patterns, colour, perilesional erythema, pigmentary halo, peripheral grey spots) were studied in 130 cutaneous melanoma metastases and compared with those of 350 melanomas, 150 common naevi, 40 blue naevi, 40 haemangiomas and 50 basal cell carcinomas. The saccular and vascular patterns (especially polymorphic atypical vessels and winding vessels), as well as pigmentary halo and peripheral grey spots, seem to be the most significant elements suggestive of cutaneous melanoma metastases. The interest in and importance of the dermoscopic aspects of cutaneous melanoma metastases cannot be neglected if the American Joint Committee has determined that microsatellitosis and micrometastases are fundamental in the new TNM staging classification for cutaneous melanoma.

Adult↗