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Biomedical subjects

M Cristofolini

Publications and source records attributed to M Cristofolini.

At least 19 recordsLinked to original sources

Digital epiluminescence microscopy: usefulness in the differential diagnosis of cutaneous pigmentary lesions. A statistical comparison between visual and computer inspection.

Epiluminescence light microscopy (ELM) has been confirmed to be a useful tool for the diagnosis of pigmented skin lesions. The application of digital systems to epiluminescence represents the latest attempt to improve the diagnosis of cutaneous melanoma. The aim of this study was to compare the diagnostic accuracy of one of these systems, the DB-Dermo MIPS, with the accuracy of well-trained dermatologists using the ELM technique in order to establish the real usefulness of this instrument and to verify how much it can help the clinician make a diagnosis in a clinical setting. During a campaign for the early diagnosis of cutaneous melanoma, 311 patients with non-melanocytic lesions, common naevi, dysplastic naevi and melanomas underwent clinical diagnosis using ELM, computerized evaluation with DB-Dermo MIPS and skin biopsy. Sensitivity, specificity, true and negative predictive value were evaluated for epiluminescence and digital epiluminescence. Our study revealed that the inspection of pigmented skin lesions by digital epiluminescence has a better diagnostic accuracy than that of a trained dermatologist using the epiluminescence technique only. In our experience, this computerized system can play an essential role in the detection of early melanomas.

Diagnosis, Computer-Assisted↗

Critical effects of intense sun exposure on the expression of epiluminescence microscopy features of acquired melanocytic nevi.

BACKGROUND: Current knowledge of the histologic counterparts of epiluminescence microscopy (ELM) features in pigmented skin lesions is limited. As a particular aspect of this problem, the transient effects of intense sun exposure on the morphological characteristics of melanocytic nevi may influence the expression of ELM features as well as the demonstration of stable and consistent histologic correlates. OBSERVATIONS: Forty melanocytic nevi from 11 subjects living in Northern Italy were examined by digital ELM before and after 5 to 13 days of sun exposure at latitudes of 5 degrees north to 3 degrees south. A number of multifaceted changes were observed. In particular, 3 lesions showed the expression of some structures compatible with radial streaming, pseudopods, and gray-blue areas. These features are considered to have often severe histologic correlates. In a third image, obtained 5 to 6 weeks later, they showed partial or total regression. Another case showed a massive regression of the pigment network as a result of a progressive inflammatory reaction with marked asymmetry in the distribution of pigmentation. CONCLUSIONS: Digital ELM has the potential to detect subtle changes in the structure of nevi after intense sun exposure. The transient observation of certain ELM features often associated with severe histologic substrates casts doubts on the ability of ELM to characterize sun-exposed nevi by a single examination.

Adult↗

Morphometric analysis in prognostic evaluation of stage I thick cutaneous melanomas.

OBJECTIVE: To determine if morphometric analysis could be useful in distinguishing between good and adverse prognosis in thick melanomas. STUDY DESIGN: The study group consisted of 30 cutaneous melanomas (CM) (18 superficial spreading, 11 nodular and 1 acral lentiginous) measuring 1.5-14.8 mm in diameter. Area, perimeter, roundness and aspect ratio of 200 nuclei (100 in the superficial areas and 100 in the lower area) were morphometrically studied. After five years of follow-up, 18 patients were alive, and 12 had died of the tumor. The data were evaluated with univariate and multivariate (Cox's proportional hazard model) analysis. RESULTS: Univariate analysis showed that area and perimeter of superficial and deep nuclei were significantly larger in CM patients than in controls (10 acquired intradermal nevi). Regarding the prognostic role of the variables considered, aspect ratio of the deep nuclei (SD only) was significantly associated with prognosis. Otherwise, size factors (area and perimeter) had no prognostic value. CONCLUSION: Morphometric evaluation of nuclear shape factors in the subset of thick CM represents an additional prognostic tool with statistical significance.

Adult↗

The multicentre south European study 'Helios'. I: Skin characteristics and sunburns in basal cell and squamous cell carcinomas of the skin.

The aim of this study was to investigate constitutional and environmental determinants of non-melanocytic skin cancer among different populations from south Europe. Between 1989 and 1993 we interviewed incident cases and a random population sample of controls from five centres where a cancer registry was operating, whereas we selected a sample of hospital-based cases and controls from three other centres. Controls were stratified according to the age and sex distribution of cases. In all, 1549 cases of basal cell carcinoma (BCC), 228 of squamous cell carcinoma (SCC) and 1795 controls were interviewed. Both cancers affected primarily sun-exposed sites such as face, head and neck, but the prevalence of BCC on the trunk was higher than for SCC. Pigmentary traits such as hair and eye colour as well as tendency to sunburn were strong and independent indicators of risk for both BCC and SCC. In SCC, adjusted odds ratios (ORs) ranged from 1.6 for fair hair colour to 12.5 for red hair. Light-blonde hair entailed a risk of about 2 for BCC. Pale eye colour was associated with a risk of 1.8 for SCC and 1.4 for BCC. Subjects who always burn and never tan showed an adjusted OR of 2.7 for BCC and 2.0 for SCC. A history of sunburns and a young age at first sunburn were associated with an increased risk for BCC only (OR 1.7). Pigmentary traits and sun sensitivity of the skin confirmed their role as risk indicators. The effect of sunburns, as an indicator of both exposure and sun sensitivity of the skin, is less clear. Nevertheless, its association with BCC suggests, by analogy with melanoma, a relationship with intense sun exposure. Conversely, SCC would require prolonged exposure to sunlight.

Adolescent↗

Risk of cutaneous melanoma associated with pigmentation characteristics and freckling: systematic overview of 10 case-control studies. The International Melanoma Analysis Group (IMAGE).

Using individual subject data from 10 case-control studies, comprising over 3000 cases and almost 4000 controls, we have estimated the relative risk of melanoma associated with aspects of complexion, namely, hair, eye and skin colour and freckling in adulthood, and have examined the relationships between these factors and naevus count in terms of melanoma risk. Compared with individuals with black or dark brown hair, the relative risks for developing melanoma in those with light brown, blonde and red hair were 1.49 (95% CI 1.31, 1.70), 1.84 (95% CI 1.54, 2.21) and 2.38 (95% CI 1.90, 2.97), respectively. Individuals with blue eyes had a risk 1.55 (95% CI 1.35, 1.78) times that for those with brown eyes, or 1.15 (95% CI 0.94, 1.40) after adjusting for hair colour and freckling in adulthood. The relative risks associated with hair and eye colour were independent of those for naevus count and skin colour. Light skin colour and high freckle density were also highly significant risk factors, independent of each other and of naevus count and hair and eye colour. The risks associated with these factors, while individually modest, are largely independent, and thus pigmentation characteristics and freckling tendency should be useful in identifying high risk groups to be targeted for prevention.

Case-Control Studies↗

[Di George's syndrome with neutropenia in an adult patient].

The clinical data of a thirty-nine old inpatient woman are reported, whose main complaints were non-operable vulvo-vaginal condylomata, recurrent bacterial infections, complicated chickenpox and prominent lymphopenia. The peculiar facies get us to suggest the diagnosis of a case of the Di George syndrome in an adult patient. Was probably the associated neutropenia congenital and combined with immunodeficiency syndrome?

Adult↗

Dermatoscopy: usefulness in the differential diagnosis of cutaneous pigmentary lesions.

Dermatoscopy has been reported to give valid information in the differential diagnosis of cutaneous pigmentary lesions. Using a dermatoscopy Delta 10 Heine optotechnique, we evaluated 220 pigmented lesions during a health campaign for the early diagnosis of cutaneous melanoma and compared clinical and dermatoscopic diagnosis. Histologic diagnosis was carried out after removal of the lesions. Sensitivity, specificity, positive predictive value, negative predictive value and overall agreement were evaluated. In our experience clinical and dermatoscopic diagnosis gave similar results; sensitivity and specificity were slightly better for dermatoscopy than for clinical diagnosis. The agreement between clinical and dermatoscopic diagnosis was better in histologically negative lesions. Dermatoscopy is useful in the diagnosis of pigmentary lesions, but clinical diagnosis by experienced dermatological staff, is unreplaceable, especially during a health campaign for the early diagnosis of cutaneous melanoma.

Dermatology↗

Analysis of the cost-effectiveness ratio of the health campaign for the early diagnosis of cutaneous melanoma in Trentino, Italy.

BACKGROUND: The cost-effectiveness ratio of a health campaign for the early diagnosis of cutaneous melanoma (CM), currently the only means to reduce mortality from this melanoma, was calculated for the Trentino region in Italy. METHODS: Health campaigns in Trentino were carried out, and comparisons were made with neighboring regions where there had been no campaigns. To do this, the trend of the mortality rates calculated according to sex and age using the direct standardized method and data provided by ISTAT (the Central Italian Institute of Statistics) was considered. RESULTS: It was determined that 22.3 lives were saved by early diagnosis during the period 1977-1985, resulting in a savings of $494,636 to the Italian National Health Service in avoided treatments. The total cost to the Health Service of the campaign was $70,800. The cost per year of lives saved was calculated to be $400. CONCLUSIONS: The outcome of this campaign was a recommendation for the use of such programs in other countries and regions.

Aged↗

Effectiveness of the health campaign for the early diagnosis of cutaneous melanoma in Trentino, Italy.

BACKGROUND: To reduce the mortality rate from cutaneous melanoma in Trentino, a health campaign for early diagnosis aimed at the general public was organized. OBJECTIVE: The mortality rate from cutaneous melanoma in Trentino before and after our health campaign was analyzed and compared with the mortality rates in three neighboring regions where no campaigns were carried out. METHODS: The mortality for cutaneous melanoma was analyzed using data from the death certificates provided by ISTAT for the pre- and postcampaign periods. The two summary methods: cumulative rate and the standard mortality ratio were used. RESULTS: The cumulative mortality rates in the neighboring regions show a tendency to increase over the three periods whereas the increase in Trentino is less evident. The standard mortality ratios confirmed this result. CONCLUSION: We feel that this type of campaign is to be recommended in the reduction of mortality from cutaneous melanoma.

Death Certificates↗

p53 Protein expression in nevi and melanomas.

p53 Protein immunohistochemical expression is a wide-spread feature of the malignant phenotype; most melanomas are reported as p53 positive, while nevi are reported as p53 negative. We investigate a series of 75 benign nevi and 47 melanomas (40 primary and seven metastatic) to evaluate their pattern of p53 immunoreactivity with a panel of specific antibodies (PAb1801, PAb240, DO7, and CM1) in view of a possible diagnostic role of p53 immunostaining. Our results demonstrate that 15% of nevi show p53 immunoreactive nuclei (usually in less than 1% of the cells) and that 30% of melanomas show p53 immunoreactive nuclei (one case with 20% immunoreactive cells, six cases with 1% to 5% positive cells, and four cases with less than 1% positive nuclei). p53 Positivity was seen also in basal and suprabasal keratinocytes. p53 Positivity in nevi is at variance with literature data supporting that nevi are p53 negative. p53 Positivity in nevi and in epidermis may be related to mechanisms of DNA repair, apoptosis, or to a specific phase of the cell cycle. In our series, p53 expression in melanomas is not as frequent as reported in the literature. Population-based differences or differences in case selection and sample handling may account for the above discrepancies. The demonstration of p53 positivity in benign skin lesions greatly hinders the possibility of a diagnostic use of p53 immunostaining in dermatopathology.

Adolescent↗

The epidemiology of cutaneous malignant melanoma: aetiology and European data.

Increases in cutaneous malignant melanoma (CMM) incidence and mortality rates have occurred in the last decades in virtually all white populations, more markedly in those which permanently (immigrants) or temporarily (tourists/vacationers) reside in very sunny areas distant from their original living environment. The strong relationship between sex and site of CMM in these upward trends (ie trunk in males, lower limbs and, more recently, trunk as well in females) points to intense intermittent ultraviolet light exposure as the cause of the CMM epidemic. In Europe the highest rates of melanoma are seen in Denmark, The Netherlands, the United Kingdom, Ireland and Germany, where many individuals have light complexion with tendency to burn. Increases of 2 to 7% per year in mortality rates appeared earlier in these countries, but were subsequently seen also in relatively low-risk areas such as southern European countries. The interpretation of data from case-control studies is, however, hampered by the difficulties in quantifying retrospectively CMM risk correlates (ie host factors, sun exposure, clothing habits, sunburns etc) in various periods during the life span.

Adult↗

Malignant blue nevus. Report of four new cases and review of the literature.

Malignant blue nevus is a rare melanotic tumor of the skin arising from a pre-existing blue nevus. To date only few cases have been reported. The diagnosis of malignant blue nevus is frequently difficult. Generally accepted criteria do exist, but their application may be controversial. The present paper reports four new cases of malignant blue nevus with follow-up of 3-5 years. Our present data, along with those of the literature, suggest that malignant blue nevus may be more aggressive than generally thought.

Adult↗

Azapsoralens: new potential photochemotherapeutic agents for psoriasis.

New bioisoters of psoralen, obtained by replacing carbon 8 of the central benzene ring with a nitrogen, were studied from the photochemical, photobiological and phototherapeutic points of view. In particular, 4,4'-, 4',5'-dimetyl, 4,4',5'-trimethyl and 3,4,4',5'-tetramethylazapsoralen were studied. The crystal and molecular structure of 4,4',5'-trimethylazapsoralen, obtained by X ray diffraction, was also reported. Like psoralen, these compounds form a molecular complex with DNA, undergoing intercalation inside the double helix of the macromolecule. When irridiated with long ultraviolet light (365 nm), the intercalated drug photoconjugates covalently to the macromolecule, forming mono- and diadducts. The photobinding rate show the following order of magnitude: 4,4',5'-trimetylazapsoralen (4,4',5'-TMAP) = 3,4,4',5'-tetramethylazapsoralen (3,4,4',5'-TMAP) greater than 4',5'-dimethylazapsoralen (4',5'-DMAP) = 4,4'-dimethylazapsoralen (4,4'-DMAP). The DNA photobinding rate of 8-methoxypsoralen (8-MOP), taken as reference compound, is similar to that of the two dimetylazapsoralens but lower than tri- and tetramethyl derivatives. The ability of azapsoralens to form cross-links in DNA is lower than that of 8-MOP. However, capacity to induce cross-links does not parallel the DNA photobinding rate; it is higher for trimethyl derivate and lower for tetramethylazapsoralen. Azapsoralens show evident antiproliferative activity. The trimethyl derivative is the most active, followed by tetrametyl, both these compounds showing activity slightly higher than that of 8-MOP. The two dimethylderivatives are less active. The mautagenic activity of azapsoralens on E. coli WP2 TM6 is lower than that of 8-MOP in the same conditions. The new compounds do not show any skin phototoxicity on guinea pig skin. On the basis of its DNA photobinding, antiproliferative activity, mutagenicity and lack of skin phototoxicity, 4,4',5'-TMAP was chosen for clinical evaluation. Clinical results obtained by topical treatment of psoriatic plaques reveal evident therapeutic effectiveness and clearing is between good and moderate, although 8-MOP, used as reference compound, is more effective.

Animals↗

6-Methylangelicins: new monofunctional photochemotherapeutic agents for psoriasis.

The monofunctional furocoumarins, the 6-methylangelicins, were tested for their antiproliferative activity with various animal models and for genotoxicity in micro-organisms and in mammalian cells. The most active compound was 6,4,4'-trimethylangelicin, which showed a high antiproliferative effect and reduced genotoxicity in comparison with 8-methoxypsoralen (8-MOP). Some of these compounds were also tested clinically by topical application on 17 patients with psoriasis. They appeared to be more active than 8-MOP in clearing psoriasis without inducing skin phototoxicity. The methylangelicins also caused skin pigmentation.

Animals↗

Risk factors for cutaneous malignant melanoma in a northern Italian population.

The relationship between cutaneous malignant melanoma (CMM) and the colour of skin, hair and eyes, the extent of sun exposure and reaction to it, education, and the occurrence of skin neoplasms in patients and their families was evaluated in a case-control study of 103 cases of CMM and 205 control subjects hospitalized for acute conditions other than malignant or hormonal disease. A significantly higher risk was associated with fair skin as compared to dark/medium skin (RR = 4.0; 95% CI: 1.5-10.5) and positive family history for CMM (RR = 8.1; 95% CI: 1.0-200.9). CMM seemed to occur more frequently, but not significantly so, in individuals with brown or blond hair, higher education and clinically diagnosed dysplastic naevi. Outdoor occupation and heavy sun exposure in the last 20 years seemed to increase the risk of CMM in sun-exposed sites but to be negatively associated with CMM in normally unexposed sites.

Adult↗