Τρίτη 4 Ιουλίου 2017
Correlation of CD4 counts with clinical and histopathological findings in disseminated histoplasmosis: a 10-year retrospective study
Abstract
Background
Disseminated cutaneous histoplasmosis (DCH) is one of the manifestations of systemic histoplasmosis infection in HIV-positive patients. Interaction between host immune status and histoplasmosis infection is still poorly understood. It is thought that immune status, represented by CD4 counts, may be correlated with clinical and histopathological findings.
Objective
To correlate the CD4 counts with the different clinical and histopathological findings in cutaneous histoplasmosis.
Methods
This was a serial case report of seven HAART-treated HIV positive patients with disseminated histoplasmosis observed within the period of January 2004 through December 2014 from the Dermatology and Venereology Department, Cipto Mangunkusumo Hospital, Jakarta, Indonesia. The patients came with different complaints and clinical findings. CD4 counts were recorded prior to lesion biopsy.
Results
The CD4 counts were independent from clinical morphology and distribution of lesions. Lower CD4 counts were associated with the presence of intraepidermal yeast-like cells, whereas there is the ability of forming granulomas at higher CD4 counts.
Conclusion
CD4 count correlates to histopathological findings of cutaneous histoplasmosis.
http://ift.tt/2sEuor6
Top 10 Myths Regarding the Diagnosis and Treatment of Cellulitis
Source:The Journal of Emergency Medicine
Author(s): Erin K. McCreary, Melissa E. Heim, Lucas T Schulz, Robert Hoffman, Jeffrey Pothof, Barry Fox
BackgroundCellulitis is commonly treated in the emergency department (ED). Patients who present with cellulitis incur significant health care costs and may be overtreated with antibiotics. The accurate diagnosis and treatment of cellulitis plays an important role in cost-effective, high-quality medical care, as well as appropriate antibiotic utilization.ObjectiveWe aim to describe common fallacies regarding cellulitis. We present 10 myths that result in misdiagnosis, overtreatment, or inappropriate empiric management of cellulitis. Clinical presentation, including swelling and redness, is explored in depth, along with incidence of community-acquired methicillin-resistance Staphylococcus aureus, management of tick bites, and effective antibiotic therapy for cellulitis.DiscussionPatients are often treated for cellulitis unnecessarily or inappropriately. Awareness of these myths will help guide providers in clinical decision making in order to effectively tailor treatment for these infections.ConclusionsCellulitis is not as simple as it might seem, and is commonly misdiagnosed in the ED. Noninfectious causes of local symptoms, including lymphedema, venous stasis, and deep vein thrombosis need to be considered. Cellulitis should be treated with empiric antimicrobial therapy based on patient risk factors and regional susceptibility patterns. This review will assist providers in managing cellulitis and avoiding treatment errors that lead to high costs, unwanted side effects for patients, and overuse of antibiotics.
http://ift.tt/2sKJXbI
Back Pain in a Healthy Teenager
Source:The Journal of Emergency Medicine
Author(s): Kelly Gardner, Sigmund Kharasch, Ali Raja, Rene Balza, Kriti Bhatia, Emily S. Miller
http://ift.tt/2tflpuV
Physicochemical properties, in vitro cytotoxic and genotoxic effects of PM 1.0 and PM 2.5 from Shanghai, China
Abstract
Exposure to ambient particulate matter (PM) links with a variety of respiratory diseases. However, compared with coarse particles (PM10) and fine particles (PM2.5), submicrometer particles (PM1.0) may be a more important indicator of human health risks. In this study, the cytotoxic and genotoxic effects of PM1.0 samples from Shanghai were examined using A549 cells, and compared with the effects of PM2.5, to better understand the health effects of PM1.0 in this area. The PM1.0 and PM2.5 samples were characterized for morphology, water-soluble inorganic ions, organic and elemental carbon, and metal elements. The cytotoxicity of PMs was measured using cell viability and cell membrane damage assays. The genotoxic effects of PMs were determined using the comet assay, and DNA damage was quantified using olive tail moment (OTM) values. The physicochemical characterization indicated that PM1.0 was enriched in carbonaceous elements and hazardous metals (Al, Zn, Pb, Mn, Cu, and V), whereas PM2.5 was more abundant in large, irregular mineral particles. The biological results revealed that both PM1.0 and PM2.5 could induce significant cytotoxicity and genotoxicity in A549 cells, and that exposure to PM1.0 caused more extensive toxic effects than exposure to PM2.5. The greater cytotoxic effects of PM1.0 can be attributed to the combined effects of size and chemical composition, whereas the genotoxic effects of PM1.0 may be mainly associated with chemical species.
http://ift.tt/2sE1jfi
Interpositional Lateral Thoracic Vein Graft for DIEP Flap Salvage in Setting of Superficial Venous System Dominance
http://ift.tt/2solkCb
Contextual fear conditioning is enhanced in mice lacking functional sphingosine kinase 2
Source:Behavioural Brain Research, Volume 333
Author(s): Mona Lei, Adeena Shafique, Kani Shang, Timothy A. Couttas, Hua Zhao, Anthony S. Don, Tim Karl
The lipid sphingosine 1-phosphate (S1P) is a potent neuroprotective signalling molecule that signals through its own family of five G-protein coupled receptors. S1P signalling enhances presynaptic glutamate release and is essential for neural development. S1P is synthesized by the enzymes sphingosine kinases 1 and 2 (SPHK1 and SPHK2), of which SPHK2 mRNA and activity is more abundant in the brain. In this study we investigated the consequences of global SphK2 knockout (SphK2−/−) on basic motor capabilities, anxiety, learning, and memory in mice, using a range of tests including the elevated plus maze, the cheeseboard, contextual and cued fear conditioning, and fear extinction. Loss of SphK2 resulted in an 85–90% reduction in brain S1P levels, and was associated with a notably higher freezing response in a novel context. SphK2 knockout mice also exhibited increased contextual fear conditioning but the extinction of contextual fear memory was similar to control mice. SphK2−/− mice, contrary to their control littermates, did not respond to cue presentation with increased freezing. Anxiety measures in the elevated plus maze were not different between SphK2−/− mice and control littermates. Also, knockout mice showed no deficits in neurological reflexes or motor functions, and performed as well as their control littermates in the spatial memory test. Our findings demonstrate that SphK2 is responsible for the vast majority of S1P synthesis in the mouse brain, and plays a role in freezing responses as evaluated in the fear conditioning paradigm.
http://ift.tt/2sotWsK
The lateral parabrachial nucleus and central angiotensinergic mechanisms in the control of sodium intake induced by different stimuli
Source:Behavioural Brain Research, Volume 333
Author(s): Camila F. Roncari, Richard B. David, Patrícia M. De Paula, Débora S.A. Colombari, Laurival A. De Luca Jr., Eduardo Colombari, José V. Menani
Angiotensin II (ANG II) is a typical facilitatory stimulus for sodium appetite. Surprisingly, hyperosmolarity and central cholinergic stimulation, two classical antinatriorexigenic stimuli, also facilitate NaCl intake when they are combined with injections of the α2-adrenoceptor/imidazoline agonist moxonidine into the lateral parabrachial nucleus (LPBN). In the present study, we tested the relative importance of central angiotensinergic and cholinergic mechanisms for the control of water and NaCl intake by combining different dipsogenic or natriorexigenic stimuli with moxonidine injection into the LPBN. Adult male Holtzman rats (n=9–10/group) with stainless steel cannulas implanted in the lateral ventricle and LPBN were used. Bilateral injections of moxonidine (0.5 nmol) into the LPBN increased water and 0.3M NaCl intake in rats that received furosemide+captopril injected subcutaneously, ANG II (50ng) or carbachol (cholinergic agonist, 4 nmol) injected intracerebroventricularly (icv) or 2M NaCl infused intragastrically (2ml/rat). Losartan (AT1 antagonist, 100μg) or atropine (muscarinic antagonist, 20 nmol) injected icv abolished the effects on water and 0.3M NaCl of moxonidine combined to either 2M NaCl intragastrically or carbachol icv. However, atropine icv did not change 0.3M NaCl intake produced by direct central action of ANG II like that induced by ANG II icv or furosemide+captopril combined with moxonidine into the LPBN. The results suggest that different stimuli, including hyperosmolarity and central cholinergic stimulation, share central angiotensinergic activation as a common mechanism to facilitate sodium intake, particularly when they are combined with deactivation of the LPBN inhibitory mechanisms.
http://ift.tt/2tHFJpX
Hypoxic postconditioning improves behavioural deficits at 6 weeks following hypoxic-ischemic brain injury in neonatal rats
Source:Behavioural Brain Research, Volume 333
Author(s): Jonathan D. Teo, Margaret J. Morris, Nicole M. Jones
Hypoxic-ischemic (HI) brain injury in newborns is associated with high morbidity and mortality, with many babies suffering neurological deficits. Recently, we showed that hypoxic postconditioning (PostC) immediately post injury can protect against HI up to one week in neonatal rats. Here, we aimed to examine whether long term functional deficits were also improved by PostC. Sprague-Dawley rats were assigned to control (C) or HI group on postnatal day 7 (P7). The HI group underwent unilateral carotid artery occlusion followed by hypoxia (7% oxygen, 3h). Half of each group were randomly assigned to the PostC group (8% oxygen, 1h/day for 5days post-injury), or normoxic group, where animals were kept under ambient conditions. Righting reflex and negative geotaxis tests were performed on P8 and P14. On P42, rats underwent further behavioural tests of motor function and memory (forelimb grip strength, grid walking and novel object recognition tasks). Brain injury was assessed using histological scoring of brain sections. At P14, PostC reduced the righting reflex deficit compared to HI alone. Long-term (6 weeks) behavioural deficits were observed in grid walking and novel object recognition tests after HI alone, with both functions improved following PostC. Following HI, there was an increase in brain injury assessed by histological scoring compared to control, and this damage was reduced by PostC. This novel finding of long-term histological neuroprotection accompanied by functional improvements by PostC further demonstrates the clinical potential of mild hypoxia for the treatment of HI brain injury.
http://ift.tt/2soLYem
Effect of a change in housing conditions on body weight, behavior and brain neurotransmitters in male C57BL/6J mice
Source:Behavioural Brain Research, Volume 333
Author(s): Noemi Pasquarelli, Patrizia Voehringer, Julia Henke, Boris Ferger
The development of modern housing regimes such as individually ventilated cage (IVC) systems has become very popular and attractive in order to reduce spreading of pathogenic organisms and to lower the risk to develop a laboratory animal allergy for staff members. Additionally, optimal housing of laboratory animals contributes to improve animal health status and ensures high and comparable experimental and animal welfare standards. However, it has not been clearly elucidated whether 1) a change to IVC systems have an impact on various physiological phenotypic parameters of mice when compared to conventional, standard cages and 2) if this is further affected by changing from social to single housing. Therefore, we investigated the influence of a change in housing conditions (standard cages with social housing changed to standard or IVC cages combined with social or single housing) on body weight, behavior and a neurochemical fingerprint of male C57BL/6J mice. Body weight progression was significantly reduced when changing mice to single or social IVC cages as well as in single standard cages when compared to social standard housing. Automated motor activity measurement in the open field showed that mice maintained in social husbandry with standard cages displayed the lowest exploratory behavior but the highest activity difference upon amphetamine treatment. Elevated plus maze test revealed that a change to IVC single and social housing as well as single standard housing produced anxiety-related behavior when compared to maintenance in social standard housing. Additionally, postmortem neurochemical analysis of the striatum using high-performance liquid chromatography coupled to electrochemical detection showed significant differences in striatal dopamine and serotonin turnover levels. In summary, our data indicate a crucial influence of a change in housing conditions on several mouse phenotype parameters. We propose that the maintenance of well-defined housing conditions is mandatory to ensure reproducible and comparable results and contributes to the application of the 3R refinement principle in animal studies by contributing to welfare and hygienical standards.
http://ift.tt/2tGWlOy
Chronic mild stress impairs latent inhibition and induces region-specific neural activation in CHL1-deficient mice, a mouse model of schizophrenia
Source:Behavioural Brain Research, Volume 333
Author(s): Mona Buhusi, Daniel Obray, Bret Guercio, Mitchell J. Bartlett, Catalin V. Buhusi
Schizophrenia is a neurodevelopmental disorder characterized by abnormal processing of information and attentional deficits. Schizophrenia has a high genetic component but is precipitated by environmental factors, as proposed by the 'two-hit' theory of schizophrenia. Here we compared latent inhibition as a measure of learning and attention, in CHL1-deficient mice, an animal model of schizophrenia, and their wild-type littermates, under no-stress and chronic mild stress conditions. All unstressed mice as well as the stressed wild-type mice showed latent inhibition. In contrast, CHL1-deficient mice did not show latent inhibition after exposure to chronic stress. Differences in neuronal activation (c-Fos-positive cell counts) were noted in brain regions associated with latent inhibition: Neuronal activation in the prelimbic/infralimbic cortices and the nucleus accumbens shell was affected solely by stress. Neuronal activation in basolateral amygdala and ventral hippocampus was affected independently by stress and genotype. Most importantly, neural activation in nucleus accumbens core was affected by the interaction between stress and genotype. These results provide strong support for a 'two-hit' (genes x environment) effect on latent inhibition in CHL1-deficient mice, and identify CHL1-deficient mice as a model of schizophrenia-like learning and attention impairments.
http://ift.tt/2soFFY2
Observational fear learning in degus is correlated with temporal vocalization patterns
Source:Behavioural Brain Research, Volume 332
Author(s): Navdeep K. Lidhar, Nathan Insel, June Yue Dong, Kaori Takehara-Nishiuchi
Some animals learn to fear a situation after observing another individual come to harm, and this learning is influenced by the animals' social relationship and history. An important but sometimes overlooked factor in studies of observational fear learning is that social context not only affects observers, but may also influence the behavior and communications expressed by those being observed. Here we sought to investigate whether observational fear learning in the degu (Octodon degus) is affected by social familiarity, and the degree to which vocal expressions of alarm or distress contribute. 'Demonstrator' degus underwent contextual fear conditioning in the presence of a cagemate or stranger observer. Among the 15 male pairs, observers of familiar demonstrators exhibited higher freezing rates than observers of strangers when returned to the conditioning environment one day later. Observer freezing during testing was, however, also related to the proportion of short- versus long- inter-call-intervals (ICIs) in vocalizations recorded during prior conditioning. In a regression model that included both social relationship and ICI patterns, only the latter was significant. Further investigation of vocalizations, including use of a novel, directed k-means clustering approach, suggested that temporal structure rather than tonal variations may have been responsible for communicating danger. These data offer insight into how different expressions of distress or fear may impact an observer, adding to the complexity of social context effects in studies of empathy and social cognition. The experiments also offer new data on degu alarm calls and a potentially novel methodological approach to complex vocalizations.
http://ift.tt/2tHp05S
Adjuvant intensity-modulated whole abdominal radiotherapy for high-risk patients with ovarian cancer FIGO stage III– first results of a prospective phase-II-study
Publication date: Available online 4 July 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): N. Arians, M. Kieser, L. Benner, N. Rochet, S. Katayama, F. Sterzing, K. Herfarth, K. Schubert, L. Schröder, Ch. Leitzen, A. Schneeweiss, Ch. Sohn, J. Debus, K. Lindel
PurposeTo assess treatment tolerance and toxicity rates of consolidative whole abdominal radiotherapy (WART) following cytoreductive surgery and carboplatin/paclitaxel chemotherapy in high risk patients with advanced ovarian cancer FIGO stage III using IMRT.Methods/Design: The xxx study is a multicenter single-arm phase-II-trial. 20 patients with optimally debulked ovarian cancer FIGO stage III with complete remission after chemotherapy were treated with intensity-modulated WART as a consolidation therapy. A total dose of 30 Gy in 20 fractions of 1.5 Gy was applied to the entire peritoneal cavity. Primary endpoint was treatment tolerability defined as lack of any CTC AE Grade 4 toxicity within 10 weeks after start of treatment; secondary objectives were acute and chronic toxicity, quality of life, rates of therapy disruption and abortion, progression-free and overall survival.ResultsIntensity-modulated WART resulted in excellent coverage of the whole peritoneal cavity with effective sparing of all organs at risk. The primary analysis included all 20 enrolled patients of which 19 did not experience CTC Grade 4 toxicity. Only one patient experienced acute Grade 4 hematological toxicity. Thus, the tolerability rate of intensity-modulated WART was significantly higher than 70%. No gastrointestinal acute toxicities > Grade 2 have been observed. During WART mean global health status decreased for 18.1 points (95%-CI: 7.1-29.0). 6 weeks after WART global health status already increased with a no lower difference of 4.6 (-11.1-20.4), compared to baseline. Similar characteristics were observed for all function scale scores.ConclusionIntensity-modulated WART after aggressive surgery and carboplatin/paclitaxel chemotherapy is associated with an acceptable risk of acute toxicity and a treatment tolerability rate significantly higher than 70%. Together with our knowledge about clinical feasibility meaning excellent coverage of the PTV and effective sparing of OARs, intensity-modulated WART could offer a new therapeutic option for consolidation treatment of patients with advanced ovarian cancer.
Teaser
Patients with advanced stage ovarian cancer have a poor prognosis with intraperitoneally disease recurrence being a common pattern of relapse. This prospective multicenter phase-II-study tested treatment tolerability of whole abdominal radiotherapy using IMRT as one possible treatment option to improve survival. Results show excellent treatment tolerability rates of 95% (lower limit of the one-sided 95% CI 80.4%), thus making IMRT a promising treatment option in addition to established chemotherapy regimens.http://ift.tt/2so4O5m
Riga-Fede disease in the upper jaw in an infant
Abstract
Riga-Fede disease is a benign and uncommon mucosal disorder. This illness is an ulceration of the oral mucosa and arises from repetitive traumatic injuries. The disease is usually caused by the sharp edges of new erupted teeth. The aim of the present case report is to present Riga-Fede disease and its treatment. We reported a 11-month-old healthy female infant diagnosed as Riga-Fede disease based on clinical features. After the conservative treatment that focused on eliminating the source of trauma, total healing was observed. Riga-Fede disease is rare. This illness can be confused with malignancies. Therefore, the diagnosis and treatment of this disease are very important for physicians and patients.
http://ift.tt/2sKJ3Mz
Superiority of a vitamin B12-barrier cream compared with standard glycerol-petrolatum-based emollient cream in the treatment of atopic dermatitis: A randomized, left-to-right comparative trial
Abstract
Atopic dermatitis (AD) is a result of complex genetic, epigenetic, environmental, and immunological interactions with an overlapping epidermal barrier defect. The study evaluates the efficacy and tolerability of topical Vitamin B12-barrier cream (MB12) compared with standard glycerol-petrolatum-based emollient cream (GPC) used three times a day for mild AD. The study was conducted as a on one hemi-body randomized, controlled, single-blind, intra-patient left-to-right comparative trial by patients with clinical diagnosis of mild AD measured with total SCORAD index over 4 months. MB12 was compared on one hemi-body treated (GPC). The comparisons of score values were performed primarily by using non-parametric procedures: Mann–Whitney-U test (for independent samples) and Wilcoxon test (for dependent samples). All 22 patients were randomized (left or right side treated with MB12 or GPC). At week 12 a reduction from baseline in SCORAD index was assessed in both body sites with 77.6% SCORAD index reduction in the MB12 treated body sites versus 33.5% in the GPC treated body sites. These results suggest that MB12 could represent a new option in the treatment of mild AD.
http://ift.tt/2tfcGJo
Riga-Fede disease in the upper jaw in an infant
Abstract
Riga-Fede disease is a benign and uncommon mucosal disorder. This illness is an ulceration of the oral mucosa and arises from repetitive traumatic injuries. The disease is usually caused by the sharp edges of new erupted teeth. The aim of the present case report is to present Riga-Fede disease and its treatment. We reported a 11-month-old healthy female infant diagnosed as Riga-Fede disease based on clinical features. After the conservative treatment that focused on eliminating the source of trauma, total healing was observed. Riga-Fede disease is rare. This illness can be confused with malignancies. Therefore, the diagnosis and treatment of this disease are very important for physicians and patients.
http://ift.tt/2sKJ3Mz
Superiority of a vitamin B12-barrier cream compared with standard glycerol-petrolatum-based emollient cream in the treatment of atopic dermatitis: A randomized, left-to-right comparative trial
Abstract
Atopic dermatitis (AD) is a result of complex genetic, epigenetic, environmental, and immunological interactions with an overlapping epidermal barrier defect. The study evaluates the efficacy and tolerability of topical Vitamin B12-barrier cream (MB12) compared with standard glycerol-petrolatum-based emollient cream (GPC) used three times a day for mild AD. The study was conducted as a on one hemi-body randomized, controlled, single-blind, intra-patient left-to-right comparative trial by patients with clinical diagnosis of mild AD measured with total SCORAD index over 4 months. MB12 was compared on one hemi-body treated (GPC). The comparisons of score values were performed primarily by using non-parametric procedures: Mann–Whitney-U test (for independent samples) and Wilcoxon test (for dependent samples). All 22 patients were randomized (left or right side treated with MB12 or GPC). At week 12 a reduction from baseline in SCORAD index was assessed in both body sites with 77.6% SCORAD index reduction in the MB12 treated body sites versus 33.5% in the GPC treated body sites. These results suggest that MB12 could represent a new option in the treatment of mild AD.
http://ift.tt/2tfcGJo
Prevention of 5-fluorouracil-induced early severe toxicity by pre-therapeutic dihydropyrimidine dehydrogenase (DPD) deficiency screening: The multiparametric approach is not convincing
Publication date: Available online 4 July 2017
Source:Seminars in Oncology
Author(s): Marie-Christine Etienne-Grimaldi, Chantal Barin Le Guellec, Jean-Christophe Boyer, Etienne Chatelut, Alexandre Evrard, Marie-Anne Loriot, Angelo Paci, Bernard Royer, Fabienne Thomas, Joseph Ciccolini
http://ift.tt/2tnLkze
Biomarker-Driven and Molecular Targeted Therapies for Colorectal Cancers
Publication date: Available online 4 July 2017
Source:Seminars in Oncology
Author(s): Marta Schirripa, Stacey A. Cohen, Francesca Battaglin, Heinz-Josef Lenz
The improved clinical selection and the identification of new molecules and innovative strategies widened treatment options and increased overall survival in metastatic colorectal cancer patients in recent years. Biomarker-driven therapies represent an emerging issue in this field and new targeted treatments are under investigation and will be probably soon adopted in the daily clinical practice. In the present review the role RAS, BRAF mutations, Her2 amplification, microsatellite instability and CpG Island Methylator Phenotype are reviewed and discussed according to their possible role as prognostic, predictive markers as well as possible biomarker-driven treatment options.
http://ift.tt/2sEs9nA
Age-Associated Intracellular Superoxide Dismutase Deficiency Potentiates Dermal Fibroblast Dysfunction During Wound Healing
Abstract
Reactive oxygen species (ROS) impair wound healing through destructive oxidation of intracellular proteins, lipids, and nucleic acids. Intracellular superoxide dismutase (SOD1) regulates ROS levels and plays a critical role in tissue homeostasis. Recent evidence suggests that age-associated wound healing impairments may partially result from decreased SOD1 expression. We investigated the mechanistic basis by which increased oxidative stress links to age-associated impaired wound healing. Fibroblasts were isolated from unwounded skin of young and aged mice, and myofibroblast differentiation was assessed by measuring α-smooth muscle actin and collagen gel contraction. Excisional wounds were created on young and aged mice to study the healing rate, ROS levels, and SOD1 expression. A mechanistic link between oxidative stress and fibroblast function was explored by assessing the TGF-β1 signaling pathway components in young and aged mice. Age-related wounds displayed reduced myofibroblast differentiation and delayed wound healing, consistent with a decrease in the in vitro capacity for fibroblast-myofibroblast transition following oxidative stress. Young fibroblasts with normal SOD1 expression exhibited increased phosphorylation of ERK in response to elevated ROS. In contrast, aged fibroblasts with reduced SOD1 expression displayed a reduced capacity to modulate intracellular ROS. Collectively, age-associated wound healing impairments are associated with fibroblast dysfunction that is likely the result of decreased SOD1 expression and subsequent dysregulation of intracellular ROS. Strategies targeting these mechanisms may suggest a new therapeutic approach in the treatment of chronic non-healing wounds in the aged population.
This article is protected by copyright. All rights reserved.
http://ift.tt/2tOVQ5j
Neurological and psychiatric associations in bullous pemphigoid – more than skin deep?
Abstract
In elderly patients, bullous pemphigoid (BP) is associated with several comorbidities; the strongest association occurs between BP and neurological diseases. Different types of dementia, Parkinson's disease, cerebrovascular disorders and epilepsy all have a significant association with BP but patients with multiple sclerosis have the highest risk of BP. An existing neurological disorder appears to increase the risk for subsequent BP, but an increased risk for developing some neurological diseases has also been reported following BP diagnosis. BP seems to be associated with several psychiatric diseases such as schizophrenia, uni- and bipolar disorder, schizotypal and delusional disorders, and personality disorders, but the risk ratios are usually lower than with neurological diseases. In addition to the skin, the BP autoantigens BP180 and BP230 are expressed in the central nervous system. This finding together with the strong epidemiological association between neurological disorders and BP has led to an assumption that neurodegeneration or neuroinflammation could lead to a cross-reactive immunoresponse between neural and cutaneous antigens and the failure of self-tolerance. A subpopulation of patients with Alzheimer's disease or Parkinson's disease have circulating IgG autoantibodies against BP180, but currently their significance for the development of BP is unclear, since these anti-neural BP180 antibodies neither bind to the cutaneous basement membrane nor cause BP like symptoms. Further studies analyzing large and well-characterized populations of neurological and psychiatric patients are required to understand better the role of autoimmunization against neural BP autoantigens in the pathogenesis of BP.
This article is protected by copyright. All rights reserved.
http://ift.tt/2uohx9p
Imiquimod-applied Interleukin-10 deficient mice better reflects severe and persistent psoriasis with systemic inflammatory state
Abstract
Previous studies have shown that imiquimod-induced psoriasis-like skin inflammation in mice resembles phenotypic changes and cytokine profiles of human psoriasis. However, a psoriasis animal model reflecting the chronic inflammatory course and comorbidities has not yet been established. We aimed to evaluate the imiquimod-applied interleukin (IL)-10 deficient mouse model in comparison to previous models. IL-10 deficient and wild type (WT) mice received either imiquimod or vehicle cream for 12 days and were sacrificed on day 15. For earlier time point data, either imiquimod or vehicle cream was applied for 2 days and the mice were sacrificed on day 3.
Imiquimod-applied IL-10 deficient mice showed more persistent psoriasis-like inflammation and higher severity index than did WT between day 8 and 15. Histopathologically, they demonstrated significantly thicker epidermis and larger number of CD45+, myeloperoxidase+, and IL-17+ cell counts on day 15. Quantitative reverse transcription-polymerase chain reaction with skin tissue revealed significantly higher imiquimod-induced IL-23p19 expression in imiquimod-applied IL-10 deficient mice on day 15. IL-10 deficient mice also showed significantly higher serum levels of imiquimod-induced IL-17A and tumour necrosis factor-α by enzyme-linked immunosorbent assay on day 15. Furthermore, IL-10 deficient mice showed more prominent increase of spleen weight and decrease of bodyweight in response to imiquimod application on day 3 and 15. In conclusion, IL-10 deficient mice model with imiquimod application may better reflect severe and persistent psoriasis with systemic inflammatory state.
This article is protected by copyright. All rights reserved.
http://ift.tt/2tOzKjv
Ultraviolet radiation and skin mast cells: Effects, mechanisms, and relevance for skin diseases
Abstract
Mast cells (MCs) are well-known as versatile effector cells in allergic reactions and several other immune responses. Skin MCs and cutaneous MC responses are subject to the effects of environmental factors including ultraviolet radiation (UVR). Numerous studies have assessed the effects of UVR on MCs, in vitro and in vivo. Interestingly, UVR seems to have variable effects on nonactivated and activated mast cells. In general, UV therapy is beneficial in the treatment of urticaria and mastocytosis, but the effects are variable depending on treatment regimen and type of UVR.
Here, we review and summarize key reports from the older and current literature on the crosstalk of UVR and skin MCs. Specifically, we present the literature and discuss published reports on the effects of UVR on skin MCs in rodents and humans. In addition, we review the role of MCs in UVR-driven skin diseases and the influence of UV light on MC-mediated skin diseases. This summary of our current understanding of the interplay of skin MCs and UVR may help to improve the management of patients with urticaria and other MC disorders, to identify current gaps of knowledge, and to guide further research.
This article is protected by copyright. All rights reserved.
http://ift.tt/2unFZb1
In vitro and in vivo antimicrobial activity of a synthetic peptide derived from the C-terminal region of human chemokine CCL13 against Pseudomonas aeruginosa
Source:Peptides
Author(s): Mayte Cossio-Ayala, Mariana Domínguez-López, Erika Mendez-Enriquez, María del Carmen Portillo-Téllez, Enrique García-Hernández
Chemokines are important mediators of immunological responses during inflammation and under steady-state conditions. In addition to regulating cell migration, some chemotactic cytokines have direct effects on bacteria. Here, we characterized the antibacterial ability of the synthetic oligopeptide CCL1357-75, which corresponds to the carboxyl-terminal region of the human chemokine CCL13. In vitro measurements indicated that CCL1357-75 disrupts the cell membrane of Pseudomonas aeruginosa through a mechanism coupled to an unordered-helicoidal conformational transition. In a murine pneumonic model, CCL1357-75 improved mouse survival and bacterial clearance and decreased neutrophil recruitment, proinflammatory cytokines and lung pathology compared with that observed in untreated infected animals. Overall, our study supports the ability of chemokines and/or chemokine-derived oligopeptides to act as direct defense agents against pathogenic bacteria and suggests their potential use as alternative antibiotics.
http://ift.tt/2uI6OGo
Advances towards fully automated in vivo assessment of oral epithelial dysplasia by nuclear endomicroscopy – A pilot study
Abstract
Background
uncertainties in detection of oral epithelial dysplasia (OED) frequently result from sampling error especially in inflammatory oral lesions. Endomicroscopy allows non-invasive, "en face" imaging of upper oral epithelium but parameters of OED are unknown.
Methods
mucosal nuclei were imaged in 34 toluidine blue stained oral lesions with a commercial endomicroscope. Histopathological diagnosis showed 4 biopsies in "dys-/ neoplastic", 23 in "inflammatory", 7 in "others" disease groups. Strength of different assessment strategies of nuclear scoring, nuclear count and automated nuclear analysis were measured by area under ROC–curve (AUC) to identify histopathological "dys-/neoplastic" group. Nuclear objects from automated image analysis were visually corrected.
Results
best performing parameters of nuclear-to-image ratios were the count of large nuclei (AUC=.986) and 6-nearest-neighborhood relation (AUC=.896) and for parameters of nuclear polymorphism the count of atypical nuclei (AUC=.996) and compactness of nuclei (AUC=.922). Excluding low grade OED nuclear scoring and count reached 100% sensitivity and 98% specificity for detection of dys-/neoplastic lesions. In automated analysis, combination of parameters enhanced diagnostic strength. Sensitivity of 100% and specificity of 87% was seen for distances of 6-nearest-neighbors and aspect ratios even in uncorrected objects. Correction improved measures of nuclear polymorphism only. The hue of background color was stronger than nuclear density (AUC=.779 vs. .687) to detect dys-/neoplastic group indicating that macroscopic aspect is biased.
Conclusions
nuclear-to-image ratios are applicable for automated optical in vivo diagnostics for oral potentially malignant disorders. Nuclear endomicroscopy may promote non-invasive, early detection of dys-/neoplastic lesions by reducing sampling error.
This article is protected by copyright. All rights reserved.
http://ift.tt/2uIkjWi
Endogenous hydrogen sulfide-mediated MAPK inhibition preserves endothelial function through TXNIP signaling
Publication date: September 2017
Source:Free Radical Biology and Medicine, Volume 110
Author(s): Danyang Tian, Jinghui Dong, Sheng Jin, Xu Teng, Yuming Wu
Mounting evidence demonstrated deficient cystathionine-γ-lyase (CSE)/H2S implicated the development of cardiovascular disease. The present study aimed to evaluating the favorable action of CSE derived H2S on endothelial function in CSE-/- mice. CSE-/- mice exhibited attenuated endothelium-dependent relaxations, coupled with reduction of endothelial nitric oxide synthase (eNOS) phosphorylation at site of Ser1177, increase of thioredoxin interacting protein (TXNIP) level and MAPK phosphorylation, which were corrected by sodium hydrosulfide chronic treatment for 8 weeks. Impaired relaxations to ACh and upregulated TXNIP of CSE-/- mice aorta were partially corrected by p38 inhibitor, extracellular regulated protein kinase (ERK) inhibitor and c-Jun N-terminal kinase (JNK) inhibitor and totally corrected by combined treatment. Pharmacological inhibition of CSE with DL-propargylglycine (PPG) in vivo and ex vivo induced endothelial dysfunction. PPG stimulated the phosphorylation of p38, JNK and ERK in human umbilical vein endothelial cells (HUVECs). MAPK inhibition by combined treatment of p38, JNK and ERK inhibitors normalized the endothelial changes of eNOS phosphorylation and TXNIP protein level in CSE-/- mice aorta and PPG-treated HUVECs. NaHS offered similar effect with MAKP inhibitors. TXNIP siRNA prevented against endothelial function by PPG and TXNIP overexpression mimics the detrimental effect of PPG treatment on endothelial function, whereas MAPK inhibitor or NaHS has no beneficial effect. In a word, Endogenous CSE/H2S benefits against endothelial dysfunction through suppressing MAPK/TXNIP cascade. CSE deficiency and consequently lowered endogenous H2S level should be considered as risk factors and biomarkers for endothelial dysfunction.
Graphical abstract
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EphB2 signaling-mediated Sirt3 expression reduces MSC senescence by maintaining mitochondrial ROS homeostasis
Publication date: Available online 4 July 2017
Source:Free Radical Biology and Medicine
Author(s): Young Hyun Jung, Hyun Jik Lee, Jun Sung Kim, Sei-Jung Lee, Ho Jae Han
Disruption of mitochondrial reactive oxygen species (mtROS) homeostasis is a key factor inducing UCB-MSC senescence. Accordingly, preventing mtROS accumulation will help in suppressing the UCB-MSC senescence. In this study, we observed that the expressions of EphrinB2 and EphB2 were inversely regulated by UCB-MSC passage-dependent manner. EphB2 signaling induced mitochondrial translocation of Sirt3. The knockdown of SIRT3 inhibited the effect of EphB2 signaling in UCB-MSCs. Subsequently, EphrinB2-Fc induced the nuclear translocation of Nrf-2 via c-Src phosphorylation dependent manner, and Sirt3 expression was regulated by Nrf-2. Among Sirt3 target genes, EphB2 signaling increased MnSOD and reduced the mtROS level of UCB-MSCs. Furthermore, the deacetylase effect of Sirt3 enhanced the MnSOD activity by deacetylation at the lysine 68 residue and therapeutic effect of UCB-MSCs on skin-wound healing was increased by EphB2 activation. In conclusion, the EphB2 can serve as a novel target for the optimizing the therapeutic use of UCB-MSCs in wound repair by MnSOD-mediated mtROS scavenging through EphB2/c-Src signaling pathway and Nrf-2-dependent Sirt3 expression.
Graphical abstract
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Long sleep duration and health outcomes: A systematic review, meta-analysis and meta-regression
We examined the dose-response relationship between long sleep duration and health outcomes including mortality and the incidence of diabetes mellitus, hypertension, cardiovascular diseases, stroke, coronary heart diseases, obesity, depression and dyslipidemia. We collected data from 5,134,036 participants from 137 prospective cohort studies. For the independent variable, we categorized participants at baseline as having long sleep duration or normal sleep duration. Risk ratios (RRs) for mortality and incident health conditions during follow-up were calculated through meta-analyses of adjusted data from individual studies.
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Chemical constituents and pharmacological actions of carob pods and leaves (Ceratonia siliqua L.) on the gastrointestinal tract: A review
Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Kaïs Rtibi, Slimen Selmi, Dhekra Grami, Mohamed Amri, Bruno Eto, Jamel El-benna, Hichem Sebai, Lamjed Marzouki
Carob tree, Ceratonia siliqua L., is a medicinal plant used in Tunisian traditional medicine for the treatment of the gastro-intestinal (GI) disorders. In this respect, a relatively large number of scientific publications on the carob tree have been published in recent years. Therefore, the present review was aimed to analyze the traditional uses, phytochemical constituents and pharmacological activities of Ceratonia siliqua on the GI tract. Indeed, previous investigations on the carob pods and leaves have revealed the presence of a number of compounds including high amounts of carbohydrates, dietary fibers, minerals, polyphenols, flavonoids and low amounts of protein and lipids. This plant possesses anti-inflammatory, antimicrobial, anti-diarrheique, antioxidant, anti-ulcer, anti-constipation and anti-absorptive of glucose activities in the gastrointestinal tract. Based on the chemical and pharmacological characteristics of C. siliqua, we concluded that this species has beneficial preventive and therapeutic properties, especially, in digestive tract.
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Phytotherapeutic potential of natural herbal medicines for the treatment of mild-to-severe atopic dermatitis: A review of human clinical studies
Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Zahid Hussain, Hnin Ei Thu, Ahmad Nazrun Shuid, Prashant Kesharwani, Shahzeb Khan, Fahad Hussain
For many decades, natural herbal medicines, polyherbal formulations and/or decoctions of plant-derived materials have widely been accepted as alternative complementary therapies for the treatment, cure or prevention of a wide range of acute and chronic skin diseases including chronic herpes, prurigo, acute and chronic wounds, psoriasis and atopic dermatitis (AD). This review was aimed to summarize and critically discuss about the therapeutic viability and clinical applicability of natural herbal medicines for the treatment of AD in human. The critical analysis of the literature revealed that oral (in the form of capsules, syrup or granules) and/or topical application (alone or in conjunction with wet-wrap dressing and/or acupuncture) of natural herbal medicines exhibit remarkable potential for the treatment of mild-to-severe AD in adults, children, infants and in the pregnant women. In this review, the clinical efficacy of various herbal formulations such as Chinese herbal therapies, Korean medicines, Iranian medicines, honey, natural herbal oils (coconut oil, olive oil and mineral oil), beeswax, dodder seeds and whey for the treatment of AD has been discussed. The clinical anti-AD efficacy of these complementary therapies has been observed in terms of down-regulation in Scoring Atopic Dermatitis (SCORAD) index, erythematic intensity, Children's Dermatology Life Quality Index (CDLQI), Dermatology Life Quality Index (DLQI), pruritus and itching frequency, transepidermal water loss (TEWL) and expression of AD-mediated chemokines. Conclusively, we recognized that natural herbal medicines demonstrate remarkable clinical efficacy when used alone or in conjunction with other complementary therapies for the treatment of AD in patients of all ages as well as pregnant women.
Graphical abstract
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Dexamethasone increases production of C-type natriuretic peptide in the sheep brain
Although C-type natriuretic peptide (CNP) has high abundance in brain tissues and cerebrospinal fluid (CSF), the source and possible factors regulating its secretion within the central nervous system (CNS) are unknown. Here we report the dynamic effects of a single IV bolus of dexamethasone or saline solution on plasma, CSF, CNS and pituitary tissue content of CNP products in adult sheep, along with changes in CNP gene expression in selected tissues. Both CNP and NTproCNP (the amino-terminal product of proCNP) in plasma and CSF showed dose responsive increases lasting 12-16 h after dexamethasone whereas other natriuretic peptides were unaffected. CNS tissue concentrations of CNP and NTproCNP were increased by dexamethasone in all of the 12 regions examined. Abundance was highest in limbic tissues, pons and medulla oblongata. Relative to controls, CNP gene expression (NPPC) was upregulated by dexamethasone in 5 of 7 brain tissues examined. Patterns of responses differed in pituitary tissue. Whereas the abundance of CNP in both lobes of the pituitary gland greatly exceeded that of brain tissues, neither CNP nor NTproCNP concentration was affected by dexamethasone — despite an increase in NPPC expression. This is the first report of enhanced production and secretion of CNP in brain tissues in response to a corticosteroid. Activation of CNP secretion within CNS tissues by dexamethasone, not exhibited by other natriuretic peptides, suggests an important role for CNP in settings of acute stress. Differential findings in pituitary tissues likely relate to altered processing of proCNP storage and secretion.
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Macrophage 11{beta}-HSD1 deficiency promotes inflammatory angiogenesis
11β-hydroxysteroid dehydrogenase-1 (11β-HSD1) predominantly converts inert glucocorticoids into active forms, thereby contributing to intracellular glucocorticoid levels. 11β-HSD1 is dynamically regulated during inflammation, including in macrophages where it regulates phagocytic capacity. The resolution of inflammation in some disease models including inflammatory arthritis, is impaired by 11β-HSD1 deficiency or inhibition. However, 11β-HSD1 deficiency/inhibition also promotes angiogenesis, which is beneficial in mouse models of surgical wound healing, myocardial infarction or obesity. The cell types responsible for the anti-inflammatory and anti-angiogenic roles of 11β-HSD1 have not been characterised. Here, we generated Hsd11b1MKO mice with LysM-Cre mediated deletion of Hsd11b1 to investigate whether 11β-HSD1 deficiency in myeloid phagocytes is pro-angiogenic and/or affects the resolution of inflammation. Resolution of inflammatory K/BxN-induced arthritis was impaired in Hsd11b1MKO mice to a similar extent as in mice globally deficient in 11β-HSD1. This was associated with >2-fold elevation in levels of the endothelial marker Cdh5 mRNA, suggesting increased angiogenesis in joints of Hsd11b1MKO mice following arthritis. A pro-angiogenic phenotype was confirmed by measuring angiogenesis in subcutaneously implanted polyurethane sponges, in which Hsd11b1MKO mice showed 20% greater vessel density than their littermate controls, associated with higher expression of Cdh5. Thus, 11β-HSD1 deficiency in myeloid phagocytes promotes angiogenesis. Targeting 11β-HSD1 in macrophages may be beneficial in tissue repair.
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TNFRp55 deficiency promotes the development of ectopic endometriotic-like lesions in mouse
Endometriosis is an inflammatory disease depending on estradiol, with TNF-α being one of the most representative cytokines involved in its pathogenesis. TNF-α acts through its bond to the TNFRp55 and TNFRp75 membrane receptors. The aim of the present study was to analyze the effect of the TNFRp55 deficiency on the development of ectopic endometriotic-like lesions. Endometriosis was induced surgically in mice of the C57BL/6 strain, wild type (WT) and TNFRp55-/- (KO). After four weeks, the peritoneal fluid was collected and the lesions were counted, measured with a caliper, removed, weighed, fixed or kept at -80°C. We evaluated the cell proliferation by proliferating cell nuclear antigen (PCNA) immunohistochemistry and apoptosis by TUNEL technique in the ectopic lesions. MMP-2 and MMP-9 activities (factors involved in invasiveness) were measured by zymography in the peritoneal fluid; estradiol and progesterone levels were measured by radioimmunoassay in the lesions and in the peritoneal fluid. We found that in KO animals the mean number of lesions established per mouse, the lesion volume, weight and cell proliferation increased and apoptosis decreased. In addition, the activity of MMP-2 and the estradiol level increased, whereas the progesterone level was not significantly modified. In conclusion, the deficiency of TNFRp55 promoted the establishment and development of endometriosis through an increase in the lesion size and high levels of estradiol which correlate with an increase in the MMP-2 activity. This is evidence of the possible association of the deregulation of the TNFRp55 expression and the survival of the endometriotic tissue in ectopic sites.
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In utero vitamin D deficiency predisposes offspring to long-term adverse adipose tissue effects
The fetal period represents an important window of susceptibility for later obesity and metabolic disease. Maternal Vitamin D deficiency (VDD) during pregnancy is a global concern that may have long-lasting consequences on offspring metabolic health. We sought to determine whether a VDD in utero environment affects fetal adipose tissue development and offspring metabolic disease predisposition in adulthood. Furthermore, we sought to explore the extent to which the VDD intrauterine environment interacts with genetic background or postnatal environment to influence metabolic health. Eight-week-old P0 female C57BL/6J mice were fed either a VDD diet or sufficient diet (VDS) from four weeks before pregnancy (periconception) then bred to male Avy/a mice. Females were maintained on the diets throughout gestation. At weaning, Avy/a and a/a male F1 offspring were randomized to low-fat (LFD) or high-fat diet (HFD) until 19 weeks of age, at which point serum and adipose tissue were harvested for analyses. Mice born to VDD dams weighed less at weaning than offspring born to VDS dams but experienced rapid weight gain in the four weeks postweaning; and acquired a greater ratio of perigonadal (PGAT) to subcutaneous (SQAT) than control offspring. Additionally, these mice were more susceptible to HFD-induced adipocyte hypertrophy. Offspring of VDD dams also had greater expression of Pparg transcript. These novel findings demonstrate that in utero VDD, an easily correctable but highly prevalent health concern, predisposes offspring to long-term adipose tissue consequences and possible adverse metabolic health complications.
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Summertime Blues? A Re-Examination of the Seasonality of Web Searches for Restless Legs and Leg Cramps
Studies examining internet searches for restless legs and leg cramps have found a strong seasonal effect with peaks in summer and troughs in winter months. This study used an econometric approach to examine the seasonality of such searches in greater detail.
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The Short and Long of Adolescent Sleep: The Unique Impact of Day Length
Variation in day length is proposed to impact sleep, yet it is unknown whether this is above the influence of behavioural factors. Day length, sleep hygiene and parent-set bedtime were simultaneously explored, to investigate the relative importance of each on adolescents' sleep.
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Sleepiness in subjects with possible attention-deficit hyperactivity disorder
Ito et al. investigated the relationship between excessive daytime sleepiness (EDS) and attention deficit/hyperactivity disorder (ADHD) symptoms in adults with possible ADHD [1]. Compared with non-ADHD participants, participants with possible ADHD showed an evening chronotype, depressive symptoms, sleepiness and sleep disturbances. Hierarchical logistic regression analyses revealed that adjusted odds ratio (95% CI) of possible ADHD symptoms for EDS was 1.91 (1.59-2.29). Furthermore, the inattention score in relation to ADHD was significantly higher in the severe EDS group compared with the moderate and non-EDS groups.
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Periorbital Integrated Potentials: Useful phasic REM sleep markers
Although mentioned as one of the rapid eye movement (REM) sleep phasic events in the 1970s [1-3], periorbital integrated potentials (PIPs) have generally escaped the attention of contemporary sleep clinicians. There are certain situations where it is difficult to identify the classical REM sleep physiologic criteria (REM atonia, rapid eye movements [REMs] and desynchronized EEG with or without saw tooth waves). Such situations include inadequate impedance reduction in chin EMG making it difficult to identify muscle atonia or hypotonia, REM sleep behavior disorder (RBD), REM without atonia (RWA), status dissociatus, parasomnia overlap disorder, agrypnia excitata and in patients on antidepressants (eg., selective serotonin and norepinephrine reuptake inhibitors [ SSRIs and SNRIs]).
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A Rare Case of Primary Bilateral Adrenal Lymphoma
Lymphoma may involve the adrenal glands, but primary lymphoma is rare. Only a few cases have been reported in medical literature. Primary adrenal lymphoma is extremely rare, accounting for
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Reduced need for surgery in severe nasal polyposis with mepolizumab: randomised trial
This was the first study to show that mepolizumab treatment added to daily nasal corticosteroids offers a viable alternative to surgery in patients with severe, recurrent nasal polyposis requiring surgery.
http://ift.tt/2sKdPoK
Mepolizumab Efficacy in Patients with Severe Eosinophilic Asthma Receiving Different Controller Therapies
This post hoc analysis of the MENSA study demonstrates that mepolizumab reduced the annualized exacerbation rate relative to placebo in patients with severe eosinophilic asthma irrespective of the number or type of background controller therapies.
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Distribution of lymphoid neoplasms in Northwest China: Analysis of 3244 cases according to WHO classification in a single institution
Publication date: Available online 12 May 2017
Source:Annals of Diagnostic Pathology
Author(s): Chun Cao, Juan Feng, Hongtao Gu, Hailong Tang, Li Xu, Hongjuan Dong, Baoxia Dong, Mimi Shu, Qingxian Bai, Rong Liang, Tao Zhang, Lan Yang, Zhe Wang, Xiequn Chen, Guangxun Gao
To explore the distribution of lymphoid neoplasms in Northwest China, the clinical and pathological data of lymphoma patients from 2006 to 2014 were analyzed according to the WHO classification in Xijing Hospital. Of the 3244 cases, mature B-cell neoplasms occupied 60.7%, while mature T/NK-cell neoplasms and Hodgkin's lymphomas (HL) occupied 26.2% and 8.1%, respectively. The most common subtype of lymphoma was diffuse large B-cell lymphoma (35.0%), followed by extranodal NK/T-cell lymphoma, nasal type (ENKTCL) (12.9%) and marginal zone B-cell lymphoma (7.8%). Mixed cellularity (34.0%) was the most common subtype of HL. The especially high proportion of ENKTCL was the most outstanding feature of our study in comparison to previous reports. The mean age of all lymphoid neoplasms cases was 51years and most subtypes showed male predominance, with an average male-female ratio of 1.6. Extranodal lymphomas took up about 60% of all cases and gastrointestinal tract was the most frequently involved site. In conclusion, the distribution of lymphoid neoplasms of Northwest China showed some features similar to previous reports of China and other countries, but some subtypes presented distinct features.
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Accuracy and interobserver agreement of retroareolar frozen sections in nipple-sparing mastectomies
Publication date: August 2017
Source:Annals of Diagnostic Pathology, Volume 29
Author(s): David A. Suarez-Zamora, Luis E. Barrera-Herrera, Mauricio A. Palau-Lazaro, Fabio Torres-Franco, Alejandro Orozco-Plazas, Lisette Barreto-Hauzeur, Paula A. Rodriguez-Urrego
In the last decades, surgical treatment of breast cancer has enormously changed. As a result, nipple-sparing mastectomy (NSM) has evolved as an oncologically safe and cosmetic approach. NSM includes a subareolar frozen section to evaluate malignancy. We determined the accuracy of subareolar frozen section diagnosis, analyzed the discrepancy factor, and estimated the interobserver agreement of frozen section in NSM. A retrospective review of all NSMs at our institution from 2009 to 2015 was performed. Frozen sections were compared to the final diagnoses to analyze the accuracy of subareolar frozen sections. Discordant results were rigorously evaluated to identify discrepancy factors. Some cases were randomly chosen to assess the interobserver agreement (kappa) among pathologists. The agreement results were evaluated with and without knowledge of the tumor morphology. Among 34 NSMs, the frozen section false-negative and false-positive rate was 5.9% and 8.8%, respectively. The sensitivity and specificity was 77.8% and 88.0%, respectively. Sampling errors and diathermy artifacts explained our false-negative diagnoses. Freezing artifacts and an intraductal papilloma explained our false-positive diagnoses. The interobserver agreement between breast and general pathologists was 0.87 (p<0.0001) and 0.31 (p=0.0001), respectively. The interobserver agreement increased to 0.35 (p<0.0001) in general pathologists with knowledge of the tumor morphology. Subareolar frozen section showed to be a specific test with moderate sensitivity. Papillary lesions can mimic atypical cells and influence the frozen section interpretation. Frozen section in NSM had a better performance in breast pathologists (almost perfect) versus general pathologists (fair). Interobserver agreement may improve with knowledge of tumor morphology.
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Low-grade fibromyxoid sarcoma: Clinical, morphologic and genetic features
Publication date: June 2017
Source:Annals of Diagnostic Pathology, Volume 28
Author(s): Mustafa Mohamed, Cyril Fisher, Khin Thway
Low-grade fibromyxoid sarcoma (LGFMS) is a bland spindle cell neoplasm that typically arises in the deep soft tissues of the proximal extremities or trunk of young adults. The majority of LGFMS are characterized by a recurrent (7;16)(q34;p11) translocation, resulting in the FUS-CREB3L2 fusion gene, which generates a chimeric protein with transcriptional regulatory activity. Small numbers harbor a FUS-CREB3L1 fusion resulting from t(11;16)(p11;p11), whilst rare cases harbor the EWSR1-CREB3L1 fusion. LGFMS is of low to moderate cellularity and consists of bland spindle cells with small, angulated nuclei and scant, wispy cytoplasm, arranged in a whorled growth pattern and typically showing abrupt transition from myxoid to fibrous areas. Immunohistochemical expression of MUC4 is a consistent finding. Hyalinized spindle cell tumor with giant rosettes (HSCTGR) is a morphological variant of LGFMS that shares the same balanced translocation, and is also immunoreactive for MUC4. A potential relationship between LGFMS and sclerosing epithelioid fibrosarcoma (SEF), a rare fibroblastic neoplasm that most commonly arises in the deep soft tissues of the lower extremities, limb girdles or trunk, has also been suggested. SEF is classically composed of nests and cords of epithelioid cells with clear or eosinophilic cytoplasm embedded within densely sclerotic stroma. In some cases, areas indistinguishable from LGFMS are present, and these have been shown to contain FUS-CREB3L2 fusion transcripts. The majority of pure SEF tumors harbor EWSR1 rearrangements, with EWSR1-CREB3L1 and more rarely EWSR1-CREB3L2 gene fusions more common than those involving FUS. MUC4 immunoreactivity is also seen in approximately 70% of SEF. Surgical resection of these tumors with clear margins is the treatment of choice. Correct diagnosis is important because of the significant potential for recurrence and late metastatic spread. We review LGFMS and SEF, discussing morphology and immunohistochemistry, genetics and molecular findings, and the differential diagnosis.
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Phenotypic alterations in breast cancer associated with neoadjuvant chemotherapy: A comparison with baseline rates of change
Publication date: December 2017
Source:Annals of Diagnostic Pathology, Volume 31
Author(s): Nosaibah Hariri, Andres A. Roma, Farnaz Hasteh, Vighnesh Walavalkar, Oluwole Fadare
Several studies have documented phenotypic alterations in breast cancer associated with neoadjuvant chemotherapy [NACT], but many of these studies are limited by the fact that they did not account for the baseline rate of expected phenotypic change between biopsies and resections in the absence of NACT. Herein, we assess whether the NACT-associated rate of phenotypic change is significantly different than would be expected in a control population of patients that did not receive NACT. From a pathologic database, we documented the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2/neu) phenotypes of consecutive invasive breast carcinomas (n=826), as well as the subset in which at least one of these tests was assessed in both the biopsy and resection (n=340). We then compared the rates of phenotypic change in the patients that did (n=65) and did not (n=275) receive NACT. Respectively, 49.2% and 36% of the NACT and non-NACT groups showed a biopsy-to-resection change in status for at least one biomarker (p=0.0005). The NACT and non-NACT groups showed the following respective rates of a biopsy-to-resection change in phenotype: ER (9.2% vs 2.5%, p=0.02); PR (30.7% vs 8%, p=0.000006); Her2/neu-IHC (25% vs 22.3%, p=0.7), Her2/neu-FISH (7% vs 3%, p=0.6). The direction of change in the NACT group was positive in the biopsy to negative in the resection in >70% of cases for all markers. For ER and PR, there was no statistically significant difference between cases that showed a biopsy-to-excision change in phenotype and those that were more phenotypically stable regarding a wide array of clinicopathologic variables. The average percentage of ER/PR-immunoreactive tumor cells in the pre-NACT biopsies was significantly lower in the phenotypically altered cases as compared to the phenotypically stable cases. Our findings confirm that phenotypic alterations in breast cancer occur after NACT, and that these changes are more pronounced for hormone receptors (especially PR); Significant NACT-associated alterations were not apparent for HER2/neu. A distinct pathologic profile for cases displaying a phenotypic change within the NACT group was not demonstrable. The pre-NACT levels of ER and PR may affect the likelihood of a phenotypic change. These results highlight the need for repeat testing in residual tumors after NACT.
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Usefulness of a direct immunofluorescence in the diagnosis of plaque type oral lichen planus
Publication date: December 2017
Source:Annals of Diagnostic Pathology, Volume 31
Author(s): Patricia Alejandra Masquijo-Bisio, Mariana Silvia Gandolfo, Alicia Keszler, Maria Elina Itoiz, María Luisa Paparella
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Lymphocytic thrombophilic arteritis: A distinct inflammatory type I interferon and C5b-9 mediated subcutaneous endovasculitis
Publication date: December 2017
Source:Annals of Diagnostic Pathology, Volume 31
Author(s): Cynthia M. Magro, Jad Saab
BackgroundLymphocytic thrombophilic arteritis is a recently recognized subcuticular larger vessel vasculitis characterized by striking vascular luminal thrombosis.MethodsThe clinical features, histopathology and phenotypic profile of ten patients with lymphocytic thrombophilic arteritis were explored in an attempt to better define the entity from a clinical and pathophysiologic perspective.ResultsThe patients were all female (mean age of 43) presenting with generally asymptomatic lower and upper extremity hyperpigmented macules. A consistent picture diagnostic of a connective tissue disease syndrome was not seen. The disease was not progressive although it was typically persistent.The morphology was characterized by a temporally heterogeneous subcutaneous arteritis targeting the endothelium and intima with changes ranging from incipient intimal expansion by hyaluronic acid to concentric intimal fibrin deposition to one of an end stage acellular intraluminal obliterative fibrous arteriopathy. The infiltrate was predominated by lymphocytes and histiocytes. The intimal elastic lamina was intact in most cases. All tested cases showed intimal and endothelial C5b-9 deposition, an upregulated type I interferon microenvironment and marked upregulation of the inducible interferon gamma 16 protein.ConclusionsLymphocytic thrombophilic arteritis is a unique form of C5b-9 mediated arteritic endotheliopathy where the brunt of the changes involves the endothelium and intima and that is morphologically distinct from the transmural arteritis of benign cutaneous polyarteritis nodosa.
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Oral Lymphomatoid papulosis type C: A diagnostic pitfall, often confused with T-cell lymphoma
Publication date: Available online 16 June 2017
Source:Annals of Diagnostic Pathology
Author(s): Ziv Schwartz, Morton Coleman, Jennifer P. Toyohara, Paul D. Freedman, Cynthia M. Magro
Eosinophilic ulcer of the oral mucosa (EUOM) is a rare, benign, self-resolving lymphoproliferative disorder, which typically presents with asymptomatic to mildly tender ulcers. Histological findings of EUOM are characterized by a polymorphic infiltrate with many eosinophils often extending into the underlying muscle. Although this entity is well documented within the dental literature, it is not well known to physicians. The pathogenesis of the condition is unclear, although reports dating back to 1997 suggest that at least a subset of EUOM represents CD30 positive lymphoproliferative disorder (LPD30). More specifically the original report and subsequent authors suggest that the patients fall on the spectrum of LPD30 most reminiscent of Lymphomatoid papulosis (LyP) seen in the skin. This oral variant of LyP would be expected to have the same diverse morphologic spectrum as that seen in cutaneous LyP. We present five EUOM patients whose biopsies showed an atypical lymphocytic infiltrate most compatible with Type C LyP, a histologically unique subset of LyP, reminiscent of the biopsy findings encountered in the reported case by Ficarra and co-workers. (Ficarra, et al., 1997) In four of the five cases, the biopsies were interpreted by expert hematopathologists as an aggressive form of peripheral T cell lymphoma resulting in recommendations to administer systemic chemotherapy to four of the patients, the scheduling of one patient for induction therapy and transplantation before revision of the diagnosis, and administration of chemotherapy to one of the patients. The natural clinical course of spontaneous regression refuted the original diagnoses as a form of aggressive peripheral T cell lymphoma. Recognition of oral LyP is critical to avoid inadvertent exposure to potentially toxic chemotherapeutic regimens intended for the treatment of high grade lymphoma.
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Three cases of adrenocortical tumors mistaken for hepatocellular carcinomas/diagnostic pitfalls and differential diagnosis
Publication date: December 2017
Source:Annals of Diagnostic Pathology, Volume 31
Author(s): Won Young Park, Hyung Il Seo, Kyung Un Choi, Ahrong Kim, Young Keum Kim, So Jeong Lee, Chang Hun Lee, Gi Yeong Huh, Do Youn Park
Adrenocortical adenomas and carcinomas in other parenchyma are extremely rare, with few cases reported and because of the rarity of these tumors, they occasionally cause problems during diagnosis. Adrenal cortical neoplasms in liver parenchyma can be present in 3 forms, including direct invasion or adhesion to liver parenchyma, tumors arising in adrenohepatic fusion tissue or in ectopic adrenal gland tissue. We report 3 cases of adrenal cortical tumors that were misdiagnosed as hepatocellular carcinoma in the preoperative state. The first case involved an adrenocortical adenoma arising in adrenohepatic fusion tissue. The remaining 2 cases involved an adrenocortical carcinoma and an adrenocortical oncocytoma arising in ectopic adrenal tissue in the liver. We describe the clinical presentations, gross, microscopic findings, immunohistochemical findings with respect to each case, with emphasis on differential diagnosis from hepatocellular carcinoma.
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Editorial Board
Publication date: April 2017
Source:Annals of Diagnostic Pathology, Volume 27
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Utility of different immunostains for diagnosis of metastatic breast carcinomas in both surgical and cytological specimens
Publication date: October 2017
Source:Annals of Diagnostic Pathology, Volume 30
Author(s): Yanjun Hou, Rulong Shen, Shweta Chaudhary, Dena Tonkovich, Zaibo Li
ObjectiveA panel of immunostains is usually performed to confirm a metastatic carcinoma origin. GATA3 is a transcription factor and has been proven to be a useful marker for breast carcinoma. Other immunostains including mammaglobin (MGB), gross cystic disease fluid protein 15 (GCDFP-15), estrogen receptor (ER) and progesterone receptor (PR) are also used in diagnosing metastatic breast cancer. In this study, we aimed to compare the performance of these immunostains in the work up of metastatic breast carcinoma in both surgical and cytological specimens.Study designThis study cohort was composed of 242 metastatic breast carcinomas (142 surgical and 100 cytological specimens) during a study period from October 2013 to December 2015. Immunostain results of GATA3, CK7, MGB, GCDFP-15, ER and PR and their correlations were examined.ResultsIn surgical specimens, GATA3 and CK7 were highly expressed (88% and 87%), but MGB and GCDFP-15 showed much lower positivity rates (43% and 29%). In cytological specimens, GATA3, CK7 and MGB showed similar positivity rates to those in surgical specimens; but GCDFP-15, ER and PR showed significantly lower positivity rates than those in surgical specimens. All ER-positive cases were positive for GATA3 in both surgical and cytological specimens; however, GATA3 positivity showed a significantly stronger correlation with ER positivity in surgical specimens than in cytological specimens.ConclusionsGATA3 and CK7 performed better than other immunostains to detect metastatic breast carcinoma in both surgical and cytological specimens. GATA3 expression was positively correlated with ER expression, and the correlation was stronger in surgical specimens than in cytological specimens.
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IMP3 contributes to poor prognosis of patients with metaplastic breast carcinoma: A clinicopathological study
Publication date: December 2017
Source:Annals of Diagnostic Pathology, Volume 31
Author(s): Ryuji Ohashi, Maoka Sangen, Shigeki Namimatsu, Hiroyuki Takei, Zenya Naito
Metaplastic breast carcinoma (MBC) is a rare type of tumor with heterogenous histological patterns. We investigated the immunohistochemical expression of IMP3, an oncofetal protein, in 31 MBC patients in association with histological subtypes and clinical outcomes. The cohort consisted of spindle cell carcinoma (SPC) (n=11), squamous cell carcinoma (SCC) (n=14), matrix-producing carcinoma (MPC) (n=4), carcinoma with osteocartilaginous elements (COC) (n=1), and low grade adenosquamous cell carcinoma (ASC) (n=1). IMP3 expression was identified in 7 cases of SPC (64%) and 6 patients of all the other subtypes (p=0.051). In comparison between IMP3 high (n=13) and low (n=18) groups, a large-sized tumor (≥4.0cm) was identified in 9 IMP3 high patients, and 14 IMP3 low patients had a small-sized tumor (p=0.01). High Ki67 positivity was detected in all of the IMP3 high patients and in 7 of the IMP3 low patients (p=0.002). During the follow-up period, 9 IMP3 high patients died, whereas 15 of the 18 IMP3 low patients remained alive (p=0.004). A univariate analysis revealed that IMP3 expression and tumor size were significantly associated with poor clinical outcomes (p=0.03 and <0.001, respectively). The IMP3 high group was likely to be associated with reduced overall survival compared to the IMP3 low group (p=0.06). These findings indicate that IMP3 may contribute to the aggressive behavior of MBC, and that this expression could potentially be a prognostic marker of MBC.
http://ift.tt/2tey6Go
Beta-catenin and p53 expression in topographic compartments of colorectal cancer and its prognostic value following surgery
Publication date: December 2017
Source:Annals of Diagnostic Pathology, Volume 31
Author(s): Juan Daniel Prieto, Martina Álvarez, María Isabel Hierro, Isabel García, Luis Vicioso
Colorectal cancer (CRC) is the third most prevalent neoplasm worldwide and the fourth cause of cancer-related death. From Vogelstein's initial model, new molecular knowledge has been incorporated which includes an elevated number of genetic mutations, many of them located in the Wnt pathway, which affect its principle effector: β-catenin. Additionally, it is necessary to keep the heterogeneity of CRCs in mind, both in terms of morphology and biology. The aim of this work is to study the interaction between the Wnt molecular pathway, by means of immunoexpression of β-catenin, in CRC and other molecular mechanisms, such as the p53 pathway, in order to determine the pattern - if one exists - of different immunohistochemical expression of β-catenin and p53 in the superficial and deep tumor components, and lastly, to determine the impact of these markers on prognosis.Our cases showed an increasing gradient of β-catenin immunoexpression that parallels depth in the tumor, with a greater degree of nuclear immunoexpression in the deep compartment. We observe that in those cases with positivity for nuclear p53 and an absence of immunostaining of β-catenin show higher rates of survival, whereas one of the lowest rates was observed in patients who co-expressed p53 and β-catenin. We conclude that a combined analysis of β-catenin and p53 could have prognostic importance as markers for predicting the disease's progression and contribute to the identification of patients with a high risk of mortality.
http://ift.tt/2sKn2gD
Comparison of HER2 status determination methods in HER2 (2+) patients: Manual fluorescent in situ hybridization (FISH) vs. dual silver enhanced in situ hybridization (SISH)
Publication date: December 2017
Source:Annals of Diagnostic Pathology, Volume 31
Author(s): Burcin Pehlivanoglu, Gurdeniz Serin, Levent Yeniay, Osman Zekioglu, Erhan Gokmen, Necmettin Ozdemir
HER2 amplification has been demonstrated in 15–25% of invasive breast carcinomas and can be assessed using immunohistochemical and in situ hybridization methods. Here, we compared the accuracy of dual SISH to manual FISH in HER2 (2+) breast carcinoma and evaluated the feasibility of dual SISH method in routine practice. Sixty HER2 (2+) consecutive tumor samples diagnosed between January 2009 and February 2013 were selected. Demographic, histological and immunohistochemical features and FISH results were recruited from patient records and compared to dual SISH results. Nine (15%) of the 60 tumor samples were excluded from statistical analysis due to lack of interpretable SISH signals. HER2 staining percentages by immunohistochemistry differed between 20 and 80%. HER2 amplification was shown in 7 (13.7%) and 8 (15.7%) patients by FISH and SISH, respectively. Very good agreement was observed between FISH and SISH methods (kappa value: 0.92). Significant correlation was found between HER2 staining percentage and FISH positivity, in contrast to SISH positivity (p=0.012 vs. p=0.069). Our results are consistent with previously reported literature, indicating SISH can be used to determine HER2 status. However, preanalytical and analytical problems may cause inadequate or uncountable signals, making interpretation impossible for the pathologist and highlighting the importance of standardization and quality control programs.
http://ift.tt/2tey6pS
AMPK expression patterns are significantly associated with poor prognosis in breast cancer patients
Publication date: August 2017
Source:Annals of Diagnostic Pathology, Volume 29
Author(s): Jaudah Al-Maghrabi, Kaltoom Al-Sakkaf, Imtiaz Ahmad Qureshi, Nadeem Shafique Butt, Lila Damnhory, Mohamed Elshal, Basim Al-Maghrabi, Alia Aldahlawi, Sawsan Ashoor, Barry Brown, Pauline Dobson, Mohamad Nidal Khabaz
Many investigators have examined the functions of AMP-activated protein kinase (AMPK) in cancer biology and its anti-neoplastic features in cancer models. The goal of this research is to assess the association of the immunohistochemical expression of AMPK in human mammary tumours with the clinical data of breast cancer patients. 449 cases of previously diagnosed breast cancer, and 27 tissue samples of fibroadenomas and normal breast were utilized for detection of AMPK expression using tissue microarrays and immunohistochemistry. Brownish nuclear and cytoplasmic staining were present in epithelial cells and stromal cells in 333 (74.16%) and 348 (77.5%) cancer cases respectively indicating AMPK expression. Twenty two (81.48%) control cases showed AMPK immunoexpression in both epithelial and stromal cells. Significant statistical association has been found between advanced stages of breast cancer and increased intensity of AMPK immunostaining only in epithelial cells (p-value=0.0001). Histotypes have been correlated with AMPK immunostaining in epithelial cells only (p-value=0.029). Low AMPK immunostaining scores were more dominant in DCIS, ductal and mixed type's ductal and mucinous histotypes, while high intense staining was more common in the lobular type. Furthermore, breast tumour cases with lymph node metastases showed significant AMPK expression in both epithelial and stromal cells (p-value=0.0001 and p-value=0.026). Low scores of AMPK immunostaining were common in breast cancer cases with positive vascular invasion (p-value=0.007) and disease recurrence (p-value=0.008). No significant differences in survival behavior distributions were observed for the different categories of AMPK immunostaining in epithelial and stromal cells.In conclusion, our results showed decreased AMPK expression in breast cancer in comparison with the control group. AMPK expression was significantly correlated with some clinicopathological factors like advanced stage, lymph node involvement, vascular invasion and disease recurrence which give indications for poor clinical outcomes. Immunohistochemical staining of AMPK protein is a valuable method which could predict cases of breast cancer with poor prognosis.
http://ift.tt/2sKieIn
Expression of pRb, Ki67 and HER 2/neu in gastric carcinomas: Relation to different histopathological grades and stages
Publication date: October 2017
Source:Annals of Diagnostic Pathology, Volume 30
Author(s): Azza Abdel-Aziz, Rehab Allah Ahmed, Afaf Taha Ibrahiem
http://ift.tt/2teSxTJ
Editorial Board
Publication date: June 2017
Source:Annals of Diagnostic Pathology, Volume 28
http://ift.tt/2sKJAhc
Expression of dog1 in low-grade fibromyxoid sarcoma: A study of 19 cases and review of the literature
Publication date: October 2017
Source:Annals of Diagnostic Pathology, Volume 30
Author(s): Ana Vallejo-Benítez, Enrique Rodríguez-Zarco, Sara Pabón Carrasco, Sofia Pereira-Gallardo, Javier Brugal Molina, Antonio García-Escudero, Antonio Robles Frías, David Marcilla, Ricardo González-Cámpora
DOG1 is a highly-sensitive marker often included in the immunohistochemical panel for the diagnosis of gastrointestinal stromal tumors (GISTs). Recent research has shown that DOG1 may also be expressed by low-grade fibromyxoid sarcomas (LGFMSs); this may give rise to diagnostic error when the sarcoma is located in the abdominal cavity. This paper reports on immnohistochemical expression of DOG1 in 19 LGFMSs using two different monoclonal antibodies: K9 (Leica, Novocastra Laboratories, Newcastle upon Tyne, UK) and SP31 (Thermo Scientific, Freemont, USA). All LGFMSs displayed the standard histological pattern of alternating myxoid and fibrous areas, low cellularity and bland spindle-cell morphology. Positive staining for MUC4 was observed in 18/19 cases (94.7%), while there was rearrangement of the FUS gene in 14/19 (73.7%) cases and of the EWR1 gene in 2/19 (10.5%). The sarcoma staining negative for MUC4 displayed FUS gene rearrangement. Whole-section immunohistochemistry revealed positive staining for DOG1 in 8/19 cases (42.1%), though only with clone K9. Cytoplasmic as well as membrane staining was observed in all cases; staining was focal (10–30%) and of varying intensity (1+ to 2+).In conclusion, DOG1 clone K9 exhibited low sensitivity (42.1%) for the diagnosis of LGFMS, although higher than clone SP31. Since the two clones display similar sensitivity and specificity for GIST diagnosis, SP31 would appear to be more specific for this purpose, since no reaction was observed here with LGFMS, a GIST-mimicking lesion.
http://ift.tt/2tf0etb
Histological, immunohistochemical features and pathogenesis of pseudoangiosarcomatous urothelial carcinoma
Publication date: October 2017
Source:Annals of Diagnostic Pathology, Volume 30
Author(s): Pelin Yıldız, Kemal Behzatoğlu, Ezgi Hacıhasanoğlu, Oğuzhan Okcu, Haydar Durak, Uğur Yücetaş
http://ift.tt/2sK9XEg
Chronic inflammation in refractory hippocampal sclerosis-related temporal lobe epilepsy
Publication date: October 2017
Source:Annals of Diagnostic Pathology, Volume 30
Author(s): Jordan M. Gales, Richard A. Prayson
Emerging evidence suggests chronic inflammation may play a role in hippocampal sclerosis-associated temporal lobe epilepsy. We sought to systematically evaluate for its presence in a group of 315 patients who underwent surgery for medically-refractory epilepsy and who had hippocampal sclerosis. Upon histologic review of hematoxylin and eosin stained tissue sections, 95 (41%) cases demonstrated the presence of lymphocytes within the perivascular region and diffusely within the brain parenchyma. Those cases with chronic inflammation evident on hematoxylin and eosin staining were significantly more likely to experience a post-operative seizure recurrence than those without it (p=0.03). In 9 cases of hippocampi with chronic inflammation observed on hematoxylin and eosin stained sections, there was a mixture of both T (CD3+) and B (CD20+) lymphocytes located around blood vessels and interspersed within the brain parenchyma and a predominance of CD4 positive T cells versus CD8 positive cells. Ten hippocampi, apparently devoid of chronic inflammation upon inspection with hematoxylin and eosin stained sections, were stained with the lymphocyte common antigen CD45. In all 10 cases, scattered lymphoid cells were observed in the brain parenchyma, suggesting some level of chronic inflammation may be present in more cases than casual inspection might suggest. This study was the first to evaluate the incidence of chronic inflammation within a large temporal lobe epilepsy population. The study findings suggest chronic inflammation may be a more common component of hippocampal sclerosis -associated temporal lobe epilepsy than previously believed.
http://ift.tt/2tf2IHM
Table of Contents
Publication date: June 2017
Source:Annals of Diagnostic Pathology, Volume 28
http://ift.tt/2sKiUNG
Letter to the Editor regarding: Rat model of chronic tympanic membrane perforation: Ventilation tube with mitomycin C and dexamethasone
We would like to address the manuscript titled "Rat model of chronic tympanic membrane perforation: Ventilation tube with mitomycin C and dexamethasone" by Wang et al.1 This is an interesting study. The creation of an ideal animal model of chronic tympanic membrane perforation (TMP) will be of great importance in the development of biological graft materials for myringoplasty. However, we believe that the technique used by Wang et al. is not reliable, and it is also different from human chronic TMP with chronic suppurative otitis media (CSOM).
http://ift.tt/2sDQJ82
In response to the letter to the editor regarding: Rat model of chronic tympanic membrane perforation: Ventilation tube with mitomycin C and dexamethasone
Thanks for the opportunity to respond to Dr Lou's letter on our successfully animal model of chronic tympanic membrane perforation (TMP) in rats with ventilation tube (VT) insertion in conjunction with mitomycin C and dexamethasone (M/D) [1]. This letter will be the fifteenth to an Editor written by Lou within the last 15 months from February 2016 to May 2017, which are all alternatives from his own work [2–4]. The average frequency of one letter to Editor per month is too frequent not to be a concern of overly self-promoting.
http://ift.tt/2tnu8cV
Evaluation of ototoxicity of intratympanic administration of Methotrexate in rats
Methotrexate is a dihydrofolate reductase enzyme inhibitor with very high selectivity, and it is an antiproliferative folic acid antagonist used for the treatment of autoimmune diseases. In this study, our objective was to evaluate the effect of intratympanic Methotrexate application in the inner ear.
http://ift.tt/2tnu7Wp
Formula for the prediction of apnea / hypopnea index in children with obstructive sleep apnea without polysomnography according to the clinical parameters: Is it reliable?
The aim of the study was to propose "the risk formula" for obstructive sleep apnea in children according to the general and local clinical parameters and findings relevant for obstructive sleep apnea (OSA) severity. The unmet need for this formula arises from the economic burden of polysomnography (device, staff, training, special sleep centers, etc) as the golden standard for the diagnostics.
http://ift.tt/2sDQIRw
The effect of pneumococcal conjugate vaccines on incidence and microbiology associated with complicated acute otitis media
The objectives of this study were to investigate the incidence of complicated acute otitis media (cAOM) as well as the associated microbiology before and after introduction of the 7- and 13-valent pneumococcal conjugate vaccines (PCV-7 and -13), respectively. CAOM comprises "heavy" AOM (AOM demanding hospitalization), mastodismus (M) and acute mastoiditis (AM).
http://ift.tt/2tnHRR1
A simple technique for the correction of maxillonasal dysplasia using customized expanded polytetrafluoroethylene (ePTFE) implants
The treatment of maxillonasal dysplasia in Binder's syndrome using autologous costal bone and cartilage is well established, but postoperative results may be compromised by scarring, unpredictable absorption of transferred autologous tissue, and donor site morbidity. Here, we propose a simple surgical technique to improve maxillonasal dysplasia using an expanded polytetrafluoroethylene (ePTFE) implant.
http://ift.tt/2unfsdV
High resolution residual stress gradient characterization in W/TiN-stack on Si(100): Correlating in-plane stress and grain size distributions in W sublayer
Publication date: 15 October 2017
Source:Materials & Design, Volume 132
Author(s): René Hammer, Juraj Todt, Jozef Keckes, Bernhard Sartory, Georg Parteder, Jochen Kraft, Stefan Defregger
Residual stress gradient characterization by the ion beam layer removal method (ILR), using a milling step of 10nm, was applied to W/TiN stacks processed on thermal SiO2-insulated standard silicon wafers. The stress profiles indicate a pronounced stress gradient with high tensile, as well as compressive stress concentrations in polycrystalline W and amorphous TiN sublayers ranging between 3.5 and −4GPa. Electron backscatter diffraction shows that the W sublayer exhibits zone T microstructure with nano-sized crystallites in the nucleation region at the interface to TiN and above that columnar or V-shaped grain morphology typical for competitive grain growth. In the W sublayer, the stress distributions correlate well with this in-plane crystallite size distribution on the base of a Hall-Petch mechanism, reaching a tensile maximum in the transition region between the nucleation layer and the region with columnar microstructure.
Graphical abstract
http://ift.tt/2tJZxZo
Stability of biodegradable metal (Mg-Ca-Zn alloy) screws compared with absorbable polymer and titanium screws for sagittal split ramus osteotomy of the mandible using the finite element analysis model
Mg-Ca-Zn alloy has been suggested for the application of fixation materials during maxillofacial surgery. We investigated the stability of Mg-Ca-Zn alloy for clinical application during orthognathic surgery. The finite element model for the fixation of sagittal split ramus osteotomy was constructed. In the bicortical screw fixation of the mandible setback condition, the stress distributions of Mg-Ca-Za alloy, polylactic acid polymer, and titanium were evaluated using the virtual model with occlusal loading of 132 N.
http://ift.tt/2sDuIGy
Automatic repositioning of jaw segments for three-dimensional virtual treatment planning of orthognathic surgery
To develop a computer-based method for automating the repositioning of jaw segments in the skull during three-dimensional virtual treatment planning of orthognathic surgery. The method speeds up the planning phase of the orthognatic procedure, releasing surgeons from laborious and time-consuming tasks.
http://ift.tt/2tnDJAu
Three-Dimensional analysis of the pharyngeal airway space and hyoid bone position after orthognathic surgery
The aim of this study was to evaluate changes in the pharyngeal airway space (PAS) and hyoid bone position after orthognathic surgery with cone-beam computed tomography (CBCT).
http://ift.tt/2sDRDBC
Clinicopathological features, management and outcome of patients with poorly-differentiated oral and oropharyngeal squamous cell carcinoma
The purpose of this study was to explore the clinicopathological features, risk factors, and management of poorly differentiated oral and oropharyngeal squamous cell carcinoma (OOSCC) patients in the northern Chinese population.
http://ift.tt/2tnLy9o
Electromyographic analysis of superior orbicularis oris muscle function in children surgically treated for unilateral complete cleft lip and palate
The aim of this study was to assess the electrical activity of the superior orbicularis oris muscle in children surgically treated for unilateral complete cleft lip and palate (UCCLP).
http://ift.tt/2tnpVpA
Erratum to “Changing prevalence and treatment outcomes of patients with p16 human papillomavirus related oropharyngeal squamous cell carcinoma in New Zealand” [Br. J. Oral Maxillofac. Surg. 54 (8) (2016) 898–903]
The publisher regrets that the below figure (Fig. 3) was omitted from the above mentioned paper and apologises for the error.
http://ift.tt/2sDmX3i
Age-related changes in the morphological relationship between the supratubal recess and the Eustachian tube
To study age-related changes in the morphology of the supratubal recess (STR) and its relationship with the Eustachian tube (ET).
http://ift.tt/2snzFPu
Age-related changes in the morphological relationship between the supratubal recess and the Eustachian tube
To study age-related changes in the morphology of the supratubal recess (STR) and its relationship with the Eustachian tube (ET).
http://ift.tt/2snzFPu
Plasmatic and Intracellular Markers of Oxidative Stress in Normal Weight and Obese Patients with Polycystic Ovary Syndrome
Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-111241
Introduction Insulin resistance (IR) is associated with polycystic ovary syndrome (PCOS). Oxidative stress (OS) is, in turn, related to IR. Studies in PCOS evidenced an increase in OS markers, but they are mainly performed in obese patients, while the complex picture of normal weight PCOS is still poorly investigated. Matherials and Methods To investigate OS in PCOS and relationship with hormonal and metabolic picture, we performed a case-control study in 2 PCOS groups: normal weight (N-PCOS, n=21, age 18–25 ys, mean±SEM BMI 20.7±0.2 kg/m2) and obese (OB-PCOS, n=15, 20–30 ys, BMI 32.8±1.1), compared with control groups matched for BMI: normal (N-C, n=10, 20–30 ys, BMI 21.6±0.9) and obese (OB-C, n=20, 21–31ys, BMI 36.8±1.0). Malondialdehyde (MDA) in blood plasma and peripheral mononuclear cells, obtained by density-gradient centrifugation, was assayed spectrophotometrically by TBARS assay. CoenzymeQ10 (CoQ10) in plasma and cells was assayed by HPLC. Plasma Total Antioxidant Capacity (TAC) was also measured by spectrophotometric method. Results PCOS patients exhibited higher Testosterone levels than controls, but OB-PCOS had highest HOMA (Homeostasis Model Assessment) index, suggesting marked insulin resistance. Despite plasma MDA levels were not significantly different (N-PCOS 3380±346.94 vs. N-C 7 120±541.66; OB-PCOS 5 517.5±853.9 vs. OB. 3 939.66±311.2 pmol/ml), intracellular MDA levels were significantly higher in N-PCOS than controls (mean 3 259±821.5 vs. 458±43.2 pmol/106/cells) and higher than OB-PCOS, although not significantly (1363.1±412.8 pmol/106/cells). Intracellular CoenzymeQ10 was higher in N-PCOS than in N-C, but the highest levels were found in OB-C. Conclusions Our data, while confirming the presence of OS in obese PCOS patients in agreement with literature, suggest that OS could be present also in normal weight PCOS, but it can be revealed in tissue rather than in plasma. The relationship with metabolic status remains to be established, but could be a physiopathological basis for antioxidant treatment in such patients.
[...]
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
http://ift.tt/2ungRB8
Risk Factors for Premature Death in Diabetes Patients who Undergo Amputations below Ankle Level
Exp Clin Endocrinol Diabetes
DOI: 10.1055/s-0043-109700
Aim To identify risk factors for early death in diabetes patients who undergo amputations below the ankle. Methods A retrospective study, where all hospital records of all diabetes patients who had undergone minimum one amputation below the ankle at the CWHC Bispebjerg Hospital, Denmark, in the period 1996–2013, were examined. The amputations were mainly trans-metatarsal amputations and partial amputations of toes. The participants were found via ICD10-codes. The included patients were followed from their first contact to the last registered contact. The statistical analysis in this article is performed on patients with a of minimum 5-year follow-up. Results The 5 year mortality was 42% for patients with type 2 diabetes, and 29% for patients with type 1 diabetes. For patients with type 2 diabetes, multivariable analysis showed that high age, peripheral arterial insufficiency and short time from first admission to amputation were independently statistically significantly associated with increased 5-years mortality. Use of statins was associated with decreased mortality. 35% died as a result of their diabetes, mostly due to cardiovascular causes. Conclusion Short time from first admission to amputation is a risk factor for early death. Arterial insufficiency and high age is also associated with increased mortality, whereas use of statin is associated with decreased mortality, in patients with type 2 diabetes.
[...]
© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
Table of contents | Abstract | Full text
http://ift.tt/2tOI3f4
Heavy metals and minerals contents in pikeperch ( Sander lucioperca ), carp ( Cyprinus carpio ) and flathead grey mullet ( Mugil cephalus ) from Sidi Salem Reservoir (Tunisia): health risk assessment related to fish consumption
Abstract
The aim of this study was to investigate heavy metals and selected minerals contents in filets of pikeperch (Sander lucioperca), carp (Cyprinus carpio) and flathead grey mullet (Mugil cephalus), the major fish species produced in Sidi-Salem reservoir; the largest Tunisian freshwater ecosystem. Concentrations of Ca, Mg, Fe, Zn, Cd, Pb and Hg were determined by inductively coupled plasma-optical emission spectrometry, while concentrations of Na and P were determined by flame photometry and spectrophotometry, respectively. Results concerning heavy metals are considered quantitatively reliable for Hg and Cd but must be taken with precautions concerning Pb levels as the LOD (limit of detection) of the analytical process was higher than acceptable limit. They showed greater accumulations of both Hg and Cd in filets of pikeperch than in filets of carp and mullet, but none of the values exceeded the normative maximum levels (0.500 and 0.050 mg kg−1 w.w., respectively). Considering provisional intakes, target hazard quotient and hazard index, estimated for a fish portion per week, consumption of any of the species did not appear to be potentially hazardous for the health as they were far below threshold values. A fish portion would provide substantial amounts (>15% of daily requirements) in essential mineral nutrients (P, Mg and Fe) and thus should be considered an interesting contribution to a healthy diet. It is strongly advocated to authorities including freshwater fish in the official national annual control survey of contaminants in fishery products, which in addition to guaranteeing security of consumers, would also allow diversifying valorisation opportunities and thus increase the economic value of this fish production.
http://ift.tt/2sKbiLl
Age-related changes in the morphological relationship between the supratubal recess and the Eustachian tube
Source:Auris Nasus Larynx
Author(s): Juan Hong, Keguang Chen, Huiying Lyu, Dongming Yin, Lin Yang, Tianyu Zhang, Peidong Dai
ObjectiveTo study age-related changes in the morphology of the supratubal recess (STR) and its relationship with the Eustachian tube (ET).MethodsSeventy randomly selected computed tomography (CT) images of non-pathological temporal bones of 49 patients were reviewed retrospectively. The patients were grouped according to age into 4 age groups: group A (0–3 years), group B (4–8 years), group C (9–18 years) and group D (19–50 years). Space analytic geometry was assessed to directly calculate the morphology of the STR and the ET.ResultsIn normal temporal bones, the STR was mostly presented with a solitary cell in life. The length of the STR was significantly longer in group C than that in group A (P<0.05). The width of the STR was declined with age and presented with significant difference among age groups (P<0.05). No significant difference was observed in the height of the STR in whole age groups (P>0.05). The aeration of the STR was intimately related with age-related morphological changes in the ET. But the important factors influencing the aeration of the STR were not always the same in different age stages.ConclusionThe extended length and declined width of the STR with age were mostly related with the prolonging bony part and inwardly bending cartilaginous part of the ET in children and adolescent aged from 0 to 18 years old. In adults aged more than 18 years old, the narrowed caliber of the tympanic orifice of the ET could induce the decline in the width of the STR with age, but unfolded horizontal cartilaginous part of the ET contributed to stable length and height in aeration of the STR.
http://ift.tt/2sK0fSk
Operative Procedure of Anterior Commissure for Type II Thyroplasty
We reviewed the clinical anatomy of the anterior commissure and examined the effectiveness of a specialized spreader developed for optimal, efficient spreading of the thyroid cartilage in type II thyroplasty.
http://ift.tt/2sDQ0DN
Response to Aichinger and Kubin Re: Letter to the Editor “Acoustic and Perceptual Classification of Within-Sample Normal, Intermittently Dysphonic, and Consistently Dysphonic Voice Types”
Thanks to Drs Aichinger and Kubin for their consideration of our recent article "Acoustic and Perceptual Classification of Within-sample Normal, Intermittently Dysphonic, and Consistently Dysphonic Voice Types" and for their interesting comments. Our study was an initial attempt at using measures of the cepstral peak prominence (CPP) distribution to identify intermittently dysphonic samples that can be difficult to accurately classify both perceptually and acoustically. In addition to examination of the moments of the CPP distribution (mean, standard deviation, skewness, and kurtosis), we also considered measures for the detection of extreme CPP values used in statistical process control and measures of the relative percentage of dysphonia duration in our analyses.
http://ift.tt/2tnDDJc
Secondary encephalocele in infant following subdural empyema repaired endoscopically-A case report
Publication date: Available online 4 July 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): Roshan K. Verma, Navjot Kaur
Subdural empyema (SDE) is an uncommon entity, mostly associated with meningitis and can be life threatening in infants. Rarely, a subdural empyema can lead to nasal encephalocele which can be challenging situation to manage especially in infant. We present a case of 7 month old infant who presented with subdural empyema that led to formation of nasal encaphalocele after 4 months which was managed endoscopic route.
http://ift.tt/2uHTnpP
The effect of pneumococcal conjugate vaccines on incidence and microbiology associated with complicated acute otitis media
Publication date: Available online 4 July 2017
Source:International Journal of Pediatric Otorhinolaryngology
Author(s): B.B. Laursen, C.S. Danstrup, S. Hoffmann, N. Nørskov-Lauritsen, A.L.B. Christensen, T. Ovesen
ObjectivesThe objectives of this study were to investigate the incidence of complicated acute otitis media (cAOM) as well as the associated microbiology before and after introduction of the 7- and 13-valent pneumococcal conjugate vaccines (PCV-7 and -13), respectively. CAOM comprises "heavy" AOM (AOM demanding hospitalization), mastodismus (M) and acute mastoiditis (AM).MethodsA retrospective cohort study of the incidence and microbiology associated with cAOM during the non-PCV era, the PCV-7 and 13 eras, respectively. Clinical and microbiological data were prospectively registered in a local database. The incidences of cAOM as well as the distribution of various bacterial strains in the three eras were compared.ResultsA total of 246 cases of cAOM (125 in the pre-vaccine period (2001-2006), 50 in the PCV-7 period (2007-2010) and 71 in the PCV-13 period (2011-2015)) were identified.The incidence of hAOM decreased by 62% in the PCV7-era but increased to almost pre-vaccine levels in the PCV-13 era. In the M + AM group, a decrease by almost 21 % in the PCV7-era was found compared to the pre vaccine era, whereas the decrease was only 12 % in the PCV13-era.The three most common findings in both hAOM and M + AM were Streptococcus pneumonia (SP), group A streptococcus (GAS) and "no growth". In the hAOM group, SP decreased from 38% in the pre-vaccine era to 31% in the PCV7-era and further to 16% in the PCV13-era. GAS decreased from 17% in the pre-vaccine era to 0% in the PCV7-era and 16% in the PCV13-era. The percentage of "no growth" increased from 12 % to 38 % and 44 %, respectively.In the M + AM group, SP decreased to 10 % in the PCV13-era compared with 44 % in the pre-vaccine era and 41 % in the PCV7-era. An increase in GAS from 15 % in the pre-vaccine era and PCV7-era to 30 % in the PCV13-era was observed. The "no growth" percentage increased from 13 % in the pre-vaccine era to 26% in the PCV7-era and 33% in the PCV13-era.ConclusionIntroduction of PCV7 and PCV13 has been associated with an overall reduction of cAOM in Central Region Denmark. Pneumococci were still one of the two most common bacteria species related to cAOM though a decrease in pneumococci positive cases was observed. We found an increase in M + AM induced by GAS and a relatively large increase in "no growth", which might be caused by a more aggressive pre-hospital approach to treatment with antibiotics. Consequently, it is not evident whether the reduction of incidences is caused by the vaccines or a more aggressive antimicrobial attitude to manage AOM. The shift to GAS from SP is worrisome, and therefore continuous surveillance of the microbiology associated with AOM is warranted.
http://ift.tt/2tJOteA
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