Skin improvement with two different oestroprogestins in patients affected by acne and polycystic ovary syndrome: clinical and instrumental evaluation.

BACKGROUND: Despite it is accepted that acne is mostly caused by an hyper-responsiveness of the pilo-sebaceous unit to normal circulating androgen hormones, in a few patients, especially women, acneic lesions can be associated with increased serum androgen levels (hyperandrogenism), of which polycystic ovary syndrome (PCOS) is the most common cause. In women with acne and proven PCOS therapy with estroprogestins (EPs) can be an excellent option. OBJECTIVE: The aim of the study was to assess the effects of two estroprogestins (EPs), ethinyl-estradiol (EE) 30 mcg/drospirenone (DRSP) 3 mg, and ethinyl-estradiol (EE) 30 mcg/chlormadinone acetate (CMA) 2 mg, both on increased serum androgen levels and on several skin parameters in women affected by mild to severe acne and polycystic ovary syndrome (PCOS). METHODS: Fifty-nine women were randomized to receive EE/DRSP (n = 32) or EE/CMA (n = 27) for six months. Evaluation of serum androgen levels, grading of acne and hirsutism (respectively with Pillsbury and Ferriman-Gallwey score) and non-invasive assessment of skin hydration, transepidermal water loss (TEWL) and skin homogeneity were performed at baseline, at 3 and 6 months (end of treatment). RESULTS: Both treatments were well tolerated and showed a significant improvement of skin and hormonal parameters, although EE/DRSP showed a more potent effect on acne and seborrhea. CONCLUSIONS: Estroprogestins represent an effective and safe treatment in women with acne and polycystic ovary syndrome (PCOS). Nevertheless, the combination EE 30 mcg/DRSP 3 mg appears to be a more potent therapeutic option.

[Short-term effect of an estroprogestin containing ethinylestradiol 20 mcg + drospirenone 3 mg in 24+4 regimen at hormonal and cutaneous level in ovarian hyperandrogenism]. / Effecto a breve termine di un estroprogestinico contenente etinilestradiolo 20 mcg+drospirenone 3mg in schema 24 + 4 a livello ormonale e cutaneo nell'iperandrogenismo ovarico.

AIM: evaluate the efficacy of an estroprogestin EP containing 20 mcg ethinilestradiol (EE) and 3 mg drospirenone (DRSP) in the treatment of hyperandrogenism. METHODS: In this study, twenty hyperandrogenic patients were treated with an EP containing EE 20 mcg and DRSP 3 mg in 24+4 regimen for three months. Skin evaluation was performed both quantitatively and qualitatively. RESULTS AND CONCLUSION: This EP combination showed, after a short-term treatment (three months) to decrease significantly seborrhea, acne, and circulating androgens (testosterone, deidroepiandrosterone sulphate, and androstenedione), while increased sex hormone binding globulin levels. Moreover, this EE 20 mcg/DRSP 3mg EP combination changed some parameters of skin quality, increasing corneometry (a parameter related to skin hydration), and reduced trans epidermal water loss (TEWL, a parameter related to skin evaporation), and erythema (a parameter related to skin inflammation). These results could be taken into account in individualizing the treatment of hyperandrogenic patients.

Idiopathic environmental intolerances (IEI): from molecular epidemiology to molecular medicine.

Inherited or acquired impairment of xenobiotics metabolism is a postulated mechanism underlying environment-associated pathologies such as multiple chemical sensitivity, fibromyalgia, chronic fatigue syndrome, dental amalgam disease, and others, also collectively named idiopathic environmental intolerances (IEI). In view of the poor current knowledge of their etiology and pathogenesis, and the absence of recognised genetic and metabolic markers of the diseases. They are often considered "medically unexplained syndromes",. These disabling conditions share the features of polysymptomatic multi-organ syndromes, considered by part of the medical community to be aberrant responses triggered by exposure to low-dose organic and inorganic chemicals and metals, in concentrations far below average reference levels admitted for environmental toxicants. A genetic predisposition to altered biotransformation of environmental chemicals, drugs, and metals, and of endogenous low-molecular weight metabolites, caused by polymorphisms of genes coding for xenobiotic metabolizing enzymes, their receptors and transcription factors appears to be involved in the susceptibility to these environment-associated pathologies, along with epigenetic factors. Free radical/antioxidant homeostasis may also be heavily implicated, indirectly by affecting the regulation of xenobiotic metabolizing enzymes, and directly by causing increased levels of oxidative products, implicated in the chronic damage of cells and tissues, which is in part correlated with clinical symptoms. More systematic studies of molecular epidemiology, toxico- and pharmaco-genomics, elucidating the mechanisms of regulation, expression, induction, and activity of antioxidant/detoxifying enzymes, and the possible role of inflammatory mediators, promise a better understanding of this pathologically increased sensitivity to low-level chemical stimuli, and a solid basis for effective individualized antioxidant- and/or chelator-based treatments.

Efficacy and safety of biologicals against immune-mediated diseases: do benefits outweigh risks?

The success of molecular biology in identifying molecular pathways underlying chronic immune-mediated diseases and the rapid development of gene/cell engineering biotechnologies has resulted in the development of a number of targeted biological drugs, which have revolutionized the therapy of these diseases. Numerous data published over the last 10-15 years demonstrate a dramatic improvement in the clinical efficacy of biologics compared with conventional drugs. However, professional and public concern about serious biological drug-associated adverse events has also been growing steadily. We critically analyze recent literature on the efficacy and safety of biologics in the management of rheumatoid arthritis, psoriasis, psoriatic arthritis and immune thrombocytopenia. Our analysis of benefits, resistance to the therapy, risk of infections, tumors and other serious complications related to chronic administration of biologics is based on the molecular/cellular mechanisms of their interaction with the immune system. We also address whether it is feasible to attenuate the risks associated with biologics without limiting their benefits.

Excimer laser ablation in the treatment of total chronic obstructions in critical limb ischaemia in diabetic patients. Sustained efficacy of plaque recanalisation in mid-term results.

This prospective study aims to evaluate the impact of the excimer laser technology as the first-line endovascular treatment of critical limb ischaemia (CLI) in diabetic patients. The protocol allowed the use of laser ablation of obstructive lesions when conventional endoluminal guidewire crossing of the plaque was unsuccessful. We extrapolate the data of consecutive patients treated, who completed at least 12 months of follow-up, extending the observation to a 26-month time frame. During this period, 67 diabetic patients with CLI were brought to the Cath Lab for 'operative angioplasty' and to be treated with endovascular techniques. Of the 67 cases, laser was used on 35 patients to treat 51 lesions. All patients had type C or D occlusive lesions, according to the TACS II classification, showing a single type D plaque or multiple tandem C/D occlusive plaques ranging from 4 to 23 cm in length. The immediate clinical success, defined as restored direct arterial flow to the foot, was 88.2%. The lesions were successfully crossed by laser in 45 out of 51 attempts. Stents were required in 25% of the patients with 21% lesions. Patency rates were assessed using the Kaplan-Meier survival curves. The patency rates of the successfully treated lesions (freedom from target lesion revascularisation) were 96.6% at 12 months and 82.7% at 24 months. Limb-salvage rate at 12 and 24 months were 100% and 94%, respectively. Our study showed that the excimer laser-assisted angioplasty, when feasible, is effective in granting event-free survival in CLI patients with diabetes, and that endoluminal-driven atherectomy allows long-term success in reducing the need of stents in the lower limb arteries.

Identification of categories at risk for high quality of life impairment in patients with vitiligo.

BACKGROUND: Quality of life (QoL) in patients with vitiligo is strongly impaired. Therefore, it seems inadequate to describe the severity of the disease using only physical indicators. OBJECTIVES: To investigate the QoL of patients with vitiligo, identifying categories at risk for high impairment, also analysing single questions from a QoL instrument. METHODS: The Skindex-29 questionnaire, a QoL dermatology-specific instrument, was completed by 181 consecutive patients with vitiligo. Answers to the Skindex-29 items were given on a five-point scale, from 'never' to 'all the time'. Results The QoL problems more frequently experienced 'often' or 'all the time' were: worry of the disease getting worse (60%), anger (37%), embarrassment (34%), depression (31%), having social life affected (28%), and shame (28%). The prevalence of patients with probable depression or anxiety, evaluated using the 12-item General Health Questionnaire, was 39%, and the prevalence of patients with alexithymia, evaluated using the 20-item Toronto Alexithymia Scale, was 24%. The association of QoL impairment with psychological problems was very strong for all the items, and remained significant also when taking into account simultaneously gender, age, clinical severity, family history, and localization of vitiligo. CONCLUSIONS: Detailed information on QoL in patients with vitiligo may lead dermatologists to pay particular attention to patient categories at risk for a high QoL impairment.

[Effect on skin and hormonal hyperandrogenic manifestations of an oral estroprogestin association containing ethynilestradiol 30 mg and drospirenone 3 mg]. / Effetto sulle manifestazioni iperandrogeniche a livello cutaneo ed ormonale dell'associazione orale estroprogestinica contenente Etinilestradiolo 30 mg e Drospirenone 3 mg.

AIM: This study evaluated hormonal and skin effects in hyperandrogenic women of an oral estroprogestin (EP) association containing ethynilestradiol 30 mcg plus drospirenone 3 mg. METHODS: Thirty two women with signs and symptoms of hyperandrogenism (seborrhea, acne, increased hair); hormonal assessment (follicle-stimulating hormone, [FSH]; luteinizing hormone, LH; 17-hydroxi-progesterone, 17OHP; androstenedione, A, testosterone, T; dehydroepiandrosterone sulfate, DHEAS; sex hormone binding globulin, [SHBG]; Free Androgen Index [FAI, Tx100/SHBG] was performed before the start of treatment, and after 3 and 6 months of administration of EP. The impact on seborrhea, acne, and hair pattern (Ferriman-Gallwey score) was assessed, and, by non-invasive technique, hydration, water transpiration, and homogeneity of the skin were evaluated. RESULTS: Treatment with this EP for 6 months decreased significantly circulating androgen levels (A, T, DHEAS) and FAI, and increased SHBG levels, also reducing seborrhea, acne and hirsutism. Moreover, EE/DRSP increased hydration and improved overall appearance of skin surface (homogeneity). CONCLUSION: Treatment with EE 30 mcg+DRSP 3 mg improves hormonal pattern and skin appearance in hyperandrogenic patients, potentially with subsequent, beneficial effects on quality of life of these women.

Permanent repigmentation of piebaldism by erbium:YAG laser and autologous cultured epidermis.

BACKGROUND: Several surgical techniques have been proposed for the treatment of piebaldism. These procedures, however, are poorly suited for the treatment of large leucodermal lesions, can cause scars and require multiple donor sites. Recently, it has been reported that autologous cultured epidermis induces scarless repigmentation of large vitiligo lesions, using a single small donor site. OBJECTIVES: To induce permanent repigmentation of large achromic lesions in patients suffering from piebaldism by means of autologous cultured epidermal grafts using a rapid, simple and non-invasive surgical procedure. METHODS: Six patients with piebaldism were enrolled in this study. Achromic epidermis was removed by means of appropriately set erbium:YAG laser and autologous cultured epidermal grafts were applied on to the recipient bed. Melanocyte content was evaluated by 3,4-dihydroxyphenylalanine reaction. The percentage of repigmentation was calculated using a semiautomatic image analysis system. RESULTS: Autologous cultured epidermis, bearing a controlled number of melanocytes, induced repigmentation of all piebald lesions. The mean percentage repigmentation was 95.45% (2791.5 cm2 repigmented/2924.2 cm2 transplanted). CONCLUSIONS: Autologous cultured epidermal grafts induce permanent and complete repigmentation of piebald lesions, in the absence of scars. Erbium:YAG laser surgery is a rapid and precise tool for disepithelialization, hence allowing treatment of large piebald lesions during a single surgical operation.

Patient monitoring using personal area networks of wireless intelligent sensors.

A wearable device for monitoring multiple physiological signals (polysomnograph) usually includes multiple wires connecting sensors and the monitoring device. In order to integrate information from intelligent sensors, all devices must be connected to a Personal Area Network (PAN). This system organization is unsuitable for longer and continuous monitoring, particularly during the normal activity. For instance, monitoring of athletes and computer assisted rehabilitation commonly involve unwieldy wires to arms and legs that restrain normal activity. We propose a wireless PAN of intelligent sensors as a system architecture of choice, and present a new design of wireless personal area network with physiological sensors for medical applications. Intelligent wireless sensors perform data acquisition and limited processing. Individual sensors monitor specific physiological signals (such as EEG, ECG, GSR, etc.) and communicate with each other and the personal server. Personal server integrates information from different sensors and communicates with the rest of telemedical system as a standard mobile unit. We present our prototype implementation of Wireless Intelligent SEnsor (WISE) based on a very low power consumption microcontroller and a DSP-based personal server. In future we expect all components of WISE integrated in a single chip for use in a variety of new medical applications and sophisticated human computer interfaces. Existing growth of wireless infrastructure will allow a range of new telemedical applications that will significantly improve the quality of health care.

Thermistor-based breathing sensor for circadian rhythm evaluation.

One of the most frequently used methods to sense breathing pattern is to detect airflow using a nasal thermistor or a thermocouple sensor. Prolonged, minimally intrusive measurement of the breathing pattern is particularly important for polysomnography, sleeping disorders, stress monitoring, biofeedback techniques, and circadian rhythm analysis. Although most applications require only breathing pattern, some applications and diagnostic procedures require monitoring of the rhythm of change of dominant nostril. In this paper we present our design of a differential thermistor-based breathing sensor for prolonged monitoring during the normal activity. The system is designed using a low power microcontroller Texas Instruments MSP430F149 with an on-chip A/D converter for data acquisition and signal processing. We use wireless RF link to a PC for long-term data acquisition and storage. Precise measurement requires decreasing zero and sensitivity errors of the measurement. We discuss signal processing methods, calibration and parameters used to characterize breathing patterns necessary for circadian breathing rhythm evaluation.

[Significance of QT dispersion in the onset of ventricular arrhythmia in patients with heart failure]. / Znacaj QT disperzije za nastanak komorskih poremcaja ritma kod bolesnika sa srcanom slaboscu.

UNLABELLED: Prolonged QT dispersion which has been proposed as a marker of repolarisation inhomogeneity, may predispose to ventricular arrhythmias in a variety of cardiac disorders. The aim of this study was to compare some indices of QT dispersion in patients with heart failure compared to normal subjects. We have also tested the hypothesis that QT dispersion is a useful method for identifying the patients at high risk for ventricular arrhythmias. METHODS: There were 84 patients, divided into two groups. In the first group there were 62 patients with heart failure, in the sinus rhythm, while in second group there were 22 sex- and age-matched healthy subjects. Simultaneous 12-channel ECGs were recorded at a paper speed 50 mm/sec. Ventricular arrhythmias were quantified by 24-h Holter ECG and classified according to the Lown classification system. Only those patients with a class IVa, IVb, and V arrhythmia were considered to have complex ventricular premature contractions (PVCs). Measurements of QT, JT, and RR intervals were performed manually. Heart rate corrected QT and JT intervals (QTc and JTc) were calculated by Bazett's formula. RESULTS: RR intervals were similar in both groups (862 +/- 120 vs 840 +/- 86; ns). QT dispersion and rate corrected QT dispersion were significantly greater in heart failure patients than in controls (76 +/- 13 ms vs 37 +/- 11 ms and 89 +/- 21 ms vs 40 +/- 17 ms; p < 0.05). When, on the basis of the existing complex PVCs, heart failure patients were divided into two subgroups, QT dispersion and rate corrected QT dispersion were significantly greater in the subgroup with complex PVCs compared to patients without complex PVCs (84 +/- 14 ms vs 61 +/- 18 ms and 98 +/- 26 ms vs 66 +/- 21 ms; p < 0.05). CONCLUSION: All indices of QT dispersion were significantly higher in heart failure patients. QT dispersion is useful, noninvasive method for identifying heart failure patients at high risk for ventricular arrhythmia.