Efficacy of betamethasone valerate mousse in comparison with standard therapies on scalp psoriasis: an open,multicentre, randomized,controlled, cross-over study on 241 patients

BACKGROUND: The scalp is a common area for plaque psoriasis. Corticosteroid-based lotions are the most widely used therapy in this clinical setting. A new formulation of betamethasone valerate 0.12% in a thermophobic, low-residue foam vehicle (Bettamousse trade mark, Mipharm, Italy; BVM) is available for the treatment of scalp dermatoses. OBJECTIVES: In an open, investigator-blinded, multicentre (28 dermatology clinics), randomized, cross-over study, the efficacy, safety and patient acceptability of BVM in scalp psoriasis were evaluated in comparison with standard therapies (ST, i.e. corticosteroids or vitamin D analogues). ST were chosen by each centre according to its usual therapeutic protocols. METHODS: In total, 241 patients with moderate to severe scalp psoriasis participated in the trial. After a 2-week run-in period, each active treatment (BVM or ST) was applied for 4 weeks, with a wash-out period between the two active treatment phases of at least 4 weeks. Efficacy was evaluated by investigators unaware of treatment sequence analysing a 'target' lesion for erythema, scaling, itching and burning using a five-point grading score. Patient treatment acceptability and assessment of the influence on Psoriasis Disability Index were evaluated using an eight-item modified Finlay-Khan questionnaire at baseline and at the end of each treatment period. Safety was evaluated by recording any adverse event occurring during the study duration. BVM was applied twice daily, and ST were applied once or twice daily, according to the approved scheduled regimens. RESULTS: Analyses were by intention-to-treat. Two hundred and ten patients concluded the study. Fifteen patients withdrew from the study during BVM treatment, and 16 during ST (not significantly different). Both treatments were well tolerated. At baseline, the mean +/- SD clinical global score (the 'Sum' score = erythema + scaling + itching + burning) was 7.6 +/- 2.6. The ST chosen were topical corticosteroids (55% of cases; mainly mometasone and betamethasone dipropionate) or calcipotriol lotion (45% of cases). At the end of active treatments, BVM was significantly superior to ST (P < 0.001) in reducing, as compared with baseline, the mean +/- SD Sum score (1.5 +/- 1.9 with BVM and 3.1 +/- 2.7 with ST). During BVM treatment, 88% (95% confidence interval, CI 82-94%) of patients had a complete or nearly complete resolution of scaling in comparison with 66% (95% CI 58-74%) during ST therapy (P < 0.001). BVM was also considered an easier and more convenient formulation to use in comparison with ST (P < 0.01). CONCLUSIONS: BVM is more effective than lotion-based ST commonly used in the treatment of scalp psoriasis, and has higher patient acceptability.     

Immunogenicity and safety of a DNA prime/adenovirus boost vaccine against rhesus CEA in nonhuman primates

Scaling up experimental protocols from rodents to humans is often not a straightforward procedure, and this particularly applies to cancer vaccines, where vaccination technology must be especially effective to overcome a variety of immune suppressive mechanisms. DNA electroporation (DNA-EP) and adenoviral vectors (Ad) have shown high potency and therapeutic efficacy for different antigens in several pre-clinical models. To evaluate the ability of DNA-EP and Ad to break tolerance to a self-antigen in large animals, we have cloned the CEA homologue (rhCEA) from rhesus monkeys (Macaca mulatta) colon tissue samples. rhCEA is a 705 aa protein and shares 78.9% homology to human CEA protein. Immunogenicity of rhCEA expressing vectors was tested in mice and subsequently in rhesus monkeys. To further increase the immunogenic potency of these vectors, a synthetic codon optimized rhCEA cDNA (rhCEAopt) was constructed. Genetic vaccination of rhesus monkeys was effective in breaking immune tolerance to rhCEA in all immunized animals, maintaining over time the elicited immune response, and most importantly, neither autoimmunity nor other side-effects were observed upon treatment. Our data confirm the efficacy of genetic cancer vaccines in large animals such as nonhuman primates and show that development of modified expression cassettes that result in increased potency of plasmid DNA and adenovirus may have a significant impact on vaccine development against malignancies expressing tumor associated antigens in patients.     

Communication: expression of the novel inhibitor of apoptosis survivin in normal and neoplastic skin.

Apoptosis plays a fundamental part in epidermal homeostasis, and apoptotic cells have been detected in normal and diseased skin. Little is known, however, on the inhibitory mechanisms of apoptosis at the skin level. In addition to bcl-2, a novel inhibitor of apoptosis designated survivin and structurally analogous to IAP apoptosis inhibitors has been recently identified. The expression of survivin in normal and pathologic skin was investigated. Immunohistochemical studies revealed that survivin is expressed in basal keratinocytes, but not in suprabasal epidermal layers, with a pattern similar to bcl-2. In western blots, the anti-survivin antibody recognized a single band of 16.5 kDa in protein extracts from normal human keratinocytes in culture, in agreement with the predicted size of survivin. In addition, survivin immunoreactivity was detected in benign and malignant melanocytic lesions, with strong expression in invasive lesions of melanomas. Whereas survivin staining was undetectable in benign epithelial tumors, such as seborrheic keratoses, it was observed in all epidermal layers in Bowen's disease. Interestingly, at variance with bcl-2, survivin was markedly expressed in squamous cell carcinoma, but virtually lacking in basal cell carcinoma, suggesting that these two apoptosis inhibitors may act through different anti-apoptotic pathways. Deregulation of survivin may influence both epidermal homeostasis and the development of melanoma and nonmelanoma skin cancer.     

Metabolic abnormalities associated with initiation of systemic treatment for psoriasis: evidence from the Italian Psocare Registry

Objective To evaluate variations in laboratory parameters and diagnoses of selected clinical conditions up to 16 weeks after starting a new systemic psoriasis treatment for Psocare Registry enrollees. Design Prospective cohort study. Setting Italian public referral centres for psoriasis treatment. Patients First‐time recipients (n = 10,539) of continuous systemic psoriasis treatment for at least 16 weeks. Main outcome measure Mean variations in (weeks 8 and 16) and proportions of patients reaching a clinically meaningful increase in serum levels (week 16) of total and low‐density lipoprotein cholesterol, triglycerides, aspartate amino transferase, alanine amino transferase and creatinine, as well as week‐16 cumulative incidences of new diagnoses of diabetes mellitus and arterial hypertension. Results Mean cholesterol and triglyceride levels significantly increased in patients treated with acitretin or cyclosporine. Mean triglyceride levels also increased in efalizumab‐ and etanercept‐treated patients. Mean transaminase values increased in methotrexate‐treated patients, and mean aspartate amino transferase levels increased in infliximab‐treated patients. The average serum creatinine value increased in cyclosporine‐treated patients. Acitretin and cyclosporine were associated with risk of hypercholesterolaemia (odds ratios 1.51 and 1.34) and acitretin with risk of hypertriglyceridaemia (odds ratio 1.43). Methotrexate and infliximab were associated with risk of more than doubling the upper normal aspartate amino transferase (odds ratios 2.06 and 1.87) and alanine amino transferase (odds ratios 2.38 and 1.74) values. The relative risk of developing arterial hypertension and diabetes was increased for patients receiving cyclosporine (odds ratios 3.31 and 2.88). Conclusion Systemic treatments for psoriasis resulted in heterogeneous effects on the parameters analysed.     

A mobile laminar airflow unit to reduce air bacterial contamination at surgical area in a conventionally ventilated operating theatre

The aim of this study was to evaluate the efficacy of a mobile laminar airflow (LAF) unit in reducing bacterial contamination at the surgical area in an operating theatre supplied with turbulent air ventilation. Bacterial sedimentation was evaluated during 76 clean urological laparotomies; in 34 of these, a mobile LAF unit was added. During each operation, settle plates were placed at four points in the operating theatre (one at the patient area and three at the perimeter), a nitrocellulose membrane was placed on the instrument table and an additional membrane near the wound. During four operations, particle counting was performed to detect particles > or =0.5 microm. Mean bacterial sedimentation on the nitrocellulose membrane on the instrument table was 2730 cfu/m(2)/h under standard ventilation conditions, whereas it decreased significantly to a mean of 305 cfu/m(2)/h when the LAF unit was used, i.e. within the suggested limit for ultraclean operating theatres (P=0.0001). The membrane near the wound showed a bacterial sedimentation of 4031 cfu/m(2)/h without the LAF unit and 1608 cfu/m(2)/h with the unit (P=0.0001). Particle counts also showed a reduction when the LAF unit was used. No significant difference was found at the four points in the operating theatre between samplings performed with, and without, the LAF unit. Use of a mobile LAF unit with turbulent air ventilation can reduce bacterial contamination at the surgical area in high-risk operations (e.g. prosthesis implant).     

Optical sensor for interstitial pH measurements

An optical fiber sensor for measuring the pH in interstitial fluid is described. Microdialysis is the approach followed for extracting the sample from the subcutaneous adipose tissue. The interstitial fluid drawn flows through a microfluidic circuit formed by a microdialysis catheter in series with a pH glass capillary. The pH indicator (phenol red) is covalently immobilized on the internal wall of the glass capillary. An optoelectronic unit that makes use of LEDs and photodetectors is connected to the sensing capillary by means of optical fibers. Optical fibers are used to connect the interrogating unit to the sensing capillary. A resolution of 0.03 pH units and an accuracy of 0.07 pH units are obtained. Preliminary in vivo tests are carried out in pigs with altered respiratory function.     

Alexithymia and its relationships with body checking and body image in a non-clinical female sample

The aim of the present study was to evaluate in a non-clinical sample of undergraduate women, the relationships between alexithymia, body checking and body image, identifying predictive factors associated with the possible risk of developing an Eating Disorder (ED). The Toronto Alexithymia Scale (TAS-20), Body Checking Questionnaire (BCQ), Eating Attitudes Test (EAT-26), Body Shape Questionnaire (BSQ), Interaction Anxiousness Scale (IAS), Rosenberg Self-Esteem Scale (RSES) and the Beck Depression Inventory (BDI) were completed by 254 undergraduate females. We found that alexithymics had more consistent body checking behaviors and higher body dissatisfaction than nonalexithymics. In addition, alexithymics also reported a higher potential risk for ED (higher scores on EAT-26) when compared to nonalexithymics. Difficulty in identifying and describing feelings subscales of TAS-20, Overall appearance and Specific Body Parts subscales of BCQ as well as lower self-esteem was associated with higher ED risk in a linear regression analysis. Thus, a combination of alexithymia, low self-esteem, body checking behaviors and body dissatisfaction may be a risk factor for symptoms of ED at least in a non-clinical sample of university women.