bluuebunny/crossref_metadata_2025 huggingface dataset:
T Cell Activation State in the Induced Sputum of Asthmatics Treated with Budesonide
Authors: Vatrella A. , Perna F. , Pelaia G. , Parrella R. , Maselli R. , Marsico S.A. , Calabrese C.
Published: January 2017

Bronchial hyperresponsiveness and airway infiltration with eosinophils and T lymphocytes are key features of asthma. In particular, CD4+ T cells are currently believed to play a pivotal role as initiators and coordinators of the asthmatic inflammatory response and, therefore, they represent a crucial target of corticosteroid treatment. The aim of the present investigation is thus to evaluate, in patients with mild asthma, the effects of inhaled corticosteroid therapy on the following parameters: (i) functional state of CD4+ T cells; (ii) airway eosinophilia; (iii) bronchial hyperresponsiveness to methacholine. The study was completed by twenty asthmatic, atopic subjects, subdivided into two groups of ten and treated for 12 weeks with either inhaled budesonide (200 μg twice daily) or terbutaline alone (500 μg twice daily), respectively. Expression of CD4+ T cell activation markers was measured in induced sputum at baseline and after 1, 4, 8 and 12 weeks of treatment by flow cytometry, which showed a down-regulation of HLA-DR and CD25 surface proteins in the budesonide group, compared with the control group; these differences resulted as being statistically significant through weeks 4–12. Budesonide also induced a quick, sharp reduction in the percentage of eosinophils detectable in induced sputum, as well as a more gradual progressive improvement in airway hyperresponsiveness to methacholine. Therefore, in addition to assessing various indices of bronchial inflammation, flow cytometry can be reliably applied to induced sputum in order to monitor, even in mildly symptomatic patients, the effects of anti-asthma treatments on T cell activation.
NA+/H+ Exchanger 1-and Aquaporin-1-Dependent Hyperosmolarity Changes Decrease Nitric Oxide Production and Induce VCAM-1 Expression in Endothelial Cells Exposed to High Glucose
Authors: Madonna R. , Montebello E. , Lazzerini G. , Zurro M. , De Caterina R.
Published: January 2017

Since diabetic hyperglycaemia causes hyperosmolarity, we investigated the contribution of hyperosmolarity in the proinflammatory endothelial effects of hyperglycemia, and sought to unravel the mechanisms involved. Human aortic endothelial cells (HAEC) were incubated for short-term (1–3 days) or long-term (1–2 weeks) exposures to 5.5 mmol/L glucose (normoglycemia, basal), high glucose (25 and 45 mmol/L, HG), or a hyperosmolar control (mannitol 25 and 45 mmol/L, HM), in the presence or absence of the aquaporin-1 (AQP1) inihibitor dimethylsulfoxide (DMSO), the Na+/H+ exchanger 1 (NHE-1) inihibitor cariporide (CA), the protein kinase C (PKC) inihibitor calphostin C or the PKCβ isoform inhibitor LY379196 (LY). Both short- and long-term exposures to HG and HM decreased the expression of the active, phosphorylated form of endothelial nitric oxide synthase (Ser1146-eNOS) and, in parallel, increased vascular cell adhesion molecule(VCAM)-1 protein at immunoblotting. After 24 h incubation with HG/HM, we observed a significant similar and concentration-dependent enhancement of AQP1 expression. DMSO and CA inhibited hyperosmolarity-induced VCAM-1 expressions, while increasing nitrite levels and Ser1146-eNOS expression. Gene silencing by small interfering RNA reduced the expression of AQP1, and suppressed HG- and HM-stimulated VCAM-1 expression. Calphostin C and LY blunted hyperosmolarity-induced VCAM-1 expression, while increasing the expression of Ser1146-eNOS and nitrite production. Thus HG decreases eNOS activation and induces total VCAM-1 expression in HAEC through a hyperosmolar mechanism. These effects are mediated by activation of the water channels AQP1 and NHE-1, and a PKCβ-mediated intracellular signaling pathway. Targeting osmosignaling pathways may represent a novel strategy to reduce vascular effects of hyperglycemia.
Can Cyclosporine-A Associated to Methotrexate Maintain Remission Induced by Anti-TNF Agents in Rheumatoid Arthritis Patients? (Cynar Pilot Study)
Authors: Migliore A. , Bizzi E. , Massafra U. , Vacca F. , Martin L.S. Martin , Ferlito C. , Podestà E. , Granata M. , Laganà B.
Published: January 2017

Biological therapies, such as etanercept, adalimumab and infliximab, have demonstrated good efficacy in inducing rheumatoid arthritis to low disease activity levels. Nevertheless, their cost, as well as the related risk of side effects, especially in long-term therapies, are still high. Furthermore, there is a good deal of evidence proving loss of efficacy of such therapies in the long term, often necessitating the shift from one specific anti-TNF biological treatment to another. There are also other open debates on the amount of time a patient should undergo an anti-TNF therapy, on the possibility of inducing a complete remission in early arthritis and, once remission or low disease activity is obtained, on the possibility of interrupting the anti-TNF-based therapy. In this study we investigated whether A-Cyclosporin and Methotrexate association may be effective in maintaining low disease activity obtained by anti-TNF therapies. Twenty-three rheumatoid arthritis-affected patients, whose diagnosis was made according to ACR criteria, with a disease duration of less than 3 years, and DAS28<3.2 that reached a level of low disease activity within 6–8 months from beginning anti-TNF and Methotrexate therapy, were enrolled in the study. After the suspension of anti-TNF therapy, patients were started on A-Cyclosporine (2–3 mg/kg/day) and Methotrexate (15mg/week) therapy. DAS28, Pain VAS, Erythrosedimentation Rate (ESR), and C Reactive Protein (CRP) were all tested at time 0 and at 6 months, as well as liver and kidney profiles, after the interruption of the anti-TNF therapy and the beginning of A-Cyclosporine and Methotrexate therapy. Side effects were also recorded. Of 23 patients undergoing the A-Cyclosporin and Methotrexate therapy for maintaining low disease activity in rheumatoid arthritis obtained by 6–8 months of anti-TNF therapy, 21 completed the study with a 6 month follow-up. Thirteen patients maintained clinical parameters within low disease activity values, while 8 patients showed an increase in DAS28 and other parameters. Only two patients showed an increase in blood pressure that was diagnosed after two months from the beginning of the A-Cyclosporin and Methotrexate therapy. The reduction in the dosage of A-Cyclosporin from 3mg/kg/day to 2mg/kg/day caused a slow normalization of blood pressure values. Our data seem to suggest that more than half of the patients undergoing A-Cyclosporin and Methotrexate therapy seemed to maintain low disease activity parameters of rheumatoid arthritis, obtained after 6–8 months of anti-TNF therapy. Further studies on larger populations are necessary in order to confirm such results and identify predictor factors for different responses.
In Vivo Characterization of Zirconia Toughened Alumina Material: A Comparative Animal Study
Authors: Maccauro G. , Cittadini A. , Magnani G. , Sangiorgi S. , Muratori F. , Manicone P.F. , Iommetti P. Rossi , Marotta D. , Chierichini A. , Raffaelli L. , Sgambato A.
Published: January 2017

The development of a new chromia-doped Zirconia Toughened Alumina (ZTA) material was previously reported as displaying mechanical properties suitable for implants with load bearing applications, such as orthopaedic and dental implants. This type of biomaterial is expected to be in contact with living tissues for a long period of time and its long-term toxicity must be carefully evaluated. In this study the suitability of this ZTA material as a candidate biomaterial for orthopaedic implants and dental devices was further investigated in vivo in comparison to alumina and zirconia, which are currently used in orthopaedic and dental surgery. Cylinders of the materials were implanted in vivo in white rabbits, and local and systemic tissue reactions were analyzed at different time intervals after surgery. Radiologic examinations displayed the absence of radiolucence around cylinders and no signs of implant loosening up to twelve months. No tumours developed in the animals either locally (at the site of implantation), or systemically in the peripheral organs. The results obtained suggest that this new ZTA material does not display any long term pathogenic effect in vivo. These findings extend our previous observations on the biocompatibility and the absence of any long-term carcinogenic effect in vitro of this material which displays interesting properties for biomedical applications. In conclusion, we report the in vivo characterization of a new chromia-doped ZTA material and confirm its suitability as a candidate biomaterial for orthopaedic implants and dental devices since it does not give any local nor systemic toxicity even after a long period of time after implantation.
Allergic and Non-Allergic Drug Hypersensitivity Reactions in Children
Authors: Buonomo A. , Altomonte G. , De Pasquale T. , Lombardo C. , Pecora V. , Sabato V. , Colagiovanni A. , Rizzi A. , Aruanno A. , Pascolini L. , Patriarca G. , Nucera E. , Schiavino D.
Published: January 2017

Adverse drug reactions (ADR) are an important medical problem. The aim of this study is to investigate the clinical characteristics of children with ADR and to assess the tolerability of alternative drugs in children (under 16 yrs of age) with a history of ADR. We studied 278 children (132 males and 146 females). Patients were studied by recording personal history and performing in vivo skin testing, in vitro laboratory tests and challenge tests. Patients who had experienced mild adverse reactions underwent challenge tests without any premedication; patients with a clinical history of moderate reactions, received a premedication with sodium cromolyn 30 min before the oral challenge; patients with a clinical history of severe reactions or undergoing parenteral challenges, were given an antihistamine 30 minutes before. A total of 660 adverse events were reported with 126 different drugs involved. Antimicrobial agents were the most involved drugs (51.7%). Non-steroidal anti-inflammatory drugs were involved in 22.7% of episodes. The most reported symptoms were cutaneous. Allergy testing was negative in 272 patients. A diagnosis of drug allergy was reported for 6 patients. A total of 669 challenge tests were performed. 639 were negative at first attempt while 22 were positive. Eight were repeated using a different premedication and resulted negative. Hypersensitivity drug reactions in children are mainly non-allergic. A premedication with sodium cromolyn or with oral H1-antihistamines may be useful in preventing ADR.
The Plasminogen Activator System in Fibroblasts from Systemic Sclerosis
Authors: Postiglione L. , Montuori N. , Riccio A. , Di Spigna G. , Salzano S. , Rossi G. , Ragno P.
Published: January 2017

Systemic sclerosis (SSc) is characterized by excessive fibrosis throughout the body. There are two major subsets of SSc, diffuse cutaneous Systemic sclerosis (dSSc) and limited cutaneous Systemic sclerosis (ISSc). Fibroblasts play a key role in SSc. The expression and function of the urokinase (uPA)-mediated plasminogen activation (PA) system, a well-characterized system of serine-proteases involved in several pathological processes, has been investigated in SSc fibroblasts. The expression of the components of the PA system, including uPA, its type-1 and type-2 inhibitors (PAI-1 and PAI-2) and its receptor (uPAR), was examined by Western blot in fibroblasts from patients affected by limited and diffuse forms of SSc. uPA and PAI-1 secretion increased only in fibroblasts from ISSc lesions compared to normal fibroblasts. PAI-2 levels were decreased in fibroblasts from both SSc forms. Interestingly, fibroblasts from areas not adjacent to the lesions (not-affected) of the diffuse form showed reduced levels of PAI-1 and increased uPAR expression. Adhesion experiments showed reduced adherence to VN of fibroblasts from ISSc lesions and from non-affected areas of the diffuse form, as compared to normal controls. These results suggest a role for uPA and PAI-1 in the ISSc form, likely related to the activation of latent forms of cytokines and to the accumulation of ECM components, whereas a role for uPAR can be hypothesized in the evolvement of the diffuse form, based on its up-regulation in the non-affected areas.
Homocysteine, Vitamin B12 and Folic Acid Levels in Psoriatic Patients and Correlation with Disease Severity
Authors: Brazzelli V. , Grasso V. , Fornara L. , Moggio E. , Gamba G. , Villani S. , Borroni G.
Published: January 2017

Hyperhomocysteinaemia represents an independent risk factor for atherosclerotic cardiovascular disease, stroke, peripheral arterial occlusive disease and venous thrombosis. Psoriasis is a chronic inflammatory skin disease associated with increased atherothrombosis and cardiovascular risk profile. The aim of this study is to investigate homocysteine, folic acid and vitamin B12 levels in a cohort of psoriatic patients and its relationship with the severity of the disease. A retrospective observational study in 98 patients with chronic plaque psoriasis and 98 healthy controls was performed. Total plasma homocysteine level, folic acid, vitamin B12 and PASI index were assessed in every patient. Patients with psoriasis had plasma homocysteine levels higher than controls (57% of cases and 25% of controls; p<0.0001). Folic acid and vitamin B12 plasma levels were lower in psoriatic patients than in controls (p = NS), lower levels of vitamin B12 were found in patients with hyperhomocysteinaemia compared to patients with a normal value of homocysteine (p = 0.0009). The severity of psoriasis assessed according to PASI (19.51±16.26) did not directly correlate either with higher levels of homocysteine or with vitamin B12 and folic acid plasma levels. In conclusion, a significantly higher prevalence of hyperhomocysteinaemia was found in psoriatic patients compared to healthy controls. A significant correlation between hyperhomocysteinaemia and lower vitamin B12 levels, but not folic acid, was evidenced. On the contrary, our data do not correlate the high level of homocysteine with higher PASI scores or psoriasis type, suggesting that homocysteine level can be considered an independent risk factor in psoriatic patients.
JC Viral Reactivation in a Pediatric Patient with Crohn's Disease
Authors: Bellizzi A. , Barucca V. , Di Nardo G. , Fioriti F. , Iebba V. , Schippa S. , Conte M.P. , Checchi M. Proietti , Colosimo M.T. , Cucchiara S. , Oliva S. , Chiarini F. , Pietropaolo V.
Published: January 2017

This is a report concerning human polyomavirus JC (JCV) reactivation in a pediatric patient with Crohn's disease (CD) during the treatment with 5-aminosalicylic acid (5-ASA), a non-steroidal anti-inflammatory drug (NSAID). We examined 9 bioptic samples from three different bowel districts (ileum, cecum, rectum) of this child. These samples were analyzed by Quantitative PCR (Q-PCR) to investigate the presence of JCV DNA. JCV DNA was detected in one rectum biopsy taken two months after 5-ASA treatment. Although our result must be validated in a larger group of subjects and with a longer follow-up period, it underlines the importance of JCV monitoring in CD patients.
Bioavailability of Sandimmun® versus Sandimmun Neoral®: A Meta-Analysis of Published Studies
Authors: Colombo D. , Egan C.G.
Published: January 2017

For the past 25 years, cyclosporine A(CyA) has played a pivotal role in transplant immunosuppressant therapy. From the availability of the 2 primary marketed formulations (Sandimmun® and Sandimmun Neoral®, Novartis), confusion has existed with regard to whether these two formulations are bioequivalent. Due to the underlying clinical relevance of this information, we therefore conducted a meta-analysis of all available comparative pharmacokinetic studies to assess whether the two different CyA formulations, Sandimmun® and Sandimmun Neoral®, can be considered bioequivalent. All clinical studies that compared the bioavailability of the 2 formulations in organ transplant recipients were considered for analysis. We searched computerised databases (Embase/Excerpta Medica and Medline/PubMed) from their inception to May 2010. Only studies with AUC values determined at 12 hours were considered for analysis. Relative bioavailability was calculated with 90% confidence intervals (CI) for Sandimmun® (test substance) versus Sandimmun Neoral® (reference substance) according to Schuirmann's Two One-sided Tests Procedure and the Classical Shortest CI. Homogeneity of data was tested using the χ2 test. Fifteen studies were considered for meta-analysis and none of these studies reported AUC values in the 80%–125% range required for the bioequivalence of two formulations. The overall bioavailability for Sandimmun® versus the microemulsion formulation Sandimmun Neoral® was 76%, with upper CI limits lower than 80% in some cases. Mean AUC values for Sandimmun® were significantly lower than those for Sandimmun Neoral® ( p<0.01). This study demonstrates that the 2 main cyclosporine formulations, Sandimmun® and Sandimmun Neoral®, cannot be considered bioequivalent.
Bosentan Treatment for Raynaud's Phenomenon and Skin Fibrosis in Patients with Systemic Sclerosis and Pulmonary Arterial Hypertension: An Open-Label, Observational, Retrospective Study
Authors: Giordano N. , Puccetti L. , Papakostas P. , Di Pietra N. , Bruni F. , Pasqui A.L. , Acampa M. , Bocchi V. , Donati V. , Voglino M. , Fioravanti A. , Montella A. , Auteri A. , Nuti R. , Pastorelli M.
Published: January 2017

Raynaud's phenomenon (RP) and cutaneous fibrosis are the distinctive manifestations of scleroderma, in which Endothelin-1 plays a fundamental pathogenetic role. Bosentan, an Endothelin-1 receptor antagonist used for the treatment of pulmonary arterial hypertension, retards the beginning of new sclerodermic digital ulcers (DU). This open-label, observational, retrospective study verified the effect of Bosentan on RP and skin fibrosis in sclerodermic outpatients affected by pulmonary arterial hypertension without DU. Fourteen subjects (13 women, 1 man; mean age 60 ± 7.5 years; ten with limited and four with diffuse scleroderma) were observed at baseline (T0) and after four (T1), twelve (T2), twenty-four (T3) and forty-eight (T4) weeks during treatment with Bosentan. They were evaluated for daily quantity and duration of RP attacks and skin thickness (using modified Rodnan total skin score, MRSS). Videocapillaroscopic evaluation was performed at TO and T4. Bosentan decreased significantly the number and duration of RP attacks, beginning at T2 (p<0.05). Videocapillaroscopy showed significant improvement of microcirculatory patterns at T4 (p<0.05). MRSS decreased throughout the study, reaching the statistical significance at T3 and T4 (p<0.01) in the whole cohort. The present data suggest that Bosentan is effective in stabilmng the microcirculation involvement and in improving skin fibrosis irrespective of scleroderma patterns.
C-Reactive Protein and Markers for Thrombophilia in Patients with Chronic Plaque Psoriasis
Authors: Gisondi P. , Malerba M. , Malara G. , Guerra A. Puglisi , Sala R. , Radaeli A. , Calzavara-Pinton P. , Girolomoni G.
Published: January 2017

Chronic plaque psoriasis is associated to an increased risk of cardiovascular events. The aim of our study is to test patients with psoriasis for common markers of acquired and inherited thrombophilia. A cross-sectional study on 172 patients with psoriasis and 198 controls was carried out. The plasma levels of coagulation protein C, coagulation protein S, homocysteine, folic acid, C-reactive protein (CRP) and fibrinogen as well as activated protein C resistance and antithrombin III activity, were measured. CRP and homocysteine levels were higher in patients with psoriasis than in controls (5.9 ± 7.1 vs 3.1 ± 2.4 mg/L, p=0.0003 and 16.3 ± 12.8 vs 10.4 ± 4.6 umol/L, p=0.0001; mean ± SD) whereas folic acid was lower in psoriatic patients compared to controls (4.3 ± 7.2 vs 12.6 ± 7.9 p=0.006). Levels of coagulation protein C, coagulation protein S, fibrinogen as well as activated protein C resistance, antithrombin III activity were within normal ranges both in cases and controls. In a multivariate regression analysis, psoriasis severity was an independent predictor of higher CRP. In conclusion, high levels of serum CRP and homocysteine were found in patients with psoriasis, related to the severity of the disease. These data suggest that the increased risk of thrombotic cardiovascular events observed in psoriasis patients should be ascribed to an acquired rather than inherited thrombophilic status.
The Presence of Non-Segmental Vitiligo Modifies Intracellular Cytokine Subsets in Patients with Chronic Lymphocytic Thyroiditis
Authors: Santaguida M.G. , Del Duca S.C. , Virili C. , Gargano L. , Centanni M.
Published: January 2017

Chronic lymphocytic thyroiditis and vitiligo often occur in association and seem to be characterized by a prevalent Th1-driven autoimmune process. The aim of this study is to analyze selected intracellular Th1 and Th2 cytokines in patients with Hashimoto's thyroiditis when associated with non-segmental vitiligo. We analyzed intracellular interleukin-2, interferon-γ (Th1) and interleukin-4 (Th2), in peripheral blood lymphocytes of 23 patients with isolated Hashimoto's thyroiditis (group A) and of 11 patients with Hashimoto's thyroiditis associated with non-segmental vitiligo (group B). Peripheral blood lymphocytes were stimulated and incubated with specific monoclonal antibodies. Intracellular cytokines were assayed by flow cytometric analysis. Interleukin-2 and interferon-γ positive cells were increased in almost all patients but the median values were similar in patients with isolated Hashimoto's thyroiditis and in those with concurrent vitiligo. In contrast, the number of patients with increased interleukin-4 positive cells was higher in patients with thyroiditis and vitiligo (9/11) than in those with isolated thyroiditis (2/23; p<0.0001). The median values of IL-4 positive cells in the two groups confirmed this difference (A: 5.8%, vs B: 20.6%; p=0.0011). Increased interleukin-4 positive lymphocytes characterize Hashimoto's thyroiditis when associated with non-segmental vitiligo, suggesting a modified balance from highly prevalent Th1 to mixed Th1/Th2 subset.
Nasal Disease and Asthma
Authors: Marseglia Gl , Merli P , Caimmi D , Licari A , Labò E , Marseglia A , Ciprandi G , La Rosa M
Published: January 2017

The nose plays a primary role within the airways, working as “a filter and air-conditioner”, together with other important functions. Thus, it is not surprising that nasal diseases are associated with several other comorbidities, including both upper and lower airways, such as bronchial hyperresponsiveness (BHR) and asthma. Several studies have investigated the relationship existing between the upper and the lower airways and new insights are rising. Nevertheless, some uncertainties still remain, mainly because nasal disorders are quite heterogeneous, overlapping (i.e. rhinitis-rhinosinusitis-sinusitis, acute or chronic, allergic or non-allergic) and difficult to diagnose, so that, frequently, many studies don't differentiate between the various conditions. For this reason, the purpose of this review is to systematically analyze present epidemiological, pathophysiological and clinical data on the relationship between nasal diseases and asthma, splitting up three main conditions: allergic rhinitis, chronic rhinosinusitis and nasal polyposis.
Adipokines and Their Role in Allergies
Authors: Ciprandi G , Caimmi D , Raschetti R , Del Giudice M Miraglia , Salpietro C , Caimmi S , Castellazzi AM
Published: January 2017

Both allergic disorders and obesity keep increasing in industrialized countries. Even though a strong association between obesity and allergy-related diseases has been reported in several studies, no published data show a scientific and firm link in-between the two conditions. In general, obesity and weight gain have been associated with an increased risk of asthma and allergic rhinitis. Asthma, allergic rhinitis and obesity have a common inflammatory pattern that could therefore justify their association. In fact, the chronic inflammation that characterizes the increase in white adipose tissue typically pushes the immune system toward a Th2 pattern. Such a polarization might, consequentially, worsen a pre-existing allergic disease or even stimulate the evolution from a sensitization to a respiratory form of allergy. Several studies have been published on the role of different adipokines on allergic diseases. We focus our review on the role of adipokines on asthma and allergic rhinitis.
Allergic Rhinitis and Quality of Life in Children
Authors: Del Giudice Miraglia M , Marseglia A , Leonardi S , La Rosa M , Salpietro C , Brunese FP , Arrigo T , Perrone L
Published: January 2017

Allergic rhinitis is a respiratory disease caused by an inflammatory process related to IgE mediated reaction versus allergens to which the subject is sensitized. Allergic rhinitis is not an isolated disease because the nasal mucosa inflammation involves paranasal sinuses and lower airways, thus worsening the asthmatic symptoms. Recently, a new classification of allergic rhinitis based on the duration and severity of clinical symptoms has been proposed. This classification takes into consideration both the quality of life and the possible impact of the symptoms on school, work and free-time activities. Children's quality of life is severely compromised by frequent night awakenings, easy fatigue, defects of language and irritability, which can have a negative influence on learning abilities. Allergic rhinitis has a negative impact on the quality of life of the whole family because it can cause interference on social life, and financial costs.
Gene-Environment Interaction in Childhood Asthma
Authors: Rigoli L , Briuglia S , Caimmi S , Ferraù V , Gallizzi R , Leonardi S , La Rosa M , Salpietro C
Published: January 2017

The importance of early life environmental influences on the etiology of asthma is implied by the observed geographic and temporal variation in the prevalence of the disease among children. There is evidence pointing to the role of exposure to allergen, various aspects of diet and hygiene-related factors in the etiology of asthma. There is also evidence that heritable factors influence the impact of hygiene-related exposures on the risk of having asthma. A number of important gene-environment interactions have been identified. These interactions point to the biology of environmental exposures as the involved genetic variation is suggestive of certain underlying mechanisms. Polymorphisms within genes coding for the toll-like receptor-lipopolysaccharide (TLR-LPS) signaling pathway may underlie variations in effects of hygiene-related exposures, including specifically endotoxin, on the risk of developing allergic sensitization and allergic disease. This review presents recent findings illustrating the role of gene-environment interactions in childhood asthma susceptibility.
Adenoid Assessment in Paediatric Patients: The Role of Flexible Nasal Endoscopy
Authors: Pagella F , Pusateri A , Chu F , Cairello F , Benazzo M , Matti E , Marseglia Gl
Published: January 2017

Adenoid hypertrophy is the most common cause of nasal obstruction in paediatric patients. Over the years, various methods to assess the adenoid size were proposed such as the posterior rhinoscopy and the radiological examination of the nasopharynx. Nasal endoscopy was introduced for children in the 80's, and nowadays this is a known and diffuse method in routine practice. The purpose of this article is to describe the personal experience in the assessment of the adenoid size in children, with a particular regard to the flexible nasal endoscopy, and to analyse the literature reports. The personal technique is described in performing nasal endoscopy in paediatric patients, reporting advantages and possible disadvantages of the procedure. A retrospective analysis was conducted on 6036 children since 1999 to 2010. In most cases children fully collaborated to complete the exam. No major or minor complications (such as nose bleedings or other traumatic injuries) were observed. No topical intranasal decongestant, local or general anaesthesia were used in our series. In our opinion, nasal endoscopy in children is a reliable, safe, accurate, easily tolerated and dynamic diagnostic method to assess the adenoid size.
The Evolution of the Adenoidectomy: Analysis of Different Power-Assisted Techniques
Authors: Pagella F , Pusateri A , Canzi P , Caputo M , Marseglia A , Pelizzo G , Mattie E
Published: January 2017

Techniques and instruments for adenoidectomy have considerably changed over the years. With the introduction in Otolaryngology of power-assisted instruments for endoscopic sinus surgery, the classic adenoidectomy performed with curette or adenotome has evolved, with an improved patients' outcome and a better satisfaction of the surgeon. The purpose of this article is to describe and critically analyze the literature reports about different methods of power-assisted adenoidectomy. We performed a literature search (Medline) to identify all available reports. We discussed the surgical techniques and reviewed advantages and disadvantages of each method. The techniques can be schematically divided in non-endoscopic, usually performed with a laryngeal mirror, and endoscopic-assisted. The endoscopic control can be obtained either trans-nasally or trans-orally, as well as the microdebrider can be inserted in the nasal cavity or maneuvered through the oral cavity. Some authors reported the usage of the power-assisted instruments in performing the entire adenoidectomy; while, according with other authors, the microdebrider can be used as a step of the surgical procedure, for a combined adenoidectomy. In conclusion, all the methods seem to be safe and effective, and the personal experience of the surgeon should guide the choice of the instruments. However, we personally consider the endoscopic techniques as the most suitable, and among these the Transoral Endonasal-Controlled Combined Adenoidectomy (TECCA) should be considered as the most ergonomic technique to perform a power-assisted adenoidectomy.
Specific Immunotherapy in Children: The Evidence
Authors: La Rosa M , Lionetti E , Leonardi S , Salpietro A , Bianchi L , Salpietro C , Del Giudice Miraglia M , Ciprandi G , Marseglia Gl
Published: January 2017

Specific immunotherapy (SIT) is the only treatment able to not only act on the symptoms of allergy but also act on the causes. At present, SIT may be administered in two forms: subcutaneous (SCIT) and sublingual immunotherapy (SLIT). SCIT represents the standard modality of treatment while SLIT has recently been introduced into clinical practice and today represents an accepted alternative to SCIT. The main advantages of SIT that are lacking with drug treatment are long-lasting clinical effects and alteration of the natural course of the disease. This prevents the new onset of asthma in patients with allergic rhinitis and the onset of new sensitizations. The mechanism of action of both routes is similar; they modify peripheral and mucosal Th2-responses into a prevalent Th1-polarization with subsequent reduction of the allergic inflammatory reaction. Both have long-term effects for years after they have been discontinued, although for SLIT these evidences are insufficient To date several guidelines have defined indications, contraindications, side-effects, and clinical aspect for SCIT and SLIT. New forms of immunotherapy, allergen products and approaches to food allergy and atopic eczema represents the future of SIT.
Agonist-Induced Release of Neuropeptide Y by Platelets
Authors: Duarte A. Torres , Zukowska-Grojec Z. , Myers A.K.
Published: January 2017

Neuropeptide Y (NPY) is a multi-functional peptide localized in a number of tissues besides the brain, and its expression is high in strains of mice with autoimmune disease. Functionally, along with its neurotransmitter role, NPY has multiple effects on both vascular tissues and tissues involved in immune responses. Previous studies demonstrated that immunoreactive NPY (i-NPY) exists in large quantities in platelets and bone marrow of some species, and suggested its release during platelet aggregation by collagen. Because NPY has been hypothesized to have a role in a number of pathophysiological states in which platelets are involved, including immune responses, hypertension and vascular smooth muscle proliferation, we sought to further characterize platelet i-NPY content and release by a diverse group of physiological platelet agonists.

Platelet rich plasma and gel filtered platelets were prepared from citrated whole blood of male Sprague Dawley rats. Platelet content and concentration of i-NPY were quantified by RIA. Platelet aggregation responses (turbidometric method) and release of i-NPY were measured in rat platelet preparations stimulated by a thromboxane agonist (U44069), collagen, thrombin and ADP. All agents induced dose-dependent aggregation, although ADP and U44069 were weak agonists in citrated platelet rich plasma, ADP only inducing primary aggregation. Total i-NPY content in platelet rich plasma of Sprague-Dawley rats was 32.1±3.8 pmol/ml; more than 20 pmol/ml was released into supernatant of aggregating platelets stimulated with high dose thrombin or collagen during secondary, irreversible aggregation. Although U44069 and ADP both stimulated i-NPY release in a dose-dependent manner, release was substantially lower than with the other agonists.

We conclude that i-NPY release from rat platelets is associated mainly with secondary, irreversible aggregation, and can be produced by a variety of platelet stimulating agents as part of the platelet release reaction. The present study and other recent studies demonstrate wide variability in platelet i-NPY content between and within species. Investigation of the genetic regulation of i-NPY content in platelets could offer new insights into the relationship between NPY and pathophysiology of the immune and cardiovascular systems.
Serum Levels of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in a Group of Patients with Systemic Sclerosis
Authors: Riccio A. , De Caterina M. , Natale D. , Grimaldi E. , Pronesti G. , Montagnani S. , Postiglione L.
Published: January 2017

In this report we investigate the behaviour of the serum levels of Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) in the course of Systemic Sclerosis (SS). This cytokine is produced mainly by T and NK cells, and its possible role in the pathogenesis of SS has not been previously described in the literature. Serum GM-CSF levels were assayed in 10 female patients, ageing from 35 to 70, affected by SS. These patients were not suffering from other disorders and were not being treated with steroids or immunosuppressive drug. A solid phase immunoenzymatic method was used to assess the serum levels of GM-CSF. Reference values were previously determined in a control group of 36 healthy women blood donors (19 premenopausal and 17 postmenopausal) (x̄=20.1 ±12.3 pg/ml). All the patients but one showed significantly increased serum levels of GM-CSF (x̄= 120.9 ±125.5 pg/ml). The highest levels were found in the two oldest patients, who also had the longest clinical history of SS, but a clear correlation with age, disease duration or clinical manifestations was not evident, even if the postmenopausal age group patients showed a higher mean value of GM-CSF (x̄= 148.0±144.1 pg/ml) than that found in the premenopausal age group (x̄= 57.7±1.4 pg/ml) (in contrast with the findings in the control group). The absence of other pathogenic conditions in our patients suggests that the increase in serum levels of GM-CSF might be linked to the fibroblast proliferation which is typical of SS. However, our results do not explain the role played by this factor in the fibroblastic proliferation process and an in vitro study is necessary to clarify this aspect.
5α-Reductases and Their Inhibitors
Authors: Spera G. , Lubrano C.
Published: January 2017

5α reductase is a key enzyme in androgen metabolism. Altered enzyme function and/or regulation is responsible for numerous human pathologies such as benign prostatic hyperplasia, acne, hirsutism and male pattern baldness. In order to block androgen action through inhibition of this enzyme, numerous compounds have been synthesized during the past two decades. Among them, 4-azasteroids and in particular finasteride have been extensively studied and used in the treatment of human diseases.
An Abstinence-Oriented Program for Substance Use Disorders: Poorer Outcome Associated with Opiate Dependence
Authors: Paraherakis Antonios , Charney Dara A , Palacios-Boix Jorge , Gill Kathryn
Published: January 2017

Objectives:

To evaluate the characteristics of patients with various substance-related disorders, and to examine rates of retention in treatment.

Methods:

We assessed the demographic characteristics, substance abuse, and psychological distress of 239 men and women at admission. Six-month performance was evaluated, using as criteria length of stay in treatment, abstinence, attendance in therapy sessions, and completion status at discharge.

Results:

Moderate to severe psychological distress was observed among these individuals. Higher levels of depression were found among women and in individuals with alcohol and sedative use disorders. The primary drug of abuse, frequency of use, and reason for entering treatment were the most significant predictors of retention.

Conclusions:

Opiate-addicted clients had the worst prognosis and treatment profiles. Further research is needed to identify factors that would optimize treatment for opiate dependence.
Traumatismes, Stress Traumatique, et Dépression à La Suite de Catastrophes Aériennes
Authors: Birmes Philippe , Ducassé Jean-Louis , Warner Barbara A , Payen Alain , Schmitt Laurent
Published: January 2017

Objectifs:

Les réactions de stress aigu à la suite de traumatismes représentent des indices de vulnérabilité à l'état de stress post-traumatique (ESPT); d'autre part, la comorbidité ESPT et dépression est fréquemment observée. Une exposition traumatique antérieure peut être un facteur de risque supplémentaire de développement de l'ESPT.

Méthode:

Huit blessés, hospitalisés à la suite d'une catastrophe aérienne, sont suivis et évalués pendant un mois. Les symptômes d'état de stress aigu (ESA), d'ESPT et de dépression sont évalués selon les critères du DSM-IV immédiatement après l'accident, puis chaque semaine. La passation de l'échelle de l'impact de l'événement (IES) est effectuée au 30e jour (J30).

Résultats:

Quatre sujets présentent un ESA, 3 d'entre eux présentent un ESPT à J30. Parmi ces 3 sujets « ESPT », 2 présentent une dépression associée. Ces 2 sujets avaient été exposés à un événement traumatique antérieur à la catastrophe aérienne; une relation significative est observée entre l'anamnèse d'un traumatisme antérieur et un ESPT avéré associé à une dépression.

Conclusion:

Les victimes traumatisées ayant des antécédents d'événements traumatiques antérieurs semblent plus vulnérables au développement d'un ESPT associé à une dépression.
Prescription Medication Use among an Aboriginal Population Accessing Addiction Treatment
Authors: Wardman Dennis , Khan Nadia , el-Guebaly Nady
Published: January 2017

Objectives:

Inappropriate prescription medication use can have significant consequences. Although it is suspected that Aboriginal populations within Canada have high rates of inappropriate use, published information is lacking. To better understand this issue, we studied an Aboriginal population seeking addiction treatment.

Methods:

We surveyed Aboriginal clients who accessed addiction treatment in Calgary, Alberta, for prescription medication use in the previous year, frequency of medication use, and medication source(s), if inappropriately used.

Results:

Sixty-nine percent of the clients completed the survey ( n = 144). Most respondents were aged 31 to 50 years (56%), and 52% were male. Of the respondents, 48% reported that they used prescription medication inappropriately, 8% indicated appropriate use, and the rest indicated no medication use. Sedatives or relaxants were most frequently used inappropriately. Among those who inappropriately used medication, 47% used medication more than 10 times in the previous year. Common sources for those who used medication inappropriately included medication given by a friend or a stranger (52%), medication bought on the street (45%), and medication prescribed by a physician (41%). Age greater than or equal to 30 years was associated with inappropriate use. Sex, residence, and Aboriginal status were not found to be associated with inappropriate use.

Conclusion:

Inappropriate prescription medication use was a significant problem among an Aboriginal population that sought addiction treatment, and many of these individuals accessed medication from a prescribing physician.
Preliminary Assessment of Intrahemispheric QEEG Measures in Bipolar Mood Disorders
Authors: Oluboka OJ , Stewart SL , Sharma V , Mazmanian D , Persad E
Published: January 2017

Objective:

This study assessed the quantitative electroenchephalographic (QEEG) absolute power and coherence differences between a group of patients with bipolar I mood disorder (BMD I) and a group of patients with schizophrenia. We also examined the correlation between QEEG measures and family history of BMD.

Method:

Using the National Institutes of Mental Health (NIMH) Global Rating Scale, we rated 18 adult inpatients with a DSM-III-R diagnosis of BMD I for the severity of the current episode. We also collected data on the family history of the illness. This group was then matched for age, sex, and handedness with an equal number of inpatients with a DSM-III-R diagnosis of schizophrenia. QEEG absolute power and coherence was calculated for the alpha bandwidth (8.0 to 12.0 Hz), assessed at 18 pairs of electrodes in both hemispheres during resting, eyes-closed condition in all the patients.

Results:

The patients with schizophrenia showed significantly higher coherence ( P = 0.047) at 6 pairs of electrodes on the right side. The group with BMD showed significantly higher power ( P = 0.042) at 2 pairs of electrodes on the right side. Correlational analysis showed that QEEG measures were significantly correlated ( P = 0.01) with positive family history of BMD.

Conclusion:

These findings suggest that the patients with BMD are more disorganized in the right anterior hemisphere and that there is a significant positive correlation between the QEEG measures and the presence of family history of BMD. Further studies in a larger sample are required to confirm these preliminary findings.
Medication Strategies in Childhood Aggression: A Review
Authors: Bassarath Lindley
Published: January 2017

Objective:

To review studies of psychopharmacological management of aggression in common childhood psychiatric disorders.

Method:

Using OVID software, we searched Medline for studies that were undertaken in the last 30 years. Controlled and uncontrolled data are summarized for each condition.

Results:

A paucity of evidence-based information currently exists. Even so, specific indications from the existing literature can be suggested for several classes of psychotropics, particularly in conduct disorder (CD), attention-deficit hyperactivity disorder (ADHD), mood disorders, and other conditions.

Conclusions:

Clinicians can use findings from reviewed controlled and, where necessary, uncontrolled studies to inform pharmacologic practice. This review offers suggestions for future research directions that will aid clinical practice.
Lithium Augmentation Therapy in Refractory Depression: Clinical Evidence and Neurobiological Mechanisms
Authors: Bauer Michael , Adli Mazda , Baethge Christopher , Berghöfer Anne , Sasse Johanna , Heinz Andreas , Bschor Tom
Published: January 2017

Objective:

This systematic review examines the evidence and discusses the clinical relevance of lithium augmentation as a treatment strategy for refractory major depressive episodes. It also examines hypotheses on the mode of action of lithium augmentation, with a focus on serotonin (5-HT) and neuroendocrine systems, and proposes recommendations for future research.

Method:

We searched the Medline computer database and the Cochrane Library for relevant original studies published in English from January 1966 to February 2003. The key words were as follows: lithium, augmentation strategies, lithium augmentation, major depression, refractory depression, treatment-resistant depression, neuroendocrinology, and serotonin.

Results:

Of 27 prospective clinical studies published since 1981, 10 were double-blind, placebo-controlled trials, 4 were randomized comparator trials, and 13 were open-label trials. Five of 9 acute-phase placebo-controlled trials demonstrated that lithium augmentation had substantial efficacy. In the acute-treatment trials, the average response rate in the lithium group was 45%, and in the placebo group, 18% ( P < 0.001). One placebo-controlled trial showed the efficacy of lithium augmentation in the continuation-phase treatment. Summarizing the open and controlled data, approximately 50% of patients responded to lithium augmentation within 2 to 6 weeks. Animal studies offer robust evidence that lithium augmentation increases 5-HT neurotransmission, possibly by a synergistic action of lithium and the antidepressant on brain 5-HT pathways.

Conclusions:

Augmentation of antidepressants with lithium is the best-documented augmentation therapy in the treatment of refractory depression. Emerging data from animal studies suggest that the 5-HTergic system is involved in the augmentatory effect of lithium.
Prophylaxis Latency and Outcome in Bipolar Disorders
Authors: Baethge Christopher , Tondo Leonardo , Bratti Irene M , Bschor Tom , Bauer Michael , Viguera Adele C , Baldessarini Ross J
Published: January 2017

Objective:

To analyze new and reviewed findings to evaluate relations between treatment response and latency from onset of bipolar disorder (BD) to the start of mood-stabilizer prophylaxis.

Method:

We analyzed our own new data and added findings from research reports identified by computerized searching.

Results:

We found 11 relevant studies, involving 1485 adult patients diagnosed primarily with BD. Reported latency to prophylaxis averaged 9.6 years (SD 1.3), and follow-up in treatment averaged 5.4 years (SD 3.1). Greater illness intensity and shorter treatment latency were closely associated, resulting in a greater apparent reduction in morbidity with earlier treatment. However, this finding was not sustained after correction for pretreatment morbidity, and treatment latency did not predict morbidity during treatment. Therefore, assessments based on improvement with treatment, or without correction for pretreatment morbidity, can be misleading.

Conclusions:

Available evidence does not support the proposal that delayed prophylaxis may limit response to prophylactic treatment in BD and related disorders.