Publication date: Available online 10 February 2017
Source:Allergology International
Author(s): Etsuko Takamura, Eiichi Uchio, Nobuyuki Ebihara, Shigeaki Ohno, Yuichi Ohashi, Shigeki Okamoto, Naoki Kumagai, Yoshiyuki Satake, Jun Shoji, Yayoi Nakagawa, Kenichi Namba, Kazumi Fukagawa, Atsuki Fukushima, Hiroshi Fujishima
The definition, classification, pathogenesis, test methods, clinical findings, criteria for diagnosis, and therapies of allergic conjunctival disease are summarized based on the Guidelines for Clinical Management of Allergic Conjunctival Disease (Second Edition) revised in 2010. Allergic conjunctival disease is defined as "a conjunctival inflammatory disease associated with a Type I allergy accompanied by some subjective or objective symptoms." Allergic conjunctival disease is classified into allergic conjunctivitis, atopic keratoconjunctivitis, vernal keratoconjunctivitis, and giant papillary conjunctivitis. Representative subjective symptoms include ocular itching, hyperemia, and lacrimation, whereas objective symptoms include conjunctival hyperemia, swelling, folliculosis, and papillae. Patients with vernal keratoconjunctivitis, which is characterized by conjunctival proliferative changes called giant papilla accompanied by varying extents of corneal lesion, such as corneal erosion and shield ulcer, complain of foreign body sensation, ocular pain, and photophobia. In the diagnosis of allergic conjunctival diseases, it is required that type I allergic diathesis is present, along with subjective and objective symptoms accompanying allergic inflammation. The diagnosis is ensured by proving a type I allergic reaction in the conjunctiva. Given that the first-line drug for the treatment of allergic conjunctival disease is an antiallergic eye drop, a steroid eye drop will be selected in accordance with the severity. In the treatment of vernal keratoconjunctivitis, an immunosuppressive eye drop will be concomitantly used with the abovementioned drugs.
http://ift.tt/2lu3jTk
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- Japanese guidelines for allergic conjunctival dise...
- Japanese guidelines for atopic dermatitis 2017
- Pilot study to evaluate a plasma device for the tr...
- Fingolimod and melanoma risk: is there sufficient ...
- Letter to the Editor: Prognosis and risk in consid...
- Authors' Reply: Prognosis and risk in considering ...
- Thrombin and activated coagulation factor X stimul...
- Intranasal corticosteroids compared with oral anti...
- Letter to the Editor: Sinonasal polyposis recurren...
- Authors' Reply: Sinonasal polyposis recurrence rat...
- Removable sinus stent for endoscopic sinus surgery...
- Anosmia: Differential diagnosis, evaluation, and m...
- Peripheral blood T-helper cells and eosinophil pop...
- Delving into the unknown in rhinology and allergy
- Allergic sensitization does not predispose to sinu...
- Specific nasal provocation test with Dermatophagoi...
- The association of allergic sensitization with rad...
- Sinonasal imaging findings in granulomatosis with ...
- Oral corticosteroid prescribing habits for rhinosi...
- Efficacy and safety of sublingual immunotherapy fo...
- Involvement of the maxillary sinus in bisphosphona...
- Nasal rinsing with an atomized spray improves muco...
- Factors influencing the need for endoscopic sinus ...
- A novel technique for the quantitative examination...
- Delayed Donor Bone Marrow Infusion Induces Liver T...
- Hepatitis C Positive Kidney Transplant Recipients-...
- Familial Mediterranean fever is associated with in...
- Regulation of Clinical Xenotransplantation - Time ...
- Chronic spontaneous urticaria associated with viti...
- Lymphangioma-like classic Kaposi sarcoma
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- Histopathological aspects of cutaneous erythematou...
- Cutaneous human immunodeficiency virus (HIV)-assoc...
- Nonsexually acquired genital ulcers in a 79-year-o...
- First report of SLC39A4 mutation in acrodermatitis...
- Evaluation of skin disorders of lower limb amputat...
- Investigation of the clinical features of geograph...
- Imaging and cell count in cleared intact cochlea i...
- Injectable chondroplasty: Enzymatic reshaping of c...
- Successful Desensitization in a Patient with Hyper...
- Early Developmental Disruption of Type 2 Deiodinas...
- Increased Tumor-Infiltrating Plasmacytoid Dendriti...
- Effect of fluoride toothpaste with nano-sized trim...
- Increased Tumor-Infiltrating Plasmacytoid Dendriti...
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- Application of Monoclonal Antibodies Against Mouse...
- Production of Monoclonal Antibody Against Excretor...
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Παρασκευή 10 Φεβρουαρίου 2017
Japanese guidelines for allergic conjunctival diseases 2017
Japanese guidelines for atopic dermatitis 2017
Publication date: Available online 10 February 2017
Source:Allergology International
Author(s): Ichiro Katayama, Michiko Aihara, Yukihiro Ohya, Hidehisa Saeki, Naoki Shimojo, Shunsuke Shoji, Masami Taniguchi, Hidekazu Yamada
Given the importance of appropriate diagnosis and appropriate assessment of cutaneous symptoms in treatment of atopic dermatitis, the basics of treatment in this guideline are composed of (1) investigation and countermeasures of causes and exacerbating factors, (2) correction of skin dysfunctions (skin care), and (3) pharmacotherapy, as three mainstays. These are based on the disease concept that atopic dermatitis is an inflammatory cutaneous disease with eczema by atopic diathesis, multi-factorial in onset and aggravation, and accompanied by skin dysfunctions. These three points are equally important and should be appropriately combined in accordance with the symptoms of each patient. In treatment, it is important to transmit the etiological, pathological, physiological, or therapeutic information to the patient to build a favorable partnership with the patient or his/her family so that they may fully understand the treatment. This guideline discusses chiefly the basic therapy in relation to the treatment of this disease. The goal of treatment is to enable patients to lead an uninterrupted social life and to control their cutaneous symptoms so that their quality of life (QOL) may meet a satisfactory level.The basics of treatment discussed in this guideline are based on the "Guidelines for the Treatment of Atopic Dermatitis 2008" prepared by the Health and Labour Sciences Research and the "Guidelines for the Management of Atopic Dermatitis 2015 (ADGL2015)" prepared by the Atopic Dermatitis Guidelines Advisory Committee, Japanese Society of Allergology in principle. The guidelines for the treatment of atopic dermatitis are summarized in the "Japanese Guideline for the Diagnosis and Treatment of Allergic Disease 2016" together with those for other allergic diseases.
http://ift.tt/2lAZoRr
Pilot study to evaluate a plasma device for the treatment of onychomycosis
Summary
Onychomycosis is a fungal infection of the nail unit, and is the most common of the nail disorders. Current therapies for onychomycosis have less than ideal efficacy and have the potential for adverse effects. As previous studies have shown that nonthermal plasma inhibits the in vitro growth of Trichophyton rubrum, we conducted a pilot study on 19 participants with toenail onychomycosis. The primary endpoint was safety of the device, and secondary outcome measures were clinical efficacy and mycological cure. Patient satisfaction was measured using questionnaires at the completion of the study. All but one patient met the primary endpoint of safety and there were no long-term sequelae. The overall clinical cure was 53.8% and the mycological cure was 15.4%. The majority of patients were satisfied with the treatment. Our conclusions are that nonthermal plasma is a safe treatment and may have a beneficial effect on toenail onychomycosis.
http://ift.tt/2l3TzOJ
Letter to the Editor: Prognosis and risk in considering extensive vs functional endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps and asthma
http://ift.tt/2kZrfxo
Authors' Reply: Prognosis and risk in considering extensive vs functional endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps and asthma
http://ift.tt/2lB31H1
Thrombin and activated coagulation factor X stimulate the release of cytokines and fibronectin from nasal polyp fibroblasts via protease-activated receptors
http://ift.tt/2kZzLfP
Intranasal corticosteroids compared with oral antihistamines in allergic rhinitis: A systematic review and meta-analysis
http://ift.tt/2lB1K2I
Letter to the Editor: Sinonasal polyposis recurrence rate and quality of life in the elderly
http://ift.tt/2kZFDW9
Peripheral blood T-helper cells and eosinophil populations in patients with atopic and nonatopic chronic rhinosinusitis
http://ift.tt/2kZuftq
Allergic sensitization does not predispose to sinus inflammation in externalized paranasal sinuses
http://ift.tt/2kZE3Uf
Specific nasal provocation test with Dermatophagoides pteronyssinus, monitored by acoustic rhinometry, in children with rhinitis
http://ift.tt/2lB6fu1
Sinonasal imaging findings in granulomatosis with polyangiitis (Wegener granulomatosis): A systematic review
http://ift.tt/2lB7nOv
Oral corticosteroid prescribing habits for rhinosinusitis: The American Rhinologic Society membership
http://ift.tt/2kZz3iw
Efficacy and safety of sublingual immunotherapy for allergic rhinitis in pediatric patients: A meta-analysis of randomized controlled trials
http://ift.tt/2lAIBOi
Involvement of the maxillary sinus in bisphosphonate-related osteonecrosis of the jaw: Radiologic aspects
http://ift.tt/2kZucOg
Nasal rinsing with an atomized spray improves mucociliary clearance and clinical symptoms during peak grass pollen season
http://ift.tt/2lAZt7T
Factors influencing the need for endoscopic sinus surgery in adult patients with cystic fibrosis
http://ift.tt/2kZJzpR
Delayed Donor Bone Marrow Infusion Induces Liver Transplant Tolerance.
http://ift.tt/2kfQ1VA
Hepatitis C Positive Kidney Transplant Recipients-When is The Best Time to Treat with Direct Acting Antiviral Agents (DAAs)?.
Familial Mediterranean fever is associated with increased mortality after kidney transplantation - a 19 years' single center experience.
http://ift.tt/2kfOqyW
Regulation of Clinical Xenotransplantation - Time for a Reappraisal.
http://ift.tt/2l3T9aP
Chronic spontaneous urticaria associated with vitiligo and thyroiditis (autoimmune polyglandular syndrome IIIC): case series
http://ift.tt/2lBdWjV
The role of dermoscopy using a triple light source in the diagnosis of pityriasis rosea: an observational pilot study
http://ift.tt/2lAQQdo
Histopathological aspects of cutaneous erythematous-papular eruptions induced by immune checkpoint inhibitors for the treatment of metastatic melanoma
Abstract
Background
Immune checkpoint blockade therapy (ICBT) for the treatment of melanoma has led to an important improvement of overall survival in advanced stage patients. However, secondary cutaneous maculopapular eruptions (CMPEs) are frequent and remain poorly characterized.
Methods
We performed a retrospective analysis of melanoma patients from our institution who developed CMPEs during ICBT. Clinical information was retrieved, and histopathological and immunohistochemical characterization was performed by two pathologists. For comparison, a group of biopsies from CMPE caused by anti-v-raf murine sarcoma viral oncogene homolog B1 (BRAF) therapy was analyzed.
Results
Eleven patients met the inclusion criteria. On clinical grounds, CMPE developed mainly on early onset of immunotherapy and were of low grade. Typical lesions included erythematous papules and macules affecting the trunk and/or extremities with associated pruritus. The histopathological patterns consisted of a superficial perivascular lymphocytic dermatitis (SPLD) with eosinophils followed by a granulomatous dermatitis. Other patterns included lichenoid, spongiotic, and a case of Grover's disease. The inflammatory infiltrate consisted of T lymphocytes (CD3+) with a predominance of CD4+ over CD8+ cells; isolated Foxp3+ cells were invariably present, and PD-1 was not expressed. Biopsies from CMPE caused by anti-BRAF therapy showed an SPLD and a similar lymphocytic immunophenotype.
Conclusions
Our study showed the clinical features of a group of melanoma patients with CMPE for ICBT and emphasized the wide spectrum of histological findings as well as their immunohistochemical profile. Differential diagnosis can be difficult with CMPE provoked by other therapies as was seen in our comparison group of anti-BRAF-induced eruptions.
http://ift.tt/2kZnXKl
Cutaneous human immunodeficiency virus (HIV)-associated lymphomatoid granulomatosis: complete regression following antiretroviral therapy
http://ift.tt/2lAYNiQ
First report of SLC39A4 mutation in acrodermatitis enteropathica family from the Middle East
http://ift.tt/2lAZqca
Evaluation of skin disorders of lower limb amputation sites: is there a common denominator?
http://ift.tt/2kZsUCS
Investigation of the clinical features of geographic tongue: unveiling its relationship with oral psoriasis
Abstract
Background
Few studies have examined the clinical features of geographic tongue (GT), an inflammatory lesion, making diagnosis and the investigation of oral psoriasis difficult.
Purpose
To investigate the clinical features of GT to facilitate its identification and understand its relationship with psoriasis.
Methods
A total of 96 participants diagnosed with GT underwent stomatological and dermatological examinations. The parameters assessed were burning sensation; number, classification, and location of lesions; loss of papillae; severity of GT lesions; and association with fissured tongue (FT). Psoriatic patients (PS) and those without psoriasis (NPS) were compared.
Results
Burning sensation was reported by 45 (47%) patients, 67 (70%) patients showed active GT, 68 (71%) presented with typical lesions, and 59 (61%) exhibited moderate lesions. GT was associated with FT in 75% of the cases and exhibited a diffused pattern associated with severe lesions. It was also more frequent in the PS group. The comparative analysis between the PS and NPS groups showed significant differences between the groups with regard to gender, presence of burning sensation, and GT severity.
Conclusion
GT is a symptomatic lesion with a thick halo. In contrast, psoriatic patients are frequently asymptomatic and exhibit severe lesions with greater loss of papillae that are associated with severe FT. The present study is the first to demonstrate clinical differences in the GT of patients with and without psoriasis, suggesting that some GT cases may represent true oral psoriasis and some cases may represent only GT.
http://ift.tt/2lAWRqz
Imaging and cell count in cleared intact cochlea in the Mongolian gerbil using laser scanning confocal microscopy
Publication date: Available online 9 February 2017
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): M. Risoud, J. Sircoglou, G. Dedieu, M. Tardivel, C. Vincent, N.-X. Bonne
ObjectivesTo draw up a clearing protocol for Mongolian gerbil cochlea, and to assess the feasibility of quantifying and analyzing 3D cell architecture in the transparent cochleae.Materials and methodsFreshly dissected inner ears were prepared on a 13-day protocol: fixation, microdissection, post-fixation, decalcification, pretreatment (signal enhancement, permeabilization and blocking), fluorescent labeling (indirect immunolabeling and direct labeling), dehydration, clearing in Spalteholz solution (MSBB: methyl salicylate and benzyl benzoate) and mounting. Image acquisition used laser scanning confocal microscopy. ImageJ software was used to measure the length of the organ of Corti thus available for analysis and to count inner and outer hair cells.ResultsFour cochleas underwent imaging. 3D reconstruction enabled organ of Corti length to be measured, at a mean 1269±346μm. Mean inner and outer hair-cell count per organ of Corti length was 142±44 and 400±122, respectively.ConclusionCochlear clearing by MSBB was feasible in Mongolian gerbils and provided high-resolution immunofluorescence-labeled inner-ear images. To our knowledge, this was the first application of the technique in this species. Cell count could thus be performed along the organ of Corti length without traumatic dissection.
http://ift.tt/2kfDP72
Injectable chondroplasty: Enzymatic reshaping of cartilage grafts
Publication date: Available online 10 February 2017
Source:European Annals of Otorhinolaryngology, Head and Neck Diseases
Author(s): J.R. Gandy, A. Foulad, K.K. Chao, B.J.F. Wong
Objective/hypothesisTo develop an injection-based enzymatic technique that selectively softens cartilage tissue for reshaping cartilaginous structures in the head and neck.Materials and methodsTwo groups were formed using fresh rabbit ears: (1) whole rabbit ear group; (2) composite graft group (2.5mm×3.0cm specimens sectioned from the central region of the pinna). Subperichondrial injections using three enzymes (hyaluronidase, pronase, and collagenase II) in sequence were performed for the experimental specimens from both groups. In the control specimens, phosphate buffered saline was injected in a similar fashion. The whole ear specimens were then photographed while held upright in the anatomical vertical position to evaluate for buckling, which corresponds to the integrity of the cartilage. In addition, backlight photography was performed for all specimens to further evaluate the effect of the enzymes, such that increased light intensity represents increased cartilage digestion.ResultsThe application of the digestive enzymes resulted in marked reduction of cartilage tissue matrix resiliency, while preserving overlying skin layers. Enzymatically treated whole pinnae buckled at the site where enzymes were delivered. Backlit images revealed increased local light intensity at the regions of digestion. There was no obvious destruction of the overlying skin upon visual inspection.ConclusionsThis study demonstrates the feasibility of injectable chondroplasty as a potential alternative method to conventional surgery for auricular cartilage reshaping. Sequential injection of hyaluronidase, pronase, and collagenase II into the subperichondrial space can be performed to digest and soften cartilage structure with minimal involvement of surrounding tissue. Future studies will need to include chondrocyte viability testing and optimization of delivery techniques.
http://ift.tt/2l3Obeq
Successful Desensitization in a Patient with Hypersensitivity Reaction to Laronidase
Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.
http://ift.tt/2l3H5X7
Early Developmental Disruption of Type 2 Deiodinase Pathway in Mouse Skeletal Muscle Does Not Impair Muscle Function
Thyroid , Vol. 0, No. 0.
http://ift.tt/2kdtCgp
Increased Tumor-Infiltrating Plasmacytoid Dendritic Cells Predicts Poor Prognosis in Oral Squamous Cell Carcinoma
Publication date: Available online 10 February 2017
Source:Archives of Oral Biology
Author(s): Nannan Han, Zun Zhang, Shengwen Liu, Andrew Ow, Min Ruan, Wenjun Yang, Chenping Zhang
ObjectiveAccumulating evidence suggests that plasmacytoid dendritic cells (pDC) have a dual role not only in initiating anti-tumor immune responses but also in inducing immune tolerance to facilitate cancer development. The aim of this study was to investigate the distribution and function of tumor-infiltrating pDCs in primary oral squamous cell carcinoma (OSCC) and their relation to patient outcome.MethodsThe distribution of pDCs in 10 normal oral mucosa and 60 OSCC tissues was detected by immunohistochemistry. The population of pDCs in six OSCC patients and six healthy donors was evaluated by flow cytometry. The relationship between tumor-infiltrating pDCs and clinicopathological data and patient outcome was analyzed accordingly. The capacity of pDCs to produce cytokines, such as IFN-α, IL-6, IL-8 and TNF-α in response to TLR-9 ligands (CpG-ODN) was measured by ELISA.ResultPDCs were detected at high levels in 38.3% of the OSCC tissues, primarily in the stroma, but were absent in normal oral mucosa. The frequency of pDCs in OSCC tissue was significantly higher than that observed in normal oral mucosa. However, the distribution and population of circulating pDCs was similar between healthy donors and OSCC patients. Kaplan-Meier analysis revealed a significant association of increasing number of tumor infiltrating pDCs with lymph node metastasis and overall survival. Multivariate analysis confirmed that high levels of tumor-infiltrating pDCs was an independent prognostic factor. Further cytokine analysis revealed a decreased secretion of IFN-α, IL-6 and TNF-α, which indicated an impaired function of tumor-infiltrating pDCs.ConclusionsThe increased number of tumor-infiltrating pDCs correlates with an adverse outcome in primary OSCC patients. This finding is not only suggestive of the contribution of pDCs in the progression of oral cancer but also presents an opportunity and a new target for OSCC immune therapy in oral cancer management.
http://ift.tt/2l3wBXI
Effect of fluoride toothpaste with nano-sized trimetaphosphate on enamel demineralization: An in vitro study
Publication date: Available online 10 February 2017
Source:Archives of Oral Biology
Author(s): Marcelle Danelon, Juliano Pelim Pessan, Francisco Nunes Souza Neto, Emerson Rodrigues De Camargo, Alberto Carlos Botazzo Delbem
ObjectiveThis study evaluated the effect of toothpastes containing 1100ppm F associated or not with micrometric or nano-sized sodium trimetaphosphate (TMP) on enamel demineralization in vitro, using a pH cycling model.DesignBovine enamel blocks (4mm×4mm, n=96) were randomly allocated into eight groups (n=12), according to the test toothpastes: Placebo (without fluoride or TMP); 1100ppm F (1100F); 1100F plus micrometric TMP at concentrations of 1%, 3% or 6%; and 1100F plus nanosized TMP at 1%, 3% or 6%. Blocks were treated 2x/day with slurries of toothpastes and submitted to a pH cycling regimen for five days. Next, final surface hardness (SHf), integrated hardness loss (IHL), differential profile of integrated hardness loss (ΔIHL) and enamel fluoride (F) concentrations were determined. Data were analyzed by ANOVA and Student-Newman-Keuls' test (p<0.05).ResultsThe use of 1100F/3%TMPnano led to SHf 30% higher (p<0.001) and IHL∼80% lower (p<0.001) when compared to 1100F. This toothpaste also resulted in ∼64% reduction of mineral loss (ΔIHL) when compared to 1100F. Moreover, the addition of nano-sized TMP promoted increases in enamel F uptake of 90%, 160% and 100%, respectively for the concentrations of 1%, 3% and 6%, when compared to 1100F (p<0.001).ConclusionThe addition of nano-sized TMP at 3% to a conventional toothpaste significantly decreased enamel demineralization when compared to its counterparts without TMP or supplemented with micrometric TMP.
http://ift.tt/2kfo7ZJ
Increased Tumor-Infiltrating Plasmacytoid Dendritic Cells Predicts Poor Prognosis in Oral Squamous Cell Carcinoma
Publication date: Available online 10 February 2017
Source:Archives of Oral Biology
Author(s): Nannan Han, Zun Zhang, Shengwen Liu, Andrew Ow, Min Ruan, Wenjun Yang, Chenping Zhang
ObjectiveAccumulating evidence suggests that plasmacytoid dendritic cells (pDC) have a dual role not only in initiating anti-tumor immune responses but also in inducing immune tolerance to facilitate cancer development. The aim of this study was to investigate the distribution and function of tumor-infiltrating pDCs in primary oral squamous cell carcinoma (OSCC) and their relation to patient outcome.MethodsThe distribution of pDCs in 10 normal oral mucosa and 60 OSCC tissues was detected by immunohistochemistry. The population of pDCs in six OSCC patients and six healthy donors was evaluated by flow cytometry. The relationship between tumor-infiltrating pDCs and clinicopathological data and patient outcome was analyzed accordingly. The capacity of pDCs to produce cytokines, such as IFN-α, IL-6, IL-8 and TNF-α in response to TLR-9 ligands (CpG-ODN) was measured by ELISA.ResultPDCs were detected at high levels in 38.3% of the OSCC tissues, primarily in the stroma, but were absent in normal oral mucosa. The frequency of pDCs in OSCC tissue was significantly higher than that observed in normal oral mucosa. However, the distribution and population of circulating pDCs was similar between healthy donors and OSCC patients. Kaplan-Meier analysis revealed a significant association of increasing number of tumor infiltrating pDCs with lymph node metastasis and overall survival. Multivariate analysis confirmed that high levels of tumor-infiltrating pDCs was an independent prognostic factor. Further cytokine analysis revealed a decreased secretion of IFN-α, IL-6 and TNF-α, which indicated an impaired function of tumor-infiltrating pDCs.ConclusionsThe increased number of tumor-infiltrating pDCs correlates with an adverse outcome in primary OSCC patients. This finding is not only suggestive of the contribution of pDCs in the progression of oral cancer but also presents an opportunity and a new target for OSCC immune therapy in oral cancer management.
http://ift.tt/2l3wBXI
Effect of fluoride toothpaste with nano-sized trimetaphosphate on enamel demineralization: An in vitro study
Publication date: Available online 10 February 2017
Source:Archives of Oral Biology
Author(s): Marcelle Danelon, Juliano Pelim Pessan, Francisco Nunes Souza Neto, Emerson Rodrigues De Camargo, Alberto Carlos Botazzo Delbem
ObjectiveThis study evaluated the effect of toothpastes containing 1100ppm F associated or not with micrometric or nano-sized sodium trimetaphosphate (TMP) on enamel demineralization in vitro, using a pH cycling model.DesignBovine enamel blocks (4mm×4mm, n=96) were randomly allocated into eight groups (n=12), according to the test toothpastes: Placebo (without fluoride or TMP); 1100ppm F (1100F); 1100F plus micrometric TMP at concentrations of 1%, 3% or 6%; and 1100F plus nanosized TMP at 1%, 3% or 6%. Blocks were treated 2x/day with slurries of toothpastes and submitted to a pH cycling regimen for five days. Next, final surface hardness (SHf), integrated hardness loss (IHL), differential profile of integrated hardness loss (ΔIHL) and enamel fluoride (F) concentrations were determined. Data were analyzed by ANOVA and Student-Newman-Keuls' test (p<0.05).ResultsThe use of 1100F/3%TMPnano led to SHf 30% higher (p<0.001) and IHL∼80% lower (p<0.001) when compared to 1100F. This toothpaste also resulted in ∼64% reduction of mineral loss (ΔIHL) when compared to 1100F. Moreover, the addition of nano-sized TMP promoted increases in enamel F uptake of 90%, 160% and 100%, respectively for the concentrations of 1%, 3% and 6%, when compared to 1100F (p<0.001).ConclusionThe addition of nano-sized TMP at 3% to a conventional toothpaste significantly decreased enamel demineralization when compared to its counterparts without TMP or supplemented with micrometric TMP.
http://ift.tt/2kfo7ZJ
Application of Monoclonal Antibodies Against Mouse Dermokine
Monoclonal Antibodies in Immunodiagnosis and Immunotherapy , Vol. 0, No. 0.
http://ift.tt/2l3iIJ8
Production of Monoclonal Antibody Against Excretory-Secretory Antigen of Fasciola hepatica and Evaluation of Its Efficacy in the Diagnosis of Fascioliasis
Monoclonal Antibodies in Immunodiagnosis and Immunotherapy , Vol. 0, No. 0.
http://ift.tt/2kfs806
The role and choice criteria of antihistamines in allergy management – Expert opinion
Publication date: Available online 10 February 2017
Source:Alergologia Polska - Polish Journal of Allergology
Author(s): Piotr Kuna, Dariusz Jurkiewicz, Magdalena M. Czarnecka-Operacz, Rafał Pawliczak, Jarosław Woroń, Marcin Moniuszko, Andrzej Emeryk
Allergic diseases are the most common chronic conditions lasting throughout the patient's life. They not only cause significant deterioration in the quality of life of patients but also lead to significant absenteeism and reduced productivity, resulting in very high costs for society. Effective and safe treatment of allergic diseases is therefore one of the main challenges for public health and should be carried out by all the specialists in family medicine, internists and paediatricians in collaboration with allergists, otorhinolaryngologists and dermatologists. Antihistamines are most commonly used in the treatment of allergies. Several dozen drugs are available on the pharmaceutical market, and their generic forms are advertised widely as very effective drugs for the treatment of allergic diseases. What is the truth? What are the data from clinical trials and observational studies? Are all drugs equally effective and safe for the patient? According to a panel of experts representing various fields of medicine, inappropriate treatment of allergies can be very risky for patients, and seemingly equally acting medications may differ greatly. Therefore, a panel of experts gathered the latest data from the entire scientific literature and analyzed the latest standards and recommendations prepared by scientific societies. This paper provides a summary of these studies and highlights the importance for the patient of the proper choice of drug to treat his allergies.
http://ift.tt/2kROo2k
Melanoma and pregnancy
Abstract
Melanoma is the most common cancer in women during their reproductive years and kills more young Australians than any other single cancer. Care of women whose pregnancy is complicated by a diagnosis of malignancy is complex. The risk of delaying treatment to the mother, the short-term and long-term risks of premature delivery to the child, and the immediate risks to the foetus and long-term risks to the child of maternal treatment with surgery, radiotherapy or medical therapies must be considered.
http://ift.tt/2lAf0Vh
Facial nerve paralysis after super-selective intra-arterial chemotherapy for oral cancer
Facial nerve paralysis (FNP) after super-selective intra-arterial chemotherapy (SSIAC) is a relatively rare local side effect of SSIAC to the maxillary artery (MA) or the middle meningeal artery (MMA). The incidence and prognosis of FNP after SSIAC in 381 patients with oral cancer (133 with catheterization of the MA, 248 without) was investigated retrospectively. Only three patients (two male and one female) had FNP, for an incidence of 0.8%. All patients with FNP had undergone catheterization of the MA, and the incidence of FNP in this group was 2.3% (3/133).
http://ift.tt/2ltgDr4
Space-maintaining management in maxillary sinus lifting: a novel technique using a resorbable polymeric thermo-reversible gel
Several techniques have been proposed to achieve sinus floor elevation and the formation of new bone through the grafting of autologous, heterologous, or alloplastic materials. The grafted materials act as a scaffold for bone formation inside the maxillary sinus. This study investigated a non-graft sinus lifting procedure using a resorbable polymeric thermo-reversible gel. A space-maintaining approach to sinus lifting, using a resorbable polymeric thermo-reversible gel, was applied in 11 patients undergoing implant treatment in the atrophic posterior maxilla.
http://ift.tt/2keRBXE
Endocultivation: continuous application of rhBMP-2 via mini-osmotic pumps to induce bone formation at extraskeletal sites
The continuous presence of recombinant human bone morphogenetic protein 2 (rhBMP-2) inside a scaffold may be crucial to the outcome in bone tissue engineering. This study investigated whether the release of the growth factor rhBMP-2 via different continuous application schemes influences histomorphological aspects of the hard and soft tissues induced. Three-dimensionally printed hydroxyapatite scaffolds were implanted into one latissimus dorsi muscle of 42 female Lewis rats. Simultaneously implanted mini-osmotic pumps were used to provide a continuous application of rhBMP-2 over 1, 2, or 4 weeks (total dose 200μg).
http://ift.tt/2lttJVm
ASA physical status assignment by non-anesthesia providers: Do surgeons consistently downgrade the ASA score preoperatively?
The American Society of Anesthesiologists physical status (ASA-PS) is associated with increased morbidity and mortality in the perioperative period. When surgeries are scheduled by surgeons and their staff at our large institution a presumed ASA-PS is chosen. This is because our institution (and, anecdotally, others in our hospital system and elsewhere), recognizing the relationship between higher ASA-PS and poorer postoperative outcomes, requires all patients with higher ASA-PS levels (≥3) to undergo enhanced preoperative workup.
http://ift.tt/2ltrYY5
Non-invasive cardiac output monitor validation study in pediatric cardiac surgery patients
To validate a non-invasive cardiac output monitor in pediatric cardiac surgery patients.
http://ift.tt/2lyCwRW
Successful Desensitization in a Patient with Hypersensitivity Reaction to Laronidase
Pediatric Allergy, Immunology, and Pulmonology , Vol. 0, No. 0.
http://ift.tt/2kePtPr
Complement’s hidden arsenal: New insights and novel functions inside the cell
Publication date: Available online 10 February 2017
Source:Molecular Immunology
Author(s): M. Kathryn Liszewski, Michelle Elvington, Hrishikesh S. Kulkarni, John P. Atkinson
A key component of both innate and adaptive immunity, new understandings of the complement system are expanding its roles beyond that traditionally appreciated. Evidence is accumulating that complement has an intracellular arsenal of components that provide not only immune defense, but also assist in key interactions for host cell functions. Although early work has primarily centered on T cells, the intracellular complement system likely functions in many if not most cells of the body. Some of these functions may trace their origins to the primitive complement system that began as a primeval form of C3 likely tasked for protection from intracellular pathogen invasion. This later expanded to include extracellular defense as C3 became a secreted protein to patrol the vasculature. Other components were added to the growing system including regulators to protect host cells from the indiscriminate effects of this potent system. Contemporary cells may retain some of these vestigial remnants. We now know that a) C3 serves as a damage-associated molecular pattern (in particular by coating pathogens that translocate into cells), b) most cells store C3 and recycle C3(H2O) for immediate use, and c) C3 assists in cellular survival and metabolic reprogramming. Other components also are part of this hidden arsenal including C5, properdin, factors H and B, and complement receptors. Importantly, better definition of the intracellular complement system may translate into new target discovery to assist in creating the next generation of complement therapeutics.
http://ift.tt/2lzsUaa
Lipoprotein(a) and its role in inflammation, atherosclerosis and malignancies
Abstract
Lipoprotein (a) (Lp(a)) is a modified low-density lipoprotein (LDL) particle with an additional specific apolipoprotein (a), covalently attached to apolipoprotein B‑100 of LDL by a single thioester bond. Increased plasma Lp(a) level is a genetically determined, independent, causal risk factor for cardiovascular disease.
The precise quantification of Lp(a) in plasma is still hampered by mass-sensitive assays, large particle variation, poor standardization and lack of assay comparability.
The physiological functions of Lp(a) include wound healing, promoting tissue repair and vascular remodeling. Similarly to other lipoproteins, Lp(a) is also susceptible for oxidative modifications, leading to extensive formation of pro-inflammatory and pro-atherogenic oxidized phospholipids, oxysterols, oxidized lipid-protein adducts in Lp(a) particles, that perpetuate atherosclerotic lesion progression and intima-media thickening through induction of M1-macrophages, inflammation, autoimmunity and apoptosis. The oxidation-specific epitopes of modified lipoproteins are major targets of pre-immune, natural IgM antibodies, that may attenuate the pro-inflammatory and pro-atherogenic effects of Lp(a).
Although the data are still insufficient, recent studies suggest a potential anti-neoplastic role of Lp(a).
http://ift.tt/2l2bwx3
Erratum
Publication date: Available online 10 February 2017
Source:Annals of Allergy, Asthma & Immunology
http://ift.tt/2kQT746
Unexpected extrapyramidal symptoms and pulmonary aspergillosis in exertional heatstroke with fulminant liver failure: a case report
Exertional heatstroke is a life-threatening condition with high mortality because of the rapid progress of multiple organ dysfunction syndrome even if aggressive treatments are initiated rapidly. Mild to moder...
http://ift.tt/2l1UsY2
p16 and p53 in HPV Positive versus HPV Negative Oral Squamous Cell Carcinoma (OSCC): Do Pathways Differ?
Abstract
Background
p16 overexpression and wild-type p53 expression is associated with human papilloma virus (HPV) in cervical and oropharyngeal cancer. Role of HPV-related carcinogenesis in the etiology of oral squamous cell carcinoma (OSCC) is still vague in Indian population. We aimed to explore the expression pattern of p16 and p53 in HPV positive and HPV negative OSCC to elicit differences, if any. Further their effect on survival of patients was studied.
Methods
Thirty-one consecutive HPV positive as well as 31 age and sex matched HPV negative OSCC cases from a case series of 369 histologically diagnosed cases of OSCC were included in this study. HPV was detected by two methods viz. real time PCR and conventional PCR in biopsy samples. p16 and p53 protein expression was assessed by immunohistochemsitry and p16 mRNA expression was quantified with real time PCR using SYBR Green assay.
Results
p16 was expressed in 6(19.4%) HPV positive and in 4(12.9%) HPV negative cases. Overall mutant-type p53 expression in 62 OSCC cases was 54.8%. Out of ten p16 positive cases, eight expressed mutant-type p53 and only 2 cases expressed wild-type p53. Risk factors including oral tobacco consumption and alcohol were present in all these ten p16 positive cases. Survival of patients was not affected by HPV, p16 and p53 status.
Conclusions
Presence of mutated p53 and exposure to tobacco related risk factors in both HPV positive and negative cases suggests existence of p53 related carcinogenesis in HPV positive cases in Indian population.
This article is protected by copyright. All rights reserved.
http://ift.tt/2kuJsz9
Is chronic ulcerative stomatitis a variant of lichen planus, or a distinct disease?
Abstract
Chronic ulcerative stomatitis is an immune-mediated mucocutaneous disorder characterized clinically by erosions or ulcers. Most cases are limited to the mouth. The histopathological features are non-specific or mimic those of oral lichen planus, and studies by immunoflorescent microscopy are essential for definitive diagnosis. The defining immunopathogenic mechanism is the binding of IgG to the nuclear protein deltaNp63alpha of keratinocytes in the basal and parabasal cell layers of the oral stratified epithelium. DeltaNp63alpha functions as a regulator of epithelial stem cell activity and as an anti-apoptotic agent, and regulates the expression of cell-to-cell and cell-to-basement membrane adhesion molecules. The autoimmune IgG-deltaNp63alpha interaction is thought to result in damage to the structural attachment of keratinocytes to one another and to the epithelial basement membrane zone, and in dysregulation of the cell cycle and apoptosis of basal keratinocytes with the development of erosions or ulcers. The aims of treatment are to suppress the pathogenic immuno-inflammatory responses, to prevent local infection and to promote healing.
The purpose of this article is to provide a succinct review of the diagnostic, clinical and aetiopathogenic features of, and treatment guidelines for chronic ulcerative stomatitis, and to argue that this disease should be regarded as a variant of oral lichen planus, rather than as a distinct entity.
This article is protected by copyright. All rights reserved.
http://ift.tt/2kXBCl5
Re-evaluation of epidermodysplasia verruciformis: Reconciling more than 90 years of debate
Epidermodysplasia verruciformis (EV) is a rare genodermatosis characterized by abnormal susceptibility to cutaneous human beta-papillomavirus infections causing persistent flat warts or pityriasis versicolor–like lesions. This generalized verrucous skin disorder resembles generalized verrucosis, but these 2 conditions are distinguished by differences in clinical manifestation and the human papillomavirus types involved. A breakthrough in our understanding of EV was the discovery that homozygous inactivating mutations in TMC6 (EVER1) and TMC8 (EVER2) determine susceptibility to this disorder; however, they have not solved all EV cases fully.
http://ift.tt/2kdjJu2
Propranolol treatment of infantile hemangioma is not associated with psychological problems at 7 years of age
Concern has been raised about the potential long-term effects of propranolol treatment for infantile hemangioma (IH).
http://ift.tt/2lslbxK
The histopathological differentiation between palmar psoriasis and hand eczema: A retrospective review of 96 cases
The histopathologic differences among palmar psoriasis (PP), hand eczema (HE), and hyperkeratotic hand dermatitis (HHD) have been poorly described.
http://ift.tt/2kdqhsB
Erratum
In the article entitled "Manifestations of hereditary angioedema" (Ann Allergy Asthma Immunol 2017;118:119-120), the word "Neurologic" was inadvertently removed from the title. The full article title is "Neurologic manifestations of hereditary angioedema."
http://ift.tt/2kdtcl5
Transoral laser microsurgery as standard approach to hypopharyngeal cancer survival analysis in a hospital based population
Publication date: Available online 10 February 2017
Source:Acta Otorrinolaringológica Española
Author(s): Eduardo Breda, Raquel Catarino, Eurico Monteiro
ObjectiveCancer of the hypopharynx remains one of the most challenging chapters in head and neck oncology. The objective of this study is to ascertain the relevance of a transoral laser approach as a valid functional option for treatment of cancer of the hypopharynx in Portugal, and additionally, to confirm the reproducibility of survival and functional outcomes described in other reference centers.Subjects and methodsThe outcomes of 37 out of 60 patients presenting hypopharyngeal carcinoma primarily treated by TLM (transoral laser microsurgery) and neck dissection and or adjuvant treatment when needed, with curative intention in tertiary referral center, were retrospectively evaluated and compared with published results.ResultsThere were no patients in stage I. Three-year and five-year overall survival (Kaplan–Meier) were 83.5% and 63.5% for stage II (n=12), 57.1% (only 3-year overall survival evaluable for this stage) for stage III (n=7), and 53.1% and 39.8% for stage IVa (n=18), respectively. Five-year local control rates were 90% for stage II and 87.5% for stage IVa, respectively; only three-year local control rates were possible to evaluate for stage III, with a 100% control rate. Five-year total larynx preservation rate was 97.3%.ConclusionsTLM, alone or with neck dissection and adjuvant therapy, is a valid procedure for treatment of hypopharyngeal cancer in different stages. Furthermore, this kind of approach can be replicated in different oncologic centers with similar oncologic and functional results.
http://ift.tt/2kbFsru
Fournier's gangrene: diagnosis and management aided by repeated clinical examination and ultrasound
We describe a case of a man aged 57 years admitted to our tertiary centre via his general practitioner, presenting with a 1-week history of scrotal pain, testicular swelling and fluctuance. He was initially managed in the community with flucoclaxacillin for 1 week, but failed to respond to treatment. Clinical history was suggestive of Fournier's gangrene, but initial examination was not conclusive. Repeated examination over the next hour aided diagnosis and helped to track the progression of the condition. The patient was treated with intravenous antibiotics and prepared for theatre. Since there was a delay in getting the patient to theatre, an ultrasound scan was performed to help ascertain the extent of the disease to aid surgical planning. Following successful debridement and skeletalisation of the testicles and ward recovery, he was transferred for plastic reconstruction.
http://ift.tt/2lwLMWK
Metformin-associated lactic acidosis treated with continuous renal replacement therapy
Metformin-associated lactic acidosis (MALA) is a rare but life-threatening complication. We report a case of MALA in a man aged 71 years who was treated with continuous renal replacement therapy (CRRT). The patient was brought to the hospital for prolonged and gradual worsening gastrointestinal symptoms. Although he received intravenous treatment, he developed catecholamine-resistant shock, and blood gas analysis revealed lactic acidosis. Bicarbonate and antibiotics for possible sepsis were initiated, but with no clear benefit. Owing to haemodynamic instability with metabolic acidosis, urgent CRRT was given: it was immediately effective in reducing lactate levels; pH values completely normalised within 18 hours, and he was stabilised. MALA sometimes presents with non-specific symptoms, and is important to consider when treating unexplainable metabolic acidosis. In severe cases, CRRT has potential merit, particularly in haemodynamically unstable patients. It is important to be familiar with MALA as a medical emergency, even for emergency physicians.
http://ift.tt/2kAnXPY
Indomethacin therapy effective in a patient with depletion syndrome from secretory villous adenoma
This paper details the case of a 26-year-old woman with depletion syndrome and the effectiveness of her treatment with indomethacin. Villous adenomas are benign neoplasms with a high incidence of becoming malignant. A small percentage of villous adenomas are known to cause depletion syndrome, also referred to as the McKittrick-Wheelock syndrome, a condition characterised by secretory diarrhoea, dehydration, hyponatremia, hypokalaemia, hypochloraemia, metabolic acidosis and acute renal failure. Prostaglandin-E2 mediates the hypersecretion mechanism observed in depletion syndrome, and can be inhibited by cyclo-oxygenase inhibitors. This case study measured the effectiveness of prostaglandin inhibition on a patient with oral and parenteral electrolyte replacement refractory depletion syndrome. Fluid loss and prostaglandin levels were measured before and after pharmacological treatment. This case demonstrates a 49% decrease in rectal effluent and a marked commensurate decrease in daily replenishment requirements within 48 hours of indomethacin treatment initiation, resulting in subsequent electrolyte stabilisation.
http://ift.tt/2lwRuHT
Hidradenitis suppurativa, neutrophilic dermatoses and diverticular disease in a young African-American patient
Hidradenitis suppurativa (HS) is a chronic skin disorder of the terminal follicular epithelium of apocrine sweat glands, manifesting as painful and exudative papules, pustules, cysts or nodules. This inflammatory condition often presents with other systemic and cutaneous disorders. We present the case of an African-American man with HS who was also diagnosed with neutrophilic dermatoses and diverticular disease. Neutrophilic dermatosis was identified based on histopathology findings. Our patient underwent multiple surgeries for flaring of his skin condition. Colchicine and doxycycline were started, but the patient was not able to tolerate them. Humira was planned for treatment of HS and neutrophilic dermatosis but could not be pursued because of the pericolic abscess. Colonoscopy and radiological investigation revealed multiple colonic diverticuli, for which he initially underwent percutaneous drainage followed by surgical removal of sigmoid mass and colocutaneous fistula. Culture from the specimen revealed abnormal growth of Actinomyces.
http://ift.tt/2kAnNIo
Cerebral cryptococcoma mimicking glioblastoma
Cryptococcus neoformans and C. gattii cause invasive fungal disease, with meningitis being the most common manifestation of central nervous system (CNS) disease. Encapsulated cryptococcomas occur rarely, predominantly in immunocompetent hosts, usually related to C. gattii. Our patient was an immunocompetent man who presented with headache and a large cystic CNS lesion thought to be glioblastoma. Biopsy of a concomitant lung lesion confirmed cryptococcoma and empiric antifungal therapy was started for presumed CNS cryptococcoma. Antifungal therapy failed to shrink the CNS lesion, and surgical excision confirmed C. gattii CNS cryptococcoma. Following surgery he had complete resolution of symptoms. This case highlights that cryptococcoma cannot be distinguished from tumour on clinical or imaging findings. A combined medical and surgical approach is optimal for the management of large or surgically accessible cryptococcomas, as antifungal therapy alone is unlikely to penetrate large lesions sufficiently to lead to a cure.
http://ift.tt/2lwQ00r
Peritoneal amyloidosis with myopathy in primary systemic (AL) amyloidosis
Description
We present an unusual case of primary systemic amyloidosis presenting with myopathy and peritoneal amyloid deposition. Peritoneal amyloid is a rare disease with few published cases.1
An 85-year-old man was referred to rheumatology with walking difficulties and elevation of serum creatine kinase (CK). Initial tests revealed elevated erythrocyte sedimentation rate (ESR) 76 mm/hour; normal C reactive protein (CRP) and serum CK of 525 IU/L. Antinuclear and extractable nuclear antibodies (including anti-Jo1) were negative. Investigations for myopathy included MRI Stir sequence (figure 1) demonstrated increased signal in the hip adductors bilaterally, consistent with symmetrical myositis. CT scan of the chest, abdomen and pelvis, requested to exclude occult cancer, revealed diffuse infiltration of the mesentery and retroperitoneal fat (figure 2), despite lack of abdominal symptoms. This appearance was initially considered suspicious of malignancy without an obvious primary lesion; however, mesenteric biopsy reported only hyaline fatty...
http://ift.tt/2kAnXzs
Recombinant EphB4-HSA Fusion Protein and Pembrolizumab, MK-3475
Interventions: Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab; Biological: Recombinant EphB4-HSA Fusion Protein
Sponsors: University of Southern California; National Cancer Institute (NCI)
Not yet recruiting - verified February 2017
http://ift.tt/2kQ7rd5
Olfactory Training in Improving Sense of Smell After Radiation Therapy in Patients With Paranasal Sinus or Nasopharyngeal Cancer
Interventions: Other: Physiologic Testing; Other: Quality-of-Life Assessment; Procedure: Sham Intervention; Procedure: Therapeutic Procedure; Other: rose essential oil; Other: lemon essential oil; Other: clove essential oil; Other: eucalyptus essential oil; Other: canola oil
Sponsor: Stanford University
Not yet recruiting - verified February 2017
http://ift.tt/2l1cdXx
Rhinoplastik
Zusammenfassung
Die gezielte Durchtrennung und Neupositionierung des Knochens der Nasenpyramide ist ein wesentlicher Schritt bei der Rhinoplastik. Jeder Knochenschnitt sollte wohl geplant und technisch präzise ausgeführt werden, denn eine falsche Osteotomie ist kaum korrigierbar. Deshalb haben die Auswahl der Osteotome und die optimale Technik der Ausführung großen Einfluss auf den Erfolg einer Rhinoplastik. Die Forderung, dass keine ästhetische Rhinoplastik auf Kosten der Nasenatmung geht, wird immer wieder postuliert. Dennoch ist klar, dass Osteotomien sehr wohl Einfluss auf die Nasenatmung, insbesondere auf die Weite der Nasenklappenregion haben können. Der Beitrag bietet ein Update der neuesten technischen und instrumentellen Innovationen.
http://ift.tt/2lrDFyu
Chlorothiazide-induced photoaggravation of psoriatic lesion during narrowband ultraviolet B treatment in a case of psoriasis vulgaris
http://ift.tt/2kWBaUp
Adjuvant rituximab treatment for pemphigus: A retrospective study of 45 patients at a single center with long-term follow up
Abstract
To evaluate the long-term outcomes of rituximab in the treatment of pemphigus and the influence of disease duration and different dose of rituximab on the clinical response, 45 patients with refractory pemphigus treated with at least one cycle of two infusions of rituximab (375 mg/m2 per infusion weekly) were retrospectively studied. All patients were followed up for more than 2 years. All patients achieved complete or partial remission within 8 months of the first cycle. Thirty-four (76%) patients relapsed at a median of 17 months. All patients who received additional cycles after relapse achieved new remissions. Early use of rituximab within 1 year of disease duration and high-dose therapy induced better outcomes, although the results in early use were not statistically significant. Acute respiratory distress syndrome occurred in one patient. Rituximab is effective in treating pemphigus, but relapses are frequent during long-term follow up, and additional cycles are beneficial in relapsed cases. Early and high-dose rituximab therapy may be more effective.
http://ift.tt/2kc6bPx
Analysis of clinical symptoms and ABCC6 mutations in 76 Japanese patients with pseudoxanthoma elasticum
Abstract
Pseudoxanthoma elasticum (PXE) is a hereditary disease, causing calcification and degeneration of elastic fibers, which affects the skin, eye, cardiovascular systems and gastrointestinal tract. PXE is caused by mutations in the ABCC6 gene. Neither detailed nor large-scale analyses have been accomplished in Japanese patients with PXE. We, therefore, investigated clinical symptoms and ABCC6 gene mutations in 76 Japanese patients. Japanese PXE patients (n = 76) had a significantly lower incidence of vascular lesions than 505 PXE patients in the Leiden Open Variation Database (LOVD) (38.7% vs 65.1%, respectively; P = 1.34E-06); however, the incidences of the skin, eye, cardiac and gastrointestinal lesion symptoms were not significantly different. Symptom severity scores for skin, eye and vascular lesions, calculated using the Phenodex™ system, were significantly lower in Japanese PXE patients than in LOVD PXE patients. Genetic analysis revealed three nonsense, four frame-shift, one exon deletion and 13 missense mutations in ABCC6 in 73 patients; however, we were unable to detect pathogenic mutations in three patients. Frequent mutations differed between Japanese and LOVD PXE patients. In Japanese PXE patients, the top five mutations accounted for more than 60% of all pathogenic changes, suggesting the presence of founder effects. Consistent with previous reports, no obvious correlations between genotypes and phenotypes were identified in this study. In conclusion, we consider that the milder clinical phenotypes, observed even in older Japanese PXE patients, could be attributed to environmental factors such as dietary habits and lifestyle, as well as genetic background.
http://ift.tt/2kWxZvZ
Measuring acute postoperative pain using the visual analog scale: the minimal clinically important difference and patient acceptable symptom state
<span class="paragraphSection"><strong>Background.</strong> The 100 mm visual analog scale (VAS) score is widely used to measure pain intensity after surgery. Despite this widespread use, it is unclear what constitutes the minimal clinically important difference (MCID); that is, what minimal change in score would indicate a meaningful change in a patient's pain status.<strong>Methods.</strong> We enrolled a sequential, unselected cohort of patients recovering from surgery and used a VAS to quantify pain intensity. We compared changes in the VAS with a global rating-of-change questionnaire using an anchor-based method and three distribution-based methods (0.3 <span style="text-transform:lowercase;font-variant:small-caps;">sd</span>, standard error of the measurement, and 5% range). We then averaged the change estimates to determine the MCID for the pain VAS. The patient acceptable symptom state (PASS) was defined as the 25th centile of the VAS corresponding to a positive patient response to having made a good recovery from surgery.<strong>Results.</strong> We enrolled 224 patients at the first postoperative visit, and 219 of these were available for a second interview. The VAS scores improved significantly between the first two interviews. Triangulation of distribution and anchor-based methods resulted in an MCID of 9.9 for the pain VAS, and a PASS of 33.<strong>Conclusions.</strong> Analgesic interventions that provide a change of 10 for the 100 mm pain VAS signify a clinically important improvement or deterioration, and a VAS of 33 or less signifies acceptable pain control (i.e. a responder), after surgery.</span>
http://ift.tt/2kWegfS
Pulmonary aspiration during procedural sedation: a comprehensive systematic review
http://ift.tt/2kbJ0VJ
Risk prediction models for delirium in the intensive care unit after cardiac surgery: a systematic review and independent external validation
<span class="paragraphSection">Numerous risk prediction models are available for predicting delirium after cardiac surgery, but few have been directly compared with one another or been validated in an independent data set. We conducted a systematic review to identify validated risk prediction models of delirium (using the Confusion Assessment Method-Intensive Care Unit tool) after cardiac surgery and assessed the transportability of the risk prediction models on a prospective cohort of 600 consecutive patients undergoing cardiac surgery at a university hospital in Hong Kong from July 2013 to July 2015. The discrimination (c-statistic), calibration (GiViTI calibration belt), and clinical usefulness (decision curve analysis) of the risk prediction models were examined in a stepwise manner. Three published high-quality intensive care unit delirium risk prediction models (<span style="font-style:italic;">n</span>=5939) were identified: Katznelson, the original PRE-DELIRIC, and the international recalibrated PRE-DELIRIC model. Delirium occurred in 83 patients (13.8%, 95% CI: 11.2–16.9%). After updating the intercept and regression coefficients in the Katznelson model, there was fair discrimination (0.62, 95% CI: 0.58–0.66) and good calibration. As the original PRE-DELIRIC model was already validated externally and recalibrated in six countries, we performed a logistic calibration on the recalibrated model and found acceptable discrimination (0.75, 95% CI: 0.72–0.79) and good calibration. Decision curve analysis demonstrated that the recalibrated PRE-DELIRIC risk model was marginally more clinically useful than the Katznelson model. Current models predict delirium risk in the intensive care unit after cardiac surgery with only fair to moderate accuracy and are insufficient for routine clinical use.</span>
http://ift.tt/2kbBDNZ
Postoperative pulmonary complications
<span class="paragraphSection">Postoperative pulmonary complications (PPCs) are common, costly, and increase patient mortality. Changes to the respiratory system occur immediately on induction of general anaesthesia: respiratory drive and muscle function are altered, lung volumes reduced, and atelectasis develops in > 75% of patients receiving a neuromuscular blocking drug. The respiratory system may take 6 weeks to return to its preoperative state after general anaesthesia for major surgery. Risk factors for PPC development are numerous, and clinicians should be aware of non-modifiable and modifiable factors in order to recognize those at risk and optimize their care. Many validated risk prediction models are described. These have been useful for improving our understanding of PPC development, but there remains inadequate consensus for them to be useful clinically. Preventative measures include preoperative optimization of co-morbidities, smoking cessation, and correction of anaemia, in addition to intraoperative protective ventilation strategies and appropriate management of neuromuscular blocking drugs. Protective ventilation includes low tidal volumes, which must be calculated according to the patient's ideal body weight. Further evidence for the most beneficial level of PEEP is required, and on-going randomized trials will hopefully provide more information. When PEEP is used, it may be useful to precede this with a recruitment manoeuvre if atelectasis is suspected. For high-risk patients, surgical time should be minimized. After surgery, nasogastric tubes should be avoided and analgesia optimized. A postoperative mobilization, chest physiotherapy, and oral hygiene bundle reduces PPCs.</span>
http://ift.tt/2kWob4M
Change in end-tidal carbon dioxide outperforms other surrogates for change in cardiac output during fluid challenge
<span class="paragraphSection"><strong>Background.</strong> During fluid challenge, volume expansion (VE)-induced increase in cardiac output (Δ<sub>VE</sub>CO) is seldom measured.<strong>Methods.</strong> In patients with shock undergoing strictly controlled mechanical ventilation and receiving VE, we assessed minimally invasive surrogates for Δ<sub>VE</sub>CO (by transthoracic echocardiography): fluid-induced increases in end-tidal carbon dioxide (Δ<sub>VE</sub>E′CO2); pulse (Δ<sub>VE</sub>PP), systolic (Δ<sub>VE</sub>SBP), and mean systemic blood pressure (Δ<sub>VE</sub>MBP); and femoral artery Doppler flow (Δ<sub>VE</sub>FemFlow). In the absence of arrhythmia, fluid-induced decrease in heart rate (Δ<sub>VE</sub>HR) and in pulse pressure respiratory variation (Δ<sub>VE</sub>PPV) were also evaluated. Areas under the receiver operating characteristic curves (AUC<sub>ROC</sub>s) reflect the ability to identify a response to VE (Δ<sub>VE</sub>CO ≥15%).<strong>Results.</strong> In 86 patients, Δ<sub>VE</sub>E′CO2 had an AUC<sub>ROC</sub>=0.82 [interquartile range 0.73–0.90], significantly higher than the AUC<sub>ROC</sub> for Δ<sub>VE</sub>PP, Δ<sub>VE</sub>SBP, Δ<sub>VE</sub>MBP, and Δ<sub>VE</sub>FemFlow (AUC<sub>ROC</sub>=0.61–0.65, all <span style="font-style:italic;">P</span> <0.05). A value of Δ<sub>VE</sub>E′CO2 >1 mm Hg (>0.13 kPa) had good positive (5.0 [2.6–9.8]) and fair negative (0.29 [0.2–0.5]) likelihood ratios. The 16 patients with arrhythmia had similar relationships between Δ<sub>VE</sub>E′CO2 and Δ<sub>VE</sub>CO to patients with regular rhythm (<span style="font-style:italic;">r</span><sup>2</sup>=0.23 in both subgroups). In 60 patients with no arrhythmia, Δ<sub>VE</sub>E′CO2 (AUC<sub>ROC</sub>=0.84 [0.72–0.92]) outperformed Δ<sub>VE</sub>HR (AUC<sub>ROC</sub>=0.52 [0.39–0.66], <span style="font-style:italic;">P</span><0.05) and tended to outperform Δ<sub>VE</sub>PPV (AUC<sub>ROC</sub>=0.73 [0.60–0.84], <span style="font-style:italic;">P</span>=0.21). In the 45 patients with no arrhythmia and receiving ventilation with tidal volume <8 ml kg<sup>−1</sup>, Δ<sub>VE</sub>E′CO2 performed better than Δ<sub>VE</sub>PPV, with AUC<sub>ROC</sub>=0.86 [0.72–0.95] <span style="font-style:italic;">vs</span> 0.66 [0.49–0.80], <span style="font-style:italic;">P</span>=0.02.<strong>Conclusions.</strong> Δ<sub>VE</sub>E′CO2 outperformed Δ<sub>VE</sub>PP, Δ<sub>VE</sub>SBP, Δ<sub>VE</sub>MBP, Δ<sub>VE</sub>FemFlow, and Δ<sub>VE</sub>HR and, during protective ventilation, arrhythmia, or both, it also outperformed Δ<sub>VE</sub>PPV. A value of Δ<sub>VE</sub>E′CO2 >1 mm Hg (>0.13 kPa) indicated a likely response to VE.</span>
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Predictive performance of eleven pharmacokinetic models for propofol infusion in children for long-duration anaesthesia
<span class="paragraphSection"><strong>Background.</strong> Predictive performance of eleven published propofol pharmacokinetic models was evaluated for long-duration propofol infusion in children.<strong>Methods.</strong> Twenty-one aged three–11 yr ASA I–II patients were included. Anaesthesia was induced with propofol or sevoflurane, and maintained with propofol, remifentanil, and fentanyl. Propofol was continuously infused at rates of 4–14 mg kg <sup>−</sup><sup>1</sup> h<sup>−</sup><sup>1</sup> after an initial bolus of 1.5–2.0 mg kg <sup>−</sup><sup>1</sup>. Venous blood samples were obtained every 30–60 min for five h and then every 60–120 min after five h from the start of propofol administration, and immediately after the end of propofol administration. Model performance was assessed with prediction error (PE) derivatives including divergence PE, median PE (MDPE), and median absolute PE (MDAPE) as time-related PE shift, measures for bias, and inaccuracy, respectively.<strong>Results.</strong> We collected 85 samples over 270 (130) (88–545), mean (SD) (range), min. The Short model for children, and the Schüttler general-purpose model had acceptable performance (–20%≤MDPE ≤ 20%, MDAPE ≤ 30%, –4% h<sup>−</sup><sup>1 </sup>≤<sup> </sup>divergence PE ≤ 4% h<sup>−</sup><sup>1</sup>). The Short model showed the best performance with the maximum predictive performance metric. Two models developed only using bolus dosing (Shangguan and Saint-Maurice models) and the Paedfusor of the remaining nine models had significant negative divergence PE (≤–6.1% h<sup>−</sup><sup>1</sup>).<strong>Conclusions.</strong> The Short model performed well during continuous infusion up to 545 min. This model might be preferable for target-controlled infusion for long-duration anaesthesia in children.</span>
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Biochemical changes on the repair of surgical bone defects grafted with biphasic synthetic micro-granular HA + β-tricalcium phosphate induced by laser and LED phototherapies and assessed by Raman spectroscopy
Abstracts
This work aimed the assessment of biochemical changes induced by laser or LED irradiation during mineralization of a bone defect in an animal model using a spectral model based on Raman spectroscopy. Six groups were studied: clot, laser (λ = 780 nm; 70 mW), LED (λ = 850 ± 10 nm; 150 mW), biomaterial (biphasic synthetic micro-granular hydroxyapatite (HA) + β-tricalcium phosphate), biomaterial + laser, and biomaterial + LED. When indicated, defects were further irradiated at a 48-h interval during 2 weeks (20 J/cm2 per session). At the 15th and 30th days, femurs were dissected and spectra of the defects were collected. Raman spectra were submitted to a model to estimate the relative amount of collagen, phosphate HA, and carbonate HA by using the spectra of pure collagen and biomaterials composed of phosphate and carbonate HA, respectively. The use of the biomaterial associated to phototherapy did not change the collagen formation at both 15 and 30 days. The amount of carbonate HA was not different in all groups at the 15th day. However, at the 30th day, there was a significant difference (ANOVA, p = 0.01), with lower carbonate HA for the group biomaterial + LED compared to biomaterial (p < 0.05). The phosphate HA was higher in the groups that received biomaterial grafts at the 15th day compared to clot (significant for the biomaterial; p < 0.01). At the 30th day, the phosphate HA was higher for the group biomaterial + laser, while this was lower for all the other groups. These results indicated that the use of laser phototherapy improved the repair of bone defects grafted with the biomaterial by increasing the deposition of phosphate HA.
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Cochlear implant treatment of patients with single-sided deafness or asymmetric hearing loss
Abstract
Background
The rehabilitation of patients with single-sided deafness (SSD) or asymmetric hearing loss can be achieved with conventional (Bi)CROS hearing aids ((Bi)CROS-HA, (Bi)CROS), bone conduction devices (BCI) or with cochlear implants (CI). Unfortunately, only small case series have been published on the treatment outcomes in SSD patients after CI surgery and there are only a few comparative studies evaluating rehabilitation outcomes.
Objective
The aim of this study was to provide evidence of successful treatment of SSD and asymmetric hearing loss with a CI compared to the untreated, monaural hearing condition and the therapy options of BCI and (Bi)CROS in a large number of patients.
Materials and methods
In a single-centre study, 45 patients with SSD and 40 patients with asymmetric hearing loss were treated with a CI after careful evaluation for CI candidacy. Monaural speech comprehension in noise and localisation ability were examined with (Bi)CROS-HA and BCI devices (on a test rod) both preoperatively and at 12 months after CI switch-on. At the same intervals, subjective evaluation of hearing ability was conducted using the Speech, Spatial and Qualities of Hearing Scale (SSQ).
Results and discussion
This report presents the first evidence of successful binaural rehabilitation with CI in a relatively large patient cohort and the advantages over (Bi)CROS and BCI in smaller subgroups, thus confirming the indication for CI treatment. Moreover, patients with long-term acquired deafness (>10 years) show a benefit from the CI comparable to that observed in patients with shorter-term deafness.
http://ift.tt/2kznvRU
Older women may not be offered breast reconstruction after mastectomy
A national study from England indicates that older women are often not offered immediate breast reconstruction following a mastectomy, even though guidelines state that surgeons should discuss...
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Ophthalmia Secondary to Cobra Venom Spitting in the Volta Region, Ghana: A Case Report
Case Rep Ophthalmol 2017;8:99–103
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Metformin effects on head and neck squamous carcinoma microenvironment: Window of opportunity trial
Objective
The tumor microenvironment frequently displays abnormal cellular metabolism, which contributes to aggressive behavior. Metformin inhibits mitochondrial oxidative phosphorylation, altering metabolism. Though the mechanism is unclear, epidemiologic studies show an association between metformin use and improved outcomes in head and neck squamous cell carcinoma (HNSCC). We sought to determine if metformin alters metabolism and apoptosis in HNSCC tumors.
Study Design
Window of opportunity trial of metformin between diagnostic biopsy and resection. Participants were patients with newly diagnosed HNSCC. Fifty patients were enrolled, and 39 completed a full-treatment course. Metformin was titrated to standard diabetic dose (2,000 mg/day) for a course of 9 or more days prior to surgery.
Methods
Immunohistochemistry (IHC) for the metabolic markers caveolin-1 (CAV1), B-galactosidase (GALB), and monocarboxylate transporter 4 (MCT4), as well as the Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) apoptosis assay and Ki-67 IHC, were performed in pre- and postmetformin specimens. Exploratory mass spectroscopy imaging (MSI) to assess lactate levels also was performed in three subjects.
Results
Metformin was well tolerated. The average treatment course was 13.6 days. Posttreatment specimens showed a significant increase in stromal CAV1 (P < 0.001) and GALB (P < 0.005), as well as tumor cell apoptosis by TUNEL assay (P < 0.001). There was no significant change in stromal MCT4 expression or proliferation measured by Ki67. Lactate levels in carcinoma cells were increased 2.4-fold postmetformin (P < 0.05), as measured by MSI.
Conclusion
Metformin increases markers of reduced catabolism and increases senescence in stromal cells as well as carcinoma cell apoptosis. This study demonstrates that metformin modulates metabolism in the HNSCC microenvironment.
Level of Evidence
4. Laryngoscope, 2017
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Title Page
Publication date: March 2017
Source:Journal of Allergy and Clinical Immunology, Volume 139, Issue 3, Supplement
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Table of Contents
Publication date: March 2017
Source:Journal of Allergy and Clinical Immunology, Volume 139, Issue 3, Supplement
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Epicutaneous sensitization to house dust mite allergen requires IRF4-dependent dermal dendritic cells
Publication date: Available online 9 February 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Julie Deckers, Dorine Sichien, Maud Plantinga, Justine Van Moorleghem, Manon Vanheerswynghels, Esther Hoste, Bernard Malissen, David Dombrowicz, Martin Guilliams, Karolien De Bosscher, Bart N. Lambrecht, Hamida Hammad
BackgroundExposure to allergens like house dust mite (HDM) via the skin often precedes allergic inflammation in the lung. It was proposed that Th2 sensitization via the skin occurs when skin barrier function is disrupted for example by genetic predisposition, mechanical damage or enzymatic activity of allergens.ObjectiveTo study how HDM applied to unmanipulated skin leads to Th2 sensitization and to study which antigen presenting cells mediate this processMethodsHDM was applied epicutaneously by painting HDM on unmanipulated ear skin, or under an occlusive tape. HDM challenge was via the nose. Mouse strains lacking different dendritic cell (DC) populations were used, and 1-DER T cells carrying a transgenic TCR reactive to Der p 1 allergen used as readout for antigen presentation. The Th2-inducing capacity of sorted skin-derived DC subsets was determined by adoptive transfer to naïve mice.ResultsEpicutaneous HDM application led to Th2 sensitization and eosinophilic airway inflammation upon intranasal HDM challenge. Skin sensitization did not require prior skin damage or enzymatic activity within HDM extract, yet was facilitated by applying the allergen under an occlusive tape. Primary proliferation of 1-DER T cells occurred only in the regional skin draining lymph nodes. Epicutaneous sensitization was found to be driven by two variants of IRF4-dependent dermal conventional dendritic cell (cDC2) subsets, and not by epidermal Langerhans cells.ConclusionThese findings identify skin cDC2 as crucial players in Th2 sensitization to common inhaled allergens that enter the body through the skin, and can provoke features of allergic asthma.
Teaser
Our findings identify skin IRF4-dependent cDC2 and not Langerhans cells as crucial players in Th2 sensitization to HDM. How alterations in skin-expressed proteins or cytokines in patients at risk for developing asthma could interfere with this basic mechanism of DC-driven type 2 immunity will need to be addressed.http://ift.tt/2kz9Om8
Maternal house dust mite exposure during pregnancy enhances severity of HDM-induced asthma in murine offspring
Publication date: Available online 9 February 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Phoebe K. Richgels, Amnah Yamani, Claire A. Chougnet, Ian P. Lewkowich
BackgroundAtopic status of the mother and maternal exposure to environmental factors is associated with increased asthma risk. Moreover, animal models demonstrate that exposure to allergens in strongly sensitized mothers influences offspring asthma development, suggesting that in utero exposures can influence offspring asthma. However, it is unclear whether maternal exposure to common human allergens like house dust mite (HDM), in the absence of additional adjuvants, influences offspring asthma development.ObjectiveTo determine if maternal HDM exposure influences asthma development in offspring.MethodsPregnant female mice were exposed to PBS or HDM during pregnancy. Using offspring of PBS or HDM-exposed mothers, the magnitude of HDM or Aspergillus fumigatus (AF) extract-induced airway hyperresponsiveness (AHR), airway inflammation, immunoglobulin production, Th2-associated cytokine synthesis and pulmonary dendritic cell activity was assessed.ResultsCompared to offspring of PBS-exposed mothers, offspring of HDM-exposed mothers demonstrate increased AHR, airway inflammation, Th2 cytokine production, immunoglobulin levels and a modest decrease in the phagocytic capacity of pulmonary macrophage populations following HDM exposure. Increased sensitivity to AF-induced airway disease was not observed. Offspring of HDM-exposed B cell deficient mothers also demonstrated increased HDM-induced AHR, suggesting transfer of maternal immunoglobulins is not required.ConclusionsOur data demonstrate that maternal exposure to HDM during pregnancy increases asthma sensitivity in offspring in an HDM-specific manner, suggesting that vertical transmission of maternal immune responses may be involved. These findings have important implications for regulation of asthma risk, and suggest that exposure to HDM in the developed world may have under-appreciated influences on the overall prevalence of allergic asthma.
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Cover 1
Publication date: March 2017
Source:Journal of Allergy and Clinical Immunology, Volume 139, Issue 3, Supplement
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Prediction of peanut allergy in adolescence by early childhood storage protein-specific IgE signatures: the BAMSE population-based birth cohort
Publication date: Available online 9 February 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Anna Asarnoj, Carl Hamsten, Christian Lupinek, Erik Melén, Niklas Andersson, Josep M. Anto, Jean Bousquet, Rudolf Valenta, Marianne van Hage, Magnus Wickman
Teaser
IgE signatures to peanut allergen measured in early childhood allow predicting the likelihood of peanut allergy in adolescence. Peanut symptoms and Ara h 2 IgE >2.0 ISU-E at 4 years predict peanut allergy in adolescence.http://ift.tt/2ly6k1z
The role of ST2 and ST2 genetic variants in schistosomiasis
Publication date: Available online 9 February 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Xin Long, Michelle Daya, Jianping Zhao, Nicholas Rafaels, Huifang Liang, Joseph Potee, Monica Campbell, Bixiang Zhang, Maria Ilma Araujo, Ricardo R. Oliveira, Rasika A. Mathias, Li Gao, Ingo Ruczinski, Steve N. Georas, Donata Vercelli, Terri H. Beaty, Kathleen C. Barnes, Xiaoping Chen, Qian Chen
BackgroundChronic schistosomiasis and its severe complication, periportal fibrosis, are characterized by a predominant Th2 response. To date, specific SNPs in ST2 have been some of the most consistently associated genetic variants for asthma.ObjectivesWe investigated the role of ST2 (a receptor for the Th2 cytokine IL-33) in chronic and late-stage schistosomiasis caused by S. japonicum, and the potential effect of ST2 genetic variants on stage of disease and ST2 expression.Methods947 adult participants (339 with end-stage schistosomiasis and liver cirrhosis, 307 with chronic infections without liver fibrosis, and 301 health controls) were recruited from a S. japonicum-endemic area (Hubei, China). Six ST2 SNPs were genotyped. Serum sST2 was measured by ELISA, and ST2 expression in normal liver tissues, HBV-induced fibrotic liver tissues and S. japonicum-induced fibrotic liver tissues was measured by immunohistochemistry.Results: sST2 levels were significantly higher in the end-stage group (36.04 [95 %CI 33.85;38.37]) compared to chronic cases and controls (22.7 [95% CI 22.0;23.4], p-value < 1E-10). In addition, S. japonicum-induced fibrotic liver tissues showed increased ST2 staining compared to normal liver tissues (p-value=0.0001). Markers rs12712135, rs1420101 and rs6543119 were strongly associated with sST2 levels (p-values 2E-10, 5E-05 and 6E-05 respectively), and these results were replicated in an independent cohort from Brazil living in a S. mansoni endemic region.ConclusionWe demonstrate for the first time that end-stage schistosomiasis is associated with elevated sST2 levels, and show that ST2 genetic variants are associated with sST2 levels in patients with schistosomiasis.
Teaser
ST2 mediates a Th2 response characteristic of both allergic and parasitic disease. We demonstrate that end-stage schistosomiasis is associated with sST2 levels and ST2 polymorphisms associated with asthma are associated with sST2 in schistosomiasis.http://ift.tt/2kzhk0r
A phase III randomized controlled trial of tiotropium add-on therapy in children with severe symptomatic asthma
Publication date: Available online 9 February 2017
Source:Journal of Allergy and Clinical Immunology
Author(s): Stanley J. Szefler, Kevin Murphy, Thomas Harper, Attilio Boner, István Laki, Michael Engel, Georges El Azzi, Petra Moroni-Zentgraf, Helen Finnigan, Eckard Hamelmann
BackgroundStudies in adults and adolescents have demonstrated that tiotropium is efficacious as an add-on therapy to inhaled corticosteroids (ICS) with or without other maintenance therapies in patients with moderate or severe symptomatic asthma.ObjectiveTo assess the efficacy and safety of once-daily tiotropium Respimat add-on therapy to high-dose ICS with 1 or more controller medications, or medium-dose ICS with 2 or more controller medications, in the first phase III trial of tiotropium in children with severe symptomatic asthma.MethodsIn this 12-week, double-blind, placebo-controlled, parallel-group trial, 401 participants aged 6-11 years were randomized to receive once-daily tiotropium 5 μg (2 puffs of 2.5 μg) or 2.5 μg (2 puffs of 1.25 μg), or placebo (2 puffs), administered through the Respimat device as add-on to background therapy.ResultsCompared with placebo, tiotropium 5 μg add-on therapy, but not 2.5 μg, improved the primary endpoint, peak forced expiratory volume in 1 second (FEV1) within 3 hours after dosing (5 μg, 139 mL [95% CI, 75-203; P < 0.001]; 2.5 μg, 35 mL [95% CI, −28-99; P = 0.27]), and the key secondary endpoint, trough FEV1 (5 μg, 87 mL [95% CI, 19-154; P = 0.01]; 2.5 μg, 18 mL [95% CI, −48-85; P = 0.59]). The safety and tolerability of tiotropium were comparable with those of placebo.ConclusionOnce-daily tiotropium Respimat 5 μg improved lung function and was well tolerated as add-on therapy to ICS with other maintenance therapies in children with severe symptomatic asthma.
Teaser
Once-daily tiotropium Respimat 5 μg as add-on therapy to ICS with other maintenance therapy has been shown for the first time to provide improved lung function in children with severe symptomatic asthma.http://ift.tt/2ly0vS3
Pathology of infectious diseases: what does the future hold?
Abstract
The demand for expertise in pathology for the diagnosis of infectious diseases (ID) is continually growing, due to an increase in ID in immunocompromised patients and in the (re)-emergence of common and uncommon diseases, including tropical infections and infections with newly identified microbes. The microbiology laboratory plays a crucial role in diagnosing infections, identifying the responsible infectious agents and establishing sensitivity of pathogens to drug therapy. Pathology, however, is the only way to correlate the presence of an infectious agent with the reaction it evokes at cell and tissue level. For pathologists working in the field of ID pathology, it is essential to dispose of competence in cell and tissue pathology as well as in microbiology. Expertise in ID includes understanding of taxonomy and classification of pathogens as well as morphological criteria supporting their identification. Moreover, ID pathologists must master the methods used to detect pathogens in fixed cell and tissue samples, notably immunohistochemistry, in situ hybridization and the polymerase chain reaction. Paradoxically, the increasing frequency of lesions caused by pathogens and diagnosed in a pathology laboratory appears to be paralleled by a gradual loss of expertise of pathologists in the field of infectious and tropical diseases. We contend that this may be due at least in part to the continuously increasing number of samples of tumor tissue pathologists deal with and the rapidly expanding number of tissue based biomarkers with predictive value for new anti-cancer therapies. In this review, we highlight current and future issues pertaining to ID pathology, in order to increase awareness of its importance for surgical and molecular pathology. The intention is to contribute to the development of best practice in ID pathology.
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Factors that may influence polymorphous low-grade adenocarcinoma growth
Abstract
There is mounting evidence on the importance of some biological processes in tumor growth, such as vascular supply, apoptosis, autophagy, and senescence. We have investigated these processes in polymorphous low-grade adenocarcinoma (PLGA), in an attempt to identify those that are relevant for this particular lesion. We analyzed 31 cases of PLGA using immunohistochemistry to antibodies against CD34 and CD105 to detect blood vessels; against D2-40 to detect lymphatic vessels; against Bax, Bcl-2, and survivin to explore cell apoptosis; and against Beclin and LCB3 to investigate autophagy and against p21 and p16 to assess senescence. Our results showed that PLGA growth does not depend on newly formed vessels but only on preexisting vasculature. Furthermore, PLGA is promoted by autophagy, sustained by both anti-apoptotic and anti-senescence signals, and stimulated by Bcl-2 and survivin.
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Patients with McCune-Albright syndrome have a broad spectrum of abnormalities in the gastrointestinal tract and pancreas
Abstract
McCune-Albright Syndrome (MAS) is a rare sporadic syndrome caused by post-zygotic mutations in the GNAS oncogene, leading to constitutional mosaicism for these alterations. Somatic activating GNAS mutations also commonly occur in several gastrointestinal and pancreatic neoplasms, but the spectrum of abnormalities in these organs in patients with MAS has yet to be systematically described. We report comprehensive characterization of the upper gastrointestinal tract in seven patients with MAS and identify several different types of polyps, including gastric heterotopia/metaplasia (7/7), gastric hyperplastic polyps (5/7), fundic gland polyps (2/7), and a hamartomatous polyp (1/7). In addition, one patient had an unusual adenomatous lesion at the gastroesophageal junction with high-grade dysplasia. In the pancreas, all patients had endoscopic ultrasound findings suggestive of intraductal papillary mucinous neoplasm (IPMN), but only two patients met the criteria for surgical intervention. Both of these patients had IPMNs at resection, one with low-grade dysplasia and one with high-grade dysplasia. GNAS mutations were identified in the majority of lesions analyzed, including both IPMNs and the adenomatous lesion from the gastroesophageal junction. These studies suggest that there is a broad spectrum of abnormalities in the gastrointestinal tract and pancreas in patients with MAS and that patients with MAS should be evaluated for gastrointestinal pathology, some of which may warrant clinical intervention due to advanced dysplasia.
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Thermal analysis and stability of commercially available endodontic obturation materials
Abstract
Objectives
The purpose of this study was to evaluate the thermal stability of 23 commercially-available endodontic obturation materials.
Materials and methods
Specimens (n = 10) were sealed in aluminum differential scanning calorimetry (DSC) crucibles and subjected to thermal scan series consisting of a 25 to 70 °C at 5 °C/min followed by a rapid increase to 230 °C, followed by a second scan from 25 to 70 °C at 5 °C/min. The first scan evaluated the materials as-received followed by a worse-case-scenario thermal challenge simulating temperatures involved with warm vertical condensation obturation techniques. The second thermal scan observed any phase changes from the high temperature challenge. This two-scan process was repeated twice to observe changes encountered by repeat high heat exposure during obturation. Mean thermal enthalpies were analyzed with Kruskal-Wallis and Games-Howell post-hoc test. (p = 0.05).
Results
Thermal behavior was material dependent. During the first thermal scan, materials typically demonstrated broad endothermic enthalpy curves suggesting either a gutta-percha phase mixture and/or an alpha crystalline phase. The first high-heat challenge produced definitive alpha/beta thermal phase signatures usually associated with gutta-percha. Changes in beta-phase enthalpies were noted with Therarmafil Plus and UltraFil Firmset while increase in alpha-phases was observed with GuttaCore, K3, Lexicon, and Schein Accessory Points.
Conclusions
Commercial endodontic gutta-percha obturation materials displayed thermal characteristics that were material dependent. However, all demonstrated stability at temperatures in excess to that experienced during warm vertical condensation techniques.
Clinical relevance
The gutta-percha obturation materials evaluated in this evaluation can be used successfully in warm vertical condensation techniques without fear of degradation.
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Severe Intraoperative Hyperglycemia Is Independently Associated With Postoperative Composite Infection After Craniotomy: An Observational Study.
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Novel Pump Control Technology Accelerates Drug Delivery Onset in a Model of Pediatric Drug Infusion.
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Study Design Rigor in Animal-Experimental Research Published in Anesthesia Journals.
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Prophylactic Plasma Transfusion Is Not Associated With Decreased Red Blood Cell Requirements in Critically Ill Patients.
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