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Παρασκευή 3 Φεβρουαρίου 2017

A study of the association of acanthosis nigricans with subclinical atherosclerosis

Elizabeth Guevara-Gutiérrez, Alberto Tlacuilo-Parra, Pedro Gutiérrez-Fajardo, Tania Sánchez-Tenorio, Fernando Barba-Gómez, Alejandra Miranda-Díaz

Indian Journal of Dermatology, Venereology, and Leprology 2017 83(2):190-194

Background: Hyperinsulinism is related to the presence of acanthosis nigricans and atherosclerosis; however, we were unable to find any study on the prevalence of atherosclerosis in acanthosis nigricans. Aims: To evaluate the prevalence of carotid atherosclerosis and metabolic alterations in Mexican patients with acanthosis nigricans. Methods: We carried out a cross-sectional study that included 45 patients with acanthosis nigricans, age- and gender-matched with 45 healthy participants. Volunteers with any comorbidity or taking weight reduction, glucose- and/or lipid-lowering medication or drugs capable of causing acanthosis nigricans were not included in the study. B-mode ultrasound tests were done to measure the carotid intima-media thickness. Body mass index, insulin, glucose and lipid blood serum levels were measured. Chi-square or Fisher's exact test and paired Student t-test were used for statistical analysis. Results: Carotid intima-media thickness was greater in patients with acanthosis nigricans (mean 0.52 mm vs. 0.46 mm, P = 0.002). The prevalence of abnormal intima-media thickness was higher in patients with acanthosis nigricans versus healthy participants (62.2% vs. 35.5%, P = 0.02). The same occurred with hyperinsulinemia (73.3% vs. 13.3%, P< 0.001), insulin resistance (86.6% vs. 33.3%, P< 0.001), obesity (86.6% vs. 13.3%, P< 0.001) and dyslipidemia (95.5% vs. 77.7%, P = 0.01). Limitations: The sample size is small and serum markers of cardiovascular risk were not measured. Conclusion: Acanthosis nigricans is a skin marker for metabolic disturbances and is also associated with carotid atherosclerosis, a finding which is not well documented. We propose that individuals with acanthosis nigricans should be routinely evaluated for these cardiovascular risks.

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Development of a single-dose recombinant CAMP factor entrapping poly(lactide-co-glycolide) microspheres-based vaccine against Streptococcus agalactiae

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Publication date: Available online 2 February 2017
Source:Vaccine
Author(s): Gang Liu, Jinhua Yin, Herman W. Barkema, Liben Chen, Muhammad Shahid, Otto Szenci, Jeroen De Buck, John P. Kastelic, Bo Han
Streptococcus agalactiae is an important contagious bovine mastitis pathogen. Although it is well controlled and even eradicated in most Northern European and North American dairy herds, the prevalence of this pathogen remains very high in China. However, research on development of a vaccine against S. agalactiae mastitis is scarce. The aims of the present study were to: (1) develop a single-dose vaccine against S. agalactiae based on poly(lactic-co-glycolic acid) (PLGA) microspheres (MS) encapsulated CAMP factor, a conserved virulent protein encoded by S. agalactiae's cfb gene; and (2) evaluate its immunogenicity and protective efficacy in a mouse model. The cfb gene was cloned and expressed in a recombinant Escherichia coli strain Trans1-T1. The CAMP factor was tested to determine a safe dose range and then encapsulated in MS of PLGA (50:50) to assess its release pattern in vitro and immune reaction in vivo. Furthermore, a mouse model and a histopathological assay were developed to evaluate bacterial burden and vaccine efficacy. In the low dosage range (<100μg), CAMP factor had no obvious toxicity in mice. The release pattern in vitro was characterized by an initial burst release (44%), followed by a sustained and slower release over 7wk. In mice immunized with either pure CAMP factor protein or PLGA-CAMP, increased antibody titers were detected in the first 2wk, whereas only PLGA-CAMP immunization induced a sustained increase of antibody titers. In mice vaccinated with PLGA-CAMP, mortality and bacteria counts were lower (compared to a control group) after S. agalactiae challenge. Additionally, no pathological lesions were detected in the vaccinated group. Therefore, PLGA-CAMP conferred protective efficacy against S. agalactiae in our mouse model, indicating its potential as a vaccine against S. agalactiae mastitis. Furthermore, the slow-release kinetics of PLGA MS warranted optimism for development of a single-dose vaccine.



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Intralesional methotrexate as an adjuvant treatment for pyoderma gangrenosum: A case report

Constanza del Puerto, Cristián P Navarrete-Dechent, Juan E Carrasco-Zuber, Cristián Vera-Kellet

Indian Journal of Dermatology, Venereology, and Leprology 2017 83(2):277-277



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Doses per vaccine vial container: An understated and underestimated driver of performance that needs more evidence

Publication date: Available online 3 February 2017
Source:Vaccine
Author(s): Alexis Heaton, Kirstin Krudwig, Tina Lorenson, Craig Burgess, Andrew Cunningham, Robert Steinglass
The widespread use of multidose vaccine containers in low and middle income countries' immunization programs is assumed to have multiple benefits and efficiencies for health systems, yet the broader impacts on immunization coverage, costs, and safety are not well understood. To document what is known on this topic, how it has been studied, and confirm the gaps in evidence that allow us to assess the complex system interactions, the authors undertook a review of published literature that explored the relationship between doses per container and immunization systems. The relationships examined in this study are organized within a systems framework consisting of operational costs, timely coverage, safety, product costs/wastage, and policy/correct use, with the idea that a change in dose per container affects all of them, and the optimal solution will depend on what is prioritized and used to measure performance.Studies on this topic are limited and largely rely on modeling to assess the relationship between doses per container and other aspects of immunization systems. Very few studies attempt to look at how a change in doses per container affects vaccination coverage rates and other systems components simultaneously. This article summarizes the published knowledge on this topic to date and suggests areas of current and future research to ultimately improve decision making around vaccine doses per container and increase understanding of how this decision relates to other program goals.



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Neurological diseases and bullous pemphigoid: A case–control study in Iranian patients

Maryam Daneshpazhooh, Javad Khorassani, Kamran Balighi, Narges Ghandi, Hamidreza Mahmoudi, Hamidreza Tohidinik, Shahin Hamzelou, Cheyda Chams-Davatchi

Indian Journal of Dermatology, Venereology, and Leprology 2017 83(2):195-199

Introduction: Neurological diseases are important co-morbidities found in association with bullous pemphigoid. Various neurological conditions (stroke, Parkinson's disease, dementia, epilepsy and multiple sclerosis) have been reported as associations of this bullous disease; whether these are significant has not been definitely proved. However, the presence of neurological conditions is a predictor of poorer prognosis. Objectives: Our aim was to examine the association of bullous pemphigoid and neurological diseases in Iranian bullous pemphigoid patients. Methods: The medical records of one hundred and sixty consecutive bullous pemphigoid patients who presented to the Autoimmune Bullous Diseases Research Center, Tehran, Iran, from 2006 to 2011 were examined for evidence of any neurological disease. The control group comprised of 317 age- and sex-matched subjects. Results: Neurological diseases were seen in 42 (26.4%) patients with bullous pemphigoid and in 29 (9.1%) controls (odds ratio: 3.53 (2.1–5.9), P< 0.001). Comparing cases to controls, stroke was seen in 17.5% versus 4.1%, odds ratio 4.96 (2.49–9.88); dementia in 5.6% versus 1.9%, odds ratio 3.09 (1.08–8.84); Parkinson's disease in 2.5% versus 2.2%, odds ratio 1.14 (0.33–3.94); epilepsy in 2.5% versus 0.6%, odds ratio 4.04 (0.73–22.3); and multiple sclerosis in 0 versus 0.3% odds ratio 1.00 (0.98–1.01). Limitations: The main limitations of our study were referral bias, retrospective design and a rather low sample size. Conclusions: Neurological diseases in general, and stroke and dementia in particular, were significantly associated with bullous pemphigoid in our study.

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Metabolites as biomarkers of adverse reactions following vaccination: A pilot study using nuclear magnetic resonance metabolomics

Publication date: Available online 3 February 2017
Source:Vaccine
Author(s): Bruce M. McClenathan, Delisha A. Stewart, Christina E. Spooner, Wimal W. Pathmasiri, Jason P. Burgess, Susan L. McRitchie, Y. Sammy Choi, Susan C.J. Sumner
An Adverse Event Following Immunization (AEFI) is an adverse reaction to a vaccination that goes above and beyond the usual side effects associated with vaccinations. One serious AEFI related to the smallpox vaccine is myopericarditis. Metabolomics involves the study of the low molecular weight metabolite profile of cells, tissues, and biological fluids, and provides a functional readout of the phenotype. Metabolomics may help identify a particular metabolic signature in serum of subjects who are predisposed to developing AEFIs. The goal of this study was to identify metabolic markers that may predict the development of adverse events following smallpox vaccination. Serum samples were collected from military personnel prior to and following receipt of smallpox vaccine. The study population included five subjects who were clinically diagnosed with myopericarditis, 30 subjects with asymptomatic elevation of troponins, and 31 subjects with systemic symptoms following immunization, and 34 subjects with no AEFI, serving as controls. Two-hundred pre- and post-smallpox vaccination sera were analyzed by untargeted metabolomics using 1H nuclear magnetic resonance (NMR) spectroscopy. Baseline (pre-) and post-vaccination samples from individuals who experienced clinically verified myocarditis or asymptomatic elevation of troponins were more metabolically distinguishable pre- and post-vaccination compared to individuals who only experienced systemic symptoms, or controls. Metabolomics profiles pre- and post-receipt of vaccine differed substantially when an AEFI resulted. This study is the first to describe pre- and post-vaccination metabolic profiles of subjects who developed an adverse event following immunization. The study demonstrates the promise of metabolites for determining mechanisms associated with subjects who develop AEFI and the potential to develop predictive biomarkers.



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Oral involvement in disseminated superficial porokeratosis

Riti Bhatia, Vishal Gupta, Neena Khanna

Indian Journal of Dermatology, Venereology, and Leprology 2017 83(2):244-246



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Impact of vaccination on influenza mortality in children <5years old in Mexico

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Publication date: Available online 2 February 2017
Source:Vaccine
Author(s): Evelyn L. Sánchez-Ramos, Joel Monárrez-Espino, Daniel E. Noyola
BackgroundInfluenza is a leading cause of respiratory tract infections among children. In Mexico, influenza vaccination was included in the National Immunization Program since 2004. However, the population health effects of the vaccine on children have not been fully described. Thus, we estimated the impact of influenza immunization in terms of mortality associated with this virus among children younger than 5years of age in Mexico.MethodsMortality rates and years of life lost associated with influenza were estimated using national mortality register data for the period 1998–2012. Age-stratified and cause-specific mortality rates were estimated for all-cause, respiratory and cardiovascular events. Influenza-associated mortality was compared between the period prior to introduction of the influenza vaccine as part of the National Immunization Program (1998–2004) and the period thereafter (2004–2012).ResultsDuring the 1998–2012 winter seasons, the average number of all-cause, respiratory and cardiovascular deaths attributable to influenza were 1186, 794 and 21, respectively. Influenza-associated mortality was higher prior to the vaccination period than after influenza was included in the immunization program for all-cause (mean 1660 vs. 780) and respiratory (mean 1063 vs. 563) mortality, but no reduction was seen for cardiovascular mortality. The proportion of all-cause and respiratory deaths attributable to influenza was significantly lower in the post-vaccine period compared with the pre-vaccine period (P<0.001), but no reduction was seen in the proportion of cardiovascular deaths. There was an average annual reduction of 66,558years of life lost in the post-vaccine compared with the pre-vaccine period.ConclusionThe introduction of influenza vaccination within the Mexican Immunization Program was associated with a reduction in mortality rates attributable to this virus among children younger than 5years of age.



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Variables affecting interpretation of skin prick test results

Suhan Günasti Topal, Bilge Fettahlıoğlu Karaman, Varol L Aksungur

Indian Journal of Dermatology, Venereology, and Leprology 2017 83(2):200-204

Background: Both performer- and device-dependent variabilities have been reported in sizes of wheal responses to skin prick tests. Objective: We aimed to evaluate whether or not variabilities in sizes of wheal responses influence the final interpretation of skin prick tests; in other words, the decision on whether or not there is an allergy to a given antigen. Methods: Skin prick tests with positive and negative controls and extracts of Dermatophagoides farinae and Dermatophagoides pteronyssinus were done for 69 patients by two different persons, using two different puncturing devices- disposable 22-gauge hypodermic needles and metal lancets. Results: Among four different skin prick tests, the average coefficients of variation in sizes of wheal responses were near to or higher than 20% for all of them. On the other hand, in the final interpretation of results, kappa values indicated substantial or almost perfect agreements between these tests. However, the frequency of establishing allergy to the house dust mites widely ranged in these tests (20.8–35.8% for D. farinae and 20.8–28.3% for D. pteronyssinus). Limitations: The conduction of the study in a single center and the comparisons of results of only two performers. Conclusion: We feel that variabilities in sizes of wheal responses of skin prick test can influence its categorical results.

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Early sexual debut warrants HPV vaccination at an earlier age

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Publication date: Available online 2 February 2017
Source:Vaccine
Author(s): Abbey B. Berenson, Sharon Croisant




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Extensive and refractory genital herpes in human immunodeficiency virus-infected patient successfully treated with imiquimod: Case report and literature review

Helena Reich Camasmie, Caroline Barbosa, Omar Lupi, Ricardo Barbosa Lima, Marcio Serra, Antonio Macedo D'Acri, Carlos José Martins

Indian Journal of Dermatology, Venereology, and Leprology 2017 83(2):256-259



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Safety of quadrivalent live attenuated influenza vaccine in subjects aged 2–49years

Publication date: Available online 2 February 2017
Source:Vaccine
Author(s): Roger Baxter, Abigail Eaton, John Hansen, Laurie Aukes, Herve Caspard, Christopher S. Ambrose
BackgroundQuadrivalent live attenuated influenza vaccine (Q/LAIV) was licensed in 2012 and replaced trivalent live attenuated influenza vaccine in the United States during the 2013–2014 influenza season. This study assessed the safety of Q/LAIV in children and adults aged 2–49years.MethodsThis was a prospective observational cohort study using data collected from Kaiser Permanente Northern California. Post-vaccination events of interest were any hospitalization, hospitalization for lower respiratory tract infection, and the following medically attended events: hypersensitivity, seizures/convulsions, lower respiratory tract infection, wheezing, Guillain-Barré syndrome, Bell's palsy, encephalitis, neuritis, vasculitis, and narcolepsy/cataplexy. The rates of these events during the risk interval post-vaccination were compared with rates observed during reference periods later in the follow-up (within-cohort analysis) and with rates observed in frequency-matched unvaccinated controls and inactivated influenza vaccine (IIV) recipients.ResultsA total of 62,040 eligible Q/LAIV recipients were identified during the 2013–2014 influenza season. Within-cohort comparisons of all Q/LAIV recipients as well as comparisons between Q/LAIV recipients and unvaccinated controls or IIV recipients did not show any significantly higher risk of hospitalizations or medically attended events following administration of Q/LAIV. Additional analyses by setting (clinic visits, emergency department visits, and hospital admissions) and age group (2–4, 5–8, 9–17, and 18–49years) also did not reveal clinically consistent findings that suggested any increased risk after administration of Q/LAIV.ConclusionIn this large population study of individuals aged 2–49years, no safety signals associated with the administration of Q/LAIV were observed. A much larger study population would be needed to confidently reject any association between Q/LAIV and very rare events, specifically those with an incidence of <1 event/10,000 person-years.Trial registration: ClinicalTrials.gov NCT01985997



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Cutaneous problems in elderly diabetics: A population-based comparative cross-sectional survey

N Asokan, VG Binesh

Indian Journal of Dermatology, Venereology, and Leprology 2017 83(2):205-211

Background: There are few population-based studies on prevalence of cutaneous problems in diabetes mellitus. Aims: To identify skin problems associated with diabetes mellitus among elderly persons in a village in Kerala. Methods: In this population-based cross-sectional survey, we compared the prevalence of skin problems among 287 elderly diabetics (aged 65 years or more) with 275 randomly selected elderly persons without diabetes mellitus. Results: Numbness, tingling and burning sensation of extremities,"prayer sign", finger pebbling, skin tags, stiff joints and acanthosis nigricans were noted more frequently in diabetics as compared to non-diabetics. Ache in extremities, dermatophytosis, candidiasis, seborrheic keratoses/dermatosis papulosa nigra, xerosis/ichthyosis, idiopathic guttate hypomelanosis, nonspecific itching, and eczema were equally frequent in both groups. Among the diagnostic categories, neurovascular, metabolic and autoimmune findings were associated with diabetes mellitus, whereas bacterial and fungal infections were not. Limitations: Initial misclassification errors, no laboratory confirmation of dermatological diagnosis during survey, coexistence of findings related to aging and not analyzing the effects of glycemic level, concurrent diseases and medications. Conclusions: Numbness, tingling and burning sensation of extremities, prayer sign, finger pebbling, skin tags, stiff joints and acanthosis nigricans were associated with diabetes mellitus among elderly persons in a village in Kerala.

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Giant eccrine hidrocystoma of the eyelid

Manpreet Singh, Manpreet Kaur, Natasha Gautam

Indian Journal of Dermatology, Venereology, and Leprology 2017 83(2):267-267



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Paronychia and onychomadesis due to pemphigus vulgaris

Sushil S Savant, Anupam Das, Piyush Kumar

Indian Journal of Dermatology, Venereology, and Leprology 2017 83(2):212-212



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Metastatic tubercular abscess associated with bone and lymph node involvement

Karan Sancheti, Indrashis Podder, Maitrayee Saha, Satyendra Nath Chowdhury, Debabrata Bandyopadhyay

Indian Journal of Dermatology, Venereology, and Leprology 2017 83(2):276-276



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Nevoid sebaceous hyperplasia mistaken as nevus sebaceous: Report of four cases

Rajesh Kumar Mandal, Anupam Das, Indranil Chakrabarti, Priyanka Agarwal

Indian Journal of Dermatology, Venereology, and Leprology 2017 83(2):213-216



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Erratum: Neurological diseases and bullous pemphigoid: A case-control study in Iranian patients



Indian Journal of Dermatology, Venereology, and Leprology 2017 83(2):278-278



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Multifocal lupus vulgaris with involvement of palpebral conjunctiva

Jayanta Kumar Barua, Deep Anurag, Shabab Ahmed Damji, Gautam Banerjee

Indian Journal of Dermatology, Venereology, and Leprology 2017 83(2):216-218



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The receptor for advanced glycation end products RAGE is involved in corneal healing

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Publication date: Available online 3 February 2017
Source:Annals of Anatomy - Anatomischer Anzeiger
Author(s): Norbert Nass, Stefanie Trau, Friedrich Paulsen, Delia Kaiser, Thomas Kalinski, Saadettin Sel
Impaired corneal healing is still a major cause of blindness. As RAGE (receptor for advanced glycation endproducts) is involved in inflammation and wound healing in other tissues, we here investigated its relevance for corneal wound healing.Corneal re-epithelialization after alkaline injury was analysed in an ex-vivo approach with cultured, enucleated eyes from mice either of the C57Bl/6 NChR genotype (RAGE+/+) and mice of the same strain lacking the RAGE gene (RAGE −/-). The wound area was determined time dependently by fluorescence imaging using fluorescein staining. The eyes of RAGE −/- mice showed a significantly slower re-epithelialization than eyes of the RAGE+/− and the RAGE+/+ genotype.In immunohistochemistry, RAGE expression was increased in wounded corneas whereas the abundance of the RAGE ligand HMGB1 was unaffected, but an increase in S100b-like proteins was revealed upon injury. However, neither the addition of the RAGE agonist HMGB1 or an HMGB1 antagonising antibody nor bovine S100b protein to the culture medium of the wounded eyes had an effect on corneal wound closure in ex-vivo. Further gene expression analysis by RT-PCR demonstrated an increase in RAGE expression on the mRNA level, no significant regulation of HMGB1 and a differential regulation of the S100 gene family after alkaline burn of the cornea.In conclusion, RAGE is clearly involved in corneal re-epithelialization most probably mediated by signalling via S100 proteins.



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