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Biomedical subjects

S Sestini

Publications and source records attributed to S Sestini.

At least 19 recordsLinked to original sources
PubMed2006

Dermoscopy in black people.

BACKGROUND: Little is known about the use of dermoscopy in nonwhite-skinned populations and whether it can influence diagnostic performance. OBJECTIVES: To evaluate for the first time the utility and efficacy of dermoscopy in a black population for the diagnosis of pigmented cutaneous lesions. METHODS: In total, 100 consecutive clinically doubtful or equivocal pigmented skin lesions in black patients were submitted to dermoscopic examination. The lesions were observed using dermoscopy by two groups of dermatologists, one in Brazil (in vivo) and the other in Italy (on slide images). Besides diagnosis, each group recorded on the same type of form the dermoscopic features present. RESULTS: Of 100 clinically suspicious cases, 79 were Clark naevi, 15 seborrhoeic keratoses, four blue naevi, one dermatofibroma and one melanoma. The two groups of observers succeeded in identifying and classifying all the lesions to such a margin of diagnostic accuracy that only a few cases (three Clark naevi) were subjected to surgical excision to confirm diagnosis. CONCLUSIONS: Darker pigmentation of the skin does not impede the identification of single dermoscopic features. As in lighter-skinned populations, dermoscopy in black people can also lead to early and accurate diagnosis of melanoma, thereby significantly reducing the number of unnecessary excisions.

Black People↗
PubMed2005

Cutaneous collision tumour (melanocytic naevus, basal cell carcinoma, seborrhoeic keratosis): a clinical, dermoscopic and pathological case report.

The association of contiguous or 'collision' tumours in the same biopsy specimen is not uncommon and is often reported in the literature. The most common association, basal cell carcinoma (BCC) and naevus, is very difficult to diagnose clinically. We describe a 38-year-old woman with a previous history of melanoma, who presented with a modified pigmented lesion of the hip that had begun to change 6 months earlier. Histologically, the lesion was a melanocytic compound naevus and a BCC with a seborrhoeic keratosis. The case was investigated clinically and by focusing on the dermoscopic features and their pathological correlates. Cutaneous collision tumours are extremely difficult to diagnose preoperatively, even with the help of dermoscopy, in particular when one of the lesions is melanocytic.

Adult↗
PubMed2004

Are allopurinol and metabolites found in HPRT deficient erythrocytes responsible for increased NAD synthesis?

Aim of this study was to ascertain whether allopurinol, usually administered to hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficient patients, or metabolites abnormally increased in HPRT deficient erythrocytes (NAD, PPribP) could be directly responsible for the reported increased activities of nicotinic acid phosphoribosyltransferase (NAPRT) and NADsynthetase (NADs) in these patients. No direct effect of the mentioned metabolites was demonstrated.

Allopurinol↗
PubMed2003

Encephalopathy associated with Hashimoto's thyroiditis: an additional case.

A 35-year-old female with a history of Hashimoto's thyroiditis (HT) presented with episodic dysphasia and a burst of axial jerks with abdominal muscle contraction and asymmetric blepharospasm as manifestations of encephalopathy associated with HT. Brain magnetic resonance imaging (MRI) showed scattered supratentorial white matter hyperintense T2 foci. Brain single photon emission computerized tomography (SPECT) demonstrated a cortical hypoperfusion in the upper frontal and parietal areas. Corticosteroid therapy induced a rapid improvement of the clinical picture.

Journal Article↗
PubMed2003

Pattern analysis, not simplified algorithms, is the most reliable method for teaching dermoscopy for melanoma diagnosis to residents in dermatology.

BACKGROUND: Simplified algorithms for dermoscopy in melanoma diagnosis were developed in order to facilitate the use of this technique by non-experts. However, little is known about their reliability compared with classic pattern analysis when taught to untrained observers. OBJECTIVES: To investigate the diagnostic performance of three different methods, i.e. classic pattern analysis and two of the most used algorithms (the ABCD rule of dermoscopy and the seven-point check-list) when used by newly trained residents in dermatology to diagnose melanocytic lesions. Methods Five residents in dermatology (University of Florence Medical School) were submitted to a teaching programme in dermoscopy based on both formal lessons and training and self-assessment using a newly developed, interactive CD-ROM on dermoscopy. The performance of the three diagnostic methods was analysed in a series of 200 clinically equivocal melanocytic lesions including 44 early melanomas (median thickness 0.30 mm; 25th-75th percentile 0.00-0.58 mm). RESULTS: Pattern analysis yielded the best mean diagnostic accuracy (68.7%), followed by the ABCD rule (56.1%) and the seven-point check-list (53.4%, P = 0.06). The best sensitivity was associated with the use of the seven-point check-list (91.9%), which, however, provided the worst specificity (35.2%) of the methods tested. The interobserver reproducibility, as shown by kappa statistics, was low for all the methods (range 0.27-0.33) and did not show any statistical difference among them. CONCLUSIONS: Pattern analysis, i.e. simultaneous assessment of the diagnostic value of all dermoscopy features shown by the lesion, proved to be the most reliable procedure for melanoma diagnosis to be taught to residents in dermatology.

Algorithms↗
PubMed2001

Metabolic fate of extracellular NAD in human skin fibroblasts.

Extracellular NAD is degraded to pyridine and purine metabolites by different types of surface-located enzymes which are expressed differently on the plasmamembrane of various human cells and tissues. In a previous report, we demonstrated that NAD-glycohydrolase, nucleotide pyrophosphatase and 5'-nucleotidase are located on the outer surface of human skin fibroblasts. Nucleotide pyrophosphatase cleaves NAD to nicotinamide mononucleotide and AMP, and 5'-nucleotidase hydrolyses AMP to adenosine. Cells incubated with NAD, produce nicotinamide, nicotinamide mononucleotide, hypoxanthine and adenine. The absence of ADPribose and adenosine in the extracellular compartment could be due to further catabolism and/or uptake of these products. To clarify the fate of the purine moiety of exogenous NAD, we investigated uptake of the products of NAD hydrolysis using U-[(14)C]-adenine-NAD. ATP was found to be the main labeled intracellular product of exogenous NAD catabolism; ADP, AMP, inosine and adenosine were also detected but in small quantities. Addition of ADPribose or adenosine to the incubation medium decreased uptake of radioactive purine, which, on the contrary, was unaffected by addition of inosine. ADPribose strongly inhibited the activity of ecto-NAD-hydrolyzing enzymes, whereas adenosine did not. Radioactive uptake by purine drastically dropped in fibroblasts incubated with (14)C-NAD and dipyridamole, an inhibitor of adenosine transport. Partial inhibition of [(14)C]-NAD uptake observed in fibroblasts depleted of ATP showed that the transport system requires ATP to some extent. All these findings suggest that adenosine is the purine form taken up by cells, and this hypothesis was confirmed incubating cultured fibroblasts with (14)C-adenosine and analyzing nucleoside uptake and intracellular metabolism under different experimental conditions. Fibroblasts incubated with [(14)C]-adenosine yield the same radioactive products as with [(14)C]-NAD; the absence of inhibition of [(14)C]-adenosine uptake by ADPribose in the presence of alpha-beta methyleneADP, an inhibitor of 5' nucleotidase, demonstrates that ADPribose coming from NAD via NAD-glycohydrolase is finally catabolised to adenosine. These results confirm that adenosine is the NAD hydrolysis product incorporated by cells and further metabolized to ATP, and that adenosine transport is partially ATP dependent.

Adenosine Triphosphate↗
PubMed2001

Recruitment of dendritic cells and enhanced antigen-specific immune reactivity in cancer patients treated with hr-GM-CSF (Molgramostim) and hr-IL-2. results from a phase Ib clinical trial.

Experimental findings suggest that granulocyte-monocyte-colony stimulating factor (GM-CSF) synergistically interacts with interleukin-2 (IL-2) in generating an efficient antigen-specific immune response. We evaluated the toxicity, antitumour activity and immunobiological effects of human recombinant (hr)-GM-CSF and hr-IL-2 in 25 cancer patients who subcutaneously (s.c.) received hr-GM-CSF 150 microg/day for 5 days, followed by hrIL-2 s.c. for 10 days and 15 days rest. Two of the most common side-effects were bone pain and fever. Of the 24 patients evaluable for response, 3 achieved partial remission, 13 experienced stable disease, and 8 progressed. Cytokine treatment increased the number of monocytes, dendritic cells (DC), and lymphocytes (memory T cells) in the peripheral blood and enhanced the antigen-specific immunoreactivity of these patients. Our results show that the hr-GM-CSF and hr-IL-2 combination is active and well tolerated. Its biological activity may support tumour associated antigen (TAA)-specific anticancer immunotherapy by increasing antigen presenting cell (APC) activity and T cell immune competence in vivo.

Aged↗
PubMed2000

Enzyme activities leading to NAD synthesis in human lymphocytes.

Pyridine nucleotide levels and the activities of enzymes involved in NAD synthesis (nicotinic acid phosphoribosyltransferase, nicotinic acid- and nicotinamide mononucleotide-adenylyltransferase) have been assayed in human normal lymphocytes by an HPLC method using radioactive or nonradioactive substrates. NAD concentration was 46.4 +/- 17.2 pmol 10(-6) cells, and that of NADP was 14.5 +/- 3.9 pmol 10(-6) cells (mean +/- standard deviation). The adenylyltransferase activity using nicotinic acid mononucleotide as substrate was 1.530 +/- 0.216 nmol h(-1) 10(-6) cells, using nicotinamide mononucleotide was 1.466 +/- 0.354 nmol h(-1) 10(-6) cells. The apparent K(M) values were 0.015 mM for the former substrate and 0.167 mM for the latter. The mean activity of nicotinic acid phosphoribosyltransferase was 0.038 +/- 0.014 nmol h(-1) 10(-6) cells, and the apparent K(M) for nicotinic acid was 0.165 mM. The proposed methods, easy and rapid to perform, are reliable and sensitive, avoiding the use of radiolabels except for NAPRT and displaying a very low activity. The reported findings, together with the previous ones in human erythrocytes, can provide an useful base to investigate NAD metabolism in humans through the study of blood cells.

Adenosine Triphosphate↗
PubMed2000

Use of technetium-99m hexamethylpropylene amine oxime SPET for the study of cerebral blood flow reactivity after acetazolamide infusion in patients with Behçet's disease.

The purpose of this study was to characterise the nature of the baseline perfusion defects found in patients with Behçet's disease using hexamethylpropylene amine oxime single-photon emission tomography in conjunction with acetazolamide test (Acz SPET). Eleven patients underwent both baseline and Acz SPET. Regions of interest (ROIs) were drawn on the areas with decreased perfusion (D-ROI) and, in the same section, on areas with normal perfusion (N-ROI). The ROIs were then repositioned on the corresponding section on Acz SPET. The mean ROI counts were then transformed into a perfusion index value (PIV) with reference to the global brain counts. In total we found 24 D-ROIs (17 in the cortical and 7 in subcortical grey matter). The influence of Acz infusion was selectively registered in the D-ROIs, where PIVs changed from 1.23+/-0.17 (baseline SPET) to 1.63+/-0.23 (Acz SPET) (P<0.001). No significant difference was seen in the N-ROIs (1.46+/-0.21 and 1.40+/-0.17, respectively, on baseline SPET and Acz SPET). Our results demonstrate that Acz infusion increases the regional cerebral blood flow within baseline grey matter perfusion defects. This finding suggests that baseline perfusion abnormalities could reflect a disconnection rather than local vasculitic involvement.

Acetazolamide↗
PubMed2000

Progestin regulation of 11beta-hydroxysteroid dehydrogenase expression in T-47D human breast cancer cells.

This study examined the enzymatic characteristics and steroid regulation of the glucocorticoid-metabolizing enzyme 11beta-hydroxysteroid dehydrogenase (11beta-HSD) in the human breast cancer cell line T-47D. In cell homogenates, exogenous NAD significantly increased the conversion of corticosterone to 11-dehydrocorticosterone, while NADP was ineffective. There was no conversion of 11-dehydrocorticosterone to corticosterone either with NADH or NADPH demonstrating the lack of reductase activity. In keeping with these results, RT-PCR analysis indicated a mRNA for 11beta-HSD2 in T-47D cells, while 11beta-HSD1 mRNA levels were undetectable. In T-47D cells treated for 24 h with medroxyprogesterone acetate (MPA), 11beta-HSD catalytic activity was elevated 11-fold, while estrone (E(1)), estradiol (E(2)) and the synthetic glucocorticoid dexamethasone (DEX) were ineffective. The antiprogestin mifepristone (RU486) acted as a pure antagonist of the progestin-enhanced 11beta-HSD activity, but did not exert any agonistic effects of its own. In addition, RT-PCR analysis demonstrated that MPA was a potent inducer of 11beta-HSD2 gene expression, increasing the steady-state levels of 11beta-HSD2 mRNA. Taken together, these results demonstrate that 11beta-HSD2 is the 11beta-HSD isoform expressed by T-47D cells under steady-state conditions and suggest the existence of a previously undocumented mechanism of action of progestins in breast cancer cells.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed1999

Hypoxanthine-guanine phosphoribosyltransferase deficiency and erythrocyte synthesis of pyridine coenzymes.

Purine and pyridine metabolism were studied in ten Lesch-Nyhan patients, with virtually no hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity in erythrocytes. Increased NAD erythrocyte concentrations were found in all patients. Raised activities of two enzymes catalysing NAD synthesis from nicotinic acid (nicotinic acid phosphoribosyltransferase: NAPRT, and NAD synthetase: NADs) was found in erythrocyte lysates from all patients. The two enzymes had normal apparent Km for their substrates and increased Vmax. The rate of synthesis of pyridine nucleotides from nicotinic acid by intact erythrocytes in vitro was also increased in most patients. These findings suggest that raised NAD concentrations in HPRT- erythrocytes are due to enhanced synthesis as a result of increased enzyme activities.

Adolescent↗
PubMed1999

Expression of 11 beta-hydroxysteroid dehydrogenase in early pregnancy: implications in human trophoblast-endometrial interactions.

Glucocorticoid hormone action in target tissues is modulated by 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), which interconverts active cortisol and corticosterone and their inert 11-keto metabolites, cortisone and 11-dehydrocorticosterone. Two different 11 beta-HSD isoforms exist: a low-affinity NADP-dependent dehydrogenase/oxoreductase (11 beta-HSD1) and a high-affinity NAD-dependent dehydrogenase (11 beta-HSD2). This brief review describes the expression and distribution of 11 beta-HSD isoforms in human placenta. In particular, it discusses the results of studies dealing with the expression of 11 beta-HSD activity in experimental models representative of the fetomaternal interface in the early gestation. The findings have implications in terms of protection of the fetus against corticosteroid toxicity and modulation of active glucocorticoid levels and their biological effects in early pregnancy.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1999

Detecting myocardial salvage after primary PTCA: early myocardial contrast echocardiography versus delayed sestamibi perfusion imaging.

UNLABELLED: The extent of myocardial salvage after primary percutaneous transluminal coronary angioplasty (PTCA) in acute myocardial infarction (AMI) is variable and cannot be predicted on the basis of either vessel patency or early regional wall motion assessment. The aim of this study was to evaluate the reliability of microvascular integrity, as shown by myocardial contrast echocardiography (MCE), as an indicator of tissue salvage and a predictor of late functional recovery, and to compare MCE with the quantification of tracer activity in sestamibi perfusion imaging. METHODS: Twenty-six patients with AMI who received successful treatment with primary PTCA were examined with MCE during cardiac catheterization immediately before and after vessel recanalization. Myocardial contrast effect was scored as 0 (absent), 0.5 (partial) or 1 (normal). Wall motion was assessed by two-dimensional echocardiography on admission and 1 mo later with a 16-segment model and 4-point score. Resting sestamibi SPECT was collected within 1 wk after AMI. The risk area was defined by MCE as the sum of the segments with no perfusion (score 0) before PTCA. Myocardial viability was defined by MCE as an increase in contrast score in the same segments after PTCA and by sestamibi SPECT as a preserved tracer activity (>60% of peak activity). The functional recovery after 1 mo detected by two-dimensional echocardiography was the reference standard for viability. RESULTS: A total of 50 segments showed perfusion defects before PTCA (risk area). Immediately after PTCA, the MCE score increased in 44 of 50 segments, whereas sestamibi SPECT showed preserved activity in 22 of 50 segments. After 1 mo, the wall motion score decreased in 22 of 50 segments (viable segments) and was unchanged in the remaining 28 segments. Thus, MCE showed a sensitivity of 91% and a specificity of 14% in detecting viable myocardium, whereas sestamibi SPECT showed a lower sensitivity (68%) but a significantly higher specificity (75%; P < 0.00001). The positive predictive values were 45% and 68% for MCE and SPECT (P < 0.005), respectively, and the negative predictive values were 67% and 71%, respectively. On a patient basis, SPECT was more specific (79% versus 21%; P < 0.01) and showed a higher overall predictive accuracy (88% versus 50%; P < 0.01) than MCE. CONCLUSION: The demonstration of microvascular integrity by MCE performed immediately after primary PTCA has a limited diagnostic value in predicting salvaged myocardium. Conversely, tracer activity quantification in resting sestamibi SPECT performed in a later stage is confirmed to be a reliable approach for recognizing myocardial stunning and predicting functional recovery.

Angioplasty, Balloon, Coronary↗
PubMed1998

11Beta-hydroxysteroid dehydrogenase expression in first trimester human trophoblasts.

This study evaluated the levels and the enzymatic characteristics of 11beta-hydroxysteroid dehydrogenase activity (11beta-HSD) of chorionic villi isolated from first trimester human placenta. The results demonstrated a predominant expression of the NAD-dependent dehydrogenase isoform (11beta-HSD2) over the NADP-dependent oxoreductase (11beta-HSD1). Thus, in tissue homogenates exogenous NAD increased the conversion of corticosterone to 11-dehydrocorticosterone of about 14-fold while NADP was ineffective. There was no conversion of 11-dehydrocorticosterone to corticosterone either with NADH or NADPH demonstrating the lack of reductase activity. In keeping with these results, RT-PCR analysis indicated a mRNA for 11beta-HSD2 in villous tissue while 11beta-HSD1 mRNA levels were undetectable. In addition, immunohistochemical staining localized the 11beta-HSD2 protein to syncytiotrophoblasts and cell columns of the chorionic villi. These results suggest roles for the trophoblast-associated 11beta-HSD2 oxidative activity in modulating the exposure of the embryo to active glucocorticoids in the early gestation and in regulating trophoblasts invasion of the uterine wall.

11-beta-Hydroxysteroid Dehydrogenases↗