Novel CNS syndrome and ectodermal dysplasia.
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Biomedical subjects
Publications and source records attributed to R Perotti.
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BACKGROUND: Early detection of melanomas by means of diverse screening campaigns is an important step towards a reduction in mortality. Computer-aided analysis of digital images obtained by dermoscopy has been reported to be an accurate, practical and time-saving tool for the evaluation of pigmented skin lesions (PSLs). A prototype for the computer-aided diagnosis of PSLs using artificial neural networks (NNs) has recently been developed: diagnostic and neural analysis of skin cancer (DANAOS). OBJECTIVES: To demonstrate the accuracy of PSL diagnosis by the DANAOS expert system, a multicentre study on a diverse multinational population was conducted. METHODS: A calibrated camera system was developed and used to collect images of PSLs in a multicentre study in 13 dermatology centres in nine European countries. The dataset was used to train an NN expert system for the computer-aided diagnosis of melanoma. We analysed different aspects of the data collection and its influence on the performance of the expert system. The NN expert system was trained with a dataset of 2218 dermoscopic images of PSLs. RESULTS: The resulting expert system showed a performance similar to that of dermatologists as published in the literature. The performance depended on the size and quality of the database and its selection. CONCLUSIONS: The need for a large database, the usefulness of multicentre data collection, as well as the benefit of a representative collection of cases from clinical practice, were demonstrated in this trial. Images that were difficult to classify using the NN expert system were not identical to those found difficult to classify by clinicians. We suggest therefore that the combination of clinician and computer may potentially increase the accuracy of PSL diagnosis. This may result in improved detection of melanoma and a reduction in unnecessary excisions.
BACKGROUND: The term 'common mole', often used to describe a subset of benign pigmented skin lesions, is traditionally defined on the basis of morpho-chromatic features. In recent years, certain research groups have developed equipment and methods, such as digital dermoscopy analysis, that enable objective evaluation of pigmented skin lesions. OBJECTIVE: In this study we use a digital dermoscopy analyser trained for the recognition of pigmented skin lesions to compare the subjective definition of 'common' and the mathematical concept of 'close to the mean of measurements'. METHODS: A subset (100) of digital images of flat pigmented lesions, obtained in daily practice, were classified by trained and non-expert clinicians as common moles (60) or clear-cut melanoma (40), and processed with a DB-Mips analyser. The resulting parameters, validated by a classifier, were used to evaluate Hotelling's T2 multivariate distances from the mean. RESULTS: 'Common' moles could not be clearly defined in terms of closeness to the means of objectively evaluated parameters. Their diagnosis indudes many other evaluations and clusters of variables. CONCLUSION: The clinical semantics of the term 'common' does not conform to any unambiguous mathematical definition.
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We report on a 2-year-old girl with a de novo mutation [45,XX,der(5),t(5;14) (pter;q11.2)] with corpus callosum agenesis, multiple cysts (cerebral and cardiac), subtle eye abnormalities, and at least two different skin defects, strongly indicating neuroectodermal involvement, as a neuromuscular choristoma (hamartoma) and an eccrine hamartoma. Fluorescent in situ hybridization with different single-locus probes showed that chromosome 5 has a very small deletion, confined to a region composed of repetitive sequences. By contrast, the long (q) arm of chromosome 14 seems to be much more involved in the rearrangement, with partial monosomy spanning from the centromere to the D14S72 and D14S261 loci. The extent of the deleted region of chromosome 14 is approximately 16 cM. To our knowledge, this is the smallest reported deletion involving the chromosome 14q11.2 region to be associated with a developmental disorder resulting in variable eye, skin, and brain anomalies. We suggest that a new syndrome, mimicking in some ways the MLS phenotype, is caused by a deletion in the chromosome 14q11.2 region.
Epiluminescence light microscopy (ELM) has proven useful in the diagnosis of pigmented skin lesions (PSLs). However, in some cases this technique does not sufficiently increase the diagnostic accuracy in distinguishing pigmented Spitz naevi (PSNs) from melanoma. With the aim of obviating these problems of qualitative interpretation, methods based on the mathematical analysis of PSLs, such as digital dermoscopy analysis (DDA), have recently been developed. In the present study we used a digital dermoscope (DBDermo-MIPS, Dell'Eva-Burroni) to analyse PSNs and melanomas with similar clinical and dermoscopic features for any correlation between variables and to determine its discriminating power with respect to histological diagnosis. The 100 lesions underwent histological examination by three experienced dermatopathologists and were identified as PSNs (43) or melanomas (57). Thirty-six parameters were identified as possible discriminating variables and were grouped in four categories: geometry, colour, texture, and islands of colour. Statistical analysis was used to identify the variables with the highest discriminating power. Stepwise discriminant analysis selected only four variables: entropy, minimum diameter, red lesion value and peripheral dark (the means of these variables were higher in melanomas than in PSNs). Thus the combined use of digital dermoscopy and stepwise logistic discriminant analysis made it possible to single out the best objective variables for distinguishing PSN and melanoma.
Telomerase plays a key role in carcinogenesis. It is activated in most immortal cell lines and human cancers, including cutaneous melanoma (CM). Increased cell proliferation and deregulation of the cell cycle occur in human cancers. Links between telomerase activity (TA), cell proliferation, cell death and expression of cell-cycle regulators have not been extensively elucidated in CM. In this study, we investigated TA, mitotic index (MI), apoptotic index (AI), Ki-67 and nuclear positivity of cyclins D1 and A (Ki-67+ N/1,000, cyclin D1+N/1,000, cyclin A+N/1,000) in 42 primary cutaneous melanomas (PCMs). TA was detected in all cases and directly correlated with MI, Ki-67+N/1,000, cyclin D1+N/1,000 and cyclin A+N/1,000 (p < 0.001); it was not correlated with AI. When subdividing PCMs into radial and vertical growth phase melanomas (RGPMs, VGPMs), a correlation was maintained only with MI (p < 0.005) and cyclin D1 +N/1,000 (p < 0.005). Although MI and Ki-67+N/1,000 were highly correlated with cyclin D1+N/1,000 and cyclin A+N/1,000 (p < 0.001) when considering all cases together, a high correlation was found in the RGPM and VGPM groups between cyclin A+N/1,000 and Ki-67+N/1,000 only (p < 0.001), thus suggesting that cyclin A is more closely correlated with cell proliferation than cyclin D1. Our results further support the association between TA, tumor cell proliferation and cyclin D1 and A expression in PCM, though it is possible that links between TA and proliferation, on the one hand, and TA and cyclin D1 expression, on the other, might occur following various pathways.
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OBJECTIVES: To use a digital dermoscopy analyzer with a series of "borderline" pigmentary skin lesions (ie, clinically atypical nevi and early melanoma) to find correlation between the studied variables and to determine their discriminating power with respect to histological diagnosis. DESIGN: A total of 147 pigmentary skin lesions were histologically examined by 3 experienced dermatopathologists and identified as nevi (n = 90) and melanomas (n = 57). The system evaluated 36 variables to be studied as possible discriminant variables, grouped into 4 categories: geometries, colors, textures, and islands of color. SETTING: University medical department. PATIENTS: A sample of patients with excised pigmentary skin lesions (nevi and melanomas). MAIN OUTCOME MEASURES: Sensitivity, specificity, and accuracy of the model for evaluating "borderline" pigmentary skin lesions. RESULTS: After multivariate stepwise discriminant analysis, only 13 variables were selected to compute the canonical discriminant function. CONCLUSION: The present method made it possible to determine which objective variables are important for distinguishing atypical benign pigmentary skin lesions and early melanoma.
A modern AmpHel pH-meter permits the easy determination of dental materials pH. This new instrument has allowed, analysing seven cements and two varnishes used for pulpodentinal protection, continuously to specify this important parameter's modifications in the long run. The results of this study, conducted for six hours after cement mixing or varnishes application, certified glass ionomer cements' (Ketac-Cem, Fuji-Ionomer II) strong acidity, even higher than well known zinc phosphates' acidity is. A cavity liner's (Tubulitec) pH from an initial value of 6.07 decreased to 5.04 at sixth hour. On the contrary, much lower were the acidity of a modified ZOE (Temrex) and the one of a cavity varnish (Copalite): both showed a physiological pH from the beginning of the test.
Aim of the study was to assess the relative susceptibility to the development of nitroglycerin tolerance in the arterial and venous circulation in man and to evaluate the interactions between nitroglycerin and N-acetylcysteine. Twenty patients with coronary artery disease underwent a continuous 24-h nitroglycerin infusion followed by a bolus administration of N-acetylcysteine. Forearm blood flow (ml/100 ml/min) and venous volume (ml/100 ml) were measured by strain gauge plethysmography under control conditions, at the end of nitroglycerin titration, after 24 h of infusion and after N-acetylcysteine; vascular resistance was calculated as mean cuff blood pressure/flow. After 24 h of nitroglycerin infusion, the initial increase in venous volume was reduced by 48% (p < 0.01), while the acute effects on vascular resistance were not attenuated in the whole group. N-acetylcysteine restored nitroglycerin venodilator effects in all 10 patients who developed venous tolerance but did not change significantly vascular resistance in 5 patients in whom attenuation of the arterial effects was observed during the infusion period. In conclusion, the results indicate that the susceptibility to the development of nitrate tolerance in man is higher in the venous than in the arterial circulation and that the sulphydryl group donor N-acetylcysteine is more effective in reversing nitroglycerin tolerance in the venous than in the arterial circulation.
BACKGROUND AND METHODS: We analyzed the complications of 1729 pacemakers implants (from October 1980 to December 1992) divided according to the way of leads insertion. The approaches from the subclavian vein was used in 1220 cases, the cephalic vein was used in 431 implants and the external jugular vein in 78. RESULTS: Major complications were: pocket bleeding (108 cases), pocket erosion (15 cases), infection (2 cases), lead fracture (5 cases), lead dislodgement (20 cases), pneumothorax (4 cases, only for subclavian puncture). There were no significative differences in the complications between the three approaches. On the other hand, the subclavian puncture reduces the time of the procedure, is less traumatic and allows to insert and to position several leads. CONCLUSIONS: We suggest to use the subclavian vein approach as first choice to implant one or more leads, being this way safe and fast.
BACKGROUND: Tolerance to the effects of organic nitrates develops rapidly during continuous exposure to these drugs; its main mechanism seems to be an intracellular sulfhydryl group depletion. However, the relative susceptibility to the development of nitroglycerin tolerance of the arterial or venous circulation in humans is still a matter of dispute. METHODS AND RESULTS: Twenty patients with coronary artery disease underwent a continuous 24-hour nitroglycerin infusion followed by a bolus administration of N-acetylcysteine. Forearm blood flow (ml/100 ml/min) and venous volume (ml/100 ml) were measured by strain gauge plethysmography under control conditions, at the end of nitroglycerin titration, after 24-hour infusion, and after N-acetylcysteine; vascular resistance was calculated as mean cuff blood pressure divided by flow. After 24 hours of nitroglycerin infusion, the initial increase in venous volume was reduced 48% (p less than 0.01), whereas the acute effects on vascular resistance were not attenuated in the whole group. N-Acetylcysteine completely restored nitroglycerin venodilator effects in all 10 patients in whom attenuation of the venous effects was observed during the infusion period. CONCLUSIONS: The data indicate that the susceptibility to the development of nitrate tolerance in humans is higher in the venous than in the arterial circulation, and that the sulfhydryl group donor N-acetylcysteine is extremely effective in reversing nitroglycerin tolerance in the venous circulation in humans.
The surface and solubility of some glass ionomer cements have been assessed after exposure to four acids (acetic, formic, lactic and propionic), that are usually present in the bacterial plaque. Therefore, we prepared 80 samples--20 for earl of 4 commercial products; after 7 days and, then after 30 other days, the samples were examined by microscope and weighed. Finally, those showing the most significant modifications were photographed.
The purpose of this study was to evaluate the hemodynamic benefits of atrioventricular (A-V) sequential pacing. 30 pts implanted with DDD pacemakers underwent M-mode, B-mode and Doppler echocardiography. In each patient, left ventricular (LV) stroke volume was assessed by measuring the time-velocity integral of mitral inflow in the following modes and rates: VOO at 70 ppm or at the minimum stimulation rate and at 120 ppm; DOO at the same rates with different A-V delay (100, 150, 200, 250 and, whenever possible, 300 msec). The increase in stroke volume obtained with dual chamber pacing at the optimal A-V delay was 45 +/- 25% at 75 ppm and 29 +/- 14% at 120 ppm (p less than 0.05 75 vs 120 ppm). This increase was significantly higher in pts with than in pts without LV hypertrophy (respectively: 51.9 +/- 20.4 vs 36.9 +/- 20.8% at 75 ppm, p less than 0.05 and 33 +/- 13.4 vs 25.4 +/- 14.5% at 120 ppm, p = 0.08). Concerning the A-V delay, we noted that at 75 ppm stroke volume was significantly higher in DOO than in VOO with any A-V delay ranging +/- 100 msec from the optimal one; at 120 ppm the hemodynamic benefit of DOO pacing was observed only when the programmed A-V delay was the optimal one or very near to it. In conclusion, atrio-ventricular sequential pacing allows a significant increase in LV stroke volume over single chamber ventricular pacing both at 75 and 120 ppm. Programming the optimal A-V delay is absolutely necessary to obtain this hemodynamic benefit at the higher stimulation rate.
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