Clinical assessment of the efficacy of photodynamic therapy in the treatment of oral lichen planus

The study objective was clinical assessment of the efficacy of photodynamic therapy (PDT) in the treatment of oral lichen planus (OLP). There were 23 patients aged 31–82 included in the study with oral lichen planus diagnosed clinically and histopathologically. In all patients photodynamic therapy was performed with the use of chlorin e6 (Photolon^®), containing 20 % chlorin e6 and 10 % dimethyl sulfoxide as a photosensitizer. PDT was performed using a semiconductor laser, with power up to 300 mW and a wavelength of 660 nm. A series of illumination sessions was conducted with the use of superficial light energy density of 90 J/cm². Changes of lesion size were monitored at one, two, five, and ten PDT appointments from the series of ten according to the authors' own method. The sizes of clinical OLP lesions exposed to PDT were reduced significantly (on average by 55 %). The best effects were observed for the lesions on the lining mucosa (57.6 %). The therapy was statistically significantly less effective when masticatory mucosa was affected (reduction, 30.0 %). Due to substantial efficacy and noninvasiveness, PDT can be useful in the treatment of OLP lesions.     

Validity of an automated telephonic system to assess COPD exacerbation rates

Current tools for recording chronic obstructive pulmonary disease (COPD) exacerbations are limited and often lack validity testing. We assessed the validity of an automated telephonic exacerbation assessment system (TEXAS) and compared its outcomes with existing tools. Over 12 months, 86 COPD patients (22.1% females; mean age 66.5 yrs; mean post-bronchodilator forced expiratory volume in 1 s 53.4% predicted) were called once every 2 weeks by TEXAS to record changes in respiratory symptoms, unscheduled healthcare utilisation and use of respiratory medication. The responses to TEXAS were validated against exacerbation-related information collected by observations made by trained research assistants during home visits. No care assistance was provided in any way. Diagnostic test characteristics were estimated using commonly used definitions of exacerbation. Detection rates, compliance and patient preference were assessed, and compared with paper diary cards and medical record review. A total of 1,824 successful calls were recorded, of which 292 were verified by home visits (median four calls per patient, interquartile range three to five calls per patient). Independent of the exacerbation definition used, validity was high, with sensitivities and specificities between 66% and 98%. Detection rates and compliance differed extensively between the different tools, but were highest with TEXAS. Patient preference did not differ. TEXAS is a valid tool to assess COPD exacerbation rates in prospective clinical studies. Using different tools to record exacerbations strongly affects exacerbation occurrence rates.     

Resistant hypertension in visceral obesity

BackgroundVisceral obesity increases the risk of arterial hypertension (78% of cases of hypertension in men and 65% of cases in women). The aim of the study is to assess the role of visceral obesity in causing resistant hypertension (RH).MethodsThe survey was performed on 5065 hypertensive patients with visceral obesity. BP control was analyzed on the basis of office and home BP measurements. Patients reporting non-compliance were excluded from the study.ResultsThe percentage of RH after excluding undertreated patients (receiving less than 3 drugs or on at least 3-drug regimen without diuretic and without reaching target BP goal) was 13.9%. RH was more frequent only in obese with BMI ≥ 35 and < 40 kg/m² (16.2%) and in morbidly obese individuals (26.5%). Patients with BMI ≥ 35 and < 40 kg/m² and with morbid obesity were receiving three-drug therapy more frequently than patients with visceral obesity and BMI < 30 kg/m². A multiple regression analysis revealed that obesity was associated with RH independent from longer than 5-year period of antihypertensive therapy, diabetes, smoking cigarettes, cardiovascular disease and heart failure. The analysis of home BP measurement revealed that in 11.1% of patients RH was in fact “white coat” hypertension.ConclusionsUndertreatment, underuse of diuretics in multidrug regimens, and the “white-coat” effect are the most common reasons for over-diagnosing resistant hypertension in patients with visceral obesity. Obesity is an independent risk factor for the occurrence of RH.     

Matrix composition regulates three-dimensional network formation by endothelial cells and mesenchymal stem cells in collagen/fibrin materials

Co-cultures of endothelial cells (EC) and mesenchymal stem cells (MSC) in three-dimensional (3D) protein hydrogels can be used to recapitulate aspects of vasculogenesis in vitro. MSC provide paracrine signals that stimulate EC to form vessel-like structures, which mature as the MSC transition to the role of mural cells. In this study, vessel-like network formation was studied using 3D collagen/fibrin (COL/FIB) matrices seeded with embedded EC and MSC and cultured for 7 days. The EC:MSC ratio was varied from 5:1, 3:2, 1:1, 2:3 and 1:5. The matrix composition was varied at COL/FIB compositions of 100/0 (pure COL), 60/40, 50/50, 40/60 and 0/100 (pure FIB). Vasculogenesis was markedly decreased in the highest EC:MSC ratio, relative to the other cell ratios. Network formation increased with increasing fibrin content in composite materials, although the 40/60 COL/FIB and pure fibrin materials exhibited the same degree of vasculogenesis. EC and MSC were co-localized in vessel-like structures after 7 days and total cell number increased by approximately 70%. Mechanical property measurements showed an inverse correlation between matrix stiffness and network formation. The effect of matrix stiffness was further investigated using gels made with varying total protein content and by crosslinking the matrix using the dialdehyde glyoxal. This systematic series of studies demonstrates that matrix composition regulates vasculogenesis in 3D protein hydrogels, and further suggests that this effect may be caused by matrix mechanical properties. These findings have relevance to the study of neovessel formation and the development of strategies to promote vascularization in transplanted tissues.     

Cost-effectiveness of tobacco control policies in Vietnam: the case of personal smoking cessation support

Aims To examine the cost‐effectiveness of personal smoking cessation support in Vietnam. Design, setting and participants We followed‐up the population aged 15 years and over in 2006 to model the costs and health gains associated with five interventions: physician brief advice; nicotine replacement therapy (patch and gum); bupropion; and varenicline. Threshold analysis was undertaken to determine the price levels of pharmaceuticals for the interventions to be cost‐effective. A multi‐state life table model was constructed such that the interventions affect the smoking cessation behaviour of the age cohorts, and the resulting smoking prevalence defines their health outcomes. A health‐care perspective was employed. Measurements Cost‐effectiveness is measured in 2006 Vietnamese Dong (VND) per disability‐adjusted life year (DALY) averted. We adopted the World Health Organization thresholds of being ‘cost‐effective’ if less than three times gross domestic product (GDP) per capita (VND 34 600 000) and ‘very cost‐effective’ if less than GDP per capita (VND 11 500 000). Findings The cost‐effectiveness result of physician brief advice was VND 1 742 000 per DALY averted (international dollars 543), which was ‘very cost‐effective’. Varenicline dominated bupropion and nicotine‐replacement therapies, although it did not fall within the range of being ‘cost‐effective’ under different scenarios. The threshold analysis revealed that prices of pharmaceuticals must be substantially lower than the levels from other countries if pharmacological therapies are to be cost‐effective in Vietnam. Conclusions Physician brief advice is a cost‐effective intervention and should be included in the priority list of tobacco control policy in Vietnam. Pharmacological therapies are not cost‐effective, and so they are not recommended in Vietnam at this time unless pharmaceuticals could be produced locally at substantially lower costs in the future.     

CLT1 targets angiogenic endothelium through CLIC1 and fibronectin

Angiogenesis is important for tumor growth and metastasis. CLT1 (CGLIIQKNEC), a peptide that binds to tumor interstitial spaces in the presence of fibrin-fibronectin, has structural similarity to the anti-angiogenic β-sheet peptides anastellin and anginex. This similarity is reflected in the ability of CLT1 to form co-aggregates with fibronectin that induce an unfolded protein response and cause autophagic cell death in proliferating endothelial cells. CLT1 cytotoxicity is mediated at least in parts by a novel CLT1 binding protein, Chloride Intracellular Channel 1 (CLIC1), which promotes internalization of CLT1-fibronectin co-aggregates in a mechanism that depends on the LIIQK amino acid sequence of CLT1. LIIQK encompasses amino acid residues relevant for CLT1 binding to CLIC1 and in addition, facilitates the formation of CLT1-fibronectin co-aggregates, which in turn promote translocation of CLIC1 to the endothelial cell surface through ligation of integrin αvβ3. Paralleling the in vitro results, we found that CLT1 co-localizes with CLIC1 and fibronectin in angiogenic blood vessels in vivo, and that CLT1 treatment inhibited angiogenesis and tumor growth. Our findings show that CLT1 is a new anti-angiogenic compound, and its mechanism of action is to form co-aggregates with fibronectin, which bind to angiogenic endothelial cells through integrins, become internalized through CLIC1 and elicit a cytotoxic unfolded protein response. The simple structure and high potency of CLT1 make it a potentially useful compound for anti-angiogenic treatments.     

What's your diagnosis?: Skin lesions in a young female with Behcet's disease

A young female with known Behcet's disease presented with skin lesions over lower limbs. The lesions were biopsied and found to be pyoderma gangrenosum. The lesions responded to oral steroids for 6 weeks.