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Treatment of multiple cutaneous and subcutaneous melanoma metastases is still represents a therapeutic challenge for both dermatologists and oncologists. Electrochemotherapy (ECT) is a promising therapeutic procedure, owing to its ability to improve the penetration of cytotoxic drugs into cancer cells by application of current electric pulses. The aim of our study is to evaluate efficacy, tolerability and long-term efficacy of ECT in the treatment of advanced metastatic melanoma. Thirty patients affected by a total of 654 cutaneous and subcutaneous melanoma metastatic nodules were recruited. All patients were treated after they had undergone to a mild general anesthesia. Intravenous Bleomicina solution was administered 8 minutes before the application of electric pulses, generated by a Cliniporator (TM) (the device validated for ECT). The objective response rate of 100% (67.28% complete response and 32.72% partial response) was observed. A total of 214 metastatic lesions from 24 patients received a second ECT session, among them 141 showed a further complete response. Twenty-four months later, the local tumor control rate was 72%. The results of this study seem to demonstrate that ECT is an effective and valid therapeutic tool for the treatment of cutaneous metastases from melanoma. ECT can be considered a first-line palliative treatment since it is able to alleviate pain and reduce the tumor's spontaneous bleeding with a significant improve of patients' quality of life.

A new wound dressing made of gelatin and Ag, was evaluated for the management of tissue reconstitution in rats. The gelatin–based dressing, with metabolic stimulation properties that favored the recovery of the skin was made of stiff sheets to supply the repairingtissue with mechanical support. The gelatin sheets enhanced the development of collagen fibers and subsequently cell proliferation at the level of stromal and vascular elements. A protocol based on the utilization of natural biomaterials in the presence of low concentrations of a biocidal was proposed which could control microbiocidal activities principally in burned and debilitated patients.

Treatment of multiple cutaneous and subcutaneous melanoma metastases is still represents a therapeutic challenge for both dermatologists and oncologists. Electrochemotherapy (ECT) is a promising therapeutic procedure, owing to its ability to improve the penetration of cytotoxic drugs into cancer cells by application of current electric pulses. The aim of our study is to evaluate efficacy, tolerability and long-term efficacy of ECT in the treatment of advanced metastatic melanoma. Thirty patients affected by a total of 654 cutaneous and subcutaneous melanoma metastatic nodules were recruited. All patients were treated after they had undergone to a mild general anesthesia. Intravenous Bleomicina solution was administered 8 minutes before the application of electric pulses, generated by a Cliniporator (TM) (the device validated for ECT). The objective response rate of 100% (67.28% complete response and 32.72% partial response) was observed. A total of 214 metastatic lesions from 24 patients received a second ECT session, among them 141 showed a further complete response. Twenty-four months later, the local tumor control rate was 72%. The results of this study seem to demonstrate that ECT is an effective and valid therapeutic tool for the treatment of cutaneous metastases from melanoma. ECT can be considered a first-line palliative treatment since it is able to alleviate pain and reduce the tumor's spontaneous bleeding with a significant improve of patients' quality of life.

A therapeutic support for the less effective steps in skin’s recovery should improve reparative capacity. A morphological and immunohistochemical evaluation of tissue repair in rats in the presence...

Early menopause in the fragile X carriers has been well documented in several reports. All surveys demonstrated that 13-25% of fragile X carriers experienced premature ovarian failure (POF), defined as menopause before the age of 40 years. In 1995 we started screening two groups of subjects as a part of a Fragile X Research Program: 1) women previously diagnosed as fragile X carriers from the register of our center and 2) women with POF and without a family history of fragile X or other forms of mental retardation. In this study we report the preliminary data collected from 75 fragile X families; in 30 of them, POF was present in one or several subjects, all of whom had a fragile X premutation. None of the women with a full mutation experienced POF in our series of patients. We also identified 89 families without a family history of fragile X or mental retardation, and there were 108 subjects who experienced POF, of which 6.5% had a fragile X premutation. This is 70-fold higher than the background prevalence of fragile X premutation in the Italian population and suggests an association with POF. These data confirm the results of other surveys.

A new bipolar four-quadrant operational amplifier operating at a power supply voltage of 0.8 V and with a supply current of 800 μA is here presented and illustrated. It features low input offset, low bias current, low noise, low crossover distortion and a rail-to-rail output swing. Control circuits ensuring minimum and maximum current limits for the output transistors have been incorporated. The biasing circuitry follows a PTAT scheme. A simple compensation topology allows the reduction of the area. The chip, whose area is about 2 mm^2, has been fabricated in HF2CMOS 2 μ/6 GHz technology. Finally, Spice simulations and experimental results, which confirm the expected overall performances of the low voltage op-amp, are reported.

The reactive and reparative capacity of injured tissue when treated with either Pulsed Electromagnetic Fields (PEMFs) or with immunomodulator drugs (Prostaglandin E2 and Thymopentin) was evaluated. A morphological and quantitative evaluation was made of the interactions and the interferences on the structural stages of tissue repair processes. When PEMFs were used the time required for new tissue to completely cover the wound was 26 days after surgery, instead of 30 days for control conditions or for treatment with PGE2 or Thymopentin. PEMFs showed accelerated healing process. Both PGE2 and Thymopentin should be considered, in association with other drugs, in an attempt to strengthen the various immunomodulative phases of the reconstitution of injured tissue.

The use of heterologous collagen in skin repair processes has proved to be an efficacious approach for the reconstitution of injured tissue. A morphological and quantitative evaluation of the reactive and reparative ca pacity of injured tissue treated either with conventional medications or with heterologous collagen (Condress) in the form of sponges was carried out. We have analyzed experimental surgical lesions on an animal model and evalu ated the repair processes of the lesions, including the excision of the cutaneous and subcutaneous tissue. The heterologous collagen sponges provided biologi cal support to obtain healed skin of better quality. Tissue lesions healed more rapidly, thus reducing the risk of recurrence. This experimental study provides morphological and structural data for further investigation.

In order to achieve the most satisfactory results in tissue expansion, a cream containing human recombinant epidermal growth factor (EGF) was applied daily to the expanding skin. The capacity of EGF to stimulate tissue repair has been evaluated on expanded skin flaps, comparing surgical procedures carried out with and without EGF. The present clinical, morphological, immunohistochemical and morphometric results demonstrate that EGF used together with the tissue expander may improve skin repair after mechanical stretching. In EGF-expanded skin flaps, clinical results show a reduction in teleangectasiae and histological evidence of a more regular texture in the dermal tissue, together with a significant thickening of the epidermal malpighian layer. Without EGF some signs of immaturity, such as abundance of fibronectin, persist for longer. EGF seems to be a helpful support to improve the tissue expansion process.

Donor areas on patients undergoing plastic surgery were treated with epidermal growth factor (EGF) to stimulate tissue regeneration. Mor phometric analyses showed that cutaneous explants, treated with EGF, pre sented a higher number of microvessels ( p < 0.01) and mesenchimal cells ( p < 0.01), than untreated areas, while EGF did not improve epidermal thick ening. By electron microscopy, better histoarchitectural maturation of cellular and extracellular dermal compartments was observed after EGF application. This work provides evidence that EGF does stimulate skin repair by promoting the formation of mature cutaneous tissue.

High voltage and power are essential for successful MtM product creation. This chapter gives an introduction for the basics of high-voltage and power technologies. Application examples of solid-state lighting and hybrid cars are presented.

Summary Two cases of well-differentiated angiosarcoma following radiotherapy together with an immunocytochemical and electron-microscopical study are reported. Both cases occurred in young females (16- and 22-yr-old respectively) who had been irradiated after birth for an “angiomatous” lesion. These cases have to be added to 34 similar cases reported in the literature.

This paper presents the design and the laboratory results of an integrated half-bridge driver for power electronic systems in a 0.35 mum bipolar CMOS DMOS (BCD) technology. The proposed solution is designed for frequency applications up to several hundred of KHz and it has a driving current capability up to 50 mA. This work features a design configuration and a digital control to reduce electromagnetic interference (EMI). Moreover it includes short circuit protection, programmability of voltage references and a digital control circuitry implementing mechanism to prevent dangerous failures of the driver. After a deep description of the circuit we show the laboratory results of the half-bridge driver used to drive a 20 KHz antenna.

To better define the efficacy and the safety of intra-arterial infusion performed with or without hemofiltration for recurrent limb melanoma.Patients with the following characteristics were included in the study: recurrent limb melanoma not indicated for surgical resection, measurable disease in the extremity,18 years, performances status (Eastern Cooperative Oncology Group ) was 0-1 and life expectancy of at least 6 mo. Twenty nine consecutive patients were enrolled in the study. Patients underwent fluoroscopic placement of angiographic arterial and venous catheters to infuse the drug in the artery [isolated limb infusion (ILI)], and to stop the out flow (venous). Melphalan was rapidly infused into the isolated limb via the arterial catheter after the inflation of venous balloon catheter. Then the circulation of the limb was completely blocked with a pneumatic cuff at the root of the limb. Haemofiltration (HF) was available only in the main center, and was performed with an extracorporeal perfusion system, in order to reduce high systemic toxic peaks of drug.Thirty seven ILI were done in 29 cases (31 ILI-HF and 6 ILI) between 2001 and 2014 at Ancona and Pesaro Hospitals, Italy. Clinical outcomes were monitored 30 d after treatment. Eleven patients (38%) received infusion of melphalan alone, 7 (24%) melphalan associated to mitomicin C and 7 (24%) melphalan associated to cisplatin, the remaining 4 were treated with cisplatin, melphalan and epirubicin or cisplatin and mitomicin C. The overall response rate was 66%, in particular, 3 patients (10%) were complete responders and 16 (56%) were partial responders; whereas 7 patients (24%) had stable disease, and 3 (10%) showed progressive disease. Limb toxicity was assessed adopting Wieberdink scale, with evidence of 90% of low grade (I and II) toxicity.ILI-HF and ILI are effective and safe treatments for recurrent non-resectable limb melanoma. They present evidence of favorable clinical benefit and is effective in delaying progression.

This IC, together with an external 8 b microcontroller, implements all signal conditioning, measuring and power actuation functions required by a photographic camera. All IC functions are programmed by an external microcontroller through a 16 b SPI interface. The internal low-drop regulator (0.1 V drop, 30 mA) supplies both the internal circuitry and the external microcontroller. A bandgap voltage reference is used for low sensitivity to temperature variation. To preserve battery life, the micro can shut down itself and the system by writing a bit that switches off the regulator and brings system current consumption under 500 nA.

In this paper, we present an instrument to identify the behaviour of NiCd and NiMH batteries from the measured values of voltage and temperature during the charge and discharge phases. The instrument represents a useful tool for controlling the battery charge phase through methods based on the increase of the voltage or of the derivative of the temperature with respect to time, avoiding damage due to overcharging. It can also be used to validate new algorithms for detecting the end of the charge.

This paper reports about the implementation of a single-chip smart-power IC embedding an 8-bit microcontroller, analog circuits for data processing as well as a full protected power element (an H-bridge DMOS power stage capable of 60 V, 4 A) and intended to directly control a hydraulic servo-valve. Optimized for automotive applications (active suspensions, power steering, servo-braking), it can be, for its versatility, used as well in others applications like industrial, public works, etc.

Skin flap survival is a significant problem in skin surgery; in particular, inadequate arterial or venous blood supply results in necrosis of the distalmost portion. The aim of this study was to evaluate the ability of Vascular Endothelial Growth Factor (VEGF) of modifying the morphological features of skin flaps. Bilateral epigastric skin flaps were raised in 16 Wistar male rats. The epigastric artery and vein of the left flaps were clamped and then injected with rhVEGF (8 rats) or saline (8 rats). The right flaps were not clamped and received rhVEGF or saline systemically. The rats were euthanized on the seventh day and flap skin samples collected. Tissue fragments were subject to immunohistochemical (rhVEGF, VEGFr, VIII factor, CD34 antibodies), ultrastructural and morphostructural investigations. The results showed that rhVEGF improved the condition of flaps and that systemic administration was effective in promoting the development of an adequate vascular network.

We report a direct DNA sequencing analysis of the MECP2 gene undertaken on a further 64 Italian patients with Rett syndrome by using a LICOR 4200 Automated Sequencer. All of the girls entering the study had a consistent clinical diagnosis for this disorder. All coding regions and the flanking intronic splice site sequences were amplified as three non-overlapping fragments by using both forward and reverse primers. The results were then compared to the MECP2 reference sequences published in GenBank. Mutations of the MECP2 gene were identified in 64 of 75 (85.33%) unrelated sporadic Rett syndrome girls. Genotype/phenotype correlation studies, in particular in groups of patients with the same mutation, did not offer definitive and interesting data.

The early stages of mycosis fungoides (MF) can be treated but not cured by photochemotherapy (PUVA) alone; some recent studies of the effect of a combination of human interferon-alpha (IFN(alpha)) and PUVA reported a high degree of response. The aim of our study was to evaluate the activity of a low dose of IFN-alpha2b combined with PUVA.Twenty-five patients were included: 16 men and 9 women aged between 23-80 years; 19 patients ahd stage I and 6 stage II disease. In the induction phase, the dose of IFNalpha was gradually raised over 6-8 weeks to the target dose of 18 MU/week; in the maintenance phase, the combination with PUVA allowed IFNalpha to be reduced to a maximum dose of 6 MU/week; in this way the cumulative administration of IFNalpha and PUVA was considerably lower than in similar combination protocols. Treatment success was analyzed in terms of freedom from treatment failure (FFTF).After the induction phase 9/25 patients (36%) achieved complete remission (CR) and 15/25 (56%) achieved partial remission (PR). One to five months from the beginning of the maintenance phase, a CR was recorded in 19/25 patients (76%) and a PR in 5/25 patients (20%) accounting for an overall response rate of 96%. The median of FFTF was not reached; probability of FFTF was 82% at 12 months and 62% at 24 months. Disease free survival projected to 48 months was 75%.Even with low doses of IFNalpha plus PUVA it is possible to achieve excellent clinical responses,many of which are long-lasting, in patients with early MF.

Early menopause in the fragile X carriers has been well documented in several reports. All surveys demonstrated that 13-25% of fragile X carriers experienced premature ovarian failure (POF), defined as menopause before the age of 40 years. In 1995 we started screening two groups of subjects as a part of a Fragile X Research Program: 1) women previously diagnosed as fragile X carriers from the register of our center and 2) women with POF and without a family history of fragile X or other forms of mental retardation. In this study we report the preliminary data collected from 75 fragile X families; in 30 of them, POF was present in one or several subjects, all of whom had a fragile X premutation. None of the women with a full mutation experienced POF in our series of patients. We also identified 89 families without a family history of fragile X or mental retardation, and there were 108 subjects who experienced POF, of which 6.5% had a fragile X premutation. This is 70-fold higher than the background prevalence of fragile X premutation in the Italian population and suggests an association with POF. These data confirm the results of other surveys.

The preliminary results of an international collaborative study examining premature menopause in fragile X carriers are presented. A total of 760 women from fragile X families was surveyed about their fragile X carrier status and their menstrual and reproductive histories. Among the subjects, 395 carried a premutation, 128 carried a full mutation, and 237 were noncarriers. Sixty-three (16%) of the premutation carriers had experienced menopause prior to the age of 40 compared with none of the full mutation carriers and one (0.4%) of the controls. Based on these preliminary data, there is a significant association between fragile X premutation carrier status and premature menopause.

Establishing guidelines and experimental models preclinical and clinical evaluations of new agents for treatment, and/or prevention of human diseases has become a task of crucial importance. Psoriasis is such one disease holding great interest for dermatology owing to its high rate of incidence and complexity of treatment. However the absence of psoriatic lesions in animals and the inability to induce them, calls for experimental techniques both in vitro and in vivo. The purpose of this study was to evaluate experimentally the effects of tacalcitol on cell proliferation and differentiation process. Thereafter a human pilot study on psoriatic patients has been developed.

Skin flap survival is a significant problem in skin surgery; in particular, inadequate arterial or venous blood supply results in necrosis of the distalmost portion. The aim of this study was to evaluate the ability of Vascular Endothelial Growth Factor (VEGF) of modifying the morphological features of skin flaps. Bilateral epigastric skin flaps were raised in 16 Wistar male rats. The epigastric artery and vein of the left flaps were clamped and then injected with rhVEGF (8 rats) or saline (8 rats). The right flaps were not clamped and received rhVEGF or saline systemically. The rats were euthanized on the seventh day and flap skin samples collected. Tissue fragments were subject to immunohistochemical (rhVEGF, VEGFr, VIII factor, CD34 antibodies), ultrastructural and morphostructural investigations. The results showed that rhVEGF improved the condition of flaps and that systemic administration was effective in promoting the development of an adequate vascular network.

This paper describes a multi-source energy harvester IC for arrays of independent transducers, designed in a 0.32μm STMicroelectronics BCD technology, that can manage up to 5 AC-DC channels (e.g. piezoelectric transducers). The IC implements a boost converter based on synchronous electrical charge extraction. A single external inductor is time-shared among all transducers and access conflicts are handled by an arbiter circuit implemented as an asynchronous FSM. The designed converter is fully autonomous and suitable for battery-less operation. The circuit area is 4.6 mm 2 and has a power consumption of 175 nW/source at 2.5 V while efficiency ranges between 70% and over than 85%.